 |
CARLO SALVARANI
Professore Ordinario
Dipartimento Chirurgico,Medico,Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa - Sede Arcispedale Santa Maria Nuova
|
Home |
Curriculum(pdf) |
Didattica |
Pubblicazioni
2024
- A comprehensive review on the role of mesenchymal stromal/stem cells in the management of rheumatoid arthritis
[Articolo su rivista]
Pignatti, Elisa; Maccaferri, Monia; Pisciotta, Alessandra; Carnevale, Gianluca; Salvarani, Carlo
abstract
Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease with systemic manifestations. Although the success of immune modulatory drug therapy is considerable, about 40% of patients do not respond to treatment. Mesenchymal stromal/stem cells (MSCs) have been demonstrated to have therapeutic potential for inflammatory diseases. Areas covered: This review provides an update on RA disease and on pre-clinical and clinical studies using MSCs from bone marrow, umbilical cord, adipose tissue, and dental pulp, to regulate the immune response. Moreover, the clinical use, safety, limitations, and future perspective of MSCs in RA are discussed. Using the PubMed database and ClincalTrials.gov, peer-reviewed full-text papers, abstracts and clinical trials were identified from 1985 through to April 2023. Expert opinion: MSCs demonstrated a satisfactory safety profile and potential for clinical efficacy. However, it is mandatory to deepen the investigations on how MSCs affect the proinflammatory deregulated RA patients' cells. MSCs are potentially good candidates for severe RA patients not responding to conventional therapies but a long-term follow-up after stem cells treatment and standardized protocols are needed. Future research should focus on well-designed multicenter randomized clinical trials with adequate sample sizes and properly selected patients satisfying RA criteria for a valid efficacy evaluation.
2024
- Baseline Ultrasound Assessment Improves the Response to Apremilast in Patients with Psoriatic Arthritis: Results from a Multicentre Study
[Articolo su rivista]
Farina, Antonella; Del Medico, Patrizia; Parisi, Simone; Becciolini, Andrea; Visalli, Elisa; Biagio Molica-Colella, Aldo; Lumetti, Federica; Caccavale, Rosalba; Scolieri, Palma; Andracco, Romina; Girelli, Francesco; Bravi, Elena; Colina, Matteo; Volpe, Alessandro; Ianniello, Aurora; Franchina, Veronica; Platè, Ilaria; Di Donato, Eleonora; Amato, Giorgio; Salvarani, Carlo; Lucchini, Gianluca; De Lucia, Francesco; Dal Bosco, Ylenia; Molica Colella, Francesco; Santilli, Daniele; Ferrero, Giulio; Marchetta, Antonio; Arrigoni, Eugenio; Riva, Michele; Foti, Rosario; Sandri, Gilda; Bruzzese, Vincenzo; Paroli, Marino; Fusaro, Enrico; Ariani, Alarico
abstract
ound: Psoriatic arthritis (PsA) phenotypes show different responses to the many available drugs. For a tailored medicine, it is important to choose the most effective treatment according to patients’ characteristics. Apremilast is recommended in PsA with moderate activity. In clinical practice, the most suitable PsA patients for apremilast are those affected by the peripheral oligoarticular arthritis. However, it is not so straightforward to definitely identify this phenotype. Musculoskeletal ultrasound (MUS) is a good tool for detecting the joints actually involved by PsA. The aim of this study is to verify if MUS assessment is useful in selecting the best PsA responders to apremilast. Methods: The following data of all consecutive PsA patients from 15 centres were recorded: anamnestic data, disease activity, PsA phenotype, apremilast treatment duration and reason of suspension. MUS assessment before apremilast treatment was the criteria which clustered patients in two groups. Apremilast retention rate estimate the drug’s effectiveness. The Cox analysis revealed the risk factors associated with treatment persistence. Mann-Whitney U and Chi-squared tests assessed the intergroup differences. Results: Only 40% of 356 patients (M:F: 152/204; median age 60 yrs) received MUS examination. In MUS group the moderate disease (median DAPSA 22.9 vs 26.9; p=0.0006) and the oligo-articular phenotype (63.6% vs 36.1%, p<0.0001) were more common. The retention rate was higher in MUS group (HR 0.55 IC95% 0.32-0.94; p=0.03). Conclusion: In apremilast treated PsA patients, baseline MUS assessment is related to an increased retention rate. MUS may identify patients’ characteristics favourable to apremilast response.
2024
- Effectiveness and safety of a 26-week taper regimen of glucocorticoid in GCA patients: Results from a prospective cohort study
[Articolo su rivista]
Muratore, F.; Marvisi, C.; Castrignano, P.; Croci, S.; Bonacini, M.; Boiardi, L.; Ricordi, C.; Galli, E.; Besutti, G.; Spaggiari, L.; Versari, A.; Giorgi Rossi, P.; Pipitone, N.; Salvarani, C.
abstract
Objectives: To assess the effectiveness and safety of the 26-week tapering regimen of glucocorticoids (GC) used in the GiACTA trial in a prospective cohort of treatment-naive, biopsy-proven GCA patients. Methods: Patients with a new diagnosis of biopsy-proven GCA enrolled in the GC arm of the START project (molecular stratification of patients with GCA to tailor GC and tocilizumab therapy) were included. All patients were treated with the 26-week taper regimen of GC used in the GiACTA trial. The primary endpoint was the rate of relapse-free remission at week 52. The secondary endpoints were the proportion of patients with incident aortic damage, cumulative GC doses and GC-related adverse events (AE). Results: 22 patients were included between December 2018 and February 2022. At week 52, 10 patients (45 %, 95 % CI 24–68) were in relapse-free remission. After a median (IQR) follow-up of 35 (22–40) months, 7 patients (32 %, 95 % CI 14–55) were in relapse-free remission. 18 patients with baseline large-vessel imaging underwent CT angiography at the end of the follow-up. No patients had evidence of new aortic dilation, significant progression of aortic damage or large vessel stenosis. 15/22 patients (68 %) had at least one relapse during follow-up. No patients developed visual or cerebrovascular manifestations during relapses. 15/22 (68 %) patients had at least one GC-related AE. Conclusions: A 26 week taper regimen of GC was effective and safe in inducing and maintaining remission in a sizeable proportion of newly diagnosed GCA patients. However, the frequency of GC-related adverse events was high.
2023
- Age at diagnosis influences the clinical phenotype, treatment strategies and outcomes in patients with giant cell arteritis: results from the observational GCAGE study on a large cohort of 1004 patients
[Articolo su rivista]
Monti, Sara; Milanesi, Alessandra; Klersy, Catherine; Tomelleri, Alessandro; Dagna, Lorenzo; Campochiaro, Corrado; Farina, Nicola; Muratore, Francesco; Galli, Elena; Marvisi, Chiara; Bond, Milena; Berti, Alvise; Bortolotti, Roberto; Padoan, Roberto; Schiavon, Franco; Felicetti, Mara; Nannini, Carlotta; Cantini, Fabrizio; Giollo, Alessandro; Rossini, Maurizio; Conticini, Edoardo; Frediani, Bruno; Conti, Fabrizio; Priori, Roberta; Sebastiani, Marco; Cassone, Giulia; Quartuccio, Luca; Treppo, Elena; Bettio, Silvano; Hoxha, Ariela; Lovisotto, Marco; Emmi, Giacomo; Mattioli, Irene; Leccese, Pietro; Caporali, Roberto; Argolini, Lorenza Maria; Foti, Rosario; Visalli, Elisa; Colaci, Michele; Salvarani, Carlo; Montecucco, Carlomaurizio
abstract
Background: Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce. Methods: Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old. Results: The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors. Conclusions: The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.
2023
- Assessing the Ability of Human Dental Pulp Stem Cells to Modulate the Macrophages Phenotype.
[Poster]
Maccaferri, M; Pisciotta, A; Carnevale, G; Salvarani, C; Pignatti, E.
abstract
2023
- COVID-19 vaccination rate and safety profile in a multicentre Italian population affected by mixed cryoglobulinaemic vasculitis
[Articolo su rivista]
Vacchi, Caterina; Testoni, Sofia; Visentini, Marcella; Zani, Roberta; Lauletta, Gianfranco; Gragnani, Laura; Filippini, Davide; Mazzaro, Cesare; Fraticelli, Paolo; Quartuccio, Luca; Padoan, Roberto; Castelnovo, Laura; Zignego, Anna Linda; Ferri, Clodoveo; Scarpato, Salvatore; Casato, Milvia; Hoxha, Ariela; Salvarani, Carlo; Monti, Giuseppe; Galli, Massimo; Sebastiani, Marco
abstract
Mixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterised by heterogeneous clinical manifestations mainly involving lymphatic system, skin, kidney and peripheral nervous system. Although MCV patients have been included in priority programs for vaccination against SARS-CoV-2 in Italy, limited information is available for these patients. Aims of this multicentre Italian study were to investigate SARS-CoV-2 vaccination rate in MCV patients and its safety profile.
2023
- Checkpoint immunitari sulle cellule staminali della polpa dentale umana modulati in vitro da linfociti e monociti da pazienti con artrite reumatoide
[Poster]
Rossi, Alessandro; Bonacini, Martina; Ferrigno, Ilaria; Carnevale, Gianluca; Pisciotta, Alessandra; DI TINCO, Rosanna; Pignatti, Elisa; Catanoso, Mariagrazia; Crescentini, Filippo; Citriniti, Giorgia; Magnani, Luca; Caruso, Andrea; Germanò, Giuseppe; Brandolino, Fabio; Chiapparoli, Ilaria; Dardani, Lucia; Cocchiara, Emanuele; Zerbini, Alessandro; Salvarani, Carlo; Croci, Stefania
abstract
2023
- Covid-19, a new possible mimicker of interstitial lung disease related to primary Sjögren’s syndrome: a case report.
[Articolo su rivista]
Laneri, Alessia; Cerri, Stefania; DELLA CASA, Giovanni; Moretti, Antonio; Manfredi, Andreina; Sebastiani, Marco; Clini, Enrico; Salvarani, Carlo
abstract
Introduction: Acute exacerbation of interstitial lung disease (ILD) and COVID-19 pneumonia show many similarities, but also COVID-19 sequelae, mainly when fibrotic features are present, can be difficult to distinguish from chronic ILD observed in connective tissue diseases (CTD).
Case report: In 2018, a 52-year-old woman, was diagnosed with pSS. The patient complained of no respiratory symptoms and a chest x-Ray was normal.
During March 2020, the patient was hospitalized for acute respiratory failure related to COVID-19 pneumonia. Three months later, follow-up chest HRCT showed ground glass opacity (GGO) and interlobular interstitial thickening. Pulmonary function tests (PFT) showed slight restrictive deficit and mild reduction in diffusion lung of carbon monoxide (DLCO). The patient complained of asthenia and exertional dyspnoea. A multidisciplinary discussion including rheumatologist, pulmonologist, and thoracic radiologist didn’t allow a definitive differential diagnosis between COVID-19 persisting abnormalities and a previous or new-onset pSS-ILD. A wait and see approach was decided, monitoring clinical conditions, PFTs and chest HRCT over time.
Only 2 years after the hospitalization, a slight improvement of clinical symptoms was reported; PFT also improved; a follow-up HRCT showed almost complete resolution of GGO and interlobular interstitial thickening, confirming the diagnostic hypothesis of long-COVID lung manifestations.
Discussion: In the above-reported case report, 3 differential diagnoses were possible: a COVID-19 related ILD, a pre-existing pSS-ILD or a new-onset pSS-ILD triggered by COVID-19. Regardless of the diagnosis, the persistence of clinical and PFT alterations, suggested a chronic disease but, surprisingly, clinical and radiologic manifestations rapidly disappeared after about 2 years.
2023
- EFFETTO DEL MICROAMBIENTE INFIAMMATORIO INDOTTO DAI MONOCITI SUI FIBROBLASTI E AZIONE MODULATORIA DELLE CELLULE STAMINALI DELLA POLPA DENTALE UMANA
[Poster]
Maccaferri, Monia; Corbelli, Tommaso; Lazzari, Giorgia; Pisciotta, Alessandra; Carnevale, Gianluca; Salvarani, Carlo; Pignatti, Elisa
abstract
2023
- Effect of the Inflammatory Microenvironment Induced by Monocytes on Fibroblasts and Modulatory Action of Human Dental Pulp Stem Cells.
[Poster]
Maccaferri, M; Pisciotta, A; Carnevale, G; Salvarani, C; Pignatti, E.
abstract
2023
- Evolution of Rheumatoid-Arthritis-Associated Interstitial Lung Disease in Patients Treated with JAK Inhibitors: A Retrospective Exploratory Study
[Articolo su rivista]
Venerito, Vincenzo; Manfredi, Andreina; Carletto, Antonio; Gentileschi, Stefano; Atzeni, Fabiola; Guiducci, Serena; Lavista, Marlea; La Corte, Laura; Pedrollo, Elisa; Scardapane, Arnaldo; Tomassini, Caterina; Frediani, Bruno; Salvarani, Carlo; Iannone, Florenzo; Sebastiani, Marco
abstract
2023
- Fibrosing Progressive Interstitial Lung Disease in Rheumatoid Arthritis: A Multicentre Italian Study
[Articolo su rivista]
Sebastiani, M.; Venerito, V.; Laurino, E.; Gentileschi, S.; Atzeni, F.; Canofari, C.; Andrisani, D.; Cassone, G.; Lavista, M.; D'Alessandro, F.; Vacchi, C.; Scardapane, A.; Frediani, B.; Cazzato, M.; Salvarani, C.; Iannone, F.; Manfredi, A.
abstract
2023
- Giant Cell Arteritis and Polymyalgia Rheumatica
[Capitolo/Saggio]
Villiger, P. M.; Christ, L.; Seitz, L.; Scholz, G.; Tappeiner, C.; Muratore, F.; Salvarani, C.; Mollan, S.; Quick, V.; Dejaco, C.; Lee, M.; Basu, N.; Miller, N.; Stone, J. H.
abstract
• Giant cell arteritis (GCA) is the most common primary form of vasculitis in adults. GCA has a predilection for involving large- and medium-sized arteries. (It does not involve veins.) • Arteries of the head and neck are often affected by GCA, as are the aorta and its primary branches. • Polymyalgia rheumatica (PMR) can occur simultaneously with or independently of GCA. • The occurrence of GCA or PMR in an individual younger than 50 years of age is exceptionally rare. (Some experts believe, in fact, that such events do not occur at all.) • The GCA/PMR disease spectrum is approximately three times more common in women than in men. • The most dreaded complication of GCA is the acute and permanent loss of vision, which usually occurs through the mechanism of anterior ischemic optic neuropathy (AION). Other feared long-term complications are those related to large-vessel events such as aortic aneurysms. • Temporal artery biopsy has been the traditional gold standard for the diagnosis of GCA. The sensitivity of this test is not known for certain, but it is probably poor—on the order of 60–70%. Large-vessel imaging studies are playing an increasing role in the diagnosis of GCA. The most important diagnostic test, however, remains the clinical history taken by an astute clinician. • The diagnosis of PMR is a clinical one, based essentially entirely upon the history and physical examination. • When considering the diagnosis of PMR, it is crucial to exclude the concomitant occurrence of GCA and the alternative diagnosis of rheumatoid arthritis. • Acute phase reactants are usually elevated in patients with GCA and PMR, but cases of these diagnoses occurring with completely normal values of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are well documented. • Glucocorticoids remain a cornerstone of treating GCA and PMR, but clinicians should move quickly to steroid-sparing agents in the interest of reducing glucocorticoid toxicity. Interleukin-6 receptor (IL6-R) blockade is an excellent treatment for GCA.
2023
- Human dental pulp stem cells (hDPSCs) promote the lipofibroblast transition in the early stage of a fibro-inflammatory process
[Articolo su rivista]
Pisciotta, Alessandra; DI TINCO, Rosanna; Bertani, Giulia; Orlandi, Giulia; Bertoni, Laura; Pignatti, Elisa; Orciani, Monia; Sena, Paola; Bertacchini, Jessika; Salvarani, Carlo; Carnevale, Gianluca
abstract
Introduction: In autoimmune diseases, particularly in systemic sclerosis and chronic periaortitis, a strict correlation between chronic inflammation and fibrosis exists. Since the currently used drugs prove mostly effective in suppressing inflammation, a better comprehension of the molecular mechanisms exerted by cell types implicated in fibro-inflammation is needed to develop novel therapeutic strategies. Mesenchymal stromal/stem cells (MSCs) are being matter of deep investigation to unveil their role in the evolution of fibrogenetic process. Several findings pointed out the controversial implication of MSCs in these events, with reports lining at a beneficial effect exerted by external MSCs and others highlighting a direct contribution of resident MSCs in fibrosis progression. Human dental pulp stem cells (hDPSCs) have demonstrated to hold promise as potential therapeutic tools due to their immunomodulatory properties, which strongly support their contribution to tissue regeneration.
Methods: Our present study evaluated hDPSCs response to a fibro-inflammatory microenvironment, mimicked in vitro by a transwell co-culture system with human dermal fibroblasts, at early and late culture passages, in presence of TGF-β1, a master promoter of fibrogenesis.
Results and Discussion: We observed that hDPSCs, exposed to acute fibro-inflammatory stimuli, promote a myofibroblast-to-lipofibroblast transition, likely based on BMP2 dependent pathways. Conversely, when a chronic fibro-inflammatory microenvironment is generated, hDPSCs reduce their anti-fibrotic effect and acquire a pro-fibrotic phenotype. These data provide the basis for further investigations on the response of hDPSCs to varying fibro-inflammatory conditions.
2023
- Interstitial lung disease in microscopic polyangiitis and granulomatosis with polyangiitis: demographic, clinical, serological and radiological features of an Italian cohort from the Italian Society for Rheumatology
[Articolo su rivista]
Manfredi, Andreina; Cassone, Giulia; Izzo, Raffaella; Dallagiacoma, Gloria; Felicetti, Mara; Cariddi, Adriana; Berti, Alvise; Giollo, Alessandro; Nannini, Carlotta; Bettio, Silvano; Monti, Sara; Conticini, Edoardo; Govoni, Marcello; Quartuccio, Luca; Argolini, Lorenza Maria; Kaleci, Shaniko; Emmi, Giacomo; Dejaco, Christian; Padoan, Roberto; Dagna, Lorenzo; Rossini, Maurizio; Cantini, Fabrizio; Montecucco, Carlomaurizio; Frediani, Bruno; De Vita, Salvatore; Caporali, Roberto; Muratore, Francesco; Sebastiani, Marco; Salvarani, Carlo
abstract
2023
- Intracranial Stenosis Treated with Stenting in Patients with Suspected Cerebral Vasculitis: Two Case Reports
[Articolo su rivista]
Vandelli, G; Giacobazzi, L; Ciolli, L; Dell'Acqua, Ml; Vandelli, L; Picchetto, L; Rosafio, F; Borzi, Gm; Ricceri, R; Meletti, S; Vallone, S; Salvarani, C; Sebastiani, M; Sacchetti, F; Verganti, L; Merolla, S; Zelent, G; Bigliardi, G
abstract
Central nervous system vasculitis (CNSV) is an uncommon and poorly understood form of vasculitis. Early recognition is important because medical treatment might improve the outcome. However, randomized clinical trials on CNSV treatment do not exist. Endovascular treatment has been reported in few cases, but no data exist for intracranial stenting. We report 2 cases of patients with suspected CNSV and recurrent clinical episodes, treated with intracranial stenting. A 48-year-old man had relapsing episodes of right hemiparesis. Neuroradiological exams showed severe left carotid terminus stenosis. Despite immunosuppressive therapy, neuroradiological follow-up exams showed a worsening of the aforementioned stenosis with many transient episodes of weakness in the right limbs and aphasia. A 64-year-old woman had a sudden onset of dysarthria and transient aphasia. Neuroradiological exams showed a severe arterial stenosis involving the origin of left anterior cerebral artery and middle cerebral artery (MCA). Despite dual antiplatelet therapy, she presented an acute onset of severe aphasia, due to an occlusion of the left carotid terminus and proximal MCA. In both cases, endovascular procedure and intracranial stenting was performed, with marked improvement of cerebral blood flow. No more clinical episodes were reported. Intracranial stenting may be a valid therapeutic option in selected patients with CNSV and involvement of medium or large size vessels with clinical worsening despite best medical treatment.
2023
- Lancet Respir Med 2023 (vol 11, pg 3, 2023 )
[Articolo su rivista]
Manfredi, A; Salvarani, C; Sebastiani, M
abstract
2023
- Management of psoriatic arthritis: a consensus opinion by expert rheumatologists
[Articolo su rivista]
D'Angelo, Salvatore; Atzeni, Fabiola; Benucci, Maurizio; Bianchi, Gerolamo; Cantini, Fabrizio; Caporali, Roberto Felice; Carlino, Giorgio; Caso, Francesco; Cauli, Alberto; Ciccia, Francesco; D'Agostino, Maria Antonietta; Dagna, Lorenzo; Dejaco, Christian; Epis, Oscar Massimiliano; Ferrucci, Maria Grazia; Franceschini, Franco; Fusaro, Enrico; Gabini, Marco; Gerli, Roberto; Giacomelli, Roberto; Govoni, Marcello; Gremese, Elisa; Guggino, Giuliana; Iagnocco, Annamaria; Iannone, Florenzo; Laganà, Bruno; Lubrano, Ennio; Montecucco, Carlomaurizio; Peluso, Rosario; Ramonda, Roberta; Rossini, Maurizio; Salvarani, Carlo; Sebastiani, Gian Domenico; Sebastiani, Marco; Selmi, Carlo; Tirri, Enrico; Marchesoni, Antonio
abstract
Background: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease involving several articular and extra-articular structures. Despite the important progresses recently made in all of the aspects of this disease, its management is still burdened by unresolved issues. The aim of this exercise was to provide a set of statements that may be helpful for the management of PsA. Methods: A group of 38 Italian rheumatologists with recognized expertise in PsA selected and addressed the following four topics: "early PsA," "axial-PsA," "extra-articular manifestations and comorbidities," "therapeutic goals." Relevant articles from the literature (2016-2022) were selected by the experts based on a PubMed search. A number of statements for each topic were elaborated. Results: Ninety-four articles were selected and evaluated, 68 out of the 1,114 yielded by the literature search and 26 added by the Authors. Each of the four topic was subdivided in themes as follows: transition from psoriasis to PsA, imaging vs. CASPAR criteria in early diagnosis, early treatment for "early PsA"; axial-PsA vs. axialspondyloarthritis, diagnosis, clinical evaluation, treatment, standard radiography vs. magnetic resonance imaging for "axial PsA"; influence of inflammatory bowel disease on the therapeutic choice, cardiovascular comorbidity, bone damage, risk of infection for "comorbidities and extra-articular manifestations"; target and tools, treat-to-target strategy, role of imaging for "therapeutic goals." The final document consisted of 49 statements. Discussion: The final product of this exercise is a set of statements concerning the main issues of PsA management offering an expert opinion for some unmet needs of this complex disease.
2023
- One-year clinical experience on the use of Nintedanib in Systemic Sclerosis
[Articolo su rivista]
Magnani, Luca; Spinella, Amelia; Testoni, Sofia; Lumetti, Federica; Scelfo, Chiara; Dardani, Lucia; Bajocchi, Gianluigi; Clini, Enrico; Salvarani, Carlo; Giuggioli, Dilia
abstract
AIM- Systemic Sclerosis (SSc) is a complex autoimmune disease characterized by vascular damage, immune activation and fibrosis of the skin and internal organs. Interstitial lung disease (ILD) is one of the most common causes of death. In 2019 Nintedanib was approved for SSc-related ILD, due to randomized clinical trials (RCTs) demonstrating a reduction in the annual rate of decline in Forced Vital Capacity (FVC).
METHODS
We reviewed eleven patients with SSc-related ILD from January 2020 to January 2021 and who started Nintedanib 150 mg twice a day.
RESULTS- Non-Specific Interstitial Pneumonia (NSIP) was the most frequent HRCT pattern, followed by Usual Interstitial Pneumonia (UIP) and UIP/NSIP pattern. The mean of Modified Rodnan Skin Score (mRSS) at baseline was 9.23 (±10SD) points without any significant improvement during the follow-up. Patients continued their ongoing therapy for lung involvement. Mean FVC was 2233.6 ml [+/- 1066 ml] (61.3% predicted) at beginning and remained stable during the follow-up period. The mean modified British Council Medical Questionnaire (mmRC) decreased from 3 at baseline to 2.5 at the end of follow up and the mean of the Borg scale of dyspnea ameliorated from 7.27 at baseline to 6 at twelve months. Both the differences were not significant. Two patients stop therapy: one for partial intestinal obstruction and one for incoercible diarrhea.
CONCLUSION- Nintedanib was generally well tolerated and we did not record any serious adverse event
2023
- POS0855 EVOLUTION OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE IN PATIENTS TREATED WITH JAK INHIBITORS: A MULTICENTER RETROSPECTIVE STUDY
[Abstract in Rivista]
Venerito, V.; Manfredi, A.; Carletto, A.; Gentileschi, S.; Atzeni, F.; Guiducci, S.; Lavista, M.; La Corte, L.; Pedrollo, E.; Scardapane, A.; Tomassini, C.; Frediani, B.; Salvarani, C.; Iannone, F.; Sebastiani, M.
abstract
2023
- Predictors of DAPSA Response in Psoriatic Arthritis Patients Treated with Apremilast in a Retrospective Observational Multi-Centric Study (2023-02-07)
[Articolo su rivista]
Becciolini, Andrea; Parisi, Simone; Del Medico, Patrizia; Farina, Antonella; Visalli, Elisa; Biagio Molica Colella, Aldo; Lumetti, Federica; Caccavale, Rosalba; Scolieri, Palma; Andracco, Romina; Girelli, Francesco; Bravi, Elena; Colina Alessandro Volpe, Matteo; Ianniello, Aurora; Chiara Ditto, Maria; Nucera, Valeria; Franchina, Veronica; Platè, Ilaria; Di Donato, Eleonora; Amato, Giorgio; Salvarani, Carlo; Bernardi, Simone; Lucchini, Gianluca; De Lucia, Francesco; Molica Colella, Francesco; Santilli, Daniele; Mansueto, Natalia; Ferrero, Giulio; Marchetta, Antonio; Arrigoni, Eugenio; Foti, Rosario; Sandri, Gilda; Bruzzese, Vincenzo; Paroli, Marino; Fusaro, Enrico; Ariani, Alarico
abstract
Background: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. Methods: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann–Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. Results: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804–0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883–0.939; p < 0.01). Conclusions: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA.
2023
- Prevalence and distribution of vascular calcifications at CT scan in patients with and without large vessel vasculitis: A matched cross-sectional study
[Articolo su rivista]
Besutti, G.; Marvisi, C.; Mancuso, P.; Fari, R.; Monelli, F.; Revelli, M.; Durmo, R.; Galli, E.; Muratore, F.; Spaggiari, L.; Ottone, M.; Luminari, S.; Pattacini, P.; Giorgi Rossi, P.; Salvarani, C.
abstract
Objectives The aim of this study was to compare the prevalence, entity and local distribution of arterial wall calcifications evaluated on CT scans in patients with large vessel vasculitis (LVV) and patients with lymphoma as reference for the population without LVV. Methods All consecutive patients diagnosed with LVVs with available baseline positron emission tomography-CT (PET-CT) scan performed between 2007 and 2019 were included; non-LVV patients were lymphoma patients matched by age (±5 years), sex and year of baseline PET-CT (≤2013; >2013). CT images derived from baseline PET-CT scans of both patient groups were retrospectively reviewed by a single radiologist who, after setting a threshold of minimum 130 Hounsfield units, semiautomatically computed vascular calcifications in three separate locations (coronaries, thoracic and abdominal arteries), quantified as Agatston and volume scores. Results A total of 266 patients were included. Abdominal artery calcifications were equally distributed (mean volume 3220 in LVVs and 2712 in lymphomas). Being in the LVVs group was associated with the presence of thoracic calcifications after adjusting by age and year of diagnosis (OR 4.13, 95% CI 1.35 to 12.66; p=0.013). Similarly, LVVs group was significantly associated with the volume score in the thoracic arteries (p=0.048). In patients >50 years old, calcifications in the coronaries were more extended in non-LVV patients (p=0.027 for volume). Conclusion When compared with patients without LVVs, LVVs patients have higher calcifications in the thoracic arteries, but not in coronary and abdominal arteries.
2023
- Pros and cons of TNF inhibitors and tocilizumab in the treatment of large-vessel vasculitis
[Articolo su rivista]
Marvisi, C.; Ricordi, C.; Galli, E.; Muratore, F.; Boiardi, L.; Macchioni, P. L.; Pipitone, N.; Macaluso, F.; Salvarani, C.; Brandolino, F.
abstract
Large-vessel vasculitides (LVVs) include giant cell arteritis (GCA) and Takayasu’s arteritis (TAK). Even if similar, these two entities differ in terms of treatment and outcomes. High doses of glucocorticoids (GCs) are still the first choice for the treatment of both conditions. However, adjunctive therapies are recommended in selected patients in order to decrease the risk of relapse and the amount of side effects related to GCs. Tumour necrosis factor a inhibitors (TNFis) and tocilizumab (TCZ) are used for the treatment of LVVs, with some differences. In GCA, TCZ has been proved to be effective and safe in inducing remission with some open questions still remaining, whereas data about TNFis are scarce and non-conclusive. On the contrary, in TAK either TNFis or TCZ seem to be able to control symptoms and angiographic progression in refractory forms. However, their place in the management of treatment must still be clarified, and as a result the American College of Rheumatology and EULAR guidelines slightly differ in the recommendations about when and what treatment to start. Thus, the aim of this review is to look at the evidence on the use of TNFis and TCZ in LVVs, outlining the pros and cons of both therapies.
2023
- Reduced Graphene Oxide Electrolyte-Gated Transistor Immunosensor with Highly Selective Multiparametric Detection of Anti-Drug Antibodies
[Articolo su rivista]
Sensi, M.; de Oliveira, R. F.; Berto, M.; Palmieri, M.; Ruini, E.; Livio, P. A.; Conti, A.; Pinti, M.; Salvarani, C.; Cossarizza, A.; Cabot, J. M.; Ricart, J.; Casalini, S.; Gonzalez-Garcia, M. B.; Fanjul-Bolado, P.; Bortolotti, C. A.; Samori, P.; Biscarini, F.
abstract
The advent of immunotherapies with biological drugs has revolutionized the treatment of cancers and auto-immune diseases. However, in some patients, the production of anti-drug antibodies (ADAs) hampers the drug efficacy. The concentration of ADAs is typically in the range of 1-10 pm; hence their immunodetection is challenging. ADAs toward Infliximab (IFX), a drug used to treat rheumatoid arthritis and other auto-immune diseases, are focussed. An ambipolar electrolyte-gated transistor (EGT) immunosensor is reported based on a reduced graphene oxide (rGO) channel and IFX bound to the gate electrode as the specific probe. The rGO-EGTs are easy to fabricate and exhibit low voltage operations (& LE; 0.3 V), a robust response within 15 min, and ultra-high sensitivity (10 am limit of detection). A multiparametric analysis of the whole rGO-EGT transfer curves based on the type-I generalized extreme value distribution is proposed. It is demonstrated that it allows to selectively quantify ADAs also in the co-presence of its antagonist tumor necrosis factor alpha (TNF-alpha), the natural circulating target of IFX.
2023
- Reply
[Articolo su rivista]
Muratore, F.; Marvisi, C.; Galli, E.; Boiardi, L.; Salvarani, C.
abstract
2023
- Reply to Comment on: Vasculitis, fibromuscular dysplasia or hereditary aneurysms? by Marvisi et al
[Articolo su rivista]
Marvisi, C.; Castrignano, P.; Besutti, G.; Spaggiari, L.; Caruso, A.; Muratore, F.; Salvarani, C.
abstract
2023
- Rituximab for connective tissue disease-associated interstitial lung disease
[Articolo su rivista]
Manfredi, Andreina; Salvarani, Carlo; Sebastiani, Marco
abstract
2023
- Steroid-sparing agents in polymyalgia rheumatica: how will they fit into the treatment paradigm?
[Articolo su rivista]
Ricordi, C.; Pipitone, N.; Marvisi, C.; Muratore, F.; Salvarani, C.
abstract
Introduction: Polymyalgia rheumatica is a common inflammatory rheumatic disease in subjects aged 50 years or older and classically presents with shoulder and/or pelvic girdle pain and prolonged morning stiffness. Glucocorticoids represent the standard of treatment; glucocorticoid therapy is usually required for 1–2 years and often results in significant glucocorticoid-related side effects, especially in the elderly. Areas covered: In this review, we aimed to provide a comprehensive overview of the management of polymyalgia rheumatica, with a particular focus on adjunctive therapies to the standard glucocorticoid treatment. Expert opinion: Given the high frequency of disease relapses (one-third of patients) and the adverse events related to prolonged glucocorticoid use, the need for glucocorticoid-sparing agents remains an important issue in the management of polymyalgia rheumatica. In selected patients, who are at risk for glucocorticoid-related side effects or in those with glucocorticoid-refractory disease, the addition of a glucocorticoid-sparing agent, either a synthetic or biologic disease-modifying anti-rheumatic drug, may represent a reasonable and effective therapeutic approach.
2023
- Studio in vitro dei tempi di risposta dei sinoviociti di tipo fibroblastico allo stimolo infiammatorio
[Poster]
Maccaferri, M.; Corbelli, T.; Lazzari, G.; Salvarani, C.; Pignatti, E.
abstract
2023
- Subclinical giant cell arteritis in polymyalgia rheumatica: Concurrent conditions or a common spectrum of inflammatory diseases?
[Articolo su rivista]
Salvarani, C.; Padoan, R.; Iorio, L.; Tomelleri, A.; Terrier, B.; Muratore, F.; Dasgupta, B.
abstract
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common conditions in older adults. Their clinical connection has been recognized over time, with many patients experiencing both conditions separately, simultaneously or in temporal sequence to each other. Early GCA detection is essential to prevent vascular damage, but identifying subclinical GCA in PMR patients remains a challenge and routine screening is not standard practice. Subclinical GCA prevalence in newly diagnosed PMR patients ranges from 23 to 29%, depending on the screening method. Vessel wall imaging and temporal artery biopsy can detect subclinical GCA. Epidemiology and trigger factors show similarities between the two conditions, but PMR is more common than GCA. Genetic and pathogenesis studies reveal shared inflammatory mechanisms involving dendritic cells, pro-inflammatory macrophages, and an IL-6 signature. However, the inflammatory infiltrates differ, with extensive T cell infiltrates seen in GCA while PMR shows an incomplete profile of T cell and macrophage-derived cytokines. Glucocorticoid treatment is effective for both conditions, but the steroid requirements vary. PMR overall mortality might be similar to the general population, while GCA patients with aortic inflammatory aneurysms face increased mortality risk. The GCA-PMR association warrants further research. Considering their kinship, recently the term GCA-PMR Spectrum Disease (GPSD) has been proposed.
2023
- Takayasu arteritis and large-vessel giant cell arteritis in Italian population. Comprehensive analysis from a single institutional cohort of 184 cases
[Articolo su rivista]
Boiardi, Luigi; Galli, Elena; Macchioni, Pierluigi; Muratore, Francesco; Klinowski, Giulia; Hunder, Gene G; Casali, Massimiliano; Besutti, Giulia; Spaggiari, Lucia; Versari, Annibale; Croci, Stefania; Mancuso, Pamela; Rossi, Paolo Giorgi; Marvisi, Chiara; Salvarani, Carlo
abstract
Objective: To compare clinical and imaging characteristics in patients with Takayasu arteritis (TAK) and large vessel-giant cell arteritis (LV-GCA) in an Italian population. Methods: We conducted a retrospective monocenter study comparing characteristics and outcomes of a cohort of 59 patients with TAK and a cohort of 127 patients with LV-GCA diagnosed between 1996 and 2016. Most of them (92%) were followed up for at least 24 months at Reggio Emilia Hospital (Italy). We also reviewed the literature discussing the results of the published manuscripts comparing LV-GCA to TAK Results: LV-GCA patients had a higher prevalence of males (p = 0.003), and more frequently presented with cranial symptoms (p = 0.001), fever >= 38 degrees C (p = 0.007), polymyalgia rheumatica (p = 0.001), and hypertension (p = 0.001), and they had higher ESR levels at diagnosis (p = 0.0001). Differently, TAK patients had longer delay to diagnosis from the beginning of symptoms (p = 0.048), they presented more frequently with loss of pulses of large arteries (p = 0.0001), vascular bruits (p = 0.001), limb claudication (p = 0.003), myocardial infarction/ angina (p = 0.03), and hypertension induced by renal artery stenosis (p = 0.001). Regarding treatment, TAK patients received a higher total and at 1 year cumulative prednisone doses (p = 0.0001 and p = 0.001, respectively), they had a longer duration of prednisone therapy (p = 0.008), and received during follow-up more frequently traditional immunosuppressants (p = 0.0001) and biological agents (p = 0.0001). Flares were more frequently observed in TAK patient (p = 0.001), while no differences were observed for long-term remission. New vascular procedures during the follow-up were more frequently performed in TAK patients (p = 0.0001). Regarding imaging at diagnosis, TAK patients had more frequently vascular stenosis/occlusion (p = 0.0001) and a higher number of vessels with structural damage per person (p = 0.0001), while LV-GCA patients had a higher number of inflamed vessels per person (p = 0.0001).
2023
- The Role of PET in the Diagnosis and Disease Activity Assessment in Large Vessel Vasculitis
[Articolo su rivista]
Marvisi, C.; Galli, E.; Ricordi, C.; Durmo, R.; Roncali, M.; Muratore, F.; Salvarani, C.; Versari, A.
abstract
The role of 18F-fluorodeoxyglucose (FDG) positron emission tomography (18F-FDG PET) in the diagnosis of large vessel vasculitis (LVV) is well established. It permits us to assess the extent and the grade of vascular involvement and to rule out the other causes in clinical scenarios characterized by less specific symptoms. The advantages of 18F-FDG PET are far less clear in monitoring disease activity over time. Studies looking for the role of 18F-FDG PET as a potential biomarker had conflicting results and whether and when to repeat it during follow-up is based on clinical experience. A comprehensive assessment, including clinical, laboratory and morphological imaging is still required to monitor patients with large-vessel vasculitis over time. The aim of this review is to present more recent data about the utility of 18 F-FDG PET in the diagnosis and follow-up of LVV.
2023
- The importance of defining which Janus kinases are activated in giant cell arteritis
[Articolo su rivista]
Bonacini, M.; Rossi, A.; Ferrigno, I.; Muratore, F.; Salvarani, C.; Croci, S.
abstract
2023
- The usual Interstitial pneumonia pattern in autoimmune rheumatic diseases
[Articolo su rivista]
Luppi, Fabrizio; Manfredi, Andreina; Faverio, Paola; Andersen, Michael Brun; Bono, Francesca; Pagni, Fabio; Salvarani, Carlo; Bendstrup, Elisabeth; Sebastiani, Marco
abstract
: Usual Interstitial Pneumonia (UIP) is characterized by progression of lung parenchyma that may be observed in various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis and connective tissue diseases. From a diagnostic point of view, a UIP pattern related to ARDs may display imaging and pathological features able to distinguish it from that related to IPF, such as the "straight-edge" sign at HRCT and lymphoplasmacytic infiltrates at histologic specimens. Multidisciplinary approach (MDD), involving at least pulmonologist, rheumatologist and radiologist, is fundamental in the differential diagnosis process, but MDD is also required in the evaluation of severity, progression and response to treatment, that is based on the combination of changes in symptoms, pulmonary function trends, and, in selected patients, serial CT evaluation. Differently from IPF, in patients with ARDs both functional evaluation and patient-reported outcomes may be affected by systemic involvement and comorbidities, including musculoskeletal manifestations of disease. Finally, in regards to pharmacological treatment, immunosuppressants have been considered the cornerstone of therapy, despite the lack of solid evidence in most cases; recently, antifibrotic drugs were also proposed for the treatment of progressive fibrosing ILDs other than IPF. In ARD-ILD, the therapeutic choice should balance the need for the control of systemic and lung involvements with the risk of adverse events from multi-morbidities and -therapies. Purpose of this review is to summarize the definition, the radiological and morphological features of the UIP pattern in ARDs, together with risk factors, diagnostic criteria, prognostic evaluation, monitoring and management approaches of the UIP-ARDs.
2023
- Therapeutic Effects of Apremilast on Enthesitis and Dactylitis in Real Clinical Setting: An Italian Multicenter Study
[Articolo su rivista]
Lo Gullo, A.; Becciolini, A.; Parisi, S.; Del Medico, P.; Farina, A.; Visalli, E.; Dal Bosco, Y.; Molica Colella, A. B.; Lumetti, F.; Caccavale, R.; Scolieri, P.; Andracco, R.; Girelli, F.; Bravi, E.; Colina, M.; Volpe, A.; Ianniello, A.; Ditto, M. C.; Nucera, V.; Franchina, V.; Plate, I.; Di Donato, E.; Amato, G.; Salvarani, C.; Bernardi, S.; Lucchini, G.; De Lucia, F.; Molica Colella, F.; Santilli, D.; Mansueto, N.; Ferrero, G.; Marchetta, A.; Arrigoni, E.; Foti, R.; Sandri, G.; Bruzzese, V.; Paroli, M.; Fusaro, E.; Ariani, A.
abstract
Introduction: Enthesitis and dactylitis are difficult-to-treat features of psoriatic arthritis (PsA), leading to disability and affecting quality of life. Objective: The aim of this study is to evaluate enthesitis (using the Leed enthesitis index (LEI)) and dactylitis at 6 and 12 months in patients treated with apremilast. Methods: Patients affected by PsA from fifteen Italian rheumatological referral centers were screened. The inclusion criteria were: (a) enthesitis or dactylitisphenotype; (b) treatment with apremilast 30 mg bid. Clinical and treatment history, including PsA disease activity, were recorded. Mann–Whitney and chi-squared tests were used to assess the differences between independent groups, and Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. A p-value of <0.05 was considered statistically significant. Results: The Eph cohort consisted of 118 patients (median LEI 3); the Dph cohort included 96 patients with a median dactylitis of 1 (IQR 1–2). According to an intention to treat analysis, 25% and 34% of patients with enthesitis achieved remission (i.e., LEI = 0) in T1 and T2. The remission of dactylitis was 47% in T1 and 44% in T2. The per protocol analysis (patients observed for at least 12 months) showed that both dactylitis and LEI significantly improved in T1 (median LEI 1 (IQR 1–3)) and T2 (median LEI 0 (IQR 1–2)). Conclusion: Eph and Dph PsA patients treated with apremilast experienced a significant improvement in enthesitis and dactylitis activity. After 1 year, enthesitis and dactylitis remission was achieved in more than one-third of patients.
2023
- Topical Cannabidiol in the Treatment of digital ulcers in patients with Scleroderma: comparative Analysis and Literature Review
[Articolo su rivista]
Spinella, Amelia; DE PINTO, Marco; Baraldi, Carlo; Galluzzo, Claudio; Testoni, Sofia; Lumetti, Federica; Parenti, Luca; Guerzoni, Simona; Salvarani, Carlo; Giuggioli, Dilia
abstract
OBJECTIVE To explore the effect of topical cannabidiol (CBD) in treating digital ulcers in patients with systemic sclerosis (SSc). METHODS In total, 45 patients with SSc who had digital ulcers were consecutively enrolled between January 2019 and December 2019. Of the participants, 25 were treated with CBD during surgical debridement and 20 were treated with standard local therapy. A numeric rating scale for pain and Health Assessment Questionnaire Disability Index were administered at the baseline and at the end of treatment. RESULTS Local treatment with CBD was significantly associated with lower pain scores, higher health assessment scores, and an increase in participants' total hours of sleep. Patients in the control group more frequently required additional analgesic therapy. CONCLUSIONS Topical CBD may be a valuable tool to treat pain related to digital ulcers in patients with SSc.
2023
- Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study
[Articolo su rivista]
Luchetti Gentiloni, M. M.; Paci, V.; Carletto, A.; Zabotti, A.; Ramonda, R.; Chimenti, M. S.; Dagna, L.; Luciano, N.; Piccinelli, A.; Giovannini, I.; Striani, G.; Boffini, N.; Sandri, G.; Possemato, N.; Pantano, I.; Benfaremo, D.; Salvarani, C.; Ciccia, F.; Selmi, C.; Moroncini, G.
abstract
Background: Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA. Methods: One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis. Results: At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs. At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 ± 13.5 (p < 0.001) for DAPSA and 1.21 ± 0.97 (p < 0.001) for ASDAS-CRP. Thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03-6.25 p = 0.043), being naïve to biological DMARDs (OR 4.13, 95% CI 1.34-12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02-6.12, p = 0.046) were associated with MDA response at week 24. Conclusions: This is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6 months.
2023
- Updates on the diagnosis and monitoring of giant cell arteritis
[Articolo su rivista]
Monti, Sara; Schäfer, Valentin Sebastian; Muratore, Francesco; Salvarani, Carlo; Montecucco, Carlomaurizio; Luqmani, Raashid
abstract
: This mini-review offers a critical appraisal of the currently employed imaging or histopathological tools to diagnose and monitor giant cell arteritis (GCA). An overview of the most updated evidence and current application of color duplex ultrasonography (US), temporal artery biopsy (TAB), 18-fluorodeoxyglucose [18F] FDG-PET/CT, magnetic resonance imaging, and computed tomography angiography is provided. The main limitations of each tool, and the most relevant research developments are discussed. The review highlights the complementary value of the available modalities to ensure a correct diagnosis of GCA, and to provide valuable prognostic information. Novel evidence is accumulating to support the role of imaging, and particularly US, as a monitoring tool for the disease, opening new perspectives for the future management of large vessel vasculitis.
2022
- 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis With Polyangiitis
[Articolo su rivista]
Grayson, P. C.; Ponte, C.; Suppiah, R.; Robson, J. C.; Craven, A.; Judge, A.; Khalid, S.; Hutchings, A.; Luqmani, R. A.; Watts, R. A.; Merkel, P. A.; Gatenby, P.; Hill, C.; Ranganathan, D.; Kronbichler, A.; Blockmans, D.; Barra, L.; Carette, S.; Pagnoux, C.; Dhindsa, N.; Fifi-Mah, A.; Khalidi, N.; Liang, P.; Milman, N.; Pineau, C.; Tian, X.; Wang, G.; Wang, T.; Zhao, M. -H.; Tesar, V.; Baslund, B.; Hammam, N.; Shahin, A.; Pirila, L.; Putaala, J.; Hellmich, B.; Henes, J.; Lamprecht, P.; Neumann, T.; Schmidt, W.; Sunderkoetter, C.; Szekanecz, Z.; Danda, D.; Das, S.; Gupta, R.; Rajasekhar, L.; Sharma, A.; Wagh, S.; Clarkson, M.; Molloy, E.; Salvarani, C.; Schiavon, F.; Tombetti, E.; Vaglio, A.; Amano, K.; Arimura, Y.; Dobashi, H.; Fujimoto, S.; Harigai, M.; Hirano, F.; Hirahashi, J.; Honma, S.; Kawakami, T.; Kobayashi, S.; Kono, H.; Makino, H.; Matsui, K.; Muso, E.; Suzuki, K.; Ikeda, K.; Takeuchi, T.; Tsukamoto, T.; Uchida, S.; Wada, T.; Yamada, H.; Yamagata, K.; Yumura, W.; Lai, K. S.; Flores-Suarez, L. F.; Hinojosa, A.; Rutgers, B.; Tak, P. -P.; Grainger, R.; Quincey, V.; Stamp, L.; Suppiah, R.; Besada, E.; Diamantopoulos, A.; Sznajd, J.; Azevedo, E.; Geraldes, R.; Rodrigues, M.; Santos, E.; Song, Y. -W.; Moiseev, S.; Hocevar, A.; Cid, M. C.; Moreno, X. S.; Atukorala, I.; Berglin, E.; Mohammed, A.; Segelmark, M.; Daikeler, T.; Direskeneli, H.; Hatemi, G.; Kamali, S.; Karadag, O.; Pehlevan, S.; Adler, M.; Basu, N.; Bruce, I.; Chakravarty, K.; Dasgupta, B.; Flossmann, O.; Gendi, N.; Hassan, A.; Hoyles, R.; Jayne, D.; Jones, C.; Klocke, R.; Lanyon, P.; Laversuch, C.; Luqmani, R.; Robson, J.; Magliano, M.; Mason, J.; Maw, W. W.; Mcinnes, I.; Mclaren, J.; Morgan, M.; Morgan, A.; Mukhtyar, C.; O'Riordan, E.; Patel, S.; Peall, A.; Robson, J.; Venkatachalam, S.; Vermaak, E.; Menon, A.; Watts, R.; Yee, C. -S.; Albert, D.; Calabrese, L.; Chung, S.; Forbess, L.; Gaffo, A.; Gewurz-Singer, O.; Grayson, P.; Liang, K.; Matteson, E.; Merkel, P. A.; Springer, J.; Sreih, A.
abstract
Objective: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1 × 109/liter (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti–proteinase 3 ANCA positivity (−3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1), and hematuria (−1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% confidence interval [95% CI] 77–91%) and the specificity was 99% (95% CI 98–100%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for EGPA demonstrate strong performance characteristics and are validated for use in research.
2022
- Adalimumab and ABP 501 in the Treatment of a Large Cohort of Patients with Inflammatory Arthritis: A Real Life Retrospective Analysis
[Working paper]
Becciolini, Andrea; Parisi, Simone; Caccavale, Rosalba; Bravi, Elena; Lumetti, Federica; Andracco, Romina; Volpe, Alessandro; Gardelli, Lucia; Girelli, Francesco; Di Donato, Eleonora; Santilli, Daniele; Lucchini, Gianluca; Ditto, Maria Chiara; Platè, Ilaria; Arrigoni, Eugenio; Mozzani, Flavio; Riva, Michele; Marchetta, Antonio; Fusaro, Enrico; Sandri, Gilda; Salvarani, Carlo; Paroli, Marino; Ariani, Alarico
abstract
The recent introduction of ABP 501, an adalimumab biosimilar, in the treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand, observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking. The main aim of this study is to compare the clinical outcomes of the treatment with adalimumab, both the originator and ABP 501, in a large cohort of patients affected by autoimmune arthritis in a real life setting. We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or ABP 501) from January 2003 to December 2020. We stratified the study population according to adalimumab use: naive to original (oADA), naive to ABP 501 (bADA) and switched from original to ABP 501 (sADA). The oADA, bADA and sADA groups included, respectively, 724, 129 and 193 patients. In each group, the majority of patients had a diagnosis of rheumatoid arthritis. The total observation period was 9805.6 patient-months. The 18-month retentions rate in oADA, bADA and sADA was, respectively, 81.5%, 84.0% and 88.0% (p > 0.05). The factors influencing the adalimumab retention rate were an axial spondylarthritis diagnosis (Hazard Ratio (HR) 0.70; p = 0.04), switch from oADA to ABP 501 (HR 0.53; p = 0.02) and year of prescription (HR 1.04; p = 0.04). In this retrospective study, patients naive to the adalimumab originator and its biosimilar ABP 501 showed the same retention rate. Patients switching from the originator to biosimilar had a higher retention rate, even though not statistically significant, when compared to naive.
2022
- Apremilast retention rate in clinical practice: observations from an Italian multi-center study
[Articolo su rivista]
Ariani, A1; Parisi, S2; Del Medico, P3; Farina, A4; Visalli, E5; Molica Colella, Ab6; Lumetti, F7; Caccavale, R8; Scolieri, P9; Andracco, R10; Girelli, F11; Bravi, E12; Colina, M13; Volpe, A14; Ianniello, A15; Franchina, V16; Platè, I12; Di Donato, E1; Amato, G5; Salvarani, C17; Lucchini, G1; De Lucia, F5; Molica Colella, F18; Santilli, D1; Ferrero, G19; Marchetta, A14; Arrigoni, E12; Mozzani, F1; Foti, R5; Sandri, G; Bruzzese, V9; Paroli, M8; Fusaro, E2; Becciolini, A1
abstract
Objective There are few real-world setting studies focused on apremilast efectiveness (i.e., retention rate) in psoriatic
arthritis (PsA). The main aim of this retrospective observational study is the assessment of apremilast 3-year retention ratein real-world PsA patients. Moreover, the secondary objective is to report the reasons of apremilast discontinuation and thefactors related to treatment persistence.
Methods In ffteen Italian rheumatological referral centers, all PsA consecutive patients who received apremilast were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline were recorded. The Kaplan–Meier curve and the Coxanalysis computed the apremilast retention rate and treatment persistence-related risk factors. A p-value<0.05 was considered statistically
signifcant.
Results The 356 enrolled patients (median age 60 [interquartile range IQR 52–67] yrs; male prevalence 42.7%) median
observation period was 17 [IQR 7–34] months (7218 patients-months). The apremilast retention rate at 12, 24, and 36 months was, respectively, 85.6%, 73.6%, and 61.8%. The main discontinuation reasons were secondary inefcacy (34% of interruptions), gastro-intestinal intolerance (24%), and primary inefcacy (19%). Age and oligo-articular phenotype were related to
treatment persistence (respectively hazard ratio 0.98 IQR 0.96–0.99; p=0.048 and 0.54 IQR 0.31–0.95; p=0.03).
Conclusion Almost three-ffths of PsA patients receiving apremilast were still in treatment after 3 years. This study confrmed its efectiveness and safety profle. Apremilast appears as a good treatment choice in all oligo-articular PsA patients and in those ones burdened by relevant comorbiditie
2022
- Aqueous Humor Analysis in Overlapping Clinical Diagnosis of Cytomegalovirus and Rubella Virus Anterior Uveitis
[Articolo su rivista]
Gozzi, F.; Belloni, L.; Aldigeri, R.; Gentile, P.; Mastrofilippo, V.; De Simone, L.; Bolletta, E.; Alessandrello, F.; Bonacini, M.; Croci, S.; Zerbini, A.; Cavallini, G. M.; Salvarani, C.; Cimino, L.
abstract
Background and Objectives: A cross-sectional single-center study was conducted to investigate the etiology in hypertensive anterior uveitis whose clinical features are not fully distinctive from cytomegalovirus or from rubella virus and to demonstrate the possible coexistence of both these viruses in causing anterior uveitis. Materials and Methods: The clinical charts of a cohort of patients with hypertensive viral anterior uveitis of uncertain origin consecutively seen in a single center from 2019 to 2022 were retrospectively reviewed; data on the clinical features, aqueous polymerase chain reaction, and antibody response to cytomegalovirus and rubella virus were collected. Results: Forty-three eyes of as many subjects with viral anterior uveitis of uncertain origin were included. Thirty-two patients had an aqueous polymerase chain reaction or antibody index positive to cytomegalovirus only, while 11 cases had an aqueous antibody response to both cytomegalovirus and rubella virus. This latter overlapping group had a statistically significant higher rate of hypochromia and anterior vitritis (p-value: 0.02 and < 0.001, respectively). Conclusions: The simultaneous presence of intraocular antibodies against cytomegalovirus and rubella virus could redefine the differential diagnosis of hypertensive viral anterior uveitis, demonstrating a possible "converged" immune pathway consisting in a variety of stimuli.
2022
- COVID-19 VACCINATION RATE AND SAFETY PROFILE IN PATIENTS AFFECTED BY MIXED CRYOGLOBULINEMIC VASCULITIS
[Abstract in Rivista]
Vacchi, C; Testoni, S; Visentini, M; Zani, R; Lauletta, G; Gragnani, L; Filippini, Da; Mazzaro, C; Fraticelli, P; Quartuccio, L; Padoan, R; Castelnovo, L; Zignego, Al; Ferri, C; Hoxha, A; Salvarani, C; Monti, G; Galli, M; Sebastiani, M
abstract
2022
- Clinical Features and Prevalence of Spondyloarthritis in a Cohort of Italian Patients Presenting with Acute Nongranulomatous Anterior Uveitis
[Articolo su rivista]
Bolletta, E.; Macchioni, P.; Citriniti, G.; Mastrofilippo, V.; Aldigeri, R.; De Simone, L.; Gozzi, F.; Adani, C.; Sangiovanni, A.; Posarelli, C.; Figus, M.; Muratore, F.; Pipitone, N.; Salvarani, C.; Cimino, L.
abstract
Purpose. To describe the clinical features of acute nongranulomatous anterior uveitis (NGAU) patients and to estimate the prevalence of concomitant spondyloarthritis (SpA). Methods. Retrospective study of consecutive patients affected by NGAU referred to the Ocular Immunology Unit of the AUSL-IRCCS di Reggio Emilia, Italy, between January 2016 and January 2019. All patients underwent ophthalmic evaluation and blood test with HLA-B27 typing and were referred to a rheumatologist to identify any undiagnosed SpA. SpA was classified according to the Assessment of SpondyloArthritis international Society (ASAS) criteria in axial or peripheral SpA. Patients were divided into two groups: NGAU with associated SpA (SpA+) and NGAU without SpA (SpA-). Clinical and demographic features of the two groups, including sex, HLA-B27, family history of rheumatic disease, uveitis laterality, course, and severity of ocular inflammation, complications, and treatment, were compared. Results. Ninety-nine patients with NGAU were enrolled, of whom 36 (36%) with a diagnosis of SpA: 14 with peripheral SpA and 22 with axial SpA. The prevalence of SpA was higher in HLA-B27-positive patients than in HLA-B27-negative patients (50% vs. 15%, p<0.0001). The multivariate logistic regression (R2=0.28) for SpA diagnosis identified as significant predictive factors: age at diagnosis (odds ratio OR=0.95, 95% confidence interval [CI]: 0.91-0.99) and HLA-B27+ (OR=5.32, 95% CI: 1.80-15.70). Conclusions. Our results confirmed the high prevalence of undiagnosed SpA in patients with NGAU, suggesting that, regardless of HLA-B27 status, in the presence of IBP and/or peripheral arthritis, patients with NGAU must be referred to the rheumatologist to allow earlier diagnosis.
2022
- Clinical Relevance of Subcentimetric Lymph Node Biopsy in the Diagnosis of Ocular Sarcoidosis
[Articolo su rivista]
Bolletta, E.; Mastrofilippo, V.; Invernizzi, A.; Aldigeri, R.; Spaggiari, L.; Besutti, G.; Borrelli, R.; Lo Coco, F.; Ricchetti, T.; Rapicetta, C.; Cavazza, A.; Musci, G.; De Simone, L.; Gozzi, F.; Salvarani, C.; Pipitone, N.; Paci, M.; Cimino, L.
abstract
Purpose: To evaluate the clinical relevance of subcentimetric lymph node biopsy via mediastinoscopy in patients with presumed ocular sarcoidosis (OS). Methods: Retrospective study of consecutive patients who underwent biopsy via mediastinoscopy for suspected OS. The biopsy outcomes and clinical features of patients with subcentimetric nodes and of those with lymph nodes >1 cm were compared. Results: A total of 67 patients with presumed OS were included. Forty-two patients (63%) had lymph nodes ≥1 cm in diameter, while 25(37%) showed subcentimetric lymph nodes. Biopsy was consistent with sarcoidosis in 83% of patients with lymph nodes ≥1 cm and in 76% of patients with subcentimetric lymph nodes (p = .60). Patients with OS who had subcentimetric lymph nodes had less lymphopenia (p = .01), lower lysozyme values (p = .03) and a longer diagnostic delay compared to those with larger lymph nodes. Conclusions: The biopsy of subcentimetric lymph nodes via mediastinoscopy may provide a histological diagnosis and reduce diagnostic delay.
2022
- Complement activation predicts negative outcomes in COVID-19: The experience from Northen Italian patients
[Articolo su rivista]
Meroni, P. L.; Croci, S.; Lonati, P. A.; Pregnolato, F.; Spaggiari, L.; Besutti, G.; Bonacini, M.; Ferrigno, I.; Rossi, A.; Hetland, G.; Hollan, I.; Cugno, M.; Tedesco, F.; Borghi, M. O.; Salvarani, C.
abstract
Coronavirus disease 19 (COVID-19) may present as a multi-organ disease with a hyperinflammatory and prothrombotic response (immunothrombosis) in addition to upper and lower airway involvement. Previous data showed that complement activation plays a role in immunothrombosis mainly in severe forms. The study aimed to investigate whether complement involvement is present in the early phases of the disease and can be predictive of a negative outcome. We enrolled 97 symptomatic patients with a positive RT-PCR for SARS-CoV-2 presenting to the emergency room. The patients with mild symptoms/lung involvement at CT-scan were discharged and the remaining were hospitalized. All the patients were evaluated after a 4-week follow-up and classified as mild (n. 54), moderate (n. 17) or severe COVID-19 (n. 26). Blood samples collected before starting any anti-inflammatory/immunosuppressive therapy were assessed for soluble C5b-9 (sC5b-9) and C5a plasma levels by ELISA, and for the following serum mediators by ELLA: IL-1β, IL-6, IL-8, TNFα, IL-4, IL-10, IL-12p70, IFNγ, IFNα, VEGF-A, VEGF-B, GM-CSF, IL-2, IL-17A, VEGFR2, BLyS. Additional routine laboratory parameters were measured (fibrin fragment D-dimer, C-reactive protein, ferritin, white blood cells, neutrophils, lymphocytes, monocytes, platelets, prothrombin time, activated partial thromboplastin time, and fibrinogen). Fifty age and sex-matched healthy controls were also evaluated. SC5b-9 and C5a plasma levels were significantly increased in the hospitalized patients (moderate and severe) in comparison with the non-hospitalized mild group. SC5b9 and C5a plasma levels were predictive of the disease severity evaluated one month later. IL-6, IL-8, TNFα, IL-10 and complement split products were higher in moderate/severe versus non-hospitalized mild COVID-19 patients and healthy controls but with a huge heterogeneity. SC5b-9 and C5a plasma levels correlated positively with CRP, ferritin values and the neutrophil/lymphocyte ratio. Complement can be activated in the very early phases of the disease, even in mild non-hospitalized patients. Complement activation can be observed even when pro-inflammatory cytokines are not increased, and predicts a negative outcome.
2022
- Corrigendum to: Increased expression of interleukin-22 in patients with giant cell arteritis
[Articolo su rivista]
Zerbini, A.; Muratore, F.; Boiardi, L.; Ciccia, F.; Bonacini, M.; Belloni, L.; Cavazza, A.; Cimino, L.; Moramarco, A.; Alessandro, R.; Rizzo, A.; Parmeggiani, M.; Salvarani, C.; Croci, S.
abstract
2022
- Could different aqueous humor and plasma cytokine profiles help differentiate between ocular sarcoidosis and ocular tuberculosis?
[Articolo su rivista]
De Simone, L.; Bonacini, M.; Aldigeri, R.; Alessandrello, F.; Mastrofilippo, V.; Gozzi, F.; Bolletta, E.; Adani, C.; Zerbini, A.; Cavallini, G. M.; Fontana, L.; Salvarani, C.; Croci, S.; Cimino, L.
abstract
Objective and design: A cross-sectional single-center study was conducted to assess cytokine levels in aqueous humor (AH) and plasma of three different uveitis entities: definite ocular sarcoidosis (OS), definite OS associated with QuantiFERON®-TB Gold test positivity (Q + OS) and presumed tubercular uveitis (TBU). Subjects: Thirty-two patients (15 OS, 5 Q + OS, 12 TBU) were included. Methods: Quantification of selected cytokines was performed on blood and AH samples collected before starting any treatment. Statistical analysis was conducted using the Kruskal–Wallis test, the Mann–Whitney or Fisher test and the Principal Component Analysis (PCA). Results: IL-6, IL-8 and IP-10 levels were higher in AH samples than in peripheral blood. In AH samples, BLC, IL-8 and IP-10 were significantly higher in definite OS than in presumptive TBU. There were no statistically significant differences in terms of cytokine levels between Q + OS and presumptive TBU. PCA showed a similar cytokine pattern in the latter two groups (IFNγ, IL-15, IL-2, IP-10, MIG), while the prevalent expression of BLC, IL-10 and MIP-3 α was seen in definite OS. Conclusions: The different AH and plasma cytokine profiles observed in OS compared to Q + OS and TBU may help to differentiate OS from TBU in overlapping clinical phenotypes of granulomatous uveitis (Q + OS).
2022
- Diagnosi di crioproteinemia: preziosa collaborazione tra laboratorio e clinica
per la corretta gestione di una patologia rara
[Articolo su rivista]
Natali, Patrizia; Debbia, Daria; Sheldon, Joanna; Bari, Alessia; Basile, Umberto; Lavatelli, Francesca; Patel, Dina; Galli, Massimo; Villa, Erica; Salvarani, Carlo; Palladini, Giovanni; Mascia, Maria Teresa; Sandri, Gilda
abstract
Cryoglobulinemia is a rare pathologic condition that can be difficult to diagnose both clinically and in the laboratory,
which is why close collaboration between the clinic and laboratory is essential. The laboratory needs the skills and
experience to interpret the laboratory tests and the clinician should not hesitate to contact the laboratory when the
result is not supported by the clinical signs. To strengthen this collaboration, the Protein Study Group of the Italian
Society of Clinical Biochemistry (SIBioC) in collaboration with the Italian Association for the Fight against
Cryglobulinemia (ALCRI) under the patronage of the University of Modena and Reggio Emilia, organised a
conference in Modena on September 2021 entitled "Cryoglobulinemia: laboratory and clinic, a virtuous collaboration
for the correct management of a rare pathology". This collective paper is aimed to summarize the topics discussed
during the meeting. The conference consisted of two parts: the first aimed at highlighting the critical components of
the pre-, intra- and post-analytical phases of cryoglobulin investigation. Cryoprotein testing remains totally manual
and operator dependent so it was important to identify areas where best practice guidance or even harmonisation of
the laboratory investigation would be beneficial. The second part of the conference focused on clinical aspects and
the effects of therapies, including antiviral drugs with direct action against HCV. These drugs are able to eradicate the
virus, but the elimination of HCV-related cryoglobulins is seen in only about half of cases. Finally, the clinical
consequences of the diagnosis of cryoglobulinemia and the multidisciplinary implications that this entails were
highlighted, underlining how the continuous dialogue between the laboratory and clinic is crucial for the correct
management of the patient.
2022
- EVALUATION OF INTERNAL CONSISTENCY, FEASIBILITY, AND RELIABILITY OF THE ITALIAN VERSION OF ANCA-ASSOCIATED VASCULITIS PATIENT-REPORTED OUTCOME (AAV-PRO_ITA) QUESTIONNAIRE: PRELIMINARY RESULTS FROM A MULTICENTER STUDY ON A LARGE COHORT OF ITALIAN PATIENTS
[Abstract in Rivista]
Treppo, E; Isola, M; De Martino, M; Padoan, R; Urban, Ml; Monti, S; Sartorelli, S; Giollo, A; Argolini, Lm; Marvisi, C; Ferro, F; Cassone, G; Motta, F; Berti, A; Conticini, E; Manfredi, A; Frediani, B; Bortolotti, R; Selmi, C; Baldini, C; Emmi, G; Caporali, R; Rossini, M; Dagna, L; Montecucco, C; Schiavon, F; Salvarani, C; De Vita, S; Quartuccio, L
abstract
2022
- Effectiveness of Infliximab and Interferon Alpha-2a for the Treatment of Behçet’s Uveitis: Customizing Therapy according to the Clinical Features
[Articolo su rivista]
De Simone, L.; Invernizzi, A.; Aldigeri, R.; Mastrofilippo, V.; Marvisi, C.; Gozzi, F.; Bolletta, E.; Adani, C.; Pipitone, N.; Muratore, F.; Fontana, L.; Salvarani, C.; Cimino, L.
abstract
Purpose: To report long term results of biologic treatment of severe and refractory Behçet’s uveitis (BU) choosing a different biologic agent according to the uveitis clinical features. Methods: Retrospective cohort of patients with BU refractory to conventional therapy, who received Interferon (IFN) alpha-2a or Infliximab (IFX) for at least 3 months. Results: Twenty-two patients were included (mean age 29 ± 10 years, 63% males); Fifteen received IFN and 7 IFX, for a mean treatment period of 30 ± 24(SD) months. Twenty (90%) patients discontinued treatment, in most cases for complete remission (77%). Seven patients (32%) showed relapses during treatment and five (23%) after discontinuation. Visual acuity improved significantly in IFN group and all eyes showed a significant decrease in central macular thickness at 12 months. Conclusions: Both IFX and IFN Alpha-2a were effective and well tolerated in the treatment of refractory BU using a customized approach based on the uveitis features.
2022
- Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-Life Long-Term Study
[Articolo su rivista]
Parisi, S.; Becciolini, A.; Ditto, M. C.; Rozza, D.; Zanetti, A.; Lagana, A.; Peroni, C. L.; Centanaro Di Vittorio, C.; Degiovanni, R.; Realmuto, C.; Scire, C. A.; Priora, M.; Di Donato, E.; Santilli, D.; Mozzani, F.; Lucchini, G.; Ariani, A.; Gardelli, L.; Girelli, F.; Arrigoni, E.; Plate, I.; Bravi, E.; Paroli, M.; Caccavale, R.; Salvarani, C.; Sandri, G.; Lumetti, F.; Volpe, A.; Marchetta, A.; Fusaro, E.
abstract
We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, pre-viously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan–Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontin-uation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 ± 13.8 years and with an ETA duration of 4.1 ± 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients.
2022
- Efficacy and safety of TNF-α antagonists and tocilizumab in Takayasu arteritis: Multicenter retrospective study of 209 patients
[Articolo su rivista]
Mekinian, Arsène; Biard, Lucie; Dagna, Lorenzo; Novikov, Pavel; Salvarani, Carlo; Espita, Olivier; Sciscia, Savino; Michaud, Martin; Lambert, Marc; Hernández-Rodríguez, José; Schleinitz, Nicolas; Awisat, Abid; Puéchal, Xavier; Aouba, Achille; Pons, Helene Munoz; Smitienko, Ilya; Gaultier, Jean Baptiste; Edwige, Le Mouel; Benhamou, Ygal; Perlat, Antoinette; Jego, Patrick; Goulenok, Tiphaine; Sacre, Karim; Lioger, Bertrand; Nolan, Hassold; Broner, Jonathan; Dufrost, Virginie; Sene, Thomas; Seguier, Julie; Maurier, Francois; Berthier, Sabine; Belot, Alexandre; Frikha, Faten; Denis, Guillaume; Audemard-Verger, Alexandra; Pault, Isabelle Kone; Humbert, Sebastien; Woaye-Hune, Pascal; Tomelleri, Alessandro; Baldissera, Elena; Kuwana, Masataka; Logullo, Alberto; Gaches, Francis; Zeminsky, Pierre; Galli, Elena; Alvarado, Moya; Luigi, Patricia Boiardi; Muratore, Francesco; Vautier, Mathieu; Campochiaro, Corrado; Moiseev, Sergey; Cacoub, Patrice; Fain, Olivier; Saadoun, David
abstract
To assess safety and efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK).
2022
- Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial
[Articolo su rivista]
Cid, M. C.; Unizony, S. H.; Blockmans, D.; Brouwer, E.; Dagna, L.; Dasgupta, B.; Hellmich, B.; Molloy, E.; Salvarani, C.; Trapnell, B. C.; Warrington, K. J.; Wicks, I.; Samant, M.; Zhou, T.; Pupim, L.; Paolini, J. F.
abstract
OBJECTIVES: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is implicated in pathogenesis of giant cell arteritis. We evaluated the efficacy of the GM-CSF receptor antagonist mavrilimumab in maintaining disease remission. METHODS: This phase 2, double-blind, placebo-controlled trial enrolled patients with biopsy-confirmed or imaging-confirmed giant cell arteritis in 50 centres (North America, Europe, Australia). Active disease within 6 weeks of baseline was required for inclusion. Patients in glucocorticoid-induced remission were randomly assigned (3:2 ratio) to mavrilimumab 150 mg or placebo injected subcutaneously every 2 weeks. Both groups received a 26-week prednisone taper. The primary outcome was time to adjudicated flare by week 26. A prespecified secondary efficacy outcome was sustained remission at week 26 by Kaplan-Meier estimation. Safety was also assessed. RESULTS: Of 42 mavrilimumab recipients, flare occurred in 19% (n=8). Of 28 placebo recipients, flare occurred in 46% (n=13). Median time to flare (primary outcome) was 25.1 weeks in the placebo group, but the median was not reached in the mavrilimumab group (HR 0.38; 95% CI 0.15 to 0.92; p=0.026). Sustained remission at week 26 was 83% for mavrilimumab and 50% for placebo recipients (p=0.0038). Adverse events occurred in 78.6% (n=33) of mavrilimumab and 89.3% (n=25) of placebo recipients. No deaths or vision loss occurred in either group. CONCLUSIONS: Mavrilimumab plus 26 weeks of prednisone was superior to placebo plus 26 weeks of prednisone for time to flare by week 26 and sustained remission in patients with giant cell arteritis. Longer treatment is needed to determine response durability and quantify the glucocorticoid-sparing potential of mavrilimumab. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number: NCT03827018, Europe (EUdraCT number: 2018-001003-36), and Australia (CT-2018-CTN-01 865-1).
2022
- Efficacy of Rituximab Treatment in Vogt-Koyanagi-Harada Disease Poorly Controlled by Traditional Immunosuppressive Treatment
[Articolo su rivista]
Bolletta, E.; Gozzi, F.; Mastrofilippo, V.; Pipitone, N.; De Simone, L.; Croci, S.; Invernizzi, A.; Adani, C.; Iannetta, D.; Coassin, M.; Fontana, L.; Salvarani, C.; Cimino, L.
abstract
Purpose: To evaluate the efficacy of Rituximab (RTX) therapy in patients affected by Vogt-Koyanagi-Harada (VKH) disease poorly controlled by traditional immunosuppressive treatment. Methods: Retrospective case series of recurrent VKH uveitis treated with intravenous RTX between January 2019 and November 2020. All patients were treated with intravenous RTX and underwent complete ophthalmic examination, best-corrected visual acuity (BCVA), fundus photography, subfoveal choroidal thickness (SFCT) measurement on enhanced depth imaging optical-coherence tomography (EDI-OCT), fluorescein, and indocyanine green angiography. Results: Five patients were included. All patients received at least 3 RTX infusions. Mean BCVA improved from 20/32 Snellen equivalent at baseline before RTX treatment to 20/28 Snellen equivalent (p = .008). Mean SFCT on EDI-OCT showed a reduction from 564.4 µm(SD = 176.2) to 280.0 µm(SD = 140.4) (p = .015). Follow-up ranged from 12 to 21 months, with a mean of 18.2 ± 3.7 months. Conclusions: In these case series, RTX was effective in VHK disease poorly controlled by traditional immunosuppressive treatment.
2022
- Follow-Up CT Patterns of Residual Lung Abnormalities in Severe COVID-19 Pneumonia Survivors: A Multicenter Retrospective Study
[Articolo su rivista]
Besutti, G.; Monelli, F.; Schiro, S.; Milone, F.; Ottone, M.; Spaggiari, L.; Facciolongo, N.; Salvarani, C.; Croci, S.; Pattacini, P.; Sverzellati, N.
abstract
Prior studies variably reported residual chest CT abnormalities after COVID-19. This study evaluates the CT patterns of residual abnormalities in severe COVID-19 pneumonia survivors. All consecutive COVID-19 survivors who received a CT scan 5–7 months after severe pneumonia in two Italian hospitals (Reggio Emilia and Parma) were enrolled. Individual CT findings were retrospectively collected and follow-up CT scans were categorized as: resolution, residual non-fibrotic abnormalities, or residual fibrotic abnormalities according to CT patterns classified following standard definitions and international guidelines. In 225/405 (55.6%) patients, follow-up CT scans were normal or barely normal, whereas in 152/405 (37.5%) and 18/405 (4.4%) patients, non-fibrotic and fibrotic abnormalities were respectively found, and 10/405 (2.5%) had post-ventilatory changes (cicatricial emphysema and bronchiectasis in the anterior regions of upper lobes). Among non-fibrotic changes, either barely visible (n = 110/152) or overt (n = 20/152) ground-glass opacities (GGO), resembling non-fibrotic nonspecific interstitial pneumonia (NSIP) with or without organizing pneumonia features, represented the most common findings. The most frequent fibrotic abnormalities were subpleural reticulation (15/18), traction bronchiectasis (16/18) and GGO (14/18), resembling a fibrotic NSIP pattern. When multiple timepoints were available until 12 months (n = 65), residual abnormalities extension decreased over time. NSIP, more frequently without fibrotic features, represents the most common CT appearance of post-severe COVID-19 pneumonia.
2022
- From Raynaud Phenomenon to Systemic Sclerosis in COVID-19: A Case Report
[Articolo su rivista]
Giuggioli, Dilia; Spinella, Amelia; De, Pinto; Mascia, Maria TeresA; Salvarani, Carlo
abstract
ABSTRACT: In 2019, the novel SARS-CoV-2 infection emerged, causing the disease called COVID-19, which primarily affects the respiratory tract and lung at alveolar and interstitial levels. Systemic sclerosis (SSc) is an autoimmune connective disease characterized by vascular abnormalities and diffuse and progressive fibrosis of the skin and internal organs. Raynaud phenomenon (RP) occurs in virtually all patients affected by SSc and, in most cases, is an onset symptom of the disease; that is, RP may appear several years before overt illness. Although the exact pathophysiologic pathways leading to RP and SSc are still unknown, several infectious agents, especially viruses, have been suggested as possible triggering factors. Here, the authors describe the first case of RP secondary to SSc following SARS-CoV-2 infection.
2022
- Inflammatory burden and persistent CT lung abnormalities in COVID-19 patients
[Articolo su rivista]
Besutti, G.; Giorgi Rossi, P.; Ottone, M.; Spaggiari, L.; Canovi, S.; Monelli, F.; Bonelli, E.; Fasano, T.; Sverzellati, N.; Caruso, A.; Facciolongo, N.; Ghidoni, G.; Simonazzi, A.; Iori, M.; Nitrosi, A.; Fugazzaro, S.; Costi, S.; Croci, S.; Teopompi, E.; Gallina, A.; Massari, M.; Dolci, G.; Sampaolesi, F.; Pattacini, P.; Salvarani, C.
abstract
Inflammatory burden is associated with COVID-19 severity and outcomes. Residual computed tomography (CT) lung abnormalities have been reported after COVID-19. The aim was to evaluate the association between inflammatory burden during COVID-19 and residual lung CT abnormalities collected on follow-up CT scans performed 2–3 and 6–7 months after COVID-19, in severe COVID-19 pneumonia survivors. C-reactive protein (CRP) curves describing inflammatory burden during the clinical course were built, and CRP peaks, velocities of increase, and integrals were calculated. Other putative determinants were age, sex, mechanical ventilation, lowest PaO2/FiO2 ratio, D-dimer peak, and length of hospital stay (LOS). Of the 259 included patients (median age 65 years; 30.5% females), 202 (78%) and 100 (38.6%) had residual, predominantly non-fibrotic, abnormalities at 2–3 and 6–7 months, respectively. In age- and sex-adjusted models, best CRP predictors for residual abnormalities were CRP peak (odds ratio [OR] for one standard deviation [SD] increase = 1.79; 95% confidence interval [CI] = 1.23–2.62) at 2–3 months and CRP integral (OR for one SD increase = 2.24; 95%CI = 1.53–3.28) at 6–7 months. Hence, inflammation is associated with short- and medium-term lung damage in COVID-19. Other severity measures, including mechanical ventilation and LOS, but not D-dimer, were mediators of the relationship between CRP and residual abnormalities.
2022
- Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia, A double-blind, randomised, placebo-controlled trial
[Articolo su rivista]
Salvarani, Carlo; Massari, Marco; Costantini, Massimo; Franco Merlo, Domenico; Lucia Mariani, Gabriella; Viale, Pierluigi; Nava, Stefano; Guaraldi, Giovanni; Dolci, Giovanni; Boni, Luca; Savoldi, Luisa; Bruzzi, Paolo; Turrà, Caterina; Catanoso, Mariagrazia; Maria Marata, Anna; Barbieri, Chiara; Valcavi, Annamaria; Franzoni, Francesca; Cavuto, Silvio; Mazzi, Giorgio; Corsini, Romina; Trapani, Fabio; Bartoloni, Alessandro; Barisione, Emanuela; Barbieri, Chiara; Jole Burastero, Giulia; Pan, Angelo; Inojosa, Walter; Scala, Raffaele; Burattini, Cecilia; Luppi, Fabrizio; Codeluppi, Mauro; Eldin Tarek, Kamal; Cenderello, Giovanni; Salio, Mario; Foti, Giuseppe; Dongilli, Roberto; Bajocchi, Gianluigi; Alberto Negri, Emanuele; Ciusa, Giacomo; Fornaro, Giacomo; Bassi, Ilaria; Zammarchi, Lorenzo; Aloè, Teresita; Facciolongo, Nicola
abstract
Rationale: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. Methods: In this multicenter, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with Covid-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for 3 consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of the patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need of supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. Results: Overall, 112 of 151 (75.4%) patients in the pulse methylprednisolone arm and 111 of 150 (75.2%) in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups [15 days (95% confidence interval (CI), 13.0 to 17.0) and 16 days (95%CI, 13.8 to 18.2); hazard ratio (HR), 0.92; 95% CI 0.71-1.20; p=0.528]. No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to Intensive Care Unit with orotracheal intubation or death (20.0% versus 16.1%; HR, 1.26; 95%CI, 0.74-2.16; p=0.176), or overall mortality (10.0% versus 12.2%; HR, 0.83; 95%CI, 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. Conclusions: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia. Message of the study: Pulse glucocorticoid therapy is used for severe and/or life threatening immuno-inflammatory diseases. The addition of pulse glucocorticoid therapy to the standard low dose of dexamethasone scheme was not of benefit in patients with COVID-19 pneumonia.
2022
- Long-term Outcome of Children Born to Women with Autoimmune Rheumatic Diseases: A Multicentre, Nationwide Study on 299 Randomly Selected Individuals
[Articolo su rivista]
Andreoli, L.; Nalli, C.; Lazzaroni, M. G.; Carini, C.; Dall'Ara, F.; Reggia, R.; Rodrigues, M.; Benigno, C.; Baldissera, E.; Bartoloni, E.; Basta, F.; Bellisai, F.; Bortoluzzi, A.; Campochiaro, C.; Cantatore, F. P.; Caporali, R.; Ceribelli, A.; Chighizola, C. B.; Conigliaro, P.; Corrado, A.; Cutolo, M.; D'Angelo, S.; De Stefani, E.; Doria, A.; Favaro, M.; Fischetti, C.; Foti, R.; Gabrielli, A.; Generali, E.; Gerli, R.; Gerosa, M.; Larosa, M.; Maier, A.; Malavolta, N.; Meroni, M.; Meroni, P. L.; Montecucco, C.; Mosca, M.; Padovan, M.; Paolazzi, G.; Pazzola, G.; Peccatori, S.; Perricone, R.; Pettiti, G.; Picerno, V.; Prevete, I.; Ramoni, V.; Romeo, N.; Ruffatti, A.; Salvarani, C.; Sebastiani, G. D.; Selmi, C.; Serale, F.; Sinigaglia, L.; Tani, C.; Trevisani, M.; Vadacca, M.; Valentini, E.; Valesini, G.; Visalli, E.; Vivaldelli, E.; Zuliani, L.; Tincani, A.
abstract
The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.
2022
- MODULAZIONE DEI MONOCITI NEI PROCESSI INFIAMMATORI CON IL CONTRIBUTO DELLE CELLULE STAMINALI DELLA POLPA DENTALE UMANA (hDPSC)
[Poster]
Pignatti, E.; Maccaferri, M.; Pisciotta, A.; Di Tinco, R.; Bertani, G.; Bertoni, L.; Croci, S.; Bonacini, M.; Carnevale, G.; Salvarani, C.
abstract
2022
- Modifications of Chest CT Body Composition Parameters at Three and Six Months after Severe COVID-19 Pneumonia: A Retrospective Cohort Study
[Articolo su rivista]
Besutti, Giulia; Pellegrini, Massimo; Ottone, Marta; Bonelli, Efrem; Monelli, Filippo; Farì, Roberto; Milic, Jovana; Dolci, Giovanni; Fasano, Tommaso; Canovi, Simone; Costi, Stefania; Fugazzaro, Stefania; Massari, Marco; Ligabue, Guido; Croci, Stefania; Salvarani, Carlo; Pattacini, Pierpaolo; Guaraldi, Giovanni; Giorgi Rossi, Paolo
abstract
We aimed to describe body composition changes up to 6-7 months after severe COVID-19 and to evaluate their association with COVID-19 inflammatory burden, described by the integral of the C-reactive protein (CRP) curve. The pectoral muscle area (PMA) and density (PMD), liver-to-spleen (L/S) ratio, and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) were measured at baseline (T0), 2-3 months (T1), and 6-7 months (T2) follow-up CT scans of severe COVID-19 pneumonia survivors. Among the 208 included patients (mean age 65.6 ± 11 years, 31.3% females), decreases in PMA [mean (95%CI) -1.11 (-1.72; -0.51) cm2] and in body fat areas were observed [-3.13 (-10.79; +4.52) cm2 for TAT], larger from T0 to T1 than from T1 to T2. PMD increased only from T1 to T2 [+3.07 (+2.08; +4.06) HU]. Mean decreases were more evident for VAT [-3.55 (-4.94; -2.17) cm2] and steatosis [L/S ratio increase +0.17 (+0.13; +0.20)] than for TAT. In multivariable models adjusted by age, sex, and baseline TAT, increasing the CRP interval was associated with greater PMA reductions, smaller PMD increases, and greater VAT and steatosis decreases, but it was not associated with TAT decreases. In conclusion, muscle loss and fat loss (more apparent in visceral compartments) continue until 6-7 months after COVID-19. The inflammatory burden is associated with skeletal muscle loss and visceral/liver fat loss.
2022
- Mortality Prediction of COVID-19 Patients Using Radiomic and Neural Network Features Extracted from a Wide Chest X-ray Sample Size: A Robust Approach for Different Medical Imbalanced Scenarios
[Articolo su rivista]
Iori, M.; Di Castelnuovo, C.; Verzellesi, L.; Meglioli, G.; Lippolis, D. G.; Nitrosi, A.; Monelli, F.; Besutti, G.; Trojani, V.; Bertolini, M.; Botti, A.; Castellani, G.; Remondini, D.; Sghedoni, R.; Croci, S.; Salvarani, C.
abstract
Aim: The aim of this study was to develop robust prognostic models for mortality prediction of COVID-19 patients, applicable to different sets of real scenarios, using radiomic and neural network features extracted from chest X-rays (CXRs) with a certified and commercially available software. Methods: 1816 patients from 5 different hospitals in the Province of Reggio Emilia were included in the study. Overall, 201 radiomic features and 16 neural network features were extracted from each COVID-19 patient’s radiography. The initial dataset was balanced to train the classifiers with the same number of dead and survived patients, randomly selected. The pipeline had three main parts: balancing procedure; three-step feature selection; and mortality prediction with radiomic features through three machine learning (ML) classification models: AdaBoost (ADA), Quadratic Discriminant Analysis (QDA) and Random Forest (RF). Five evaluation metrics were computed on the test samples. The performance for death prediction was validated on both a balanced dataset (Case 1) and an imbalanced dataset (Case 2). Results: accuracy (ACC), area under the ROC-curve (AUC) and sensitivity (SENS) for the best classifier were, respectively, 0.72 ± 0.01, 0.82 ± 0.02 and 0.84 ± 0.04 for Case 1 and 0.70 ± 0.04, 0.79 ± 0.03 and 0.76 ± 0.06 for Case 2. These results show that the prediction of COVID-19 mortality is robust in a different set of scenarios. Conclusions: Our large and varied dataset made it possible to train ML algorithms to predict COVID-19 mortality using radiomic and neural network features of CXRs.
2022
- Photobiomodulation Therapy: A New Light in the Treatment of Systemic Sclerosis Skin Ulcers
[Articolo su rivista]
Spinella, Amelia; de Pinto, Marco; Galluzzo, Claudio; Testoni, Sofia; Macripò, Pierluca; Lumetti, Federica; Parenti, Luca; Magnani, Luca; Sandri, Gilda; Bajocchi, Gianluigi; Starnoni, Marta; De Santis, Giorgio; Salvarani, Carlo; Giuggioli, Dilia
abstract
Introduction: Skin ulcers (SU) represent one of the most frequent manifestations of systemic sclerosis (SSc), occurring in almost 50% of scleroderma patients. SSc-SU are often particularly difficult to treat with conventional systemic and local therapies. In this study, a preliminary evaluation of the role and effectiveness of blue light photobiomodulation (PBM) therapy with EmoLED® in the treatment of scleroderma skin ulcers (SSc-SU) was performed. Methods: We retrospectively analyzed 12 consecutive SSc patients with a total of 15 SU on finger hands. All patients were treated with adequate systemic therapy and local treatment for SU; after a standard skin ulcer bed preparation with debridement of all lesions, EmoLED® was performed. All patients were locally treated every week during 2 months of follow-up; SU data were collected after 4 weeks (T4) and 8 weeks (T8). Eight SSc patients with comparable SU were also evaluated as controls. Results: The application of EmoLED® in addition to debridement apparently produced faster healing of SU. Complete healing of SU was recorded in 41.6% cases during EmoLED® treatment. Significant improvements in SU area, length, and width, wound bed, and related pain were observed in EmoLED® patients from T0 to T8. Control subjects treated with standard systemic/local therapies merely showed an amelioration of SU area and width at the end of the follow-up. No procedural or post-procedural adverse events were reported. Conclusions: The positive clinical results and the absence of side effects suggest that EmoLED® could be a promising tool in the management of SSc-SU, with an interesting role to play in the healing process in addition to conventional systemic and local treatments.
2022
- Pneumopathie interstitielle fibrosante dans le syndrome de Gougerot-Sjögren primitif
[Articolo su rivista]
Manfredi, A.; Vacchi, C.; Della Casa, G.; Cerri, S.; Cassone, G.; Di Cecco, G.; Luppi, F.; Salvarani, C.; Sebastiani, M.
abstract
Objectifs: La pneumopathie interstitielle (PI) représente la principale atteinte pulmonaire dans le syndrome de Gougerot-Sjögren primitif (SGSp). Un certain nombre de patients atteints de SGSp développent une forme fibrosante progressive de PI, mais il n'existe aucune donnée sur la prévalence de telles présentations.L'objectif de cette étude transversale monocentrique était d'explorer la prévalence des formes fibrosantes chez les patients atteints de SGSp présentant une PI. Méthodes: Tous les patients consécutifs remplissant les critères de classification du SGSp et présentant une PI existante ou nouvellement diagnostiquée ont été inclus dans l’étude. Le diagnostic de PI était toujours établi par TDM-HR et les différentes formes ont été déterminées sur la base des critères de classification en vigueur et réparties dans deux groupes selon qu'une forme fibrosante était détectée ou non. Résultats: Trente-quatre patients présentant un SGSp avec PI ont été inclus dans l’étude (3 hommes et 31 femmes, âge médian 69,5 ans, durée moyenne du SGSp 47,5 mois). Une forme fibrosante a été identifiée chez 52,9 % des patients (groupe 1) : pneumopathie interstitielle commune (PIC) chez 13 patients (38,2 %), pneumopathie interstitielle non spécifique (PINS) fibrosante chez 4 patients (11,8 %) et pneumopathie organisée (PO) fibrosante chez 1 patient (2,9 %). Le groupe 2 (16 patients, 47,1 %) comprenait la PINS chez 6 patients (17,6 %), la PO chez 4 patients (11,8 %), la PIL chez 2 patients (5,9 %) et la pneumopathie interstitielle inclassable chez 4 patients (11,8 %). Dans le groupe 1, les patients étaient plus jeunes et la durée du SGSp au moment du diagnostic de PI plus courte. Notamment, la PI a été diagnostiquée avant ou en même temps que le SGSp dans 83,3 % des cas, contre 62,5 % dans le groupe 2 de forme non fibrosante (p < 0,05). Conclusion: Nos données suggèrent une forte prévalence de ce phénotype clinique pulmonaire chez les patients présentant un SGSp avec PI. Compte tenu de l’évolution habituelle des pneumopathies fibrosantes progressives vers une insuffisance respiratoire, ce résultat justifie des études complémentaires.
2022
- Predictive factors of clinical outcomes in patients with COVID-19 treated with tocilizumab: A monocentric retrospective analysis
[Articolo su rivista]
Cassone, G.; Dolci, G.; Besutti, G.; Braglia, L.; Pavone, P.; Corsini, R.; Sampaolesi, F.; Iotti, V.; Teopompi, E.; Massari, M.; Fontana, M.; Ghidoni, G.; Matei, A.; Croci, S.; Negri, E. A.; Costantini, N.; Facciolongo, N.; Salvarani, C.
abstract
Objective The aim of this retrospective observational study is to analyse clinical, serological and radiological predictors of outcome in patients with COVID-19 pneumonia treated with tocilizumab, providing clinical guidance to its use in real-life. Method This is a retrospective, monocentric observational cohort study. All consecutive patients hospitalized between February the 11th and April 14th 2020 for severe COVID-19 pneumonia at Reggio Emilia AUSL and treated with tocilizumab were enrolled. The patient's clinical status was recorded every day using the WHO ordinal scale for clinical improvement. Response to treatment was defined as an improvement of one point (from the status at the beginning of tocilizumab treatment) during the follow-up on this scale. Bivariate association of main patients' characteristics with outcomes was explored by descriptive statistics and Fisher or Kruskal Wallis tests (respectively for qualitative or quantitative variables). Each clinically significant predictor was checked by a loglikelihood ratio test (in univariate logistic models for each of the considered outcomes) against the null model. Results A total of 173 patients were included. Only hypertension, the use of angiotensin-converting enzyme inhibitors, PaO2/FiO2, respiratory rate and C-reactive protein were selected for the multivariate analysis. In the multivariable model, none of them was significantly associated with response. Conclusions Evaluating a large number of clinical variables, our study did not find new predictors of outcome in COVID19 patients treated with tocilizumab. Further studies are needed to investigate the use of tocilizumab in COVID-19 and to better identify clinical phenotypes which could benefit from this treatment.
2022
- RUOLO DEI MACROFAGI IN CONDIZIONI PRO- ED ANTI-INFIAMMATORIE E MECCANISMI DI REGOLAZIONE INDOTTI DALLE hDPSCs
[Poster]
Maccaferri, M.; Pisciotta, A.; Di Tinco, R.; Bertani, G.; Bertoni, L.; Carnevale, G.; Salvarani, C.; Pignatti, E.
abstract
2022
- Rehabilitation Interventions for Post-Acute COVID-19 Syndrome: A Systematic Review
[Articolo su rivista]
Fugazzaro, S.; Contri, A.; Esseroukh, O.; Kaleci, S.; Croci, S.; Massari, M.; Facciolongo, N. C.; Besutti, G.; Iori, M.; Salvarani, C.; Costi, S.
abstract
Increasing numbers of individuals suffer from post-acute COVID-19 syndrome (PACS), which manifests with persistent symptoms, the most prevalent being dyspnea, fatigue, and musculoskeletal, cognitive, and/or mental health impairments. This systematic review investigated the effectiveness of rehabilitation interventions for individuals with PACS. We searched the MEDLINE, Embase, Cochrane Register of Controlled Trials, CINHAL, Scopus, Prospero, and PEDro databases and the International Clinical Trials Registry Platform for randomized controlled trials (RCTs) up to November 2021. We screened 516 citations for eligibility, i.e., trials that included individuals with PACS exposed to exercise-based rehabilitation interventions. Five RCTs were included, accounting for 512 participants (aged 49.2–69.4 years, 65% males). Based on the revised Cochrane risk-of-bias tool (RoB 2.0), two RCTs had “low risk of bias”, and three were in the “some concerns” category. Three RCTs compared experimental rehabilitation interventions with no or minimal rehabilitation, while two compared two active rehabilitation interventions. Rehabilitation seemed to improve dyspnea, anxiety, and kinesiophobia. Results on pulmonary function were inconsistent, while improvements were detected in muscle strength, walking capacity, sit-to-stand performance, and quality of life. Pending further studies based on qualitatively sound designs, these first findings seem to advocate for rehabilitation interventions to lessen disability due to PACS.
2022
- Residual inflammation in psoriatic arthritis patients in stable minimal disease activity
[Articolo su rivista]
Macchioni, P.; Marchesoni, A.; Ciancio, G.; Sandri, G.; Zabotti, A.; Vukatana, G.; Montaguti, L.; Focherini, M.; Govoni, M.; Spinella, A.; Malavolta, N.; Zuliani, F.; Bruschi, M.; Mascella, F.; Salvarani, C.
abstract
Background: In psoriatic arthritis (PsA), low disease activity as defined by the Minimal Disease Activity (MDA) index is considered a good treatment target. However, as MDA is based only on clinical findings, it might not capture pauci-symptomatic inflammation. Sensitive imaging such as ultrasound (US) might disclose residual inflammatory signs in PsA patients in MDA. Methods: In this cross-sectional multicentre study, adult PsA patients on biologic treatment in MDA for at least 6 months were consecutively enrolled for a thorough clinical and US examination. Data collection included demographics, personal history, main patient's reported outcomes, clinical and US findings of joints, tendon sheaths, tendons, bursae, and entheses involvement. All centers performed the US investigation in B-mode and Power Doppler (PD)-mode using a similar US machine equipped with a 18–6 and 13–5 MHz multifrequency linear probe. Statistical analysis included comparisons between groups and correlation tests. Results: The 72 PsA patients enrolled in the study had a median duration of MDA of 12 (6–65) months. Overall, US examination revealed a low number of acute lesions. However, 54% of patients had at least one PD signal in the examined tissues. A joint or enthesis positive PD signal was found in about 19 and 24% of patients, respectively. Synovial hypertrophy, at least one acute entheseal lesions, and bursitis were the most common changes, detected in 41.7, 41.7 and 26% of patients, respectively. Conclusions: PsA patients in a stable state of MDA may still have residual inflammation in peripheral articular structures detectable by US examination.
2022
- Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials
[Articolo su rivista]
Burmester, G. R.; Winthrop, K.; Blanco, R.; Nash, P.; Goupille, P.; Azevedo, V. F.; Salvarani, C.; Rubbert-Roth, A.; Lesser, E.; Lippe, R.; Lertratanakul, A.; Mccaskill, R. M.; Liu, J.; Ruderman, E. M.
abstract
Introduction: This integrated analysis describes the safety profile of upadacitinib, an oral Janus kinase inhibitor, at 15 and 30 mg once daily for up to 3 years of exposure in patients with active psoriatic arthritis (PsA) who had a prior inadequate response or intolerance to ≥ 1 non-biologic or biologic disease-modifying antirheumatic drug. Methods: Safety data were pooled and analyzed from two randomized, placebo-controlled phase 3 trials. Both trials evaluated upadacitinib 15 mg and 30 mg once daily, and one trial also evaluated adalimumab 40 mg every other week. Treatment-emergent adverse events (TEAEs) and laboratory data were summarized for four groups: pooled placebo, pooled upadacitinib 15 mg, pooled upadacitinib 30 mg, and adalimumab. TEAEs were reported as exposure-adjusted event rates (events per 100 patient-years [E/100 PY]) up to a data cut-off of June 29, 2020. Results: A total of 2257 patients received ≥ 1 dose of upadacitinib 15 mg (N = 907) or 30 mg (N = 921) for 2504.6 PY of exposure or adalimumab (N = 429) for 549.7 PY of exposure. Upper respiratory tract infection, nasopharyngitis, and increased creatine phosphokinase (CPK) were the most common TEAEs with upadacitinib. Rates of malignancies, adjudicated major adverse cardiovascular events (MACEs) and venous thromboembolic events (VTEs), and deaths were similar across treatment groups. Rates of herpes zoster (HZ) and opportunistic infections (OI; excluding tuberculosis, HZ, and oral candidiasis) were higher with upadacitinib versus adalimumab. Serious infection, anemia, and CPK elevations were most frequent with upadacitinib 30 mg. Potentially clinically significant laboratory abnormalities were uncommon. Conclusions: Upadacitinib 15 mg and adalimumab had similar safety profiles with the exception of HZ and OIs, consistent with what was observed in rheumatoid arthritis. Rates of malignancies, MACEs, VTEs, and deaths were comparable among patients receiving upadacitinib and adalimumab. No new safety risks emerged with longer-term exposure to upadacitinib. Trial Registration Numbers: SELECT-PsA 1: NCT03104400; SELECT-PsA 2: NCT03104374.
2022
- Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology
[Articolo su rivista]
De Angelis, R.; Giuggioli, D.; Bajocchi, G.; Dagna, L.; Zanframundo, G.; Foti, R.; Cacciapaglia, F.; Cuomo, G.; Ariani, A.; Rosato, E.; Guiducci, S.; Girelli, F.; Riccieri, V.; Zanatta, E.; Bosello, S.; Cavazzana, I.; Ingegnoli, F.; Santis, M.; Murdaca, G.; Abignano, G.; Romeo, N.; Della Rossa, A.; Caminiti, M.; Iuliano, A.; Ciano, G.; Beretta, L.; Bagnato, G.; Lubrano, E.; De Andres, I.; Giollo, A.; Saracco, M.; Agnes, C.; Lumetti, F.; Spinella, A.; Magnani, L.; Campochiaro, C.; De Luca, G.; Codullo, V.; Visalli, E.; Masini, F.; Gigante, A.; Bellando-Randone, S.; Pellegrino, G.; Pigatto, E.; Dall'Ara, F.; Lazzaroni, M. G.; Generali, E.; Mennillo, G.; Barsotti, S.; Mariano, G. P.; Calabrese, F.; Furini, F.; Vultaggio, L.; Parisi, S.; Peroni, C. L.; Risa, A. M.; Rozza, D.; Zanetti, A.; Carrara, G.; Landolfi, G.; Scire, C. A.; Bianchi, G.; Fusaro, E.; Sebastiani, G. D.; D'Angelo, S.; Cozzi, F.; Doria, A.; Iannone, F.; Salvarani, C.; Matucci-Cerinic, M.; Ferri, C.; Govoni, M.
abstract
OBJECTIVE: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. METHODS: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. RESULTS: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. CONCLUSION: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.
2022
- Survival and Recurrence in Vitreoretinal Lymphoma Simulating Uveitis at Presentation: The Possible Role of Combined Chemotherapy
[Articolo su rivista]
Gozzi, F.; Aldigeri, R.; Mastrofilippo, V.; De Simone, L.; Bolletta, E.; Marzano, J.; Iannetta, D.; Coassin, M.; Ilariucci, F.; Ferrari, A.; Luminari, S.; Merli, F.; Croci, S.; Zerbini, A.; Farnetti, E.; Nicoli, D.; Valli, R.; Tamagnini, I.; Cavazza, A.; Salvarani, C.; Fontana, L.; Cimino, L.
abstract
Purpose: To investigate the role of combined systemic and local chemotherapy in improving the survival of patients with vitreoretinal lymphoma (VRL). Methods: Patients with VRL consecutively seen from 2006 to 2020 were retrospectively reviewed; data on the presence and time of central nervous system (CNS) involvement and treatment regimen (systemic, local or combined chemotherapy) were collected. Overall survival (OS) and progression-free survival (PFS) were calculated for each group. Results: Forty-three eyes of 22 subjects with histology-proven VRL were included. Mean time of survival was 64.8 months (SE±10.8). Twelve patients (57%) presented CNS involvement, which was significantly associated with progression (r = 0.48, P =.03) and death (r = 0.56, P =.009). The isolated primary VRL group had a 5-year OS of 80%. Combined systemic and local chemotherapy reduced the risk of death by 82% (hazard ratio 0.18[0.04– 0.85]) in the entire cohort. Conclusion: Combined systemic and local chemotherapy significantly improved OS but not PFS of patients affected by VRL.
2022
- The role of PET/CT in disease activity assessment in patients with large vessel vasculitis
[Articolo su rivista]
Galli, E.; Muratore, F.; Mancuso, P.; Boiardi, L.; Marvisi, C.; Besutti, G.; Spaggiari, L.; Casali, M.; Versari, A.; Giorgi Rossi, P.; Salvarani, C.
abstract
Objectives To evaluate the accuracy of PET/CT and of PET vascular activity score (PETVAS) in assessing disease activity and the ability of PETVAS in predicting relapses in a large single-centre cohort of patients with large vessel vasculitis (LVV). Methods We conducted a retrospective cohort study of prospectively collected data of consecutive patients diagnosed with LVV who underwent at least one PET/CT scan between 2007 and 2020. The nuclear medicine physician's interpretation of each PET/CT scan (active/inactive vasculitis) was compared with disease activity clinical judgement (active disease/remission). For each PET/CT scan, the PETVAS score was calculated and its accuracy in assessing disease activity was evaluated. The ability of PETVAS in predicting subsequent relapses was evaluated. Results A total of 100 consecutive LVV patients (51 large vessel GCA, 49 Takayasu arteritis) underwent a total of 476 PET/CT scans over a mean follow-up period of 97.5 months. Physician-determined PET/CT grading was able to distinguish between clinically active and inactive LVV with a sensitivity of 60% (95% CI 50.9, 68.7) and specificity of 80.1% (95% CI 75.5, 84.1); the area under the curve (AUC) was 0.70 (95% CI 0.65, 0.75). PETVAS was associated with disease activity, with an age and sex-adjusted odds ratio for active disease of 1.15 (95% CI 1.11, 1.19). A PETVAS >= 10 provided 60.8% sensitivity and 80.6% specificity in differentiating between clinically active and inactive LVV; the AUC was 0.73 (95% CI 0.68, 0.79). PETVAS was not associated with subsequent relapses, with an age and sex-adjusted hazard ratio of 1.04 (95% CI 0.97, 1.11). Conclusions The visual PET/CT grading scale and PETVAS had moderate accuracy to distinguish active LVV from remission. PETVAS did not predict disease relapses.
2022
- Use of ultrasonography to discriminate psoriatic arthritis from fibromyalgia: A post‐hoc analysis of the ulisse study
[Articolo su rivista]
Marchesoni, A.; Macchioni, P.; Gasparini, S.; Perricone, C.; Perrotta, F. M.; Grembiale, R. D.; Silvagni, E.; Ramonda, R.; Costa, L.; Zabotti, A.; Curradi, G.; Gualberti, G.; Marando, F.; Salvarani, C.
abstract
In psoriatic arthritis (PsA) patients with concomitant chronic widespread pain, the differential diagnosis with fibromyalgia syndrome (FMS) can be challenging. We evaluated whether ultrasound (US) examination of entheseal sites can distinguish pain from (PsA) enthesitis versus FMS. PsA and FMS patients underwent clinical evaluation and gray‐scale (GS; B‐mode) and power Doppler (PD) US examination of the entheses. At least one enthesis with GS‐ and PD‐mode changes was found in 90% and 59.3% of PsA patients (n = 140) and 62.7% and 35.3% of FMS patients (n = 51), respectively. GS and PD identified changes in 49.5% and 19.2% of the 840 PsA entheses and 22.5% and 7.9% of the 306 FMS entheses, respectively. Receiver operating characteristic curve analysis showed an area under the curve of 0.77 and 0.66 for B‐ and PD‐mode, respectively, 3.5 being the best cut‐off GS‐score to discriminate the two conditions. Multivariate regression showed that Achilles and proximal patellar tendon enthesitis (B‐mode) were strongly associated with PsA (odds ratio, ~2). Principal component analysis (B‐mode) confirmed that PsA patients have a higher number of involved entheses and patterns of entheseal involvement than FMS patients. US evaluation of the entheses may help differentiate chronic widespread pain from PsA versus FMS.
2022
- VECTOR: An algorithm for the detection of COVID-19 pneumonia from velcro-like lung sounds
[Articolo su rivista]
Pancaldi, F.; Pezzuto, G. S.; Cassone, G.; Morelli, M.; Manfredi, A.; D'Arienzo, M.; Vacchi, C.; Savorani, F.; Vinci, G.; Barsotti, F.; Mascia, M. T.; Salvarani, C.; Sebastiani, M.
abstract
The coronavirus disease 2019 (COVID-19) has severely stressed the sanitary systems of all countries in the world. One of the main issues that physicians are called to tackle is represented by the monitoring of pauci-symptomatic COVID-19 patients at home and, generally speaking, everyone the access to the hospital might or should be severely reduced. Indeed, the early detection of interstitial pneumonia is particularly relevant for the survival of these patients. Recent studies on rheumatoid arthritis and interstitial lung diseases have shown that pathological pulmonary sounds can be automatically detected by suitably developed algorithms. The scope of this preliminary work consists of proving that the pathological lung sounds evidenced in patients affected by COVID-19 pneumonia can be automatically detected as well by the same class of algorithms. In particular the software VECTOR, suitably devised for interstitial lung diseases, has been employed to process the lung sounds of 28 patient recorded in the emergency room at the university hospital of Modena (Italy) during December 2020. The performance of VECTOR has been compared with diagnostic techniques based on imaging, namely lung ultrasound, chest X-ray and high resolution computed tomography, which have been assumed as ground truth. The results have evidenced a surprising overall diagnostic accuracy of 75% even if the staff of the emergency room has not been suitably trained for lung auscultation and the parameters of the software have not been optimized to detect interstitial pneumonia. These results pave the way to a new approach for monitoring the pulmonary implication in pauci-symptomatic COVID-19 patients.
2022
- VEXAS Syndrome: A Case Series From a Single-Center Cohort of Italian Patients With Vasculitis
[Articolo su rivista]
Muratore, F.; Marvisi, C.; Castrignano, P.; Nicoli, D.; Farnetti, E.; Bonanno, O.; Longo, R.; Zaldini, P.; Galli, E.; Balanda, N.; Beck, D. B.; Grayson, P. C.; Pipitone, N.; Boiardi, L.; Salvarani, C.
abstract
Objective: To identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) from a single-center cohort of Italian patients with vasculitis, using a clinically oriented phenotype-first approach. Methods: We retrospectively reviewed the clinical records of 147 consecutive male patients followed up in our vasculitis clinic from 2013 to date. All patients with a diagnosis of vasculitis and treatment-resistant manifestations of inflammation, persistently elevated inflammation markers, and hematologic abnormalities were identified. Bone marrow aspirates were examined for the presence of vacuoles. Sequencing of ubiquitin-activating enzyme E1 (UBA-1) was performed using genomic DNA from peripheral blood leukocytes or bone marrow tissue. Results: Seven patients with vasculitis and concomitant features of VEXAS syndrome were identified. A final diagnosis of VEXAS syndrome was made in 3 of the 5 patients who underwent sequencing of UBA-1 (diagnosis was made postmortem for 1 patient). In all 3 patients, examination of the bone marrow aspirate revealed vacuoles characteristic of VEXAS syndrome, and all 3 patients met the definitive World Health Organization criteria for myelodysplastic syndrome. Cytogenetic analysis showed normal karyotypes in all 3 patients. Conclusion: To our knowledge, this is the first report of VEXAS syndrome associated with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Our data emphasize the need to consider VEXAS syndrome when evaluating patients with various forms of systemic vasculitis. The novel association between VEXAS syndrome and ANCA-associated vasculitis reported herein warrants further investigation.
2022
- Vasculitis, fibromuscular dysplasia or hereditary aneurysms?
[Articolo su rivista]
Marvisi, C.; Castrignano, P.; Besutti, G.; Spaggiari, L.; Caruso, A.; Muratore, F.; Salvarani, C.
abstract
2022
- Vessel inflammation and morphological changes in patients with large vessel vasculitis: A retrospective study
[Articolo su rivista]
Besutti, G.; Muratore, F.; Mancuso, P.; Ferrari, M.; Galli, E.; Spaggiari, L.; Monelli, F.; Casali, M.; Versari, A.; Boiardi, L.; Marvisi, C.; Ligabue, G.; Pattacini, P.; Giorgi Rossi, P.; Salvarani, C.
abstract
Objective The aim was to identify any association between imaging signs of vessel wall inflammation (positron emission tomography-CT (PET-CT) score and CT/MR wall thickening) and synchronous and subsequent vascular damage (stenoses/dilations) in patients with large vessel vasculitis (LVV). Methods Consecutive patients with LVV referred to a tertiary centre in 2007-2020 with baseline PET-CT and morphological imaging (CT/MR angiography) performed within 3 months were included. All available PET-CT and CT/MR scans were reviewed to assess PET-CT uptake (4-point semi-quantitative score), wall thickening, stenoses and dilations for 15 vascular segments. The associations of baseline PET score and CT/MR wall thickening with synchronous and incident stenoses/dilations at CT/MR performed 6-30 months from baseline were evaluated in per-segment and per-patient analyses. Respective areas under the receiver operating characteristic curve (AUC) were calculated. Results We included 100 patients with LVV (median age: 48 years, 22% males). Baseline PET score and wall thickening were strongly associated (Cuzick non-parametric test for trend across order groups (NPtrend) <0.001). The association with synchronous stenoses/dilations was weak for PET score (NPtrend=0.01) and strong for wall thickening (p<0.001). In per-patient analyses, sensitivity/specificity for ≥1 synchronous stenoses/dilations were 44%/67% for PET score ≥2 and 66.7%/60.5% for wall thickening. Subsequent CTs/MRs were available in 28 patients, with seven incident stenoses/dilations. Baseline PET score was strongly associated with incident stenoses/dilations (p=0.001), while baseline wall thickening was not (p=0.708), with AUCs for incident stenoses/dilations of 0.80 for PET score and 0.52 for wall thickening. Conclusion PET score and wall thickening are strongly associated, but only baseline PET score is a good predictor of incident vessel wall damage in LVV.
2022
- What to Know About Biopsy Sampling and Pathology in Vasculitis?
[Articolo su rivista]
Marvisi, C.; Muratore, F.; Cabassi, C.; Galli, E.; Boiardi, L.; Piana, S.; Mengoli, M. C.; Salvarani, C.; Cavazza, A.
abstract
PURPOSE OF REVIEW: To summarize the histologic findings of vasculitis, and to give some practical considerations on biopsy samples. RECENT FINDINGS: The larger use of imaging and the discoveries of serological markers in the diagnosis of vasculitis have increased the clinical recognition of these entities. Nevertheless, biopsy remains the gold standard for diagnosis in most cases. So far, biopsies are also useful to obtain information about prognosis and to guide a more specific treatment. In recent years, less invasive diagnostic approaches have become available, lowering the risks related to the procedure and permitting a definite diagnosis in most cases. Histological examination permits a definite diagnosis of vasculitis. However, the findings may be nonspecific if not evaluated in the proper clinical setting. The interaction between clinicians and pathologists is crucial to obtain a definite diagnosis.
2022
- mRNA-COVID19 Vaccination Can Be Considered Safe and Tolerable for Frail Patients
[Articolo su rivista]
Lupo-Stanghellini, M. T.; Di Cosimo, S.; Costantini, M.; Monti, S.; Mantegazza, R.; Mantovani, A.; Salvarani, C.; Zinzani, P. L.; Inglese, M.; Ciceri, F.; Apolone, G.; Ciliberto, G.; Baldanti, F.; Morrone, A.; Sinno, V.; Locatelli, F.; Notari, S.; Turola, E.; Giannarelli, D.; Silvestris, N.
abstract
Background: Frail patients are considered at relevant risk of complications due to coronavirus disease 2019 (COVID-19) infection and, for this reason, are prioritized candidates for vaccination. As these patients were originally not included in the registration trials, fear related to vaccine adverse events and disease worsening was one of the reasons for vaccine hesitancy. Herein, we report the safety profile of the prospective, multicenter, national VAX4FRAIL study (NCT04848493) to evaluate vaccines in a large trans-disease cohort of patients with solid or hematological malignancies and neurological and rheumatological diseases. Methods: Between March 3 and September 2, 2021, 566 patients were evaluable for safety endpoint: 105 received the mRNA-1273 vaccine and 461 the BNT162b2 vaccine. Frail patients were defined per protocol as patients under treatment with hematological malignancies (n = 131), solid tumors (n = 191), immune-rheumatological diseases (n = 86), and neurological diseases (n = 158), including multiple sclerosis and generalized myasthenia. The impact of the vaccination on the health status of patients was assessed through a questionnaire focused on the first week after each vaccine dose. Results: The most frequently reported moderate–severe adverse events were pain at the injection site (60.3% after the first dose, 55.4% after the second), fatigue (30.1%–41.7%), bone pain (27.4%–27.2%), and headache (11.8%–18.9%). Risk factors associated with the occurrence of severe symptoms after vaccine administration were identified through a multivariate logistic regression analysis: age was associated with severe fever presentation (younger patients vs. middle-aged vs. older ones), female individuals presented a higher probability of severe pain at the injection site, fatigue, headache, and bone pain; and the mRNA-1237 vaccine was associated with a higher probability of severe pain at the injection site and fever. After the first dose, patients presenting a severe symptom were at a relevant risk of recurrence of the same severe symptom after the second one. Overall, 11 patients (1.9%) after the first dose and 7 (1.2%) after the second one required postponement or suspension of the disease-specific treatment. Finally, two fatal events occurred among our 566 patients. These two events were considered unrelated to the vaccine. Conclusions: Our study reports that mRNA-COVID-19 vaccination is safe also in frail patients; as expected, side effects were manageable and had a minimum impact on patient care path.
2021
- 18F-FDG PET-CT versus contrast enhanced CT for the diagnosis of fever of unknown origin
[Articolo su rivista]
Pipitone, N.; Casali, M.; Salvarani, C.
abstract
2021
- Acute exacerbation of interstitial lung disease associated with rheumatic disease
[Articolo su rivista]
Luppi, F.; Sebastiani, M.; Salvarani, C.; Bendstrup, E.; Manfredi, A.
abstract
Interstitial lung disease (ILD) is a cause of morbidity and mortality in patients with rheumatic diseases, such as connective-tissue diseases, rheumatoid arthritis and systemic vasculitis. Some patients with ILD secondary to rheumatic disease (RD–ILD) experience acute exacerbations, with sudden ILD progression and high mortality during or immediately after the exacerbation, and a very low 1-year survival rate. In the ILD subtype idiopathic pulmonary fibrosis (IPF), an acute exacerbation is defined as acute worsening or development of dyspnoea associated with new bilateral ground-glass opacities and/or consolidations at high-resolution CT, superimposed on a background pattern consistent with fibrosing ILD. However, acute exacerbation in RD–ILD (AE–RD–ILD) currently has no specific definition. The aetiology and pathogenesis of AE–RD–ILD remain unclear, but distinct triggers might include infection, mechanical stress, microaspiration and DMARD treatment. At this time, no effective evidence-based therapeutic strategies for AE–RD–ILD are available. In clinical practice, AE–RD–ILD is often empirically treated with high-dose systemic steroids and antibiotics, with or without immunosuppressive drugs. In this Review, we summarize the clinical features, diagnosis, management and prognosis of AE–RD–ILD, enabling the similarities and differences with acute exacerbation in IPF to be critically assessed.
2021
- Adult Primary Central Nervous System Vasculitis
[Capitolo/Saggio]
Salvarani, C.; Brown, R. D.; Giannini, C.; Hunder, G. G.
abstract
Primary CNS vasculitis is an uncommon disorder of unknown cause that is restricted to brain and spinal cord. The median age of onset is 50 years. The neurological manifestations are diverse, but generally consist of headache, altered cognition, focal weakness, or stroke. Serological markers of inflammation are usually normal. Cerebrospinal fluid is abnormal in about 80–90% of patients. Diagnosis is unlikely in the presence of a normal MRI of the brain. Biopsy of CNS tissue showing vasculitis is the only definitive test; however, angiography has often been used for diagnosis even though it has only moderate sensitivity and specificity. Granulomatous vasculitis is the most common pattern of vasculitis (around 60% of cases), and β-amyloid deposition is present in almost 50% of these patients. Several subsets of PCNSV have been identified, which differ in terms of outcomes and optimal management. The size of the affected vessels varies and determines outcome and response to treatment. Early recognition is important because treatment with corticosteroi15ds with or without cytotoxic drugs can often prevent serious outcomes. Cyclophosphamide (CYC) and mycophenolate mofetil appear to be effective for the induction of remission. Rituximab may be helpful in patients who are intolerant or respond poorly to CYC. The differential diagnosis includes reversible cerebral vasoconstriction syndromes and secondary cerebral vasculitis.
2021
- Anti-drug antibody detection with label-free electrolyte-gated organic field-effect transistors
[Articolo su rivista]
Sensi, Matteo; Berto, Marcello; Gentile, Sara; Pinti, Marcello; Conti, Andrea; Pellacani, Giovanni; Salvarani, Carlo; Cossarizza, Andrea; Bortolotti, Carlo Augusto; Biscarini, Fabio
abstract
The efficacy of immunotherapy can be undermined by the development of an immune response against a drug/antibody mediated by anti-drug antibodies (ADAs) in treated patients. We present the first label-free EGOFET immunosensor that integrates a biological drug, Nivolumab (Opdivo©), as a specific recognition moiety to quantitatively and selectively detect ADAs against the drug. The limit of detection is 100 fM. This demonstration is a prelude to the detection of ADAs in a clinical setting in the treatment of different pathologies, and it also enables rapid screening of biological drugs for immunogenicity.
2021
- Aortic dilatation in a patient with Takayasu arteritis treated with tocilizumab
[Articolo su rivista]
Muratore, Francesco; Salvarani, Carlo
abstract
In recent years there has been growing interest in the use of tocilizumab for the treatment of large vessel vasculitis. Although the primary endpoint (time to relapse) was not met in the first randomised, placebo-controlled trial evaluating the efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis, the results suggested favour for tocilizumab over placebo without new safety concerns. We report a patient with disease progression despite tocilizumab therapy.
2021
- Association Between Specimen Length and Number of Sections and Diagnostic Yield of Temporal Artery Biopsy for Giant Cell Arteritis
[Articolo su rivista]
Muratore, F.; Boiardi, L.; Cavazza, A.; Tiengo, G.; Galli, E.; Aldigeri, R.; Pipitone, N.; Cimino, L.; Bonacini, M.; Croci, S.; Salvarani, C.
abstract
Objective: To investigate the association between specimen length and number of sections evaluated and the diagnostic yield of temporal artery biopsy (TAB) for giant cell arteritis (GCA). Methods: A pathologist reviewed all TABs performed for suspected GCA between January 1991 and December 2012. The blocks of all the inadequate and negative biopsy specimens were recut, and further slides at deeper levels were stained with hematoxylin and eosin in order to avoid missing inflammatory changes. Results: In total, findings from 662 TABs were included in the study (71% female; mean age 73.2 years). A total of 427 TAB specimens (65%) were classified as negative, and 235 (35%) were classified as positive for GCA. Compared to those with negative TAB results, patients with positive TAB results were older and more frequently female. There was no difference in postfixation TAB specimen length between TAB specimens negative and positive for GCA (mean 6.5 mm versus 6.9 mm; P = 0.068). Cuts of additional biopsy sections revealed inflammation at deeper levels in 26 of 408 TAB specimens (6.4%) originally reported as uninflamed. The inflamed section was the second in 14 TAB specimens, the third in 9 specimens, and the fourth in 3 specimens. Piecewise logistic regression identified 5 mm as the TAB specimen length change point for diagnostic sensitivity. Compared to a TAB specimen length of <5 mm, the age- and sex-adjusted odds ratio for positive TAB results in samples ≥5 mm long was 1.5 (95% confidence interval 1.0–2.0), P = 0.032. Conclusion: A postfixation TAB specimen length of at least 5 mm should be sufficient to make a histologic diagnosis of GCA. In order not to miss inflammatory changes, at least 3 further sections at deeper levels should be evaluated in all negative TAB specimens.
2021
- Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes
[Articolo su rivista]
Monti, S.; Craven, A.; Klersy, C.; Montecucco, C.; Caporali, R.; Watts, R.; Merkel, P. A.; Luqmani, R.; Achilleos, K.; Adler, M.; Alba, M. A.; Albert, D. A.; Alibaz-Oner, F.; Allcoat, P.; Amano, K.; Amarasuriya, M.; Amudala, N. A.; Andrews, J.; Archer, A. M.; Arimura, Y.; Atukorala, I.; Azevedo, E.; Bajad, S.; Baldwin, C.; Barra, L. J.; Baslund, B.; Basu, N.; Baykal, M.; Berger, C.; Berglin, E.; Besada, E.; Bhardwaj, M.; Bischof, A.; Blockmans, D.; Blood, J.; Draibe, J. B.; Brand, S.; Brandao, M.; Bruce, I. N.; Butler, A.; Calabrese, L. H.; Ferrer, D. C.; Carette, S.; Carmona, D.; Ceunen, H.; Chakravarty, K.; Chapman, P. T.; Chocova, Z.; Chung, S. A.; Ci, W.; Cid, M. C.; Clark, T. M.; Clarkson, M. R.; De Jesus Contreras-Rodriguez, F.; Conway, R.; Cooke, K.; Viros, X. C.; Cordeiro, A.; Costa, A.; Craven, A.; Culfear, K.; Daikeler, T.; Danda, D.; Das, S. K.; Dasgupta, B.; De Castro, A. M.; Dehghan, N.; Devassy, R.; Dhindsa, N.; Diamantopoulos, A. P.; Direskeneli, H.; Dobashi, H.; Juan, D.; Durrani, M.; Edelsten, C.; Eifert, J.; Elhayek, S.; Elsideeg, S.; Endo, T.; Erden, A.; Erer, B.; Eriksson, P.; Erturk, Z.; Espigol-Frigole, G.; Felicetti, M.; Ferraro, A.; Ferro, J. M.; Fifi-Mah, A.; Flores-Suarez, L. F.; Flossmann, O.; Flynn, D.; Fonseca, J. E.; Foot, J.; Foote, M.; Forbess, L.; Fujimoto, S.; Fukuoka, K.; Furtado, C.; Furuta, S.; Gaffo, A. L.; Gallagher, P.; Gao, N.; Gatenby, P.; Gendi, N.; Geraldes, R.; Gerits, A.; Gioffredi, A.; Gomples, L.; Goncalves, M. J.; Gondo, P.; Graham, A.; Grainger, R.; Gray, D. T.; Grayson, P. C.; Griffiths, L.; Guo, Y.; Gupta, R.; Gylling, M.; Hajj-Ali, R. A.; Hammam, N.; Harigai, M.; Hartley, L.; Haslett, J.; Hassan, A.; Hatemi, G.; Hellmich, B.; Henckaerts, L.; Henes, J. C.; Hepburn, J.; Herd, V.; Hess, C.; Hill, C.; Hinojosa-Azaola, A.; Hirahashi, J.; Hirano, F.; Hocevar, A.; Holle, J.; Hollinger, N.; Homma, S.; Howard, T.; Hoyles, R. K.; Hruskova, Z.; Hutcheon, G.; Ignacak, M.; Igney-Oertel, A.; Ikeda, K.; Ikegaya, N.; Jagadeesh, S.; Jaquith, J.; Jayne, D. R. W.; Jewell, T.; Jones, C.; Joshi, A.; Kalyoncu, U.; Kamall, S.; Kamath, S.; Lai, K. S.; Kaname, S.; Kanchinadham, S.; Karadag, O.; Karube, M.; Kaszuba, M.; Kaur, R.; Kawakami, T.; Kawashima, S.; Khalidi, N.; Khan, A.; Kikuchi, M.; Kilic, L.; Kimura, M.; King, M. J.; Klapa, S.; Klocke, R.; Kobayashi, T.; Kobayashi, S.; Komagata, Y.; Kronbichler, A.; Kuczia, P.; Kumar, M. S.; Kurosawa, M.; Lamprecht, P.; Langford, C. A.; Lanyon, P.; Laversuch, C.; Lee, S. J.; Leoni, S.; Li, J.; Liang, K.; Liang, P.; Liao, H.; Lee, L. A.; Luqmani, R. A.; Lyle, A.; Macdonald, M.; Mackie, S. L.; Madden, L.; Magliano, M.; Makino, H.; Makol, A.; Malaiya, R.; Malaviya, A.; Manthri, R.; Maritati, F.; Da Silva, A. M.; Mason, J. C.; Matara, C.; Matsui, K.; Matteson, E. L.; Mcbride, D.; Mccullough, K.; Mcgeoch, L.; Mclaren, J.; Mcmillian, C.; Mendiratta, N.; Menon, A.; Merinopoulos, D.; Merkel, P. A.; Merkel, P.; Messier, S.; Micheletti, R. G.; Mills, K.; Milman, N.; Minoda, M.; Minz, R. W.; Mock, C.; Mohammad, A. J.; Moiseev, S.; Moitinho, M.; Molloy, E.; Monach, P. A.; Montgomery, M.; Moosig, F.; Moradizadeh, M.; Morgan, M.; Morgan, A. W.; Morgan, A. -M.; Muir, A.; Mukhtyar, C.; Muller, A.; Muratore, F.; Muso, E.; Nada, R.; Nakajima, H.; Nakajima, T.; Nakano, H.; Nandagudi, A.; Neumann, T.; Ng, Y. F.; Ng, K. H.; Nogueira, E. L.; Nolkha, N.; Nordstrom, D.; Novikov, P.; Nugaliyadde, A.; O'Donnell, J. L.; O'Donoghue, J.; O'Neill, L.; O'Riordan, E.; Oatley, M.; Okubo, K.; Oliva, E.; Oshikawa, H.; Ota, Y.; Padoan, R.; Pagnoux, C.; Pan, L.; Panaritis, K.; Park, J. K.; Patel, S.; Patil, P.; Pazzola, G.; Peall, A.; Pearce, F.; Pehlevan, S.; Pereira, L.; Pettersson, T.; Pineau, C. A.; Pirila, L.; Poglodek, B.; Ponte, C.; Prieto-Gonzalez, S.; Priya, S. R.; Purewal, B.; Purschke, S.; Putaala, J.; Quickert, S.; Quincey, V.; Raghuvanshi, S.; Rajasekhar, L.; Ranganathan, D.; Rathi, M.; Rees, D.; Rees, F.; Renken, U.; Restuccia, G.; Rhee, R. L.; Rice, B.; Robins, D.; Robson, J.;
abstract
Objectives: ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- A nd older-onset patients are still incompletely understood. Methods: We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: <65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative). Results: A total of 1338 patients with AAV were included: 66% had disease onset at <65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03]. Conclusion: Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.
2021
- Autologous fat grafting in the treatment of a scleroderma stump-skin ulcer: a case report
[Articolo su rivista]
Giuggioli, Dilia; Spinella, Amelia; Cocchiara, Emanuele; de Pinto, Marco; Pinelli, Massimo; Parenti, Luca; Salvarani, Carlo; De Santis, Giorgio
abstract
Here we describe the case of a 60-year-old-woman with systemic sclerosis sent to our Scleroderma Unit to treat digital stumps. The stumps were successfully treated with autologous fat grafting (crown-shape infiltration). Our technique of autologous lipotransfer improved wound healing in a scleroderma patient with stump-digital ulcers where all other options failed.
2021
- Baricitinib and the Risk of Incident Interstitial Lung Disease: A Descriptive Clinical Case Report from Clinical Trials
[Articolo su rivista]
Salvarani, C.; Sebastiani, M.; Dieude, P.; Garcia, M.; Deberdt, W.; Rogai, V.; de la Torre, I.; Inciarte-Mundo, J.; Balsa, A.
abstract
Objectives: Interstitial lung disease (ILD) occurs in up to 30% of patients with rheumatoid arthritis (RA), resulting in increased morbidity and death in the absence of proven therapies. The aim of this study is to estimate the number of incident ILD cases reported through development studies with baricitinib in patients with RA. Methods: Estimates were based on 3770 patients with RA from eight randomized clinical trials (four phase 3, three phase 2, one phase 1b) and one long-term extension study on baricitinib for which ILD was not an exclusion criterion with 12,358 patient-years of exposure (PYE). Results: Twenty-one non-infectious cases of ILD were reported with an exposure-adjusted incidence rate (EAIR) of 0.17 per 100 PYE. Of the 21 cases, six were reported as serious and 15 as non-serious resulting in an incidence rate of 0.05 per 100 PYE and 0.12 per 100 PYE, respectively. There were also 11 cases caused by an infectious agent: seven serious (IR: 0.06 per 100 PYE) and four non-serious cases (IR: 0.03 per 100 PYE). Conclusions: The findings of this analysis in patients with RA treated with baricitinib are consistent with a low risk to develop non-infectious ILD during baricitinib treatment, similar to that observed with other Janus kinase inhibitors.
2021
- CLINICAL AND PATHOLOGICAL FEATURES OF BREAST CANCER IN PATIENTS WITH SYSTEMIC SCLEROSIS: PRELIMINARY DATA FROM THE SCLERO-BREAST STUDY
[Abstract in Rivista]
Toss, Angela; Spinella, Amelia; Isca, Chrystel; Vacchi, Caterina; Ficarra, Guido; Fabbiani, Luca; Iannone, Anna; Magnani, Luca; Castrignanò, Paola; Macripo', Pierluca; Gasparini, Elisa; Piana, Simonetta; Cortesi, Laura; Maiorana, Antonino; Salvarani, Carlo; Dominici, Massimo; Giuggioli, Dilia
abstract
Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients.
2021
- Cataract Surgery with Intraocular Lens Implantation in Juvenile Idiopathic Arthritis-Associated Uveitis: Outcomes in the Era of Biological Therapy
[Articolo su rivista]
Bolletta, Elena; Coassin, Marco; Iannetta, Danilo; Mastrofilippo, Valentina; Aldigeri, Raffaella; Invernizzi, Alessandro; de Simone, Luca; Gozzi, Fabrizio; De Fanti, Alessandro; Cappella, Michela; Adani, Chantal; Neri, Alberto; Moramarco, Antonio; De Maria, Michele; Salvarani, Carlo; Fontana, Luigi; Cimino, Luca
abstract
This study compared the outcomes of cataract surgery with intraocular lens (IOL) implantation in patients with juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis treated with antimetabolite drugs and systemic corticosteroids (Non-Biological Group) versus patients treated with antimetabolites and biological drugs (Biological Group). A cohort of patients with cataract in JIA-associated uveitis undergoing phacoemulsification with IOL implantation was retrospectively evaluated. The main outcome was a change in corrected distance visual acuity (CDVA) in the two groups. Ocular and systemic complications were also recorded. The data were collected preoperatively and at 1, 12, and 48 months after surgery. Thirty-two eyes of 24 children were included: 10 eyes in the Non-Biological Group and 22 eyes in the Biological Group. The mean CDVA improved from 1.19 +/- 0.72 logMAR preoperatively to 0.98 +/- 0.97 logMAR at 48 months (p = 0.45) in the Non-Biological Group and from 1.55 +/- 0.91 logMAR preoperatively to 0.57 +/- 0.83 logMAR at 48 months (p = 0.001) in the Biological Group. The postoperative complications, including synechiae, cyclitic membrane, IOL explantation, glaucoma, and macular edema, were not statistically different between the two groups. An immunosuppressive treatment with biological drugs can improve the visual outcome after cataract surgery in patients with JIA-associated uveitis, but it does not significantly reduce postoperative ocular complications.
2021
- Chronic periaortitis presenting with isolated pulmonary artery involvement: description of two cases
[Articolo su rivista]
Galluzzo, Claudio; Marvisi, Chiara; Besutti, Giulia; Spaggiari, Lucia; Muratore, Francesco; Pazzola, Giulia; Bajocchi, Gianluigi; Salvarani, Carlo
abstract
2021
- Clinical and Pathological Features of Breast Cancer in Systemic Sclerosis: Results from the Sclero-Breast Study
[Articolo su rivista]
Toss, Angela; Spinella, Amelia; Isca, Chrystel; Vacchi, Caterina; Ficarra, Guido; Fabbiani, Luca; Iannone, Anna; Magnani, Luca; Castrignanò, Paola; Macripò, Pierluca; Gasparini, Elisa; Piana, Simonetta; Cortesi, Laura; Maiorana, Antonino; Salvarani, Carlo; Dominici, Massimo; Giuggioli, Dilia
abstract
Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients.
2021
- Comments on: “Unexpected detection of SARS-CoV-2 antibodies in the prepandemic period in Italy”
[Articolo su rivista]
Palermo, A.; Salvarani, C.; Sarti, M.; Boaretto, G.; Manni, L.; Mascia, M. T.
abstract
2021
- Correction to: Heritable and non-heritable uncommon causes of stroke (Journal of Neurology, (2020), 10.1007/s00415-020-09836-x)
[Articolo su rivista]
Bersano, A.; Kraemer, M.; Burlina, A.; Mancuso, M.; Finsterer, J.; Sacco, S.; Salvarani, C.; Caputi, L.; Chabriat, H.; Oberstein, S. L.; Federico, A.; Tournier-Lasserve, E.; Hunt, D.; Dichgans, M.; Arnold, M.; Debette, S.; Markus, H. S.
abstract
The original version of this article unfortunately contained a mistake. Figure 3 caption is incorrect and co-author name should be E.Tournier-Lasserve.
2021
- Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)
[Articolo su rivista]
Perrone, F.; Piccirillo, M. C.; Ascierto, P. A.; Salvarani, C.; Parrella, R.; Marata, A. M.; Popoli, P.; Ferraris, L.; Marrocco-Trischitta, M. M.; Ripamonti, D.; Binda, F.; Bonfanti, P.; Squillace, N.; Castelli, F.; Muiesan, M. L.; Lichtner, M.; Calzetti, C.; Salerno, N. D.; Atripaldi, L.; Cascella, M.; Costantini, M.; Dolci, G.; Facciolongo, N. C.; Fraganza, F.; Massari, M.; Montesarchio, V.; Mussini, C.; Negri, E. A.; Botti, G.; Cardone, C.; Gargiulo, P.; Gravina, A.; Schettino, C.; Arenare, L.; Chiodini, P.; Gallo, C.; Piccirillo, M. C.; Schettino, C.; Gravina, A.; Gargiulo, P.; Arenare, L.; Ascierto, P. A.; Vitale, M. G.; Trojaniello, C.; Palla, M.; Bianchi, A. A. M.; Botti, G.; De Feo, G.; Miscio, L.; Gallo, C.; Chiodiniy, P.; Ferraris, L.; Marrocco-Trischitta, M. M.; Froldi, M.; Menicanti, L.; Cuppone, M. T.; Gobbo, G.; Baldessari, C.; Valenti, V.; Castelvecchio, S.; Poli, F.; Giacomazzi, F.; Piccinni, R.; Annnunziata, M. L.; Biondi, A.; Bussolari, C.; Mazzoleni, M.; Giachi, A.; Filtz, A.; Manini, A.; Poletti, E.; Masserini, F.; Conforti, F.; Gaudiano, G.; Favero, V.; Moroni, A.; Viva, T.; Fancoli, F.; Ferrari, D.; Niro, D.; Resta, M.; Ballotta, A.; Poli, M. D.; Ranucci, M.; Ripamonti, D.; Binda, F.; Tebaldi, A.; Gritti, G.; Pasulo, L.; Gaglio, L.; Del Fabbro, R.; Alborghetti, L.; Giustinetti, G.; Columpsi, P.; Cazzaniga, M.; Capici, S.; Sala, L.; Di Sciacca, R.; Mosca, G.; Pirozzi, M. R.; Castelli, F.; Muiesan, M. L.; Franceschini, F.; Roccaro, A.; Salvetti, M.; Paini, A.; Corda, L.; Ricci, C.; Tomasoni, L.; Nasta, P.; Lorenzotti, S.; Odolini, S.; Foca, E.; Roldan, E. Q.; Metra, M.; Magrini, S.; Borghetti, P.; Latronico, N.; Piva, S.; Filippini, M.; Tomasi, G.; Zuccala, F.; Cattaneo, S.; Scolari, F.; Bossini, N.; Gaggiotti, M.; Properzi, M.; Lichtner, M.; Del Borgo, C.; Marocco, R.; Belvisi, V.; Tieghi, T.; De Masi, M.; Zuccala, P.; Fabietti, P.; Vetica, A.; Mercurio, V. S.; Carraro, A.; Fondaco, L.; Kertusha, B.; Curtolo, A.; Del Giudice, E.; Lubrano, R.; Zotti, M. G.; Puorto, A.; Ciuffreda, M.; Sarni, A.; Monteforte, G.; Romeo, D.; Viola, E.; Damiani, C.; Barone, A.; Mantovani, B.; Di Sanzo, D.; Gentili, V.; Carletti, M.; Aiuti, M.; Gallo, A.; Meliante, P. G.; Martellucci, S.; Riggio, O.; Cardinale, V.; Ridola, L.; Bragazzi, M. C.; Gioia, S.; Valenzi, E.; Graziosi, C.; Bina, N.; Fasolo, M.; Ricci, S.; Gioacchini, M. T.; Lucci, A.; Corso, L.; Tornese, D.; Nijhawan, P.; Equitani, F.; Cosentino, C.; Palladino, M.; Leonetti, F.; Leto, G.; Gnessi, C.; Campagna, G.; Cesareo, R.; Marrocco, F.; Straface, G.; Mecozzi, A.; Cerbo, L.; Isgro, V.; Parrocchia, S.; Visconti, G.; Casati, G.; Calzetti, C.; Ariani, A.; Donghi, L.; Salerno, N. D.; Tacconelli, E.; Bertoldi, M.; Cattaneo, P.; Lambertenghi, L.; Motta, L.; Omega, L.; Albano, G.; Parrella, R.; Fraganza, F.; Atripaldi, L.; Montesarchio, V.; Scarano, F.; De Rosa, A.; Buglione, A.; Lavoretano, S.; Gaglione, G.; De Marco, M.; Sangiovanni, V.; Fusco, F. M.; Viglietti, R.; Manzillo, E.; Rescigno, C.; Pisapia, R.; Plamieri, G.; Maraolo, A.; Calabria, G.; Catalano, M.; Fiorentino, G.; Annunziata, A.; Polistina, G.; Imitazione, P.; Mollica, M.; Esposito, V.; D'Abraccio, M.; Punzi, R.; Bianco, V.; Sbreglia, C.; Del Vecchio, R. F.; Bordonali, A.; Franco, A.; Massari, M.; Salsi, P.; Fontana, M.; Virzi, G.; Calderone, O.; Molteni, A.; Gennarini, S.; Gnudi, U.; Ricci, M. A.; Titolo, G.; Mensi, G.; Vuotto, P.; Gasperini, B.; Mancini, M.; Pasquini, Z.; Spanu, P.; Clementi, S.; Pierini, S.; Bokor, D.; Gori, D.; Ciofetti, M.; Caimi, M.; Bettazzi, L.; Allevi, E.; Furiani, S.; Capitanio, C.; Mastropasqua, B.; Fara, C.; Pulitano, G.; Matsuno, J. S.; Porta, F. D.; Dolfini, V.; Beyene, N. B.; Bezzi, M.; Novali, M.; Viale, P.; Tedeschi, S.; Pascale, R.; Bruno, R.; Di Filippo, A.; Sachs, M.; Oggionni, T.; Di Stefano, M.; Mengoli, C.; Facchini, C.; De Nardo, D.; Frausini, G.; Mucci, L.; Tedesco, S.; Girolimetti, R.; Manfredini, E.; Di Carlo, A. M.; Espinosa, E.; Dennetta, D.; Ticinesi, A.; Meschi, T.
abstract
Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article.
2021
- Definition of fibromyalgia severity: findings from a cross-sectional survey of 2339 Italian patients
[Articolo su rivista]
Salaffi, F.; Di Carlo, M.; Bazzichi, L.; Atzeni, F.; Govoni, M.; Biasi, G.; Di Franco, M.; Mozzani, F.; Gremese, E.; Dagna, L.; Batticciotto, A.; Fischetti, F.; Giacomelli, R.; Guiducci, S.; Guggino, G.; Bentivegna, M.; Gerli, R.; Salvarani, C.; Bajocchi, G.; Ghini, M.; Iannone, F.; Giorgi, V.; Farah, S.; Cirillo, M.; Bonazza, S.; Barbagli, S.; Gioia, C.; Santilli, D.; Capacci, A.; Cavalli, G.; Carubbi, F.; Nacci, F.; Riccucci, I.; Sinigaglia, L.; Masullo, M.; Polizzi, B. M.; Cutolo, M.; Sarzi-Puttini, P.
abstract
OBJECTIVE: To establish optimal cut-off values for the scores of the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromialgia Assessment Scale (FAS 2019mod), and the Polysymptomatic Distress Scale (PDS) in order to distinguish five levels of FM disease severity. METHODS: Consecutive FM patients were evaluated with the three clinimetric indices, and each patient was required to answer the anchor question: 'In general, would you say your health is 1 = very good, 2 = good, 3 = fair, 4 = poor, or 5 = very poor?'-which represented the external criterion. Cut-off points were established through the interquartile reconciliation approach. RESULTS: The study sample consisted of 2181 women (93.2%) and 158 men (6.8%), with a mean age of 51.9 (11.5) years, and mean disease duration was 7.3 (6.9) years. The overall median FIQR, FAS 2019 mod and PDS scores (25th-75th percentiles) were respectively 61.16 (41.16-77.00), 27.00 (19.00-32.00) and 19.0 (13.00-24.00). Reconciliation of the mean 75th and 25th percentiles of adjacent categories defined the severity states for FIQR: 0-23 for remission, 24-40 for mild disease, 41-63 for moderate disease, 64-82 for severe disease and >83 for very severe disease; FAS 2019 mod: 0-12 for remission, 13-20 for mild disease, 21-28 for moderate disease, 29-33 for severe disease and >33 for very severe disease; PDS: 0-5 for remission, 6-15 for mild disease, 16-20 for moderate disease, 21-25 for severe disease and >25 for very severe disease. CONCLUSIONS: Disease severity cut-offs can represent an important improvement in interpreting FM.
2021
- Durable renal response and safety with add-on belimumab in patients with lupus nephritis in real-life setting (BeRLiSS-LN). Results from a large, nationwide, multicentric cohort
[Articolo su rivista]
Gatto, M.; Saccon, F.; Andreoli, L.; Bartoloni, E.; Benvenuti, F.; Bortoluzzi, A.; Bozzolo, E.; Brunetta, E.; Canti, V.; Cardinaletti, P.; Ceccarelli, F.; Ciccia, F.; Conti, F.; De Marchi, G.; de Paulis, A.; De Vita, S.; Emmi, G.; Faggioli, P.; Fasano, S.; Fredi, M.; Gabrielli, A.; Gasparotto, M.; Gerli, R.; Gerosa, M.; Govoni, M.; Gremese, E.; Laria, A.; Larosa, M.; Mosca, M.; Orsolini, G.; Pazzola, G.; Petricca, L.; Ramirez, G. A.; Regola, F.; Rossi, F. W.; Rossini, M.; Salvarani, C.; Scarpato, S.; Tani, C.; Tincani, A.; Ubiali, T.; Urban, M. L.; Zen, M.; Doria, A.; Iaccarino, L.
abstract
Background: Belimumab was recently approved for treatment of lupus glomerulonephritis (LN). Aim: To evaluate renal response and its predictors in LN patients receiving belimumab in real-life. Patients and methods: We considered all patients fulfilling the SLEDAI-2K renal items and/or having estimated glomerular filtration rate (eGFR)≤60 ml/min/1.73 m2, with positive anti-dsDNA and/or low C3/C4 enrolled in the multicentre Italian lupus cohort BeRLiSS (BElimumab in Real LIfe Setting Study), treated with monthly IV Belimumab 10 mg/kg over standard treatment. Primary efficacy renal response (PERR), defined as proteinuria ≤0.7 g/24 h, eGFR≥60 ml/min/1.73 m2 without rescue therapy, was considered as primary outcome. Complete renal response (CRR; proteinuria <0.5 g/24 h, eGFR≥90 ml/min/1.73 m2) was considered as secondary outcome. Prevalence and predictors of PERR were evaluated at 6, 12, 24 months by multivariate logistic regression. Results: Among the 466 SLE patients of BeRLiSS, 91 fulfilled the inclusion criteria, 79 females, median age 41.0 (33.0–47.0) years, median follow-up 22.0 (12.0–36.0) months. Sixty-four (70.3%) achieved PERR, of whom 38.4% reached CRR. Among patients achieving PERR at 6 months, 86.7% maintained response throughout the follow-up. At multivariable analysis, hypertension (OR [95%CI]: 0.28 [0.09–0.89], p = 0.032), high baseline serum creatinine (0.97 [0.95–0.99], p = 0.01) and high baseline proteinuria (0.37, [0.19–0.74], p = 0.005) negatively predicted PERR. Positive predictors of PERR at 12 and 24 months were baseline anti-Sm positivity (OR [95%CI]: 6.2 [1.21–31.7], p = 0.029; 19.8 [2.01–186.7], p = 0.009, respectively) and having achieved PERR at 6 months (14.4 [3.28–63.6]; 11.7 [2.7–48.7], p = 0.001 for both). Conclusions: Add-on therapy with belimumab led to durable renal response in patients with LN in a real-life setting.
2021
- EULAR guidelines on ANCA-associated vasculitis in the real life
[Articolo su rivista]
Marvisi, Chiara; Galli, Elena; Manzini, Carlo Umberto; Sandri, Gilda; Salvarani, Carlo
abstract
Anti-neutrophil cytoplasmic antibodies-associated vasculitides
(AAVs) are a heterogenous group of inflammatory diseases which
primarily involve small vessels and include granulomatosis with
polyangiitis (GPA), microscopic polyangiitis (MPA) and
eosinophilic granulomatosis with polyangiitis (EGPA). They present heterogeneous clinical manifestations, while their diagnosis and
management still remain a challenge for clinicians.
Nowadays, the treatment is based on two different regimens:
the remission-induction treatment and the remission-maintenance
treatment.
The therapeutic armamentarium has grown over the years, with
the aim to lessen adverse effects, improve quality of life of patients
and maintain the disease under control. Biological treatments are
the future: they act on different pathogenic pathways and may offer
in the future a personalized management approach tailored to actual
clinical manifestations.
The latest guidelines were published in 2015 by the European
League Against Rheumatism (EULAR) and still represent the vade
mecum for the management of AAVs.
In this review, we will focus on the principal strategies to treatAAVs. We discuss the remission-induction therapy and the remission-maintenance therapy; we have also distinguished the management of GPA and MPA from that of EGPA, because of their different clinical pictures
2021
- Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized with COVID-19 Pneumonia: A Randomized Clinical Trial
[Articolo su rivista]
Salvarani, C.; Dolci, G.; Massari, M.; Merlo, D. F.; Cavuto, S.; Savoldi, L.; Bruzzi, P.; Boni, F.; Braglia, L.; Turra, C.; Ballerini, P. F.; Sciascia, R.; Zammarchi, L.; Para, O.; Scotton, P. G.; Inojosa, W. O.; Ravagnani, V.; Salerno, N. D.; Sainaghi, P. P.; Brignone, A.; Codeluppi, M.; Teopompi, E.; Milesi, M.; Bertomoro, P.; Claudio, N.; Salio, M.; Falcone, M.; Cenderello, G.; Donghi, L.; Del Bono, V.; Colombelli, P. L.; Angheben, A.; Passaro, A.; Secondo, G.; Pascale, R.; Piazza, I.; Facciolongo, N.; Costantini, M.
abstract
Importance: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile. Objective: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia. Design, Setting, and Participants: Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. Interventions: Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy. Main Outcome and Measures: The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2ratio less than 150 mm Hg, whichever came first. Results: A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility. Conclusions and Relevance: In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease. Trial Registration: ClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37.
2021
- Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: A 24-month prospective, multicentre study
[Articolo su rivista]
Ramonda, R.; Lorenzin, M.; Carriero, A.; Chimenti, M. S.; Scarpa, R.; Marchesoni, A.; Lubrano, E.; Salvarani, C.; Cauli, A.; Semeraro, A.; Santo, L.; Ortolan, A.; Doria, A.; Fracassi, E.; Virelli, G.; Masia, M.; Fanizzi, R.; Visalli, E.; Amato, G.; Carletto, A.; Foti, R.
abstract
Objectives To evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) differences in the outcomes according to the biological treatment line: biologic-naïve patients (group A) versus multifailure (group B) patients. Methods Consecutive patients with PsA receiving secukinumab were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical values were recorded at baseline (T0), 6(T6), 12(T12) and 24(T24) months. Effectiveness was evaluated overtime with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and MDA at T6. Infections and adverse events were recorded. Results 608 patients (41.28% men; mean (SD) age 52.78 (11.33)) were enrolled; secukinumab was prescribed as first-line biological treatment in 227 (37.34%) patients, as second (or more)-line biological treatment in 381 (62.66%). Effectiveness of secukinumab was shown with an improvement in several outcomes, such as Ankylosing Spondylitis Disease Activity Score (T0=3.26 (0.88) vs T24=1.60 (0.69);p=0.02) and Disease Activity Index for Psoriatic Arthritis (T0=25.29 (11.14) vs T24=7.69 (4.51); p<0.01). At T24, group A showed lower Psoriasis Area Severity Index (p=0.04), erythrocyte sedimentation rate and C reactive protein (p=0.03;p=0.05) and joint count (p=0.03) compared with group B. At T24, MDA was achieved in 75.71% of group A and 70.37% of group B. Treatment was discontinued in 123 (20.23%) patients, mainly due to primary/secondary loss of effectiveness, and in 22 due to adverse events. Retention rate at T24 was 71% in the whole population, with some difference depending on secukinumab dosage (p=0.004) and gender (p=0.05). Conclusions In a real-life clinical setting, secukimumab proved safe and effective in all PsA domains, with notable drug retention rate.
2021
- Efficacy and safety of mycophenolate mofetil in the treatment of rheumatic disease-related interstitial lung disease: a narrative review
[Articolo su rivista]
Cassone, Giulia; Sebastiani, Marco; Vacchi, Caterina; Erre, Gian Luca; Salvarani, Carlo; Manfredi, Andreina
abstract
Mycophenolate mofetil (MMF) is an antimetabolite with a potent inhibitory effect on proliferation of T and B lymphocytes used since the early 1990s for the prevention of acute allograft rejection after organ transplant. MMF is also widely used for the treatment of a variety of rheumatic diseases (RDs) and their pulmonary involvement. Interstitial lung disease (ILD) is a heterogeneous group of progressive fibrotic diseases of the lung, which is often secondary to RD and represents a major cause of morbidity and mortality. MMF is considered the main alternative to cyclophosphamide as a first-line agent to treat RD-related ILD or as possible maintenance therapy after cyclophosphamide, with a lower rate of side-effects. However, as for other immunosuppressive agents, the use of MMF in RD-ILD is supported by poor scientific evidence. In this narrative review, we describe the available data and recent advances on the effectiveness and safety of MMF for the treatment of ILD related to RD, including rheumatoid arthritis, systemic sclerosis, primary Sjögren syndrome, systemic lupus erythematosus, idiopathic inflammatory myopathies, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features and antineutrophil cytoplasmic antibody-associated vasculitis.
2021
- Efficacy and safety of rituximab in the treatment of connective tissue disease-related interstitial lung disease
[Articolo su rivista]
Vacchi, Caterina; Manfredi, Andreina; Cassone, Giulia; Erre, Gian Luca; Salvarani, Carlo; Sebastiani, Marco
abstract
Interstitial lung disease (ILD) represents a severe pulmonary complication of connective tissue diseases, rheumatoid arthritis (RA), and antineutrophil cytoplasmic antibody-associated vasculitis. Treatment of ILD, mainly based on immunosuppression, remains challenging. Rituximab (RTX), a monoclonal antibody binding to CD20, is considered a valuable therapeutic choice in cases of refractory ILD. Here, we review the available efficacy and safety data on the use of RTX in the treatment of rheumatic disease-related ILD. Despite controversial efficacy data, RTX seems to be able to stabilize or improve ILD related to RA and antisynthetase syndrome and in established and severe ILD complicating systemic sclerosis. Fewer data are available regarding ILD related to Sjögren syndrome, systemic lupus erythematosus, and antineutrophil cytoplasmic antibody-associated vasculitis. To date, few prospective studies are available and randomized trials are still ongoing with the purpose of exploring the role of RTX in this condition, including the supposed relationship between efficacy and ILD radiologic patterns and safety data, up to now derived mainly from RA studies. Despite an overall acceptable safety profile, concerns remain regarding an increased infectious disease risk in patients with ILD as well as possible lung toxicity and the increased rate of immune-mediated reactions in patients with connective tissue diseases. In conclusion, RTX is a relevant therapeutic option for rheumatic disease-related ILD despite the existing uncertainties; ongoing trials are expected to clarify its use.
2021
- Empowering Patients in the Therapeutic Decision-Making Process: A Glance Into Behçet's Syndrome
[Articolo su rivista]
Marinello, D.; Di Cianni, F.; Del Bianco, A.; Mattioli, I.; Sota, J.; Cantarini, L.; Emmi, G.; Leccese, P.; Lopalco, G.; Mosca, M.; Padula, A.; Piga, M.; Salvarani, C.; Taruscio, D.; Talarico, R.
abstract
Behçet's syndrome (BS) represents a challenging condition, characterized by a variable spectrum of disease profile and associated with a significant limitation of the daily activities as well as a potential negative impact on relationships and psychological status. Considering also the complexity of the therapeutic management of BS, that often includes biological off-label treatments, the participation in the therapeutic decision-making process of the BS patients is essential to ensure the integration of the care process into the life of the patient. For this reason, the empowerment of BS patients represents a crucial need and the present work is aimed at fully exploring all the potential variables implicated in the BS patient empowerment, also highlighting major points to consider and concrete actions to be planned in the immediate future in order to implement a pragmatic facilitation of the patients' empowerment.
2021
- Erratum: Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: Data from 21 clinical trials (Rheumatology (2020) 59 (38353845) DOI: 10.1093/rheumatology/keaa189)
[Articolo su rivista]
Genovese, M. C.; Mysler, E.; Tomita, T.; Papp, K. A.; Salvarani, C.; Schwartzman, S.; Gallo, G.; Patel, H.; Lisse, J. R.; Kronbergs, A.; Leage, S. L.; Adams, D. H.; Xu, W.; Marzo-Ortega, H.; Lebwohl, M. G.
abstract
In the originally published version of this manuscript, there were errors in the rate of latent TB reported for IXE PsA population. These errors have been corrected online. Specifically, the following changes have been made: The definition of latent tuberculosis in the methods section has been corrected to: ‘Latent tuberculosis (TB) infection was based by either latent tuberculosis or a positive result on any of the following annual tests: tuberculin skin test, interferon-gamma release assay, or mycobacterium tuberculosis complex test.’ Discontinuation in the PsA population in the results section has been corrected to: ‘The main causes of discontinuation in the PsA population were latent TB (either latent tuberculosis or a positive result on any of the following annual tests: tuberculin skin test, interferon-gamma release assay, or mycobacterium tuberculosis complex test; n ¼ 20, IR ¼ 0.8 per 100 PY), ISR (n ¼ 5, IR 0.2 per 100 PY) and pneumonia (n ¼ 3, IR 0.1 per 100 PY).’ Table 3, line ‘~Latent tuberculosis infections’, column ‘~Pooled PsA IXE’ has been corrected to: n (%) 35(2.5), IR 1.6, and 95% CI 1.1, 2.2. Table 3, footnote ‘a’ has been corrected to: ‘Includes either latent tuberculosis or a positive result on any of the following annual tests: tuberculin skin test, interferon-gamma release assay, or mycobacterium tuberculosis complex test.’ A sentence in the results section has been corrected to: ‘Latent TB infection was reported by105 patients with PsO (IR 0.6 per 100 PY), 35 patients with PsA (IR 1.6 per 100 PY), and 1 patient with axSpA (IR 0.1 per 100 PY).’ A sentence in the discussion section has been corrected to: ‘Overall, annual TB testing revealed 141 patients across populations (PsO n ¼ 105, PsA n ¼35, axSpA n ¼ 1) with latent TB infections.’ The following sentence has been removed from the discussion section: ‘No cases of positive TB seroconversion were reported in the axSpA population.’ And another sentence in the discussion section has been corrected to: ‘Positive TB tests led to discontinuation (which was protocol-specified for a portion of the studies) for 67 patients with PsO and 20 patients with PsA. However, no confirmed cases of TB reactivation occurred in the ixekizumab clinical trials, including patients with latent or previously treated Mycobacterium tuberculosis infection’.
2021
- Failure of first anti-TNF agent in Takayasu's arteritis: to switch or to swap?
[Articolo su rivista]
Campochiaro, C.; Tomelleri, A.; Galli, E.; Cocchiara, E.; Sartorelli, S.; Muratore, F.; Malattia, C.; Caorsi, R.; Catanoso, M. G.; Baldissera, E.; Ravelli, A.; Salvarani, C.; Dagna, L.
abstract
OBJECTIVES: Biologic drugs (bDMARD), especially TNF-α-inhibitors (TNFi), are used in refractory Takayasu's arteritis (TAK) patients. Up to 23% of patients are switched to a different bDMARD because of inefficacy. No data are available on which strategy is more efficient after TNFi failure. The aim of our study is to evaluate whether a switch or swap strategy should be preferred in TAK patients failing TNFis. METHODS: TAK patients treated with a second bDMARD after the failure of the first TNFi were identified from 3 referral centres. Patients were classified as switch if treated with a different TNFi, and swap if treated with a non-TNFi bDMARD. Baseline features were evaluated. Efficacy and safety of the second bDMARD at 6 and 12 months were assessed and a comparison between switch and swap patients was made. RESULTS: Twenty-four TAK patients were identified. Eleven patients (46%) were switched and 13 patients (54%) were swapped (12 to tocilizumab, 1 to ustekinumab). Baseline features of patients in the 2 groups were comparable. At 12 months, the second bDMARD was suspended in 4 switch (36%) and in 5 swap (42%) patients. Second biologic drug survival and relapse-free survival were equivalent between the two groups at 6 and 12 months. A vascular worsening was observed in 4 switch (40%) and 2 swap (25%) patients. Severe infections, myocardial infarction, ischemic stroke or cancer were recorded in no patient. CONCLUSIONS: Our retrospective study suggests that in first-line TNFi failure TAK patients both switch and swap strategies can be considered suitable approaches.
2021
- Fibrosing interstitial lung disease in primary Sjogren syndrome
[Articolo su rivista]
Manfredi, A.; Vacchi, C.; Dellacasa, G.; Cerri, S.; Cassone, G.; Di Cecco, G.; Luppi, F.; Salvarani, C.; Sebastiani, M.
abstract
Objectives: Interstitial lung disease (ILD) represents the main pulmonary involvement in primary Sjogren syndrome (pSS). A proportion of patients with pSS develop a progressive fibrosing form of ILD, but no data are available about the prevalence of these patterns in pSS patients. Aim of this monocentric, cross-sectional study was to investigate the prevalence of fibrosing patterns in pSS patients with ILD. Methods: All consecutive patients fulfilling classification criteria for pSS with a new or previous diagnosis of ILD were enrolled in the study. Diagnosis of ILD was always performed by mean of HRCT and specific patterns were identified according to current classification criteria and divided in two groups according to the detection of a fibrotic pattern. Results: Thirty-four pSS-ILD patients were enrolled in the study (males/females 3/31, median age 69.5 years, median pSS duration 47.5 months). Fibrotic pattern was detected in 52.9% of patients, namely: UIP (13 patients, 38.2%), fibrotic NSIP (4, 11.8%), fibrotic OP (1 2.9%) and group 2 (16 pts, 47.1%) including NSIP (6, 17.6%), OP (4, 11.8%), LIP (2, 5.9%) and unclassifiable (4, 11.8%). These patients were younger and with a shorter pSS duration at ILD diagnosis, in particular ILD diagnosis was prior or concurrent to pSS in 83.3% of cases compared to 62.5% in the group of nonfibrotic pattern (P < 0.05). Conclusion: Our data suggest a high prevalence of this pulmonary clinical phenotype in pSS-ILD patients. Since the course of progressive fibrosing pneumonia generally results in respiratory failure, this result could be worthy of further studies.
2021
- Genetic Association of a Gain-of-Function IFNGR1 Polymorphism and the Intergenic Region LNCAROD/DKK1 With Behçet’s Disease
[Articolo su rivista]
Ortiz Fernandez, L.; Coit, P.; Yilmaz, V.; Yentur, S. P.; Alibaz-Oner, F.; Aksu, K.; Erken, E.; Duzgun, N.; Keser, G.; Cefle, A.; Yazici, A.; Ergen, A.; Alpsoy, E.; Salvarani, C.; Casali, B.; Kisacik, B.; Kotter, I.; Henes, J.; Cinar, M.; Schaefer, A.; Nohutcu, R. M.; Zhernakova, A.; Wijmenga, C.; Takeuchi, F.; Harihara, S.; Kaburaki, T.; Messedi, M.; Song, Y. -W.; Kasifoglu, T.; Carmona, F. D.; Guthridge, J. M.; James, J. A.; Martin, J.; Gonzalez Escribano, M. F.; Saruhan-Direskeneli, G.; Direskeneli, H.; Sawalha, A. H.
abstract
Objective: Behçet’s disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. This study was undertaken to investigate genetic associations with Behçet’s disease in a diverse multiethnic population. Methods: A total of 9,444 patients and controls from 7 different populations were included in this study. Genotyping was performed using an Infinium ImmunoArray-24 v.1.0 or v.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. Results: We identified 2 novel genetic susceptibility loci for Behçet’s disease, including a risk locus in IFNGR1 (rs4896243) (odds ratio [OR] 1.25; P = 2.42 × 10−9) and within the intergenic region LNCAROD/DKK1 (rs1660760) (OR 0.78; P = 2.75 × 10−8). The risk variants in IFNGR1 significantly increased IFNGR1 messenger RNA expression in lipopolysaccharide-stimulated monocytes. In addition, our results replicated the association (P < 5 × 10−8) of 6 previously identified susceptibility loci in Behçet’s disease: IL10, IL23R, IL12A-AS1, CCR3, ADO, and LACC1, reinforcing the notion that these loci are strong genetic factors in Behçet’s disease shared across ancestries. We also identified >30 genetic susceptibility loci with a suggestive level of association (P < 5 × 10−5), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behçet’s disease revealed their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated. Conclusion: We performed the largest genetic association study in Behçet’s disease to date. Our findings reveal novel putative functional variants associated with the disease and replicate and extend the genetic associations in other loci across multiple ancestries.
2021
- Heritable and non-heritable uncommon causes of stroke
[Articolo su rivista]
Bersano, A.; Kraemer, M.; Burlina, A.; Mancuso, M.; Finsterer, J.; Sacco, S.; Salvarani, C.; Caputi, L.; Chabriat, H.; Oberstein, S. L.; Federico, A.; Lasserve, E. T.; Hunt, D.; Dichgans, M.; Arnold, M.; Debette, S.; Markus, H. S.
abstract
Despite intensive investigations, about 30% of stroke cases remains of undetermined origin. After exclusion of common causes of stroke, there is a number of rare heritable and non-heritable conditions, which often remain misdiagnosed, that should be additionally considered in the diagnosis of cryptogenic stroke. The identification of these diseases requires a complex work up including detailed clinical evaluation for the detection of systemic symptoms and signs, an adequate neuroimaging assessment and a careful family history collection. The task becomes more complicated by phenotype heterogeneity since stroke could be the primary or unique manifestation of a syndrome or represent just a manifestation (sometimes minor) of a multisystem disorder. The aim of this review paper is to provide clinicians with an update on clinical and neuroradiological features and a set of practical suggestions for the diagnostic work up and management of these uncommon causes of stroke. The identification of these stroke causes is important to avoid inappropriate and expensive diagnostic tests, to establish appropriate management measures, including presymptomatic testing, genetic counseling, and, if available, therapy. Therefore, physicians should become familiar with these diseases to provide future risk assessment and family counseling.
2021
- High-dose glucocorticoids pulse-Therapy for beta-coronaviridae pneumonia: A systematic literature review and case-series of coronavirus disease-2019
[Articolo su rivista]
Dolci, G.; Cassone, G.; Venturelli, F.; Besutti, G.; Revelli, M.; Corsini, R.; Sampaolesi, F.; Pavone, P.; Contardi, G.; Riva, N.; Marini, G.; Lazzaretti, C.; Mezzadri, S.; Milic, J.; Massari, M.; Costantini, M.; Salvarani, C.
abstract
Objective. The results of the RECOVERY trial identified dexamethasone as the first pharmacological therapy that reduces mortality in patients with COVID-19. The aim of this paper is to conduct a systematic literature review on safety and efficacy of pulse glucocorticoid therapy for Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV), Middle East Respiratory Syndrome (MERS)-CoV or SARS-CoV-2 infections and describe a case-series of COVID-19 patients treated with off-label pulse doses of methylprednisolone. Methods. We performed a systematic literature review on safety and efficacy of pulse therapy for betacoronaviridae infections as described in the protocol registered on PROSPERO (CRD42020190183). All consecutive patients admitted to Arcispedale Santa Maria Nuova di Reggio Emilia or Guastalla Hospital with COVID-19 between March 1st and April 30th 2020 and treated with methylprednisolone 1 gram/ day for at least three days were included in the case series. A retrospective review of available computed tomography (CT) scan and chest x-ray was performed independently by two radiologists blinded to clinical data, and discordances were resolved by consensus. Results. Twenty papers were included for SARS, but only two were comparative and were included in the primary endpoint analysis. Likewise, eleven papers were included for COVID-19, four of which were comparative and were considered for the primary outcome analysis. Included studies for both SARS and COVID-19 are mostly retrospective and highly heterogeneous, with lethality ranging from 0% to 100% and ICU admission rate ranging from 9% to 100%. Fourteen patients were included in our case series, 7 males and 7 females. Conclusion. No randomised controlled trial is available yet for corticosteroids pulse-Therapy defined as at least ≥500mg/day methylprednisolone in patients with emerging coronavirus pneumonia. Lethality among our cohort is high (4/14), but this finding should be interpreted with caution due to the fact that in our setting pulse-steroids were used in patients not eligible for other treatments because of comorbidities or as rescue therapy. The incidence of steroid-related adverse events seems low in our cohort. The quality of the evidence on glucocorticoid pulse-Therapy in SARS, MERS and COVID-19 is poor. Randomised controlled trials are greatly needed.
2021
- Human Dental Pulp Stem Cells Modulate Cytokine Production in vitro by Peripheral Blood Mononuclear Cells From Coronavirus Disease 2019 Patients
[Articolo su rivista]
Croci, S.; Bonacini, M.; Dolci, G.; Massari, M.; Facciolongo, N.; Pignatti, E.; Pisciotta, A.; Carnevale, G.; Negro, A.; Cassone, G.; Muratore, F.; Belloni, L.; Zerbini, A.; Salvarani, C.
abstract
A subset of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developed a condition of hyper-inflammation, which can cause multi-organ damage and the more severe forms of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) can promote tissue regeneration and modulate immune responses and, thus, have the rational requirements to be used to counteract SARS-CoV-2-induced pneumonia and hyper-inflammation. The aim of the present study was to gain insight into possible mechanisms of action of MSCs obtained from human dental pulp [dental pulp stem cells (DPSCs)] in COVID-19 patients. We investigated the concentrations of 18 cytokines in supernatants of peripheral blood mononuclear cells (PBMCs) obtained from COVID-19 patients cultured in vitro alone and in contact with DPSCs. The modulation of cytokines in PBMCs was confirmed by real-time PCR. IL-6 was the sole cytokine detected in supernatants of DPSCs. In resting conditions, co-culture increased IL-1β, IL-2, IL-5, IL-6, IL-10, IL-18, TNFα, and granulocyte macrophage colony-stimulating factor (GM-CSF) levels. When PBMCs were activated with anti-CD3/CD28 antibody-coated beads, co-culture increased IL-6 and GM-CSF, whereas it decreased IFNγ, TNFα, IL-2, IL-5, IL-9, IL-10, IL-12 (p70), IL-17A, IL-18, IL-21, IL-23, and IL-27 levels. Concentrations of IL-1β, IL-4, IL-13, and IL-22 were not affected. The comparison of cytokine concentrations in supernatants of PBMCs from COVID-19 patients vs. healthy subjects revealed lower concentrations of IL-10 and higher concentrations of IL-18 in supernatants of CD3/CD28-activated PBMCs from COVID-19 patients. Results are explorative but indicate that DPSCs can modulate the production of cytokines deregulated in COVID-19 patients, supporting their potential use in COVID-19.
2021
- Improvement in Patient-Reported Outcomes in Patients with Psoriatic Arthritis Treated with Upadacitinib Versus Placebo or Adalimumab: Results from SELECT-PsA 1
[Articolo su rivista]
Strand, V.; Mease, P. J.; Soriano, E. R.; Kishimoto, M.; Salvarani, C.; Saffore, C. D.; Zueger, P.; McDearmon-Blondell, E.; Kato, K.; Gladman, D. D.
abstract
Introduction: The aim of this work is to assess the effect of upadacitinib versus adalimumab and placebo on patient-reported outcomes (PROs) in psoriatic arthritis (PsA) patients with inadequate responses to ≥ 1 non-biologic disease-modifying anti-rheumatic drugs (non-bDMARD-IR) in SELECT PsA-1. Methods: In this placebo- and active comparator, phase 3 randomized, controlled trial, patients received daily upadacitinib 15 or 30 mg, placebo, or adalimumab 40 mg every other week through 56 weeks. At week 24, placebo-assigned patients were rerandomized to upadacitinib 15 or 30 mg. PROs included Patient Global Assessment of Disease Activity (PtGA), pain, Health Assessment Questionnaire Disability Index (HAQ-DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Short Form 36 Health Survey (SF-36), EQ-5D-5L index score, Bath Ankylosing Spondylitis Disease Activity Index, morning stiffness, Self-Assessment of Psoriasis Symptoms, and Work Productivity and Activity Impairment. Mean changes from baseline in PROs, improvements ≥ minimum clinically important differences (MCID), scores ≥ normative values, and sustained clinically meaningful responses were compared between treatment groups. Results: At weeks 12 and 24, upadacitinib treatment resulted in improvements from baseline versus placebo across all PROs as well as improvements versus adalimumab in HAQ-DI and SF-36 Physical Component Summary score (nominal p < 0.05). Improvements in PtGA, pain, and HAQ-DI were reported as early as week 2. At week 12, significantly (nominal p < 0.05) more upadacitinib- versus placebo-treated patients reported improvements ≥ MCID across all PROs including seven SF-36 domains. The proportions of upadacitinib-treated patients reporting clinically meaningful improvements at week 12 were similar to or greater than with adalimumab and sustained through week 56. Significantly (nominal p < 0.05) more upadacitinib-treated (both doses) patients reported scores ≥ normative values at week 12 versus placebo, and scores were generally similar to or greater than adalimumab. Conclusions: Upadacitinib treatment provides rapid, sustained, and clinically meaningful improvements in PROs in non-bDMARD-IR patients with PsA. SELECT-PsA 1 ClinicalTrials.gov number, NCT03104400.
2021
- Incidence and prevalence of large vessel vasculitis (giant cell arteritis and Takayasu arteritis) in northern Italy: A population-based study
[Articolo su rivista]
Muratore, F.; Boiardi, L.; Mancuso, P.; Restuccia, G.; Galli, E.; Marvisi, C.; Macchioni, P.; Rossi, P. G.; Salvarani, C.
abstract
Objectives: To investigate the epidemiology of the entire spectrum of large vessel vasculitis (LVV) in a well-defined population from a Northern Italian area. Methods: All patients with incident giant cell arteritis (GCA) diagnosed from 2005 to 2016 and all patients with incident Takayasu arteritis (TAK) diagnosed from 1998 to 2016 living in the Reggio Emilia area were identified. Only patients satisfying the modified inclusion criteria of the GiACTA trial, and the 1990 ACR classification criteria for TAK were included. The epidemiology of cranial- and LV-GCA was separately evaluated. Results: 207 patients were diagnosed with GCA and 5 with TAK. 123 patients had cranial-GCA, 53 patients had LV-GCA, and the remaining 31 patients had overlapping features. The standardized annual incidence rate of GCA was 8.3 (95% CI 7.1, 9.4) per 100,000 population ages ≥50 years. The standardized annual incidence rate of cranial-GCA (6.1 [95% CI 5.1, 7.1] per 100,000 population ages ≥50 years) was double the rate of LV-GCA (3.4 [95% CI 2.7, 4.2]). The age-specific incidence rates were similar in the <70 and >90 years age groups, but they were higher in cranial-GCA than in LV-GCA in the age groups 70–79 and 80–89 years. The age- and sex-adjusted annual incidence rate of TAK was 0.5 (95% CI 0.1, 1.2) per 1,000,000 population. Conclusion: Incidence of GCA is higher than previously reported by study evaluating only biopsy-proven or ACR classification criteria confirmed cases. Cranial-GCA and LV-GCA have epidemiological differences. TAK is an extremely rare disease also in Italy.
2021
- Infections of scleroderma digital ulcers: A single center cohort retrospective study
[Articolo su rivista]
Giuggioli, Dilia; Magnani, Luca; Spinella, Amelia; Bajocchi, Gianluigi; Palermo, Adalgisa; Lumetti, Federica; Cocchiara, Emanuele; Salvarani, Carlo
abstract
2021
- Interstitial lung disease and anti-myeloperoxidase antibodies: not a simple association
[Articolo su rivista]
Sebastiani, Marco; Luppi, Fabrizio; Sambataro, Gianluca; Castillo Villegas, Diego; Cerri, Stefania; Tomietto, Paola; Cassone, Giulia; Bocchino, Marialuisa; Atienza-Mateo, Belen; Cameli, Paolo; Moya Alvarado, Patricia; Faverio, Paola; Bargagli, Elena; Vancheri, Carlo; Gonzalez-Gay, Miguel A; Clini, Enrico; Salvarani, Carlo; Manfredi, Andreina
abstract
Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) 29
antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). 30
However, their role remains unclear and only 7-23% of these patients develops clinically overt vas- 31
culitis. We aimed to investigate the clinical, serological and radiological features, and prognosis of 32
anti-MPO-positive interstitial lung disease (ILD) patients. 33
Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing 34
serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clini- 35
cal data, lung function testing, chest high resolution computed tomography (HRCT) pattern, and 36
survival were recorded. 37
Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual 38
interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the pa- 39
tients’ survival. In fact, while the 52-week survival of the overall population was 71.4%±7.5, signif- 40
icantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. 41
Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7% and 41.5% 42
of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. 43
A careful clinical history and evaluation should be always performed in ILD patients with anti- 44
MPO antibodies to early identify patients developing a systemic rheumatic disease.
2021
- Interstitial lung disease in ANCA-associated vasculitis: another step forward
[Articolo su rivista]
Sebastiani, M.; Manfredi, A.; Faverio, P.; Salvarani, C.; Luppi, F.
abstract
2021
- Interstitial pneumonia with autoimmune features: Why rheumatologist–pulmonologist collaboration is essential
[Articolo su rivista]
Sebastiani, M.; Faverio, P.; Manfredi, A.; Cassone, G.; Vacchi, C.; Stainer, A.; Pozzi, M. R.; Salvarani, C.; Pesci, A.; Luppi, F.
abstract
In 2015 the European Respiratory Society (ERS) and the American Thoracic Society (ATS) “Task Force on Undifferentiated Forms of Connective Tissue Disease-associ-ated Interstitial Lung Disease” proposed classification criteria for a new research category defined as “Interstitial Pneumonia with Autoimmune Features” (IPAF), to uniformly de-fine patients with interstitial lung disease (ILD) and features of autoimmunity, without a definite connective tissue disease. These classification criteria were based on a variable combination of features obtained from three domains: a clinical domain consisting of extra-thoracic features, a serologic domain with specific autoantibodies, and a morphologic domain with imaging patterns, histopathological findings, or multicompartment in-volvement. Features suggesting a systemic vasculitis were excluded. Since publication of ERS/ATS IPAF research criteria, various retrospective studies have been published focusing on prevalence; clinical, morphological, and serological features; and prognosis of these patients showing a broad heterogeneity in the results. Recently, two prospective, cohort studies were performed, confirming the existence of some peculiarities for this clinical entity and the possible progression of IPAF to a defined connective tissue disease (CTD) in about 15% of cases. Moreover, a non-specific interstitial pneumonia pattern, an anti-nuclear antibody positivity, and a Raynaud phenomenon were the most common findings. In comparison with idiopathic pulmonary fibrosis (IPF), IPAF patients showed a better performance in pulmonary function tests and less necessity of oxygen delivery. However, at this stage of our knowledge, we believe that further prospective studies, possibly derived from multicenter cohorts and through randomized control trials, to further validate the proposed classification criteria are needed.
2021
- Invited Response on: Comments on "Autologous Fat Grafting for the Oral and Digital Complications of Systemic Sclerosis: Results of a Prospective Study"
[Articolo su rivista]
Pignatti, Marco; Spinella, Amelia; Cocchiara, Emanuele; Boscaini, Giulia; Lusetti, Irene Laura; Citriniti, Giorgia; Lumetti, Federica; Setti, Giacomo; Dominici, Massimo; Salvarani, Carlo; De Santis, Giorgio; Giuggioli, Dilia
abstract
2021
- Long-term effect of tocilizumab in patients with giant cell arteritis: open-label extension phase of the Giant Cell Arteritis Actemra (GiACTA) trial
[Articolo su rivista]
Stone, J. H.; Han, J.; Aringer, M.; Blockmans, D.; Brouwer, E.; Cid, M. C.; Dasgupta, B.; Rech, J.; Salvarani, C.; Spiera, R.; Unizony, S. H.; Bao, M.
abstract
Background: The combination of tocilizumab plus a glucocorticoid taper is effective in maintaining clinical remission without requiring additional glucocorticoid therapy in patients with giant cell arteritis, as shown in part one of the Giant Cell Arteritis Actemra (GiACTA) trial. However, the duration of the tocilizumab effect after discontinuation is unknown. Here, we explored the maintenance of efficacy 1 year after discontinuation of tocilizumab treatment, the effectiveness of retreatment with tocilizumab after relapse, and the long-term glucocorticoid-sparing effect of tocilizumab. Methods: In part one of the GiACTA trial, 251 patients were randomly assigned (2:1:1:1) to receive subcutaneous tocilizumab (162 mg) once a week or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. Patients in clinical remission stopped masked injections at 1 year (the conclusion of part one). In part two, treatment was at the investigators' discretion and could consist of no treatment, tocilizumab, glucocorticoids, methotrexate, or combinations of these, for two years. Maintenance of efficacy as assessed by clinical remission (defined as absence of relapse determined by the investigator), cumulative glucocorticoid dose, and long-term safety were exploratory objectives in part two of the trial. This trial is registered at ClinicalTrials.gov, NCT01791153. Findings: 215 patients participated in part two of the trial; 81 patients who were randomly assigned to tocilizumab once a week in part one were in clinical remission after 1 year, of whom 59 started part two on no treatment. 25 of these 59 patients (42%) maintained tocilizumab-free and glucocorticoid-free clinical remission throughout part two. Median (95% CI) cumulative glucocorticoid doses over 3 years were 2647 mg (1987–3507) for tocilizumab once a week, 3948 mg (2352–5186) for tocilizumab-every-other-week, 5277 mg (3944–6685) for placebo with a 26-week prednisone taper, and 5323 mg (3900–6951) for placebo with a 52-week prednisone taper (van Elteren p≤0·001, tocilizumab once a week vs placebo groups; p<0·05, tocilizumab-every-other-week vs placebo groups). Tocilizumab-based regimens restored clinical remission among patients who experienced relapse in part two and were treated (median time to remission: 15 days for tocilizumab alone [n=17]; 16 days for tocilizumab plus glucocorticoids [n=36]; and 54 days for glucocorticoids alone [n=27]). No new or unexpected safety findings were reported over the full 3 years of the study. Interpretation: Giant cell arteritis remains a chronic disease that entails ongoing management and careful vigilance for disease relapse, but continuous indefinite treatment with immunosuppressive drugs is not required for all patients. A substantial proportion of patients treated with tocilizumab for one year maintain drug-free remission during the two years after tocilizumab cessation. For patients who experience relapse, tocilizumab can be used to manage relapses, but it remains prudent to include prednisone for patients who experience relapse because of the risk for vision loss. Funding: F Hoffmann-La Roche.
2021
- Management of Systemic Sclerosis Patients in the COVID-19 Era: The Experience of an Expert Specialist Reference Center
[Articolo su rivista]
Spinella, A.; Magnani, L.; De Pinto, M.; Marvisi, C.; Parenti, L.; Bajocchi, G.; Salvarani, C.; Mascia, M. T.; Giuggioli, D.
abstract
Objective: COVID-19 pandemic represents a serious health emergency that severely compromised our Public Health system, resulting in a rapid and forced reorganization and involved the management of chronic diseases too. The Scleroderma Unit of Modena and Reggio Emilia follows more than 600 patients suffering from systemic sclerosis (SSc) and recently became the referral center (HUB) in Emilia-Romagna for this rare connective tissue disease. The aim of the present study was to evaluate the extent by which the lockdown and the pandemic has impacted the activity of admissions to Scleroderma Unit of Modena and Reggio Emilia. Methods: Our daily clinical activity is characterized by outpatient visits, videocapillaroscopy exam, ulcers treatment, therapeutic infusions in day hospital regimen, multidisciplinary visits following our dedicated SSc care pathway, and clinical trials. Our activity has been quickly rescheduled to ensure the proper assistance to our SSc patients during the COVID-19 pressure. Results: The use of telemedicine has certainly assured a robust continuity of health care. Furthermore, telephone pre-triage, nurse/medical triage, proper physical distancing and use of PPE/DPI allowed us to re-organize and continue SSc daily activity. Specifically, therapeutic infusions in day hospital regimen and outpatient visits, including ulcers treatment, was guaranteed and maximized. Conclusion: The management of scleroderma patients by an expert specialist reference center is crucial in order to ensure continuity of care and pursue the best SSc practice.
2021
- Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis (EGPA): a European multicenter observational study
[Articolo su rivista]
Bettiol, Alessandra; Urban, Maria Letizia; Dagna, Lorenzo; Cottin, Vincent; Franceschini, Franco; Del Giacco, Stefano; Schiavon, Franco; Neumann, Thomas; Lopalco, Giuseppe; Novikov, Pavel; Baldini, Chiara; Lombardi, Carlo; Berti, Alvise; Alberici, Federico; Folci, Marco; Negrini, Simone; Sinico, Renato Alberto; Quartuccio, Luca; Lunardi, Claudio; Parronchi, Paola; Moosig, Frank; Espígol-Frigolé, Georgina; Schroeder, Jan; Kernder, Anna Luise; Monti, Sara; Silvagni, Ettore; Crimi, Claudia; Cinetto, Francesco; Fraticelli, Paolo; Roccatello, Dario; Vacca, Angelo; Mohammad, Aladdin J; Hellmich, Bernhard; Samson, Maxime; Bargagli, Elena; Cohen Tervaert, Jan Willem; Ribi, Camillo; Fiori, Davide; Bello, Federica; Fagni, Filippo; Moroni, Luca; Ramirez, Giuseppe Alvise; Nasser, Mouhamad; Marvisi, Chiara; Toniati, Paola; Firinu, Davide; Padoan, Roberto; Egan, Allyson; Seeliger, Benjamin; Iannone, Florenzo; Salvarani, Carlo; Jayne, David; Prisco, Domenico; Vaglio, Augusto; Emmi, Giacomo
abstract
Mepolizumab proved efficacious for eosinophilic granulomatosis with polyangiitis (EGPA, former Churg-Strauss) at the dosage of 300mg/4 weeks in the randomized controlled MIRRA trial. Few successful real-life experiences with the dosage approved for severe eosinophilic asthma (100mg/4 weeks) were recently reported. We retrospectively assessed the effectiveness and safety of mepolizumab 100 and 300mg/4 weeks in a large European EGPA cohort.
2021
- Methylprednisolone as rescue therapy after tocilizumab failure in patients with severe COVID-19 pneumonia
[Articolo su rivista]
Guaraldi, Giovanni; Banchelli, Federico; Milic, Jovana; Dolci, Giovanni; Massari, Marco; Corsini, Romina; Meschiari, Marianna; Girardis, Massimo; Busani, Stefano; Cossarizza, Andrea; Salvarani, Carlo; Mussini, Cristina; D'Amico, Roberto
abstract
2021
- New insights into the pathogenesis of giant cell arteritis: are they relevant for precision medicine?
[Articolo su rivista]
Ciccia, F.; Macaluso, F.; Mauro, D.; Nicoletti, G. F.; Croci, S.; Salvarani, C.
abstract
Giant cell arteritis is a primary granulomatous vasculitis characterised by a strict tissue tropism for large and medium-size vessels, occurring in people older than 50 years. Although considerable progress in understanding some of the pathophysiological mechanisms involved in the pathogenesis of giant cell arteritis has been made in the past 10 years, specific triggers of disease and mechanisms of chronic damage have not yet been identified. The definition of a specific pro-inflammatory hierarchy between the multiple cell types and the different cytokines or chemokines involved in the inflammatory process are still unexplored areas of study. The overall goal of precision medicine is to identify the best possible therapeutic approach for an individual or group of individuals with a given disease. The fundamental prerequisite of this approach is the identification, at baseline, of clinical and imaging findings and of molecular biomarkers that allow a precise stratification of patients and an adequate prediction of the therapeutic response. In this regard, the possibility of obtaining temporal artery biopsies for diagnostic purposes offers incredible exploratory possibilities to define different disease pathotypes potentially susceptible to different therapeutic interventions. In this Series paper, we will describe the most recent evidence relating to the pathogenesis of giant cell arteritis, trying to define, if possible, a new pathogenetic-centred approach to patients with giant cell arteritis.
2021
- On- and off-label use of rituximab in rheumatic diseases
[Articolo su rivista]
Sandri, Gilda; Manzini, Carlo Umberto; Salvarani, Carlo
abstract
Steadily growing knowledge about pathogenetic mechanisms in autoimmune rheumatic diseases (RDs) has paved the way to different therapeutic approaches. In particular, the availability of biologics on the market has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients’ quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), initially used in the treatment of non- Hodgkin’s lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis. Currently, in rheumatology, RTX is also used with off-label indications in patients with systemic sclerosis, Sjögren’s syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody targeted to CD20 molecules expressed on the surface of pre-B and mature B lymphocytes. It acts by causing apoptosis of these cells with antibody- and complement-dependent cytotoxicity. As inflammatory responses to cell-associated immune complexes are key elements in the pathogenesis of several autoimmune RDs, such an approach might be effective in these patients. In fact, RTX promotes a rapid and long-term depletion of circulating and lymphoid tissue-associated B cells, thus leading to a lower recruitment of these effector cells at sites of immune complex deposition, therefore reducing inflammation and tissue damage. RTX is extremely interesting for rheumatologists, as it represents an important additional therapeutic approach. Therefore, the advent in clinical practice of approved RTX biosimilars, such as CT-P10, may help in improving treatment access as well as reducing costs
2021
- POS0837 THE USE OF CANNABIDIOL IN THE TREATMENT OF PAIN RELATED TO SCLERODERMA DIGITAL ULCERS
[Poster]
Giuggioli, D.; De Pinto, M.; Parenti, L.; Magnani, L.; Castrignanò, P.; Salvarani, C.; 2, ; Spinella, A.
abstract
Background:
Systemic Sclerosis-SSc is an autoimmune disease, characterized by fibrosis due to immune-mediated microangiopathy. Digital ulcers-DUs represent frequent complications, they are recurrent, painful and often resistant to traditional treatments. Standard therapy, in particular oral opioids, is often inadequate or limited by side effect. Cannabidiol-CBD, is the major non-psychotropic component of the Cannabis sativa, recent studies on its effectiveness as an anxiolytic, anti-inflammatory, and antipsychotic drug showed promising results, in the setting of chronic pain too.
Objectives:
We evaluated the efficacy of CBD drop in pain management in a cohort of SSc patients using standard rating scale VAS, PSQI and HAQ. We further assessed the safety profile and the potential use as opioid-sparing.
Methods:
From January to November 2019 we consecutively enrolled 31 SSc patients (F/M 26/5, mean age 53.0 …
2021
- Pathogenesis
[Capitolo/Saggio]
Croci, S.; Bonacini, M.; Muratore, F.; Boiardi, L.; Pipitone, N.; Salvarani, C.
abstract
Giant cell arteritis (GCA) is an inflammatory disease which mainly affects the extracranial branches of the carotid artery, particularly the temporal arteries. The onset of GCA requires a breakdown of arterial immunoprivilege with the infiltration of immune cells, mainly CD4+ T lymphocytes, macrophages, and dendritic cells (DCs) across the arterial wall. Local production of cytokines, chemokines, growth factors, and enzymes can lead to the amplification of the inflammatory responses and to arterial remodeling. The hyperplasia of the intimal layer can result in luminal stenosis and ischemic events. The etiology of GCA is unknown. However, age-related immune alterations, in genetically predisposed subjects, and environmental triggers seem necessary for the development of the disease. In addition, the existence of a specific GCA-inducing leukocyte repertoire in peripheral blood and the activation of arteries to allow leukocyte entry seem required for the development of GCA. Some immune effectors have been demonstrated to have a role in GCA pathogenesis: the activation of vascular DCs and T cells, TLR4, TLR5, Janus kinases 1 and 3, CD28 co-stimulation, NOTCH-Jagged pathway, CCR6 expression by T cells, defective PD-1 checkpoint; the production of IL-6, VEGF, MMP-9, IFNγ, ET-1, PDGF, IL-12, IL-23, acute-phase serum amyloid A.
2021
- Quality of life and therapeutic management of axial spondyloarthritis patients in Italy: A 12-month prospective observational study
[Articolo su rivista]
D Angelo, S.; Malavolta, N.; Scambi, C.; Salvarani, C.; Caso, F.; Tirri, E.; Ramonda, R.; Quarta, L.; Erre, G. L.; Riva, M.; Buono, R.; Furini, F.; Grembiale, R. D.; Lomater, C.; Cantini, F.; Maio, T.; Chimenti, M. S.; Scrivo, R.; Salaffi, F.; Caporali, R. F.; Volpe, P.; Gualberti, G.; Marando, F.; Marchesoni, A.
abstract
Objective To evaluate the health-related quality of life (HRQoL), disease activity, treatment adherence, and work ability in the real-world setting in patients with axial spondyloarthritis (axSpA). Methods QUASAR was a prospective 12-month, observational study involving 23 rheumatology centres across Italy, including adult patients with axSpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. Patients were followed at baseline, 3, 6, and 12 months for disease activity and health-related QoL (HRQoL), treatment adherence and work ability. Regression analysis was used to assess the association between treatment and outcome variables. Results 413 (80.7%) out of axSpA 512 patients were diagnosed with ankylosing spondylitis (AS) and 99 (19.3%) with non-radiographic axSpA (nr-AxSpA). Nr-AxSpA and AS patients had similar baseline disease activity and HRQoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs) were the most frequent medication (n=426, 83.2%). Over the 1-year follow-up, disease activity measures (joint pain and swelling, CRP, global assessment, BASDAI, ASDAS), HRQoL and work ability significantly improved, while few differences emerged between nr-AxSpA and AS patients. Treatment satisfaction and adherence questionnaires improved over the 12 months. Patients treated with bDMARDs showed improved outcomes for disease activity measures and HRQoL variables, greater benefit observed in patients with AS. Conclusion We found clinical and HRQoL improvement over 1 year in a large, real-world population of nr-AxSpA and AS patients treated with bDMARDs or conventional synthetic DMARDs.
2021
- Reply to the comment on: Hypereosinophilic bronchiolitis in ANCA-associated vasculitis: where does it stand? by Bilgin et al
[Articolo su rivista]
Sebastiani, M.; Manfredi, A.; Cassone, G.; Salvarani, C.; Luppi, F.
abstract
2021
- Resolution of vascular inflammation in patients with new-onset giant cell arteritis: data from the RIGA study
[Articolo su rivista]
Schönau, Verena; Roth, Jessica; Tascilar, Koray; Corte, Giulia; Manger, Bernhard; Rech, Juergen; Schmidt, Daniela; Cavallaro, Alexander; Uder, Michael; Crescentini, Filippo; Boiardi, Luigi; Casali, Massimiliano; Spaggiari, Lucia; Galli, Elena; Kuwert, Torsten; Versari, Annibale; Salvarani, Carlo; Schett, Georg; Muratore, Francesco
abstract
Efficacy evaluation of GCA treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT.
2021
- Response to ‘The Relevance of Restricted Inflammation in a TAB’ by Griffin KJ et al
[Articolo su rivista]
Galli, E.; Muratore, F.; Boiardi, L.; Cavazza, A.; Salvarani, C.
abstract
2021
- Response to: COVID-19 in paediatric rheumatology patients treated with b/tsDMARDs: A cross-sectional patient survey study' by Cuceoglu et al
[Articolo su rivista]
Salvarani, C.; Bajocchi, G.; Mancuso, P.; Galli, E.; Muratore, F.; Giorgi Rossi, P.
abstract
2021
- Rheumatoid arthritis related interstitial lung disease
[Articolo su rivista]
Manfredi, A.; Cassone, G.; Luppi, F.; Atienza-Mateo, B.; Cavazza, A.; Sverzellati, N.; Gonzalez-Gay, M. A.; Salvarani, C.; Sebastiani, M.
abstract
Introduction: Interstitial lung disease (ILD) represents a frequent extra-articular manifestation of rheumatoid arthritis (RA) deeply impacting both quality of life and overall prognosis. Areas covered: A literature search was performed including PubMed, Embase, Scopus, and Web of Science. Many retrospective studies investigated the possible risk factors for RA-related ILD (RA-ILD), aiming to identify patients at risk. Among them, males, smokers, positivity of anti-citrullinated peptide antibodies have been associated with RA-ILD, such as some genetic haplotypes. Usual interstitial pneumonia is the histologic and radiologic pattern most frequently observed, followed by nonspecific interstitial pneumonia. Since lung involvement can represent the RA onset, an early differential diagnosis with idiopathic interstitial pneumonia can be difficult or sometimes impossible. High-resolution computed tomography represents the gold standard for ILD diagnosis, while multidisciplinary discussion should be required to assess disease staging, severity and progression. Expert opinion: Management of RA-ILD patients is challenging due to the lack of evidence-based data regarding both assessment and treatment. Moreover, the high variability of clinical presentation and evolution makes it difficult to establish the correct therapeutic strategy. Currently, multidisciplinary approach, including at least rheumatologists, pulmonologists, and radiologists, is desirable to define therapy and follow-up strategies.
2021
- Risk of acute arterial and venous thromboembolic events in eosinophilic granulomatosis with polyangiitis (Churg–Strauss syndrome)
[Articolo su rivista]
Bettiol, A.; Sinico, R. A.; Schiavon, F.; Monti, S.; Bozzolo, E. P.; Franceschini, F.; Govoni, M.; Lunardi, C.; Guida, G.; Lopalco, G.; Paolazzi, G.; Vacca, A.; Gregorini, G.; Leccese, P.; Piga, M.; Conti, F.; Fraticelli, P.; Quartuccio, L.; Alberici, F.; Salvarani, C.; Bettio, S.; Negrini, S.; Selmi, C.; Sciascia, S.; Moroni, G.; Colla, L.; Manno, C.; Urban, M. L.; Vannacci, A.; Pozzi, M. R.; Fabbrini, P.; Polti, S.; Felicetti, M.; Marchi, M. R.; Padoan, R.; Delvino, P.; Caporali, R.; Montecucco, C.; Dagna, L.; Cariddi, A.; Toniati, P.; Tamanini, S.; Furini, F.; Bortoluzzi, A.; Tinazzi, E.; Delfino, L.; Badiu, I.; Rolla, G.; Venerito, V.; Iannone, F.; Berti, A.; Bortolotti, R.; Racanelli, V.; Jeannin, G.; Padula, A.; Cauli, A.; Priori, R.; Gabrielli, A.; Bond, M.; Tedesco, M.; Pazzola, G.; Tomietto, P.; Pellecchio, M.; Marvisi, C.; Maritati, F.; Palmisano, A.; Dejaco, C.; Willeit, J.; Kiechl, S.; Olivotto, I.; Willeit, P.; Prisco, D.; Vaglio, A.; Emmi, G.; Bargagli, E.; Becatti, M.; Beccalli, M.; Bello, F.; Bozzao, F.; Canti, V.; Cassia, M. A.; Cassone, G.; Catanoso, M.; Chieco-Bianchi, F.; Clari, R.; Coladonato, L.; De Santis, M.; Di Scala, G.; Fagni, F.; Fenaroli, P.; Fiorillo, C.; Floris, A.; Fornaro, M.; Galli, E.; Generali, E.; Giliberti, M.; Lascaro, N.; Leccese, I.; Mattioli, I.; Olivieri, B.; Osti, N.; Peyronel, F.; Radin, M.; Righetti, G.; Salvati, S.; Silvestri, E.; Susca, N.; Tamburini, C.; Taurisano, G.; Trezzi, B.; Trivioli, G.
abstract
2021
- Risk of coronavirus disease 2019 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional disease-modifying anti-rheumatic drugs in Italy
[Articolo su rivista]
Alegiani, Stefania Spila; Crisafulli, Salvatore; Rossi, Paolo Giorgi; Mancuso, Pamela; Salvarani, Carlo; Atzeni, Fabiola; Gini, Rosa; Kirchmayer, Ursula; Belleudi, Valeria; Kurotschka, Peter Konstantin; Leoni, Olivia; Ludergnani, Monica; Ferroni, Eliana; Baracco, Susanna; Massari, Marco; Trifirò, Gianluca
abstract
To ascertain if hydroxychloroquine (HCQ)/chloroquine (CLQ) and other conventional disease-modifying anti-rheumatic drugs (cDMARDs) use, and rheumatic diseases per se, may be associated with COVID-19-related risk of hospitalization and mortality.
2021
- Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells
[Articolo su rivista]
Di Tinco, R.; Bertani, G.; Pisciotta, A.; Bertoni, L.; Pignatti, E.; Maccaferri, M.; Bertacchini, J.; Sena, P.; Vallarola, A.; Tupler, R.; Croci, S.; Bonacini, M.; Salvarani, C.; Carnevale, G.
abstract
Background: Dental pulp stem cells (DPSCs) are low immunogenic and hold immunomodulatory properties that, along with their well-established multi-potency, might enhance their potential application in autoimmune and inflammatory diseases. The present study focused on the ability of DPSCs to modulate the inflammatory microenvironment through PD1/PD-L1 pathway. Methods: Inflammatory microenvironment was created in vitro by the activation of T cells isolated from healthy donors and rheumatoid arthritis (RA) patients with anti-CD3 and anti-CD28 antibodies. Direct and indirect co-cultures between DPSCs and PBMCs were carried out to evaluate the activation of immunomodulatory checkpoints in DPSCs and the inflammatory pattern in PBMCs. Results: Our data suggest that the inflammatory stimuli trigger DPSCs immunoregulatory functions that can be exerted by both direct and indirect contact. As demonstrated by using a selective PD-L1 inhibitor, DPSCs were able to activate compensatory pathways targeting to orchestrate the inflammatory process by modulating pro-inflammatory cytokines in pre-activated T lymphocytes. The involvement of PD-L1 mechanism was also observed in autologous inflammatory status (pulpitis) and after direct exposure to pre-activated T cells from RA patients suggesting that immunomodulatory/anti-inflammatory properties are strictly related to their stemness status. Conclusions: Our findings point out that the communication with the inflammatory microenvironment is essential in licensing their immunomodulatory properties.
2021
- Sensing Inflammation Biomarkers with Electrolyte-Gated Organic Electronic Transistors
[Articolo su rivista]
Burtscher, B.; Manco Urbina, P. A.; Diacci, C.; Borghi, S.; Pinti, M.; Cossarizza, A.; Salvarani, C.; Berggren, M.; Biscarini, F.; Simon, D. T.; Bortolotti, C. A.
abstract
An overview of cytokine biosensing is provided, with a focus on the opportunities provided by organic electronic platforms for monitoring these inflammation biomarkers which manifest at ultralow concentration levels in physiopathological conditions. Specifically, two of the field's state-of-the-art technologies—organic electrochemical transistors (OECTs) and electrolyte gated organic field effect transistors (EGOFETs)—and their use in sensing cytokines and other proteins associated with inflammation are a particular focus. The overview will include an introduction to current clinical and “gold standard” quantification techniques and their limitations in terms of cost, time, and required infrastructure. A critical review of recent progress with OECT- and EGOFET-based protein biosensors is presented, alongside a discussion onthe future of these technologies in the years and decades ahead. This is especially timely as the world grapples with limited healthcare diagnostics during the Coronavirus disease (COVID-19)pandemic where one of the worst-case scenarios for patients is the “cytokine storm.” Clearly, low-cost point-of-care technologies provided by OECTs and EGOFETs can ease the global burden on healthcare systems and support professionals by providing unprecedented wealth of data that can help to monitor disease progression in real time.
2021
- Sensitivity to change and clinical correlations of the novel DACtylitis glObal Sonographic (DACTOS) score in psoriatic arthritis
[Articolo su rivista]
Girolimetto, Nicolò; Zabotti, Alen; Tinazzi, Ilaria; Possemato, Niccolò; Costa, Luisa; Batticciotto, Alberto; Canzoni, Marco; Citriniti, Giorgia; De Lucia, Orazio; Figus, Fabiana; Idolazzi, Luca; McConnel, Rebecca; Peluso, Rosario; Sakellariou, Garifallia; Tullio, Annarita; Salvarani, Carlo; Scarpa, Raffaele; Iagnocco, Annamaria; Caso, Francesco; Macchioni, Pierluigi
abstract
The aim of the study is to assess the performance of the DACTOS (DACtylitis glObal Sonographic) score in a psoriatic arthritis (PsA) dactylitis clinical setting. In particular, we evaluated the ability of DACTOS to identify the affected fingers, its sensitivity to change after treatment, the correlations between DACTOS and clinical parameters, and the capacity of the score to identify the treatment responders.
2021
- Susceptibility to COVID-19 in Patients Treated With Antimalarials: A Population-Based Study in Emilia-Romagna, Northern Italy
[Articolo su rivista]
Salvarani, C.; Mancuso, P.; Gradellini, F.; Viani, N.; Pandolfi, P.; Reta, M.; Carrozzi, G.; Sandri, G.; Bajocchi, G.; Galli, E.; Muratore, F.; Boiardi, L.; Pipitone, N.; Cassone, G.; Croci, S.; Marata, A. M.; Costantini, M.; Giorgi Rossi, P.
abstract
Objective: To evaluate the susceptibility to coronavirus disease 2019 (COVID-19) in patients with autoimmune conditions treated with antimalarials in a population-based study. Methods: All residents treated with chloroquine (CQ)/hydroxychloroquine (HCQ) from July through December 2019 and living in 3 provinces of Regione Emilia-Romagna were identified by drug prescription registries and matched with the registry containing all residents living in the same areas who have had swabs and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS–CoV-2). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results: A total of 4,408 patients were identified. The prevalence of patients receiving antimalarials was 0.85 per 1,000 men and 3.3 per 1,000 women. The cumulative incidence of testing during the study period was 2.7% in the general population and 3.8% among those receiving CQ or HCQ, while the cumulative incidence of testing positive was 0.55% in the general population and 0.70% among those receiving CQ/HCQ. Multivariate models showed that those receiving CQ/HCQ had a slightly higher probability of being tested compared to the general population (OR 1.09 [95% CI 0.94–1.28]), the same probability of being diagnosed as having COVID-19 (OR 0.94 [95% CI 0.66–1.34]), and a slightly lower probability of being positive once tested (OR 0.83 [95% CI 0.56–1.23]). None of the differences were significant. Conclusion: Our findings do not support the use of antimalarials as a prophylactic treatment of COVID-19.
2021
- Systemic sclerosis cutaneous expression: Management of skin fibrosis and digital ulcers
[Articolo su rivista]
Starnoni, M.; Pappalardo, M.; Spinella, A.; Testoni, S.; Lattanzi, M.; Femino, R.; De Santis, G.; Salvarani, C.; Giuggioli, D.
abstract
Systemic sclerosis is a connective tissue disease with cutaneous involvement. Clinical manifestations result from the balance of inflammations/autoimmunity process and fibrogenesis. Patients suffer from skin ulcers, non-ulcerative lesions including digital pitting scars, telangiectasias, subungual hyperkeratosis, abrasions, fissures, and subcutaneous calcinosis. A review about the pathophysiology of the disease, the physical examination of the patients, the instrumental assessment, and possible treatments is performed.
2021
- The Italian Society of Rheumatology clinical practice guidelines for the management of large vessel vasculitis
[Articolo su rivista]
Ughi, N.; Padoan, R.; Crotti, C.; Sciascia, S.; Carrara, G.; Zanetti, A.; Rozza, D.; Monti, S.; Camellino, D.; Muratore, F.; Emmi, G.; Quartuccio, L.; Morbelli, S.; El Aoufy, K.; Tonolo, S.; Caporali, R.; De Vita, S.; Salvarani, C.; Cimmino, M. A.
abstract
Objective: Since of the last publication of last recommendations on primary large-vessel vasculitis (LVV) endorsed by the Italian Society of Rheumatology (SIR) in 2012, new evidence emerged regarding the diagnosis and the treatment with conventional and biologic immunosuppressive drugs. The associated potential change of clinical care supported the need to update the original recommendations. Methods: Using the grading of recommendations assessment, development and evaluation (GRADE)-ADOLOPMENT framework, a systematic literature review was performed to update the evidence supporting the European Alliance of Associations for Rheumatology (EULAR) guidelines on LVV as reference. A multidisciplinary panel of 12 expert clinicians, a trained nurse, and a patients’ representative discussed the recommendation in cooperation with an Evidence Review Team. Sixty-one stakeholders were consulted to externally review and rate the recommendations. Results: Twelve recommendations were formulated. A suspected diagnosis of LVV should be confirmed by imaging or histology. In active GCA or TAK, the prompt commencement of high dose of oral glucocorticoids (40-60 mg prednisone-equivalent per day) is strongly recommended to induce clinical remission. In selected patients with GCA (e.g., refractory or relapsing disease or patients at risk of glucocorticoid related adverse effects) the use of an adjunctive therapy (tocilizumab or methotrexate) is recommended. In all patients diagnosed with TAK, adjunctive therapies, such as conventional synthetic or biological immunosuppressants, should be given in combination with glucocorticoids. Conclusions: The new set of SIR recommendations was formulated in order to provide a guidance on both diagnosis and treatment of patients suspected of or with a definite diagnosis of LVV.
2021
- The association between body mass index and fibromyalgia severity: Data from a cross-sectional survey of 2339 patients
[Articolo su rivista]
Atzeni, F.; Alciati, A.; Salaffi, F.; Di Carlo, M.; Bazzichi, L.; Govoni, M.; Biasi, G.; Di Franco, M.; Mozzani, F.; Gremese, E.; Dagna, L.; Batticciotto, A.; Fischetti, F.; Giacomelli, R.; Guiducci, S.; Guggino, G.; Bentivegna, M.; Gerli, R.; Salvarani, C.; Bajocchi, G.; Ghini, M.; Iannone, F.; Giorgi, V.; Farah, S.; Bonazza, S.; Barbagli, S.; Gioia, C.; Marino, N. G.; Capacci, A.; Cavalli, G.; Cappelli, A.; Carubbi, F.; Nacci, F.; Riccucci, I.; Cutolo, M.; Sinigaglia, L.; Sarzi-Puttini, P.
abstract
Objective: Various studies have shown that overweight and obesity are central features of FM, but the real impact of a high BMI on clinical severity in patients with FM is still controversial. The aim of this study was to analyse the relationships between BMI categories and measures of symptom severity and functional impairment using data from a Web-based registry of patients with FM. Methods: Adult patients with an ACR 2010/2011 diagnosis of FM underwent a complete physical examination and laboratory tests and were asked to complete a package of questionnaires covering their sociodemographic and treatment details, in addition to the following disease-specific questionnaires: the revised Fibromyalgia Impact Questionnaire (FIQR), the modified Fibromyalgia Assessment Status questionnaire (ModFAS) and the Polysymptomatic Distress Scale (PDS). Results: A total of 2339 patients were recruited and divided into two weight categories, underweight/normal (U/N, n = 1127, 48.2%) and overweight/obese (O/O, n = 1212, 51.8%). The total and subscales of FIQR, ModFAS and PSD scores were significantly higher in the O/O patients, as were all the mean scores of the individual FIQR items (P < 0.001 for all). Conclusion: Our findings demonstrate that O/O patients with FM are significantly more impaired than U/N patients in all the symptomatological and functional domains as measured using the FIQR, ModFAS and PDS, thus suggesting that being O/O has an additional effect on symptoms and function.
2021
- The association between clinical laboratory data and chest CT findings explains disease severity in a large Italian cohort of COVID-19 patients
[Articolo su rivista]
Canovi, S.; Besutti, G.; Bonelli, E.; Iotti, V.; Ottone, M.; Albertazzi, L.; Zerbini, A.; Pattacini, P.; Giorgi Rossi, P.; Colla, R.; Fasano, T.; Costantini, M.; Grilli, R.; Marino, M.; Formoso, G.; Formisano, D.; Rossi, P. G.; Bedeschi, E.; Perilli, C.; La Rosa, E.; Bisaccia, E.; Venturi, I.; Vicentini, M.; Campari, C.; Gioia, F.; Broccoli, S.; Spaggiari, L.; Mancuso, P.; Nitrosi, A.; Foracchia, M.; Massari, M.; Ferrari, A. M.; Pinotti, M.; Facciolongo, N.; Lattuada, I.; Trabucco, L.; De Pietri, S.; Danelli, G. F.; Bellesia, E.; Canovi, S.; Corradini, M.; Magnani, E.; Pilia, A.; Polese, A.; Incerti, S. S.; Zaldini, P.; Orsola, B.; Revelli, M.; Salvarani, C.; Pinto, C.; Venturelli, F.
abstract
Background: Laboratory data and computed tomography (CT) have been used during the COVID-19 pandemic, mainly to determine patient prognosis and guide clinical management. The aim of this study was to evaluate the association between CT findings and laboratory data in a cohort of COVID-19 patients. Methods: This was an observational cross-sectional study including consecutive patients presenting to the Reggio Emilia (Italy) province emergency rooms for suspected COVID-19 for one month during the outbreak peak, who underwent chest CT scan and laboratory testing at presentation and resulted positive for SARS-CoV-2. Results: Included were 866 patients. Total leukocytes, neutrophils, C-reactive protein (CRP), creatinine, AST, ALT and LDH increase with worsening parenchymal involvement; an increase in platelets was appreciable with the highest burden of lung involvement. A decrease in lymphocyte counts paralleled worsening parenchymal extension, along with reduced arterial oxygen partial pressure and saturation. After correcting for parenchymal extension, ground-glass opacities were associated with reduced platelets and increased procalcitonin, consolidation with increased CRP and reduced oxygen saturation. Conclusions: Pulmonary lesions induced by SARS-CoV-2 infection were associated with raised inflammatory response, impaired gas exchange and end-organ damage. These data suggest that lung lesions probably exert a central role in COVID-19 pathogenesis and clinical presentation.
2021
- The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients
[Articolo su rivista]
Besutti, Giulia; Pellegrini, Massimo; Ottone, Marta; Cantini, Michele; Milic, Jovana; Bonelli, Efrem; Dolci, Giovanni; Cassone, Giulia; Ligabue, Guido; Spaggiari, Lucia; Pattacini, Pierpaolo; Fasano, Tommaso; Canovi, Simone; Massari, Marco; Salvarani, Carlo; Guaraldi, Giovanni; Rossi, Paolo Giorgi; Canovi, Simoneg; Massari, Marcoh; Salvarani, Carloi; Guaraldi, Giovannif; Rossi, Paolo Giorgie; Grilli, Roberto; Marino, Massimiliano; Formoso, Giulio; Formisano, Debora; Bedeschi, Emanuela; Perilli, Cinzia; la Rosa, Elisabetta; Bisaccia, Eufemia; Venturi, Ivano; Vicentini, Massimo; Campari, Cinzia; Gioia, Francesco; Broccoli, Serena; Iotti, Valentina; Mancuso, Pamela; Nitrosi, Andrea; Foracchia, Marco; Colla, Rossana; Zerbini, Alessandro; Ferrari, Anna Maria; Pinotti, Mirco; Facciolongo, Nicola; Lattuada, Ivana; Trabucco, Laura; de Pietri, Stefano; Danelli, Giorgio Francesco; Albertazzi, Laura; Bellesia, Enrica; Corradini, Mattia; Mag-Nani, Elena; Pilia, Annalisa; Polese, Alessandra; Incerti, Silvia Storchi; Zaldini, Piera; Bonanno, Orsola; Revelli, Matteo; Pinto, Carmine; Venturelli, Francesco; Teopompi, Elisabetta; Gallina, Annalisa; Bertellini, Annalisa; Costi, Stefania; Fugazzaro, Stefania
abstract
We assessed the impact of chest CT body composition parameters on outcomes and disease severity at hospital presentation of COVID-19 patients, focusing also on the possible mediation of body composition in the relationship between age and death in these patients. Chest CT scans performed at hospital presentation by consecutive COVID-19 patients (02/27/2020-03/13/2020) were retrospectively reviewed to obtain pectoralis muscle density and total, visceral, and intermuscular adipose tissue areas (TAT, VAT, IMAT) at the level of T7-T8 vertebrae. Primary outcomes were: hospitalization, mechanical ventilation (MV) and/or death, death alone. Secondary outcomes were: C-reactive protein (CRP), oxygen saturation (SO2), CT disease extension at hospital presentation. The mediation of body composition in the effect of age on death was explored. Of the 318 patients included in the study (median age 65.7 years, females 37.7%), 205 (64.5%) were hospitalized, 68 (21.4%) needed MV, and 58 (18.2%) died. Increased muscle density was a protective factor while increased TAT, VAT, and IMAT were risk factors for hospitalization and MV/death. All these parameters except TAT had borderline effects on death alone. All parameters were associated with SO2 and extension of lung parenchymal involvement at CT; VAT was associated with CRP. Approximately 3% of the effect of age on death was mediated by decreased muscle density. In conclusion, low muscle quality and ectopic fat accumulation were associated with COVID-19 outcomes, VAT was associated with baseline inflammation. Low muscle quality partly mediated the effect of age on mortality.
2021
- The management of large vessel vasculitides
[Articolo su rivista]
Galli, Elena; Marvisi, Chiara; Sandri, Gilda; Manzini, Carlo Umberto; Salvarani, Carlo
abstract
2021
- The value of computed tomography in assessing the risk of death in COVID-19 patients presenting to the emergency room
[Articolo su rivista]
Besutti, G.; Ottone, M.; Fasano, T.; Pattacini, P.; Iotti, V.; Spaggiari, L.; Bonacini, R.; Nitrosi, A.; Bonelli, E.; Canovi, S.; Colla, R.; Zerbini, A.; Massari, M.; Lattuada, I.; Ferrari, A. M.; Giorgi Rossi, P.; Costantini, M.; Grilli, R.; Marino, M.; Formoso, G.; Formisano, D.; Bedeschi, E.; Perilli, C.; La Rosa, E.; Bisaccia, E.; Venturi, I.; Vicentini, M.; Campari, C.; Gioia, F.; Broccoli, S.; Mancuso, P.; Foracchia, M.; Pinotti, M.; Facciolongo, N.; Trabucco, L.; De Pietri, S.; Danelli, G. F.; Albertazzi, L.; Bellesia, E.; Corradini, M.; Magnani, E.; Pilia, A.; Polese, A.; Incerti, S. S.; Zaldini, P.; Orsola, B.; Revelli, M.; Salvarani, C.; Pinto, C.; Venturelli, F.
abstract
Objective: The aims of this study were to develop a multiparametric prognostic model for death in COVID-19 patients and to assess the incremental value of CT disease extension over clinical parameters. Methods: Consecutive patients who presented to all five of the emergency rooms of the Reggio Emilia province between February 27 and March 23, 2020, for suspected COVID-19, underwent chest CT, and had a positive swab within 10 days were included in this retrospective study. Age, sex, comorbidities, days from symptom onset, and laboratory data were retrieved from institutional information systems. CT disease extension was visually graded as < 20%, 20–39%, 40–59%, or ≥ 60%. The association between clinical and CT variables with death was estimated with univariable and multivariable Cox proportional hazards models; model performance was assessed using k-fold cross-validation for the area under the ROC curve (cvAUC). Results: Of the 866 included patients (median age 59.8, women 39.2%), 93 (10.74%) died. Clinical variables significantly associated with death in multivariable model were age, male sex, HDL cholesterol, dementia, heart failure, vascular diseases, time from symptom onset, neutrophils, LDH, and oxygen saturation level. CT disease extension was also independently associated with death (HR = 7.56, 95% CI = 3.49; 16.38 for ≥ 60% extension). cvAUCs were 0.927 (bootstrap bias-corrected 95% CI = 0.899–0.947) for the clinical model and 0.936 (bootstrap bias-corrected 95% CI = 0.912–0.953) when adding CT extension. Conclusions: A prognostic model based on clinical variables is highly accurate in predicting death in COVID-19 patients. Adding CT disease extension to the model scarcely improves its accuracy. Key Points: • Early identification of COVID-19 patients at higher risk of disease progression and death is crucial; the role of CT scan in defining prognosis is unclear. • A clinical model based on age, sex, comorbidities, days from symptom onset, and laboratory results was highly accurate in predicting death in COVID-19 patients presenting to the emergency room. • Disease extension assessed with CT was independently associated with death when added to the model but did not produce a valuable increase in accuracy.
2021
- Tocilizumab in Treatment for Patients with COVID-19 - Reply
[Articolo su rivista]
Salvarani, C.; Massari, M.; Facciolongo, N.
abstract
2021
- Tofacitinib for the Treatment of Severe Interstitial Lung Disease Related to Rheumatoid Arthritis
[Articolo su rivista]
Vacchi, C.; Manfredi, A.; Cassone, G.; Cerri, S.; Della Casa, G.; Andrisani, D.; Salvarani, C.; Sebastiani, M.
abstract
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by chronic symmetrical erosive synovitis and extra-articular manifestations, including interstitial lung disease (ILD), whose treatment is nowadays challenging due to high infectious risk and possible pulmonary iatrogenic toxicity. Janus kinase inhibitors, namely, tofacitinib, baricitinib, and upadacitinib, are the latest drug class for the treatment of RA with a good safety profile. We present the case of a patient with RA-ILD successfully treated with tofacitinib. A 52-year-old man was referred to our multidisciplinary clinic for rheumatic and pulmonary diseases for an active erosive seropositive RA and progressive ILD. Previous treatments were GC, hydroxychloroquine, methotrexate, etanercept, withdrawn after ILD detection, and tocilizumab, discontinued due to relapsing infections. After our evaluation, we proposed rituximab in addition to low-dose GC and hydroxychloroquine, ineffective on joint involvement. Therefore, we proposed tofacitinib which allowed us to control joint involvement, stabilize ILD improving respiratory symptoms, and manage the frequent infectious episodes that occurred initially. The short half-life and rapid-acting of tofacitinib are two helpful characteristics regarding this aspect. Despite limited data from randomized trials and real-life, tofacitinib could represent a safe therapeutic option for RA-ILD patients. Longitudinal studies are required to confirm this encouraging report.
2021
- Ultrasound Effectiveness of Steroid Injection for hand Psoriatic Dactylitis: Results from a Longitudinal Observational Study
[Articolo su rivista]
Girolimetto, N.; Macchioni, P.; Tinazzi, I.; Possemato, N.; Costa, L.; Bascherini, V.; Peluso, R.; Citriniti, G.; Galletto, G.; Martinis, F.; Marchetta, A.; Sabbatino, V.; Tasso, M.; Passavanti, S.; Salvarani, C.; Scarpa, R.; Caso, F.
abstract
Introduction: To assess clinical and ultrasound effectiveness of steroid injection (local treatment, LT) into the digital flexor tendon sheath for the treatment of psoriatic dactylitis compared to systemic treatment (ST) alone. Methods: In this observational, multicentre, prospective study, 88 cases of symptomatic hand dactylitis were evaluated clinically and sonographically by high-frequency ultrasound (US) probe in both greyscale (GS) and power Doppler (PD). The presence of flexor tenosynovitis (FT), soft tissue oedema (STO), peritendon extensor inflammation and synovitis was assessed (including DACtylitis glObal Sonographic—DACTOS—score) before treatment, at 1-month (T1) and 3-months (T3) follow-up. LT was proposed to all patients. Patients refusing LT were treated with oral NSAIDs. Patients continued the same baseline csDMARDs and/or corticosteroid therapy during the whole follow-up period. US response was defined for DACTOS score < 3 and US remission for DACTOS score = 0. Results: At T3 evaluation the ST group showed a significantly higher persistence (grade > 1) of FT and STO (p < 0.001 for all) and MCP synovitis (p = 0.001). US remission was achieved only in the LT group (at T3 31% vs. 0, p < 0.001). The percentage of patients with DACTOS < 3 was significantly greater in the LT group compared with ST group, at both T1 (49% vs. 5%, p < 0.001) and T3 evaluation (76% vs. 7%, p < 0.001). In multiple conditional logistic regression analysis, the only factor associated with US remission was LT (T3 odds ratio = 41.21, p < 0.001). Conclusions: US confirmed the effectiveness of steroid injection for dactylitis by demonstrating that it involves the resolution of extra-articular inflammation, in particular FT and STO.
2021
- Usefulness of digital velcro crackles detection in identification of interstitial lung disease in patients with connective tissue diseases
[Articolo su rivista]
Manfredi, A.; Cassone, G.; Vacchi, C.; Pancaldi, F.; Casa, G. D.; Cerri, S.; De Pasquale, L.; Luppi, F.; Salvarani, C.; Sebastiani, M.
abstract
Objectives: This study aims to evaluate the diagnostic accuracy of the VECTOR software in patients with connective tissue diseases (CTDs), compared with the reference standard of high-resolution computed tomography (HRCT). Patients and methods: The study included 98 consecutive patients of CTD (24 males, 74 females; median age: 66 years; range, 24 to 85 years) with a recent HRCT. Patients were evaluated in a blindly manner by VECTOR and the results obtained by the algorithm were compared with the presence of interstitial lung disease (ILD) according to HRCT. Results: Interstitial lung disease was detected in 42.8% of subjects. VECTOR correctly classified 81/98 patients, with a diagnostic accuracy of 82.6%; sensitivity and specificity were 88.1% and 78.6%, respectively. Only 5/42 patients with ILD were not correctly classified by VECTOR, while false positive cases were 21.4%. No significant differences were observed according to the radiologic pattern of ILD. Conclusion: VECTOR showed high sensitivity, specificity and diagnostic accuracy, allowing selecting patients to be investigated with HRCT. The relatively high frequency rate of false positive results is acceptable if compared with the lack of effective screening methods for this complication of CTDs.
2021
- Uveitis and other ocular complications following covid-19 vaccination
[Articolo su rivista]
Bolletta, E.; Iannetta, D.; Mastrofilippo, V.; De Simone, L.; Gozzi, F.; Croci, S.; Bonacini, M.; Belloni, L.; Zerbini, A.; Adani, C.; Fontana, L.; Salvarani, C.; Cimino, L.
abstract
Coronavirus disease 2019 (COVID-19) vaccines can cause transient local and systemic post-vaccination reactions. The aim of this study was to report uveitis and other ocular complications following COVID-19 vaccination. The study included 42 eyes of 34 patients (20 females, 14 males), with a mean age of 49.8 years (range 18–83 years). The cases reported were three herpetic keratitis, two anterior scleritis, five anterior uveitis (AU), three toxoplasma retinochoroiditis, two Vogt-Koyanagi-Harada (VKH) disease reactivations, two pars planitis, two retinal vasculitis, one bilateral panuveitis in new-onset Behçet’s disease, three multiple evanescent white dot syndromes (MEWDS), one acute macular neuroretinopathy (AMN), five retinal vein occlusions (RVO), one non-arteritic ischemic optic neuropathy (NAION), three activations of quiescent choroidal neovascularization (CNV) secondary to myopia or uveitis, and one central serous chorioretinopathy (CSCR). Mean time between vaccination and ocular complication onset was 9.4 days (range 1–30 days). Twenty-three cases occurred after Pfizer-BioNTech vaccination (BNT162b2 mRNA), 7 after Oxford-AstraZeneca vaccine (ChAdOx1 nCoV-19), 3 after ModernaTX vaccination (mRNA-1273), and 1 after Janssen Johnson & Johnson vaccine (Ad26.COV2). Uveitis and other ocular complications may develop after the administration of COVID-19 vaccine.
2021
- Vogt–Koyanagi–Harada patients show higher frequencies of circulating NKG2Dpos NK and NK T cells
[Articolo su rivista]
Bonacini, M.; Cimino, L.; De Simone, L.; Bolletta, E.; Gozzi, F.; Soriano, A.; Muratore, F.; Zerbini, A.; Fontana, L.; Salvarani, C.; Croci, S.
abstract
Vogt–Koyanagi–Harada (VKH) is an autoimmune disease characterized by inflammation in tissues that contain melanocytes. We aimed to increase the knowledge regarding immunological pathways deregulated in VKH disease. We compared the percentages of circulating natural killer (NK), NK T and T cells expressing the activatory markers: CD16, CD69, NK group 2D (NKG2D), natural cytotoxicity triggering receptor 3 (Nkp30), natural cytotoxicity triggering receptor 1 (Nkp46) and the inhibitory marker: NK group 2 member A (NKG2A) in 10 active VKH patients, 20 control subjects (CTR) and seven patients with Behçet disease (BD) by flow cytometry. Cytotoxic potential of NK cells was determined through the degranulation marker CD107a expression after contact with K562 cells by flow cytometry. Moreover, plasmatic levels of 27 cytokines were determined with a multiplex bead-based assay. VKH patients showed higher percentages of NKG2Dpos NK and NK T cells versus CTR. The cytotoxic potential of NK cells induced by K562 cells was comparable between VKH patients and CTR. Finally, higher concentrations of interleukin (IL)-4, IL-5, IL-7, IL-17 and platelet-derived growth factor-subunits B (PDGF-bb) were detected in plasma of VKH patients versus CTR. The immune profile of VKH patients was similar to that of BD patients.
2020
- 2018 Update of the EULAR recommendations for the management of large vessel vasculitis
[Articolo su rivista]
Hellmich, B.; Agueda, A.; Monti, S.; Buttgereit, F.; De Boysson, H.; Brouwer, E.; Cassie, R.; Cid, M. C.; Dasgupta, B.; Dejaco, C.; Hatemi, G.; Hollinger, N.; Mahr, A.; Mollan, S. P.; Mukhtyar, C.; Ponte, C.; Salvarani, C.; Sivakumar, R.; Tian, X.; Tomasson, G.; Turesson, C.; Schmidt, W.; Villiger, P. M.; Watts, R.; Young, C.; Luqmani, R. A.
abstract
Background Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. Methods Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. Results Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. Conclusions We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
2020
- AB0611 STRAIN ANALYSIS OF THE RIGHT VENTRICLE USING 2D-SPECKLE TRACKING ECHOCARDIOGRAPHY IN A COHORT OF PATIENTS WITH SYSTEMIC SCLEROSIS
[Abstract in Rivista]
Spinella, A; Macripo, P; Cocchiara, E; Galli, E; Lumetti, F; Magnani, L; Coppi, F; Mattioli, Av; Rossi, R; Boriani, G; Salvarani, C; Giuggioli, D
abstract
Background:
Systemic Sclerosis (SSc) is a rare and life-threatening connective tissue disease with multiple organ impairment. Cardio-pulmonary involvement is common: pulmonary fibrosis, pulmonary hypertension (PH), and electrical disorders are the most serious complications and causes of increased mortality.
Objectives:
We evaluated features related with the onset and development of PH in a cohort of SSc patients. We further studied ecocardiographic abnormalities, by means of 2D-speckle tracking echocardiography (STE) with specific reference to the right ventricular strain measure (RV-strain).
Methods:
We analyzed data from 50 SSc patients (pts) referred to our University-based Rheumatology Centre and SSc Unit from January 2007 to June 2019 (F/M 45/5; lc/dcSSc 45/5; mean age 59.20±14.357 years; mean disease duration 12.08±8.75 years). All pts underwent general and cardio-pulmonary …
2020
- Accuracy of CT in a cohort of symptomatic patients with suspected COVID-19 pneumonia during the outbreak peak in Italy
[Articolo su rivista]
Besutti, G.; Giorgi Rossi, P.; Iotti, V.; Spaggiari, L.; Bonacini, R.; Nitrosi, A.; Ottone, M.; Bonelli, E.; Fasano, T.; Canovi, S.; Colla, R.; Massari, M.; Lattuada, I. M.; Trabucco, L.; Pattacini, P.; Costantini, M.; Formoso, G.; Bedeschi, M.; Perilli, C.; Venturi, I.; Bisaccia, E.; La Rosa, E.; Campari, C.; Gioia, F.; Broccoli, S.; Mancuso, P.; Foracchia, M.; Zerbini, A.; Dolci, G.; Corsini, R.; Sampaolesi, F.; Ferrari, A. M.; Pinotti, M.; Facciolongo, N.; Lattuada, I.; De Pietri, S.; Danelli, G. F.; Albertazzi, L.; Bellesia, E.; Corradini, M.; Magnani, E.; Pilia, A.; Polese, A.; Incerti, S. S.; Zaldini, P.; Orsola, B.; Revelli, M.; Salvarani, C.; Venturelli, F.
abstract
Objective: To assess sensitivity/specificity of CT vs RT-PCR for the diagnosis of COVID-19 pneumonia in a prospective Italian cohort of symptomatic patients during the outbreak peak. Methods: In this cross-sectional study, we included all consecutive patients who presented to the ER between March 13 and 23 for suspected COVID-19 and underwent CT and RT-PCR within 3 days. Using a structured report, radiologists prospectively classified CTs in highly suggestive, suggestive, and non-suggestive of COVID-19 pneumonia. Ground-glass, consolidation, and visual extension of parenchymal changes were collected. Three different RT-PCR-based reference standard definitions were used. Oxygen saturation level, CRP, LDH, and blood cell counts were collected and compared between CT/RT-PCR classes. Results: The study included 696 patients (41.4% women; age 59 ± 15.8 years): 423/454 (93%) patients with highly suggestive CT, 97/127 (76%) with suggestive CT, and 31/115 (27%) with non-suggestive CT had positive RT-PCR. CT sensitivity ranged from 73 to 77% and from 90 to 94% for high and low positivity threshold, respectively. Specificity ranged from 79 to 84% for high positivity threshold and was about 58% for low positivity threshold. PPV remained ≥ 90% in all cases. Ground-glass was more frequent in patients with positive RT-PCR in all CT classes. Blood tests were significantly associated with RT-PCR and CT classes. Leukocytes, lymphocytes, neutrophils, and platelets decreased, CRP and LDH increased from non-suggestive to suggestive CT classes. Conclusions: During the outbreak peak (in a high-prevalence setting), CT presented high PPV and may be considered a good reference to recognize COVID-19 patients while waiting for RT-PCR confirmation. Key Points: • During the epidemic peak, CT showed high positive predictive value and sensitivity for COVID-19 pneumonia when compared with RT-PCR. • Blood tests were significantly associated with RT-PCR and CT classes.
2020
- Acute-phase reactants during tocilizumab therapy for severe COVID-19 pneumonia
[Articolo su rivista]
Cassone, G.; Dolci, G.; Besutti, G.; Muratore, F.; Bajocchi, G.; Mancuso, P.; Catanoso, M.; Spaggiari, L.; Galli, E.; Palermo, A.; Pipitone, N.; Croci, S.; Massari, M.; Facciolongo, N.; Menzella, F.; Negri, E. A.; Zerbini, A.; Belloni, L.; Cimino, L.; Teopompi, E.; Sampaolesi, F.; Salsi, P.; Costantini, M.; Giorgi Rossi, P.; Aldigeri, R.; Salvarani, C.
abstract
OBJECTIVES: To identify predictors of clinical improvement and intubation/death in tocilizumab-treated severe COVID19, focusing on IL6 and CRP longitudinal monitoring. METHODS: 173 consecutive patients with severe COVID-19 pneumonia receiving tocilizumab in Reggio Emilia province Hospitals between 11 March and 3 June 2020 were enrolled in a prospective cohort study. Clinical improvement was defined as status improvement on a six-category ordinal scale or discharge from the hospital, whichever came first. A composite outcome of intubation/death was also evaluated. CRP and IL-6 levels were determined before TCZ administration (T0) and after 3 (T3), and 7 (T7) days. RESULTS: At multivariate analysis T0 and T3 CRP levels were negatively associated with clinical improvement (OR 0.13, CI 0.03-0.55 and OR 0.11, CI 0.0-0.46) (p=0.006 and p=0.003) and positively associated with intubation/death (OR 17.66, CI 2.47-126.14 and OR 5.34, CI: 1.49-19.12) (p=0.01 and p=0.004). No significant associations with IL-6 values were observed. General linear model analyses for repeated measures showed significantly different trends for CRP from day 3 to day 7 between patients who improved and those who did not, and between patients who were intubated or died and those who were not (p<0.0001 for both). ROC analysis identified a baseline CRP level of 15.8 mg/dl as the best cut-off to predict intubation/death (AUC = 0.711, sensitivity = 0.67, specificity = 0.71). CONCLUSIONS: CRP serial measurements in the first week of TCZ therapy are useful in identifying patients developing poor outcomes.
2020
- Alveolar haemorrhage in ANCA-associated vasculitis: Long-term outcome and mortality predictors
[Articolo su rivista]
Quartuccio, L.; Bond, M.; Isola, M.; Monti, S.; Felicetti, M.; Furini, F.; Murgia, S.; Berti, A.; Silvestri, E.; Pazzola, G.; Bozzolo, E.; Leccese, P.; Raffeiner, B.; Parisi, S.; Leccese, I.; Cianci, F.; Bettio, S.; Sainaghi, P.; Ianniello, A.; Ravagnani, V.; Bellando Randone, S.; Faggioli, P.; Lomater, C.; Stobbione, P.; Ferro, F.; Colaci, M.; Alfieri, G.; Carubbi, F.; Erre, G. L.; Giollo, A.; Franzolini, N.; Ditto, M. C.; Balduzzi, S.; Padoan, R.; Bortolotti, R.; Bortoluzzi, A.; Cariddi, A.; Padula, A.; Di Scala, G.; Gremese, E.; Conti, F.; D'Angelo, S.; Matucci Cerinic, M.; Dagna, L.; Emmi, G.; Salvarani, C.; Paolazzi, G.; Roccatello, D.; Govoni, M.; Schiavon, F.; Caporali, R.; De Vita, S.
abstract
Introduction: Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). Objectives: The aim of this study was to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset. Materials and methods: A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed. Results: One-hundred and six patients were included (median age at onset of 55 years [IQR 42–67]). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months [IQR 13–77] follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 [95% CI 1.4–9.51], p = 0.008) and the need for respiratory support (HR 4.58 [95% CI 1.51–13.87], p = 0.007) at AH onset were confirmed to be predictive of mortality. Conclusions: Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial.
2020
- An observational prospective study on predictors of clinical response at six months in patients with active psoriatic arthritis treated with golimumab
[Articolo su rivista]
Scrivo, Rossana; Giardino, Angela M; Salvarani, Carlo; Foti, Rosario; Afeltra, Antonella; Viapiana, Ombretta; Giacomelli, Roberto; Salaffi, Fausto; Galeazzi, Mauro; Ramonda, Roberta; Ciccia, Francesco; Valesini, Guido; Iannone, Florenzo
abstract
OBJECTIVES:
Recently, research has been focused on the identification of predictors of response to treatment in patients with active psoriatic arthritis (PsA). The objective of this study was to develop a model to predict the clinical response at 6 months in patients with PsA starting the anti-tumour necrosis factor-α golimumab.
METHODS:
This prospective observational study explored a range of factors, including demographic data and baseline characteristics of the disease, measures of disease activity and functional disability, and potential laboratory biomarkers in the prediction of response, defined as the achievement of modified-minimal disease activity (mMDA), to golimumab in PsA patients.
RESULTS:
We studied 151 PsA patients starting golimumab because of their active disease. After 6 months, the rate of drug persistence on golimumab was 80%, and mMDA was achieved in 44.3% of patients. Using univariate and multivariate logistic regression models, lower disease activity in PsA score (DAPSA) at baseline (odds ratio [OR] 0.92; 95% confidence interval [CI] 0.89-0.96, p<0.001) was independent predictor of mMDA at 6 months. High sensitivity C-reactive protein value (OR 1.06; 95% CI 1.00-1.13, p=0.026) at baseline also was a predictive factor of mMDA achievement at 6 months in the laboratory-enhanced prediction model. Golimumab was safe and well tolerated.
CONCLUSIONS:
The identification of factors predictive of response to treatment may help in better understanding the response to golimumab and in identifying PsA patients that are most likely to achieve mMDA following therapy with golimumab.
2020
- Association between Leeds Dactylitis Index and ultrasonographic features: a multicentre study on psoriatic hand dactylitis
[Articolo su rivista]
Girolimetto, N.; Macchioni, P.; Tinazzi, I.; Costa, L.; Peluso, R.; Tasso, M.; Bottiglieri, P.; Marchetta, A.; Possemato, N.; Salvarani, C.; Mcgonagle, D.; Scarpa, R.; Caso, F.
abstract
OBJECTIVES: The aim of this study was to explore the link between specific sonographic findings and Leeds Dactylitis Index basic (LDI-b) score in psoriatic arthritis (PsA) patients with hand dactylitis. METHODS: Ninety-one hand dactylitis were evaluated in a multicentre study for the presence of pain, functional limitation and tenderness (2-point scale) and LDI-b score. Dactylitic fingers were investigated using high-frequency US in grey scale (GS) and power Doppler (PD). According to median LDI-b score value of 12, fingers were then divided into two groups and categorised into quartiles on the basis of the value of ratio of circumference. RESULTS: Dactylitic fingers with a LDI-b score >12 showed a significantly higher prevalence of GS flexor tenosynovitis (p=0.015), PD flexor tenosynovitis (p=0.001) and soft tissue oedema (p=0.004), when compared with those with those with LDI-b score <12. GS synovitis at proximal interphalangeal (PIP) level (p=0.003) showed more frequent in dactylitic fingers with a LDI-b score <12, than those with a higher LDI-b value. Fingers in the fourth quartile showed a significantly higher prevalence of GS flexor tenosynovitis of grade ≥2 (p=0.046) and joint synovitis of grade ≥2 at PIP level (p=0.028). CONCLUSIONS: We found that high values of LDI are associated with US flexor tenosynovitis and soft tissue oedema in PsA dactylitis. Results suggest a potential role of PIP joint synovitis in the genesis of hand digital swelling and of extra-articular structures alterations in determining the LDI score.
2020
- Autologous Fat Grafting for the Oral and Digital Complications of Systemic Sclerosis: Results of a Prospective Study
[Articolo su rivista]
Pignatti, Marco; Spinella, Amelia; Cocchiara, Emanuele; Boscaini, Giulia; Lusetti, Irene Laura; Citriniti, Giorgia; Lumetti, Federica; Setti, Giacomo; Dominici, Massimo; Salvarani, Carlo; De Santis, Giorgio; Giuggioli, Dilia
abstract
Background: Systemic sclerosis is a connective tissue disease. Skin involvement of the mouth and hand may compromise function and quality of life. Autologous fat grafting has been described as a specific treatment of these clinical features. We report the results of our prospective study designed to treat and prevent skin complications in systemic sclerosis.
Materials and methods: We treated 25 patients with mouth and/or hand involvement (microstomia, xerostomia, skin sclerosis, Raynaud's phenomenon and long-lasting digital ulcers) with autologous fat grafting, according to the Coleman's technique, around the mouth and/or at the base of each finger. The surgical procedures were repeated in each patient every 6 months for a total of two or three times. Clinical data were collected before the first surgery and again 6 months after each surgical procedure. Pain, skin thickness, saliva production and disability were assessed with validated tests.
Results: Overall we performed 63 autologous fat grafting sessions (either on the mouth, on the hands or on both anatomical areas). Results at 6 moths after the last session included improvement of xerostomia evaluated with a sialogram, reduction of the skin tension around the mouth and, in the hands, reduction of the Raynaud phenomenon as well as skin thickness. Pain was reduced while the perception of disability improved. Digital ulcers healed completely in 8/9 patients.
Conclusions: Our results confirm the efficacy and safety of autologous fat grafting for the treatment of skin complications and digital ulcers due to systemic sclerosis. In addition, the patients' subjective well-being improved. Level of evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Keywords: Autologous fat grafting; Digital ulcers; Microstomia; Stem cell transplantation; Systemic sclerosis; Xerostomia.
2020
- CHARACTERIZATION OF ANTI-MPO POSITIVE INTERSTITIAL LUNG DISEASE. CLINICAL-SEROLOGIC AND RADIOLOGIC FEATURES AND SURVIVAL
[Abstract in Rivista]
Cassone, G; Dei, G; Sambataro, G; Manfredi, A; Cerri, S; Vacchi, C; Faverio, P; Sambataro, D; Gozzi, F; Vancheri, C; Salvarani, C; Luppi, F; Sebastiani, M
abstract
2020
- COVID-19-associated vasculitis and thrombotic complications: from pathological findings to multidisciplinary discussion
[Articolo su rivista]
Vacchi, Caterina; Meschiari, Marianna; Milic, Jovana; Marietta, Marco; Tonelli, Roberto; Alfano, Gaetano; Volpi, Sara; Faltoni, Matteo; Franceschi, Giacomo; Ciusa, Giacomo; Bacca, Erica; Tutone, Marco; Raimondi, Alessandro; Menozzi, Marianna; Franceschini, Erica; Cuomo, Gianluca; Orlando, Gabriella; Santoro, Antonella; Di Gaetano, Margherita; Puzzolante, Cinzia; Carli, Federica; Bedini, Andrea; Cossarizza, Andrea; Castaniere, Ivana; Ligabue, Guido; De Ruvo, Nicola; Manco, Gianrocco; Rolando, Giovanni; Gelmini, Roberta; Maiorana, Antonino; Girardis, Massimo; Mascia, Maria Teresa; Mussini, Cristina; Salvarani, Carlo; Guaraldi, Giovanni
abstract
Neutrophilic arterial vasculitis in COVID-19 represents a novel finding and could be responsible for thrombotic complications.
2020
- Cardiac involvement in the adult primary vasculitides
[Articolo su rivista]
Pazzola, G.; Pipitone, N.; Salvarani, C.
abstract
Introduction: Heart involvement in vasculitis is rare, but potentially severe. The ascertainment of cardiac disease in vasculitis is complex and requires an integrated multidisciplinary approach involving the Rheumatologist, Radiologist, Cardiologist, and Heart surgeon. Areas covered: the authors searched PubMed using the keywords ‘heart’[Mesh] and vasculitis”[Mesh]. Expert opinion: Virtually any vasculitis can affect the heart, but cardiac involvement is more common in some vasculitides such as Takayasu arteritis, polyarteritis nodosa, and eosinophilic granulomatosis with polyangiitis. Immunosuppressive treatment and when indicated surgery can improve the prognosis.
2020
- Clinical Features at Onset and Genetic Characterization of Pediatric and Adult Patients with TNF- α Receptor - Associated Periodic Syndrome (TRAPS): A Series of 80 Cases from the AIDA Network
[Articolo su rivista]
Gaggiano, C.; Vitale, A.; Obici, L.; Merlini, G.; Soriano, A.; Viapiana, O.; Cattalini, M.; Maggio, M. C.; Lopalco, G.; Montin, D.; Jaber, M. A.; Dagna, L.; Manna, R.; Insalaco, A.; Piga, M.; La Torre, F.; Berlengiero, V.; Gelardi, V.; Ciarcia, L.; Emmi, G.; Ruscitti, P.; Caso, F.; Cimaz, R.; Hernandez-Rodriguez, J.; Parronchi, P.; Sicignano, L. L.; Verrecchia, E.; Iannone, F.; Sota, J.; Grosso, S.; Salvarani, C.; Frediani, B.; Giacomelli, R.; Mencarelli, M. A.; Renieri, A.; Rigante, D.; Cantarini, L.
abstract
This study explores demographic, clinical, and therapeutic features of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) in a cohort of 80 patients recruited from 19 Italian referral Centers. Patients' data were collected retrospectively and then analyzed according to age groups (disease onset before or after 16 years) and genotype (high penetrance (HP) and low penetrance (LP) TNFRSF1A gene variants). Pediatric- and adult-onset were reported, respectively, in 44 and 36 patients; HP and LP variants were found, respectively, in 32 and 44 cases. A positive family history for recurrent fever was reported more frequently in the pediatric group than in the adult group (p<0.05). With reference to clinical features during attacks, pericarditis and myalgia were reported more frequently in the context of adult-onset disease than in the pediatric age (with p<0.01 and p<0.05, respectively), while abdominal pain was present in 84% of children and in 25% of adults (p<0.01). Abdominal pain was significantly associated also to the presence of HP mutations (p<0.01), while oral aphthosis was more frequently found in the LP variant group (p<0.05). Systemic amyloidosis occurred in 25% of subjects carrying HP variants. As concerns laboratory features, HP mutations were significantly associated to higher ESR values (p<0.01) and to the persistence of steadily elevated inflammatory markers during asymptomatic periods (p<0.05). The presence of mutations involving a cysteine residue, abdominal pain, and lymphadenopathy during flares significantly correlated with the risk of developing amyloidosis and renal impairment. Conversely, the administration of colchicine negatively correlated to the development of pathologic proteinuria (p<0.05). Both NSAIDs and colchicine were used as monotherapy more frequently in the LP group compared to the HP group (p<0.01). Biologic agents were prescribed to 49 (61%) patients; R92Q subjects were more frequently on NSAIDs monotherapy than other patients (p<0.01); nevertheless, they required biologic therapy in 53.1% of cases. At disease onset, the latest classification criteria for TRAPS were fulfilled by 64/80 (80%) patients (clinical plus genetic items) and 46/80 (57.5%) patients (clinical items only). No statistically significant differences were found in the sensitivity of the classification criteria according to age at onset and according to genotype (p<0.05). This study describes one of the widest cohorts of TRAPS patients in the literature, suggesting that the clinical expression of this syndrome is more influenced by the penetrance of the mutation rather than by the age at onset itself. Given the high phenotypic heterogeneity of the disease, a definite diagnosis should rely on both accurate working clinical assessment and complementary genotype.
2020
- Combination Therapy with Nintedanib and Sarilumab for the Management of Rheumatoid Arthritis Related Interstitial Lung Disease
[Articolo su rivista]
Vacchi, Caterina; Manfredi, Andreina; Cassone, Giulia; Salvarani, Carlo; Cerri, Stefania; Sebastiani, Marco
abstract
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease characterized by joint and extra-articular involvement. Among them, interstitial lung disease (ILD) is one of the most common and severe extra-articular manifestations, with a negative impact on both therapeutic approach and overall prognosis. ILD can occur at any point of the natural history of RA, sometimes before the appearance of joint involvement. Since no controlled studies are available, the therapeutic approach to RA-ILD is still debated and based on empirical approaches dependent on retrospective studies and case series. Here, we report the case of a 75-year-old patient affected by RA complicated by ILD successfully treated with a combination therapy of an antifibrotic agent, nintedanib, and an inhibitor of IL-6 receptor, sarilumab. We obtained a sustained remission of the joint involvement and, simultaneously, a stabilization of the respiratory symptoms and function, with a good safety profile. To date, this is the first report describing a combination therapy with nintedanib and a disease-modifying antirheumatic drug (DMARD) for the management of RA complicated by ILD. Future prospective studies are needed to better define efficacy and safety of this approach in the treatment of these subjects.
2020
- Comparison of biopsy-proven giant cell arteritis in North America and Southern Europe: a population-based study
[Articolo su rivista]
Muratore, F.; Crowson, C. S.; Boiardi, L.; Pinelli, A.; Koster, M. J.; Restuccia, G.; Kermani, T. A.; Matteson, E. L.; Salvarani, C.; Warrington, K. J.
abstract
OBJECTIVES: To compare clinical characteristics, treatment and prognosis of two population-based cohorts of patients with biopsy-proven giant cell arteritis (GCA) from Olmsted County, Minnesota, USA (Olmsted cohort) and the Reggio Emilia area, Northern Italy (Reggio cohort). METHODS: All patients residing in Olmsted County and the Reggio Emilia area with a new diagnosis of biopsy-proven GCA in 1986-2007 were retrospectively identified. Patients were followed from GCA diagnosis to death, migration or September 2011. RESULTS: The study included 110 patients in the Olmsted and 144 in the Reggio cohort. Compared with the Olmsted cohort, patients from the Reggio cohort had longer duration of symptoms prior to diagnosis (median 1.4 months vs. 0.7, p<0.001) and were younger (mean 74.6 years vs. 77.8, p=0.002), more likely to have cranial symptoms (93% vs. 86%, p=0.048), permanent vision loss (21% vs. 6%, p=0.001) and systemic symptoms (67% vs. 46%, p=0.001). ESR and CRP were higher (mean 88 mm/h vs. 73, and 89.0 mg/L vs. 35.2, both p<0.001) in the Reggio cohort. Patients from the Olmsted cohort received a higher initial prednisone dose (mean 53.6 mg/day vs. 49.5, p=0.001). There were no differences in relapse rates, cumulative glucocorticoid (GC) dosages at 1, 2 and 5 years, and time to first GC discontinuation. CONCLUSIONS: Geographical, genetic and/or environmental factors may contribute to the different clinical features at onset of GCA observed in this study.
2020
- Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial
[Articolo su rivista]
Burmester, G. R.; Buttgereit, F.; Bernasconi, C.; Alvaro-Gracia, J. M.; Castro, N.; Dougados, M.; Gabay, C.; van Laar, J. M.; Nebesky, J. M.; Pethoe-Schramm, A.; Salvarani, C.; Donath, M. Y.; John, M. R.; Constantin, A.; Gottenberg, J. E.; Loiseau-Peres, S.; Nguyen, M.; Schaeverbeke, T.; Alten, R. H. -E.; Amberger, C.; Biewer, W. A.; Boche, K.; Burmester, G. R.; Engel, A.; Feuchtenberger, M.; Fleck, M.; Gauler, G.; Heilig, B.; Hohle, M.; Iking-Konert, C.; Kastner, P.; Kofler, D.; Krueger, K.; Kuhne, C.; Kurthen, R.; Schulze-Koops, H.; Schwenke, H.; Sieburg, M.; Specker, C.; Tony, H. -P.; Wassenberg, S.; Wendler, J.; Caporali, R.; Epis, O.; Matucci-Cerinic, M.; Dubikov, A.; Kamalova, R.; Korolev, M.; I. Mazurov, V.; Puntus, E.; Damjanov, N.; Ilic, T.; Lazarevic, M.; Milenkovic, S.; Petronijevic, M.; Bouajina, E.; Elleuch, M.
abstract
Background: Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. Methods: The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5–15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints–erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4–6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012. Findings: Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35–0·73) with tapered prednisone and −0·08 (–0·27 to 0·12) with continued prednisone (difference 0·61 [0·35–0·88]; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71–0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency. Interpretation: In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. Funding: F Hoffmann-La Roche.
2020
- Cytokine Profiling in Aqueous Humor Samples From Patients With Non-Infectious Uveitis Associated With Systemic Inflammatory Diseases
[Articolo su rivista]
Bonacini, M.; Soriano, A.; Cimino, L.; De Simone, L.; Bolletta, E.; Gozzi, F.; Muratore, F.; Nicastro, M.; Belloni, L.; Zerbini, A.; Fontana, L.; Salvarani, C.; Croci, S.
abstract
Non-infectious uveitis are intraocular inflammatory conditions caused by dysregulated activation of the immune response without any detectable infectious agents. The aim of this study was to explore potential markers and therapeutic targets for two distinct types of non-infectious uveitis associated with Behçet's disease (BD) and Vogt Koyanagi Harada (VKH) disease. Concentrations of 27 cytokines were investigated in aqueous humor (AH) samples from patients with active uveitis vs. healthy controls (HC) (n = 10 patients with BD-associated uveitis; n = 10 patients with VKH-associated uveitis; n = 10 HC) using the Bio-Plex ProTM human cytokine group I panel. Additionally, leukocytes in AH samples were counted with hemocytometers and characterized by flow cytometry. Eleven cytokines were differentially expressed between patients with uveitis and HC with a median concentration greater than 10 pg/ml. IL-6, IP-10, G-CSF, and IFNγ showed higher concentrations in AH samples from both BD and VKH patients while IL-2, IL-8, IL-13, TNFα, eotaxin, IL-1ra showed statistically significant higher concentrations only in AH samples from BD patients. GM-CSF was the sole cytokine with an opposite profile showing decreased levels in AH samples from BD patients. IL-1ra and IL-6 were detected at higher frequencies in AH samples from BD and VKH patients compared with those from HC while IFNγ and TNFα were not detected in HC. The concentrations of IL-6, IL-8, IP-10, G-CSF, IFNγ, TNFα, eotaxin, IL-1ra positively correlated with the concentrations of leukocytes in AH, suggesting that such cytokines can be produced by immune cells and/or attract and/or promote proliferation and survival of immune cells in these types of uveitis. The correlation matrix of cytokine concentrations in AH samples revealed that IFNγ, TNFα, eotaxin, IL-6, G-CSF highly correlated each other. The ratios of cytokine concentrations between AH and plasma intra-individuals showed that IL-2, IL-6, IP-10, GM-CSF were increased intraocularly. In conclusion, AH sampling followed by multiplex analysis of cytokines should be fostered in non-infectious uveitis to identify cytokines dysregulated intraocularly in each individual laying the groundwork for precision medicine.
2020
- Early Disease and Low Baseline Damage as Predictors of Response to Belimumab in Patients With Systemic Lupus Erythematosus in a Real-Life Setting
[Articolo su rivista]
Gatto, M.; Saccon, F.; Zen, M.; Regola, F.; Fredi, M.; Andreoli, L.; Tincani, A.; Urban, M. L.; Emmi, G.; Ceccarelli, F.; Conti, F.; Bortoluzzi, A.; Govoni, M.; Tani, C.; Mosca, M.; Ubiali, T.; Gerosa, M.; Bozzolo, E.; Canti, V.; Cardinaletti, P.; Gabrielli, A.; Tanti, G.; Gremese, E.; De Marchi, G.; De Vita, S.; Fasano, S.; Ciccia, F.; Pazzola, G.; Salvarani, C.; Negrini, S.; Puppo, F.; Di Matteo, A.; De Angelis, R.; Orsolini, G.; Rossini, M.; Faggioli, P.; Laria, A.; Piga, M.; Mathieu, A.; Scarpato, S.; Rossi, F. W.; de Paulis, A.; Brunetta, E.; Ceribelli, A.; Selmi, C.; Prete, M.; Racanelli, V.; Vacca, A.; Bartoloni, E.; Gerli, R.; Larosa, M.; Iaccarino, L.; Doria, A.
abstract
Objective: To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab. Methods: In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1–60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033–4.860]) and a disease duration of ≤2 years (OR 1.94 [95% CI 1.078-3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004–6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036–2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018–8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039–13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K (OR 14.59 [95% CI 3.54–59.79) and baseline status of current smoker (OR 0.19 [95% CI 0.039–0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009). Conclusion: In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.
2020
- Effectiveness of steroid injection for hand psoriatic dactylitis: results from a multicentre prospective observational study
[Articolo su rivista]
Girolimetto, N.; Macchioni, P.; Citriniti, G.; Tinazzi, I.; Bascherini, V.; Martinis, F.; Marchetta, A.; Possemato, N.; Tasso, M.; Peluso, R.; Punzi, L.; Salvarani, C.; Scarpa, R.; McGonagle, D.; Costa, L.; Caso, F.
abstract
Objective: To assess the effectiveness of steroid injection (local treatment, LT) into the digital flexor tendon sheath of dactylitis in psoriatic arthritis (PsA) patients as compared with systemic treatment (ST). Methods: Forty-six PsA patients with a total of 73 dactylitic fingers were assessed in an observational, multicentre, prospective study by the Leeds Dactylitis Index basic (LDI-b) score and evaluated for local pain (visual analogue scale-VAS pain) and functional impairment (VAS-FI). Steroid injection was proposed to all patients. Patients refusing LT were treated with oral NSAIDs. Both the groups continued baseline csDMARDs and/or corticosteroids therapy. The clinical outcomes were measured at baseline, 1 month (T1) and 3 months (T3). Results: The reduction of VAS-pain, VAS-FI and LDI-b values was statistically significant higher in the LT group (24 patients, 38 dactylitic fingers) as compared with the ST group (22 patients, 35 dactylitic fingers), both at T1 (p < 0.001, p < 0.001 and p = 0.008, respectively) and at T3 (p < 0.001, p < 0.001 and p < 0.001, respectively). A clinically meaningful treatment response (defined as a contemporary reduction of at least 5 points in VAS-pain and VAS-FI or as values of VAS-pain and VAS-FI were both ≤ 2) was observed at T1 in 33 (87%) digits in LT group and in 6 (17%) digits in ST group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference (94% vs 31%, p < 0.001). Conclusions: For the first time, we show the effectiveness of steroid injection into the digital flexor tendon sheath in improving clinical aspects of hand psoriatic dactylitis.Key Points• Therapy with steroid injection (local treatment, LT), into the digital flexor tendon sheath for the treatment of active dactylitis in psoriatic arthritis patients, is more effective when compared with systemic treatment (ST) alone.• The reduction of VAS-pain, VAS-functional impairment (VAS-FI) and Leeds Dactylitis Index basic values was statistically significant higher in the LT group as compared with the ST group, both at T1and at T3.• A clinically meaningful response was observed at T1 in 87% of digits of patients treated with steroid injection and in 17% of digits of the systemic treatment group (p < 0.001). At T3, clinical response improved significantly in both the groups, with significant difference.• For the first time, findings from this study show that the use of steroid injections into the digital flexor tendon sheath for psoriatic dactylitis could be an effective and safe first-line therapy for psoriatic dactylitis.
2020
- Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation
[Articolo su rivista]
Menzella, F.; Fontana, M.; Salvarani, C.; Massari, M.; Ruggiero, P.; Scelfo, C.; Barbieri, C.; Castagnetti, C.; Catellani, C.; Gibellini, G.; Falco, F.; Ghidoni, G.; Livrieri, F.; Montanari, G.; Casalini, E.; Piro, R.; Mancuso, P.; Ghidorsi, L.; Facciolongo, N.
abstract
Background: The severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is extremely variable, ranging from asymptomatic patients to those who develop severe acute respiratory distress syndrome (ARDS). As for now, there are still no really effective therapies for coronavirus disease 2019 (COVID-19). Some evidences suggest that tocilizumab (TCZ) may avoid the progression of severe COVID-19. The aim of this retrospective case-control study was to analyze the efficacy and safety of TCZ in patients with COVID-19 ARDS undergoing noninvasive mechanical ventilation (NIV). Methods: Seventy-nine consecutive patients with severe COVID-19 pneumonia and worsening acute respiratory failure (ARF) were admitted to the Pulmonology Unit of Azienda USL of Reggio Emilia-IRCCS. All patients were inflamed (elevated CRP and IL-6 levels) and received NIV at admission according to the presence of a pO2/FiO2 ratio ≤ 200 mmHg. The possibility of being treated with TCZ depended on the drug availability. The primary outcome was the in-hospital mortality rate. A secondary composite outcome of worsening was represented by the patients who died in the pulmonology unit or were intubated. Results: Out of 79 patients, 41 were treated with TCZ. Twenty-eight patients received intravenous (IV) TCZ and 13 patients received subcutaneous (SC) TCZ. In-hospital overall mortality rate was 38% (30/79 patients). The probabilities of dying and being intubated during the follow-up using Kaplan-Meier method were significantly lower in total patients treated with TCZ compared to those of patients not treated with TCZ (log-rank p value = 0.006 and 0.036, respectively). However, using Cox multivariate analyses adjusted for age and Charlson comorbidity index only the association with the reduced risk of being intubated or dying maintained the significance (HR 0.44, 95%CI 0.22-0.89, p = 0.022). Two patients treated with TCZ developed cavitating lung lesions during the follow-up. Conclusions: This study shows that TCZ treatment may be effective in COVID-19 patients with severe respiratory impairment receiving NIV. More data on safety are required. Randomized controlled trials are needed to confirm these results.
2020
- Enthesitis and small cell lung carcinoma: a novel paraneoplastic syndrome not previously described
[Articolo su rivista]
Conticini, E.; Dardani, L.; Crescentini, F.; Frediani, B.; Salvarani, C.
abstract
2020
- Epidemiology and management of interstitial lung disease in ANCA-associated vasculitis
[Articolo su rivista]
Sebastiani, M.; Manfredi, A.; Vacchi, C.; Cassone, G.; Faverio, P.; Cavazza, A.; Sverzellati, N.; Salvarani, C.; Luppi, F.
abstract
Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a group of systemic vasculitides that predominantly affect small vessels, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Pulmonary involvement is frequently observed in AAV patients, with various possible phenotypes in the different diseases. In the last years, among the possible types of lung involvement, a growing interest has been addressed to the interstitial lung disease (ILD). Prevalence of ILD is higher in MPA than in GPA; in fact, ILD has been reported in up to 45% of MPA patients and in 23% of GPA. Anti-MPO antibodies are the main ANCA subtype associated to ILD, in about 46-71% of cases, while anti-PR3 antibodies are reported in 0-29% of patients. High resolution computed tomography (HRCT) frequently detects interstitial lung abnormalities in AAV, up to 66% of patients with MPA, even if with an unclear clinical relevance, specifically in asymptomatic patients. Ground glass opacities, mainly consistent with diffuse alveolar hemorrhage (DAH), are the most frequent finding in MPA patients, but reticulations, interlobular septal thickening and honeycombing are also reported. ILD significantly affects quality of life and survival, with mortality increased 2 to 4 times, particularly higher in MPA patients with pulmonary fibrosis. Currently, immunosuppressive therapy is considered also as a possible treatment of ILD. However, a careful evaluation of progression and severity of lung involvement, should guide the treatment decision in the single patient. In this review, we discuss the available evidence on clinical features, diagnostic work-up, prognosis and management of AAV-ILD.
2020
- Erratum: Acute exacerbation of interstitial lung diseases secondary to systemic rheumatic diseases: A prospective study and review of the literature (Journal of Thoracic Disease (2019) 11 (1621-1628) DOI: 10.21037/jtd.2019.03.28)
[Articolo su rivista]
Manfredi, A.; Sebastiani, M.; Cerri, S.; Vacchi, C.; Tonelli, R.; Della Casa, G.; Cassone, G.; Spinella, A.; Pancaldi, F.; Luppi, F.; Salvarani, C.
abstract
In the article that appeared on Page 1621-1628, Vol 11, No 4 (April 2019) Issue of the Journal of Thoracic Disease (1), the given and family names of author “Fabrizio Pancaldi” was incorrectly published in the original. The author's name should be corrected as Fabrizio Pancaldi, instead of Pancaldi Fabrizio. The authors regret the error.
2020
- Erratum: Management of adult-onset Still's disease with interleukin-1 inhibitors: Evidence- And consensus-based statements by a panel of Italian experts (Arthritis Res Ther (2019) 21:275 DOI: 10.1186/s13075-019-2021-9)
[Articolo su rivista]
Colafrancesco, S.; Manara, M.; Bortoluzzi, A.; Serban, T.; Bianchi, G.; Cantarini, L.; Ciccia, F.; Dagna, L.; Govoni, M.; Montecucco, C.; Priori, R.; Ravelli, A.; Sfriso, P.; Sinigaglia, L.; Alivernini, S.; Baldissera, E.; Bartoloni, E.; Berti, A.; Bugatti, S.; Camellino, D.; Cammelli, D.; Caporali, R.; Caso, F.; Cavallaro, E.; Cavalli, G.; Colaci, M.; Costa, L.; Di Scala, G.; Emmi, G.; Frassi, M.; Gerli, R.; Giacomelli, R.; Gremese, E.; Iannone, F.; Lapadula, G.; Leveghi, L.; Lopalco, G.; Manna, R.; Marotto, D.; Mathieu, A.; Neri, R.; Patisso, I.; Piga, M.; Punzi, L.; Romano, M.; Ruscitti, P.; Salvarani, C.; Scarpa, R.; Scrivo, R.; Talarico, R.; Verrecchia, E.; Viapiana, O.; Vitale, A.; Vitiello, G.
abstract
Following publication of the original article [1], it was brought to our attention that the AOSD Consensus Group was incorrectly tagged and therefore not searchable. The publishers apologize for this error.
2020
- FRI0212 THE ROLE OF AGE ON THE CLINICAL PRESENTATION AND RELAPSE RATES IN A LARGE COHORT OF 720 PATIENTS WITH GIANT CELL ARTERITIS
[Articolo su rivista]
Monti, S.; Dagna, L.; Campochiaro, C.; Tomelleri, A.; Zanframundo, G.; Klersy, C.; Muratore, F.; Boiardi, L.; Padoan, R.; Felicetti, M.; Schiavon, F.; Bond, M.; Berti, A.; Bortolotti, R.; Nannini, C.; Cantini, F.; Giollo, A.; Conticini, E.; Gattamelata, A.; Priori, R.; Quartuccio, L.; Treppo, E.; Emmi, G.; Finocchi, M.; Cassone, G.; Hoxha, A.; Foti, R.; Colaci, M.; Caporali, R.; Salvarani, C.; Montecucco, C.
abstract
2020
- Functional Progression in Patients with Interstitial Lung Disease Resulted Positive to Antisynthetase Antibodies: A Multicenter, Retrospective Analysis
[Articolo su rivista]
Dei, Giulia; Rebora, Paola; Catalano, Martina; Sebastiani, Marco; Faverio, Paola; Pozzi, Maria Rosa; Manfredi, Andreina; Cameli, Paolo; Salton, Francesco; Salvarani, Carlo; Cavagna, Lorenzo; Confalonieri, Marco; Bargagli, Elena; Luppi, Fabrizio; Pesci, Alberto
abstract
Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, "real life" study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline.
2020
- Gitelman syndrome associated with chondrocalcinosis and severe neuropathy: A novel heterozygous mutation in SLC12A3 gene
[Articolo su rivista]
Conticini, E.; Negro, A.; Magnani, L.; Ugolini, R.; Atienza-Mateo, B.; Frediani, B.; Salvarani, C.
abstract
Gitelman syndrome (GS) is an inherited salt-wasting tubulopathy characterized by hypocalciuria, hypokalemia, hypomagnesemia and metabolic alkalosis, due to inactivating mutations in the SLC12A3 gene. Symptoms may be systemic, neurological, cardiovascular, ophthalmological or musculoskeletal. We describe a 70 year-old patient affected by recurrent arthralgias, hypoesthesia and hyposthenia in all 4 limbs nd severe hypokalemia, complicated by atrial flutter. Moreover, our patient reported eating large amounts of licorice, and was treated with medium-high dosages of furosemide, thus making diagnosis very challenging. Genetic analysis demonstrated a novel heterozygous mutation in the SLC12A3 gene; therefore, we diagnosed GS and started potassium and magnesium replacement. GS combined with chondrocalcinosis and neurological involvement is quite common, but this is the first case of an EMG-proven severe neuropathy associated with GS. Herein, we underline the close correlation between hypomagnesemia, chondrocalcinosis and neurological involvement. Moreover, we report a new heterozygous mutation in exon 23 (2738G>A), supporting evidence of a large genetic heterogeneity in this late onset congenital tubulopathy.
2020
- INTERSTITIAL LUNG DISEASE RELATED TO RHEUMATOID ARTHRITIS. WHAT DO WE DON’T KNOW? THE LIRA STUDY (LUNG INVOLVEMENT IN RHEUMATOID ARTHRITIS)
[Articolo su rivista]
Sebastiani, M.; Vacchi, C.; Cassone, G.; Salvarani, C.; Sandri, G.; Atzeni, F.; Biggioggero, M.; Carriero, A.; Erre, G. L.; Fedele, A. L.; Furini, F.; Tomietto, P.; Venerito, V.; Atienza-Mateo, B.; Della Casa, G.; Cerri, S.; Palermo, A.; Galli, E.; Pancaldi, F.; González-Gay, M. A.; Manfredi on behalf of LIRA Study Group, A.
abstract
Background: Interstitial lung disease (ILD) is one of the more frequent and potentially severe extra-articular manifestation of rheumatoid arthritis (RA). ILD significantly decreases the survival and quality of life of patients and influences the treatment approach to the patient.
Despite its clinical relevance, the prevalence, incidence and survival of RA-ILD is unknown and supposed on the base of retrospective data or registry-based studies.
Objectives: For the first time, the Lung Involvement in Rheumatoid Arthritis (LIRA) study aims to investigate epidemiology, features and prognosis of RA-ILD patients in a prospective international multicentre study.
Methods: All RA patients referring to the involved centres will be evaluated every six months with a digital stethoscope and a software able to identify velcro crackles with a diagnostic accuracy of 83.9% (VECTOR). In fact, velcro crackles are virtually identified in all stages of fibrosing alveolitis like RA-ILD, and their search is as a simple and reliable method to screening patients to be undergone to high resolution computed tomography (HRCT).
For each patient, clinical and serological data are recorded at baseline and every six months; when velcro crackles or other conditions suspicious for ILD, such as cough or dyspnoea, are detected, a HRCT is requested to confirm ILD. Patients with ILD periodically perform pulmonary function tests to monitor lung function evolution.
Results: At now, 205 RA patients have been enrolled (female/male 161/44, mean age 64.8±12.9 years, mean disease duration 14.2±8.9 years), anti-citrullinated peptides antibodies (ACPA) and rheumatoid factor (RF) were positive in 77.1% and 78.1%, respectively. The prevalence of ILD was 21% (43 patients). In other 13 patients the HRCT is ongoing; therefore, we could suppose up to a prevalence of 27.3%. Patients with ILD were symptomatic in 53.5% of cases (23 patients), they are more frequently males and were older than patients without ILD (mean age 73.2±7.4 and 62.7±13.2; p<0.0001, female/male ratio 139/23 vs 22/21; p<0.0001) without significant differences regarding disease duration, positivity for ACPA or RF.
Conclusion: The prevalence and the incidence of RA-ILD is still not well defined. Preliminary data of our study confirm a prevalence of ILD higher than 20%, patients are asymptomatic in almost the half of cases and more frequently males and elderly. Our study can help to define the clinical history of these patients, the possible association with clinical and serological features and the supposed role of some drugs.
2020
- Imbalance between angiogenic and anti-angiogenic factors in sera from patients with large-vessel vasculitis
[Articolo su rivista]
Pulsatelli, L.; Boiardi, L.; Assirelli, E.; Pazzola, G.; Muratore, F.; Addimanda, O.; Dolzani, P.; Versari, A.; Casali, M.; Bottazzi, B.; Magnani, L.; Pignotti, E.; Pipitone, N.; Croci, S.; Mantovani, A.; Salvarani, C.; Meliconi, R.
abstract
OBJECTIVES: To investigate serum levels of a panel of angiogenic inducers (VEGF, FGF-2, Angiopoietin 1, -2, soluble VCAM-1) and inhibitors (angiostatin, endostatin, pentraxin-3) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK), in order to gain further insights into the molecular mechanisms driving angiogenesis dysregulation in large-vessel vasculitis (LVV). METHODS: Sera were obtained from 33 TAK patients and 14 GCA patients and from two groups of age-matched normal controls (NC). Disease activity was assessed using 18F-FDG PET/CT and clinical indices including NIH/Kerr criteria and ITAS. Angiogenic and anti-angiogenic factor serum levels were evaluated using commercial ELISA kits. Pentraxin 3 (PTX3) serum levels were evaluated by non-commercial ELISA, as already described. RESULTS: Among the angiogenic factors, only VEGF serum levels were significantly higher in TAK patients compared to NC. No difference was found between angiogenic factor levels in GCA patients compared to those detected in NC. Anti-angiogenic factor (Angiostatin, Endostatin, PTX3) serum levels were significantly higher in both GCA and TAK patients compared to NC. Significant associations were observed between VEGF and PTX3 levels and disease activity evaluated using PET scan and clinical indices. Cluster analysis based on PET scan scores in TAK patients showed significant ordered differences in VEGF and angiostatin serum levels. Indeed, we noted a progressive increase of VEGF and angiostatin from NC to the cluster including patients with the highest and more diffuse scan positivity. CONCLUSIONS: Our overall results demonstrate a circulating molecular profile characterised by a prevailing expression of anti-angiogenic soluble factors.
2020
- Improvement of Function and Its Determinants in a Group of Axial Spondyloarthritis Patients Treated with TNF Inhibitors: A Real-Life Study
[Articolo su rivista]
Lubrano, Ennio; Perrotta, Fabio Massimo; Manara, Maria; D'Angelo, Salvatore; Ramonda, Roberta; Punzi, Leonardo; Addimanda, Olga; Salvarani, Carlo; Marchesoni, Antonio
abstract
Introduction The aim of this work is to investigate the improvement of physical function and its determinants in axial spondyloarthritis (SpA) patients treated with tumor necrosis factor (TNF) inhibitors in a real clinical practice setting. Methods An observational study was conducted in patients with axial SpA treated with anti-TNF from 2010 to 2018 with a minimum 6 months of follow-up. All patients fulfilled ASAS or the modified New York criteria. The Bath Ankylosing Spondylitis Metrology Index (BASMI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) were used as objective and self-reported functional indices. The improvement of function and factors associated were evaluated for the present study, as well as disease activity and patient-reported outcome measures. Results A total of 183 patients with axial SpA were examined. Among them, 27 were non-radiographic axial SpA, while the remaining 156 were ankylosing spondylitis patients. BASFI and BASMI significantly improved during follow-up. Improvement of metrology index BASMI inverse correlated with disease duration (rho - 0.2, p = 0.009) and directly correlated with the improvement of BASDAI (rho 0.26, p = 0.003) and CRP (rho 0.26, p = 0.0003). Improvement of BASFI significantly inversely correlated with disease duration and directly correlated with the improvement of BASDAI, CRP, and baseline ESR. Male sex, lower disease duration, high ESR, and the improvement of BASDAI were found to be associated with the improvement of BASFI. Conclusions Our results showed that in real-life settings, patients improve in BASMI and BASFI. Furthermore, factors associated with this improvement were identified.
2020
- Interferon Alpha-2a Treatment for Post-Uveitic Refractory Macular Edema
[Articolo su rivista]
De Simone, L.; Sangiovanni, A.; Aldigeri, R.; Mastrofilippo, V.; Bolletta, E.; Invernizzi, A.; Fares, L.; Pipitone, N.; Fontana, L.; Salvarani, C.; Cimino, L.
abstract
Purpose: To assess the efficacy of interferon (IFN) alpha-2a in the treatment of post-uveitic refractory macular edema (ME). Methods: Retrospective cohort of patients with post-uveitic refractory ME, who received subcutaneous IFN alpha-2a injections for at least 3 months. Baseline central macular thickness (CMT) and best-corrected visual acuity (BCVA) were compared with those at follow-up visits up to 12 months. Results: Thirty-seven patients were included. Treatment duration (median [interquartile range]) was 14[8–24] months with a follow-up of 17[10–38] months. CMT (mean [standard deviation]) decreased from 438[140] to 335[119] μm after 1 month (p < 0.0001) and remained significantly lower up to 12 months (286[98] μm, p = 0.001). BCVA (0.48[0.33] logMAR at baseline) improved by 0.26[0.33] logMAR (p = 0.001) at 12 months. There were 14 recurrences. Seven patients had treatment side effects, without serious adverse events. Conclusions: IFN alpha-2a was effective, safe, and well tolerated in treating post-uveitic refractory ME.
2020
- Interstitial lung disease in Sjögren's syndrome: a clinical review
[Articolo su rivista]
Luppi, Fabrizio; Sebastiani, Marco; Silva, Mario; Sverzellati, Nicola; Cavazza, Alberto; Salvarani, Carlo; Manfredi, Andreina
abstract
Interstitial lung disease (ILD) is considered the most frequent and serious pulmonary complication in primary Sjögren's syndrome (pSS), with the majority of the studies indicating a prevalence of about 20%, and resulting in significant morbidity and mortality. Although ILD was historically described as a late manifestation of pSS, more recently, a high variability of the time of onset of pSS-ILD has been observed and from 10 to 51% of patients can develop ILD years before the onset of pSS. Lymphocytic interstitial pneumonia is highly typical for SS, but it occurs only in a few cases, while the most common ILD pattern is nonspecific interstitial pneumonia, followed by usual interstitial pneumonia and organising pneumonia. Multidisciplinary discussion can be necessary in pSS cases with ambiguous clinical findings, when differential diagnosis with IIPs might be very difficult. Up to date, available data do not allow to establish an evidence-based treatment strategy in pSS-ILD. Glucocorticoids are empirically used, usually in association to immunosuppressive drugs, such as cyclophosphamide and mycophenolate mofetil. A better understanding of the molecular mechanisms involved in the pathogenesis of pSS should facilitate the development of new therapies. Recently, a trial showed the efficacy of the antifibrotic drug nintedanib in slowing progression of various interstitial lung diseases, including patients with connective tissue diseases. The aims of this review are to describe clinical features, imaging, pathology, together with diagnostic criteria, prognosis and management of pSS-ILD patients.
2020
- Interstitial pneumonia with autoimmune features: A single center prospective follow-up study
[Articolo su rivista]
Sebastiani, M.; Cassone, G.; De Pasquale, L.; Cerri, S.; Della Casa, G.; Vacchi, C.; Luppi, F.; Salvarani, C.; Manfredi, A.
abstract
Background and objective: Recently the term “interstitial pneumonia with autoimmune features” (IPAF) has been proposed to identify patients with interstitial lung disease and autoimmune characteristics, not fulfilling the criteria for specific connective tissue diseases (CTD). Only few data are available about the clinical and serological features of IPAF patients, their survival and the possible evolution in a CTD. The aims of the study were to investigate the demographic and clinico-serologic features of patients with IPAF, their relationship to survival, and the possible evolution in a definite CTD. Patients and methods: Fifty-two patients were consecutively enrolled and prospectively followed for 45 ± 31.6 months. Data about disease onset, serological, clinical and therapeutic features, pulmonary function tests and high-resolution computed tomography were periodically repeated. The survival of patients with IPAF was compared with that of 104 patients with idiopathic pulmonary fibrosis (IPF). Results: The clinical domain for IPAF was satisfied in 44 patients, serological domain in 49 and the morphological domain in 29 patients. During the follow-up, a definite CTD was diagnosed in 7 patients, in particular Sjogren's syndrome in 4 patients, rheumatoid arthritis in 2, and polymyositis in the last. The estimated 5-year survival of IPAF patients 69.5 ± 7.8%, significantly higher than survival observed in IPF patients, and the baseline value of FVC and DLCO were the only factors associated to death. Conclusions: IPAF seems to a distinct entity, with a low tendency to evolve in a definite CTD. Nevertheless, further studies are needed to better define the clinical evolution and the outcome of IPAF.
2020
- Long-term remission, relapses and maintenance therapy in adult primary central nervous system vasculitis: A single-center 35-year experience
[Articolo su rivista]
Salvarani, C.; Brown, R. D.; Christianson, T. J. H.; Huston, J.; Giannini, C.; Hunder, G. G.
abstract
Objectives: To evaluate long-term treatment and outcomes of patients with primary central nervous system vasculitis (PCNSV). Methods: In this cohort of 191 consecutive patients with PCNSV seen at Mayo Clinic, Rochester, MN, over 35 years with long-term follow-up we analyzed response to and duration of therapy, frequency of relapses, long-term remission, efficacy of maintenance therapy and initial intravenous glucocorticoid (GC) pulses, survival and degree of disability. We also compared the efficacy of initial IV and oral cyclophosphamide (CYC). Results: A favorable initial response was observed in 83% of patients treated with prednisone (PDN) alone, 81% of those treated with PDN and CYC and 95% of those initially treated with PDN and an immunosuppressant other than CYC. One or more relapses were observed in 30% of patients, 35% had discontinued therapy by last follow-up, and 21.5% maintained remission for at least 12 months after discontinuing therapy. Maintenance therapy was prescribed in 19% of all patients and 34% of patients initially treated with CYC and PDN. High disability scores (Rankin 4–6) and deaths were less frequently observed in patients receiving maintenance therapy and more frequently in patients with Aβ-related angiitis. Large vessel involvement and cerebral infarction at diagnosis were associated with a poor treatment response. Aspirin use was positively associated with long-term remission and having gadolinium-enhanced cerebral lesions or meninges was negatively associated. A high disability score at last follow-up and higher mortality rate were associated with increasing age, cerebral infarction and cognitive dysfunction at diagnosis. Lymphocytic vasculitis on biopsy was associated with a more benign course with reduced disability and mortality. Patients initially treated with mycophenolate mofetil had better outcomes compared to those treated with CYC and PDN. No therapeutic advantages were observed in the patients initially treated with intravenous GC pulses. Intravenous and oral CYC were equally effective in inducing the remission. Conclusions: The majority of patients with PCNSV responded to treatment. We found patient subsets with different outcomes. Mycophenolate mofetil may be an effective alternative to CYC.
2020
- Lung complications of Sjogren syndrome
[Articolo su rivista]
Luppi, F.; Sebastiani, M.; Sverzellati, N.; Cavazza, A.; Salvarani, C.; Manfredi, A.
abstract
Primary Sjogren syndrome (pSS) is a systemic autoimmune disease characterised by lymphocytic infiltration of exocrine glands and by a number of systemic manifestations, including those regarding the lung. Pulmonary involvement in pSS includes interstitial lung disease (ILD) and airway disease, together with lymphoproliferative disorders.Patients with pSS-ILD report impaired health-related quality of life and a higher risk of death, suggesting the importance of early diagnosis and treatment of this type of pulmonary involvement. In contrast, airway disease usually has little effect on respiratory function and is rarely the cause of death in these patients.More rare disorders can be also identified, such as pleural effusion, cysts or bullae.Up to date, available data do not allow us to establish an evidence-based treatment strategy in pSS-ILD. No data are available regarding which patients should be treated, the timing to start therapy and better therapeutic options. The lack of knowledge about the natural history and prognosis of pSS-ILD is the main limitation to the development of clinical trials or shared recommendations on this topic. However, a recent trial showed the efficacy of the antifibrotic drug nintedanib in slowing progression of various ILDs, including those in pSS patients.
2020
- Modulation of Cell Death and Promotion of Chondrogenic Differentiation by Fas/FasL in Human Dental Pulp Stem Cells (hDPSCs)
[Articolo su rivista]
Pisciotta, Alessandra; Bertani, Giulia; Bertoni, Laura; Di Tinco, Rosanna; De Biasi, Sara; Vallarola, Antonio; Pignatti, Elisa; Tupler, Rossella; Salvarani, Carlo; de Pol, Anto; Carnevale, Gianluca
abstract
2020
- Musculoskeletal Ultrasound in Monitoring Clinical Response to Treatment in Acute Symptomatic Psoriatic Dactylitis: Results from a Multicentre Prospective Observational Study
[Articolo su rivista]
Girolimetto, Nicolò; Macchioni, Pierluigi; Possemato, Niccolò; Tinazzi, Ilaria; Bascherini, Vittoria; Citriniti, Giorgia; Mcconnell, Rebecca; Marchetta, Antonio; Peluso, Rosario; Sabbatino, Vincenzo; Salvarani, Carlo; Scarpa, Raffaele; Costa, Luisa; Caso, Francesco
abstract
This observational and prospective study evaluated the clinical correlations of sonographic lesions in consecutive psoriatic arthritis (PsA) dactylitis cases. Eighty-three dactylitic digits were evaluated clinically and sonographically before treatment and at one-month (T1) and three-month (T3) follow-up. Clinical evaluation included the Leeds Dactylitis Index-basic (LDI-b) score and the visual analogue scales for pain (VAS-p) and functional impairment (VAS-FI). High-frequency ultrasound with grey scale (GS) and power Doppler (PD) assessed flexor tenosynovitis (FT), soft tissue oedema (STO), extensor tendon paratenonitis, and joint synovitis. There was a statistically significant correlation between the clinical parameters (VAS-p, VAS-FI, and LDI-b) and FT and STO at T1 and T3. We found statistically significant improvement in FT and STO for the cases with clinically meaningful treatment responses (p < 0.001). After a multiple conditional logistic regression analysis, the only variables that correlated with a T1 clinical response were the resolutions of PD FT (OR 15.66) and PD STO (OR 6.23), while the resolution of PD FT (OR 27.77) and of GS STO (OR 7.29) correlated with a T3 clinical response. The clinical improvements of active dactylitis are linked to the regression of sonographic evidence of extracapsular inflammation (particularly FT and STO).
2020
- Pathogenesis and treatment of idiopathic and rheumatoid arthritis-related interstitial pneumonia. The possible lesson from COVID-19 pneumonia
[Articolo su rivista]
Manfredi, A; Luppi, F; Cassone, G; Vacchi, C; Salvarani, C; Sebastiani, M
abstract
Main clinical manifestations of SARS-CoV-2 infection are characterized by fever, cough, dyspnoea and interstitial pneumonia frequently evolving in an acute respiratory distress syndrome (ARDS).
2020
- Pirfenidone for the treatment of interstitial lung disease associated to rheumatoid arthritis: a new scenario is coming?
[Articolo su rivista]
Cassone, G.; Sebastiani, M.; Vacchi, C.; Cerri, S.; Salvarani, C.; Manfredi, A.
abstract
Introduction: Interstitial lung disease (ILD) is a frequent extra-articular manifestation of Rheumatoid arthritis (RA), but nowadays there are no randomized controlled clinical trials to support therapeutic guidelines. RA-ILD, especially with UIP pattern, shares some similarities with idiopathic pulmonary fibrosis, suggesting a possible role of antifibrotic therapy in these patients. To date, there are no published data supporting the use of pifenidone in RA-ILD. We describe for the first time two patients with a diagnosis of RA-ILD successfully treated with hydroxychloroquine and pirfenidone, without adverse events. Case presentation: Patient 1 and patient 2 were first diagnosed with IPF (UIP pattern at high-resolution computed tomography, no other signs or symptoms suggesting other forms of ILD, routine laboratory examinations and immunological texts negative). Patients started pirfenidone 2403 mg daily. Few months later, they referred to our multidisciplinary outpatient for arthritis. ACPA and RF were positive. A diagnosis of RA was performed and treatment with corticosteroids and hydroxychloroquine was started, in association with pirfenidone. In both cases we assessed the stabilization of articular and lung manifestations, without adverse events. Discussion: In absence of randomized controlled trials, the optimal treatment of RA-ILD has not been determined and remains challenging. When considering therapeutic options for RA-ILD, both pulmonary and extra-thoracic disease manifestations and degrees of activity should be assessed and taken into consideration. Future prospective research might change RA-ILD management, moving to a more personalized approach based on the identification of different phenotypes of the disease or to a combination of immunosuppressive and antifibrotic treatment.
2020
- Predominant ultrasonographic extracapsular changes in symptomatic psoriatic dactylitis: results from a multicenter cross-sectional study comparing symptomatic and asymptomatic hand dactylitis
[Articolo su rivista]
Girolimetto, N.; Macchioni, P.; Tinazzi, I.; Costa, L.; Peluso, R.; Tasso, M.; Bascherini, V.; Addimanda, O.; Marchetta, A.; Possemato, N.; Salvarani, C.; Mcgonagle, D.; Scarpa, R.; Caso, F.
abstract
Objective: Despite diffuse digital swelling, dactylitis may sometimes be asymptomatic. The objective of this study was to compare the clinical and ultrasonographic features of symptomatic with asymptomatic psoriatic arthritis (PsA) dactylitis. Methods: One hundred and twenty-five hand dactylitis were evaluated in a multicenter cross-sectional study for the presence of pain, subjective functional limitation, and tenderness (4-points scale) with the calculation of a Leeds Dactylitis Index (LDI) score. Fingers were subsequently investigated using high-frequency ultrasound (US) both in gray-scale (GS) and power Doppler (PD), for the presence and grading of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDUS), extensor tendon involvement, and joints synovitis. Clinical and US characteristics of symptomatic dactylitic fingers were compared with the asymptomatic dactylitic ones. Results: Symptomatic fingers (n = 80) had a significantly lower dactylitis duration compared to asymptomatic fingers (n = 36) (p < 0.001). Values of LDI, patient VAS-pain, and VAS-functional score were significantly higher in fingers with symptomatic dactylitis (p < 0.001 and p = 0.010, respectively). Symptomatic dactylitis had a higher prevalence of flexor tenosynovitis of grade > 2, soft tissue edema and subcutaneous PDUS signal (p < 0.001). Asymptomatic dactylitis showed a greater prevalence of joint synovitis (both in GS and in PD) than symptomatic dactylitis (p < 0.001). Conclusions: Digital tenderness and pain are linked to US tenosynovitis of grade > 2 and extra synovial abnormalities and conversely asymptomatic dactylitis is associated with joint-based synovitis.Key Points• Digital tenderness and local pain in psoriatic arthritis dactylitis are strongly associated with flexor tenosynovitis of grade> 2, soft tissue edema, and subcutaneous PD signal.• In psoriatic arthritis, asymptomatic dactylitis showed a greater prevalence of joint synovitis than symptomatic dactylitis.• In psoriatic arthritis, ultrasound inflammatory abnormalities are present in about 70% of cold dactylitis which is linked for disease chronicity.• In psoriatic arthritis, the flexor tendon and adjacent soft tissues play a significant role in symptomatic dactylitis.
2020
- Prevalence of SARS-CoV-2 (Covid-19) in Italians and in immigrants in an area of Northern Italy (Reggio Emilia)
[Articolo su rivista]
Grilli, Roberto; Massimiliano, Marino; Debora, Formisano; Massimo, Costantini; Formoso, Giulio; Emanuela, Badeschi; Cinzia, Perilli; Ivano, Venturi; Eufemia, Bisaccia; Elisabetta La Rosa, ; Cinzia, Campari; Francesco, Gioia; Serena, Broccoli; Marta, Ottone; Pierpaolo, Pattacini; Besutti, Giulia; Iotti, Valentina; Lucia, Spaggiari; Pamela, Mancuso; Andrea, Nitrosi; Marco, Foracchia; Rossana, Colla; Alessandro, Zerbini; Marco, Massari; Anna Maria Ferrari, ; Pinotti, Mirco; Nicola, Facciolongo; Ivana, Lattuada; Laura, Trabucco; Stefano De Pietri, ; Giorgio Francesco Danelli, ; Laura, Albertazzi; Enrica, Bellesia; Simone, Canovi; Mattia, Corradini; Fasano, Tommaso; Magnani, Elena; Annalisa, Pilia; Alessandra, Polese; Silvia Storchi Incerti, ; Zaldini, Piera; Efrem, Bonelli; Bonanno, Orsola; Matteo, Revelli; Salvarani, Carlo; Venturelli, Francesco
abstract
It has been hypothesized that bacille Calmette-Guerin (BCG), the anti-tuberculosis vaccine, can be protective against Covid-19. Using data of performed swabs and RT-PCR results for SARS-CoV-2 in the Reggio Emilia province (Emilia-Romagna Region, Northern Italy) from March 6th to March 26th, 2020, we computed age, gender, and place of birth (Italy or abroad) specific risk of being tested, prevalence of positive tests, and probability of testing positive given that a swab has been taken during the epidemic peak. We report that immigrants resident in Reggio Emilia province, mostly coming from Countries with high BCG vaccination coverage, and Italians had a similar prevalence of infection (odds ratio - OR 0.99; 95%CI 0.82-1.20) and similar probability of being tested (OR 0.93; 95%CI 0.81-1.10). Our data do not support the hypothesis that immigrants from Countries where BCG vaccination is recommended have a lower risk of Covid-19 infection.
2020
- Reading and interpreting reviews for health professionals: a practical review
[Articolo su rivista]
Antonelli, M.; Firenzuoli, F.; Salvarani, C.; Gensini, G. F.; Donelli, D.
abstract
Literature reviews can be directly used by clinicians and other health professionals to support many decision-making processes. This review aims to offer health professionals an essential practical guide to critically evaluate and properly understand results of review articles published in the scientific literature. An evidence-based methodological review with step-by-step theoretical concepts and practical suggestions was developed. Key steps of this guide are: to consider the topic and the research question (a), to check the review type (b), to evaluate the methodology (with a keen focus on review guidelines, search strategy and study-selection process, evaluation of the quality and certainty of included evidence, and statistical analysis) (c), and to define the real impact of review results (d). This guide offers a description of essential and easy-to-apply key steps which can help health professionals to evaluate the reliability and implications of a literature review, and to select the latest high-quality scientific evidence to keep updated with.
2020
- Relapses and long-term remission in large vessel giant cell arteritis in northern Italy: Characteristics and predictors in a long-term follow-up study
[Articolo su rivista]
Muratore, F.; Boiardi, L.; Restuccia, G.; Cavazza, A.; Catanoso, M.; Macchioni, P.; Spaggiari, L.; Cimino, L.; Aldigeri, R.; Pipitone, N.; Fontana, A.; Casali, M.; Croci, S.; Salvarani, C.
abstract
Objective: To evaluate characteristics and predictors of relapses and long-term remission in an Italian cohort of patients with large-vessel (LV) giant cell arteritis (GCA). Methods: We evaluated 87 consecutive patients with LV-GCA followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for at least 2 years. Patients with relapses and long-term remission were compared to those without. A group of 34 patients with biopsy proven GCA without LV vasculitis (LVV) at diagnosis was considered for comparison. Patients: 37 patients (42.5%) experienced one or more relapses. Nineteen (37.2%) of the 51 relapses were experienced during the first year after diagnosis. The majority of relapses occurred with doses of prednisone (PDN) ≤ 10 mg/day (74.5%). Polymyalgia rheumatica (PMR) (41.2%) and worsening at imaging of LVV (39.2%) were the most frequently observed relapsing manifestations. The total cumulative prednisone dose was significantly higher (p < 0.0001) and the total duration of PDN treatment longer (p < 0.0001) in relapsing patients compared to those without relapses. Relapsing patients had at diagnosis more frequently fever ≥ 38°C (p = 0.03) and visual manifestations (p = 0.03), and less frequently long-term remission (p = 0.002). In the multivariate model fever ≥ 38°C (HR 2.30, 95%CI:1.11-4.78) and total cumulative PDN dose (HR 1.18, 95%CI: 1.08-1.30) were significantly associated with an increased risk of relapses, while aortic arch involvement at imaging at diagnosis (HR 0.26, 95%CI: 0.11-0.59) and long-term remission (HR 0.27, 95%CI: 0.11-0.65) with a reduced risk. 35/84 patients (41.6%) experienced long-term remission. PMR and disease relapses were less frequently observed (p = 0.04 and p = 0.002, respectively), and the total cumulative prednisone dose was lower (p < 0.001) in patients with long-term remission compared to those without. In the multivariate model the presence of relapses (HR 0.21, 95%CI: 0.07-0.62) and the total cumulative PDN dose (HR 0.85, 95%CI: 0.77-0.95) were significantly negatively associated with long-term remission. Conclusion: In our cohort of patients with LV GCA we identified predictors of a relapsing course and long-term remission, which were observed in around half of the patients.
2020
- Reply to the Letter to the Editor: The Italian Society of Rheumatology clinical practice guidelines for the management of polymyalgia rheumatica
[Articolo su rivista]
Ughi, N.; Sebastiani, G. D.; Gerli, R.; Salvarani, C.; Parisi, S.; Ariani, A.; Prevete, I.; Manara, M.; Rumi, F.; Scire, C. A.; Bortoluzzi, A.
abstract
Not available.
2020
- Role of Colchicine Treatment in Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS): Real-Life Data from the AIDA Network
[Articolo su rivista]
Vitale, A.; Sota, J.; Obici, L.; Ricco, N.; Maggio, M. C.; Cattalini, M.; Ruscitti, P.; Caso, F.; Manna, R.; Viapiana, O.; Caggiano, V.; Emmi, G.; Insalaco, A.; Montin, D.; Licciardi, F.; Soriano, A.; Dagna, L.; Salvarani, C.; Lamacchia, V.; Hernandez-Rodriguez, J.; Giacomelli, R.; Frediani, B.; Renieri, A.; Cantarini, L.
abstract
Objective. To analyze the potential role of colchicine monotherapy in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) in terms of control of clinical and laboratory manifestations. Methods. Patients with TRAPS treated with colchicine monotherapy were retrospectively enrolled; demographic, clinical and therapeutic data were collected and statistically analysed after having clustered patients according to different times at disease onset, penetrance of mutations, dosage of colchicine, and different disease manifestations. Results. 24 patients (14 males; 15 with pediatric disease onset) treated with colchicine monotherapy were enrolled. Colchicine resulted in a complete response in 3 (12.5%) cases, partial response in 14 (58.3%) patients, and lack of response in 7 (29.2%) patients. There were not significant differences in colchicine response between pediatric and adult disease onset (p=0.42), between low- and high-penetrance mutations (p=0.62), and according to different dosages (p=0.66). No significant differences were identified in the frequency of specific disease manifestations between patients experiencing any response to colchicine and patients with lack of response. Conclusions. Colchicine monotherapy is useful in a low percentage of TRAPS patients; nevertheless, it could be attempted in patients with milder phenotypes and at a lower risk of developing reactive amyloidosis.
2020
- Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study
[Articolo su rivista]
Cassone, Giulia; Manfredi, Andreina; Atzeni, Fabiola; Venerito, Vincenzo; Vacchi, Caterina; Picerno, Valentina; Furini, Federica; Erre, Gian Luca; Tomietto, Paola; Fedele, Anna Laura; Della Casa, Giovanni; Nucera, Valeria; Giannitti, Chiara; Salvarani, Carlo; Sebastiani, Marco
abstract
Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA).
2020
- Safety of ixekizumab in adult patients with plaque psoriasis, psoriatic arthritis and axial spondyloarthritis: data from 21 clinical trials
[Articolo su rivista]
Genovese, M. C.; Mysler, E.; Tomita, T.; Papp, K. A.; Salvarani, C.; Schwartzman, S.; Gallo, G.; Patel, H.; Lisse, J. R.; Kronbergs, A.; Leage, S. L.; Adams, D. H.; Xu, W.; Marzo-Ortega, H.; Lebwohl, M. G.
abstract
Objectives: The aim of this integrated analysis is to evaluate the long-term safety and tolerability of ixekizumab in adults with psoriasis, PsA and axial SpA. Methods: Integrated safety data from 21 clinical trials are presented by indication in patients who received at least one dose of ixekizumab. Adverse events (AEs) and treatment-emergent adverse events (TEAEs) adjusted incidence rates (IRs) per 100 patient-years (PY) up to 5 years' exposure are reported. Results: A total of 8228 patients with an ixekizumab exposure of 20 895.9 PY were included in this analysis. The most common TEAEs were nasopharyngitis, upper respiratory tract infection and injection-site reactions. Across populations, IRs were low for AEs leading to discontinuation (IRs ≤5.1 per 100 PY), serious AEs (IRs ≤6.0 per 100 PY) and death (IRs ≤0.3 per 100 PY). The most reported TEAEs of special interest were infections (IRs ≤35.8 per 100 PY). Patients rarely reported malignancies (IR ≤0.8), IBD including ulcerative colitis and Crohn's disease (IR ≤0.8) and major adverse cardiovascular events (IR ≤0.5). TEAEs were most commonly reported the first 2 years of exposure with ixekizumab and IR decreased over the years (infections, injection-site reactions and depression) or remained constant over the entire treatment period (serious infections, major adverse cardiovascular events, malignancies and IBD). Conclusion: This long-term analysis on the safety of ixekizumab was consistent with previously published reports and did not show any new safety signals. The safety profile and tolerability reported in this integrated analysis remained consistent with the known safety profile for ixekizumab.
2020
- Significance of PR3-ANCA positivity in eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
[Articolo su rivista]
Papo, Matthias; Sinico, Renato A; Teixeira, Vítor; Venhoff, Nils; Urban, Maria-Letizia; Iudici, Michele; Mahrhold, Juliane; Locatelli, Francesco; Cassone, Giulia; Schiavon, Franco; Seeliger, Benjamin; Neumann, Thomas; Kroegel, Claus; Groh, Matthieu; Marvisi, Chiara; Samson, Maxime; Barba, Thomas; Jayne, David; Troilo, Arianna; Thiel, Jens; Hellmich, Bernhard; Monti, Sara; Montecucco, Carlomaurizio; Salvarani, Carlo; Kahn, Jean-Emmanuel; Bonnotte, Bernard; Durel, Cécile-Audrey; Puéchal, Xavier; Mouthon, Luc; Guillevin, Loïc; Emmi, Giacomo; Vaglio, Augusto; Terrier, Benjamin
abstract
Only a third of patients with eosinophilic granulomatosis with polyangiitis (EGPA) are ANCA-positive, mainly directed against MPO. ANCA directed against PR3 are rarely found in EGPA. We aimed to examine the significance of PR3-ANCA in EGPA.
2020
- Significance of inflammation restricted to adventitial/periadventitial tissue on temporal artery biopsy
[Articolo su rivista]
Galli, E.; Muratore, F.; Boiardi, L.; Restuccia, G.; Cavazza, A.; Catanoso, M.; Macchioni, P.; Spaggiari, L.; Casali, M.; Pipitone, N.; Fontana, A.; Girolimetto, N.; Croci, S.; Salvarani, C.
abstract
Objective: To evaluate the characteristics and significance of inflammation restricted (RI) to the adventitial and/or periadventitial tissue on temporal artery biopsy (TAB). Methods: We studied a retrospective cohort of 80 patients with RI, extending our earlier series of 39 patients. For comparison purposes, we collected the same data from 254 patients with transmural inflammation (TMI) and 81 TAB-negative patients. A review of the literature was also performed. Results: A final diagnosis of giant cells arteritis (GCA) and/or polymyalgia rheumatica (PMR) was observed in 86% of patients with RI. Compared to TMI, GCA diagnosis was significantly less frequently observed in patients with RI and in those TAB-negative (p < 0.0001), while cranial manifestations were significantly less frequent (p = 0.001) and ESR and CRP values at diagnosis significantly reduced (p < 0.0001). PMR, permanent visual loss, and large vessel involvement at diagnosis were equally present in the 3 subgroups. The median duration of prednisone therapy, the cumulative prednisone dosages, and the relapse and long-term remission rates were similar between patients with GCA-RI and those with TMI. The positive likelihood ratios (LRs) of pathological evidence of RI at TAB for GCA or GCA/PMR diagnoses were 0.88 (CI, 0.61–1.27) and 1.15 (CI, 0.67–1.99), while that of inflammation limited to adventitia was 1.37 (CI, 0.59–3.19) and 3.77 (CI, 0.53–26.72). In the literature review, the positive LR of RI for GCA diagnosis was 0.92 (CI, 0.68–1.25). Conclusion: A large part of the patients with RI have GCA/PMR, however, the diagnostic value of RI for GCA diagnosis is not relevant.
2020
- Susceptibility and severity of COVID-19 in patients treated with bDMARDS and tsDMARDs: A population-based study
[Articolo su rivista]
Salvarani, C.; Salvarani, C.; Bajocchi, G.; Mancuso, P.; Galli, E.; Muratore, F.; Boiardi, L.; Catanoso, M.; Pipitone, N.; Cassone, G.; Girolimetto, N.; Croci, S.; Cimino, L.; Gradellini, F.; Beltrami, M.; Di Lernia, V.; Dolci, G.; Massari, M.; Marata, A. M.; Costantini, M.; Giorgi Rossi, P.
abstract
2020
- THU0600 a case of systemic sclerosis complicated by renal crisis: potential etiopathogenetic role of cytomegalovirus and treatment
[Abstract in Rivista]
Palermo, A; Galli, E; Spinella, A; Cocchiara, E; Lumetti, F; Klinowski, G; Giovanella, S; Manzini, Cu; Salvarani, C; Giuggioli, D
abstract
Background:
Scleroderma renal crisis (SRC) is a rare complication of systemic sclerosis (SSc), which can be triggered by viruses, such as Cytomegalovirus (CMV). SRC presents as a new-onset accelerated-phase hypertension with/without rapidly progressive renal failure.
Objectives:
Here we describe the case of a patient developing SSc complicated by the appearance of SRC after a recent episode of acute Cytomegalovirus infection.
Methods:
A 66-year-old male was referred to our Scleroderma Unit in March 2019. He presented with widespread skin rash, exertional dyspnoea and peripheral oedemas. He reported a myocarditis due to CMV occurred in October 2018. Antibodies anti-CMV IgM were detected in his serum. The patient developed a progressive cutaneous involvement characterized by diffuse oedema, sclerosis and melanoderma. Subsequently, Raynaud’s phenomenon, puffy hands and pitting scars …
2020
- TOCIVID-19 - A multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia. Study protocol
[Articolo su rivista]
Piccirillo, Maria Carmela; Ascierto, Paolo; Atripaldi, Luigi; Cascella, Marco; Costantini, Massimo; Dolci, Giovanni; Facciolongo, Nicola; Fraganza, Fiorentino; Marata, AnnaMaria; Massari, Marco; Montesarchio, Vincenzo; Mussini, Cristina; Negri, Emanuele Alberto; Parrella, Roberto; Popoli, Patrizia; Botti, Gerardo; Arenare, Laura; Chiodini, Paolo; Gallo, Ciro; Salvarani, Carlo; Perrone, Francesco
abstract
Pneumonia is the most frequent complication of COVID-19, due to an aberrant host immune response that is associated with an acute respiratory distress syndrome, and, in most critical patients, with a "cytokine storm". IL-6 might play a key role in the cytokine storm and might be a potential target to treat severe and critical COVID-19. Tocilizumab is a recombinant humanized monoclonal antibody, directed against IL-6 receptor.
2020
- The Italian society of rheumatology clinical practice guidelines for the management of polymyalgia rheumatic
[Articolo su rivista]
Ughi, N.; Sebastiani, G. D.; Gerli, R.; Salvarani, C.; Parisi, S.; Ariani, A.; Prevete, I.; Manara, M.; Rumi, F.; Scire, C. A.; Bortoluzzi, A.
abstract
Objective: To provide evidence-based up-to-date recommendations for the management of patients with a definite diagnosis of polymyalgia rheumatica (PMR). Methods: A systematic literature review was performed to find the existing clinical practice guidelines (CPGs) on PMR and the framework of the Guidelines International Network Adaptation Working Group was used to appraise (AGREE II), synthesize, and customize the recommendations according to the needs of the Italian healthcare context. Rheumatologists on behalf of the Italian Society of Rheumatology (SIR) and from the SIR Epidemiology Unit joined the working group and identified the key health questions on PMR to guide the systematic literature review. Physicians, including general practitioners and specialists, and health professionals who manage PMR in the clinical practice were the target audience. The final recommendations were rated externally by a multi-disciplinary and multi-professional group of stakeholders. Results: From the systematic search in databases (Medline, Embase) and grey literature, 3 CPGs were identified and appraised by two independent raters. Combining the statements and the evidence from these CPGs, 9 recommendations were developed by endorsement or adaptation in response to the initial key health questions. The quality of evidence was graded and the working group discussed the final recommendations in view of their implementation in the Italian healthcare context. Conclusions: In absence of national guidelines so far, these recommendations are the first to provide guidance for the management of patients with a diagnosis of PMR in Italy and they are expected to ensure the best evidence-based clinical practice for this disease.
2020
- Therapeutic Options for the Treatment of Interstitial Lung Disease Related to Connective Tissue Diseases. A Narrative Review
[Articolo su rivista]
Vacchi, Caterina; Sebastiani, Marco; Cassone, Giulia; Cerri, Stefania; Della Casa, Giovanni; Salvarani, Carlo; Manfredi, Andreina
abstract
Interstitial lung disease (ILD) is one of the most serious pulmonary complications of connective tissue diseases (CTDs) and it is characterized by a deep impact on morbidity and mortality. Due to the poor knowledge of CTD-ILD's natural history and due to the difficulties related to design of randomized control trials, there is a lack of prospective data about the prevalence, follow-up, and therapeutic efficacy. For these reasons, the choice of therapy for CTD-ILD is currently very challenging and still largely based on experts' opinion. Treatment is often based on steroids and conventional immunosuppressive drugs, but the recent publication of the encouraging results of the INBUILD trial has highlighted a possible effective and safe use of antifibrotic drugs as a new therapeutic option for these subjects. Aim of this review is to summarize the available data and recent advances about therapeutic strategies for ILD in the context of various CTD, such as systemic sclerosis, idiopathic inflammatory myopathy and Sjogren syndrome, systemic lupus erythematosus, mixed connective tissue disease and undifferentiated connective tissue disease, and interstitial pneumonia with autoimmune features, focusing also on ongoing clinical trials.
2020
- Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial
[Articolo su rivista]
Perrone, F.; Piccirillo, M. C.; Ascierto, P. A.; Salvarani, C.; Parrella, R.; Marata, A. M.; Popoli, P.; Ferraris, L.; Marrocco-Trischitta, M. M.; Ripamonti, D.; Binda, F.; Bonfanti, P.; Squillace, N.; Castelli, F.; Muiesan, M. L.; Lichtner, M.; Calzetti, C.; Salerno, N. D.; Atripaldi, L.; Cascella, M.; Costantini, M.; Dolci, G.; Facciolongo, N. C.; Fraganza, F.; Massari, M.; Montesarchio, V.; Mussini, C.; Negri, E. A.; Botti, G.; Cardone, C.; Gargiulo, P.; Gravina, A.; Schettino, C.; Arenare, L.; Chiodini, P.; Gallo, C.
abstract
Background: Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods: A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results: In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions: Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).
2020
- Tocilizumab in patients with severe COVID-19: a retrospective cohort study
[Articolo su rivista]
Guaraldi, G; Meschiari, M; Cozzi-Lepri, A; Milic, J; Tonelli, R; Menozzi, M; Franceschini, E; Cuomo, G; Orlando, G; Borghi, V; Santoro, A; Di Gaetano, M; Puzzolante, C; Carli, F; Bedini, A; Corradi, L; Fantini, R; Castaniere, I; Tabbì, L; Girardis, M; Tedeschi, S; Giannella, M; Bartoletti, M; Pascale, R; Dolci, G; Brugioni, L; Pietrangelo, A; Cossarizza, A; Pea, F; Clini, E; Salvarani, C; Massari, M; Viale, Pl; Mussini, C.
abstract
Background- There is no approved therapy for COVID-19 pneumonia. The aim of this multicentre cohort study
was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and/or
death in patients with severe COVID-19 pneumonia who received standard of care (SoC) treatment.
Methods- The TESEO Cohort Study is a retrospective, multicentre observational cohort study of patients with
COVID-19 severe pneumonia treated with SoC with or without tocilizumab using intravenous (IV) or
subcutaneous (SC) formulations, identifying respectively treated and comparator groups. Survival
analysis was performed with participants’ follow-up accruing from the date of entry into clinics until
initiation of invasive mechanical ventilation or death, used as a composite outcome. Treatment
groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for
gender, age and baseline Sequential Organ Failure Assessment (SOFA) score.
Findings- Of 544 patients included, 179 patients were treated with tocilizumab: 88 with the IV (16.1%) and 91
with SC formulation (16.7%). Mortality was significantly higher in the comparator group (20%) as
opposed to tocilizumab IV (6.8%) and tocilizumab SC (7.7%) (p<0.001). A reduced risk of invasive
mechanical ventilation/death was shown for participants treated with tocilizumab from fitting a Cox
regression analysis adjusted for gender, age and SOFA score (aHR=0.61, 95% CI:0.40-0.92; p=0.02).
We found no evidence for a difference between IV and SC administration route of tocilizumab. With
regards to the mortality endpoint alone, a reduced risk was observed comparing tocilizumab with
the comparator group (aHR=0.38 95% CI:0.17-0.83, p=0.02) .
Interpretation- Tocilizumab, regardless of IV or SC administration may be capable of reducing invasive mechanical
ventilation or death in severe COVID-19 pneumonia. Our observations should be confirmed in
randomised studies.
Funding- This study was not funded.
2020
- Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicenter retrospective study
[Articolo su rivista]
Manfredi, Andreina; Cassone, Giulia; Furini, Federica; Gremese, Elisa; Venerito, Vincenzo; Atzeni, Fabiola; Arrigoni, Eugenio; Della Casa, Giovanni; Cerri, Stefania; Govoni, Marcello; Petricca, Luca; Iannone, Florenzo; Salvarani, Carlo; Sebastiani, Marco
abstract
Interstitial lung disease (ILD) is the most severe extra-articular manifestation of rheumatoid arthritis (RA). Although it is responsible of 10-20% of all RA mortality, no controlled studies are available for the treatment of RA-ILD and its therapeutic approach is still debated.
2020
- Tofacitinib for the treatment of refractory Takayasu's arteritis: description of 2 cases
[Articolo su rivista]
Palermo, A.; Marvisi, C.; Casali, M.; Pipitone, N.; Muratore, F.; Salvarani, C.
abstract
2020
- Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows
[Articolo su rivista]
Cassone, Giulia; Manfredi, Andreina; Vacchi, Caterina; Luppi, Fabrizio; Coppi, Francesca; Salvarani, Carlo; Sebastiani, Marco
abstract
Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5-1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10-20% of mortality, with a mean survival of 5-8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.
2020
- Ultrasonographic Evidence of Predominance of Acute Extracapsular and Chronic Intrasynovial Patterns in 100 Cases of Psoriatic Hand Dactylitis
[Articolo su rivista]
Girolimetto, N.; Macchioni, P.; Tinazzi, I.; Costa, L.; Mcgonagle, D.; Peluso, R.; Del Puente, A.; Addimanda, O.; Marchetta, A.; Possemato, N.; Tasso, M.; Salvarani, C.; Scarpa, R.; Caso, F.
abstract
OBJECTIVE: To use ultrasonography to study whether the duration of psoriatic dactylitis was associated with different patterns of extracapsular and synovial-based involvement. METHODS: One hundred cases of hand dactylitis from 85 patients with psoriatic arthritis (PsA) were consecutively enrolled in a multicenter cross-sectional study and divided into 2 groups according to dactylitis duration (shorter or longer than the median: 20 weeks). All dactylitis fingers were investigated using high-frequency ultrasound both in greyscale (GS) and power Doppler (PD), evaluating the presence of flexor tenosynovitis, soft tissue edema, subcutaneous PD signal (PDS), extensor tendon involvement, and joint synovitis. RESULTS: Cases with a shorter dactylitis duration (< 20 weeks) had a significantly higher prevalence of GS flexor tenosynovitis of grade > 2, PD flexor tenosynovitis, soft tissue edema, and subcutaneous PDS (p = 0.001, p < 0.001, p < 0.05, and p = 0.001, respectively). However, the presence of synovitis in GS and PD mode (in both cases at proximal interphalangeal level) was more frequent in patients with longer dactylitis duration (p < 0.001). When detected in the chronic form, flexor tenosynovitis was grade 2 or lower. CONCLUSION: In a large cohort of PsA hand dactylitis, we found a predominant extracapsular inflammation (flexor tenosynovitis and soft tissue edema) in early cases and a high prevalence of joint synovitis at proximal interphalangeal level in the chronic form. However, longitudinal imaging studies are needed to clarify these aspects.
2020
- Ultrasonographic and clinical assessment of peripheral enthesitis and arthritis in an Italian cohort of inflammatory bowel disease patients
[Articolo su rivista]
Bertolini, E.; Macchioni, P.; Rizzello, F.; Salice, M.; Vukatana, G.; Sandri, G.; Bertani, A.; Ciancio, G.; Govoni, M.; Zelante, A.; Malavolta, N.; Beltrami, M.; Salvarani, C.
abstract
Aims: To evaluate the prevalence of clinical and ultrasonographic musculoskeletal involvement in Italian patients with inflammatory bowel disease (IBD). Methods: In this cross-sectional multicenter study, 148 consecutive patients with IBD were evaluated by a gastroenterologist and a rheumatologist. All patients underwent a B-mode and power Doppler ultrasonographic examination of 6 pairs of entheses and of knee and ankle joints. Results: A positive history for at least one musculoskeletal manifestation was reported by 40.5% of patients, more frequently in ulcerative colitis (UC) (p = 0.033). Inflammatory back pain was reported by 13.5% of patients, and a past history of peripheral arthritis by 14.9%, entheseal inflammation by 14.2% and dactylitis by 2.7%. At clinical examination, arthritis was observed in 19.6% of patients and enthesitis in 33%. Oligoarthritis and enthesitis at clinical examination were more frequently observed in UC than in Crohn disease (CD). 37.8% of total IBD patients fulfilled ASAS classification criteria for axial and/or peripheral spondyloarthritis, 8.1% ASAS classification criteria for axial spondyloarthritis, and 29.7% ASAS classification criteria for peripheral spondyloarthritis. With ultrasonographic examination, signs of entheseal involvement were observed in 87.8% of patients, while at power Doppler, ≥1 abnormality was observed in 27.1%. ASAS+ patients compared to those ASAS- had a significantly higher frequency at ultrasonography of acute entheseal abnormalities, power Doppler entheseal positivity and joint involvement. These abnormalities at ultrasonography were also observed in 34%, 13% and 12% of ASAS- patients. Conclusions: Musculoskeletal manifestations occur frequently in patients with IBD. Ultrasonographic entheseal and joint involvement were also observed in asymptomatic patients.
2020
- Up-to-date treatment and management of myositis
[Articolo su rivista]
Pipitone, N.; Salvarani, C.
abstract
PURPOSE OF REVIEW: Myositis, or idiopathic inflammatory myopathy, is an overarching concept that includes dermatomyositis, polymyositis, immune-mediated necrotizing myopathy and the antisynthetase syndrome. Glucocorticoids are still considered the mainstay of treatment of myositis but some patients require add-on immunosuppressive therapy because of insufficient response to glucocorticoids, relapses when glucocorticoids are tapered, or because they incur glucocorticoid-related side effects. RECENT FINDINGS: The goal of this article was to review (PubMed search from January 2019 through June 2020) the efficacy and safety of standard and novel agents used in adult dermatomyositis, polymyositis, immune-mediated necrotizing myopathy and the antisynthetase syndrome. SUMMARY: Established therapies beyond glucocorticoids continue to have a major role in managing patients with myositis. In addition, novel agents are being tried for refractory manifestations of myositis.
2020
- Vasculitis in a patient with mixed cryoglobulinemia treated with rituximab biosimilar CT-P10: a case report
[Articolo su rivista]
Vacchi, Caterina; Manfredi, Andreina; Salvarani, Carlo; Sebastiani, Marco
abstract
Rituximab represents a milestone in the treatment of mixed cryoglobulinemic vasculitis. Despite usually well-tolerated, rituximab may induce different types of adverse drug reactions, including exacerbation of vasculitis. Rituximab biosimilar have been recently approved in Europe in the treatment of rheumatoid arthritis, but no data are available about effectiveness and safety of rituximab biosimilar in the treatment of mixed cryoglobulinemic vasculitis. We describe a severe skin vasculitis reactivation in a patient affected by rheumatoid arthritis and mixed cryoglobulinemic vasculitis treated with rituximab biosimilar. After 7 days from the first infusion, a severe purpuric rash at lower limbs appeared, that resolved in about 2 weeks with high dose-corticosteroid. Rituximab-induced vasculitis has also been described since 2001, but its pathophysiology is still controversial due to the anecdotical descriptions in literature and the variability of the time between the rituximab infusion and the onset of skin lesions. Up to date, this is the first report describing a vasculitic flare in a patient affected by mixed cryoglobulinemic vasculitis treated with rituximab biosimilar.
2019
- 117. PREDICTION OF LONG-TERM EVOLUTIONARY PROFILES IN EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (CHURG– STRAUSS) BASED ON BASELINE AND FOLLOW-UP CHARACTERISTICS
[Abstract in Rivista]
Papo, Matthias; Sinico, Renato; Teixeira, Vítor; Urban, Maria Letizia; Mahrhold, Juliane; Cassone, Giulia; Schiavon, Franco; Groh, Matthieu; Marvisi, Chiara; Samson, Maxime; Barba, Thomas; Jayne, David; Hellmich, Bernhard; Salvarani, Carlo; Kahn, Jean-Emmanuel; Bonnotte, Bernard; Durel, Cécile-Audrey; Cohen, Pascal; Puéchal, Xavier; Mouthon, Luc; Guillevin, Loïc; Emmi, Giacomo; Vaglio, Augusto; Terrier, Benjamin
abstract
2019
- 2018 EULAR recommendations for a core data set to support observational research and clinical care in giant cell arteritis
[Articolo su rivista]
Ehlers, L.; Askling, J.; Bijlsma, H. W. J.; Cid, M. C.; Cutolo, M.; Dasgupta, B.; Dejaco, C.; Dixon, W. G.; Feltelius, N.; Finckh, A.; Gilbert, K.; Mackie, S. L.; Mahr, A.; Matteson, E. L.; Neill, L.; Salvarani, C.; Schmidt, W. A.; Strangfeld, A.; Van Vollenhoven, R. F.; Buttgereit, F.
abstract
Giant cell arteritis (GCA) represents the most common form of primary systemic vasculitis and is frequently associated with comorbidities related to the disease itself or induced by the treatment. Systematically collected data on disease course, treatment and outcomes of GCA remain scarce. The aim of this EULAR Task Force was to identify a core set of items which can easily be collected by experienced clinicians, in order to facilitate collaborative research into the course and outcomes of GCA. A multidisciplinary EULAR task force group of 20 experts including rheumatologists, internists, epidemiologists and patient representatives was assembled. During a 1-day meeting, breakout groups discussed items from a previously compiled collection of parameters describing GCA status and disease course. Feedback from breakout groups was further discussed. Final consensus was achieved by means of several rounds of email discussions after the meeting. A three-round Delphi survey was conducted to determine a core set of parameters including the level of agreement. 117 parameters were regarded as relevant. Potential items were subdivided into the following categories: General, demographics, GCA-related signs and symptoms, other medical conditions and treatment. Possible instruments and assessment intervals were proposed for documentation of each item. To facilitate implementation of the recommendations in clinical care and clinical research, a minimum core set of 50 parameters was agreed. This proposed core set intends to ensure that relevant items from different GCA registries and databases can be compared for the dual purposes of facilitating clinical research and improving clinical care.
2019
- 354. EFFICACY OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS TREATMENTS ACCORDING TO THE TYPE OF MANIFESTATIONS BASED ON ANALYSIS OF 636 PATIENTS
[Abstract in Rivista]
Papo, Matthias; Sinico, Alberto; Teixeira, Vítor; Urban, Maria Letizia; Mahrhold, Juliane; Cassone, Giulia; Schiavon, Franco; Groh, Matthieu; Marvisi, Chiara; Samson, Maxime; Barba, Thomas; Jayne, David; Hellmich, Bernhard; Salvarani, Carlo; Kahn, Jean-Emmanuel; Bonnotte, Bernard; Durel, Cécile-Audrey; Cohen, Pascal; Puéchal, Xavier; Mouthon, Luc; Guillevin, Loïc; Emmi, Giacomo; Vaglio, Augusto; Terrier, Benjamin
abstract
2019
- 64 Cu and fluorescein labeled anti-miRNA peptide nucleic acids for the detection of miRNA expression in living cells
[Articolo su rivista]
Croci, Stefania; Manicardi, Alex; Rubagotti, Sara; Bonacini, Martina; Iori, Michele; Capponi, Pier Cesare; Cicoria, Gianfranco; Parmeggiani, Maria; Salvarani, Carlo; Versari, Annibale; Corradini, Roberto; Asti, Mattia
abstract
MiRNAs are single stranded RNAs of 18–22 nucleotides. They are promising diagnostic and prognostic markers for several pathologies including tumors, neurodegenerative, cardiovascular and autoimmune diseases. In the present work the development and characterization of anti-miRNA radiolabeled probes based on peptide nucleic acids (PNAs) for potential non-invasive molecular imaging in vivo of giant cell arteritis are described. MiR-146a and miR-146b-5p were selected as targets because they have been found up-regulated in this disease. Anti-miR and scramble PNAs were synthesized and linked to carboxyfluorescein or DOTA. DOTA-anti-miR PNAs were then labelled with copper-64 ( 64 Cu) to function as non-invasive molecular imaging tools. The affinity of the probes for the targets was assessed in vitro by circular dichroism and melting temperature. Differential uptake of fluorescein and 64 Cu labeled anti-miRNA probes was tested on BCPAP and A549 cell lines, expressing different levels of miR-146a and -146b-5p. The experiments showed that the anti-miR-146a PNAs were more effective than the anti-miR-146b-5p PNAs. Anti-miR-146a PNAs could bind both miR-146a and miR-146b-5p. The uptake of fluorescein and 64 Cu labeled anti-miR-146a PNAs was higher than that of the negative control scramble PNAs in miRNA expressing cells in vitro. 64 Cu-anti-miR-146a PNAs might be further investigated for non-invasive PET imaging of miR-146 overexpressing diseases.
2019
- AB0212 LONG-TERM TREATMENT WITH RITUXIMAB IN SYSTEMIC SCLEROSISMANAGEMENT: AN OVERVIEW OF THE CLINICAL EXPERIENCE FROM A REAL-LIFE SETTING
[Abstract in Rivista]
Lumetti, Federica; Spinella, Amelia; Colaci, Michele; Cocchiara, Emanuele; Magnani, Luca; Baiocchi, Gianluigi; Ferri, Clodoveo; Salvarani, Carlo; Giuggioli, Dilia
abstract
2019
- AB0472 PRIMARY SJOGREN SYNDROME ASSOCIATED INTERSTITIAL LUNG DISEASE: FEATURES, TREATMENT AND OUTCOME OF A MONOCENTRIC COHORT
[Abstract in Rivista]
Manfredi, Andreina; Sebastiani, Marco; Vacchi, Caterina; Luppi, Fabrizio; Cerri, Stefania; Cassone, Giulia; Salvarani, Carlo
abstract
2019
- AB0624 SAFETY OF RITUXIMAB BIOSIMILAR FOR THE TREATMENT OF CRYOGLOBULINEMIC VASCULITIS
[Abstract in Rivista]
Vacchi, Caterina; Visentini, Marcella; Cicco, Maria DI; Angelotti, Francesca; Lauletta, Gianfranco; Manfredi, Andreina; Filippini, Davide; Tavoni, Antonio; Casato, Milvia; Castelnovo, Laura; Monti, Giuseppe; Pietrogrande, Maurizio; Salvarani, Carlo; Galli, Massimo; Sebastiani, Marco
abstract
2019
- AB0645 CANNABINOIDS IN THE TREATMENT OF PAIN RELATED TO SYSTEMIC SCLEROSIS SKIN ULCERS: OUR EXPERIENCE
[Abstract in Rivista]
Cocchiara, Emanuele; Spinella, Amelia; Magnani, Luca; Lumetti, Federica; Palermo, Adalgisa; Baiocchi, Gianluigi; Salvarani, Carlo; Giuggioli, Dilia
abstract
2019
- AB1157 VALIDATION OF VECTOR (VELCRO CRACKLES DETECTOR) FOR THE DIAGNOSIS OF INTERSTITIAL LUNG DISEASE IN PATIENTS WITH CONNECTIVE TISSUE DISEASES
[Abstract in Rivista]
Manfredi, Andreina; Cassone, Giulia; Pancaldi, Fabrizio; Vacchi, Caterina; Cerri, Stefania; Casa, Giovanni Della; Salvarani, Carlo; Sebastiani, Marco
abstract
2019
- Acute exacerbation of interstitial lung diseases secondary to systemic rheumatic diseases: A prospective study and review of the literature
[Articolo su rivista]
Manfredi, A.; Sebastiani, M.; Cerri, S.; Vacchi, C.; Tonelli, R.; Casa, G. D.; Cassone, G.; Spinella, A.; Pancaldi, Fabrizio; Luppi, F.; Salvarani, C.
abstract
Acute exacerbation (AE) is a possible manifestation of interstitial lung diseases (ILD) associated to very high mortality. It’s defined as clinically significant respiratory deterioration with evidence of new widespread alveolar abnormalities on computed tomography scan. AE is better described in idiopathic pulmonary fibrosis (IPF) but also reported in ILD secondary to connective tissue diseases (CTD) and vasculitis. The main features and the real clinical impact of this severe complication in these patients are not well defined. Aim of our study was to prospectively investigate the incidence, clinical features and outcome of AE in a population of patients with ILD related to CTD and vasculitis. We consecutively enrolled all patients, with ILD secondary to rheumatic systemic diseases, referring to our multidisciplinary outpatient clinic for rare lung diseases. All patients were followed for at least 12 months (range, 12–36 months). At baseline, all patients underwent to a core set of laboratory investigations and periodically followed; data about demographic, disease onset, clinical, serological and therapeutic features were also recorded. AE occurred in 9/78 patients, with an incidence of 5.77/100 patients/year, and 5/9 patients died because of AE. The baseline value of DLCO was significantly associated to the risk of AE at Cox regression. In patients with ILD related to rheumatic systemic diseases AE can occur with an incidence similar to IPF. Rheumatologists should carefully consider this life-threatening complication as a possible natural course of all patients with ILD secondary to systemic rheumatic disease.
2019
- Anakinra drug retention rate and predictive factors of long-term response in systemic juvenile idiopathic arthritis and adult onset still disease
[Articolo su rivista]
Sota, J.; Rigante, D.; Ruscitti, P.; Insalaco, A.; Sfriso, P.; De Vita, S.; Cimaz, R.; Lopalco, G.; Emmi, G.; Torre, F. L.; Fabiani, C.; Olivieri, A. N.; Cattalini, M.; Cammelli, D.; Gallizzi, R.; Alessio, M.; Manna, R.; Viapiana, O.; Frassi, M.; Pardeo, M.; Maier, A.; Salvarani, C.; Talarico, R.; Mosca, M.; Colafrancesco, S.; Priori, R.; Maggio, M. C.; Gaggiano, C.; Grosso, S.; De Benedetti, F.; Vitale, A.; Giacomelli, R.; Cantarini, L.
abstract
Background and Objective: Only a few studies have reported long-term efficacy of interleukin (IL)-1 inhibition in systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still disease (AOSD). Herein we report on the effectiveness of anakinra (ANA), expressed in terms of drug retention rate (DRR), and evaluate the predictive factors of drug survival in a cohort of patients with sJIA and AOSD.Patients and Methods: This is a multicenter study reviewing retrospectively the medical records from 61 patients with sJIA and 76 with AOSD, all treated with ANA in 25 Italian tertiary referral centers.Results: The cumulative retention rate of ANA at 12-, 24-, 48-, and 60-month of follow-up was 74.3%, 62.9%, 49.4%, and 49.4%, respectively, without any significant differences between sJIA and AOSD patients (p = 0.164), and between patients treated in monotherapy compared with the subgroup coadministered with conventional disease-modifying antirheumatic drugs (cDMARDs) (p = 0.473). On the other hand, a significant difference in DRR was found between biologic-naive patients and those previously treated with biotechnologic drugs (p = 0.009), which persisted even after adjustment for pathology (p = 0.013). In the regression analysis, patients experiencing adverse events (AEs) hazards ratio (HR) = 3.029 [confidence interval (CI) 1.7505.242], p < 0.0001 and those previously treated with other biologic agents [HR = 1.818 (CI 1.0073.282), p = 0.047] were associated with a higher HR of ANA discontinuation. The median treatment delay was significantly higher among patients discontinuing ANA (p < 0.0001). Significant corticosteroid-sparing (p = 0.033) and cDMARD-sparing effects (p < 0.0001) were also recorded. Less than one-third of our cohort developed AEs, and 85% were deemed mild in nature, with 70% of them involving the skin.Conclusions: Our findings display an overall excellent DRR of ANA on the long run for both sJIA and AOSD, that may be further optimized by closely monitoring patients safety issues and employing this IL-1 inhibitor as a first-line biologic as early as possible. Moreover, ANA allowed a significant drug-sparing effect and showed an overall good safety profile.
2019
- Aortic dilatation in patients with large vessel vasculitis: A longitudinal case control study using PET/CT
[Articolo su rivista]
Muratore, F.; Crescentini, F.; Spaggiari, L.; Pazzola, G.; Casali, M.; Boiardi, L.; Pipitone, N.; Croci, S.; Galli, E.; Aldigeri, R.; Versari, A.; Salvarani, C.
abstract
Objective: To evaluate aortic diameter and predictors of aortic dilatation using 18FDG-PET/CT in a longitudinally followed cohort of patients with large vessel vasculitis (LVV)compared with controls. Methods: All consecutive patients with LVV who underwent at least 2 PET/CT scans between January 2008 and May 2015 were included. The first and last PET/CT study was evaluated by a radiologist and a nuclear medicine physician. Diameter and FDG uptake of the aorta was measured at 4 different levels: ascending, descending thoracic, suprarenal and infrarenal abdominal aorta. Twenty-nine age- and sex-matched patients with lymphoma who underwent at least 2 PET/CT scans in the same time interval were selected as controls. Results: 93 patients with LVV were included in the study. In the time interval between first and last PET/CT study (median time 31 months), the diameter of the ascending, descending thoracic and suprarenal abdominal aorta significantly increased in LVV patients but not in controls. At last PET/CT, patients with LVV compared with controls had higher diameter of ascending [35.41 (5.54)vs 32.97 (4.11)mm, p = 0.029], descending thoracic [28.42 (4.82)vs 25.72 (3.55)mm, p = 0.007]and suprarenal abdominal aorta, mean [25.34 (7.01)vs 22.16 (3.26)mm, p = 0.005]and more frequently had aortic dilatation [19% vs 3%, p = 0.023]. Significant predictors of aortic dilatation were male sex [OR 7.27, p = 0.001]and, only for GCA, hypertension [OR 6.30, p = 0.031]. Finally, GCA patients with aortic FDG uptake grade 3 at first PET/CT, compared to those with aortic FDG uptake ≤2, had significantly higher aortic diameter. Conclusions: Patients with LVV are at increased risk of aortic dilatation compared with age- and sex-matched controls. Significant predictors of aortic dilatation are male sex and, only for GCA, hypertension. GCA patients with aortic FDG uptake grade 3 are at increased risk of aortic dilatation.
2019
- Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: The InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device)
[Articolo su rivista]
Manfredi, A.; Cassone, G.; Cerri, S.; Venerito, V.; Fedele, A. L.; Trevisani, M.; Furini, F.; Addimanda, O.; Pancaldi, F.; Della Casa, G.; D'Amico, R.; Vicini, R.; Sandri, G.; Torricelli, P.; Celentano, I.; Bortoluzzi, A.; Malavolta, N.; Meliconi, R.; Iannone, F.; Gremese, E.; Luppi, F.; Salvarani, C.; Sebastiani, M.
abstract
Background: Interstitial lung disease (ILD) is a severe systemic manifestation of rheumatoid arthritis (RA). High-resolution computed tomography (HRCT) represents the gold standard for the diagnosis of ILD, but its routine use for screening programs is not advisable because of both high cost and X-ray exposure. Velcro crackles at lung auscultation occur very early in the course of interstitial pneumonia, and their detection is an indication for HRCT. Recently, we developed an algorithm (VECTOR) to detect the presence of Velcro crackles in pulmonary sounds and showed good results in a small sample of RA patients. The aim of the present investigation was to validate the diagnostic accuracy of VECTOR in a larger population of RA patients, compared with that of the reference standard of HRCT, from a multicentre study. Methods: To avoid X-ray exposure, we enrolled 137 consecutive RA patients who had recently undergone HRCT. Lung sounds of all patients were recorded in 4 pulmonary fields bilaterally with a commercial electronic stethoscope (ES); subsequently, all HRCT images were blindly evaluated by a radiologist, and audio data were analysed by means of VECTOR. Results: Fifty-nine of 137 patients showed ILD (43.1%). VECTOR correctly classified 115/137 patients, showing a diagnostic accuracy of 83.9% and a sensitivity and specificity of 93.2 and 76.9%, respectively. Conclusions: VECTOR may represent the first validated tool for the screening of RA patients who are suspected for ILD and who should be directed to HRCT for the diagnosis. Moreover, early identification of RA-ILD could contribute to the design of prospective studies aimed at elucidating unclear aspects of the disease.
2019
- Disease activity assessment of rheumatic diseases during pregnancy: a comprehensive review of indices used in clinical studies
[Articolo su rivista]
Andreoli, Laura; Gerardi, Maria Chiara; Fernandes, Melissa; Bortoluzzi, Alessandra; Bellando-Randone, Silvia; Brucato, Antonio; Caporali, Roberto; Chighizola, Cecilia Beatrice; Chimenti, Maria Sole; Conigliaro, Paola; Cutolo, Maurizio; Cutro, Maria Stefania; D'Angelo, Salvatore; Doria, Andrea; Elefante, Elena; Fredi, Micaela; Galeazzi, Mauro; Gerosa, Maria; Govoni, Marcello; Iuliano, Annamaria; Larosa, Maddalena; Lazzaroni, Maria Grazia; Matucci-Cerinic, Marco; Meroni, Marianna; Meroni, Pier Luigi; Mosca, Marta; Patanè, Massimo; Pazzola, Giulia; Pendolino, Monica; Perricone, Roberto; Ramoni, Véronique; Salvarani, Carlo; Sebastiani, Gian Domenico; Selmi, Carlo; Spinelli, Francesca Romana; Valesini, Guido; Scirè, Carlo Alberto; Tincani, Angela
abstract
Pregnancy requires a special management in women with inflammatory rheumatic diseases (RDs), with the aim of controlling maternal disease activity and avoiding fetal complications. Despite the heterogeneous course of RDs during pregnancy, their impact on pregnancy largely relates to the extent of active inflammation at the time of conception. Therefore, accurate evaluation of disease activity is crucial for the best management of pregnant patients. Nevertheless, there are limitations in using conventional measures of disease activity in pregnancy, as some items included in these instruments can be biased by symptoms or by physiological changes related to pregnancy and the pregnancy itself may influence laboratory parameters used to assess disease activity. This article aims to summarize the current literature about the available instruments to measure disease activity during pregnancy in RDs. Systemic lupus erythematosus is the only disease with instruments that have been modified to account for several adaptations which might interfere with the attribution of signs or symptoms to disease activity during pregnancy. No modified-pregnancy indices exist for women affected by other RDs, but standard indices have been applied to pregnant patients. The current body of knowledge shows that the physiologic changes that occur during pregnancy need to be either adapted from existing instruments or developed to improve the management of pregnant women with RDs. Standardized instruments to assess disease activity during pregnancy would be helpful not only for clinical practice but also for research purposes.
2019
- Drug Retention Rate and Predictive Factors of Drug Survival for Interleukin-1 Inhibitors in Systemic Juvenile Idiopathic Arthritis
[Articolo su rivista]
Sota, Jurgen; Insalaco, Antonella; Cimaz, Rolando; Alessio, Maria; Cattalini, Marco; Gallizzi, Romina; Maggio, Maria Cristina; Lopalco, Giuseppe; La Torre, Francesco; Fabiani, Claudia; Pardeo, Manuela; Olivieri, Alma Nunzia; Sfriso, Paolo; Salvarani, Carlo; Gaggiano, Carla; Grosso, Salvatore; Bracaglia, Claudia; De Benedetti, Fabrizio; Rigante, Donato; Cantarini, Luca
abstract
Background and Objectives: Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA.Methods: Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers.Results: Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN (p = 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (p = 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs (p = 0.038) and when distinguishing according to adverse events (AEs) occurrence (p = 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 [CI: 1.341-8.406], p = 0.01) and those experiencing AEs (HR = 2.970 [CI: 1.186-7.435], p = 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (p = 0.0002).Conclusions: Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase.
2019
- EFFICACY OF EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS TREATMENTS ACCORDING TO THE TYPE OF MANIFESTATIONS BASED ON ANALYSIS OF 636 PATIENTS
[Abstract in Rivista]
Papo, M; Sinico, Ra; Teixeira, V; Urban, Ml; Mahrhold, J; Monti, S; Cassone, G; Schiavon, F; Seeliger, B; Neumann, T; Kroegel, C; Groh, M; Marvisi, C; Samson, M; Barba, T; Jayne, D; Hellmich, B; Montecucco, C; Salvarani, C; Kahn, Je; Bonnotte, B; Durel, Ca; Puechal, X; Mouthon, L; Guillevin, L; Emmi, G; Vaglio, A; Terrier, B
abstract
2019
- Effectiveness of adalimumab for the treatment of psoriatic arthritis: An Italian real-life retrospective study
[Articolo su rivista]
D'Angelo, S.; Cantini, F.; Ramonda, R.; Cantarini, L.; Carletto, A.; Chimenti, M. S.; Sedie, A. D.; Foti, R.; Gerli, R.; Lomater, C.; Lubrano, E.; Marchesoni, A.; Zabotti, A.; Salvarani, C.; Scrivo, R.; Scarpa, R.; Tramontano, G.; Nannini, C.; Lorenzin, M.; Fabbroni, M.; Martinis, F.; Perricone, R.; Carli, L.; Visalli, E.; Rovera, G.; Perrotta, F. M.; Quartuccio, L.; Altobelli, A.; Costa, L.; Niccoli, L.; Ortolan, A.; Caso, F.
abstract
Background: Few studies have evaluated the effectiveness of adalimumab in the real-life setting in psoriatic arthritis (PsA). Objective: To evaluate the 2-year retention rate of adalimumab in PsA patients. Potential baseline parameters influencing persistence on treatment were also evaluated. Methods: PsA patients from 16 Italian Rheumatology Units treated with adalimumab as first- or second-line biological therapy were retrospectively evaluated. Adalimumab retention rate was evaluated at 12 and 24 months. Logistic regression was used to evaluate the association between predictor variables and adalimumab retention rate. Results: From 424 patients (53.5% male, aged 48.3 ± 12.8 years) who started treatment with adalimumab, 367 (86.6%) maintained treatment for 12 months and 313 (73.8%) for 2 years. At 24-months, Disease Activity in PsA (DAPSA) remission (defined as ≤4) and Low Disease Activity (LDA) (≤14) were achieved in 22.8% and 44.4% of patients, respectively. Adalimumab treatment significantly decreased the number of tender (7.0 ± 5.7 at baseline vs. 2.3 ± 3.5 at 24 months, p < 0.001) and swollen joints (2.7 ± 2.8 at baseline vs. 0.4 ± 0.9 at 24 months, p < 0.001), DAPSA (25.5 ± 10.9 at baseline vs. 11.0 ± 8.4 at 24 months, p < 0.001), PASI (5.3 ± 5.7 at baseline vs. 2.7 ± 2.8 at 24 months, p < 0.001) and CRP (3.8 ± 6.3 at baseline vs. 1.2 ± 1.7 at 24 months, p < 0.001). Among a range of laboratory and clinical variables, only female gender was associated with improved adalimumab persistence at 24 months (OR: 1.98, 95% CI: 1.2-3.2, p = 0.005). Conclusions: Independent of a range of predictor variables, adalimumab was shown to be effective, while maintaining a high retention rate after 2 years in PsA patients.
2019
- Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors
[Articolo su rivista]
Deodhar, Atul; Poddubnyy, Denis; Pacheco-Tena, Cesar; Salvarani, Carlo; Lespessailles, Eric; Rahman, Proton; Järvinen, Pentti; Sanchez-Burson, Juan; Gaffney, Karl; Lee, Eun Bong; Krishnan, Eswar; Santisteban, Silvia; Li, Xiaoqi; Zhao, Fangyi; Carlier, Hilde; Reveille, John D
abstract
To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (r-axSpA) and prior inadequate response or intolerance to 1 or 2 TNF inhibitors (TNFi).
2019
- FRI0613 THERAPEUTIC STRATEGIES AND SURVIVAL IN PATIENTS WITH INTERSTITIAL PNEUMONIA WITH AUTOIMMUNE FEATURES
[Abstract in Rivista]
Sebastiani, Marco; Vacchi, Caterina; Pasquale, Lisa De; Cerri, Stefania; Cassone, Giulia; Casa, Giovanni Della; Garofalo, Martina; Salvarani, Carlo; Manfredi, Andreina
abstract
2019
- Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
[Articolo su rivista]
Lyons, P. A.; Peters, J. E.; Alberici, F.; Liley, J.; Coulson, R. M. R.; Astle, W.; Baldini, C.; Bonatti, F.; Cid, M. C.; Elding, H.; Emmi, G.; Epplen, J.; Guillevin, L.; Jayne, D. R. W.; Jiang, T.; Gunnarsson, I.; Lamprecht, P.; Leslie, S.; Little, M. A.; Martorana, D.; Moosig, F.; Neumann, T.; Ohlsson, S.; Quickert, S.; Ramirez, G. A.; Rewerska, B.; Schett, G.; Sinico, R. A.; Szczeklik, W.; Tesar, V.; Vukcevic, D.; Akil, M.; Barratt, J.; Basu, N.; Butterworth, A. S.; Bruce, I.; Clarkson, M.; Conlon, N.; Dasgupta, B.; Doulton, T. W. R.; Espigol-Frigole, G.; Flossmann, O.; Gabrielli, A.; Gasior, J.; Gregorini, G.; Guida, G.; Hernandez-Rodriguez, J.; Hruskova, Z.; Hudson, A.; Knight, A.; Lanyon, P.; Luqmani, R.; Magliano, M.; Manfredi, A. A.; Marguerie, C.; Maritati, F.; Marvisi, C.; Mchugh, N. J.; Molloy, E.; Motyer, A.; Mukhtyar, C.; Padyukov, L.; Pesci, A.; Prieto-Gonzalez, S.; Ramentol-Sintas, M.; Reis, P.; Roccatello, D.; Rovere-Querini, P.; Salvarani, C.; Santarsia, F.; Solans-Laque, R.; Soranzo, N.; Taylor, J.; Wessels, J.; Zwerina, J.; Terrier, B.; Watts, R. A.; Vaglio, A.; Holle, J. U.; Wallace, C.; Smith, K. G. C.
abstract
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
2019
- Glucocorticoid Dosages and Acute-Phase Reactant Levels at Giant Cell Arteritis Flare in a Randomized Trial of Tocilizumab
[Articolo su rivista]
Stone, J. H.; Tuckwell, K.; Dimonaco, S.; Klearman, M.; Aringer, M.; Blockmans, D.; Brouwer, E.; Cid, M. C.; Dasgupta, B.; Rech, J.; Salvarani, C.; Schulze-Koops, H.; Schett, G.; Spiera, R.; Unizony, S. H.; Collinson, N.
abstract
Objective This study was undertaken to evaluate glucocorticoid dosages and serologic findings in patients with giant cell arteritis (GCA) flares. Methods Patients with GCA were randomly assigned to receive double-blind dosing with either subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week prednisone taper (TCZ-QW + Pred-26), every-other-week TCZ plus 26-week prednisone taper (TCZ-Q2W + Pred-26), placebo plus 26-week prednisone taper (PBO + Pred-26), or placebo plus 52-week prednisone taper (PBO + Pred-52). Outcome measures were prednisone dosage, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare. Results One hundred patients received TCZ-QW + Pred-26, 49 received TCZ-Q2W + Pred-26, 50 received PBO + Pred-26, and 51 received PBO + Pred-52. Of the 149 TCZ-treated patients, 36 (24%) experienced flare, 23 (64%) of whom were still receiving prednisone (median dosage 2.0 mg/day). Among 101 PBO + Pred-treated patients, 59 (58%) experienced flare, 45 (76%) of whom were receiving prednisone (median dosage 5.0 mg/day). Many flares occurred while patients were taking >10 mg/day prednisone: 9 (25%) in the TCZ groups and 13 (22%) in the placebo groups. Thirty-three flares (92%) in TCZ-treated groups and 20 (34%) in PBO + Pred-treated groups occurred with normal CRP levels. More than half of the PBO + Pred-treated patients had elevated CRP levels without flares. Benefits of the TCZ and prednisone combination over prednisone alone for remission induction were apparent by 8 weeks. Conclusion Most GCA flares occurred while patients were still receiving prednisone. Acute-phase reactant levels were not reliable indicators of flare in patients treated with TCZ plus prednisone or with prednisone alone. The addition of TCZ to prednisone facilitates earlier GCA control.
2019
- Interferon Alpha-2a for the Treatment of Post-Infectious Uveitis Secondary to Presumed Intraocular Tuberculosis
[Articolo su rivista]
Invernizzi, Alessandro; Iannaccone, Franca; Marchi, Sylvia; Mastrofilippo, Valentina; Coassin, Marco; Fontana, Luigi; Salvarani, Carlo; McCluskey, Peter; Cimino, Luca
abstract
PURPOSE:
To assess the efficacy and tolerability of interferon (IFN) alpha-2a in post-infectious uveitis secondary to presumed intraocular tuberculosis (IOTB).
METHODS:
Patients with chronic uveitis secondary to presumed IOTB who, after completing an antitubercular treatment, showed poor response to treatments or recurred after tapering oral corticosteroids to ≤7.5 mg/day were enrolled. All patients were treated with IFN alpha-2a subcutaneous injections. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and inflammatory signs were compared between baseline and follow-up visits up to six months.
RESULTS:
Twelve eyes (six patients) were enrolled. Mean BCVA improved from 0.64 ± 0.55 logMAR at baseline to 0.32 ± 0.31 logMAR at 6 months (p = 0.03). Mean CRT decreased from 372 ± 132.2 μm to 274.66 ± 34.9 μm at six months (p = 0.01). Inflammatory signs (vitritis, vasculitis) also decreased overtime. No major complications or tuberculosis reactivations were recorded.
CONCLUSIONS:
IFN alpha-2a was efficacious and safe in treating chronic post-infectious uveitis secondary to presumed IOTB.
2019
- Interleukin-6 expression in inflamed and non-inflamed temporal arteries from patients with giant cell arteritis
[Articolo su rivista]
Pipitone, Nicolo; Muratore, Francesco; Tamagnini, Ione; Cavazza, Alberto; Cimino, Luca; Boiardi, Luigi; Restuccia, Giovanna; Croci, Stefania; Bonacini, Martina; Salvarani, Carlo
abstract
OBJECTIVES:
To evaluate whether interleukin-6 expression in the temporal arteries could be a more sensitive marker of active inflammation compared to the presence of an inflammatory infiltrate.
METHODS:
Sixty-three formalin-fixed, paraffin-embedded temporal artery biopsies performed between 2009 and 2012 from 32 patients with biopsy-proven giant cell arteritis, 8 patients with a negative biopsy but with a final diagnosis of giant cell arteritis, and 23 controls (patients with an initial clinical suspicion of giant cell arteritis in whom an alternative diagnosis subsequently was made) were examined. Biopsy specimens showing a transmural inflammatory infiltrate were considered positive for giant cell arteritis. Immunochemistry was performed to detect interleukin-6 in the temporal artery specimens. Slides of temporal artery biopsies were independently assessed by five readers. Interleukin-6 expression was graded as 0 (absent), 1 (mild), 2 (moderate) and 3 (marked). We considered anti-IL-6 staining positive if staining was of grade 2 or 3.
RESULTS:
Temporal artery biopsies specimens from patients with biopsy-proven giant cell arteritis, biopsy-negative giant cell arteritis and controls were positive for anti-interleukin-6 staining in 59%, 13% and 48% of cases, respectively.
CONCLUSIONS:
Interleukin-6 expression does not increase the sensitivity of temporal artery biopsy in patients with giant cell arteritis who have morphologically uninflamed arteries.
2019
- Large-Vessel Vasculitis
[Capitolo/Saggio]
Muratore, F.; Croci, S.; Soriano, A.; Pipitone, N.; Salvarani, C.
abstract
Giant cell arteritis (GCA) and Takayasu arteritis are the two major forms of idiopathic large vessel vasculitis (LVV). The etiology of LVV is currently unknown, but the understanding of mechanisms involved in pathogenesis is constantly growing. The increasing availability and improvement of imaging techniques are making a profound impact in the evaluation and management of patients with LVV and will most likely play an ever more important role in the future. In this chapter, we will review the mechanisms involved in the pathogenesis of GCA and focus on the role of imaging studies in diagnosing and monitoring LVV. Finally, we will review standard and biological treatment strategies in LVV and focus on the current approaches to these diseases.
2019
- Magnetic resonance angiography versus 18F-fluorodeoxyglucose positron emission tomography in large vessel vasculitis
[Articolo su rivista]
Blockmans, D.; Luqmani, R.; Spaggiari, L.; Salvarani, C.
abstract
With advances in our understanding of the pathogenesis of large vessel vasculitides, we recognise the persistence of inflammation in large vessels, sometimes despite therapy to control clinical symptoms. Achieving an early diagnosis and establishing the extent of disease are important steps in improving our management of these diseases. Imaging is playing an increasing role in the assessment of these patients from diagnosis to prognosis. We review the current and potential role of two important and potentially complementary imaging techniques of magnetic resonance angiography and 18F-fluorodeoxyglucose positron emission tomography in the evaluation of patients with giant cell arteritis and Takayasu arteritis.
2019
- Management of Takayasu arteritis: A systematic literature review informing the 2018 update of the EULAR recommendation for the management of large vessel vasculitis
[Articolo su rivista]
Agueda, A. F.; Monti, S.; Luqmani, R. A.; Buttgereit, F.; Cid, M.; Dasgupta, B.; Dejaco, C.; Mahr, A.; Ponte, C.; Salvarani, C.; Schmidt, W.; Hellmich, B.
abstract
Objective To collect available evidence on management of large vessel vasculitis to inform the 2018 update of the EULAR management recommendations. Methods Two independent systematic literature reviews were performed, one on diagnosis and monitoring and the other on drugs and surgical treatments. Using a predefined PICO (population, intervention, comparator and outcome) strategy, Medline, Embase and Cochrane databases were accessed. Eligible papers were reviewed and results condensed into a summary of findings table. This paper reports the main results for Takayasu arteritis (TAK). Results A total of 287 articles were selected. Relevant heterogeneity precluded meta-analysis. Males appear to have more complications than females. The presence of major complications, older age, a progressive disease course and a weaker inflammatory response are associated with a more unfavourable prognosis. Evidence for details on the best disease monitoring scheme was not found. High-quality evidence to guide the treatment of TAK was not found. Glucocorticoids are widely accepted as first-line treatment. Conventional immunosuppressive drugs and tumour necrosis factor inhibitors were beneficial in case series and uncontrolled studies. Tocilizumab failed the primary endpoint (time to relapse) in a randomised controlled clinical trial; however, results still favoured tocilizumab over placebo. Vascular procedures may be required, and outcome is better when performed during inactive disease. Conclusions Evidence to guide monitoring and treatment of patients with TAK is predominantly derived from observational studies with low level of evidence. Therefore, higher-quality studies are needed in the future.
2019
- Management of large-vessel vasculitis
[Articolo su rivista]
Salvarani, Carlo; Hatemi, Gulen
abstract
PURPOSE OF REVIEW: Glucocorticoids are the mainstay of therapy for large-vessel vasculitis, but potential toxicity and frequent relapses led to studies with nonbiologic and biologic glucocorticoid-sparing agents. The aim of this review is to discuss the recent evidence for the management of giant cell arteritis (GCA) and Takayasu arteritis (TAK). RECENT FINDINGS: Tocilizumab proved to be a powerful glucocorticoid-sparing agent for GCA in a randomized placebo-controlled trial, whereas the trials with tocilizumab and abatacept failed to show a significant difference from placebo in relapse-free survival rate in TAK. Further trials are awaiting for establishing the role of abatacept and ustekinumab for GCA, and rituximab and tumor necrosis factor inhibitors, including certolizumab for TAK, as well as nonbiologic agents for both indications. SUMMARY: Despite recent randomized controlled trials with biologic agents, management of large-vessel vasculitis largely depends on observational studies. Well designed controlled trials using validated outcome measures in large number of patients, identification of biologic markers that could guide the choice of targeted treatments, and standardization of disease assessment including imaging modalities are unmet needs for the management of large-vessel vasculitis.
2019
- Management of skin, mucosa and joint involvement of Behçet's syndrome: A systematic review for update of the EULAR recommendations for the management of Behçet's syndrome
[Articolo su rivista]
Leccese, Pietro; Ozguler, Yesim; Christensen, Robin; Esatoglu, Sinem Nihal; Bang, Dongsik; Bodaghi, Bahram; Celik, Aykut Ferhat; Fortune, Farida; Gaudric, Julien; Gül, Ahmet; Kötter, Ina; Mahr, Alfred; Moots, Robert J; Richter, Jutta; Saadoun, David; Salvarani, Carlo; Scuderi, Francesco; Sfikakis, Petros P; Siva, Aksel; Stanford, Miles; Tugal-Tutkun, Ilknur; West, Richard; Yurdakul, Sebahattin; Olivieri, Ignazio; Yazici, Hasan; Hatemi, Gulen
abstract
The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet's syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS.
2019
- New perspectives in eosinophilic granulomatosis with polyangiitis (EGPA): report of the first meeting of the European EGPA Study Group
[Articolo su rivista]
Marvisi, C.; Sinico, R. A.; Salvarani, C.; Jayne, D.; Prisco, D.; Terrier, B.; Emmi, G.; Vaglio, A.; Arndt, F.; Egan, A.; Tervaert, J. W. C.; Hellmich, B.; Kahn, J. -E.; Kernder, A.; Mahr, A.; Mahrhold, J.; Neumann, T.; Schiavon, F.; Troilo, A.; Urban, M. L.; Venhoff, N.
abstract
The European Eosinophilic Granulomatosis with Polyangiitis (EGPA) study group first gathered in Firenze in December 2018. The discussion was centred around the clinical and therapeutic needs in EGPA which still remain unmet. Indeed, EGPA is a puzzling and rare disease which shares clinical features with other anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAVs) and hypereosinophilic syndromes (HESs). Some of the recommendations published in 2015 are based on data derived from EGPA-related diseases, rather than from EGPA itself, and therefore need to be updated. Thus, the aim of the meeting was to stimulate ongoing research, to promote collaborative European studies and to define the main issues on which future studies should be focused. Current fields of research on EGPA include potential serological biomarkers of disease activity and of specific organ involvement, possible links between different genetic variants and clinical phenotypes, and new therapeutic perspectives. Herein, we give an overview of the meeting with the goal to stimulate an international collaboration and new points of discussion.
2019
- Observational study on the QUality of life of Italian Axial SpondyloARthritis patients (QUASAR): baseline data.
[Articolo su rivista]
D'Angelo, Salvatore; Gilio, Michele; D'Attino, Rita M; Gualberti, Giuliana; Merolla, Rocco; di Luzio Paparatti, Umberto; Malavolta, Nazzarena; Corvaglia, Stefania; Marchetta, Antonio; Scambi, Cinzia; Romeo, Nicoletta; Pettiti, Giorgio; Salvarani, Carlo; Catanoso, Maria Grazia; Scarpa, Raffaele; Costa, Luisa; Ramonda, Roberta; Frallonardo, Paola; Muratore, Maurizio; Quarta, Laura; Passiu, Giuseppe; Erre, Gian Luca; Lubrano, Daniele; Tirri, Enrico; Govoni, Marcello; Furini, Federica; Russo, Romualdo; Buono, Rosario; Pozzi, Maria Rosa; Riva, Marta; Grembiale, Rosa Daniela; Bruno, Caterina; Gibertini, Patrizia; Marchesoni, Antonio
abstract
OBJECTIVES: To describe the baseline characteristics of the patients enrolled in the QUality of life in patients with Axial SpondyloARthritis (QUASAR) study in terms of quality of life (QoL), disease activity, therapy adherence, and work ability in a real-world setting.
METHODS: QUASAR is an Italian multicentre, prospective 12-month observational study, including consecutive adult patients classified as axial spondyloarthritis (axSpA) according to the Assessment of SpondyloArthritis international Society criteria for axSpA.
RESULTS: Of 512 patients enrolled in 23 rheumatology centres, 80.7% had ankylosing spondylitis (AS) and 19.3% had non-radiographic axSpA (nr-axSpA). Mean ages were 34.1±13.3 years at axSpA symptoms onset and 39.5±13.0 years at diagnosis. Of the patients, 51.4% presented with ≥1 extra articular manifestation (EAM); the most common were psoriasis (17.8%) and uveitis (16.4%). Patients with nr-axSpA and AS had similar EAM rates, disease activity, and QoL. Biologic disease-modifying anti-rheumatic drugs (bDMARDs; 83.2%) were the most commonly received medication, followed by conventional synthetic DMARDs (22.9%) and non-steroidal anti-inflammatory drugs (NSAIDs; 16.6%). At baseline, higher treatment satisfaction was reported with bDMARDs which, together with NSAIDs, were associated with the best overall scores for disease activity, function, and QoL in the overall population and AS subgroup.
CONCLUSIONS: QUASAR is the first Italian prospective study that comprehensively evaluated a large axSpA patient sample in a real-world setting. This interim analysis at baseline confirmed that i) patients with AS and nr-axSpA have similar QoL and disease burden, ii) nearly all axSpA patients receive treatment, and iii) bDMARDs and NSAIDs, overall, yield better disease activity and QoL.
2019
- PREDICTION OF LONG-TERM EVOLUTIONARY PROFILES IN EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (CHURG-STRAUSS) BASED ON BASELINE AND FOLLOW-UP CHARACTERISTICS
[Abstract in Rivista]
Papo, M; Sinico, Ra; Teixeira, V; Urban, Ml; Mahrhold, J; Monti, S; Cassone, G; Schiavon, F; Seeliger, B; Neumann, T; Kroegel, C; Groh, M; Marvisi, C; Samson, M; Barba, T; Jayne, D; Hellmich, B; Montecucco, C; Salvarani, C; Kahn, Je; Bonnotte, B; Durel, Ca; Mouthon, L; Puechal, X; Guillevin, L; Emmi, G; Vaglio, A; Terrier, B
abstract
2019
- Primary central nervous system vasculitis mimicking brain tumor: Comprehensive analysis of 13 cases from a single institutional cohort of 191 cases
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D.; Christianson, Teresa J. H.; Huston, John; Morris, Jonathan M.; Giannini, Caterina; Hunder, Gene G.
abstract
Objective: To describe the clinical, laboratory, and imaging features and course of patients with primary central nervous system vasculitis (PCNSV) presenting with an intracranial tumor-like mass (TLM). Methods: We retrospectively studied a cohort of 191 consecutive patients with PCNSV seen at the Mayo Clinic, Rochester, MN over a 35-year period (1982–2017). 13/191 patients presented with a TLM. We compared the findings in these 13 patients with those from the 178 without this presentation. Results: In 13 of 191 (6.8%) patients with TLM the diagnosis of PCNSV was established by cerebral biopsy. Granulomatous vasculitis was found in 11/13 patients, accompanied by vascular deposits of β-amyloid peptide in 7. Compared to the 178 patients without TLM, the patients with TLM were more likely to be male (p = 0.04), and less likely to have a transient ischemic attack (p = 0.023), bilateral cerebral infarcts (p = 0.018), or vasculitic lesions on angiography (p = 0.045). They were more likely to have seizures (p = 0.022), gadolinium-enhanced lesions (p = 0.007), and amyloid angiopathy (p = 0.046). All 13 patients responded to therapy and 8/13 (61.5%) had a Rankin disability score of 0 at last visit. Overall, high disability scores (Rankin scores 4–6) at last follow-up were associated with increasing age (odds ratio, OR, 1.49) and cerebral infarction (OR, 3.47), but were less likely in patients with gadolinium-enhanced lesions (OR, 0.36) and amyloid angiopathy (OR, 0.21). Conclusion: In PCNSV a TLM at presentation represents a definable subgroup of patients with a favourable treatment response.
2019
- Radiologist-rheumatologist multidisciplinary approach in the management of axial spondyloarthritis: a Delphi consensus statement
[Articolo su rivista]
Marchesoni, Antonio; D'Angelo, Salvatore; Anzidei, Michele; Bortolotti, Roberto; Cantini, Fabrizio; Caramella, Davide; Carotti, Marina; Chimenti, Maria Sole; Delle Sedie, Andrea; Egan, Colin Gerard; Fabbroni, Marta; Frediani, Bruno; Fusaro, Enrico; Galeazzi, Mauro; Gallazzi, Mauro Battista; Gentileschi, Stefano; Gentili, Francesco; Gerli, Roberto; Gilio, Michele; Iannone, Florenzo; La Paglia, Ernesto; Lubrano, Ennio; Macarini, Luca; Olivieri, Ignazio; Pellerito, Raffaele; Ramonda, Roberta; Salvarani, Carlo; Scarano, Enrico; Scarpa, Raffaele; Spaggiari, Lucia; Spanò, Angelo; Zawaideh, Jeries Paolo; Mazzei, Maria Antonietta
abstract
OBJECTIVES: The aim of this study was to develop a Delphi consensus statement between rheumatologists and radiologists for the diagnosis and monitoring of axial spondyloarthritis (axial-SpA).
METHODS: Following an extensive literature search to identify unmet needs and potential goals for a multidisciplinary approach, a scientific board comprising 28 Italian hospital-based rheumatologists (n=19) and radiologists (n=9) identified 8 "starting points", resulting in the development of 23 consensus statements covering issues from current practice guidelines to specific MRI protocols for the assessment of axial-SpA. Each participant anonymously expressed a level of agreement for each statement using a 5-point Likert scale (1="strongly disagree"; 5="strongly agree") via an online Delphi method.Total cumulative agreement (TCA) was defined as the sum of the percentage of response to items 4 ("agree") and 5 ("absolutely agree"). Consensus was defined as ≥80% total cumulative agreement for each statement.
RESULTS: After the first round of voting (28 participants), positive consensus was reached for 28/31 (90.3%) statements. Statements without consensus (n=3) were discussed in a face-to-face plenary session prior to the second vote (28 participants). After the second round voting, positive consensus was attained for all 31 statements, with mean final TCA of 95.5% (range 82.1-100%).
CONCLUSIONS: This Delphi consensus statement provides an aid to rheumatologists and radiologists for the diagnosis and monitoring of axial-SpA.
2019
- Red flags for appropriate referral to the gastroenterologist and the rheumatologist of patients with inflammatory bowel disease and spondyloarthritis
[Articolo su rivista]
Felice, C.; Leccese, P.; Scudeller, L.; Lubrano, E.; Cantini, F.; Castiglione, F.; Gionchetti, P.; Orlando, A.; Salvarani, C.; Scarpa, R.; Vecchi, M.; Olivieri, I.; Armuzzi, A.; Beltrami, Marina; Bossa, Fabrizio; Costa, Francesco; Fries, Walter; Galeazzi, Mauro; Giacomelli, Roberto; Lapadula, Giovanni; Malavolta, Nazzarena; Principi, Mariabeatrice; Ramonda, Roberta; Riegler, Gabriele; Triolo, Giovanni; Zoli, Giorgio
abstract
Collaboration between gastroenterologists and rheumatologists is recommended for the correct management of patients with associated spondyloarthritis (SpA) and inflammatory bowel disease (IBD). We aimed to establish the appropriateness of several red flags for a prompt specialist referral. A systematic review of the literature was performed using the GRADE method to describe the prevalence of co-existing IBD-SpA and the diagnostic accuracy of red flags proposed by a steering committee. Then, a consensus among expert gastroenterologists and rheumatologists (10 in the steering committee and 13 in the expert panel) was obtained using the RAND method to confirm the appropriateness of each red flag as ‘major’ (one sufficient for patient referral) or ‘minor’ (at least three needed for patient referral) criteria for specialist referral. The review of the literature confirmed the high prevalence of co-existing IBD-SpA. Positive and negative predictive values of red flags were not calculated, given the lack of available data. A consensus among gastroenterology and rheumatology specialists was used to confirm the appropriateness of each red flag. Major criteria to refer patients with SpA to the gastroenterologist included: rectal bleeding, chronic abdominal pain, perianal fistula or abscess, chronic diarrhoea and nocturnal symptoms. Major criteria to refer patients with IBD to the rheumatologist included: chronic low back pain, dactylitis, enthesitis and pain/swelling of peripheral joints. Several major and minor red flags have been identified for the diagnosis of co-existing IBD-SpA. The use of red flags in routine clinical practice may avoid diagnostic delay and reduce clinic overload.
2019
- Rituximab therapy for primary central nervous system vasculitis: A 6 patient experience and review of the literature
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D.; Muratore, Francesco; Christianson, Teresa J. H.; Galli, Elena; Pipitone, Nicolò; Cassone, Giulia; Iii, John Huston; Giannini, Caterina; Warrington, Kenneth; Hunder, Gene G.
abstract
Objectives: To assess the efficacy and safety of Rituximab (RTX) in adult primary central nervous system vasculitis (PCNSV). Methods: We retrospectively assessed the effect of RTX in 6 patients with PCNSV. Five of the 6 were refractory to high dose glucocorticoids (GCs) and/or conventional immunosuppressants (IS). The sixth was newly diagnosed and received RTX in combination with GCs. Clinical evaluation, laboratory tests, and imaging modalities were performed at initial RTX administration and during the follow-up. Treatment response was assessed using the treating physician's global opinion regarding response and the degree of disability using the modified Rankin scale (mRS). We also performed a literature review for previous use of RTX in PCNSV using PubMed, Ovid Medline, and the Cochrane library. Results: The six patients (3 females) had a median age at diagnosis of 50.5 years (range 17–68 years). All had active disease when RTX was started. In 4 patients, RTX administration was associated with a marked reduction in the number of flares (from 18 before starting RTX to 3 after). One patient, after an initial improvement, had 2 flares when B cells were depleted and he was not able to reduce prednisone below 20 mg/day. A 6th patient had a flare when B cells recovered and retreatment with RTX re-induced and maintained remission. The median mRS score at last visit (median: 2; range 0–4) was lower than that prior to treatment (median 3; range 1–5). The median prednisone daily dose before RTX administration was significantly higher than that at last follow-up (p =.006). In the literature review, we identified 5 papers describing 7 patients treated with RTX. Six patients responded to RTX with clinical and MRI improvement with no reported flares after RTX treatment. Conclusions: Our data support a potential role for RTX treatment in selected patients with PCNSV.
2019
- SAT0285 EVALUATION OF CHRONIC PAIN IN PATIENTS WITH SYSTEMIC SCLEROSIS COMPARED TO THOSE WITH CHRONIC HEADACHE AND RHEUMATOID ARTHRITIS
[Abstract in Rivista]
Magnani, Luca; Lumetti, Federica; Cocchiara, Emanuele; Spinella, Amelia; Baraldi, Carlo; Pini, Luigialberto; Pellesi, Lanfranco; Baiocchi, Gianluigi; Salvarani, Carlo; Giuggioli, Dilia
abstract
2019
- Survival predictors in biopsy-proven giant cell arteritis: A northern Italian population-based study
[Articolo su rivista]
MacChioni, Pierluigi; Boiardi, Luigi; Muratore, Francesco; Restuccia, Giovanna; Cavazza, Alberto; Pipitone, Nicolò; Catanoso, Mariagrazia; Mancuso, Pamela; Luberto, Ferdinando; Rossi, Paolo Giorgi; Salvarani, Carlo
abstract
Objective. To evaluate the influence of disease-related findings and treatment outcomes on survival in a populationbased cohort of Northern Italian patients with GCA. Methods. A total of 281 patients with incident temporal artery biopsy (TAB)-proven GCA, diagnosed over a 26-year period (19862012) and living in the Reggio Emilia area, were retrospectively evaluated. We analysed clinical, imaging and laboratory findings at diagnosis, pathological patterns of TAB, CS treatment and therapeutic outcomes, and traditional cardiovascular risk factors as factors predictive of survival. Results. Univariate analysis showed that increased mortality was associated with large vessel involvement at diagnosis [hazard ratio (HR) 5.84], while reduced mortality was associated with female sex (HR 0.66), PMR (HR 0.54), higher haemoglobin levels (HR 0.84) at diagnosis, long-term remission (HR 0.47) and inflammation limited to adventitia or to the adventitial vasa vasorum (HR 0.48) at TAB examination. Multivariate analysis confirmed the association between increased mortality and large vessel involvement (HR 5.14) at diagnosis, between reduced mortality and PMR (HR 0.57) at diagnosis and adventitial inflammation (HR 0.31) at TAB. Conclusion. PMR at diagnosis and inflammation limited to the adventitia at TAB appear to identify subsets of patients with more benign disease, while large vessel involvement at diagnosis is associated with reduced survival.
2019
- Symptomatic psoriatic dactylitis is associated with ultrasound determined extra-synovial inflammatory features and shorter disease duration
[Articolo su rivista]
Girolimetto, Nicolò; Costa, Luisa; Mancarella, Luana; Addimanda, Olga; Bottiglieri, Paolo; Santelli, Francesco; Meliconi, Riccardo; Peluso, Rosario; Del Puente, Antonio; Macchioni, Pierluigi; Salvarani, Carlo; Mcgonagle, Dennis; Scarpa, Raffaele; Caso, Francesco
abstract
Objectives: To explore the link between ultrasonographic features of dactylitis in psoriatic arthritis (PsA) and symptoms, digital tenderness and duration of dactylitis. Methods: Forty-eight cases of PsA dactylitis were investigated using high frequency ultrasound (US) both in grey scale (GS) and Power Doppler (PD), evaluating the presence and the degree of flexor tenosynovitis, peri-tendinous oedema, subcutaneous PD, extensor tendon involvement, GS synovitis and intra-articular PD signal (PDS) of the involved digits. Patients were compared according to the presence of local pain and digital tenderness, the duration of dactylitis and the concomitant treatment. Results: The presence of pain/tenderness was positively associated with US GS flexor tenosynovitis of grade > 2 (p < 0.001), PD-flexor tenosynovitis (p < 0.001), peri-tendinous oedema (p < 0.001) and subcutaneous PDS (p < 0.001); moreover, it was negatively associated with GS synovitis (p < 0.001) and intra-articular PD (p < 0.001). The same positive and negative association with US findings were found comparing patients with duration of dactylitis shorter or longer than the median (24 weeks) (p < 0.001 for all comparisons). Conclusions: Pain and digital tenderness are linked to dactylitis duration and earlier lesions are associated with extra synovial inflammatory changes. These findings suggest a hitherto unappreciated extra synovial basis for symptoms in PsA dactylitis.
2019
- Systematic literature review informing the 2018 update of the EULAR recommendation for the management of large vessel vasculitis: Focus on giant cell arteritis
[Articolo su rivista]
Monti, S.; Agueda, A. F.; Luqmani, R. A.; Buttgereit, F.; Cid, M.; Dejaco, C.; Mahr, A.; Ponte, C.; Salvarani, C.; Schmidt, W.; Hellmich, B.
abstract
Objectives: To analyse the current evidence for the management of large vessel vasculitis (LVV) to inform the 2018 update of the EULAR recommendations. Methods: Two systematic literature reviews (SLRs) dealing with diagnosis/monitoring and treatment strategies for LVV, respectively, were performed. Medline, Embase and Cochrane databases were searched from inception to 31 December 2017. Evidence on imaging was excluded as recently published in dedicated EULAR recommendations. This paper focuses on the data relevant to giant cell arteritis (GCA). Results: We identified 287 eligible articles (122 studies focused on diagnosis/monitoring, 165 on treatment). The implementation of a fast-track approach to diagnosis significantly lowers the risk of permanent visual loss compared with historical cohorts (level of evidence, LoE 2b). Reliable diagnostic or prognostic biomarkers for GCA are still not available (LoE 3b). The SLR confirms the efficacy of prompt initiation of glucocorticoids (GC). There is no high-quality evidence on the most appropriate starting dose, route of administration, tapering and duration of GC (LoE 4). Patients with GCA are at increased risk of dose-dependent GC-related adverse events (LoE 3b). The addition of methotrexate or tocilizumab reduces relapse rates and GC requirements (LoE 1b). There is no consistent evidence that initiating antiplatelet agents at diagnosis would prevent future ischaemic events (LoE 2a). There is little evidence to guide monitoring of patients with GCA. Conclusions: Results from two SLRs identified novel evidence on the management of GCA to guide the 2018 update of the EULAR recommendations on the management of LVV.
2019
- The right place of interleukin-1 inhibitors in the treatment of Behçet’s syndrome: a systematic review
[Articolo su rivista]
Bettiol, Alessandra; Silvestri, Elena; Di Scala, Gerardo; Amedei, Amedeo; Becatti, Matteo; Fiorillo, Claudia; Lopalco, Giuseppe; Salvarani, Carlo; Cantarini, Luca; Soriano, Alessandra; Emmi, Giacomo
abstract
Behçet’s syndrome (BS) is a chronic (auto)-inflammatory disorder characterized by different clusters of symptoms, including mucocutaneous and ocular involvements. Interleukin-1 inhibitors anakinra (ANA), canakinumab (CAN), and gevokizumab (GEV) represent a promising therapeutic alternative in BS. To date, evidence on the use of ANA, CAN, and GEV is mainly based on small isolated studies or case series, and the real place of anti-IL1 agents in the treatment of BS is still unclear. We performed a systematic review of current evidence on the efficacy and safety of anti-IL1 agents in BS. The PubMed search yielded a total of 398 references, from which we retrieved 24 studies for inclusion (4 clinical trials, 6 observational studies, 14 case reports, case series or letters to the editor). Four studies evaluated the overall efficacy of IL-1 inhibitors, 15 studies focused on the specific efficacy of ANA, whereas efficacy of CAN and GEV was evaluated in 8 and 3 studies, respectively. Both ANA and CAN were associated with good control of mucocutaneous and ocular manifestations. ANA resulted effective also for osteoarticular manifestations. GEV was studied only for ocular manifestations, but gave contrasting results. Discordant evidence supports the use of ANA and CAN in pediatric setting and for first-line treatment of general BS manifestations. Most frequent side effects were local or diffuse cutaneous reactions and injection site reactions, particularly for ANA treatment. Blocking the IL-1 pathway could be an effective therapeutic strategy in particular BS involvements.
2019
- The therapeutic potential of tuftsin-phosphorylcholine in giant cell arteritis
[Articolo su rivista]
Croci, Stefania; Bonacini, Martina; Muratore, Francesco; Caruso, Andrea; Fontana, Antonio; Boiardi, Luigi; Soriano, Alessandra; Cavazza, Alberto; Cimino, Luca; Belloni, Lucia; Perry, Ori; Fridkin, Mati; Parmeggiani, Maria; Blank, Miri; Shoenfeld, Yehuda; Salvarani, Carlo
abstract
Tuftsin-PhosphorylCholine (TPC) is a novel bi-specific molecule which links tuftsin and phosphorylcholine. TPC has shown immunomodulatory activities in experimental mouse models of autoimmune diseases. We studied herein the effects of TPC ex vivo on both peripheral blood mononuclear cells (PBMCs) and temporal artery biopsies (TABs) obtained from patients with giant cell arteritis (GCA) and age-matched disease controls. GCA is an immune-mediated disease affecting large vessels. Levels of 18 cytokines in supernatants, PBMC viability, T helper (Th) cell differentiation of PBMCs and gene expression in TABs were analyzed. Treatment ex vivo with TPC decreased the production of IL-1β, IL-2, IL-5, IL-6, IL-9, IL-12(p70), IL-13, IL-17A, IL-18, IL-21, IL-22, IL-23, IFNγ, TNFα, GM-CSF by CD3/CD28 activated PBMCs whereas it negligibly affected cell viability. It reduced Th1 and Th17 differentiation while did not impact Th22 differentiation in PBMCs stimulated by phorbol 12-myristate 13-acetate plus ionomycin. In inflamed TABs, treatment with TPC down-regulated the production of IL-1β, IL-6, IL-13, IL-17A and CD68 gene expression. The effects of TPC were comparable to the effects of dexamethasone, included as the standard of care, with the exception of a greater reduction of IL-2, IL-18, IFNγ in CD3/CD28 activated PBMCs and CD68 gene in inflamed TABs. In conclusion our results warrant further investigations regarding TPC as an immunotherapeutic agent in GCA and potentially other autoimmune and inflammatory diseases.
2019
- Therapeutic Strategies and Survival in Patients with Interstitial Pneumonia with Autoimmune Features
[Abstract in Rivista]
Sebastiani, M; Cassone, G; Vacchi, C; De Pasquale, L; Cerri, S; Della Casa, G; Salvarani, C; Manfredi, A
abstract
2019
- Thu0349 autologous fat grafting in the treatment of patients with systemic sclerosis: current experience and future prospects
[Abstract in Rivista]
Spinella, Amelia; Pignatti, Marco; Citriniti, Giorgia; Lumetti, Federica; Cocchiara, Emanuele; Palermo, Adalgisa; Sighinolfi, Gianluca; Pacchioni, Lucrezia; Zaccaria, Giovanna; Lusetti, Irene Laura; DE SANTIS, Giorgio; Salvarani, Carlo; Giuggioli, Dilia
abstract
2019
- Ultrasonographic and clinical assessment of peripheral enthesitis in patients with psoriatic arthritis, psoriasis, and fibromyalgia syndrome: The ULISSE study
[Articolo su rivista]
Macchioni, P.; Salvarani, C.; Possemato, N.; Gutierrez, M.; Grassi, W.; Gasparini, S.; Perricone, C.; Perrotta, F. M.; Grembiale, R. D.; Bruno, C.; Tripolino, C.; Govoni, M.; Ciancio, G.; Farina, I.; Ramonda, R.; Frallonardo, P.; Desiati, F.; Scarpa, R.; Costa, L.; Zabotti, A.; De Vita, S.; D'Attino, R. M.; Gualberti, G.; Merolla, R.; Di Luzio Paparatti, U.; Aldigeri, R.; Marchesoni, A.
abstract
Objective. The purpose of the ULISSE study was to evaluate the prevalence of clinical and ultrasonographic (US) entheseal involvement in patients with psoriatic arthritis (PsA), psoriasis, and fibromyalgia syndrome (FMS).Methods. In this cross-sectional multicenter study, patients with PsA and psoriasis (not taking systemic therapy) and FMS underwent a clinical evaluation of the entheses, and a B-mode and power Doppler examination of 6 pairs of entheses.Results. The study analyzed 140 patients with PsA, 51 with psoriasis, and 51 with FMS. Clinical and US examinations were performed in 1960 and 1680 entheses in the PsA group, and 714 and 612 entheses both in the psoriasis group and in the FMS group. In both per-patient and per-enthesis evaluation, the frequency of entheseal tenderness was higher in patients with FMS (92% of the patients and 46% of the entheses, compared with 66%/23% in the PsA group and 59%/18% in the psoriasis group). With US examination, signs of entheseal involvement were more frequent in both the per-patient and per-enthesis evaluation in PsA and psoriasis (about 90% of patients in both the PsA and psoriasis groups and 75% of patients in the FMS group had at least 1 site affected, and 54%, 41%, and 27% of the pairs of entheses in, respectively, PsA, psoriasis, and FMS patients showed at least 1 enthesis involved).Conclusion. The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.
2019
- Use of Neem oil and Hypericum perforatum for treatment of calcinosis-related skin ulcers in systemic sclerosis
[Articolo su rivista]
Giuggioli, D.; Lumetti, F.; Spinella, A.; Cocchiara, E.; Sighinolfi, G.; Citriniti, G.; Colaci, M.; Salvarani, C.; Ferri, C.
abstract
Objective: This study evaluated Neem oil and Hypericum perforatum (Holoil®) for treatment of scleroderma skin ulcers related to calcinosis (SU-calc). Procedure: We retrospectively analyzed 21 consecutive systemic sclerosis (SSc) patients with a total of 33 SU-calcs treated daily with Holoil® cream compared with a control group of 20 patients with 26 SU-calcs. Holoil® was directly applied to skin lesions, while the control group received only standard medication. Results: Application of Holoil® either resulted in crushing and complete resolution of calcium deposits or facilitated sharp excision of calcinosis during wound care sessions in 27/33 cases (81.8%). Complete healing of SU-calc occurred in 15/33 (45%) of cases within a time period of 40.1 ± 16.3 (mean ± SD) days, while 18/33 (55%) of lesions improved in terms of size, erythema, fibrin and calcium deposits. Patients reported a reduction of pain (mean numeric rating scale 7.3 ± 1.9 at baseline versus 2.9 ± 1.4 at follow-up) The control group had longer healing times and a higher percentage of infections. Conclusions: The efficacy of local treatment with neem oil and Hypericum perforatum suggest that Holoil® could be a promising tool in the management of SSc SU-calc.
2019
- “Disease knowledge index” and perspectives on reproductive issues: A nationwide study on 398 women with autoimmune rheumatic diseases
[Articolo su rivista]
Andreoli, L.; Lazzaroni, M. G.; Carini, C.; Dall'Ara, F.; Nalli, C.; Reggia, R.; Rodrigues, M.; Benigno, C.; Baldissera, E.; Bartoloni-Bocci, E.; Basta, F.; Bellisai, F.; Bortoluzzi, A.; Campochiaro, C.; Cantatore, F. P.; Caporali, R.; Ceribelli, A.; Chighizola, C. B.; Conigliaro, P.; Corrado, A.; Cutolo, M.; D'Angelo, S.; De Stefani, E.; Doria, A.; Favaro, M.; Fischetti, C.; Foti, R.; Gabrielli, A.; Generali, E.; Gerli, R.; Gerosa, M.; Larosa, M.; Maier, A.; Malavolta, N.; Meroni, M.; Meroni, P. L.; Montecucco, C.; Mosca, M.; Padovan, M.; Paolazzi, G.; Pazzola, G.; Peccatori, S.; Perricone, R.; Pettiti, G.; Picerno, V.; Prevete, I.; Ramoni, V.; Romeo, N.; Ruffatti, A.; Salvarani, C.; Sebastiani, G. D.; Selmi, C.; Serale, F.; Sinigaglia, L.; Tani, C.; Trevisani, M.; Vadacca, M.; Valentini, E.; Valesini, G.; Visalli, E.; Vivaldelli, E.; Zuliani, L.; Tincani, A.
abstract
Objective: The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age.Methods: We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18-55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149).Results: At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A "Disease Knowledge Index" (DKI) was created to investigate the degree of patients' information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning.Conclusion: Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication. (C) 2018 Published by Elsevier Masson SAS on behalf of Societe francaise de rhumatologie.
2018
- 2018 update of the EULAR recommendations for the management of Behçet's syndrome
[Articolo su rivista]
Hatemi, Gulen; Christensen, Robin; Bang, Dongsik; Bodaghi, Bahram; Celik, Aykut Ferhat; Fortune, Farida; Gaudric, Julien; Gul, Ahmet; Kötter, Ina; Leccese, Pietro; Mahr, Alfred; Moots, Robert; Ozguler, Yesim; Richter, Jutta; Saadoun, David; Salvarani, Carlo; Scuderi, Francesco; Sfikakis, Petros P; Siva, Aksel; Stanford, Miles; Tugal-Tutkun, Ilknur; West, Richard; Yurdakul, Sebahattin; Olivieri, Ignazio; Yazici, Hasan
abstract
Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.
2018
- A TNFSF13B functional variant is not involved in systemic sclerosis and giant cell arteritis susceptibility
[Articolo su rivista]
González-Serna, David; Carmona, Elio G.; Ortego-Centeno, Norberto; Simeón, Carmen P.; Solans, Roser; Hernández-Rodríguez, José; Tolosa, Carlos; Castañeda, Santos; Narváez, Javier; Martinez-Valle, Ferran; Witte, Torsten; Neumann, Thomas; Holle, Julia; Beretta, Lorenzo; Boiardi, Luigi; Emmi, Giacomo; Cimmino, Marco A.; Vaglio, Augusto; Herrick, Ariane L.; Denton, Christopher P.; Salvarani, Carlo; Cid, María C.; Morgan, Ann W.; Fonseca, Carmen; González-Gay, Miguel A.; Martín, Javier; Márquez, Ana
abstract
Background The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT!A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. Methods A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. Results No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75–1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91–1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. Conclusion Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.
2018
- AB0724 Cardio-pulmonary disease management in patients with systemic sclerosis: cardio-rheumatology clinic and patient care standardisation proposal
[Abstract in Rivista]
Spinella, A; Lumetti, F; Mattioli, Av; Coppi, F; Rosario, R; Cocchiara, Emanuele; Colaci, M; Ferri, C; Salvarani, C; Giuggioli, D
abstract
2018
- AB0760 Advanced oxidation protein products in serum of patients with systemic sclerosis: a possible indicator of clinical evolution
[Abstract in Rivista]
Sighinolfi, G; Colaci, M; Spinella, Amelia; Lumetti, Federica; Artoni, Erica; Salvarani, C; Giuggioli, Dilia
abstract
2018
- Advanced oxidation protein products in serum of patients with systemic sclerosis: a possible indicator of clinical evolution
[Abstract in Atti di Convegno]
Sighinolfi, GIAN LUCA; Colaci, M; Spinella, Amelia; Lumetti, Federica; Artoni, Erica; Salvarani, C; Giuggioli, Dilia
abstract
Background Systemic sclerosis (SSc) is a chronic, multisystem connective tissue disease characterised by by immune dys-regulation, obliterative microvasculopathy and fibrosis. Endothelial dysfunction, immune system imbalance and fibroblast activation constitute the three major factors of the pathogenetic process. In this context, oxidative stress could play a significant role through direct damage of endothelial cells and the persistent activation of the immune system.1,2
Objectives This study investigated the presence of advanced protein oxidation products (AOPP) in serum of patients with SSc and its correlation with disease’s features.
Methods 50 patients with SSc (M:F 1:7, mean age 57.3±11.2 SD, mean duration of disease 10±9.1 SD years), were screened for AOPP in the serum, using the AOPP OxiSelect Kit of CELL BIOLABS (San Diego, Ca, USA). Among 50 SSc patients, 39 had limited cutaneous subset, while 11 had the diffuse one. Anamnestic and clinical data were collected for all SSc patients. As a control group 50 consecutive healthy subjects, sex and age matched, were recruited.
Results We found serum levels of AOPP increased in the SSc group compared with the controls (p<0.0001) with mean values of 336.9±167.8 mmol/L and 167.5±59.2 mmol/L, respectively. In addition, higher levels of AOPP directly correlated with the diffuse cutaneous subset (p=0.0242), presence of digital ulcers (p=0.005), esophagopathy (p=0.006) and pulmonary fibrosis (p=0.0128).
Conclusions Serum AOPP levels are significantly higher in patients with SSc than in controls. In addition, the correlations of AOPP with SSc diffuse cutaneous subset, digital ulcers, and pulmonary involvement (indicative of progressive disease and worse prognosis) suggest a possible role of this marker in the identification of the cases with worse clinical evolution. The data of this preliminary study should be confirmed on larger case series and analysed in prospective studies, in order to understand its eventual usefulness during the follow-up of SSc patients.
2018
- CD3 immunohistochemistry is helpful in the diagnosis of giant cell arteritis
[Articolo su rivista]
Ciccia, Francesco; Ferrante, Angelo; Guggino, Giuliana; Cavazza, Alberto; Salvarani, Carlo; Rizzo, Aroldo
abstract
To evaluate whether CD3 staining performed routinely on temporal artery biopsy specimens might improve the sensitivity of temporal artery biopsy in patients with biopsy-negative GCA.
2018
- Cardiac and Pulmonary Artery Involvement Detected by 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Large-vessel Giant Cell Arteritis
[Articolo su rivista]
Ugolini, Raffaella; Muratore, Francesco; Salvarani, Carlo
abstract
To describe a case of Large-vessel Giant Cell Arteritis with Cardiac and Pulmonary Artery Involvement Detected by 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography
2018
- Cardio-pulmonary disease management in patients with systemic sclerosis: cardio-rheumatology clinic and patient care standardisation proposal
[Abstract in Atti di Convegno]
Spinella, A; Lumetti, F; Mattioli, Av; Coppi, F; Rosario, R; Cocchiara, Emanuele; Colaci, M; Ferri, C; Salvarani, C; Giuggioli, D
abstract
Background Systemic sclerosis (SSc) is a chronic connective tissue disease characterised by endothelial dysfunction, dysregulation of fibroblasts with excessive fibrosis of the skin and internal organs and autoimmune abnormalities. Cardio-pulmonary manifestations are common in SSc and their detection in the early stage of the disease as well as their careful follow-up are mandatory in order to counteract their impact on the overall disease outcome. Despite the need of establishing a proper methodology, literature provides few reports about this issue.
Objectives To evaluate the activity of our Cardio-Rheumatology Clinic in order to optimise diagnostic management of cardio-pulmonary disease in SSc patients.
Methods We retrospectively analysed data from 350 consecutive SSc patients referred to our University-based Rheumatology Centre and SSc Unit (F/M 308/42; lc/dcSSc 45/305; mean age 50.8±14.7 years; mean disease duration 10.9±7.0 years). All patients underwent general and cardio-pulmonary assessment, in particular they were evaluated in the Cardio-Rheumatology Clinic. The following parameters were considered: physical examination; past and current drugs; blood tests, in particular Erythrocyte sedimentation rate-ESR, C-reactive protein-CRP, CPK enzymes, troponin, NT-pro-BNP, d-dimer, serum autoantibodies, 25-OH-vitamin D; capillaroscopy; pulmonary function tests; high resolution scan of the lungs (HRCT); standard electrocardiogram (ECG) and 24 hour Holter ECG monitoring; Doppler echocardiography; cardiac stress test; coronary angiography and right heart catheterization (RHC); cardiac MRI and CT; vascular ultrasound (intima-media-thickness, carotid-femoral and brachial-ankle pulse-wave-velocity). The clinicians decided to perform these examinations according to clinical picture and current methodologies.Results In the last 12 months we assessed 300 patients with 1st-level screening (cardio-rheumatologic evaluation, standard ECG, Doppler echocardiography, pulmonary function tests, thoracic imaging). Among 2nd-level, 30 procedures of 24 hour Holter ECG and 15 RHC tests were performed. Cardiac MRI, coronary CT angiography and vascular ultrasound were assessed, when requested, as 3rd-level examinations (30 procedures). After 1 year we observed a mean time of 10±5 days between request and clinical cardio-rheumatologic evaluation, 20±12 days to perform 1st-level screening, 25±15 days to execute the 2nd-level examinations. Figure-1 shows Cardio-Rheumatology algorithm for the management of SSc cardio-pulmonary disease.
Conclusions The activity of our Cardio-Rheumatology Clinic optimises the cardio-pulmonary SSc assessment, determining an early detection of these harmful complications with reduced waiting times which are critical issues. Screening algorithms are useful to stratify the risk and to establish the most appropriate diagnostic-therapeutic protocols, improving outcome of scleroderma patients. The development of a cardio-pulmonary risk score and the standardisation of a patient care approach, according to international quality indeces, could represent further tools to optimise SSc management.
2018
- Changes in patterns of uveitis at a tertiary referral center in Northern Italy: analysis of 990 consecutive cases
[Articolo su rivista]
Cimino, L.; Aldigeri, R.; Marchi, S.; Mastrofilippo, V.; Viscogliosi, F.; Coassin, M.; Soldani, A.; Savoldi, L.; De Fanti, A.; Belloni, L.; Zerbini, A.; Parmeggiani, M.; Chersich, M.; Soriano, A.; Salvarani, C.; Fontana, L.
abstract
Purpose: The role of uveitis, an uncommon ocular disease, is often neglected in research and treatment of autoimmune conditions. The study described the spectrum of uveitis at a referral center in North Italy, and compared that to a previously published series of patients. Methods: We reviewed all patients with uveitis diagnosed from 2013 to 2015 at the Immunology Eye Unit, Arcispedale S. M. Nuova-IRCCS, Reggio Emilia, Italy. We examined patient characteristics, disease spectrum, and etiologies. Results: In total, 990 cases of uveitis were identified, who were mostly female (59%) with a median age at presentation of 44 years (interquartile range = 29–57). Anterior uveitis was most frequent (53.5%), followed by panuveitis (22.8%), posterior (16.2%), and intermediate uveitis (5.5%). Anterior herpetic uveitis (15.6%), Fuchs uveitis (9.7%), and HLA-B27 positive anterior uveitis (7.7%) were the most common specific diagnoses. Compared with the previous series, we observed an increased incidence of uveitis, and a different pattern of diagnoses. Rates of herpetic, HLA-B27 positive uveitis, and presumed ocular tuberculosis were higher, but Fuchs uveitis was less frequent. Conclusions: The pattern of uveitis appears to be changing, very likely due to population-level increases in infectious diseases, to the availability of new diagnostic tests and to the interdisciplinary approach used in patient diagnosis.
2018
- Clinical predictors of response and discontinuation of belimumab in patients with systemic lupus erythematosus in real life setting. Results of a large, multicentric, nationwide study
[Articolo su rivista]
Iaccarino, Luca; Andreoli, Laura; Bocci, Elena Bartoloni; Bortoluzzi, Alessandra; Ceccarelli, Fulvia; Conti, Fabrizio; De Angelis, Rossella; De Marchi, Ginevra; De Vita, Salvatore; Di Matteo, Andrea; Emmi, Giacomo; Emmi, Lorenzo; Gatto, Mariele; Gerli, Roberto; Gerosa, Maria; Govoni, Marcello; Larosa, Maddalena; Meroni, Pier Luigi; Mosca, Marta; Pazzola, Giulia; Reggia, Rossella; Saccon, Francesca; Salvarani, Carlo; Tani, Chiara; Zen, Margherita; Frigo, Anna Chiara; Tincani, Angela; Doria, Andrea
abstract
OBJECTIVE:
To investigate efficacy, safety and survival of belimumab and to identify predictors of drug response and drug discontinuation in patients with active SLE in clinical practice.
PATIENTS AND METHODS:
Data of SLE patients, treated with belimumab, from 11 Italian prospective cohorts were analyzed. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24-h proteinuria, CLASIa (Cutaneous LE Disease Area and Severity Index Activity) were recorded at baseline and every 6 months. SLE Responder Index-4 (SRI-4) was calculated at 12 and 24 months. Demographic and clinical features and comorbidities were included in the univariate and multivariate analysis. Adverse events were recorded at each visit. Statistics was performed using the SPSS software.
RESULTS:
We studied 188 SLE patients, mean follow-up 17.5 ± 10.6 months. The most frequent manifestations, which required the use of belimumab, were polyarthritis (45.2%) and skin rashes (25.5%). SRI-4 was achieved by 77.0% and 68.7% of patients at 12 and 24-months. Independent predictors of 12-month response were SLEDAI-2K ≥ 10 (OR 40.46, p = 0.001) and polyarthritis (OR 12.64, p = 0.001) and of 24-month response were SLEDAI-2K ≥ 10 (OR 15.97, p = 0.008), polyarthritis (OR 32.36, p = 0.006), and prednisone ≥7.5 mg/day (OR 9.94, p = 0.026). We observed a low rate of severe adverse events. Fifty-eight patients (30.8%) discontinued belimumab after a mean follow-up of 10.4 ± 7.5 months. The drug survival was 86.9%, 76.9%, 69.4%, 67.1%, and 61.9% at 6, 12, 18, 24, and 30 months, respectively. No factors associated with drug discontinuation were found.
CONCLUSION:
Belimumab is effective and safe when used in clinical practice setting.
2018
- Colonic perforation due to severe cytomegalovirus disease in granulomatosis with polyangiitis after immunosuppression
[Articolo su rivista]
Soriano, Alessandra; Smerieri, Nazareno; Bonilauri, Stefano; De Marco, Loredana; Cavazza, Alberto; Salvarani, Carlo
abstract
Granulomatosis with polyangiitis (GPA) is a small-vessel necrotizing granulomatous vasculitis typically involving upper airways, lungs, and kidneys, which may lead to end-organ damage and life-threatening complications. Major infections during GPA course represent a considerable concern in the management of the disease. Cytomegalovirus (CMV) infection and disease are rare but significant complications in the course of GPA being associated with high morbidity and mortality rates. Colonic perforation due to CMV colitis is exceedingly rare and has so far almost exclusively been documented in HIV, renal transplant, and systemic lupus erythematosus patients. We reported the case of a patient affected with upper airways-limited GPA who developed acute renal failure from rapidly progressive glomerulonephritis and then experienced colonic perforation due to CMV colitis a few weeks after immunosuppressive treatment with high-dose steroids and cyclophosphamide (CYC) for remission induction of the disease. We also reviewed the literature on CMV-related gastro-intestinal complications in the course of GPA and discussed contributing factors to severe manifestations of CMV infection and its reactivation.
2018
- Comment on: Rituximab therapy for takayasu arteritis: A seven patients experience and a review of the literature: Reply
[Articolo su rivista]
Pazzola, Giulia; Muratore, Francesco; Pipitone, Nicolò; Salvarani, Carlo
abstract
Comment on: Rituximab therapy for Takayasu arteritis: a seven patients experience and a review of the literature: reply
2018
- Consensus on the management of patients with psoriatic arthritis in a dermatology setting
[Articolo su rivista]
Gisondi, P; Altomare, G; Ayala, F; Conti, A; Dapavo, P; De Simone, C; Foti, C; Idolazzi, L; Lubrano, E; Malara, G; Marchesoni, A; Olivieri, I; Parodi, A; Peris, K; Piaserico, S; Salvarani, C; Scarpa, R; Girolomoni, G
abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disease associated with psoriasis (PsO). Early diagnosis and prompt therapeutic intervention are crucial for limiting PsA progression and prevention of disability. Dermatologists are in a privileged position to detect early PsA. The management of patients with PsA in the dermatology setting is widely variable.
2018
- Contribution of the new 2012 EULAR/ACR classification criteria for the diagnosis of polymyalgia rheumatica
[Articolo su rivista]
Muratore, F; Salvarani, C; Macchioni, P
abstract
Polymyalgia rheumatica (PMR) is one of the most common rheumatic inflammatory disorders in people aged over 50. It is characterized by aching and prolonged morning stiffness in the shoulder and pelvic girdles and neck. To date there are no specific diagnostic tests, and in clinical practice the diagnosis of PMR remains based on its characteristic clinical manifestations, laboratory evidence of systemic inflammation, rapid response to low doses of glucocorticoids and exclusion of other disorders that may present with proximal pain and stiffness. For classification purposes, several criteria have been proposed over time based on retrospective clinical series, but none have been validated and received universal acceptance. Recently, an international collaborative initiative between the EULAR and the ACR was undertaken to develop new polymyalgia rheumatica classification criteria. In this review, the provisional 2012 EULAR/ACR classification criteria will be presented and their contribution for the diagnosis of polymyalgia rheumatica will be discussed.
2018
- Distribution patterns of 18F-fluorodeoxyglucose in large vessels of Takayasu's and giant cell arteritis using positron emission tomography
[Articolo su rivista]
Soriano, Alessandra; Pazzola, Giulia; Boiardi, Luigi; Casali, Massimiliano; Muratore, Francesco; Pipitone, Nicolò; Catanoso, Mariagrazia; Aldigeri, Raffaella; Cimino, Luca; Versari, Annibale; Salvarani, Carlo
abstract
To compare patterns of vascular involvement using 18F-fluorodeoxyglucose-positron emission tomography computed tomography (FDG PET/CT) in patients with giant cell arteritis (GCA) and Takayasu's arteritis (TAK).
2018
- EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice
[Articolo su rivista]
Dejaco, Christian; Ramiro, Sofia; Duftner, Christina; Besson, Florent L; Bley, Thorsten A; Blockmans, Daniel; Brouwer, Elisabeth; Cimmino, Marco A; Clark, Eric; Dasgupta, Bhaskar; Diamantopoulos, Andreas P; Direskeneli, Haner; Iagnocco, Annamaria; Klink, Thorsten; Neill, Lorna; Ponte, Cristina; Salvarani, Carlo; Slart, Riemer H J A; Whitlock, Madeline; Schmidt, Wolfgang A
abstract
To develop evidence-based recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and Takayasu arteritis (TAK).European League Against Rheumatism (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on evidence and expert opinion, the task force consisting of 20 physicians, healthcare professionals and patients from 10 EULAR countries developed recommendations, with consensus obtained through voting. The final level of agreement was voted anonymously. A total of 12 recommendations have been formulated. The task force recommends an early imaging test in patients with suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK, respectively. CT or PET may be used alternatively. In case the diagnosis is still in question after clinical examination and imaging, additional investigations including temporal artery biopsy and/or additional imaging are required. In patients with a suspected flare, imaging might help to better assess disease activity. The frequency and choice of imaging modalities for long-term monitoring of structural damage remains an individual decision; close monitoring for aortic aneurysms should be conducted in patients at risk for this complication. All imaging should be performed by a trained specialist using appropriate operational procedures and settings. These are the first EULAR recommendations providing up-to-date guidance for the role of imaging in the diagnosis and monitoring of patients with (suspected) LVV.
2018
- Efficacy of tocilizumab in Takayasu arteritis: Multicenter retrospective study of 46 patients
[Articolo su rivista]
Mekinian, Arsene; Resche-Rigon, Mathieu; Comarmond, Cloé; Soriano, Alessandra; Constans, Joel; Alric, Laurent; Jego, Patrick; Busato, Florian; Cabon, Matthieu; Dhote, Robin; Estibaliz, Lazaro; Koné-Paut, Isabelle; Landron, Cédric; Lavigne, Christian; Lioger, Bertrand; Michaud, Martin; Ruivard, Marc; Sacre, Karim; Gottenberg, Jacques Eric; Gaches, Francis; Goulenok, Tiphaine; Salvarani, Carlo; Cacoub, Patrice; Fain, Olivier; Saadoun, David
abstract
To assess the efficacy of tocilizumab in patients with Takayasu arteritis (TA).
2018
- Erratum to: Changes in patterns of uveitis at a tertiary referral center in Northern Italy: analysis of 990 consecutive cases
[Articolo su rivista]
Cimino, Luca; Aldigeri, Raffaella; Marchi, Sylvia; Mastrofilippo, Valentina; Viscogliosi, Fabiana; Coassin, Marco; Soldani, Annamaria; Savoldi, Luisa; De Fanti, Alessandro; Belloni, Lucia; Zerbini, Alessandro; Parmeggiani, Maria; Chersich, Matthew; Soriano, Alessandra; Salvarani, Carlo; Fontana, Luigi
abstract
Erratum to: Changes in patterns of uveitis at a tertiary referral center in Northern Italy: analysis of 990 consecutive cases
2018
- FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC
[Articolo su rivista]
Slart, R. H. J. A.; Slart, R. H. J. A.; Glaudemans, A. W. J. M.; Chareonthaitawee, P.; Treglia, G.; Besson, F. L.; Bley, T. A.; Blockmans, D.; Boellaard, R.; Bucerius, J.; Carril, J. M.; Chen, W.; Cid, M. C.; Dagupta, B.; Dorbala, S.; Gheysens, O.; Hyafil, F.; Jain, S.; Klink, T.; van der Laken, C. J.; Lomena, F.; Massollo, M.; Prieto-Gonzalez, S.; Luqmani, R.; Roivainen, A.; Salvarani, C.; Saraste, A.; Schirmer, M.; Verberne, H. J.; Versari, A.; Voskuyl, A. E.; Walter, M. A.; Camellino, D.; Brouwer, E.; Cimmino, M. A.; Abidov, A.; Agostini, D.; Beanlands, R. S.; Delgado-Bolton, R. C.; Einstein, A. J.; Gimelli, A.; Miller, E. J.; Sciagra, R.; Signore, A.; Slart, R. H. J. A.; Treglia, G.
abstract
Large vessel vasculitis (LVV) is defined as a disease mainly affecting the large arteries, with two major variants, Takayasu arteritis (TA) and giant cell arteritis (GCA). GCA often coexists with polymyalgia rheumatica (PMR) in the same patient, since both belong to the same disease spectrum. FDG-PET/CT is a functional imaging technique which is an established tool in oncology, and has also demonstrated a role in the field of inflammatory diseases. Functional FDG-PET combined with anatomical CT angiography, FDG-PET/CT(A), may be of synergistic value for optimal diagnosis, monitoring of disease activity, and evaluating damage progression in LVV. There are currently no guidelines regarding PET imaging acquisition for LVV and PMR, even though standardization is of the utmost importance in order to facilitate clinical studies and for daily clinical practice. This work constitutes a joint procedural recommendation on FDG-PET/CT(A) imaging in large vessel vasculitis (LVV) and PMR from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine (EANM), the Cardiovascular Council of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), and the PET Interest Group (PIG), and endorsed by the American Society of Nuclear Cardiology (ASNC). The aim of this joint paper is to provide recommendations and statements, based on the available evidence in the literature and consensus of experts in the field, for patient preparation, and FDG-PET/CT(A) acquisition and interpretation for the diagnosis and follow-up of patients with suspected or diagnosed LVV and/or PMR. This position paper aims to set an internationally accepted standard for FDG-PET/CT(A) imaging and reporting of LVV and PMR.
2018
- FRI0442 Long-term treatment with rituximab in interstitial lung disease related to systemic sclerosis: our clinical experience
[Abstract in Rivista]
Lumetti, F; Spinella, A; Ariani, A; Cocchiara, E; Colaci, M; Silva, M; Sverzellati, N; Ferri, C; Salvarani, C; Giuggioli, D
abstract
2018
- Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D Receptor in Patients With Behçet Disease
[Articolo su rivista]
Bonacini, Martina; Soriano, Alessandra; Zerbini, Alessandro; Calò, Eleonora; Cimino, Luca; Muratore, Francesco; Fontana, Luigi; Braglia, Luca; Parmeggiani, Maria; Salvarani, Carlo; Croci, Stefania
abstract
Behçet disease (BD) is an inflammatory systemic disease with a fluctuating course, which can affect the skin, eyes, central nervous system, musculoskeletal, gastrointestinal, and vascular systems. No laboratory tests are currently available for the diagnosis of BD and monitoring disease activity. Moreover there is a lack of knowledge on BD pathogenesis. This study focused on circulating Natural Killer (NK), NKT and T cells evaluated as CD3neg CD56pos, CD3pos CD56pos, and CD3pos CD56neg. Peripheral blood mononuclear cells (PBMCs) were collected from 38 BD patients and 20 healthy controls (HC). The frequencies of NK, NKT, and T cells expressing CD16, CD69, NKG2D, Nkp30, Nkp46, and NKG2A were assessed by flow cytometry. Cytotoxic potential of NK cells was evaluated by flow cytometry as the percentage of cells expressing the degranulation marker CD107a after incubation with K562 cells. The levels of 27 cytokines were determined in plasma with a multiplex bead-based assay. Higher percentages of NK, NKT, and T cells expressing NKG2D were detected in PBMCs of BD patients than HC. ROC curve analysis showed that the evaluation of NKG2Dpos NK, NKT, and T cell percentages discriminated between BD patients and HC. Moreover, there was a positive correlation between the BD Current Activity Form (BDCAF) scores and the frequencies of NKG2Dpos NK and NKT cells. A higher frequency of NK cells expressing CD107a was induced in PBMCs from BD patients than HC after incubation with K562 cells. Concentrations of IL-5, IL-6, IL-10, IL-13, IP-10, and MIP-1β were higher in plasma of BD patients than HC. Monitoring the frequencies of NKG2Dpos lymphocytes could help the clinicians in BD patients management. In addition, the increased expression of NKG2D in BD patients is likely involved in disease pathogenesis.
2018
- Highlights of the 2nd EUVAS Vasculitis Course
[Articolo su rivista]
Emmi, Giacomo; Salvarani, Carlo; Prisco, Domenico; Jayne, David R W; Vaglio, Augusto
abstract
Highlights of the 2nd EUVAS Vasculitis Course
2018
- Imaging in polymyalgia rheumatica
[Articolo su rivista]
Possemato, N; Salvarani, C; Pipitone, N
abstract
Polymyalgia rheumatica (PMR) is a chronic, inflammatory disorder of unknown cause clinically characterized by pain and prolonged morning stiffness affecting the shoulders and often the pelvic girdle and neck. Imaging has substantially contributed to defining PMR as a disease mainly involving extra-articular structures. This review article analyses the role of the different imaging techniques in the diagnosis and follow-up of patients with PMR with particular emphasis on the role of ultrasound, PET/CT and MRI.
2018
- Impact of demography and population dynamics on the genetic architecture of human longevity
[Articolo su rivista]
Giuliani, Cristina; Sazzini, Marco; Pirazzini, Chiara; Bacalini, Maria Giulia; Marasco, Elena; Ruscone, Guido Alberto Gnecchi; Fang, Fang; Sarno, Stefania; Gentilini, Davide; Di Blasio, Anna Maria; Crocco, Paolina; Passarino, Giuseppe; Mari, Daniela; Monti, Daniela; Nacmias, Benedetta; Sorbi, Sandro; Salvarani, Carlo; Catanoso, Mariagrazia; Pettener, Davide; Luiselli, Donata; Ukraintseva, Svetlana; Yashin, Anatoliy; Franceschi, Claudio; Garagnani, Paolo
abstract
The study of the genetics of longevity has been mainly addressed by GWASs that considered subjects from different populations to reach higher statistical power. The "price to pay" is that population-specific evolutionary histories and trade-offs were neglected in the investigation of gene-environment interactions. We propose a new "diachronic" approach that considers processes occurred at both evolutionary and lifespan timescales. We focused on a well-characterized population in terms of evolutionary history (i.e. Italians) and we generated genome-wide data for 333 centenarians from the peninsula and 773 geographically-matched healthy individuals. Obtained results showed that: (i) centenarian genomes are enriched for an ancestral component likely shaped by pre-Neolithic migrations; (ii) centenarians born in Northern Italy unexpectedly clustered with controls from Central/Southern Italy suggesting that Neolithic and Bronze Age gene flow did not favor longevity in this population; (iii) local past adaptive events in response to pathogens and targeting arachidonic acid metabolism became favorable for longevity; (iv) lifelong changes in the frequency of several alleles revealed pleiotropy and trade-off mechanisms crucial for longevity. Therefore, we propose that demographic history and ancient/recent population dynamics need to be properly considered to identify genes involved in longevity, which can differ in different temporal/spatial settings.
2018
- Increased expression of interleukin-22 in patients with giant cell arteritis
[Articolo su rivista]
Zerbini, Alessandro; Muratore, Francesco; Boiardi, Luigi; Ciccia, Francesco; Bonacini, Martina; Belloni, Lucia; Cavazza, Alberto; Cimino, Luca; Moramarco, Antonio; Alessandro, Riccardo; Rizzo, Aroldo; Parmeggiani, Maria; Salvarani, Carlo; Croci, Stefania
abstract
OBJECTIVES:
GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis.
METHODS:
Patients subjected to temporal artery biopsies (TABs) naïve from therapy were enrolled: 27 biopsy-proven GCA, 8 biopsy-negative GCA, 21 biopsy-negative non-GCA patients. Expression of IL-22 was determined in TABs by immunohystochemistry, in plasma by ELISA, in peripheral blood mononuclear cells by real-time PCR and flow cytometry. Effects of IL-22 on viability and gene expression of primary cultures obtained from TABs were also evaluated.
RESULTS:
Inflamed TABs from GCA patients showed a higher expression of IL-22 and IL-22 specific receptor subunit (IL-22R1) than non-inflamed TABs. IL-22 was expressed in infiltrating immune cells and spindle shaped cells, IL-22R1 was expressed in endothelial cells. Patients with biopsy-proven GCA showed increased levels of IL-22 in plasma than patients with biopsy-negative GCA, without GCA and healthy subjects. Peripheral blood mononuclear cells from GCA patients expressed higher IL-22 transcript than healthy subjects. After stimulation in vitro with phorbol 12-myristate 13-acetate and ionomycin, the frequencies of Th22 and IL-22+ CD4+ lymphocytes were similar between patients with and without GCA. Treatment with IL-22 of primary cultures obtained from TABs increased cell viability under stress conditions and expression of B-cell activating factor.
CONCLUSION:
IL-22 is increased in patients with GCA and affects viability and gene expression of arterial cells, supporting a potential role in disease pathogenesis.
2018
- Large-Vessel Dilatation in Giant Cell Arteritis: A Different Subset of Disease?
[Articolo su rivista]
Muratore, Francesco; Kermani, Tanaz A; Crowson, Cynthia S; Koster, Matthew J; Matteson, Eric L; Salvarani, Carlo; Warrington, Kenneth J
abstract
To compare patients with large-vessel giant cell arteritis (LV-GCA) characterized by wall thickening, stenosis, and/or occlusion of subclavian arteries to those with subclavian dilatation.
2018
- Long-term treatment with rituximab in interstitial lung disease related to systemic sclerosis: our clinical experience
[Abstract in Atti di Convegno]
Lumetti, F; Spinella, A; Ariani, A; Cocchiara, E; Colaci, M; Silva, M; Sverzellati, N; Ferri, C; Salvarani, C; Giuggioli, D
abstract
Background Systemic sclerosis (SSc) is an immune-mediated disorder characterised by abnormal fibrosis and diffuse microangiopathy with skin and internal organ involvement. Interstitial lung disease (ILD) represents one of the most challenging complication of SSc, difficult to manage and correlate with a poor prognosis. Chest Computed Tomography (CT) is the gold standard for detection and evaluation of SSc-ILD by means of semi-quantitative scoring of extent of lung involvement. Some preliminary data suggest that rituximab (RTX) may be usefully employed in the treatment of SSc patients.
Objectives To investigate the role and effect of RTX on ILD in our SSc patients’ series.
Methods We retrospectively evaluated a series of 18 SSc patients (M/F 6/12, mean age 54.6±17.6 SD years, mean disease duration 11.4±6.5 SD years, L/D cutaneous subsets 6/12) who received one or more cycles of RTX (4 weekly infusions of 375 mg/m2) every 6 months for a total of 1–6 cycles. Lung involvement was studied by means of pulmonary function tests (PFTs) (18/18) and inspiratory chest CT (10/18) before and after treatment. In particular, we considered PFTs performed 6 months before RTX, at time 0, one year after the first RTX cycle, and at the end of follow-up (13.7±7.3 years). ILD extent score was assessed by the semi-quantitative method proposed by Goh et al (2008).1
Results Forced vital capacity (FVC%) significantly reduced during the year before RTX treatment [from 95.2±17.4 to 84.8±16.4; p=0.0017], as well as the diffusing capacity for carbon monoxide (DLCO%) [from 58.1±14.3 to 47.6±12.9; p=0.0002]. Conversely, FVC% and DLCO% stabilised one year after the first RTX cycle (80.8±23 and 47.8±15.7, respectively), and at the end of the follow-up (84.3±24.6 and 54.8.8±12.3, respectively; p=0.0001). In our cohort, only 7/10 patients had ILD detectable on CT before treatment. At the end of the follow-up we observed that ILD extented in 6/7 cases one patient remained stable, the three subjects without ILD did not developed pulmonary fibrosis.
Conclusions According to PFTs results, our study showed that RTX could stabilise the progression of lung function tests in SSc patients. However, the semi-quantitative visual score identified radiological pulmonary worsening in many patient with stabilised PFTs. Therefore, the correlations between functional and radiological outcomes are so weak that many Authors suggested they should be considered together in SSc-ILD assessment.
2018
- Management of cardiopulmonary disease in patients with systemic sclerosis: cardiorheumatology clinic and patient care standardization proposal
[Articolo su rivista]
Spinella, Amelia; Coppi, Francesca; Mattioli, Anna Vittoria; Lumetti, Federica; Rossi, Rosario; Cocchiara, Emanuele; Colaci, Michele; Boriani, Giuseppe; Ferri, Clodoveo; Salvarani, Carlo; Giuggioli, Dilia
abstract
Management of cardiopulmonary disease in patients with systemic sclerosis: cardiorheumatology clinic and patient care standardization proposal
2018
- Management of major organ involvement of Behçet’s syndrome: A systematic review for update of the EULAR recommendations
[Articolo su rivista]
Ozguler, Yesim; Leccese, Pietro; Christensen, Robin; Esatoglu, Sinem Nihal; Bang, Dongsik; Bodaghi, Bahram; Çelik, Aykut Ferhat; Fortune, Farida; Gaudric, Julien; Gul, Ahmet; Kötter, Ina; Mahr, Alfred; Moots, Robert J; Richter, Jutta; Saadoun, David; Salvarani, Carlo; Scuderi, Francesco; Sfikakis, Petros P; Siva, Aksel; Stanford, Miles; Tugal-Tutkun, Ilknur; West, Richard; Yurdakul, Sebahattin; Olivieri, Ignazio; Yazici, Hasan; Hatemi, Gulen
abstract
To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet's syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS.
2018
- Multidisciplinary Management of Spondyloarthritis-Related Immune-Mediated Inflammatory Disease
[Articolo su rivista]
Rizzello, Fernando; Olivieri, Ignazio; Armuzzi, Alessandro; Ayala, Fabio; Bettoli, Vincenzo; Bianchi, Luca; Cimino, Luca; Costanzo, Antonio; Cristaudo, Antonio; D'Angelo, Salvatore; Daperno, Marco; Fostini, Anna Chiara; Galeazzi, Mauro; Gilio, Michele; Gionchetti, Paolo; Gisondi, Paolo; Lubrano, Ennio; Marchesoni, Antonio; Offidani, Annamaria; Orlando, Ambrogio; Pugliese, Daniela; Salvarani, Carlo; Scarpa, Raffaele; Vecchi, Maurizio; Girolomoni, Giampiero
abstract
Immune-mediated inflammatory diseases (IMIDs) are chronic autoimmune conditions that share common pathophysiologic mechanisms. The optimal management of patients with IMIDs remains challenging because the coexistence of different conditions requires the intervention of several specialists. The aim of this study was to develop a series of statements defining overarching principles that guide the implementation of a multidisciplinary approach for the management of spondyloarthritis (SpA)-related IMIDs including SpA, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis and uveitis.
2018
- Nailfold videocapillaroscopy in antisynthetase syndrome
[Articolo su rivista]
Cassone, G.; Sebastiani, M.; Cavagna, L.; Triantafyllias, K.; Codullo, V.; Salvarani, C.; Manfredi, A.
abstract
A 57-year-old woman with a diagnosis of antisynthetase syndrome (ASSD) underwent a nailfold videocapillaroscopy (NVC) showing a scleroderma pattern. Alterations in capillary morphology have been reported in adults with inflammatory myositis (IM) but only recently have the differences in NVC findings between these two diseases been established. ASSD is currently classified as a subset of IM, for which reason only a few studies in literature evaluate its specific hallmarks, showing nonspecific features of NVC in patients with polymyositis and dermatomyositis (DM) and antisynthetase antibodies. To our knowledge, this is the first description of ASSD capillaroscopy features, and the first report of NVC in ASSD with evidence of scleroderma pattern. Further studies are needed to define clearly frequency, typical features, and possible correlation with clinical and serological data of NVC changes in ASSD, differences between microangiopathy in ASSD and systemic sclerosis or DM.
2018
- Physician's Global Assessment in Psoriatic Arthritis: A Multicenter GRAPPA Study
[Articolo su rivista]
Cauli, Alberto; Gladman, Dafna D; Mathieu, Alessandro; Olivieri, Ignazio; Porru, Giovanni; Tak, Paul P; Sardu, Claudia; Scarpa, Raffaele; Marchesoni, Antonio; Taylor, William J; Salvarani, Carlo; Kalden, Joachim; Lubrano, Ennio; Carneiro, Sueli; Piga, Matteo; Floris, Alberto; Desiati, Francesca; Flynn, John A; D'Angelo, Salvatore; van Kuijk, Arno W R; Catanoso, Maria Grazia; Caso, Francesco; Contu, Paolo; Ujfalussy, Ilona; Helliwell, Philip S; Mease, Philip J
abstract
Physician's global assessment (PGA) of disease activity is a major determinant of therapeutic decision making. This study assesses the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional use of separate VAS scales for musculoskeletal (PhysMSK) and dermatologic (PhysSk) manifestations in patients with psoriatic arthritis (PsA).
2018
- Polymyalgia rheumatica: an autoinflammatory disorder?
[Articolo su rivista]
Floris, Alberto; Piga, Matteo; Cauli, Alberto; Salvarani, Carlo; Mathieu, Alessandro
abstract
Polymyalgia rheumatica: an autoinflammatory disorder?
2018
- Primary central nervous system vasculitis associated with lymphoma
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Christianson, Teresa J H; Huston, John; Ansell, Stephen M; Giannini, Caterina; Hunder, Gene G
abstract
OBJECTIVES:
To record the clinical findings, response to therapy, and course of patients with primary CNS vasculitis (PCNSV) associated with lymphoma.
PATIENTS AND METHODS:
We reviewed the histories of 936 patients with a diagnosis of any type of vasculitis and lymphoma who were seen at the Mayo Clinic over a 32-year period. Ten patients with both PCNSV and lymphoma were identified. We compared the findings in these 10 patients with those from 158 patients with PCNSV without lymphoma seen over 29 years.
RESULTS:
Ten of a total of 168 (5.9%) patients with PCNSV also had a history of lymphoma: 6 with Hodgkin lymphoma (HL) and 4 with non-HL (NHL). A granulomatous vasculitis was found in all 8 patients with cerebral biopsies, accompanied by vascular deposits of β-amyloid peptide in 2. In 7 patients, medical diagnostic workup for PCNSV revealed the lymphoma. Compared to the 158 patients with PCNSV without lymphoma, patients with lymphoma were more frequently male (p = 0.04), had increased gadolinium leptomeningeal enhancement (p = 0.03) at presentation, and had more neurologic disability at last follow-up (p = 0.01). No significant differences in treatment response were observed in the 2 groups (p = 0.202). Considering all 168 patients, increased disability at last follow-up was associated with increasing age at diagnosis (odds ratio [OR] 1.4), lymphoma (OR 5.9), and cerebral infarction (OR 3.2), while reduced disability was associated with gadolinium-enhanced lesions (OR 0.43) and amyloid angiopathy (OR O.23).
CONCLUSIONS:
Lymphoma may be diagnosed simultaneously with PCNSV, suggesting an immunologic paraneoplastic mechanism.
2018
- Response to: 'Artery tertiary lymphoid organs in giant cell arteritis are not exclusively located in the media of temporal arteries' by Graveret al
[Articolo su rivista]
Ciccia, Francesco; Rizzo, Aroldo; Salvarani, Carlo; Triolo, Giovanni
abstract
Response to: 'Artery tertiary lymphoid organs in giant cell arteritis are not exclusively located in the media of temporal arteries' by Graveret al
2018
- Risankizumab, an IL-23 inhibitor, for ankylosing spondylitis: results of a randomised, double-blind, placebo-controlled, proof-of-concept, dose-finding phase 2 study
[Articolo su rivista]
Baeten, Dominique; Østergaard, Mikkel; Wei, James Cheng-Chung; Sieper, Joachim; Järvinen, Pentti; Tam, Lai-Shan; Salvarani, Carlo; Kim, Tae-Hwan; Solinger, Alan; Datsenko, Yakov; Pamulapati, Chandrasena; Visvanathan, Sudha; Hall, David B; Aslanyan, Stella; Scholl, Paul; Padula, Steven J
abstract
To evaluate the efficacy and safety of risankizumab, a humanised monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), in patients with active ankylosing spondylitis (AS).
2018
- Rituximab therapy for Takayasu arteritis: A seven patients experience and a review of the literature
[Articolo su rivista]
Pazzola, Giulia; Muratore, Francesco; Pipitone, Nicolò; Crescentini, Filippo; Cacoub, Patrice; Boiardi, Luigi; Spaggiari, Lucia; Comarmond, Cloe; Croci, Stefania; Saadoun, David; Salvarani, Carlo
abstract
OBJECTIVES:
To assess the efficacy and safety of rituximab (RTX) in patients with Takayasu arteritis (TAK).
METHODS:
We conducted a retrospective study on seven TAK patients treated with RTX. Six of the seven patients had a disease refractory to high dose glucocorticoids and conventional immunosuppressive and/or biologic agents. One newly diagnosed, treatment-naïve TAK patient refused glucocorticoids and received RTX alone. Clinical evaluation, laboratory tests and imaging modalities (CT or MR-angiography, and 18 F-fluorodeoxyglucose PET/CT) were performed at first RTX administration and every 6 months thereafter. Disease activity was assessed using the Kerr index. We also performed a literature review using PubMed, Ovid MEDLINE and Cochrane library.
RESULTS:
Seven patients (6 females) were included in the study. Mean ( s . d .) age was 32.4 (17.3) years. At first RTX administration, all patients had active disease according to the Kerr index (⩾2), and had also evidence of active disease at PET/CT. Despite RTX treatment, four of the seven patients had evidence of persistent disease activity and/or radiographic disease progression during follow-up. Three out of seven patients in whom RTX was employed as rescue therapy achieved complete remission. In the literature review, we identified five papers describing nine patients treated with RTX with good results in eight cases, but short follow-up.
CONCLUSION:
Our data do not support a role for RTX as first line biologic therapy in TAK patients, but it may have a role in some patients as second or third line biologic therapy.
2018
- Safety profile of the interleukin-1 inhibitors anakinra and canakinumab in real-life clinical practice: a nationwide multicenter retrospective observational study
[Articolo su rivista]
Sota, Jurgen; Vitale, Antonio; Insalaco, Antonella; Sfriso, Paolo; Lopalco, Giuseppe; Emmi, Giacomo; Cattalini, Marco; Manna, Raffaele; Cimaz, Rolando; Priori, Roberta; Talarico, Rosaria; de Marchi, Ginevra; Frassi, Micol; Gallizzi, Romina; Soriano, Alessandra; Alessio, Maria; Cammelli, Daniele; Maggio, Maria Cristina; Gentileschi, Stefano; Marcolongo, Renzo; La Torre, Francesco; Fabiani, Claudia; Colafrancesco, Serena; Ricci, Francesca; Galozzi, Paola; Viapiana, Ombretta; Verrecchia, Elena; Pardeo, Manuela; Cerrito, Lucia; Cavallaro, Elena; Olivieri, Alma Nunzia; Paolazzi, Giuseppe; Vitiello, Gianfranco; Maier, Armin; Silvestri, Elena; Stagnaro, Chiara; Valesini, Guido; Mosca, Marta; de Vita, Salvatore; Tincani, Angela; Lapadula, Giovanni; Frediani, Bruno; De Benedetti, Fabrizio; Iannone, Florenzo; Punzi, Leonardo; Salvarani, Carlo; Galeazzi, Mauro; Angotti, Rossella; Messina, Mario; Tosi, Gian Marco; Rigante, Donato; Cantarini, Luca
abstract
A few studies have reported the safety profile of interleukin (IL)-1 blockers from real life. The aim of this study is to describe anakinra (ANA) and canakinumab (CAN) safety profile in children and adults, based on data from a real-life setting. Demographic, clinical, and therapeutic data from patients treated with ANA and CAN were retrospectively collected and analyzed. Four hundred and seventy five patients were enrolled; ANA and CAN were prescribed in 421 and 105 treatment courses, respectively. During a mean follow-up of 24.39 ± 27.04 months, 89 adverse events (AE) were recorded; 13 (14.61%) were classified as serious AE (sAE). The overall estimated rate of AE and sAE was 8.4 per 100 patients/year. Safety concerns were more frequent among patients aged ≥ 65 years compared with patients < 16 years (p = 0.002). No differences were detected in the frequency of safety concerns between monotherapy and combination therapy with immunosuppressants (p = 0.055), but a significant difference was observed when injection site reactions were excluded from AE (p = 0.01). No differences were identified in relation to gender (p = 0.462), different lines of biologic therapy (p = 0.775), and different dosages (p = 0.70 ANA; p = 0.39 CAN). The overall drug retention rate was significantly different according to the occurrence of safety concerns (p value < 0.0001); distinguishing between ANA and CAN, significance was maintained only for ANA (p < 0.0001 ANA; p > 0.05 CAN). Treatment duration was the only variable associated with onset of AE (OR = 0.399 [C.I. 0.250-0.638], p = 0.0001). ANA and CAN have shown an excellent safety profile; the risk for AE and sAE tends to decrease over time from the start of IL-1 inhibition.
2018
- Standardization of red flags for referral to rheumatologists and ophthalmologists in patients with rheumatic diseases and ocular involvement: a consensus statement
[Articolo su rivista]
Olivieri, Ignazio; Accorinti, Massimo; Abicca, Irene; Bisceglia, Paola; Cimino, Luca; Latanza, Loredana; Leccese, Pietro; Lubrano, Ennio; Marchesoni, Antonio; Miserocchi, Elisabetta; Neri, Piergiorgio; Salvarani, Carlo; Scarpa, Raffaele; D'Angelo, Salvatore
abstract
Ocular involvement is a common manifestation of inflammatory rheumatic diseases, often requiring a multidisciplinary collaboration between rheumatologists and ophthalmologists. The aim of this study was to standardize "red flags" for referral for rheumatologists and ophthalmologists using a Delphi consensus for the management of rheumatic diseases with ocular involvement. The scientific board comprised 11 Italian hospital-based rheumatologists (N = 6) and ophthalmologists (N = 5). A systematic review identified potential red flags for referral. The panel developed 19 statements consisting of (a) referral from ophthalmologist to rheumatologist (b) referral from rheumatologist to ophthalmologist and (c) overarching principles relating to multidisciplinary roles/goals and management. Voting was performed anonymously using an online Delphi method. Each participant expressed a level of agreement on each statement using a 5-point scale (1="strongly disagree"; 5="strongly agree"). Total cumulative agreement was defined as the sum of the percentage of response to items 4 ("agree") and 5 ("absolutely agree"), consensus defined as ≥ 80% cumulative agreement for each statement. Positive consensus among 11 participants was reached for 15/19 (78.9%) statements. Statements not reaching consensus were discussed in a face-to-face meeting prior to the second vote (10 participants). Positive consensus was reached for all 19 statements, with final total cumulative agreement of 90-100%. This is the first Delphi consensus undertaken to standardize red flags for referral to rheumatologists and ophthalmologists for patients with rheumatic diseases and ocular involvement.
2018
- The Sex Influence on Response to Tumor Necrosis Factor-α Inhibitors and Remission in Axial Spondyloarthritis
[Articolo su rivista]
Lubrano, Ennio; Perrotta, Fabio Massimo; Manara, Maria; D'Angelo, Salvatore; Addimanda, Olga; Ramonda, Roberta; Punzi, Leonardo; Olivieri, Ignazio; Salvarani, Carlo; Marchesoni, Antonio
abstract
OBJECTIVE:
The aim of this study was to evaluate the influence of sex on response to treatment and disease remission in patients with axial spondyloarthritis (axSpA).
METHODS:
In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria for axSpA, and treated with adalimumab, etanercept, golimumab, or infliximab, were studied. We compared clinical characteristics, patient-reported outcomes, disease activity, function, and response to treatment in male and female patients with this disease.
RESULTS:
Three hundred forty patients with axSpA (270 with ankylosing spondylitis, 19 with psoriatic arthritis with axial involvement, and 51 with nonradiographic axSpA) were studied. Male subjects had a significantly higher prevalence of grade IV sacroiliitis, higher levels of serum C-reactive protein, lower Maastricht Ankylosing Spondylitis Enthesitis Score, and fatigue when compared with females. Further, Kaplan-Meier survival curves showed that the rate of partial remission, ASAS40 response, and Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement, but not ASDAS inactive disease, were significantly lower in female patients.
CONCLUSION:
Our data suggest that female sex was associated with a lower rate of response to treatment and of disease remission in patients with axSpA treated with antitumor necrosis factor-α drugs.
2018
- Tocilizumab for the treatment of giant cell arteritis
[Articolo su rivista]
Schirmer, Michael; Muratore, Francesco; Salvarani, Carlo
abstract
Giant cell arteritis (GCA) is the most frequent type of vasculitis, occurring in people older than 50 years. So far, treatment has been limited to corticosteroids and methotrexate only. Areas covered: Interleukin-6 (IL-6) plays a role in the pathophysiology of GCA. This review covers recent advances in the treatment of GCA with tocilizumab (TCZ), which specifically binds to both soluble and membrane-bound IL-6R and inhibits IL-6R-mediated signaling. Expert commentary: Two randomized controlled trials recently showed the efficacy of the IL-6 receptors inhibitor monoclonal antibody TCZ for the induction and maintenance of remission in patients with new-onset and relapsing GCA. Furthermore, addition of TCZ to prednisone led to a reduction in the cumulative prednisone doses required to control GCA. The profile of adverse events was balanced across treatment groups and no safety concerns were raised during the trial.
2018
- Treatment of inflammatory myopathies
[Articolo su rivista]
Pipitone, Nicolò; Salvarani, Carlo
abstract
The idiopathic inflammatory myopathies (IIM) dermatomyositis (DM) and polymyositis (PM) are chronic diseases affecting the striated muscles with variable involvement of other organs. Glucocorticoids are considered the cornerstone of treatment, but some patients require adjunctive immunosuppressive agents because of insufficient response to glucocorticoids, flares upon glucocorticoid tapering, or glucocorticoid-related adverse events. Areas covered: The aim of this article was to review (PubMed search until February 2018) the evidence on established and new therapies derived from randomized controlled trials (RCTs) on adult DM and PM. In addition, key data from open-label trials, case reports, and abstracts were included where data from RCT were lacking. Expert commentary: Numerous synthetic and biological immunosuppressive agents are currently available to treat the IIM, sometimes in combination. The choice of the specific medication in the individual patient depends upon the disease phenotype and patient's characteristics. Exercise improves muscle performance without causing disease flares and should be an integral part of the treatment of the IIM. Prompt diagnosis and treatment can lead to better outcome.
2018
- Unmet Needs in the Pathogenesis and Treatment of Vasculitides
[Articolo su rivista]
Muratore, Francesco; Pazzola, Giulia; Soriano, Alessandra; Pipitone, Nicolò; Croci, Stefania; Bonacini, Martina; Boiardi, Luigi; Salvarani, Carlo
abstract
Despite the progress in the last years on the field of vasculitides, there are several unmet needs regarding classification, disease activity assessment, predictors of flares and complications, and type of treatment for the different forms. The 1990 American College of Rheumatology (ACR) classification criteria currently used to define giant cell arteritis and Takayasu arteritis were designed to discriminate between different types of vasculitides but not to differentiate vasculitis from other disorders. Recently, efforts have been made to overcome the shortcomings of the ACR criteria. The lack of an accepted definition of disease activity in large-vessel vasculitides presents a major challenge in creating useful and valid outcome tools for the assessment of disease course. Identification of predictors of flares can aid in optimizing therapeutic strategies, minimizing disease flares, and reducing treatment-related side effects. It is furthermore important to recognize and characterize the risk factor that might predict the manifestations associated with poor outcome and prognosis. Two RCTs have evidenced the efficacy of tocilizumab in addition to glucocorticoids (GCs) in the treatment of giant cell arteritis (GCA). However, the role of tocilizumab or other biological agents without GCs needs to be investigated. Recent observational studies have suggested that rituximab is also effective in patients with eosinophilic granulomatosis with polyangiitis and in antineutrophil cytoplasmic antibodies (ANCA)-negative patients with granulomatosis with polyangiitis and microscopic polyangiitis. Rituximab or anti-TNF alfa may represent a possible alternative therapy in case of refractory or difficult to treat polyarteritis nodosa (PAN) patients. The new International Criteria for Behçet's Disease have shown a better sensitivity and a better accuracy compared to the older International Study Group on Behçet's Disease criteria. The EULAR recommendations for the management of Behçet's disease (BD) have been recently updated. However, the treatment of refractory disease is still a real challenge.
2018
- Usefulness of PET in recognizing and managing vasculitides
[Articolo su rivista]
Pipitone, Nicolò A M; Versari, Annibale; Salvarani, Carlo
abstract
PURPOSE OF REVIEW:
The aim of this article was to review the recent contributions to the scoring methods of PET in vasculitis as well as to its role in the diagnostic work-up.
RECENT FINDINGS:
Both visual and semiquantitative scoring methods can be used to interpret PET scans. PET has been shown to be both sensitive and specific in the diagnosis of large-vessel vasculitis. In addition, it also has a role in predicting vascular complications.
SUMMARY:
There is a need to better standardize the scoring methods used to interpret PET scans. In clinical practice, PET is useful to diagnose untreated individuals with suspected large-vessel vasculitis and contributes to identify patients at risk for vascular complications.
2017
- A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis
[Articolo su rivista]
Carmona, F. David; Vaglio, Augusto; Mackie, Sarah L; Hernández Rodríguez, José; Monach, Paul A; Castañeda, Santos; Solans, Roser; Morado, Inmaculada C; Narváez, Javier; Ramentol Sintas, Marc; Pease, Colin T; Dasgupta, Bhaskar; Watts, Richard; Khalidi, Nader; Langford, Carol A; Ytterberg, Steven; Boiardi, Luigi; Beretta, Lorenzo; Govoni, Marcello; Emmi, Giacomo; Bonatti, Francesco; Cimmino, Marco A; Witte, Torsten; Neumann, Thomas; Holle, Julia; Schönau, Verena; Sailler, Laurent; Papo, Thomas; Haroche, Julien; Mahr, Alfred; Mouthon, Luc; Molberg, Øyvind; Diamantopoulos, Andreas P; Voskuyl, Alexandre; Brouwer, Elisabeth; Daikeler, Thomas; Berger, Christoph T; Molloy, Eamonn S; O'Neill, Lorraine; Blockmans, Daniel; Lie, Benedicte A; Mclaren, Paul; Vyse, Timothy J; Wijmenga, Cisca; Allanore, Yannick; Koeleman, Bobby P. C; Barrett, Jennifer H; Cid, María C; Salvarani, Carlo; Merkel, Peter A; Morgan, Ann W; González Gay, Miguel A; Martín, Javier
abstract
Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10(-54), per-allele OR = 1.79; and rs9275592, p = 1.14 × 10(-40), OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10(-10), OR = 1.28; and rs128738, p = 4.60 × 10(-9), OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis.
2017
- A national survey on the management of psoriatic arthritis using the Delphi method
[Articolo su rivista]
Lubrano, Ennio; Cantini, Fabrizio; Mathieu, Alessandro; Olivieri, Ignazio; Salvarani, Carlo; Scarpa, Raffaele; Marchesoni, Antonio
abstract
Accurate diagnosis and appropriate management of psoriatic arthritis (PsA) is essential to avoid unnecessary morbidity. Our aim in this study was to evaluate the current approach to the management of PsA among rheumatologists.
2017
- Adult Primary Central Nervous System Vasculitis
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Hunder, Gene G.
abstract
Primary central nervous system vasculitis (PCNSV) is an
uncommon and poorly understood form of vasculitis that
it is limited to the brain and spinal cord. PCNSV represents
the most frequent vasculitis involving the central nervous
system (CNS. The neurological manifestations are
diverse and non-specific. Serological markers of inflammation
are usually normal. Cerebrospinal
fluid is abnormal in approximately
80–90% of the cases. The diagnosis
is unlikely in the presence of a
normal brain magnetic resonance
imaging (MRI) scan. Biopsy of
CNS tissue showing vasculitis is
the only definitive test; however,
angiography is often used to confirm the diagnosis. Early recognition
is important because treatment with glucocorticoids
with or without cytotoxic drugs may prevent serious or even
lethal outcomes. The differential diagnosis is broad and includes
reversible vasoconstriction syndromes, secondary cerebral vasculitis,
malignancy, and infections.
Modern recognition of PCNSV as a separate entity is generally
dated to the mid-1950s when Cravioto and Feigin
described several cases of a “non-infectious granulomatous
angiitis” with a predilection for the nervous system. The term
“granulomatous angiitis of the nervous system” was applied
because of the histopathologic findings observed in arteries
from initial cases.
Recently, major advances have been made in the field of
PCNSV. Studies of additional cases have revealed a more varied
histopathologic inflammatory picture and an association
with amyloid angiopathy. They have also recognized that
PCNSV is more heterogeneous
than previously thought, encompassing
clinical subsets that differ
in terms of prognosis and therapy.
Finally, childhood PCNSV
(cPCNSV) has been recognized as
possible cause of vascular strokes
in children. This review
aimed to provide an update on the major advances made in
adult PCNSV.
2017
- Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy
[Articolo su rivista]
Carmona, F. David; Coit, Patrick; Saruhan Direskeneli, Güher; Hernández Rodríguez, José; Cid, María C; Solans, Roser; Castañeda, Santos; Vaglio, Augusto; Direskeneli, Haner; Merkel, Peter A; Boiardi, Luigi; Salvarani, Carlo; González Gay, Miguel A; Martín, Javier; Sawalha, Amr H.
abstract
Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P = 7.54E-07; ORGCA = 1.19, ORTAK = 1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA = 5.52E-04, ORGCA = 1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus.
2017
- Assessment of disease activity in large-vessel vasculitis: Results of an international delphi exercise
[Articolo su rivista]
Aydin, S. Z.; Direskeneli, H.; Merkel, P. A.; Toloza, S.; Blockmans, D.; Sato, E. I.; De Souza, A. W. S.; Cabral, D.; Carette, S.; Famorca, L.; Khalidi, N.; Milman, N.; Yacyshyn, E.; Tesar, V.; Baslund, B.; Faurschou, M.; Guillevin, L.; Puechal, X.; Aries, P.; Hellmich, B.; Herlyn, K.; Holle, J.; Lamprecht, P.; Moosig, F.; Neumann, T.; Zwerina, J.; Tomasson, G.; Bambery, P.; Jois, R.; Rajasekhar, L.; Sharma, A.; Sivakumar, R.; Molloy, E.; Hashkes, P.; Catapano, F.; Cimino, L.; De Fanti, A.; Pipitone, N.; Salvarani, C.; Vaglio, A.; Kobayashi, S.; Suzuki, K.; Flores-Suarez, L. F.; Hinojosa-Azaola, A.; Brouwer, E.; Rutgers, A.; Stegeman, C.; Suppiah, R.; Hollan, I.; Arguis, P.; Cid, M. C.; Daikeler, T.; Alibaz-Oner, F.; Hamuryudan, V.; Hatemi, G.; Hazirolan, T.; Inanc, M.; Kalayci, M. B.; Kamali, S.; Kansu, T.; Karaaslan, Y.; Karadag, O.; Keser, G.; Onat, A. M.; Ozbalkan, Z.; Ozen, S.; Ozer, H. T. E.; Pamuk, O. N.; Yilmaz, S. G.; Basu, N.; Casian, A.; Chakravarty, K.; D'Cruz, D.; Edelsten, C.; Harper, L.; Jayne, D.; Levy, J.; Mason, J.; Robson, J.; Scott, D.; Stanford, M.; Watts, R.; Albert, D.; Amudala, N.; Beckman, J.; Chacko, B.; Chung, S.; Fessler, B.; Giardino, A.; Grayson, P.; Hunder, G.; Langford, C.; Lerman, M.; Liang, K.; Litt, H.; Mason, T.; Matteson, E.; Mikdashi, J.; Mohler, E.; Monach, P.; Rice, B.; Sharma, A.; Sreih, A.; Stone, J.; Tsapatsaris, N.; Villa-Forte, A.; Warrington, K.; Yazici, Y.; Ytterberg, S.
abstract
Objective. To arrive at consensus for candidate outcomes for disease activity assessment in largevessel vasculitis (LVV) in clinical trials. Methods.A Delphi survey including 99 items was circulated among international experts for 3 rounds. Results. Fifty-seven items were accepted for both giant cell arteritis and Takayasu arteritis. Sixty-seven percent of experts voted to have a common approach for both diseases with additional disease-specific items such as weight loss, scalp tenderness/necrosis, morning stiffness, dizziness, visual symptoms, and imaging. Conclusion. This study highlights similarities and differences in experts' perspectives for assessing clinical activity in LVV and may guide a consensus-driven core set of validated outcomes.
2017
- Behçet's Disease
[Capitolo/Saggio]
Soriano, A.; Pipitone, N.; Salvarani, C.
abstract
Behçet's disease (BD) is a systemic inflammatory disorder whose clinical hallmark is recurrent oral and genital ulcers variably associated with skin and organ involvement. BD is currently considered systemic vasculitis. Vascular involvement is typically characterized by thrombotic events and occurs in about 30% of patients, while cardiac involvement has lower frequency, ranging from 1-6% to 16.5%. Valvulopathies, coronary arteritis with or without myocardial infarction, aneurysms of the coronary arteries, myocarditis, pericarditis, endomyocardial fibrosis, arrhythmia, intracardiac thrombus formation of the heart chambers or of the aortic sinus, and pulmonary artery aneurysm are all possible manifestations of BD. Timely detection of cardiac involvement is pivotal for appropriate management. Echocardiography is the most widely used diagnostic tool and may be complemented by cardiac MRI and/or CT angiography in selected cases. Treatment of cardiac BD is challenging and still largely empirical. High-dose glucocorticoids and immunosuppressive agents are recommended. In this chapter, we review the spectrum of cardiac manifestations in the course of BD. We also analyze the role of the different imaging techniques for an accurate diagnosis, treatment options, and cardiac implications of therapy.
2017
- Chronic periaortitis with retroperitoneal fibrosis successfully treated with first line tocilizumab monotherapy: a case report
[Articolo su rivista]
Perrotta, Fabio Massimo; Fici, Michelangelo; Guerra, Germano; Brunese, Luca; Salvarani, Carlo; Lubrano, Ennio
abstract
To present a case of a 65-year-old man with chronic periaortitis successfully treated in monotherapy with first line anti-IL-6 tocilizumab.
2017
- Clinical Spectrum of Medium-Sized Vessel Vasculitis
[Articolo su rivista]
Alibaz Oner, Fatma; Koster, Matthew J; Crowson, Cynthia S; Makol, Ashima; Ytterberg, Steven R; Salvarani, Carlo; Matteson, Eric L; Warrington, Kenneth J.
abstract
Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of medium-sized visceral vessels. However, cutaneous arteritis (CA) and gastrointestinal (GI) vasculitis are forms of single-organ vasculitis having indistinguishable histopathologic findings from PAN. The aim of this study was to evaluate and compare the clinical characteristics, treatment, and outcomes of patients with systemic PAN, CA, and GI vasculitis.
2017
- Contrast-enhanced ultrasound of the carotid artery in patients with large vessel vasculitis: Correlation with positron emission tomography findings
[Articolo su rivista]
Germanò, Giuseppe; Macchioni, Pierluigi; Possemato, Niccolò; Boiardi, Luigi; Nicolini, Alberto; Massimiliano Casali, Null; Versari, Annibale; Pipitone, Nicolò; Salvarani, Carlo
abstract
To assess the findings of contrast-enhanced ultrasound (CEUS) of carotid arteries in patients with large vessel vasculitis (LVV) and to compare them with those observed using 18F-FDG positron emission tomography (FDG-PET).
METHODS:
31 consecutive patients with LVV (14 with Takayasu, 17 with giant cell arteritis with large vessel involvement) underwent both PET/CT and carotid artery colour Doppler ultrasonography (CDUS) for a total of 35 combined assessments. Right carotid artery CEUS was performed after CDUS in all assessments. Kerr's criteria, complete clinical examination and acute phase reactants were simultaneously evaluated. Intensity of vascular uptake and vascularization of carotid artery wall were compared.
RESULTS:
Ten FDG/PET scans showed active vascular 18F-FDG uptake (visual grade ≥2) in the right carotid artery. CEUS demonstrated severe vascularization (grade 2) within the right carotid artery wall in 12 examinations. Carotid CEUS vascularization grade significantly correlated with vascular 18F-FDG uptake (p<0.001) and max standardized uptake value (SUV) in right carotid artery/mean SUV in superior vena cava (p=0.001). When active vascular 18F-FDG uptake (≥2) was considered the gold standard for defining vascular inflammation, carotid CEUS had a sensitivity of 100% (95%CI 65%,100%) and a specificity of 92% (95%CI 72%, 99%). The positive LR was 12.5 (95%CI 3.3, 47.2). Severe vascularization at CEUS and active vascular 18F-FDG uptake were significantly more frequent in active disease according to Kerr's criteria compared to inactive (p = 0.001 and p = 0.002, respectively).
CONCLUSIONS:
Carotid CEUS vascularization grade and grade of vascular inflammation on FDG-PET were correlated in patients with LVV
2017
- Corrigendum: Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy
[Articolo su rivista]
Carmona, F. David; Coit, Patrick; Saruhan Direskeneli, Güher; Hernández Rodríguez, José; Cid, María C; Solans, Roser; Castañeda, Santos; Vaglio, Augusto; Direskeneli, Haner; Merkel, Peter A; Boiardi, Luigi; Salvarani, Carlo; González Gay, Miguel A; Martín, Javier; Sawalha, Amr H.
abstract
Corrigendum
2017
- Diagnosis and treatment of rheumatoid arthritis in the Emilia Romagna region: a prospective population-based study
[Articolo su rivista]
Addimanda, Olga; Marino, Massimiliano; Farina, Ilaria; Trevisani, Marica; Arrigoni, Eugenio; Lumetti, Federica; Crescentini, Filippo; Sambo, Paola; Bezzi, Alessandra; Bruschi, Marco; Santilli, Daniele; Reta, Massimo; Bosi, Simona; Delsante, Giovanni; Girelli, Francesco; Montaguti, Luca; Meliconi, Riccardo; Sebastiani, Marco; Ferri, Clodoveo; Malavolta, Nazzarena; Govoni, Marcello; Trombetti, Susanna; De Palma, Rossana; Salvarani, Carlo
abstract
OBJECTIVES:
To perform a population-based study in rheumatoid arthritis (RA) patients, in order to evaluate the efficacy and safety of pharmacologic treatments.
METHODS:
1087 patients with RA were enrolled; inclusion criteria were: newly diagnosed RA, already diagnosed RA with high disease activity (HDA) (DAS28≥4.2) starting biologic DMARDs (bDMARDs), already diagnosed RA with HDA continuing with conventional DMARDs (cDMARDs). The following data were collected: demographics, clinical and laboratory features, imaging and prescribed drugs. All parameters except immunology and imaging (performed yearly) were repeated at each follow-up evaluations (after 3, 6 and 12 months, and thereafter every 12 months). In order to evaluate clinical response, the EULAR response criteria were used as the gold standard.
RESULTS:
414 (38.1%) newly diagnosed patients with RA, 477 (43.9%) RA patients who started bDMARDs and 196 (18.0%) RA patients who continued with cDMARDs were enrolled from April 2012 to March 2015 at 12 Rheumatology Centres in the Emilia Romagna Region. Statistical analyses showed a relative risk ratio (RRR) for moderate response of 1.65 in RA patients who started bDMARDs (p=0.16) and 2.49 for newly diagnosed RA (p=0.01). Sex, age and Health Assessment Questionnaire were not statistically significant. A RRR of 2.00 has been confirmed for RA patients who started bDMARDs (p<0.0005) for a good response as well as 2.20 for newly diagnosed RA (p<0.0005). An increase in adverse events among bDMARDs was found, but when looking at infections or neoplasia, no differences were highlighted between RA which started bDMARDs and RA who continued with cDMARDs.
CONCLUSIONS:
Our results are in line with already published papers from British and Swedish Registries: a greater likelihood to have a good response is demonstrated for not longstanding RA starting cDMARDs or RA with HDA when a bDMARD is started. Also a good safety profile is demonstrated.
2017
- Do we need FDG-PET/CT to assess atherosclerosis?
[Articolo su rivista]
Pipitone, Nicolò; Salvarani, Carlo; Versari, Annibale
abstract
Do we need FDG-PET/CT to assess atherosclerosis?
2017
- Ectopic expression of CXCL13, BAFF, APRIL and LT-β is associated with artery tertiary lymphoid organs in giant cell arteritis
[Articolo su rivista]
Ciccia, Francesco; Rizzo, Aroldo; Maugeri, Rosario; Alessandro, Riccardo; Croci, Stefania; Guggino, Giuliana; Cavazza, Alberto; Raimondo, Stefania; Cannizzaro, Alessandra; Iacopino, Domenico Gerardo; Salvarani, Carlo; Triolo, Giovanni
abstract
To investigate whether artery tertiary lymphoid organs (ATLOs) are present in giant cell arteritis (GCA) and that their formation is associated with the ectopic expression of constitutive lymphoid tissue-homing chemokines. METHODS:
Reverse transcriptase PCR, immunohistochemical and immunofluorescence analysis were used to determine the presence of ectopic ATLOs in GCA and the expression of chemokines/chemokine receptors and cytokines involved in lymphoneogenesis in the temporal artery samples obtained from 50 patients with GCA and 30 controls. The presence of lymphatic conduits, of follicular dendritic cells (FDCs) precursors and lymphoid tissue inducer cells was also investigated. Finally, expression of CXCL13, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and CCL21 by isolated myofibroblasts was evaluated before and after stimulation with Toll-like receptors (TLRs) agonists and cytokines.
RESULTS:
ATLOs were observed in the media layer of 60% of patients with GCA in close proximity to high endothelial venules and independently by the age of patients and the presence of atherosclerosis. ATLO formation was also accompanied by the expression of CXCL13, BAFF, a proliferation-inducing ligand (APRIL), lymphotoxin (LT)-β, interleukin (IL)-17 and IL-7, the presence of FDC precursors and of lymphoid conduits. Stimulation of myofibroblasts with TLR agonists and cytokines resulted in the upregulation of BAFF and CXCL13.
CONCLUSIONS:
ATLOs occur in the inflamed arteries of patients with GCA possibly representing the immune sites where immune responses towards unknown arterial wall-derived antigens may be organised.
2017
- Efficacy and safety of adalimumab in Behçet's disease-related uveitis: a multicenter retrospective observational study
[Articolo su rivista]
Fabiani, Claudia; Vitale, Antonio; Emmi, Giacomo; Vannozzi, Lorenzo; Lopalco, Giuseppe; Guerriero, Silvana; Orlando, Ida; Franceschini, Rossella; Bacherini, Daniela; Cimino, Luca; Soriano, Alessandra; Frediani, Bruno; Galeazzi, Mauro; Iannone, Florenzo; Tosi, Gian Marco; Salvarani, Carlo; Cantarini, Luca
abstract
The study aim was to evaluate the efficacy of adalimumab (ADA) in a large series of Behçet's disease (BD)-related uveitis. We performed a multicenter retrospective observational study including 40 selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12 months of treatment. Primary end point was reduction of ocular inflammatory flares. Secondary end points were improvement of best corrected visual acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), and evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. During the first 12 months of ADA therapy, the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year (p < 0.0001). Similarly, BCVA improved if compared to baseline (7.4 ± 2.9 versus 8.5 ± 2.1, p = 0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.27 ± 42.8 μm at the end of follow-up (p < 0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3 months, and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3- and 12-month follow-up if compared to baseline (p < 0.0001 and p = 0.006, respectively). ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation.
2017
- Ignazio Olivieri, MD, 1953-2017
[Articolo su rivista]
Salvarani, Carlo; Khan, Muhammad Asim
abstract
In memoriam of Ignazio Olivieri, MD, 1953-2017
2017
- In memoriam: Ignazio Olivieri
[Articolo su rivista]
Salvarani, C
abstract
Not available.
2017
- Incidence, prevalence and survival of biopsy-proven giant cell arteritis in Northern Italy during a 26-year period
[Articolo su rivista]
Catanoso, Mariagrazia; Macchioni, Pierluigi; Boiardi, Luigi; Muratore, Francesco; Restuccia, Giovanna; Cavazza, Alberto; Pipitone, Nicolò; Mancuso, Pamela; Luberto, Ferdinando; Salvarani, Carlo
abstract
To investigate the epidemiology and mortality in patients with biopsy-proven giant cell arteritis (GCA) in Northern Italy.
METHODS:
All patients with incident temporal artery biopsy-positive GCA diagnosed between 1986 and 2012 living in the Reggio Emilia area were identified using pathology register and by reviewing all histopathological specimens. For each patient, we identified one comparison subject from the same geographic area matched for age and gender. Mortality rates and specific causes of death were reported.
RESULTS:
There were 285 incident cases of biopsy-proven GCA (210 women) during the 26-year study period. The overall age- and sex-adjusted incidence per 100,000 persons aged 50 years or older was 5.8 (95%CI: 5.1 to 6.5). Incidence was significantly higher in women (7.8, 95%CI: 6.7 to 8.9) than in men (3.3, 95%CI: 2.6 to 4.1) (p<0.0001). Annual age- and sex-adjusted incidence rates significantly increased by 15.9% per 3 years from 1986 to 2000, then significantly fell by -4.8% per 3 years from 2001-2012. The prevalence of GCA on December 31, 2012 was 87.9 (95%CI: 75.8 to 101.4). No significant differences in the mortality rates were observed between GCA patients (4.9 per 100 person-year, 95%CI: 4.1 to 5.8) and non-GCA subjects (5.6, 95%CI: 4.7 to 6.6). No significant differences in causes of death were observed comparing GCA patients to non-GCA subjects.
CONCLUSIONS:
This large population-based study of biopsy-proven GCA confirmed the lower incidence of GCA in Mediterranean countries and did not observe any increased mortality risk. This article is protected by copyright. All rights reserved.
2017
- Interleukin-6 and soluble interleukin-6 receptor are elevated in large-vessel vasculitis: a cross-sectional and longitudinal study
[Articolo su rivista]
Pulsatelli, Lia; Boiardi, Luigi; Assirelli, Elisa; Pazzola, Giulia; Muratore, Francesco; Addimanda, Olga; Dolzani, Paolo; Versari, Annibale; Casali, Massimiliano; Magnani, Luca; Pignotti, Elettra; Pipitone, Nicolò; Croci, Stefania; Meliconi, Riccardo; Salvarani, Carlo
abstract
To investigate serum levels of IL- 6 and soluble IL-6 receptor (sIL-6R) in patients with large-vessel vasculitis and their relationship with disease activity.
2017
- Is PET/CT essential in the diagnosis and follow-up of temporal arteritis?
[Articolo su rivista]
Salvarani, Carlo; Soriano, Alessandra; Muratore, Francesco; Shoenfeld, Yehuda; Blockmans, Daniel
abstract
The increasing availability and improvement of imaging techniques are deeply influencing diagnosis and work-up of patients affected with vasculitis, particularly those with large vessel vasculitis (LVV). Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), especially when integrated with computed tomography (CT), is taking hold as a useful diagnostic technique to examine the aorta and the other large vessels in giant cell arteritis (GCA) with concomitant large vessel involvement (LV-GCA). In this paper we examined the progresses performed in this field in the last twenty years and the evidence available so far according to two different points of view ('pros' and 'cons'), in order to give a comprehensive answer to a still open question about the role of PET/CT in the diagnosis and follow-up of GCA.
2017
- Long-term remission in biopsy proven giant cell arteritis: A retrospective cohort study
[Articolo su rivista]
Restuccia, Giovanna; Boiardi, Luigi; Cavazza, Alberto; Catanoso, Mariagrazia; Macchioni, Pierluigi; Muratore, Francesco; Soriano, Alessandra; Cimino, Luca; Aldigeri, Raffaella; Crescentini, Filippo; Pipitone, Nicolò; Salvarani, Carlo
abstract
OBJECTIVE: To evaluate the frequency of long-term remission after glucocorticoids (GCs) suspension in an Italian cohort of patients with biopsy-proven GCA and to identify factors that may predict long-term remission.
METHODS: We evaluated 131 patients with biopsy-proven transmural GCA diagnosed and followed up at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 18 months of follow-up. Long-term remission was defined as complete clinical remission without elevation of inflammatory markers for at least one year after the GC withdrawal.
RESULTS: 73 patients (56%) experienced long-term remission. Disease flares were less frequently observed in patients with long-term remission compared to those without (p = 0.002). The cumulative doses of prednisone at 1 year and for the entire followup duration were significantly lower (p < 0.0001 for both parameters) in patients with long-term remission; similarly, the duration of prednisone treatment was also significantly lower (p < 0.0001). The presence of PMR at diagnosis (HR 0.46) was significantly negatively associated with long-term remission (p = 0.008), while hemoglobin levels (HR 1.48) were significantly positively associated (p < 0.0001). Patients with long-term remission were able to reach 10 mg/day and 5 mg/day of prednisone sooner than the patients without (p = 0.02 and p < 0.0001, respectively).
CONCLUSION: In our cohort of GCA patients around half of the patients were able to attain long-term remission. Recognition of findings which predict disease course may aid decisions regarding therapy.
2017
- Multidisciplinary management of patients with coexisting inflammatory bowel disease and spondyloarthritis: A Delphi consensus among Italian experts
[Articolo su rivista]
Armuzzi, Alessandro; Felice, Carla; Lubrano, Ennio; Cantini, Fabrizio; Castiglione, Fabiana; Gionchetti, Paolo; Orlando, Ambrogio; Salvarani, Carlo; Scarpa, Raffaele; Marchesoni, Antonio; Vecchi, Maurizio; Olivieri, Ignazio
abstract
BACKGROUND:
Treatment of patients with coexisting spondyloarthritis (SpA) and inflammatory bowel disease (IBD) often requires multidisciplinary collaboration between gastroenterologists and rheumatologists.
AIM:
To describe the results of the first Delphi consensus to define shared therapeutic strategies for the best management of patients with coexisting SpA and IBD.
METHODS:
A scientific steering committee of 10 Italian experts in the field of SpA and IBD developed 27 statements on 5 possible clinical scenarios and selected 40 specialists from across Italy, both gastroenterologists and rheumatologists, to vote them using a Delphi method. Each participant expressed a level of agreement on each statement using a 5-point scale (1="absolutely disagree"; 5="absolutely agree"). Total cumulative agreement was defined as the sum of the percentage of responses to items 4 ("agree") and 5 ("absolutely agree"). Total cumulative agreement ≥70% defined consensus for each statement.
RESULTS:
After the first round, positive consensus was reached for 22 statements. Statements without consensus were discussed in a plenary session before the second vote. Positive consensus was then reached in all statements, with final total cumulative agreement ranging from 80% to 100%.
CONCLUSION:
This is the first Delphi consensus defining specific treatment algorithms for patients with coexisting SpA and IBD.
2017
- New insights into the pathogenesis of giant cell arteritis
[Articolo su rivista]
Ciccia, Francesco; Rizzo, Aroldo; Ferrante, Angelo; Guggino, Giuliana; Croci, Stefania; Cavazza, Alberto; Salvarani, Carlo; Triolo, Giovanni
abstract
Giant cell arteritis (GCA) is an inflammatory chronic disease occurring exclusively in elderly individuals. Until recently, the disease has been considered a unique disease resulting from the interaction in the walls of susceptible arteries, between an unknown infectious agents with local dendritic cells (DCs), activated CD4 T cells and effector macrophages. Recent evidence has shown that this view was too simplistic and has clarified many of the pathogenetic aspects of the disease. Many genetic studies recently published have identified different new genes, including cytokines, adhesion molecules and regulators of innate immunity, as crucial players in the development and progression of GCA. Recent evidence suggests that there is heterogeneity of histological lesions in GCA, that are correlated with different immunological Th9 and Th17 signature. The recent demonstration that Varicella-zoster virus (VZV) antigen is present in the 64% of GCA-negative TAs and in the 73% of GCA-positive TAs could represent an important point of arrival in the search for a causative agent in the pathogenesis of a metameric disease such as GCA. In this context, cytokines such as IL-32 and IL-33 that act as a danger signal following tissue damage and infection are over-expressed in GCA arteries. Artery tertiary lymphoid organs, present in up to 50% of GCA-positive arteries, could represent the sites were primary immune responses and T- and B-cell autoimmune responses against viral antigens are organized. The recently demonstrated disturbed distribution of B cells in GCA could be also relevant in the pathogenesis of the disease, possibly contributing to the enhanced IL-6 response. Altogether, these evidences may clarify many pathogenetic aspect of the disease, also suggesting complexity greater than first imagined.
2017
- Newly diagnosed vs. relapsing giant cell arteritis: Baseline data from the GiACTA trial
[Articolo su rivista]
Tuckwell, Katie; Collinson, Neil; Dimonaco, Sophie; Klearman, Micki; Blockmans, Daniel; Brouwer, Elisabeth; Cid, Maria C; Dasgupta, Bhaskar; Rech, Juergen; Salvarani, Carlo; Unizony, Sebastian H; Stone, John H.
abstract
To report entry criteria and clinical features of patients with newly diagnosed and relapsing giant cell arteritis (GCA) enrolled in a randomized trial of tocilizumab, an interleukin-6 receptor-alpha inhibitor.
2017
- No detection of varicella-zoster virus in temporal arteries of patients with giant cell arteritis
[Articolo su rivista]
Muratore, Francesco; Croci, Stefania; Tamagnini, Ione; Zerbini, Alessandro; Bellafiore, Salvatore; Belloni, Lucia; Boiardi, Luigi; Bisagni, Alessandra; Pipitone, Nicolò; Parmeggiani, Maria; Cavazza, Alberto; Salvarani, Carlo
abstract
OBJECTIVE:
Data on the presence of varicella-zoster virus (VZV) in temporal arteries of patients with giant cell arteritis (GCA) are controversial. We analyzed VZV infection in temporal arteries from Italian patients with temporal artery biopsy (TAB)-positive GCA, TAB-negative GCA, and controls.
METHODS:
A total of 79 formalin-fixed, paraffin-embedded (FFPE) TABs performed between 2009 and 2012 at a single institution from 34 TAB-positive GCA patients, 15 TAB-negative GCA patients, and 30 controls were retrieved. Six 5-μm sections of all FFPE TABs were cut. The first section was analyzed by immunohistochemistry using mouse monoclonal anti-VZVgE IgG1 antibody. DNA was extracted from the remaining five sections and analyzed by real-time polymerase chain reaction (PCR) for the presence of VZV DNA. For 10 of the 34 TAB-positive GCA patients, an additional 2-mm piece of frozen TAB was available. DNA was extracted from the entire 2-mm length frozen specimen and analyzed by PCR for the presence of VZV DNA. Thirty additional 5-μm sections were cut from the FFPE TABs of these 10 patients and analyzed by immunohistochemistry for the presence of VZV antigen.
RESULTS:
Immunohistochemical analysis detected VZV antigen in 1/34 (3%) TAB-positive GCA, 0/15 TAB-negative GCA, and 0/30 controls, and in none of the 300 sections cut from the 10 FFPE TABs positive for GCA for which the frozen specimens were available. DNA obtained from all TABs was amplifiable. VZV DNA was neither found in any of the FFPE TABs nor found in frozen TABs.
CONCLUSION:
Our data do not support in Italian patients a possible role for VZV infection in the etiopathogenesis of GCA.
2017
- Recommendations for the management of pulmonary fungal infections in patients with rheumatoid arthritis
[Articolo su rivista]
Galli, Massimo; Antinori, Spinello; Atzeni, Fabiola; Meroni, Luca; Riva, Agostino; Scirè, Carlo; Adorni, Fulvio; Quartuccio, Luca; Sebastiani, Marco; Airò, Paolo; Bazzichi, Laura; Cristini, Francesco; Del Bono, Valerio; Manfredi, Andreina; Viapiana, Ombretta; De Rosa, Francesco; Favalli, Ennio; Petrelli, Enzo; Salvarani, Carlo; Govoni, Marcello; Corcione, Silvia; Scrivo, Rossana; Sarmati, Loredana; Lazzarin, Adriano; Grassi, Walter; Mastroianni, Claudio; Gaeta, Giovanni Battista; Ferraccioli, Gianfranco; Cutolo, Maurizio; De Vita, Salvatore; Lapadula, Giovanni; Matucci-Cerinic, Marco; Armignacco, Orlando; Sarzi-Puttini, Piercarlo
abstract
Often life-threatening pulmonary fungal infections (PFIs) can occur in patients with rheumatoid arthritis (RA) receiving disease-modifying anti-rheumatic drugs (DMARDs). Most of the data concerning PFIs in RA patients come from case reports and retrospective case series. Of the ve most widely described PFIs, Pneumocystis jirovecii pneumonia (PJP) has rarely been seen outside Japan, pulmonary cryptococcosis has been diagnosed in only a small number of patients worldwide, pulmonary coccidioidomycosis has almost only been observed in endemic areas, the limited number of cases of pulmonary histoplasmosis have mainly occurred in the USA, and the rare cases of invasive pulmonary aspergillosis have only been encountered in leukopenic patients. Many aspects of the prophylaxis, diagnosis and treatment of PFIs in RA patients remain to be defined, as does the role of each DMARD in increasing the risk of infection, and the possibility of resuming biological and non-biological DMARD treatment after the infection has been cured. The recommendations for the management of PFIs described in this paper are the product of a consensus procedure promoted by the Italian group for the Study and Management of Infections in Patients with Rheumatic Diseases (the ISMIR group).
2017
- Recommendations for the use of biologics and other novel drugs in the treatment of psoriatic arthritis: 2017 update from the Italian Society of Rheumatology
[Articolo su rivista]
Marchesoni, Antonio; Olivieri, Ignazio; Salvarani, Carlo; Pipitone, Nicolò; D'Angelo, Salvatore; Mathieu, Alessandro; Cauli, Alberto; Punzi, Leonardo; Ramonda, Roberta; Scarpa, Raffaele; Maccarone, Mara; Lubrano, Ennio
abstract
OBJECTIVES:
To update the 2011 Italian Society of Rheumatology (SIR) recommendations for the use of biologics and other novel agents in the treatment of psoriatic arthritis (PsA).
METHODS:
To create this new set of recommendations, the SIR "Spondyloartritis and Psoriatic Arthritis study group - A. Spadaro" went through the following steps: literature search, identification of the items of interests for each of the four previously identified clinical domains of PsA and the different treatment phases, achievement of the consensus on all topics, and generation of the recommendations.
RESULTS:
An update on the available evidence on all of the biologics and new small molecules tested in PsA is reported, comprising the data for each of the individual articular manifestation. Indications for therapy inclusion criteria, choice of the drug, disease assessment, response definition, therapy failure management, and disease remission management for PsA peripheral joint arthritis, enthesitis, dactylitis, and spondylitis are provided. Suggestions for the treatment of patients with PsA and concomitant extra-articular manifestations are also given.
CONCLUSIONS:
These evidence-based recommendations may be used for guidance in the complex and fast-evolving field of the treatment of PsA.
2017
- Standard and biological treatment in large vessel vasculitis: guidelines and current approaches
[Articolo su rivista]
Muratore, Francesco; Pipitone, Nicolò; Salvarani, Carlo
abstract
Giant cell arteritis and Takayasu arteritis are the two major forms of idiopathic large vessel vasculitis. High doses of glucocorticoids are effective in inducing remission in both conditions, but relapses and recurrences are common, requiring prolonged glucocorticoid treatment with the risk of the related adverse events. Areas covered: In this article, we will review the standard and biological treatment strategies in large vessel vasculitis, and we will focus on the current approaches to these diseases. Expert commentary: The results of treatment trials with conventional immunosuppressive agents such as methotrexate, azathioprine, mycophenolate mofetil, and cyclophosphamide have overall been disappointing. TNF-α blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis. Observational evidence strongly supports the use of anti-TNF-α agents and tocilizumab in Takayasu patients with relapsing disease. However biological agents are not curative, and relapses remain common.
2017
- The role of ultrasound in the diagnosis and follow-up of large-vessel vasculitis: an update
[Articolo su rivista]
Germanò, Giuseppe; Monti, Sara; Ponte, Cristina; Possemato, Niccolo'; Caporali, Roberto; Salvarani, Carlo; Macchioni, Pierluigi; Pipitone, Nicolò
abstract
Large-vessel vasculitides comprise giant cell arteritis and Takayasu's arteritis. In both conditions, early changes consist of transmural inflammation of the arterial wall, while later complications include lumen changes, such as stenoses or aneurysms. Colour Doppler sonography has the ability to depict the arterial wall as well as the lumen, and is therefore ideally suited both to diagnose early vasculitis and to monitor patients over time. In this review article, we addressed the following issues: 1) the role of colour Doppler sonography in the diagnosis of large-vessel vasculitis and its common pitfalls; 2) whether colour Doppler sonography can increase the yield of temporal artery biopsy in giant cell arteritis; 3) the role of colour Doppler sonography in monitoring patients with LVV over time; and 4) how colour Doppler sonography performs compared to other imaging techniques.
2017
- Trial of Tocilizumab in Giant-Cell Arteritis
[Articolo su rivista]
Stone, John H; Tuckwell, Katie; Dimonaco, Sophie; Klearman, Micki; Aringer, Martin; Blockmans, Daniel; Brouwer, Elisabeth; Cid, Maria C; Dasgupta, Bhaskar; Rech, Juergen; Salvarani, Carlo; Schett, Georg; Schulze Koops, Hendrik; Spiera, Robert; Unizony, Sebastian H; Collinson, Neil
abstract
Giant-cell arteritis commonly relapses when glucocorticoids are tapered, and the prolonged use of glucocorticoids is associated with side effects. The effect of the interleukin-6 receptor alpha inhibitor tocilizumab on the rates of relapse during glucocorticoid tapering was studied in patients with giant-cell arteritis.
2017
- Visual loss and other cranial ischaemic complications in giant cell arteritis
[Articolo su rivista]
Soriano, Alessandra; Muratore, Francesco; Pipitone, Nicolò; Boiardi, Luigi; Cimino, Luca; Salvarani, Carlo
abstract
Giant cell arteritis (GCA) is the most common form of vasculitis in individuals aged 50 years and over. GCA typically affects large and medium-sized arteries, with a predilection for the extracranial branches of the carotid artery. Patients with GCA usually present with symptoms and signs that are directly related to the artery that is affected, with or without constitutional manifestations. The most dreaded complication of GCA is visual loss, which affects about one in six patients and is typically caused by arteritis of the ophthalmic branches of the internal carotid artery. Before the advent of glucocorticoid treatment, the prevalence of visual complications was high. Increasing awareness by physicians of the symptoms of GCA and advances in diagnostic techniques over the past twenty years have also contributed to a substantial decline in the frequency of permanent visual loss. Ischaemic brain lesions are less common than visual lesions, and mostly result from vasculitis of the extradural vertebral or carotid arteries. In the case of both the eye and the brain, ischaemic damage is thought to result from arterial stenosis or occlusion that occurs secondary to the inflammatory process. The inflammatory response at the onset of arteritis, its role as a predictor of complications and the role of traditional cardiovascular risk factors have been extensively investigated in the past decade. In this Review, the epidemiology, risk factors, clinical presentation and current therapeutic approach of GCA-related ischaemic events are discussed, with a particular emphasis on visual loss.
2016
- A Snapshot on the On-Label and Off-Label Use of the Interleukin-1 Inhibitors in Italy among Rheumatologists and Pediatric Rheumatologists: A Nationwide Multi-Center Retrospective Observational Study
[Articolo su rivista]
Vitale, Antonio; Insalaco, Antonella; Sfriso, Paolo; Lopalco, Giuseppe; Emmi, Giacomo; Cattalini, Marco; Manna, Raffaele; Cimaz, Rolando; Priori, Roberta; Talarico, Rosaria; Gentileschi, Stefano; de Marchi, Ginevra; Frassi, Micol; Gallizzi, Romina; Soriano, Alessandra; Alessio, Maria; Cammelli, Daniele; Maggio, Maria C; Marcolongo, Renzo; La Torre, Francesco; Fabiani, Claudia; Colafrancesco, Serena; Ricci, Francesca; Galozzi, Paola; Viapiana, Ombretta; Verrecchia, Elena; Pardeo, Manuela; Cerrito, Lucia; Cavallaro, Elena; Olivieri, Alma N; Paolazzi, Giuseppe; Vitiello, Gianfranco; Maier, Armin; Silvestri, Elena; Stagnaro, Chiara; Valesini, Guido; Mosca, Marta; de Vita, Salvatore; Tincani, Angela; Lapadula, Giovanni; Frediani, Bruno; De Benedetti, Fabrizio; Iannone, Florenzo; Punzi, Leonardo; Salvarani, Carlo; Galeazzi, Mauro; Rigante, Donato; Cantarini, Luca
abstract
Background: Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis. Objectives: To perform a nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults. Methods: We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016. Results: Five hundred and twenty-six treatment courses given to 475 patients (195 males, 280 females; 111 children and 364 adults) were evaluated. ANA was administered in 421 (80.04%) courses, CAN in 105 (19.96%). Sixty-two (32.1%) patients had been treated with both agents. IL-1 inhibitors were employed in 38 different indications (37 with ANA, 16 with CAN). Off-label use was more frequent for ANA than CAN (p < 0.0001). ANA was employed as first-line biologic approach in 323 (76.7%) cases, while CAN in 37 cases (35.2%). IL-1 inhibitors were associated with corticosteroids in 285 (54.18%) courses and disease modifying anti-rheumatic drugs (DMARDs) in 156 (29.65%). ANA dosage ranged from 30 to 200 mg/day (or 1.0-2.0 mg/kg/day) among adults and 2-4 mg/kg/day among children; regarding CAN, the most frequently used posologies were 150mg every 8 weeks, 150mg every 4 weeks and 150mg every 6 weeks. The frequency of failure was higher among patients treated with ANA at a dosage of 100 mg/day than those treated with 2 mg/kg/day (p = 0.03). Seventy-six patients (14.4%) reported an adverse event (AE) and 10 (1.9%) a severe AE. AEs occurred more frequently after the age of 65 compared to both children and patients aged between 16 and 65 (p = 0.003 and p = 0.03, respectively). Conclusions: IL-1 inhibitors are mostly used off-label, especially ANA, during adulthood. The high frequency of good clinical responses suggests that IL-1 inhibitors are used with awareness of pathogenetic mechanisms; adult healthcare physicians generally employ standard dosages, while pediatricians are more prone in using a weight-based posology. Dose adjustments and switching between different agents showed to be effective treatment strategies. Our data confirm the good safety profile of IL-1 inhibitors.
2016
- Adult primary central nervous system vasculitis
[Capitolo/Saggio]
Salvarani, C.; Brown, R. D.; Giannini, C.; Hunder, G. G.
abstract
Primary central nervous system vasculitis is an uncommon disorder of unknown cause that is limited to the brain and spinal cord. The median age of onset is 50 years. The neurological manifestations are diverse, but commonly include headache, altered cognition, focal weakness, or stroke. Serological markers of inflammation are usually normal. Cerebrospinal fluid is abnormal in approximately 80-90 % of the cases. The diagnosis is unlikely in the presence of a normal magnetic resonance imaging (MRI) of the brain. Biopsy of central nervous system tissue showing vasculitis is the only definitive test, however angiography has often been used for diagnosis even though it has only moderate sensitivity and specificity. The size of the vessels involved is varied and influences outcomes and response to treatment. Early recognition is important because treatment with corticosteroids, with or without cytotoxic drugs, may prevent serious outcomes. The differential diagnosis includes reversible cerebral vasoconstriction syndromes and secondary cerebral vasculitis.
2016
- Anti-TNF-α drugs differently affect the TNFa-sTNFR system and monocyte subsets in patients with psoriasis
[Articolo su rivista]
Gibellini, Lara; De Biasi, Sara; Bianchini, Elena; Bartolomeo, Regina; Fabiano, Antonella; Manfredini, Marco; Ferrar, Federica; Albertini, Giuseppe; Trenti, Tommaso; Nasi, Milena; Pinti, Marcello; Iannone, Anna; Salvarani, Carlo; Cossarizza, Andrea; Pellacani, Giovanni
abstract
TNF-a has a central role in the development and maintenance of psoriatic plaques, and its serum levels correlate with disease activity. Anti-TNF-a drugs are, however, ineffective in a relevant percentage of patients for reasons that are currently unknown. To understand whether the response to anti-TNF-a drugs is influenced by the production of anti-drug antibodies or by the modulation of the TNFa-TNFa receptor system, and to identify changes in monocyte phenotype and activity, we analysed 119 psoriatic patients who either responded or did not respond to different anti-TNF-a therapies (adalimumab, etanercept or infliximab), and measured plasma levels of TNF-a, TNF-a soluble receptors, drug and anti-drug antibodies. Moreover, we analyzed the production of TNF-a and TNF-α soluble receptors by peripheral blood mononuclear cells (PBMCs), and characterized different monocyte populations. We found that: i) the drug levels varied between responders and non-responders; ii) anti-infliximab antibodies were present in 15% of infliximab-treated patients, while anti-etanercept or anti-adalimumab antibodies were never detected; iii) plasma TNF-a levels were higher in patients treated with etanercept compared to patients treated with adalimumab or infliximab; iv) PBMCs from patients responding to adalimumab and etanercept produced more TNF-a and sTNFRII in vitro than patients responding to infliximab; v) PBMCs from patients not responding to infliximab produce higher levels of TNF-a and sTNFRII than patients responding to infliximab; vi) anti- TNF-a drugs significantly altered monocyte subsets. A complex remodelling of the TNFa-TNFa receptor system thus takes place in patients treated with anti-TNF-α drugs, that involves either the production of anti-drug antibodies or the modulation of monocyte phenotype or inflammatory activity.
2016
- Biotherapies in large vessel vasculitis
[Articolo su rivista]
Pazzola, G; Muratore, Francesco; Pipitone, N; Salvarani, Carlo
abstract
The mainstay of therapy of large vessel vasculitides (LVV) remains glucocorticoids (GC). Although most patients initially achieve disease remission, relapses and GC dependence are seen in more than two-thirds of cases. Conventional synthetic disease-modifying antirheumatic drugs (DMARDs) showed little or no steroid sparing effects, while biological agents represent a valid therapeutic option in patients with severe and/or relapsing LVV.
2016
- Cogan’s syndrome
[Capitolo/Saggio]
Cimino, L.; Fontana, L.; Salvarani, C.
abstract
Typical Cogan’s syndrome (CS) is a disease characterized by episodes of acute ocular inflammation, typically nonsyphilitic interstitial keratitis (IK) associated with vestibuloauditory dysfunction resembling Meniere-like attacks of vertigo, tinnitus, and loss of hearing, usually resulting in deafness within 1–3 months.
2016
- Complex interplay between neutral and adaptive evolution shaped differential genomic background and disease susceptibility along the Italian peninsula
[Articolo su rivista]
Sazzini, Marco; Gnecchi Ruscone, Guido Alberto; Giuliani, Cristina; Sarno, Stefania; Quagliariello, Andrea; De Fanti, Sara; Boattini, Alessio; Gentilini, Davide; Fiorito, Giovanni; Catanoso, Mariagrazia; Boiardi, Luigi; Croci, Stefania; Macchioni, Pierluigi; Mantovani, Vilma; Di Blasio, Anna Maria; Matullo, Giuseppe; Salvarani, Carlo; Franceschi, Claudio; Pettener, Davide; Garagnani, Paolo; Luiselli, Donata
abstract
The Italian peninsula has long represented a natural hub for human migrations across the Mediterranean area, being involved in several prehistoric and historical population movements. Coupled with a patchy environmental landscape entailing different ecological/cultural selective pressures, this might have produced peculiar patterns of population structure and local adaptations responsible for heterogeneous genomic background of present-day Italians. To disentangle this complex scenario, genome-wide data from 780 Italian individuals were generated and set into the context of European/Mediterranean genomic diversity by comparison with genotypes from 50 populations. To maximize possibility of pinpointing functional genomic regions that have played adaptive roles during Italian natural history, our survey included also ~250,000 exomic markers and ~20,000 coding/regulatory variants with well-established clinical relevance. This enabled fine-grained dissection of Italian population structure through the identification of clusters of genetically homogeneous provinces and of genomic regions underlying their local adaptations. Description of such patterns disclosed crucial implications for understanding differential susceptibility to some inflammatory/autoimmune disorders, coronary artery disease and type 2 diabetes of diverse Italian subpopulations, suggesting the evolutionary causes that made some of them particularly exposed to the metabolic and immune challenges imposed by dietary and lifestyle shifts that involved western societies in the last centuries.
2016
- Correlations between histopathological findings and clinical manifestations in biopsy-proven giant cell arteritis
[Articolo su rivista]
Muratore, Francesco; Boiardi, Luigi; Cavazza, Alberto; Aldigeri, Raffaella; Pipitone, Nicolò; Restuccia, Giovanna; Bellafiore, Salvatore; Cimino, Luca; Salvarani, Carlo
abstract
To correlate histopathological features of positive temporal artery biopsy (TAB) and clinical manifestations of the disease in a large single-center population-based cohort of patients with biopsy-proven giant cell arteritis (GCA).
METHODS:
A pathologist with expertise in vasculitis and blinded to clinical data and final diagnosis reviewed all TABs performed for suspected GCA at our hospital between January 1986 and December 2013. Histopathologic features evaluated were: the severity of inflammation and intimal hyperplasia, both graded on a semiquantitative scale (mild = 1, moderate = 2, severe = 3), the presence of intraluminal acute thrombosis, calcifications, giant cells, fibrinoid necrosis and laminar necrosis.
RESULTS:
274 patients had a final diagnosis of biopsy-proven GCA and were included in the study. Cranial ischemic events (CIEs) were observed in 161 (58.8%), visual manifestations in 79 (28.8%) and permanent (partial or complete) visual loss in 51 (18.6%) patients. Predictors for the development of CIEs were older age (OR = 1.057, 95% CI 1.019-1.097, p = 0.003), lower ESR values (OR = 0.990, 95% CI 0.981-0.999, p = 0.026) as well as the presence of giant cells (OR = 1.848, 95% CI 1.045-3.269, p = 0.035) and laminar necrosis at TAB (OR = 2.334, 95% CI 1.187-4.587, p = 0.014). Predictors for the development of permanent visual loss were lower CRP values (OR = 0.906, 95% CI 0.827-0.992, p = 0.033) and the presence of calcifications at TAB (OR = 3.672, 95% CI 1.479-9.121, p = 0.005). Fibrinoid necrosis was not observed in any of the TABs evaluated.
CONCLUSION:
Pathological features of TAB may predict some manifestations of GCA. These findings may have implications for patients' management.
2016
- Current approach to the management of psoriatic arthritis according to a sample of Italian rheumatologists
[Articolo su rivista]
Marchesoni, Antonio; Lubrano, Ennio; Manara, Maria; Ramonda, Roberta; Salvarani, Carlo; Olivieri, Ignazio
abstract
OBJECTIVES:
The purpose of this study was to have an overview of the current approach to psoriatic arthritis (PsA) by a group of Italian rheumatologists.
METHODS:
Rheumatologists from all around Italy were asked to participate in a survey to give their opinion on a number of statements made by a panel of rheumatologists who are experts in PsA. The survey was conducted through two rounds using a Delphi-like method. The two rounds yielded a consensus on the management of PsA.
RESULTS:
Fifty rheumatologist from 50 rheumatology centres participated in the survey. Of the 117 proposed statements, only 10 did not reach the 66% concordance threshold. The main results of the survey were that diagnosis of PsA should be made using both the CASPAR criteria and clinical judgment, that all of the features of the psoriatic disease are relevant in the assessment and therapy of PsA, that treatment recommendations are taken into account, that all of the available biological agents may be used in bio-naïve patients, that anti-drug antibody testing is still not used in daily practice, that both switching or swapping are useful options in the case of bio-failure because of lack or loss of efficacy, and that swapping is considered the best choice in the case of bio-failure due to adverse events.
CONCLUSIONS:
The results of this survey showed that a comprehensive evaluation of the patient and a therapy choice based on both patient clinical features and evidence of drug efficacy and safety are considered the current best of care for PsA patients.
2016
- Do dermatomyositis and polymyositis affect similar thigh muscles? A comparative MRI-based study
[Articolo su rivista]
Pipitone, Nicolo; Notarnicola, Antonella; Levrini, Gabriele; Spaggiari, Lucia; Scardapane, Arnaldo; Iannone, Florenzo; Lapadula, Giovanni; Pattacini, Pierpaolo; Zuccoli, Giulio; Salvarani, Carlo
abstract
OBJECTIVES: Dermatomyositis (DM) and polymyositis (PM) commonly cause weakness of the thigh muscles. However, it is debated whether DM and PM affect similar thigh muscles. Muscle oedema on fat-suppressed MRI sequences is thought to represent active inflammation. In this study, we aimed to assess which thigh muscle groups are preferentially inflamed in DM and PM, respectively, using short-tau inversion-recovery MRI sequences.
METHODS: We analysed 71 patients from 2 Rheumatology centres, 31 with DM and 40 with PM diagnosed according to the Bohan and Peter criteria. MRI oedema (1=present, 0=absent) was assessed bilaterally on fat-suppressed sequences in 17 pelvic floor and thigh muscles. An MRI oedema score (range 0-17) was calculated by adding the separate scores bilaterally and dividing them by two. Inter-rater variability was assessed by intraclass correlation coefficient. Fisher's exact test was used to compare binomial data.
RESULTS: Age and gender ratio were similar in patients with DM and PM. Disease duration (months, mean±SD) was shorter (20±31) in DM than in PM (53±69) (p=0.02). The intraclass correlation coefficient between the radiologists involved was 0.78. Muscle oedema was more common in DM than in PM except in the posterior thigh muscles. In particular, 68% of patients with DM had involvement of at least one anterior thigh muscle versus 38% of patients with PM (p=0.02).
CONCLUSIONS: Compared with PM, DM affects more thigh muscles, except those of the posterior compartment, which are equally involved in both disorders. These findings may be useful to target physiotherapy at the more frequently affected muscles.
2016
- Evidence-based algorithm for diagnosis and assessment in psoriatic arthritis: results by Italian DElphi in psoriatic Arthritis (IDEA)
[Articolo su rivista]
Lapadula, G; Marchesoni, A; Salaffi, F; Ramonda, R; Salvarani, Carlo; Punzi, L; Costa, L; Caso, F; Simone, D; Baiocchi, G; Scioscia, C; Di Carlo, M; Scarpa, R; Ferraccioli, G.
abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disease involving skin, peripheral joints, entheses, and axial skeleton. The disease is frequently associated with extrarticular manifestations (EAMs) and comorbidities. In order to create a protocol for PsA diagnosis and global assessment of patients with an algorithm based on anamnestic, clinical, laboratory and imaging procedures, we established a DElphi study on a national scale, named Italian DElphi in psoriatic Arthritis (IDEA). After a literature search, a Delphi poll, involving 52 rheumatologists, was performed. On the basis of the literature search, 202 potential items were identified. The steering committee planned at least two Delphi rounds. In the first Delphi round, the experts judged each of the 202 items using a score ranging from 1 to 9 based on its increasing clinical relevance. The questions posed to experts were How relevant is this procedure/observation/sign/symptom for assessment of a psoriatic arthritis patient? Proposals of additional items, not included in the questionnaire, were also encouraged. The results of the poll were discussed by the Steering Committee, which evaluated the necessity for removing selected procedures or adding additional ones, according to criteria of clinical appropriateness and sustainability. A total of 43 recommended diagnosis and assessment procedures, recognized as items, were derived by combination of the Delphi survey and two National Expert Meetings, and grouped in different areas. Favourable opinion was reached in 100% of cases for several aspects covering the following areas: medical (familial and personal) history, physical evaluation, imaging tool, second level laboratory tests, disease activity measurement and extrarticular manifestations. After performing PsA diagnosis, identification of specific disease activity scores and clinimetric approaches were suggested for assessing the different clinical subsets. Further, results showed the need for investigation on the presence of several EAMs and risk factors. In the context of any area, a rank was assigned for each item by Expert Committee members, in order to create the logical sequence of the algorithm. The final list of recommended diagnosis and assessment procedures, by the Delphi survey and the two National Expert Meetings, was also reported as an algorithm. This study shows results obtained by the combination of a DElphi survey of a group of Italian rheumatologists and two National Expert Meetings, created with the aim of establishing a clinical procedure and algorithm for the diagnosis and the assessment of PsA patients. In order to find accurate and practical diagnostic and assessment items in clinical practice, we have focused our attention on evaluating the different PsA domains. Hence, we conceived the IDEA algorithm in order to address PsA diagnosis and assessment in the context of daily clinical practice. The IDEA algorithm might eventually lead to a multidimensional approach and could represent a useful and practical tool for addressing diagnosis and for assessing the disease appropriately. However, the elaborated algorithm needs to be further investigated in daily practice, for evidencing and proving its eventual efficacy in detecting and staging PsA and its heterogeneous spectrum appropriately.
2016
- Extra-articular rheumatoid arthritis imaged by [18F]FDG-PET/CT
[Articolo su rivista]
Sollini, Martina; Muratore, Francesco; Roncali, Massimo; Erba, Paola Anna; Salvarani, Carlo; Versari, Annibale
abstract
Extra-articular rheumatoid arthritis imaged by [18F]FDG-PET/CT
2016
- Flares in Biopsy-Proven Giant Cell Arteritis in Northern Italy: Characteristics and Predictors in a Long-Term Follow-Up Study
[Articolo su rivista]
Restuccia, Giovanna; Boiardi, Luigi; Cavazza, Alberto; Catanoso, Mariagrazia; Macchioni, Pierluigi; Muratore, Francesco; Cimino, Luca; Aldigeri, Raffaella; Crescentini, Filippo; Pipitone, Nicolò; Salvarani, Carlo
abstract
This study evaluated the frequency, timing, and characteristics of flares in a large cohort of Italian patients with biopsy-proven giant cell arteritis (GCA) and to identify factors at diagnosis able to predict the occurrence of flares. We evaluated 157 patients with biopsy-proven transmural GCA diagnosed and followed at the Rheumatology Unit of Reggio Emilia Hospital (Italy) for whom sufficient information was available from the time of diagnosis until at least 4 years of follow-up. Fifty-seven patients (36.5%) experienced ≥1 flares. Fifty-one (46.4%) of the 110 total flares (88 relapses and 22 recurrences) were experienced during the first 2 years after diagnosis. The majority of relapses occurred with doses of prednisone ≤ 10 mg/day (82.9%), whereas only 3.4% of relapses occurred for doses ≥ 25 mg/day. Polymyalgia rheumatica (46.5%) and cranial symptoms (41.9%) were the most frequent manifestations at the time of the first relapse. Cumulative prednisone dose during the first year and total cumulative prednisone dose were significantly higher in flaring patients compared with those without flares (7.8 ± 2.4 vs 6.7 ± 2.4 g, P = 0.02; 15.5 ± 8.9 vs 10.0 ± 9.2 g, P = 0.0001, respectively). The total duration of prednisone treatment was longer in flaring patients (58 ± 44 vs 30 ± 30 months, P = 0.0001).Patients with disease flares had at diagnosis more frequently systemic manifestations (P = 0.02) and fever ≥ 38°C (P = 0.02), significantly lower hemoglobin levels (P = 0.05), more frequent presence at temporal artery biopsy (TAB) specimens of giant cells (P = 0.04) and intraluminal acute thrombosis (P = 0.007), and more moderate/severe arterial inflammation (P = 0.009) compared with those without flares. In the multivariate model fever ≥ 38 °C (hazard ratio 2.14; 95% confidence interval, 1.06-4.32, P = 0.03) and the severity of inflammatory infiltrate (moderate/severe versus mild) (hazard ratio 5.41; 95% confidence interval, 1.64-17.87, P = 0.006) were significantly associated with an increased risk of flares. In conclusion, a flaring course is common in GCA and it is associated with prolonged GC requirements. Fever at diagnosis and severity of inflammation at TAB appear to predict the development of disease flares.
2016
- Histopathologic Findings of Patients With Biopsy-Negative Giant Cell Arteritis Compared to Those Without Arteritis: A Population-Based Study
[Articolo su rivista]
Muratore, Francesco; Cavazza, Alberto; Boiardi, Luigi; Lo Gullo, Alberto; Pipitone, Nicolò; Germanò, Giuseppe; Bisagni, Alessandra; Cimino, Luca; Salvarani, Carlo
abstract
To evaluate whether there are histopathologic features of negative temporal artery biopsy (TAB) that allow differentiation between patients with giant cell arteritis (GCA) and those without.
METHODS:
All consecutive patients with negative TAB seen between January 2009 and December 2012 were selected retrospectively. Demographic, clinical, and laboratory data at presentation and at each followup visit were collected. A pathologist with expertise in vasculitis and blinded to clinical data and final diagnosis reviewed all negative TABs. Histopathologic features evaluated were the presence of a focal mediointimal scar, medial attenuation, intimal hyperplasia, fragmentation of inner elastic lamina, calcification, adventitial fibrosis, and neoangiogenesis.
RESULTS:
After a median (interquartile range [IQR]) followup period of, respectively, 19 months (9.2-31.2) and 26.3 months (4.9-36.7) (P = 0.041), 38 (55%) of 69 patients had a final diagnosis of TAB-negative GCA, while in the remaining 31 (45%) of 69 patients GCA was excluded. The American College of Rheumatology classification criteria for GCA were satisfied by 31 (81.6%) of 38 patients and 2 (6.5%) of 31 patients (P < 0.0001). Compared to non-GCA patients, those with TAB-negative GCA had more frequent cranial manifestations and higher erythrocyte sedimentation rates and C-reactive protein levels. The frequency of patients receiving prednisone, the mean dose, and the duration of prednisone treatment at TAB were similar in the 2 groups. There were no significant differences between TAB-negative GCA and non-GCA patients in the frequencies of all the histologic features evaluated.
CONCLUSION:
The histologic features of negative TABs evaluated in this study do not allow for the differentiation between GCA and non-GCA patients. In the absence of an inflammatory infiltrate, other histologic changes of the temporal artery wall are not specific for GCA.
2016
- IgG4-Related Sacroiliitis
[Articolo su rivista]
Possemato, N; Crescentini, F; Pazzola, G; Ragazzi, M; Salvarani, Carlo
abstract
To report a case of IgG4-related sacroiliitis.
2016
- Imaging Findings of Cerebral Amyloid Angiopathy, Aβ-Related Angiitis (ABRA), and Cerebral Amyloid Angiopathy-Related Inflammation: A Single-Institution 25-Year Experience
[Articolo su rivista]
Salvarani, Carlo; Morris, Jonathan M; Giannini, Caterina; Brown, Robert D; Christianson, Teresa; Hunder, Gene G.
abstract
Vascular inflammation is present in a subset of patients with cerebral amyloid angiopathy (CAA) and has a major influence in determining the disease manifestations. Radiological characterization of this subset is particularly important to achieve early recognition and treatment. We conducted this study to investigate the role of imaging in differentiating CAA with and without inflammation. We reviewed neuroimaging findings for 54 patients seen at Mayo Clinic over 25 years with pathological evidence of CAA and with available neuroimaging at the time of diagnosis. Clinical data were also recorded. Patients were grouped into CAA alone (no vascular inflammation), Aβ-related angiitis or ABRA (angiodestructive inflammation), and CAA-related inflammation or CAA-RI (perivascular inflammation). Imaging findings at presentation were compared among patient subgroups. Radiological features supporting a diagnosis of ABRA or CAA-RI were identified. Radiologic findings at diagnosis were available in 27 patients with CAA without inflammation, 22 with ABRA, and 5 with CAA-RI. On MRI, leptomeningeal disease alone or with infiltrative white matter was significantly more frequent at presentation in patients with ABRA or CAA-RI compared with those with CAA (29.6% vs. 3.7%, P = 0.02; and 40.7% vs. 3.7%, P = 0.002, respectively), whereas lobar hemorrhage was more frequent in patients with CAA (62.3% vs. 7.4%, P = 0.0001). Overall, leptomeningeal involvement at presentation was present in 70.4% of patients with ABRA or CAA-RI and in only 7.4% of patients with CAA (P = 0.0001). The sensitivity and specificity of leptomeningeal enhancement to identify patients with ABRA or CAA-RI were 70.4% and 92.6%, respectively, whereas the positive likelihood ratio (LR) was 9.5. The sensitivity and specificity of intracerebral hemorrhage to identify patients with CAA were 62.9% and 92.6%, respectively, whereas the positive LR was 8.5. Microbleeds were found in 70.4% of patients with inflammatory CAA at presentation. In conclusion, leptomeningeal enhancement and lobar hemorrhage at presentation may enable differentiation between CAA with and without inflammation. The identification at initial MRI of diffuse cortical-subcortical microbleeds in elderly patients presenting with infiltrative white matter process or prominent leptomeningeal enhancement is highly suggestive of vascular inflammatory CAA.
2016
- Imaging of vasculitis: State of the art
[Articolo su rivista]
Muratore, Francesco; Pipitone, Nicolò; Salvarani, Carlo; Schmidt, Wolfgang A.
abstract
The increasing availability and improvement of imaging techniques are making a profound impact in the evaluation and management of patients with vasculitis, particularly for those with large vessel vasculitis, and will most likely play an ever more important role in the future. Deep, large vessels can be examined by CT or MRI, while ultrasound is the method of choice for the evaluation of superficial vessels (such as temporal, carotid, and axillary arteries). PET is very sensitive in detecting large vessel inflammation, but it does not delineate the vessel wall. Imaging studies can also be used to monitor the disease course and the development of late vascular complication. This review will focus on the role of imaging studies in diagnosing and monitoring LVV, but will also mention their principal applications in medium and small-sized vessel vasculitis. Indications and limitations of the available imaging modalities will be discussed as well.
2016
- Impact of training on concordance among rheumatologists and dermatologists in the assessment of patients with psoriasis and psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Girolomoni, Giampiero; Di Lernia, Vito; Gisondi, Paolo; Tripepi, Giovanni; Egan, Colin Gerard; Marchesoni, Antonio
abstract
OBJECTIVE: To evaluate the impact of training on the reliability among dermatologists and rheumatologists in the assessment of psoriatic arthritis (PsA) patients.
METHODS: Overall, 9 hospital-based rheumatologists and 8 hospital-based dermatologists met in Reggio Emilia, Italy on October 2015 to assess 17 PsA patients. After 1 month, physicians underwent a 3-h training session by 4 recognized experts and then assessed 19 different PsA patients according to a modified Latin square design. Measures included tender (TJC) and swollen joint count (SJC), dactylitis, enthesitis, Schober test, psoriasis body surface area (BSA), Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), and static physician's global assessment of PsA disease activity (sPGA). Variance components analyses were performed to estimate the intraclass correlation coefficient (ICC).
RESULTS: TJC and enthesitis-measured pre-training by dermatologists or rheumatologists revealed moderate-substantial agreement (ICC: 0.4-0.8). In contrast, SJC and Schober test showed fair (ICC: 0.2-0.4) and moderate agreement, respectively (ICC: 0.4-0.6), while poor agreement (ICC: 0-0.2) was represented by dactylitis. Moderate-substantial (ICC: 0.4-0.8) agreement was observed for most skin measures by dermatologists and rheumatologists, apart from BSA, where fair agreement (ICC: 0.2-0.4) was observed. Agreement levels were similar before and after training for arthritis measures. In contrast, levels of agreement after training for 3 of the 4 skin measures were increased for dermatologists and all 4 skin measures were increased for rheumatologists.
CONCLUSIONS: Substantial to excellent agreement was observed for TJC, enthesitis, PASI, and sPGA. Rheumatologists benefited from training to a greater extent.
2016
- Latent tuberculosis infection detection and active tuberculosis prevention in patients receiving anti-TNF therapy: an Italian nationwide survey
[Articolo su rivista]
Cantini, Fabrizio; Lubrano, Ennio; Marchesoni, Antonio; Mathieu, Alessandro; Olivieri, Ignazio; Salvarani, Carlo; Scarpa, Raffaele; Spadaro, Antonio
abstract
AIMS: Primary: to investigate Italian rheumatology practice regarding latent
tubercular infection (LTBI) detection and tuberculosis (TB) prevention in
patients requiring anti-tumor necrosis factor (anti-TNF) therapy. Secondary: to
assess the overall number of TB cases over 10 years and their distribution by
drug.
METHODS: An anonymous, 24 multiple-response questionnaire was completed by
393/449 (87.5%) rheumatologists prescribing anti-TNF therapy. Six questions
provided setting information, and 18 the compliance with recommendations and the
recorded TB cases.
RESULTS: The Italian recommendations were used by 323 (82%) and other sets by 60
(15%). TB specialists were always consulted by 81 (21%) and occasionally by 73
(19%). LTBI screening was made using chest radiograph (CR) by 5%, tuburculin skin
test (TST) by 5.3%, CR + TST by 35.6%, interferon-gamma release assay (IGRA) by
7.4%, CR + IGRAs by 26% and CR + TST + IGRA by 20.6%. Isoniazid was initiated in
the presence of positivity of TST by 97 (24.7%), TST + IGRA by 101 (25.7%) and
IGRA by 195 (49.6%). Anti-TNF starting delay was 1 month in 63.1% of the cases,
3 months in 27.7%, concomitantly in 5.6%. Overall, 317 TB reactivation cases
occurred in 39 353 patients, with an incidence rate of 80.5 cases/100 000/year
(10 times higher than in the Italian general population). TB occurred during TB
prophylaxis in 192 (60.6%). TB cases incidence rate divided by drug was:
etanercept (ETN) 51 (16%), 28/100 000/year, adalimumab (ADA) 98 (31%),
89/100 000/year, infliximab (IFX) 137 (43.2%), 211/100 000/year, with a
significantly lower frequency in the ETN group compared to ADA and IFX groups
(χ(2) = P < 0.001).
CONCLUSION: Italian rheumatologists are highly aware of anti-TNF-related TB risk
with variable LTBI screening and TB prevention strategies. TB outcome was
significantly lower in the ETN group.
2016
- Long-term costs and outcomes in psoriatic arthritis patients not responding to conventional therapy treated with tumour necrosis factor inhibitors: the extension of the Psoriatic Arthritis Cost Evaluation (PACE) study
[Articolo su rivista]
Olivieri, Ignazio; Cortesi, Paolo A; de Portu, Simona; Salvarani, Carlo; Cauli, Alberto; Lubrano, Ennio; Spadaro, Antonio; Cantini, Fabrizio; Ciampichini, Roberta; Cutro, Maria Stefania; Mathieu, Alessandro; Matucci Cerinic, Marco; Punzi, Leonardo; Scarpa, Raffaele; Mantovani, Lorenzo G.
abstract
Poor information on long-term outcomes and costs on tumour necrosis factor (TNF) inhibitors in psoriatic arthritis (PsA) are available. Our aim was to evaluate long-term costs and benefits of TNF- inhibitors in PsA patients with inadequate response to conventional treatment with traditional disease-modifying anti-rheumatic drugs (tDMARDs).
METHODS:
Fifty-five out of 107 enrolled patients included in the study at one year, completed the 5-year follow-up period. These patients were enrolled in 8 of 9 centres included in the study at one year. Patients aged older than 18 years, with different forms of PsA and failure or intolerance to tDMARDs therapy were treated with anti-TNF agents. Information on resource use, health-related quality of life (HRQoL), disease activity, function and laboratory values were collected at baseline and through the 5 years of therapy. Costs (expressed in Euro 2011) and utility (measured by EQ-5D instrument) before TNF inhibitor therapy and after 1 and 5 years were compared.
RESULTS:
The majority of patients (46 out of 55; 83.6%) had a predominant or exclusive peripheral arthritis and 16.4% had predominant or exclusive axial involvement. There was a statistically significant improvement of the most important clinical variables after 1 year of follow-up. These improvements were maintained also after 5 years. The direct costs increased by approximately €800 per patient-month after 1 year, the indirect costs decreased by €100 and the overall costs increased by more than €700 per patient-month due to the cost of TNF inhibitor therapy. Costs at 5 year were similar to the costs at 1 year. The HRQoL parameters showed the same trends of the clinical variables. EQ-5D VAS, EQ-5D utility and SF-36 PCS score showed a significant improvement after 1 year, maintained at 5 years. SF-36 MCS showed an improvement only at 5 years.
CONCLUSIONS:
The results of our study suggest that TNF blockers have long-term efficacy. The higher cost of TNF inhibitor therapy was balanced by a significant improvement of HRQoL, stable at 5 years of follow-up. Our results need to be confirmed in larger samples of patients.
2016
- Management of primary and secondary central nervous system vasculitis
[Articolo su rivista]
Salvarani, Carlo; Pipitone, Nicolò; Hunder, Gene G.
abstract
This article summarizes the current evidence on the management of primary and secondary central nervous system (CNS) vasculitis. RECENT FINDINGS:
Two recent retrospective cohort studies have described the treatment and outcomes of patients with adult primary central nervous system vasculitis (PCNSV). Although the majority of the patients (>60%) responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide (CYC) and tended to improve during the follow-up period, an overall increased mortality was observed. The treatment response and the outcomes appeared primarily related to the size of the vessels involved in the inflammatory process. The involvement of small cortical/leptomeningeal vessels was associated with a more benign course, whereas the involvement of larger/proximal cerebral vessels was related to a less favorable prognosis and identified cases that should be treated more aggressively. Glucocorticoids combined with CYC are the mainstay of therapy for secondary CNS vasculitis. Observational studies have documented the efficacy of rituximab as induction therapy in patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV) and CNS disease, while the role of antitumor necrosis factor (TNF) agents is more controversial. Case series have demonstrated the efficacy of anti-TNF agents in patients with neuro-Behçet's disease. Tocilizumab may also be effective in this condition.
SUMMARY:
Recognition of findings at diagnosis that predict the course or outcomes of PCNSV may serve as guide for therapy. Biological agents may provide benefit to difficult-to-treat patients with CNS involvement secondary to AAV and Behçet's disease.
2016
- MicroRNA markers of inflammation and remodelling in temporal arteries from patients with giant cell arteritis
[Articolo su rivista]
Croci, Stefania; Zerbini, Alessandro; Boiardi, Luigi; Muratore, Francesco; Bisagni, Alessandra; Nicoli, Davide; Farnetti, Enrico; Pazzola, Giulia; Cimino, Luca; Moramarco, Antonio; Cavazza, Alberto; Casali, Bruno; Parmeggiani, Maria; Salvarani, Carlo
abstract
OBJECTIVES: There is increasing evidence that microRNAs (miRNAs) are deregulated
in autoimmune and cardiovascular diseases. The present study aimed to identify if
miRNAs are deregulated in giant cell arteritis (GCA), a vasculitis affecting
large-sized and medium-sized arteries, and to determine if miRNA levels might
allow to discriminate between patients with GCA and those without.
METHODS: 58 patients who had temporal artery biopsy (TAB) for suspected GCA were
included in the study and divided into three groups: patients with TAB-positive
GCA showing a transmural inflammation (n=27), patients with TAB-negative GCA
(n=8) and TAB-negative non-GCA patients with a final diagnosis different from GCA
(n=23). To identify candidate miRNAs deregulated in GCA, we profiled the
expression of 1209 miRNAs in inflamed TABs and normal TABs. Selected miRNAs were
then validated by real-time PCRs and in situ hybridisation (ISH).
RESULTS: MiR-146b-5p, -146a, -155, -150, -21 and -299-5p were significantly more
expressed in inflamed TABs from patients with GCA. miRNAs were mainly deregulated
at the tissue level because peripheral blood mononuclear cells and
polymorphonuclear cells from the three groups of patients and age-matched healthy
controls had similar levels of miRNAs. ISH showed that miR-21 was mainly
expressed by cells in the medial and intimal layers of inflamed TABs. Patients
with TAB-negative GCA had a miRNA profile similar to TAB-negative non-GCA
patients.
CONCLUSIONS: MiR-146b-5p, -146a, -21, -150, -155, -299-5p are overexpressed in
the presence of inflammation in TABs from patients with GCA.
2016
- Occasional detection of thymic epithelial tumor 4 years after diagnosis of adult onset Still disease: A challenging case report and immuno-oncological considerations coming from pertinent literature review
[Articolo su rivista]
Lococo, Filippo; Bajocchi, Gianluigi; Caruso, Andrea; Valli, Riccardo; Ricchetti, Tommaso; Sgarbi, Giorgio; Salvarani, Carlo
abstract
BACKGROUND: Thymoma is a T cell neoplasm arising from the thymic epithelium that
due to its immunological role, frequently undercover derangements of immunity
such a tumors and autoimmune diseases.
METHODS: Herein, we report, to the best of our knowledge, the first description
of an association between thymoma and adult onset Still disease (AOSD) in a
47-year-old man. The first one was occasionally detected 4 years later the
diagnosis of AOSD, and surgically removed via right lateral thoracotomy.
Histology confirmed an encapsulated thymic tumor (type AB sec.
WHO-classification).
RESULTS: The AOSD was particularly resistant to the therapy, requiring a
combination of immunosuppressant followed by anti-IL1R, that was the only
steroids-sparing treatment capable to induce and maintain the remission. The
differential diagnosis was particularly challenging because of the severe
myasthenic-like symptoms that, with normal laboratory tests, were initially
misinterpreted as fibromyalgia. The pathogenic link of this association could be
a thymus escape of autoreactive T lymphocytes causing autoimmunity.
CONCLUSION: Clinicians should be always include the possibility of a thymoma in
the differential diagnosis of an unusual new onset of weakness and normal
laboratories data, in particular once autoimmune disease is present in the
medical history.
2016
- Polyarteritis nodosa
[Capitolo/Saggio]
Pipitone, N.; Salvarani, C.
abstract
Polyarteritis nodosa (PAN) is a rare vasculitis affecting middle-sized arteries. Its annual incidence in Europe is estimated to range between 0 and 1.6 cases per million, while the prevalence is about 31 cases per million. The frequency of hepatitis B virus (HBV)-related PAN has declined in developed countries since vaccination against HBV has been implemented. Specifically, before vaccination against HBV was implemented on a large scale, more than one-third of adults with PAN were infected by HBV, whereas currently only 5 % of European adults with PAN are infected by HBV. PAN is usually considered an immune-complex-driven vasculitis. However, the evidence of abundant CD4+ T cells in vascular inflammatory infiltrates suggests that PAN may also be induced by a T-cell response. Clinically, PAN usually presents with constitutional manifestations as well as symptoms and signs related to the organs affected. Organ ischemia is thought to be due to vascular stenoses, while ruptured aneurysms can result in tissue hemorrhage. The most frequent clinical features include constitutional manifestations, myalgia, arthralgia, peripheral neuropathy and mononeuritis multiplex. There are no specific blood tests to diagnose PAN, but inflammatory markers are typically elevated. Therefore, the diagnosis rests on histological changes in affected organs, showing a transmural vessel wall infiltrate, or angiographic findings, including small saccular or fusiform aneurysms and stenoses. Treatment includes glucocorticoids in patients without poor prognostic factors or cyclophosphamide if the disease is life- or organ-threatening.
2016
- Predictors of Loss of Remission and Disease Flares in Patients with Axial Spondyloarthritis Receiving Antitumor Necrosis Factor Treatment: A Retrospective Study
[Articolo su rivista]
Lubrano, Ennio; Massimo Perrotta, Fabio; Manara, Maria; D'Angelo, Salvatore; Addimanda, Olga; Ramonda, Roberta; Punzi, Leonardo; Olivieri, Ignazio; Salvarani, Carlo; Marchesoni, Antonio
abstract
The aim of this study was to evaluate rate and predictive factors of loss of remission and disease flare in patients with axial spondyloarthritis (axSpA) receiving antitumor necrosis factor (anti-TNF) treatment.
METHODS:
In this retrospective multicenter study, patients with axSpA, according to the Assessment of Spondyloarthritis international Society (ASAS) criteria, treated with adalimumab, etanercept, or infliximab with a minimum followup of 12 months and satisfying the ASAS partial remission criteria and/or Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were studied. Disease flare was defined as a Bath Ankylosing Spondylitis Disease Activity Index score > 4.5 or ASDAS score > 2.5 on at least 1 occasion.
RESULTS:
One hundred seventy-four patients with axSpA were studied. After a median [interquartile range (IQR)] followup of 4 years (2-6), 37 patients (21.2%) experienced a loss of remission and 28 (16.1% of the whole study group) a disease flare. Median (IQR) duration of remission in patients who lost this status was 1 year (0.625-2). Higher median erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values, continuous nonsteroidal antiinflammatory drug (NSAID) use, and an ASDAS-CRP ≥ 0.8 during the remission period were significantly associated with both loss of remission and disease flare. At the multivariate analysis, continuous NSAID intake (OR 4.05, 95% CI 1.4-11.74, p = 0.010) and ESR > 15 (OR 2.90, 95% CI 1.23-6.82, p = 0.015) were the only factors predictive of disease reactivation.
CONCLUSION:
In this study, loss of remission and disease flares occurred, respectively, in about 21% and 16% of the patients with axSpA who achieved a state of remission while receiving anti-TNF therapy. Residual disease activity was associated with disease reactivation.
2016
- Recent advances in the diagnosis and treatment of polymyalgia rheumatica
[Articolo su rivista]
Muratore, Francesco; Pazzola, Giulia; Pipitone, Nicolò; Salvarani, Carlo
abstract
Polymyalgia rheumatica is one of the most common rheumatic inflammatory disorders in people older than 50 years characterized by aching and prolonged morning stiffness in the shoulder and pelvic girdle and neck.. Areas covered: In this review, we will focus on recent advances on the diagnosis and management of PMR. Expert commentary: Controversy exist whether PMR represent a single entity disease or is an umbrella term that comprises a clinical presentation common to a range of related conditions (polymyalgic syndrome). To date there are no specific diagnostic tests, and the diagnosis remains clinical, although ultrasonography, positron emission tomography scan and the recent ACR/EULAR classification criteria may help to confirm the clinical diagnosis. A step-wise process for the diagnosis of PMR has been proposed. Low-dose steroids are highly effective in the majority of patients and remain the mainstay of treatment, but relapses occur in about 50% of patients and glucocorticoid related adverse event are common. The steroid sparing effects of the immunosuppressive treatment evaluated to date are unclear.
2016
- Venous Thromboembolism and Cerebrovascular Events in Patients with Giant Cell Arteritis: A Population-Based Retrospective Cohort Study
[Articolo su rivista]
Lo Gullo, Alberto; Koster, Matthew J; Crowson, Cynthia S; Makol, Ashima; Ytterberg, Steven R; Saitta, Antonino; Salvarani, Carlo; Matteson, Eric L; Warrington, Kenneth J.
abstract
To investigate the incidence of venous thromboembolism (VTE) and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA) compared to the general population. METHODS:
A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review.
RESULTS:
The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women) and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (%) of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014) but similar rates of stroke, transient ischemic attack (TIA), and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events.
CONCLUSION:
In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects.
2016
- Whole Exome Sequencing Identifies Rare Protein-Coding Variants in Behçet's Disease
[Articolo su rivista]
Ognenovski, Mikhail; Renauer, Paul; Gensterblum, Elizabeth; Kötter, Ina; Xenitidis, Theodoros; Henes, Jörg C; Casali, Bruno; Salvarani, Carlo; Direskeneli, Haner; Kaufman, Kenneth M; Sawalha, Amr H.
abstract
Behçet's disease (BD) is a systemic inflammatory disease with an incompletely understood etiology. Despite the identification of multiple common genetic variants associated with BD, rare genetic variants have been less explored. We undertook this study to investigate the role of rare variants in BD by performing whole exome sequencing in BD patients of European descent.
METHODS:
Whole exome sequencing was performed in a discovery set comprising 14 German BD patients of European descent. For replication and validation, Sanger sequencing and Sequenom genotyping were performed in the discovery set and in 2 additional independent sets of 49 German BD patients and 129 Italian BD patients of European descent. Genetic association analysis was then performed in BD patients and 503 controls of European descent. Functional effects of associated genetic variants were assessed using bioinformatic approaches.
RESULTS:
Using whole exome sequencing, we identified 77 rare variants (in 74 genes) with predicted protein-damaging effects in BD. These variants were genotyped in 2 additional patient sets and then analyzed to reveal significant associations with BD at 2 genetic variants detected in all 3 patient sets that remained significant after Bonferroni correction. We detected genetic association between BD and LIMK2 (rs149034313), involved in regulating cytoskeletal reorganization, and between BD and NEIL1 (rs5745908), involved in base excision DNA repair (P = 3.22 × 10(-4) and P = 5.16 × 10(-4) , respectively). The LIMK2 association is a missense variant with predicted protein damage that may influence functional interactions with proteins involved in cytoskeletal regulation by Rho GTPase, inflammation mediated by chemokine and cytokine signaling pathways, T cell activation, and angiogenesis (Bonferroni-corrected P = 5.63 × 10(-14) , P = 7.29 × 10(-6) , P = 1.15 × 10(-5) , and P = 6.40 × 10(-3) , respectively). The genetic association in NEIL1 is a predicted splice donor variant that may introduce a deleterious intron retention and result in a noncoding transcript variant.
CONCLUSION:
We used whole exome sequencing in BD for the first time and identified 2 rare putative protein-damaging genetic variants associated with this disease. These genetic variants might influence cytoskeletal regulation and DNA repair mechanisms in BD and might provide further insight into increased leukocyte tissue infiltration and the role of oxidative stress in BD.
2015
- 2015 Recommendations for the Management of Polymyalgia Rheumatica: A European League Against Rheumatism/American College of Rheumatology Collaborative Initiative
[Articolo su rivista]
Dejaco, Christian; Singh, Yogesh P; Perel, Pablo; Hutchings, Andrew; Camellino, Dario; Mackie, Sarah; Abril, Andy; Bachta, Artur; Balint, Peter; Barraclough, Kevin; Bianconi, Lina; Buttgereit, Frank; Carsons, Steven; Ching, Daniel; Cid, Maria; Cimmino, Marco; Diamantopoulos, Andreas; Docken, William; Duftner, Christina; Fashanu, Billy; Gilbert, Kate; Hildreth, Pamela; Hollywood, Jane; Jayne, David; Lima, Manuella; Maharaj, Ajesh; Mallen, Christian; Martinez Taboada, Victor; Maz, Mehrdad; Merry, Steven; Miller, Jean; Mori, Shunsuke; Neill, Lorna; Nordborg, Elisabeth; Nott, Jennifer; Padbury, Hannah; Pease, Colin; Salvarani, Carlo; Schirmer, Michael; Schmidt, Wolfgang; Spiera, Robert; Tronnier, David; Wagner, Alexandre; Whitlock, Madeline; Matteson, Eric L; Dasgupta, Bhaskar
abstract
Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.
2015
- 2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative
[Articolo su rivista]
Dejaco, Christian; Singh, Yogesh P; Perel, Pablo; Hutchings, Andrew; Camellino, Dario; Mackie, Sarah; Abril, Andy; Bachta, Artur; Balint, Peter; Barraclough, Kevin; Bianconi, Lina; Buttgereit, Frank; Carsons, Steven; Ching, Daniel; Cid, Maria; Cimmino, Marco; Diamantopoulos, Andreas; Docken, William; Duftner, Christina; Fashanu, Billy; Gilbert, Kate; Hildreth, Pamela; Hollywood, Jane; Jayne, David; Lima, Manuella; Maharaj, Ajesh; Mallen, Christian; Martinez Taboada, Victor; Maz, Mehrdad; Merry, Steven; Miller, Jean; Mori, Shunsuke; Neill, Lorna; Nordborg, Elisabeth; Nott, Jennifer; Padbury, Hannah; Pease, Colin; Salvarani, Carlo; Schirmer, Michael; Schmidt, Wolfgang; Spiera, Robert; Tronnier, David; Wagner, Alexandre; Whitlock, Madeline; Matteson, Eric L; Dasgupta, Bhaskar
abstract
Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.
2015
- A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility
[Articolo su rivista]
Carmona, F. David; Mackie, Sarah L; Martín, Jose Ezequiel; Taylor, John C; Vaglio, Augusto; Eyre, Stephen; Bossini Castillo, Lara; Castañeda, Santos; Cid, Maria C; Hernández Rodríguez, José; Prieto González, Sergio; Solans, Roser; Ramentol Sintas, Marc; González Escribano, M. Francisca; Ortiz Fernández, Lourdes; Morado, Inmaculada C; Narváez, Javier; Miranda Filloy, José A; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A; Gianfreda, Davide; Santilli, Daniele; Ramirez, Giuseppe A; Soriano, Alessandra; Muratore, Francesco; Pazzola, Giulia; Addimanda, Olga; Wijmenga, Cisca; Witte, Torsten; Schirmer, Jan H; Moosig, Frank; Schönau, Verena; Franke, Andre; Palm, Øyvind; Molberg, Øyvind; Diamantopoulos, Andreas P; Carette, Simon; Cuthbertson, David; Forbess, Lindsy J; Hoffman, Gary S; Khalidi, Nader A; Koening, Curry L; Langford, Carol A; Mcalear, Carol A; Moreland, Larry; Monach, Paul A; Pagnoux, Christian; Seo, Philip; Spiera, Robert; Sreih, Antoine G; Warrington, Kenneth J; Ytterberg, Steven R; Gregersen, Peter K; Pease, Colin T; Gough, Andrew; Green, Michael; Hordon, Lesley; Jarrett, Stephen; Watts, Richard; Levy, Sarah; Patel, Yusuf; Kamath, Sanjeet; Dasgupta, Bhaskar; Worthington, Jane; Koeleman, Bobby P. C; de Bakker, Paul I. W; Barrett, Jennifer H; Salvarani, Carlo; Merkel, Peter A; González Gay, Miguel A; Morgan, Ann W; Martín, Javier
abstract
We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10(-40), OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1(∗)04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10(-43)) and HLA-DQα1 47 (p = 4.02 × 10(-46)), 56, and 76 (both p = 1.84 × 10(-45)) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10(-6), OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10(-6), OR = 1.20), and REL (rs115674477, p = 1.10 × 10(-5), OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function.
2015
- Adult primary central nervous system vasculitis treatment and course: analysis of one hundred sixty-three patients
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Christianson, Teresa J. H; Huston, John; Giannini, Caterina; Miller, Dylan V; Hunder, Gene G.
abstract
Objective. To describe the treatment and outcomes of patients with primary central nervous system (CNS) vasculitis.
Methods. We retrospectively studied a cohort of 163 consecutive patients with primary CNS vasculitis who were seen at the Mayo Clinic over a 29-year period. We analyzed treatments, treatment responses, and factors predictive of outcomes.
Results. A favorable response was observed in 85% of patients treated with prednisone alone and in 80% of patients treated with prednisone and cyclophosphamide. Relapses were observed in 27% of patients, and 25% of patients had discontinued therapy by the time of the last followup visit. Treatment with prednisone alone was associated with more frequent relapses (odds ratio [OR] 2.90), while large vessel involvement (OR 6.14) and cerebral infarcts at the time of diagnosis (OR 3.32) were associated with a poor response to treatment. Prominent gadolinium-enhanced cerebral lesions or meninges were linked with continued treatment at the last followup encounter (OR 2.28). Higher disability scores at the last followup visit were associated with increasing age at the time of diagnosis (OR 1.44) and cerebral infarctions (OR 3.74), while lower disability scores were associated with gadolinium-enhanced cerebral lesions or meninges (OR 0.35) and cerebral amyloid angiopathy (OR 0.24). Increased mortality was associated with increasing age at diagnosis (hazard ratio [HR] 1.39), diagnosis by angiography (HR 3.28), cerebral infarction (HR 4.44), and large vessel involvement (HR 4.98), while reduced mortality was associated with gadolinium-enhanced cerebral lesions or meninges (HR 0.20).
Conclusion. The majority of patients with primary CNS vasculitis responded to treatment. Recognition of findings at diagnosis that predict the course or outcome may aid in decision-making regarding therapy.
2015
- An update of the Mayo Clinic cohort of patients with adult primary central nervous system vasculitis: description of 163 patients
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Christianson, Teresa; Miller, Dylan V; Giannini, Caterina; Huston, John; Hunder, Gene G.
abstract
Primary central nervous system vasculitis (PCNSV) is an uncommon condition in which lesions are limited to vessels of the brain and spinal cord. Because the clinical manifestations are not specific, the diagnosis is often difficult, and permanent disability and death are frequent outcomes. This study is based on a cohort of 163 consecutive patients with PCNSV who were examined at the Mayo Clinic over a 29-year period from 1983 to 2011. The aim of the study was to define the characteristics of these patients, which represents the largest series in adults reported to date. A total of 105 patients were diagnosed by angiographic findings and 58 by biopsy results. The patients diagnosed by biopsy more frequently had at presentation cognitive dysfunction, greater cerebrospinal fluid total protein concentrations, less frequent cerebral infarcts, and more frequent leptomeningeal gadolinium-enhanced lesions on magnetic resonance imaging (MRI), along with less mortality and disability at last follow-up. The patients diagnosed by angiograms more frequently had at presentation hemiparesis or a persistent neurologic deficit or stroke, more frequent infarcts on MRI and an increased mortality. These differences were mainly related to the different size of the vessels involved in the 2 groups. Although most patients responded to therapy with glucocorticoids alone or in conjunction with cyclophosphamide and tended to improve during the follow-up period, an overall increased mortality rate was observed. Relapses occurred in one-quarter of the patients and were less frequent in patients treated with prednisone and cyclophosphamide compared with those treated with prednisone alone. The mortality rate and degree of disability at last follow-up were greater in those with increasing age, cerebral infarctions on MRI, angiographic large vessel involvement, and diagnosis made by angiography alone, but were lower in those with gadolinium-enhanced lesions on MRI and in those with cerebral amyloid angiopathy. The annual incidence rate of PCNSV was estimated at 2.4 cases per 1,000,000 person-years. PCNSV appears to consist of several subsets defined by the size of the vessels involved, the clinical characteristics at presentation, MRI findings, and histopathological patterns on biopsy. Early recognition and treatment may reduce poor outcomes.
2015
- Biologics in vasculitides: Where do we stand, where do we go from now?
[Articolo su rivista]
Pazzola, Giulia; Muratore, Francesco; Pipitone, Nicolò; Salvarani, Carlo
abstract
Biological agents represent a valid therapeutic option in patients with severe and/or relapsing vasculitis. Over the last years, some of these agents have become an established therapy (such as RTX in AAV or IFX for ocular BD), and some appear to hold promise to become so. In addition, there are a number of drugs in the pipeline that may contribute to further improve the prognosis of vasculitis. As the range of medications available for vasculitis widens, the need will also increase to define the best treatment schemes as well as to identify those patients that may benefit most from biological agents.
2015
- Chronic periaortitis with thoracic aorta and epiaortic artery involvement: a systemic large vessel vasculitis?
[Articolo su rivista]
Palmisano, Alessandra; Urban, Maria L; Corradi, Domenico; Cobelli, Rocco; Alberici, Federico; Maritati, Federica; Versari, Annibale; Pipitone, Nicolò; Salvarani, Carlo; Buzio, Carlo; Vaglio, Augusto
abstract
Objective. Chronic periaortitis (CP) is a rare disease characterized by fibro-inflammatory tissue surrounding the abdominal aorta and the iliac arteries. Anecdotal reports have shown that CP may also involve other vascular districts, particularly the thoracic aorta. The aim of this study was to investigate the thoracic aorta and epiaortic artery involvement in CP.
Methods. Patients were eligible if they had undergone imaging studies assessing inflammatory involvement of the thoracic aorta and its major branches (e.g. contrast CT, MRI or PET-CT). We explored the patterns of thoracic vessel involvement and compared the clinical characteristics of patients with and without thoracic disease. Where available, we also reviewed the thoracic vascular/perivascular tissue biopsies.
Results. Of 153 CP patients seen between 1999 and 2012, 77 were eligible. Of these, 28 (36%) had thoracic involvement: 15 (54%) had thoracic periaortitis, with 7 also showing epiaortic artery involvement; 6 (21%) had periaortitis surrounding a thoracic aortic aneurysm, 2 of them with epiaortic artery involvement; 7 (25%) had a thoracic aortic aneurysm without periaortitis. Patients with thoracic disease were more frequently female (P = 0.01), were older (P = 0.001) and had a higher frequency of pain and constitutional symptoms (P = 0.02). Thoracic (peri) vascular biopsies revealed adventitial and peri-adventitial fibro-inflammatory patterns similar to those observed in abdominal CP.
Conclusion. In about one-third of patients, CP also involves the thoracic aorta and the epiaortic arteries, which supports the hypothesis of a systemic inflammatory disease of the large arteries.
2015
- Cryoglobulinemic Vasculitis and Primary sjögren's Syndrome are Independent Risk Factors for Lymphoma in a Large Worldwide Population of Patients with Positive Serum Cryoglobulins
[Abstract in Rivista]
Quartuccio, L; Corazza, L; Ramos Casals, M; Retamozo, S; Ragab, Gm; Ferraccioli, G; Gremese, E; Tzioufas, A; Voulgarelis, M; Vassilopoulos, D; Koutsianas, C; Scarpato, S; Salvarani, Carlo; Guillevin, L; Terrier, B; Cacoub, P; Saccardo, F; Gabrielli, A; Fraticelli, P; Tomsic, M; Tavoni, A; Nishimoto, N; Filippini, D; Scaini, P; Zignego, Al; Ferri, Clodoveo; Sansonno, D; Monti, G; Pietrogrande, M; Galli, M; Bombardieri, S; Vita, S. De
abstract
Background Serum cryoglobulins (SC) may be found in many diseases (1), and the presence of serum cryoglobulins is a known risk factor for lymphoma evolution in some non malignant diseases.
Objectives The aim of this study was to distiguish the role of cryoglobulinemic vasculitis (CV), classified according to the recent validated criteria (1,2), and primary Sjögren's syndrome (pSS) as risk factors of lymphoma in patients positive serum cryoglobulins. Importantly, SC, CV and pSS may occur together.
Methods 950 charts from consecutive patients with positive SC were evaluated. Patients carrying both pSS and HCV infection, as well as incomplete charts, were excluded.
Results 657 patients with SC were selected, 374 with CV and 283 without CV, according to the published criteria (2,3). PSS, classified according to the American-European Group Criteria was present in 96 patients (44 with CV, 52 without). Lymphoma was reported in 61/657 (9.8%) patients with SC. Among them, CV was present in 44/61 (72,1%; 14 also with pSS), and pSS in 17/61 (27,9%; and 14/17 had CV). Patients with SC with CV showed an higher prevalence of lymphoma than patients with SC without CV (44/374, 11.5% vs.17/283, 6.3%; p=0.025, OR=1.93 [95%IC: 1.08-3.39]. Patients with pSS, SC and CV also showed a higher prevalence of lymphoma than patients with pSS, SC but without CV (14/44, 31.8% vs. 3/52, 7.4%; p=0.001, OR=7.62 [95%CI 2.02-28.74]. CV and pSS were confirmed as independent risk factor for lymphoma by multivariate analysis (OR 2,18 95%CI 1,18-3,83, p=0,012; OR 2,65 95%CI 1,04-6,76, p=0,042, respectively). Infection by the hepatitis C virus (HCV) was detected in 467/561 (83,2%) patients with SC without pSS, and did not statistically predispose to lymphoma when associated with CV in this subset (p=1,0).
Conclusions Cryoglobulinemic vasculitis and pSS are independent risk factors for lymphoma in patients with evidence of SC. Patients with both the conditions (CV and pSS) have the highest risk. In the follow-up of SC positive patients, a very high attention should be deserved to pSS, in particular when CV is present.
2015
- Cyclosporine in psoriatic arthropathy
[Articolo su rivista]
Soriano, Alessandra; Pipitone, Nicolò; Salvarani, Carlo
abstract
Psoriatic arthropathy (PsA) is an inflammatory arthropathy associated with skin or nail psoriasis with heterogeneous clinical manifestations. A pragmatic therapeutic approach to PsA is to stratify the disease manifestations according to their response to synthetic and biological agents. It is now reasonably well established that peripheral arthritis is amenable to treatment with synthetic disease-modifying anti-rheumatic drugs, while psoriatic pelvispondylitis and inflammatory tendon lesions appear to require the use of biological agents. Cyclosporine is a calcineurin inhibitor belonging to the synthetic disease-modifying anti-rheumatic drugs group. It has been shown to be effective in treating both arthritis and psoriasis. In this paper, we will briefly summarise the current knowledge about the efficacy of cyclosporine, both as a monotherapy and as an adjunctive treatment for PsA.
2015
- Difference in the expression of IL-9 and IL-17 correlates with different histological pattern of vascular wall injury in giant cell arteritis
[Articolo su rivista]
Ciccia, Francesco; Rizzo, Aroldo; Guggino, Giuliana; Cavazza, Alberto; Alessandro, Riccardo; Maugeri, Rosario; Cannizzaro, Alessandra; Boiardi, Luigi; Iacopino, Domenico Gerardo; Salvarani, Carlo; Triolo, Giovanni
abstract
Objective. GCA is a large- and medium-vessel arteritis characterized by a range of histological patterns of vascular wall injury. The aim of this study was to immunologically characterize the various histological patterns of GCA. Methods. Thirty-five consecutive patients with biopsy-proven GCA and 15 normal controls were studied. IL-8, IL-9, IL-9R, IL-17, IL-4, TGF-β and thymic stromal lymphopoietin expression was evaluated by RT-PCR and immunohistochemistry on artery biopsy specimens. Confocal microscopy was used to characterize the phenotypes of IL-9-producing and IL-9R-expressing cells. Five additional patients who had received prednisone when the temporal artery biopsy was performed were also enrolled to evaluate the effect of glucocorticoids on IL-9 and IL-17 expression. Results. IL-17 overexpression was observed mainly in arteries with transmural inflammation and vasa vasorum vasculitis. IL-9 overexpression and Th9 polarization predominated in arteries with transmural inflammation and small-vessel vasculitis. The tissue expression of both IL-9 and IL-17 was correlated with the intensity of the systemic inflammatory response. IL-4, TGF-β and thymic stromal lymphopoietin, which are involved in the differentiation of Th9 cells, were overexpressed in arteries with transmural inflammation and small-vessel vasculitis. IL-9R was also overexpressed in GCA arteries with transmural inflammation and was accompanied by increased expression of IL-8. Conclusion. Herein we provide the first evidence that distinct populations of potentially autoreactive T cells, expressing different cytokines (Th17 vs Th9), characterize patients with particular histological subsets of GCA and may thus contribute to the heterogeneity of tissue lesions observed in these patients.
2015
- Efficacy of anti-TNF alpha in severe and/or refractory Behçet's disease: Multicenter study of 124 patients
[Articolo su rivista]
Vallet, H; Riviere, S; Sanna, A; Deroux, A; Moulis, G; Addimanda, O; Salvarani, Carlo; Lambert, M; Bielefeld, P; Seve, P; Sibilia, J; Pasquali, Jl; Fraison, Jb; Marie, I; Perard, L; Bouillet, L; Cohen, F; Sene, D; Schoindre, Y; Lidove, O; Le Hoang, P; Hachulla, E; Fain, O; Mariette, X; Papo, T; Wechsler, B; Bodaghi, B; Rigon, M. Resche; Cacoub, P; Saadoun, D.
abstract
Objective: To report the efficacy and safety of anti-TNF agents in patients with severe and/or refractory manifestations of Behçet's disease (BD). Methods: We performed a multicenter study of main characteristics and outcomes of anti-TNF alpha treatments [mainly infliximab (62%), and adalimumab (30%)] in 124 BD patients [48% of men; median age of 33.5 (28-40) years]. Results: Overall response (i.e. complete and partial) rate was 90.4%. Clinical responses were observed in 96.3%, 88%, 70%, 77.8%, 92.3% and 66.7% of patients with severe and/or refractory ocular, mucocutaneous, joint, gastro-intestinal manifestations, central nervous system manifestations and cardiovascular manifestations, respectively. No significant difference was found with respect to the efficacy of anti-TNF used as monotherapy or in association with an immunosuppressive agent. The incidence of BD flares/patient/year was significantly lower during anti-TNF treatment (0.2±0.5 vs 1.7±2.4 before the use of anti-TNF, p<0.0001). The prednisone dose was significantly reduced at 6 and 12 months (p<0.0001). In multivariate analysis, retinal vasculitis was negatively associated with complete response to anti-TNF (OR=0.33 [0.12-0.89]; p=0.03). The efficacy and relapse free survival were similar regardless of the type of anti-TNF agent used. After a median follow-up of 21 [7-36] months, side effects were reported in 28% of patients, including infections (16.3%) and hypersensitivity reactions (4.1%). Serious adverse events were reported in 13% of cases. Conclusion: Anti-TNF alpha therapy is efficient in all severe and refractory BD manifestations. Efficacy appears to be similar regardless of the anti-TNF agent used (infliximab or adalimumab).
2015
- Frequency of monoclonal gammopathy in psoriatic patients receiving anti-TNF therapy compared with patients taking conventional drugs: a cross-sectional study
[Articolo su rivista]
Di Lernia, V; Ficarelli, E; Lallas, A; Possemato, N; Chiarolanza, I; Salvarani, Carlo
abstract
A cross-sectional analysis was performed to analyse the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients treated with TNF-alpha blockers for psoriasis or psoriatic arthritis (PsA) and compare it in control subjects treated with conventional antipsoriatic drugs.
2015
- Immunosuppressive treatment for giant cell arteritis: where do we stand?
[Articolo su rivista]
Pipitone, N; Salvarani, Carlo
abstract
Editorial on the treatment of giant cell arteritis
2015
- Is colour duplex sonography-guided temporal artery biopsy useful in the diagnosis of giant cell arteritis? A randomized study
[Articolo su rivista]
Germanò, Giuseppe; Muratore, Francesco; Cimino, Luca; Lo Gullo, Alberto; Possemato, Niccolò; Macchioni, Pierluigi; Cavazza, Alberto; Pipitone, Nicolò; Boiardi, Luigi; Salvarani, Carlo
abstract
Objective. The aim of this study was to assess the usefulness of colour duplex sonography (CDS)-guided temporal artery biopsy (TAB) for the diagnosis of GCA in patients with suspected GCA.
Methods. From September 2009 through December 2012, 112 consecutive patients with suspected GCA were randomized to undergo CDS-guided TAB or standard TAB. All patients underwent temporal artery physical examination and temporal artery CDS prior to TAB. CDS of the temporal artery was performed by the same ultrasonographer, who was unaware of the patient's clinical data, and all TABs were evaluated by the same pathologist. Seven patients in whom biopsy failed to sample temporal artery tissue were excluded from the analysis.
Results. Fifty patients were randomized to undergo CDS-guided TAB and 55 patients to standard TAB. Except for a younger age in patients who underwent standard TAB (P = 0.026), no significant differences were observed between the two groups. There were no significant differences in the frequencies of positive TAB for classic transmural inflammation (28% vs 18.2%) or for periadventitial small vessel vasculitis and/or vasa vasorum vasculitis (6% vs 14.5%) between the two groups. No significant differences in the frequency of positive TAB in the two groups were observed when we excluded the patients treated with glucocorticoids and when we stratified the patients of the two groups for the presence or absence of the halo sign.
Conclusion. Our study showed that CDS-guided TAB did not improve the sensitivity of TAB for diagnosing GCA.
2015
- Large-vessel giant cell arteritis: a cohort study
[Articolo su rivista]
Muratore, Francesco; Kermani, Tanaz A; Crowson, Cynthia S; Green, Abigail B; Salvarani, Carlo; Matteson, Eric L; Warrington, Kenneth J.
abstract
Objective. The aim of this study was to compare baseline variables, treatment and outcomes in patients with large-vessel GCA (LV-GCA), primarily of the upper extremities, with those with cranial disease (C-GCA). Methods. All patients > 50 years of age with radiographic evidence of subclavian LV-GCA diagnosed between 1 January 1999 and 31 December 2008 were identified and compared with those with biopsypositive C-GCA diagnosed in the same period. Results. The study included 120 LV-GCA patients and 212 C-GCA patients. Compared with C-GCA, patients with LV-GCA were younger [68.2 years (S.D. 7.5) vs 75.7 (7.4), P < 0.001] and had longer duration of symptoms at GCA diagnosis (median 3.5 vs 2.2 months, P < 0.001). A history of PMR was more common in LV-GCA patients (26% vs 15%, P = 0.012), but a smaller proportion had cranial symptoms (41% vs 83%, P < 0.001) and vision loss (4% vs 11%, P = 0.035). ACR classification criteria for GCA were satisfied in 39% of LV-GCA patients and 95% of C-GCA patients (P < 0.001). Compared with C-GCA, patients with LV-GCA had more relapses (4.9 vs 3.0/10 person-years, P < 0.001), higher cumulative corticosteroid (CS) doses at 1 year [11.4 g (S.D. 5.9) vs 9.1 (S.D. 3.7), P < 0.001] and required longer treatment (median 4.5 vs 2.2 years, P < 0.001). Conclusion. Although patients with LV-GCA had a lower rate of vision loss, they had a higher relapse rate and greater CS requirements. The ACR criteria for GCA are inadequate for the classification of patients with LV-GCA.
2015
- Mycophenolate mofetil in primary central nervous system vasculitis
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Christianson, Teresa J. H; Huston, John; Giannini, Caterina; Miller, Dylan V; Muratore, Francesco; Hunder, Gene G.
abstract
Objective: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) in adult primary central nervous system vasculitis (PCNSV).
Methods: We studied a cohort of 163 patients with PCNSV who were seen at the Mayo Clinic from 1983 to 2011. We compared patients treated with MMF and those receiving other therapies.
Results: We identified 16 patients treated with MMF. MMF in combination with GCs achieved a favorable response in most patients. A significant proportion of patients treated with MMF had a less severe disability at last follow-up compared to those receiving other therapies (p = 0.023) and cyclophosphamide and prednisone (p = 0.017). No statistically significant differences were observed regarding relapses and ability to discontinue therapy at last follow-up. A trend to a more favorable treatment response was observed in patients treated with MMF compared to those treated with other therapies (p = 0.075). Only 1 patient suspended MMF for severe leukopenia.
Conclusion: MMF seems to be an effective and safe therapy for adult PCNSV.
2015
- Nailfold capillaroscopic changes in dermatomyositis and polymyositis
[Articolo su rivista]
Manfredi, Andreina Teresa; Sebastiani, Marco; Cassone, Giulia; Pipitone, N; Giuggioli, Dilia; Colaci, Michele; Salvarani, Carlo; Ferri, Clodoveo
abstract
Inflammatory myopathies (IM) are a group of muscle diseases occurring both in children and adults. Nailfold videocapillaroscopy (NVC) alterations are described in IM, but available data are discordant, including differences between polymyositis (PM) and dermatomyositis (DM). The aim of this study was to describe the capillaroscopic differences between PM and DM patients and possible correlation with clinical and serological features. We analyzed 52 unselected patients with IM in a cross-sectional study in a 6-month period. NVC findings of 29 DM and 23 PM patients were compared with those of 52 patients with primary Raynaud's phenomenon. Tortuosities, capillary loss, enlarged and giant capillaries, microhemorrhages, and ramified capillaries were scored by a semiquantitative rating; disorganization of the vascular array, avascular areas, and scleroderma pattern were scored as presence/absence. Sex, mean age, and mean disease duration were similar in both groups. Disorganization of the vascular array, enlarged and giant capillaries, capillary loss, and scleroderma-like pattern were observed almost only in IM patients. Significant differences were observed between PM and DM with higher frequency and mean score of NVC changes in DM. In DM patients with disease duration ≤6 months (14/29 patients), capillary density was significantly reduced (P = 0.039) and giant capillaries more frequent (P = 0.027), compared with patients with longer disease duration, while a scleroderma pattern tended to be more frequent in patients with a disease duration of less than 6 months. On the contrary, no differences were observed for ramified capillaries with regard to disease duration. Capillaroscopic alterations are identified only in DM patients as expression of diffuse microangiopathy; surprisingly, more severe changes were associated with shorter disease duration, while persistence of ramified capillaries with long-standing disease.
2015
- Remission in nonradiographic axial spondyloarthritis treated with anti-tumor necrosis factor-α drugs: an Italian multicenter study
[Articolo su rivista]
Lubrano, Ennio; Perrotta, Fabio Massimo; Marchesoni, Antonio; D'Angelo, Salvatore; Ramonda, Roberta; Addimanda, Olga; Olivieri, Ignazio; Punzi, Leonardo; Salvarani, Carlo
abstract
Objective. To investigate the possibility of achieving partial remission (PR) in patients with non-radiographic axial spondyloarthritis (nr-axSpA) versus ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (TNF)-α antagonists, such as adalimumab (ADA), etanercept (ETN), and infliximab (IFX), in a real clinical practice setting. The Assessment of SpondyloArthritis international Society (ASAS) 20, ASAS40, and Ankylosing Spondylitis Disease Activity Score were also calculated. Methods. A retrospective study was conducted in patients with axSpA treated with ADA, ETN, and IFX from 2000 to 2013. All patients fulfilled the ASAS or the modified New York criteria. PR was reached when the score was < 20 mm (on a visual analog scale of 0-100 mm) in each of these domains: (1) patient global assessment, (2) pain, (3) function, and (4) inflammation. Results. A total of 321 patients with axSpA were treated. Among them, 62 were nr-axSpA while the remaining 259 were AS. Log-rank test to compare survival curves showed that the probability of obtaining PR in nr-axSpA and AS during treatment with anti-TNF-&alpha was not significantly different. At 12 weeks of exposure to the first anti-TNF-α drug, PR was achieved in 7 patients with nr-axSpA (11.3%) and in 68 patients with AS (26.2%). Conclusion. Our results, obtained from clinical practice, showed that PR is an achievable target of anti-TNF-α treatment in nr-axSpA. The PR rate, as a reliable indicator of sustained effectiveness, is similar in nr-axSpA and in AS.
2015
- Rheumatic manifestations of scurvy
[Articolo su rivista]
Ferrari, Claudia; Possemato, Niccolò; Pipitone, Nicolò; Manger, Bernhard; Salvarani, Carlo
abstract
This paper reviews the rheumatological manifestations of scurvy, based on articles published in English from 1965 until October 2014, with a particular focus on rheumatological manifestations. Scurvy is a rare, uncommon disease in developed countries. Due to its clinical heterogeneity, the disease can easily mimic rheumatologic conditions leading to a delay in diagnosis and treatment.
2015
- The Role of Tumor Necrosis Factor-α Blockers in Psoriatic Disease. Therapeutic Options in Psoriatic Arthritis
[Articolo su rivista]
Addimanda, Olga; Possemato, Niccolò; Caruso, Andrea; Pipitone, Nicolò; Salvarani, Carlo
abstract
Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting peripheral and axial joints, usually associated with psoriasis (PsO) and involving various systems and organs (eye inflammation, such as uveitis; and involvement of nail and enthesis), and it usually requires a multidisciplinary treatment approach. Tumor necrosis factor-α (TNF-α) is overexpressed in psoriatic synovium and skin plaques and its selective inhibition by anti-TNF-α agents has been demonstrated to reduce TNF-α levels in the articular environment, reversing the synovial hyperproliferative phenotype. Studies performed on anti-TNF-α agents in PsA demonstrated that they are able to reduce neutrophil and macrophage infiltration as well as vascular cell adhesion protein 1 expression with ensuing synovial thickness normalization. The efficacy of anti-TNF-α agents for all PsA manifestations (peripheral arthritis, axial involvement, enthesopathy, and skin disease) suggests that anti-TNF-α efficacy might be related to the ability to influence angiogenesis and osteoclastogenesis, reduce synovial inflammation, and slow radiological disease progression. This review describes the role of anti-TNF-α in each manifestation of PsA.
2015
- Tocilizumab for severe refractory neuro-Behçet: three cases IL-6 blockade in neuro-Behçet
[Articolo su rivista]
Addimanda, Olga; Pipitone, Nicolò; Pazzola, Giulia; Salvarani, Carlo
abstract
Objectives: To describe the response to IL-6 blockade [tocilizumab (TCZ)] in three patients affected by highly refractory neuro-Behcet disease (NBD).
Methods: Three patients who had failed synthetic immunosuppressants and TNF-alpha antagonists combined with glucocorticoids received TCZ after obtaining their informed consent. Two patients underwent TCZ infusions at 8 mg/kg every 4 weeks for a mean period of 24 months, while in one patient, the frequency of TCZ infusions was increased to every other week after 21 months due to a disease flare. Concomitant therapy with synthetic agents and low-to-medium dose glucocorticoids was continued. Clinical and imaging findings were assessed before and after the onset of TCZ therapy.
Results: In all our patients, a very short time lag between the onset of treatment with TCZ and the clinical response was observed. A partial response occurred in two patients and a nearly complete response in one. Some loss of efficacy occurred after 18 months in one patient, but there was again a significant improvement when the interval between the infusions was shortened. TCZ was overall well tolerated and no serious adverse events occurred. In two patients, the prednisone dose could successfully be tapered to about 20 mg/day, while in another patient glucocorticoids could safely be withdrawn. Brain MRI remained virtually unchanged in all patients.
Conclusions: Although TCZ has not yet been included among the medications recommended for the treatment of NBD, our data suggest that it may be considered for patients with refractory NBD.
2015
- Tracing Behçet's disease origins along the Silk Road: an anthropological evolutionary genetics perspective
[Articolo su rivista]
Sazzini, Marco; Garagnani, Paolo; Sarno, Stefania; De Fanti, Sara; Lazzano, Teresa; Yang Yao, Daniele; Boattini, Alessio; Pazzola, Giulia; Maramotti, Sally; Boiardi, Luigi; Franceschi, Claudio; Salvarani, Carlo; Luiselli, Donata
abstract
Objective. Behçet's disease is a multifactorial vasculitis that shows its highest prevalence in geographical areas historically involved in the Silk Road, suggesting that it might have originated somewhere along these ancient trade routes. This study aims to provide a first clue towards genetic evidence for this hypothesis by testing it via an anthropological evolutionary genetics approach. Methods. Behçet's disease variation at ancestry informative mitochondrial DNA control region and haplogroup diagnostic sites was characterised in 185 disease subjects of Italian descent and set into the Eurasian mitochondrial landscape by comparison with nearly 9,000 sequences representative of diversity observable in Italy and along the main Silk Road routes. Results. Dissection of the actual genetic ancestry of disease individuals by means of population structure, spatial autocorrelation and haplogroup analyses revealed their closer relationships with some Middle Eastern and Central Asian groups settled along the Silk Road than with healthy Italians. Conclusion. These findings support the hypothesis that the Behçet's disease genetic risk has migrated to western Eurasia in parallel with ancestry components typical of Silk Road-related groups. This provided new insights that are useful to improve the understanding of disease origins and diffusion, as well as to inform future association studies aimed at properly accounting for the actual genetic ancestry of the examined Behçet's disease samples in order to minimise the detection of spurious associations and to improve the identification of genetic variants with actual clinical relevance.
2014
- A candidate gene approach identifies an IL33 genetic variant as a novel genetic risk factor for GCA
[Articolo su rivista]
Márquez, Ana; Solans, Roser; Hernández Rodríguez, José; Cid, Maria C; Castañeda, Santos; Ramentol, Marc; Rodriguez Rodriguez, Luis; Narváez, Javier; Blanco, Ricardo; Ortego Centeno, Norberto; Palm, Oyvind; Diamantopoulos, Andreas P; Braun, Niko; Moosig, Frank; Witte, Torsten; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A; Vaglio, Augusto; Salvarani, Carlo; González Gay, Miguel A; Martín, Javier
abstract
Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition.
2014
- Adalimumab in the treatment of immune-mediated diseases
[Articolo su rivista]
Lapadula, G; Marchesoni, A; Armuzzi, A; Blandizzi, C; Caporali, R; Chimenti, S; Cimaz, R; Cimino, L; Gionchetti, P; Girolomoni, G; Lionetti, P; Marcellusi, A; Mennini, F. S; Salvarani, Carlo
abstract
Tumour necrosis factor (TNF) plays an important role in the pathogenesis of immune-mediated inflammatory diseases (IMIDs). TNF inhibition results in down-regulation of abnormal and progressive inflammatory processes, resulting in rapid and sustained clinical remission, improved quality of life and prevention of target organ damage. Adalimumab is the first fully human monoclonal antibody directed against TNF. In this article, we review the role and cost effectiveness of adalimumab in the treatment of IMIDs in adults and children. The efficacy and tolerability of adalimumab has been demonstrated in patients with a wide range of inflammatory conditions, leading to regulatory approval in rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis, inflammatory bowel diseases (Crohn's disease, ulcerative colitis, paediatric Crohn's disease, and intestinal Behçet's disease), ankylosing spondylitis (AS), axial spondyloarthritis (SpA) and juvenile idiopathic arthritis. The major tolerability issues with adalimumab are class effects, such as injection site reactions and increased risk of infection and lymphoma. As with all anti-TNF agents, adalimumab is immunogenic, although less than infliximab, and some patients receiving long-term adalimumab will develop anti-drug antibodies, causing a loss of response. Comparisons of its clinical utility and cost effectiveness have shown it to be a valid treatment choice in a wide range of patients. Recent data from Italian economic studies show the cost effectiveness of adalimumab to be below the threshold value for health care interventions for most indications. In addition, analysis of indirect costs shows that adalimumab significantly reduces social costs associated with RA, PsA, AS, Crohn's disease and psoriasis. The fact that adalimumab has the widest range of approved indications, many often presenting together in the same patient due to the common pathogenesis, may further improve the utility of adalimumab. Current clinical evidence shows adalimumab to be a valuable resource in the management of IMIDs. Further research, designed to identify patients who may benefit most from this drug, will better highlight the role and cost-effectiveness of this versatile TNF inhibitor.
2014
- Adult-onset Still's disease treated with canakinumab: Limited effectiveness in systemic manifestations
[Articolo su rivista]
Lo Gullo, A.; Caruso, A.; Pipitone, N.; Macchioni, P.; Pazzola, G.; Salvarani, C.
abstract
2014
- Anterior ischaemic optic neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a case report and review of the literature
[Articolo su rivista]
Padovano, Ilaria; Pazzola, Giulia; Pipitone, Nicolò; Cimino, Luca; Salvarani, Carlo
abstract
We report a 62-year-old man with mild fever, headache and acute visual loss in his right eye due to anterior ischaemic optic neuropathy (AION), followed a few days later by pain in the legs and left arm associated with numbness and weakness. Giant cell arteritis complicated by AION was suspected at the beginning and high-dose oral glucocorticoids were started. However, on the basis of the past medical history of nasal polyposis, asthma, and hypereosynophilia as well as of further investigations (biopsy of the nasal mucosa showing granulomatous inflammation with a rich eosinophilic infiltrate, electromyography demonstrating, mononeuritis multiplex and positive p-ANCA), eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome, was diagnosed. Because visual acuity in the right eye deteriorated despite glucocorticoid therapy, pulse intravenous cyclophosphamide was started, subsequently replaced by oral azathioprine, while prednisone was slowly tapered. This treatment led to gradual improvement of the neurological symptoms, whereas the right visual impairment remained unchanged. EGPA-related AION is an uncommon lesion that is probably due to vasculitic involvement of posterior ciliary and/or chorioretinal arteries. The prognosis of established AION is poor for the affected eye, even when glucocorticoid treatment is started immediately. However, early recognition of AION and prompt aggressive treatment with high-dose glucocorticoids plus cyclophosphamide can prevent visual loss in the unaffected eye.
2014
- Canakinumab in a case of adult onset Still's disease: Efficacy only on systemic manifestations
[Articolo su rivista]
Lo Gullo, A.; Caruso, A.; Pipitone, N.; Macchioni, P.; Pazzola, G.; Salvarani, C.
abstract
2014
- Canakinumab in a case of adult onset still's disease: efficacy only on systemic manifestations
[Articolo su rivista]
Lo Gullo, Alberto; Caruso, Andrea; Pipitone, Nicolò; Macchioni, Pierluigi; Pazzola, Giulia; Salvarani, Carlo
abstract
We describe the efficacy of Canakinumab only on systemic manifestations in a case of adult onset still's disease.
2014
- Catastrophic primary central nervous system vasculitis
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Morris, Jonathan M; Huston, John; Hunder, Gene G.
abstract
Primary central nervous system vasculitis (PCNSV) is an uncommon condition that affects the brain and the spinal cord. It is heterogeneous in presenting characteristics and outcomes. We report a patient with a catastrophic rapidly progressive course refractory to intensive treatment with pulses of methylprednisolone and iv cyclophosphamide. The condition rapidly deteriorated and the patient died 6 weeks after presentation. Rapidly progressive PCNSV represents the worst end of the clinical spectrum of PCNSV. These patients are characterised by bilateral, multiple, large cerebral vessel lesions on angiograms and multiple bilateral cerebral infarctions.
2014
- Clinical images: PET-CT and contrast-enhanced ultrasound in Takayasu's arteritis
[Articolo su rivista]
Possemato, Niccolò; Macchioni, Pierluigi; Germanò, Giuseppe; Pipitone, Nicolò; Versari, Annibale; Salvarani, Carlo
abstract
Clinical images: PET-CT and contrast-enhanced ultrasound in Takayasu's arteritis
2014
- Diagnosis and management of Neuro-Behçet's disease: international consensus recommendations
[Articolo su rivista]
Kalra, Seema; Silman, Alan; Akman Demir, Gulsen; Bohlega, Saeed; Borhani Haghighi, Afshin; Constantinescu, Cris S; Houman, Habib; Mahr, Alfred; Salvarani, Carlo; Sfikakis, Petros P; Siva, Aksel; Al Araji, Adnan
abstract
Neuro-Behçet's disease (NBD) is one of the more serious manifestations of Behçet's disease (BD), which is a relapsing inflammatory multisystem disease with an interesting epidemiology. Though NBD is relatively uncommon, being potentially treatable, neurologists need to consider it in the differential diagnosis of inflammatory, infective, or demyelinating CNS disorders. Evidence-based information on key issues of NBD diagnosis and management is scarce, and planning for such studies is challenging. We therefore initiated this project to develop expert consensus recommendations that might be helpful to neurologists and other clinicians, created through an extensive literature review and wide consultations with an international advisory panel, followed by a Delphi exercise. We agreed on consensus criteria for the diagnosis of NBD with two levels of certainty in addition to recommendations on when to consider NBD in a neurological patient, and on the use of various paraclinical tests. The management recommendations included treatment of the parenchymal NBD and cerebral venous thrombosis, the use of disease modifying therapies, prognostic factors, outcome measures, and headache in BD. Future studies are needed to validate the proposed criteria and provide evidence-based treatments.
2014
- Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: results from the GISEA register
[Articolo su rivista]
Sebastiani, Marco; Anelli, Maria Grazia; Atzeni, Fabiola; Bazzani, Chiara; Farina, Ilaria; Fedele, Anna Laura; Favalli, Ennio Giulio; Fineschi, Irene; Cino, Nicolò; Dal Forno, Ilaria; Gasparini, Stefania; Cassarà, Emanuele; Giardina, Rita; Bruschi, Eleonora; Addimanda, Olga; Cassone, Giulia; Lopriore, Simona; Sarzi Puttini, Piercarlo; Filippini, Matteo; Pignatti, Federica; Gremese, Elisa; Biggioggero, Martina; Manganelli, Stefania; Amato, Giorgio; Caimmi, Cristian; Salaffi, Fausto; Iannone, Florenzo; Ferri, Clodoveo; Sandri, Gilda; Lapadula, Giovanni; Gorla, Roberto; Govoni, Marcello; Ferraccioli, Gianfranco; Marchesoni, Antonio; Galeazzi, Mauro; Foti, Rosario; Carletto, Antonio; Cantini, Fabrizio; Triolo, Giovanni; Epis, Oscar Massimiliano; Salvarani, Carlo
abstract
Introduction
Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX).
Objectives
To evaluate the efficacy and safety of RTX–MTX combination therapy compared with RTX alone in the treatment of RA.
Methods
We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed.
Results
We identified 338 RA patients, 162 treated with RTX and 176 with RTX–MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX–MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX + MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX + MTX and RTX, respectively; while 12 patients (4.5% in RTX + MTX, and 2.5% in RTX group) suspended therapy for AE.
Conclusions
RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.
2014
- Efficacy and safety of tocilizumab in refractory rheumatoid arthritis: a real life cohort from a single centre
[Articolo su rivista]
Addimanda, Olga; Possemato, Niccolò; Macchioni, Pierluigi; Salvarani, Carlo
abstract
Tocilizumab (TCZ) is an effective treatment in patients with rheumatoid arthritis (RA) refractory to anti-tumour necrosis factor-α. However, only few studies in real life have evaluated the efficacy of TCZ in long-standing rheumatoid arthritis (LSRA). Our aim was to evaluate the efficacy and safety of tocilizumab in refractory LSRA.
2014
- Epidemiology of Behçet Syndrome
[Capitolo/Saggio]
Addimanda, O.; Pazzola, G.; Pipitone, N.; Salvarani, C.
abstract
Behçet disease (BD) is a systemic inflammatory disease typically characterized by oral and genital ulcers and variable manifestations affecting other organs, mainly skin and eye. Published epidemiologic studies on BD are difficult to compare because of different study designs, settings, methods and the lack of universally accepted classification criteria: 16 different sets of classification/diagnosis criteria have been published so far; in the beginning of the chapter we compare different criteria subsets with estimates of sensitivity and specificity. After that, we review epidemiologic clinical studies (registries, hospital records, district databases): consistent data point to higher incidence and prevalence rates of BD along the ancient Silk Road (stretching from the Middle Est to the Far East and Mediterranean Countries) compared to a lower prevalence in Northern European Countries and United States genetic and environmental factors have been evaluated as well as age of onset, male-to-female ratio and systems involvement.
2014
- Epidemiology of granulomatosis with polyangiitis (Wegener's granulomatosis) in Northern Italy: a 15-year population-based study
[Articolo su rivista]
Catanoso, Mariagrazia; Macchioni, Pierluigi; Boiardi, Luigi; Manenti, Lucio; Tumiati, Bruno; Cavazza, Alberto; Luberto, Ferdinando; Pipitone, Nicolò; Salvarani, Carlo
abstract
To investigate the epidemiology of granulomatosis with polyangiitis (GPA) over a 15-year period in a defined area of northern Italy.
2014
- Granulomatosis with polyangiitis presenting as a renal mass successfully treated with rituximab
[Articolo su rivista]
Lo Gullo, Alberto; Bajocchi, Gianluigi; Cassone, Giulia; Cavazza, Alberto; Zanichelli, Matteo; Salvarani, Carlo
abstract
Granulomatosis with polyangiitis (GPA) is a granulomatous disorder usually associated with vasculitis involving the small and medium-sized blood vessels that affects the upper and lower respiratory tracts and the kidneys, but almost any organ can be targeted. The typical renal involvement of GPA consists of a segmental necrotising glomerulonephritis, but, very rarely, renal disease could appear as an isolated or bilateral renal mass, requiring a differential diagnosis from neoplasms or granulomatous infections. We describe a patient who, during tests for a kidney mass, was found
to have pulmonary nodules suspected to be metastasis, successfully treated with rituximab.
2014
- Inflamed temporal artery: histologic findings in 354 biopsies, with clinical correlations
[Articolo su rivista]
Cavazza, Alberto; Muratore, Francesco; Boiardi, Luigi; Restuccia, Giovanna; Pipitone, Nicolò; Pazzola, Giulia; Tagliavini, Elena; Ragazzi, Moira; Rossi, Giulio; Salvarani, Carlo
abstract
We reviewed 888 temporal artery biopsies (TAB) performed in 871 patients in a single institution from January 1986 to December 2013. Forty-four biopsies (4.9%) were inadequate, 490 (55.2%) were devoid of inflammation and were considered negative, and 354 (39.9%) showed inflammation and were considered positive. On the basis of the localization of the inflammation, positive TABs were further classified into 4 categories: small vessel vasculitis (SVV), in which inflammation was limited to small periadventitial vessels devoid of muscular coat, with sparing of the temporal artery (32 cases, 9% of the positive biopsies); vasa vasorum vasculitis (VVV), in which inflammation was limited to the adventitial vasa vasorum (23 cases, 6.5% of the positive biopsies); inflammation limited to adventitia (ILA), in which inflammation extended from a strictly perivascular localization to the surrounding adventitia, without medial involvement (25 cases, 7% of the positive biopsies); and transmural inflammation (TMI), in which inflammation crossed the external elastic lamina and extended to the media (274 cases, 77.5% of the positive biopsies). In TMI, inflammation was generally more prominent between media and adventitia and mostly consisted of T lymphocytes and macrophages, with occasionally a significant number of plasma cells. Numerous eosinophils or neutrophils (with or without leucocytoclasia and suppurative necrosis), fibrinoid necrosis (limited to small branches of the temporal artery), and acute thrombosis were unusual, being present in 8%, 1.8%, 0.7%, and 9.5% of our biopsies with TMI, respectively. Giant cells, laminar necrosis, and calcifications prevailed along the internal elastic lamina and were present in 74.8%, 25.2%, and 20% of the biopsies with TMI, respectively. Among the 322 patients with positive TAB on whom we obtained clinical information, 317 had giant cell arteritis and 5 had a different disease: 3 (with SVV at histology) had ANCA-associated vasculitis, 1 (with SVV with amyloid deposits) had primary systemic amyloidosis, and 1 (with TMI limited to a small branch) had polyarteritis nodosa. In none of these cases the biopsy showed fibrinoid necrosis or significant numbers of eosinophils or neutrophils. Considering the 317 patients with giant cell arteritis, those with SVV and VVV compared with those with TMI had a significantly lower frequency of cranial manifestation (including headache, jaw claudication, and abnormalities of temporal arteries), lower serum levels of acute-phase reactants, and a reduced frequency of prednisone therapy at the time of TAB, of the "halo sign" at color duplex sonography of temporal arteries, and of systemic symptoms (for VVV). Polymyalgia rheumatica and blindness were equally represented in all patients groups, whereas there was a higher frequency of male sex and peripheral arthritis in patients with SVV. Patients with ILA were more similar to those with TMI, having a lower frequency of headache, of abnormalities of temporal arteries, and of a positive "halo sign" at color duplex sonography of temporal arteries. In conclusion, the histologic spectrum of inflammatory lesions that can be found in TAB is broad, and the differences have clinical implications.
2014
- Influence of the IL17A locus in giant cell arteritis susceptibility
[Articolo su rivista]
Márquez, A; Hernández Rodríguez, J; Cid, M. C; Solans, R; Castañeda, S; Fernández Contreras, M. E; Ramentol, M; Morado, I. C; Narváez, J; Gómez Vaquero, C; Martínez Taboada, V. M; Ortego Centeno, N; Sopeña, B; Monfort, J; García Villanueva, M. J; Caminal Montero, L; de Miguel, E; Blanco, R; Palm, O; Molberg, O; Latus, J; Braun, N; Moosig, F; Witte, T; Beretta, L; Santaniello, A; Pazzola, G; Boiardi, L; Salvarani, Carlo; González Gay, M. A; Martín, J.
abstract
Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes.
2014
- Isolated aortitis versus giant cell arteritis: are they really two sides of the same coin?
[Articolo su rivista]
Talarico, Rosaria; Boiardi, Luigi; Pipitone, Nicolo'; D'Ascanio, Anna; Stagnaro, Chiara; Ferrari, Claudia; Elefante, Elena; Salvarani, Carlo; Bombardieri, Stefano
abstract
The aim of the study was to compare epidemiological data, clinical findings and results of investigations in patients with isolated aortitis and those with giant cell arteritis (GCA) to establish whether patients with isolated aortitis differ from those with GCA.
2014
- Italian Expert Panel on the management of patients with coexisting spondyloarthritis and inflammatory bowel disease
[Articolo su rivista]
Olivieri, Ignazio; Cantini, Fabrizio; Castiglione, Fabiana; Felice, Carla; Gionchetti, Paolo; Orlando, Ambrogio; Salvarani, Carlo; Scarpa, Raffaele; Vecchi, Maurizio; Armuzzi, Alessandro
abstract
Spondyloarthritis (SpA) is a group of diseases with similar clinical, radiologic and serologic features, including SpA associated with inflammatory bowel disease (IBD-associated SpA). Several studies have estimated the occurrence of SpA in IBD patients as ranging from 17% to 39%, confirming that SpA is the most frequent extra-intestinal manifestation in patients with IBD. In this paper, the expert panel presents some red flags to guide clinicians - both rheumatologists and gastroenterologists - to make a correct diagnosis of IBD-associated SpA in clinical practice. IBD-associated SpA classification, clinical presentation and diagnostic work-up are also presented. From the therapeutic point of view, only separate recommendations/guidelines are currently available for the treatment of Crohn's disease, ulcerative colitis and for both axial and peripheral SpA. However, when IBD and SpA coexist, the therapeutic strategy should be modulated to take into account the variable manifestations of IBD in terms of intestinal and extra-intestinal features, and the clinical manifestations of SpA, with particular attention to peripheral enthesitis, dactylitis and anterior uveitis. To our knowledge, this is the first attempt to define therapeutic algorithms for the integrated management of different IBD-associated SpA clinical scenarios.
2014
- Large-vessel involvement in giant cell arteritis and polymyalgia rheumatica
[Articolo su rivista]
Muratore, Francesco; Pazzola, Giulia; Pipitone, Nicolò; Boiardi, Luigi; Salvarani, Carlo
abstract
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related disorders that affect people of middle age and older, and frequently occur together. With the widespread use of newer vascular imaging modalities, large-vessel involvement (LVI) has increasingly been recognised in patients with GCA and less often in those with PMR. LVI in GCA can result in complications such as aortic aneurysm and dissection, aortic arch syndrome, and limb arteries stenosis, while vascular complications in PMR are exceedingly rare. It is still controversial which patients should be investigated for LVI, and how LVI should be diagnosed, monitored and managed. In this review, we will try to address six important issues regarding LVI in GCA and PMR.
2014
- NAILFOLD CAPILLAROSCOPIC ALTERATIONS IN DERMATOMYOSITIS AND POLYMYOSITIS
[Abstract in Rivista]
Manfredi, Andreina Teresa; Sebastiani, Marco; Cassone, Giulia; Pipitone, N; Giuggioli, Dilia; Colaci, Michele; Salvarani, Carlo; Ferri, Clodoveo
abstract
NAILFOLD CAPILLAROSCOPIC ALTERATIONS IN DERMATOMYOSITIS AND POLYMYOSITIS
2014
- Performance of the new 2012 EULAR/ACR classification criteria for polymyalgia rheumatica: comparison with the previous criteria in a single-centre study
[Articolo su rivista]
Macchioni, Pierluigi; Boiardi, Luigi; Catanoso, Mariagrazia; Pazzola, Giulia; Salvarani, Carlo
abstract
To compare the performance of published classification/diagnostic criteria for polymyalgia rheumatica (PMR), including the new 2012 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, in a single-centre study.
2014
- Predictive factors for partial remission according to the Ankylosing Spondylitis Assessment Study working group in patients with ankylosing spondylitis treated with anti-TNFα drugs
[Articolo su rivista]
Perrotta, F. M; Addimanda, O; Ramonda, R; D'Angelo, S; Lubrano, E; Marchesoni, A; Olivieri, I; Punzi, L; Salvarani, Carlo; Spadaro, A.
abstract
The objective of this study was to evaluate the predictive factors for achieving partial remission (PR) in patients with ankylosing spondylitis (AS) treated with anti-TNFα. We longitudinally enrolled in a multi-center study 214 AS patients, classified according to New York criteria, treated with anti-TNFα drugs adalimumab (ADA), etanercept (ETA) and infliximab (INF) with at least 12 months of follow up. PR was reached when the score was <20 mm (on a visual analogue scale of 0-100 mm) in each of the following 4 domains: 1) patient global assessment (in the last week); 2) pain (spinal pain); 3) function [measured by the bath ankylosing spondylitis functional index (BASFI)]; 4) inflammation [mean of intensity and duration of morning stiffness, from the bath ankylosing spondylitis disease activity index (BASDAI)]. Two hundred fourteen AS patients (M/F=160/54; median age/range=43.2/19-78 years; median disease duration/ range=96/36-189 months) were treated with ADA (15.8%), ETA (28.9%) and INF (55.1%). At 12 and 24 months, high serum level of C reactive protein (CRP) (≥2 vs ≤0.8 mg/dL) were associated with higher rate of PR in AS patients treated with anti-TNFα drugs. At 24 months, PR was associated with shorter disease duration (≤36 vs ≥189 months) and higher erythrosedimentation rate (ESR) values (≥45 vs ≤17 mm/h). In male patients lower bath ankylosing spondylitis metrology index (BASMI) (≤2 vs ≥6) and absence of psoriasis were associated with higher PR rate only at 12 months. Other parameters assessed before treatment, such as BASDAI, BASFI, peripheral arthritis, inflammatory bowel disease and uveitis were not associated with PR. Our long-term longitudinal study in a setting of clinical practice showed that inflammatory parameters (i.e. CRP, ESR) and disease duration represent the most important predictive variables to achieve PR with an anti-TNFα treatment.
2014
- Primary CNS vasculitis: Pathophysiological diversity
[Capitolo/Saggio]
Pipitone, N.; Hunder, G. G.; Salvarani, C.
abstract
Primary central nervous system vasculitis (PCNSV) is a rare vasculitis that affects the brain and occasionally the spinal cord of adults and children. Extensive progress has been achieved in the recognition of clinicopathological subsets that has translated into useful nosology reflective of the natural history and response to immunosuppressant treatment. Affected patients with small-artery vasculitis characterized by positive histology, negative cerebral angiography and prominent leptomeningeal enhancement on MRI after intravenous gadolinium administration have a milder disease course and more favorable outcome compared to those with large-artery PCNSV with multiple large-artery stenoses on cerebral angiography and extensive lesions on MRI. Subsets of patients presenting with rapidly progressive PCNSV, solitary tumor-like mass lesion and vascular amyloid deposits have the worst prognosis.
2014
- Skin manifestations in giant cell arteritis
[Capitolo/Saggio]
Pipitone, N.; Salvarani, C.; Hunder, G. G.
abstract
Giant cell arteritis is a primary systemic vasculitis involving large- and medium-sized vessels which affects almost exclusively patients aged 50 years or older. Cutaneous manifestations are rare because giant cell arteritis spares the small vessels, that is, those vessels that are typically associated with skin lesions. The most common skin abnormality observed in giant cell arteritis is thickening and, less frequently, erythema or nodules of the superficial temporal arteries. Necrosis of the scalp and tongue has also been occasionally described in patients with severe vascular ischemia induced by inflammation. Glossitis and facial edema are other rare lesions that reflect active inflammation.
2014
- Skin manifestations in microscopic polyangiitis
[Capitolo/Saggio]
Pipitone, N.; Salvarani, C.; Hunder, G. G.
abstract
Microscopic polyangiitis is a pauci-immune necrotizing small- and medium-vessel vasculitis mainly involving the lung and kidneys but also the peripheral nerves and skin. A variety of skin lesions are observed in about half of patients. The most common cutaneous manifestations are palpable purpura, livedo racemosa, and skin nodules. Histology of skin lesions typically shows leukocytoclasia with fibrinoid degeneration, neutrophil infiltration, and sometimes erythrocyte extravasation around the affected capillaries and small vessels in the dermis. Direct immunofluorescence shows absence of immunoglobulin deposits. A detailed clinical history and physical examination complemented by histological studies can aid in discriminating microscopic polyangiitis from other vasculitides affecting the skin.
2014
- The INTERnational Study on Primary Angiitis of the CEntral nervous system--a call to the world
[Articolo su rivista]
Lanthier, Sylvain; Calabrese, Leonard H; Ferro, José M; Putaala, Jukka; Strbian, Daniel; Chagnon, Miguel; Frosch, Matthew P; Singhal, Aneesh B; Salvarani, Carlo; Létourneau Guillon, Laurent; Poppe, Alexandre Y; Guilbert, François; Raymond, Jean; Muccilli, Alexandra
abstract
Treatment of Primary Angiitis of the CNS (PACNS) is a challenge aiming at minimizing the risk of treatment failure and recurrent vasculitis while avoiding adverse effects of immunosuppressive agents. Identification of markers of outcome may help tailor immunosuppressive therapy. We designed an observational, prospective, multicenter, cohort study, the INTERnational Study of Primary Angiitis of the CEntral nervous system (INTERSPACE), whose primary objective is to identify predictors of death and dependence (modified Rankin Scale: 3–6) at the end of clinical follow-up (≥one-year following recruitment).
2014
- The International Criteria for Behçet's Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria
[Articolo su rivista]
Davatchi, F; Assaad Khalil, S; Calamia, Kt; Crook, Je; Sadeghi Abdollahi, B; Schirmer, M; Tzellos, T; Zouboulis, Cc; Akhlagi, M; Al Dalaan, A; Alekberova, Zs; Ali, Aa; Altenburg, A; Arromdee, E; Baltaci, M; Bastos, M; Benamour, S; Ghorbel, I; Boyvat, A; Carvalho, L; Chen, W; Ben Chetrit, E; Chams Davatchi, C; Correia, J; Crespo, J; Dias, C; Dong, Y; Paixao Duarte, F; Elmuntaser, K; Elonakov, Av; Grana Gil, J; Haghdoost, Aa; Hayani, Rm; Houman, H; Isayeva, Ar; Jamshidi, Ar; Kaklamanis, P; Kumar, A; Kyrgidis, A; Madanat, W; Nadji, A; Namba, K; Ohno, S; Olivieri, I; Vaz Patto, J; Pipitone, N; de Queiroz, Mv; Ramos, F; Resende, C; Rosa, Cm; Salvarani, Carlo; Serra, Mj; Shahram, F; Shams, H; Sharquie, Ke; Sliti Khanfir, M; Tribolet de Abreu, T; Vasconcelos, C; Vedes, J; Wechsler, B; Cheng, Yk; Zhang, Z; Ziaei, N.
abstract
Behçet's disease (BD) is a chronic, relapsing, inflammatory vascular disease with no pathognomonic test. Low sensitivity of the currently applied International Study Group (ISG) clinical diagnostic criteria led to their reassessment.
2014
- The adherence to ASAS classification criteria and to ASAS recommendations for the use of anti-TNH-alpha agents in axial spondyloarthritis
[Articolo su rivista]
Spadaro, Antonio; Lubrano, Ennio; Marchesoni, Antonio; Cauli, Alberto; Cantini, Fabrizio; Carotti, Marina; D'Angelo, Salvatore; Grassi, Walter; Lapadula, Giovanni; Macchioni, Pierluigi; Mathieu, Alessandro; Punzi, Leonardo; Ramonda, Roberta; Salaffi, Fausto; Salvarani, Carlo; Scarpa, Raffaele; Olivieri, Ignazio
abstract
To determine the adherence of practicing rheumatologists, before and after an educational project, to Assessment of SpondyloArthritis international Society (ASAS) classification criteria and to ASAS recommendations for the use of anti-tumor necrosis factor (TNF)-alpha agents in patients with axial spondyloarthritis (SpA).
2014
- The role of tumour necrosis factor in the pathogenesis of immune-mediated diseases
[Articolo su rivista]
Blandizzi, C; Gionchetti, P; Armuzzi, A; Caporali, R; Chimenti, S; Cimaz, R; Cimino, L; Lapadula, G; Lionetti, P; Marchesoni, A; Marcellusi, A; Mennini, F. S; Salvarani, Carlo; Girolomoni, G.
abstract
Immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthropathies, Crohn's disease, ulcerative colitis and juvenile idiopathic arthritis, comprise a group of chronic disorders characterized by an immune-mediated pathogenesis. Although at clinical presentation these diseases appear unrelated, they have been recognized to share similar pathogenic mechanisms. Data from epidemiological and genetic studies further support the concept that IMIDs are interrelated, as they can co-occur in the same patient and share a similar genetic susceptibility. The specific aetiologies of IMIDs remain unknown, but all are known to involve dysregulation of the immune system, including an over-expression of the pro-inflammatory cytokine tumour necrosis factor (TNF). The pivotal role played by TNF in the pathogenesis and pathophysiology of IMIDs has been documented by extensive preclinical and clinical investigations, and confirmed by the efficacy of anti-TNF biotechnological drugs, such as etanercept, infliximab and adalimumab, in the therapeutic management of these disorders. In this narrative review, we discuss the available data on the TNF-dependent pathogenesis of IMIDs and associations among the different disorders. Although much remains to be discovered about the pathogenesis and aetiology of IMIDs, their common inflammatory pathological features may explain why they can be successfully targeted by anti-TNF drugs. Among these, adalimumab, a fully human monoclonal antibody, has been approved for treatment of nine distinct IMID indications and it is likely to become a valuable therapeutic tool for this complex cluster of chronic inflammatory disorders.
2014
- Therapeutic options after treatment failure in rheumatoid arthritis or spondyloarthritides
[Articolo su rivista]
Govoni, Marcello; Bortoluzzi, Alessandra; Lo Monaco, Andrea; Adami, Silvano; Addimanda, Olga; Caimmi, Cristian; De Vita, Salvatore; Ferri, Clodoveo; Manfredi, Andreina Teresa; Orsolini, Giovanni; Possemato, Niccolò; Quartuccio, Luca; Salvarani, Carlo; Zabotti, Alen; Rossini, Maurizio
abstract
The prognosis for patients with rheumatoid arthritis or spondyloarthritides has improved dramatically due to earlier diagnosis, recognition of the need to treat early with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), alone or in combinations, the establishment of treatment targets, and the development of biological DMARDs (bDMARDs). Many patients are now able to achieve clinical remission or low disease activity with therapy, and reduce or eliminate systemic corticosteroid use. Guidelines recommend methotrexate as a first-line agent for the initial treatment of rheumatoid arthritis; however, a majority of patients will require a change of csDMARD or step up to combination therapy with the addition of another csDMARD or a bDMARD. However, treatment failure is common and switching to a different therapy may be required. The large number of available treatment options, combined with a lack of comparative data, makes the choice of a new therapy complex and often not evidence based. We summarize and discuss evidence to inform treatment decisions in patients who require a change in therapy, including baseline factors that may predict response to therapy.
2014
- Treatment of primary CNS vasculitis with rituximab: case report
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Huston, John; Morris, Jonathan M; Hunder, Gene G.
abstract
Primary CNS vasculitis (PCNSV) is an uncommon disorder of unknown cause that is restricted to brain and spinal cord. Glucocorticoids alone or in combination with cyclophosphamide achieve a favorable response in most patients.(1,2) However, some patients are intolerant or respond poorly to cyclophosphamide; therefore, there is the need for new treatment options. We report a patient with PCNSV who appeared to respond to treatment with corticosteroids and rituximab. This study was approved by the Mayo Clinic Institutional Review Board and written informed patient consent to perform the study was obtained.
2014
- Unilateral chronic relapsing primary central nervous system vasculitis
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Morris, Jonathan M; Huston, John; Hunder, Gene G.
abstract
We report a case with chronic relapsing PCNSV involving only one cerebral hemisphere.
2014
- Validation of the classification criteria for cryoglobulinaemic vasculitis
[Articolo su rivista]
Quartuccio, Luca; Isola, Miriam; Corazza, Laura; Ramos Casals, Manuel; Retamozo, Soledad; Ragab, Gaafar Mohamed; Zoheir, Mostafa Naguib; El Menyawi, Manal Abdel Moneim; Salem, Mohamed Nabil; Sansonno, Domenico; Ferraccioli, Gianfranco; Gremese, Elisa; Tzioufas, Athanasios; Voulgarelis, Michael; Vassilopoulos, Dimitris; Scarpato, Salvatore; Pipitone, Nicolò; Salvarani, Carlo; Guillevin, Loic; Terrier, Benjamin; Cacoub, Patrice; Filippini, Davide; Saccardo, Francesco; Gabrielli, Armando; Fraticelli, Paolo; Sebastiani, Marco; Tomsic, Matija; Tavoni, Antonio; Mazzaro, Cesare; Pioltelli, Pietro; Nishimoto, Norihiro; Scaini, Patrizia; Zignego, Anna Linda; Ferri, Clodoveo; Monti, Giuseppe; Pietrogrande, Maurizio; Bombardieri, Stefano; Galli, Massimo; De Vita, Salvatore
abstract
Objective. The aim of this study was to validate the classification criteria for cryoglobulinaemic vasculitis (CV).
Methods. Twenty-three centres were involved. New patients with CV (group A) and controls, i.e. subjects with serum cryoglobulins but lacking CV based on the gold standard of clinical judgment (group B) and subjects without cryoglobulins but with clinical features that can be observed in the course of CV (group C), were studied. Positivity of serum cryoglobulins was necessary for CV classification. Sensitivity and specificity of the criteria were calculated by comparing group A vs group B. The group A vs group C comparison was done to demonstrate the possible diagnostic utility of the criteria.
Results. The study included 268 patients in group A, 182 controls in group B and 193 controls in group C (small vessel vasculitis, 51.8%). The questionnaire (at least 2/3 positive answers) showed 89.0% sensitivity and 93.4% specificity; the clinical item (at least 3/4 clinical involvement) showed 75.7% sensitivity and 89.0% specificity and the laboratory item (at least 2/3 laboratory data) showed 80.2% sensitivity and 62.4% specificity. The sensitivity and specificity of the classification criteria (at least 2/3 positive items) were 89.9% and 93.5%, respectively. The comparison of group A with group C demonstrated the clinical utility of the criteria in differentiating CV from CV mimickers.
Conclusion. Classification criteria for CV were validated in a second, large, international study confirming good sensitivity and specificity in a complex systemic disease.
2014
- anti-TNF agents as therapeutic choice in immune-mediated inflammatory diseases: focus on adalimumab
[Articolo su rivista]
Armuzzi, A; Lionetti, P; Blandizzi, C; Caporali, R; Chimenti, S; Cimino, L; Gionchetti, P; Girolomoni, G; Lapadula, G; Marchesoni, A; Marcellusi, A; Mennini, F. S; Salvarani, Carlo; Cimaz, R.
abstract
The complex pathogenesis of immune-mediated inflammatory diseases (IMIDs) has been extensively investigated and dysregulation of cytokines, such as tumour necrosis factor (TNF) has been shown to play a dominant role in the pathogenesis of various IMIDs, such as rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, psoriasis and psoriatic arthritis. The subsequent development of biological agents capable of blocking TNF has led to important advances in the pharmacotherapy of such diseases and confirmed the concept of a common pathophysiology among IMIDs with TNF having a predominant role. Five TNF inhibitors have currently been approved for treatment of one or more IMIDs; these include infliximab, etanercept, adalimumab, golimumab and certolizumab pegol. Given the similarities in the pathogenic background of IMIDs, one could expect that anti-TNF agents be similarly effective and with comparable tolerability profiles; however, this may not be the case. Structural and pharmacological differences among the anti-TNF drugs are likely to result in differences in efficacy and tolerability among the agents in the different IMIDs, together with differences in potency, therapeutic dose ranges, dosing regimens, administration routes, and propensity for immunogenicity. Among the five TNF inhibitors approved for treatment of IMIDs, adalimumab has the widest range of indications. Data from controlled clinical trials of adalimumab, showing its excellent efficacy and tolerability in a wide range of indications, are supported by real-world long-term data from observational studies, which confirm the value of adalimumab as a suitable choice in the management of IMIDs.
2013
- Aβ-related angiitis: comparison with CAA without inflammation and primary CNS vasculitis
[Articolo su rivista]
Salvarani, Carlo; Hunder, Gene G; Morris, Jonathan M; Brown, Robert D; Christianson, Teresa; Giannini, Caterina
abstract
To analyze the clinical findings, response to therapy, and outcomes of patients with cerebral vascular amyloid-β (Aβ) deposition with and without inflammatory vascular infiltration.
2013
- CC chemokine receptor 5 polymorphism in Italian patients with giant cell arteritis
[Articolo su rivista]
Pazzola, Giulia; Boiardi, Luigi; Casali, Bruno; Farnetti, Enrico; Nicoli, Davide; Pipitone, Nicolò; Padovano, Ilaria; Caruso, Andrea; Catanoso, Mariagrazia; Salvarani, Carlo
abstract
To evaluate the potential role of CC chemokine receptor 5 (CCR5)Δ32 polymorphism in the susceptibility to giant cell arteritis (GCA) in a cohort of Italian patients.
2013
- CD25 blockade for refractory polymyositis
[Articolo su rivista]
Pipitone, Nicolò; Salvarani, Carlo
abstract
We report a patient with refractory PM treated with the high-affinity interleukin-2 receptor (CD25) blocker basiliximab.
2013
- Classifying idiopathic inflammatory myopathies: comparing the performance of six existing criteria
[Articolo su rivista]
Linklater, Helen; Pipitone, Nicolò; Rose, Michael R; Norwood, Fiona; Campbell, Richard; Salvarani, Carlo; Scott, D. L; Gordon, Patrick
abstract
Various criteria have been proposed to classify the inflammatory myositides (IIMs) polymyositis (PM) and dermatomyositis (DM). However, none have received universal acceptance. Our aim was to assess the performance of the main criteria used to classify IIM. Specialist consultant diagnosis was considered the gold standard.
2013
- Comparison between colour duplex sonography findings and different histological patterns of temporal artery
[Articolo su rivista]
Muratore, Francesco; Boiardi, Luigi; Restuccia, Giovanna; Macchioni, Pierluigi; Pazzola, Giulia; Nicolini, Alberto; Germanò, Giuseppe; Possemato, Niccolò; Cavazza, Alberto; Cavuto, Silvio; Cimino, Luca; Pipitone, Nicolò; Catanoso, Mariagrazia; Addimanda, Olga; Salvarani, Carlo
abstract
To assess the findings of temporal artery colour duplex sonography (CDS) in GCA characterized by a histological pattern of periadventitial small vessel vasculitis (SVV) and/or vasa vasorum vasculitis (VVV) and compare it with those observed in classic GCA with transmural vasculitis.
2013
- Discontinuation of therapies in polymyalgia rheumatica and giant cell arteritis
[Articolo su rivista]
Muratore, Francesco; Pipitone, Nicolò; Hunder, Gene G; Salvarani, Carlo
abstract
Glucocorticoids are highly effective in treating polymyalgia rheumatica and giant cell arteritis, but their use is associated with numerous adverse events. Therefore, it is important to use them for the shortest period of time possible. The published evidence suggests that discontinuation of GC is feasible in a substantial number of patients with polymyalgia rheumatica and giant cell arteritis after an adequate period of treatment, provided that glucocorticoids are tapered gradually. Recurrences are relatively infrequent in polymyalgia rheumatica and somewhat more common in giant cell arteritis. Immunosuppressive agents may be used in patients with frequently relapsing or recurring disease to decrease exposure to glucocorticoids.
2013
- Evidence of association of the NLRP1 gene with giant cell arteritis
[Articolo su rivista]
Serrano, Aurora; Carmona, F. David; Castañeda, Santos; Solans, Roser; Hernández Rodríguez, José; Cid, María C; Prieto González, Sergio; Miranda Filloy, José A; Rodríguez Rodríguez, Luis; Morado, Inmaculada C; Gomez Vaquero, Carmen; Blanco, Ricardo; Sopeña, Bernardo; Ortego Centeno, Norberto; Unzurrunzaga, Ainhoa; Marí Alfonso, Begoña; Sánchez Martín, Julio; García Villanueva, María Jesús; Hidalgo Conde, Ana; Pazzola, Giulia; Boiardi, Luigi; Salvarani, Carlo; González Gay, Miguel A; Martín, Javier
abstract
We report the evidence of association of the NLRP1 gene with giant cell arteritis
2013
- Functional impairment of systemic scleroderma patients with digital ulcerations: results from the DUO Registry
[Articolo su rivista]
Raffier, B; Hirschi, M; Trautinger, F; Schmidt, P; Stetter, M; Hundstorfer, M; Reinhart, V; Monshi, B; Pirkhammer, D; Richter, L; Hamberger, N; Metz, S; Feldmann, R; Semmelweis, K; Lackner, K; Tomi, N; Kolle, H; Hafner, F; Brodmann, M; Kuen Spiegel, M; Minmair, G; Heil, Pm; Broil, H; Holzer, G; Illmer, X; Rintelen, B; Sautner, J; Takacs, M; Thun, M; Zemanova, I; Soukup, T; Smrzova, A; Bohmova, J; Prochazkova, L; Nemec, P; Fojtik, Z; Suchy, D; Becvar, R; Olsen, Ab; Sondergaard, Kh; Luosu jarvi, R; Vidqvist, Kl; Madaule, S; Beneton, N; Maillard, H; Charlanne, H; Granelbrocard, F; Hachulla, E; Hatron, Py; Jourdain, N; Lambert, M; Launay, D; Morell, S; Woijtasik, G; Skowron, F; Zenone, T; Dadban, A; Lok, C; Ferrandiz, D; Magybertrand, N; Moiton, Mp; Taieb, A; Balquiere, S; Belin, E; Droitcourt, C; Julien, S; Prey, S; Boulon, C; Constans, J; Doutre, Ms; Kostrzwewa, E; Richez, C; Greco, M; Misery, L; Sassolas, B; Collet, E; Berthier, S; Leguy Seguin, V; Imbert, B; Carpentier, P; Blaise, S; Couraud, A; Doeffel Hantz, V; Spars, A; Bezanahary, H; Boussely, N; Dumonteil, S; Fauchais, Al; Goudran, G; Loustaud Ratti, V; Manea, P; Vidal, E; Coppere, B; Desmursclavel, H; Girard Madoux, Mh; Hot, A; Ninet, J; Granel, B; Cohen, Jd; Keynote, A; Khau van Kien, A; Le Quellec, A; Riviere, S; Rullier, P; Bessis, D; Farcas, C; Bravetti, V; Moline, T; Wahl, D; Zuily, S; Granel Brocard, F; Agard, C; Durant, C; Fuzibet, Jg; Queyrel, V; Berezne, A; Guillevin, L; Mouthon, L; Cabane, J; Tiev, K; Toledano, C; Lazareth, I; Michon Pasturel, U; Priollet, P; Reguiai, Z; Cazaletslacoste, C; Jego, P; Letremy, A; Perlat, A; Duval Modeste, Ab; Chatelus, E; Chiffot, H; Sibillia, J; Sordet, C; Adoue, D; Couret, B; Moulis, G; Pugnet, G; Sailler, L; Diot, E; Gaches, F; Farge, D; Keshtmand, H; Frances, C; von Elling, A; Bora, D; Ebel, J; Ahmadi Simab, K; Klein, E; Hahn, K; Schulze, K; Rasche, C; Riemekasten, G; Lee, Hh; Deuschle, K; Mattat, K; Becker, M; Worm, M; Mensing, C; Klings, D; Mensing, H; Messall, J; Zuper, R; Eilbacher, P; Saar, P; Kaufmann, P; Hallermann, C; Schmidt, K; Wahn, H; Schildt, K; Schuart, T; Kaczmarczyk, A; Kellner, C; von Oelhafen, J; Baron von Bildering, P; Kunze, S; Kleiner, Hj; Alsheimer, B; Schuetz, N; Miirker Hermann, E; Gottl, Kh; Weiss, E; Reischel, N; Kern, S; Goettl, Kh; Goetheuniversitiitsklinikum, Jw; Himsel, A; Henkemeier, U; Schwarting, A; Hazenbiller, A; Nichelmann, V; Rumbaur, C; Boesenberg, I; Schmeiser, T; Mueller Ladner, U; Unholzer, A; Starz, H; Welzel, J; Plaumann, K; Stoeckl, F; Sperling, S; Podda, M; Wagner, N; Rapprich, H; Niedermeier, A; Messer, G; Sardy, M; Bekou, V; Dill MUller, D; Wlodarz, M; Belloni, B; Huettig, B; Ziai, M; Hein, R; Kneitz, C; Federow, I; Schneider, K; Semmler, M; Hapke, S; Metzler, C; Stein, T; Enderlein, M; Kayser, M; Werthmann, M; Guenther, Cu; Neul, S; Hellmich, B; Loeffler, C; Pflugfelder, J; Karaenke, P; Mueglich, C; Tony, Hp; Marina, P; Popp, M; Mittag, M; Mittag, M; Baumann, C; Baumann, C; Scheib, Eg; Scheib, Eg; Brand, H; Wilhelm, Hu; Wilhelm, Hu; Bohm, J; Dyballa, J; Boehm, J; Taggeselle, J; Taggeselle, J; Luthke, K; Wuerzburg, I; Luthke, K; Niefanger, K; Niefanger, K; Mayer, L; Drabek, J; Harmuth, W; Harmuth, W; Dietl, S; Moritz, D; Dietl, S; Gause, A; Gause, A; Gaubitz, M; Hallecker, A; Gaubitz, M; Krupp, E; Rumpel, H; Moosig, F; Frey, P; Kahl, S; Linke, M; Merk, B; Bloching, Hh; Ochs, W; Kurthen, R; Kurthen, R; Eiden, E; Guertler, I; Aries, Pm; Kirchberg, S; Jahnke, K; Mettler, S; Toeller, S; Zwenger, S; Langer, He; Deininger, F; Hartmann, F; Neeck, G; Neek, G; Wernitzsch, H; Meier, L; Herr, U; Meier, U; Aaig, W; Schwarting, A; Bruckner, L; Sheikh, N; Wollenhaupt, J; Krog, B; Wollersdorfer, E; Hall, R; Diehm, C; Tiggers, C; Peters, J; Kirschke, J; Schroeder, Jo; Zeuner, R; Uhlig, S; Barth, S; Huegel, R; Glaeser, R; Schaefer, C; Monshausen, M; Mengden, T; Funkert, A; Blank, N; Lupaschko, S; Voss, B; Megahed, M; Sadeghlar, F; Seidel, M; Wasmuth, Jc; Kreuter, A; Vosswinkel, J; Pfoehler, C; Ge
abstract
OBJECTIVES: Digital ulcers (DUs) are frequent manifestations of systemic scleroderma (SSc). This study assessed functional limitations due to DUs among patients enrolled in the Digital Ulcer Outcome (DUO) Registry, an international, multicentre, observational registry of SSc patients with DU disease.
METHODS: Patients completed at enrolment a DU-specific functional assessment questionnaire with a 1-month recall period, measuring impairment in work and daily activities, and hours of help needed from others. Physician-reported clinical parameters were used to describe the population. For patients who completed at least part of the questionnaire, descriptive analyses were performed for overall results, and stratified by number of DUs at enrolment.
RESULTS: This study included 2327 patients who completed at least part of the questionnaire. For patients with 0, 1-2, and ≥3 DUs at enrolment, mean overall work impairment during the prior month among employed/self-employed patients was 28%, 42%, and 48%, respectively. Across all included patients, ability to perform daily activities was impaired on average by 35%, 54%, and 63%, respectively. Patients required a mean of 2.0, 8.7, and 8.8 hours of paid help and 17.0, 35.9, and 63.7 hours of unpaid help, respectively, due to DUs in the prior month. Patients with DUs had more complications and medication use than patients with no DUs.
CONCLUSIONS: With increasing number of DUs, SSc patients reported more impairment in work and daily activities and required more support from others.
2013
- IL-23A, IL-23R, IL-17A and IL-17R polymorphisms in different psoriatic arthritis clinical manifestations in the northern Italian population
[Articolo su rivista]
Catanoso, Maria Grazia; Boiardi, Luigi; Macchioni, Pierluigi; Garagnani, Paolo; Sazzini, Marco; De Fanti, Sara; Farnetti, Enrico; Casali, Bruno; Chiarolanza, Ilaria; Nicoli, Davide; Luiselli, Donata; Salvarani, Carlo
abstract
To investigate the genetic variability of IL-17A, IL17-RA, IL-23A and IL-23R genes on an in-depth phenotypically characterized northern Italian Psoriatic arthritis (PsA) case-control cohort, in search for associations specific to different PsA clinical sub-phenotypes. We examined 118 patients with PsA according to CASPAR criteria (mean age 57 ± 13, female 38.4 %, mean disease duration 13.9 ± 8.6 years, peripheral disease 83.8 %, axial manifestations 34.5 %, radiological erosive disease 49 %) compared with 248 controls of the same ethnic origin matched for age and sex. The presence of axial disease was defined by the clinical axial involvement and/or the presence of radiological alteration consistent with spondyloarthropathy according to New York criteria. The presence of peripheral disease (arthritis and/or enthesitis) was defined only on clinical basis. A total of 40 SNPs, mapping within the genes mentioned above, were genotyped in both groups and used to perform association analyses by subdividing the PsA sample into subgroups according to different clinical manifestations on the basis of axial and peripheral involvements. No differences between patients and controls were found in the distribution of the IL-17A, IL17-RA, IL-23A and IL-23R genes allelic variants. Comparing patients with axial disease versus those without, we found that axial manifestations were significantly associated with the presence of IL-23R rs12401432 GG homozygosity (26.8 % vs. 5.3 %, p corr = 0.019, OR 2.63 [95 % CI 1.13-6.16]). No differences in distribution of the allelic variants were found comparing patients with versus those without peripheral disease or patients with versus without radiological peripheral erosions. In PA patients of northern Italian origin, IL-17A, IL17-RA, IL-23A and IL-23R genes allelic variants are not associated with disease susceptibility. However, a strong association with the IL-23RA rs12401432 GG genotype is associated with axial involvement of the disease.
2013
- IL-33 is overexpressed in the inflamed arteries of patients with giant cell arteritis
[Articolo su rivista]
Ciccia, Francesco; Alessandro, Riccardo; Rizzo, Aroldo; Raimondo, Stefania; Giardina, Annarita; Raiata, Francesca; Boiardi, Luigi; Cavazza, Alberto; Guggino, Giuliana; De Leo, Giacomo; Salvarani, Carlo; Triolo, Giovanni
abstract
To study the expression of interleukin (IL)-33 and to evaluate its relationship with macrophage polarisation in artery biopsy specimens from patients with giant cell arteritis (GCA).
2013
- Identification of multiple independent susceptibility loci in the HLA region in Behçet's disease
[Articolo su rivista]
Hughes, Travis; Coit, Patrick; Adler, Adam; Yilmaz, Vuslat; Aksu, Kenan; Düzgün, Nursen; Keser, Gokhan; Cefle, Ayse; Yazici, Ayten; Ergen, Andac; Alpsoy, Erkan; Salvarani, Carlo; Casali, Bruno; Kötter, Ina; Gutierrez Achury, Javier; Wijmenga, Cisca; Direskeneli, Haner; Saruhan Direskeneli, Güher; Sawalha, Amr H.
abstract
Behçet's disease is an inflammatory disease characterized by recurrent oral and genital ulcers and significant organ involvement. Localizing the genetic association between HLA-B*51 and Behçet's disease and exploring additional susceptibility loci in the human leukocyte antigen (HLA) region are complicated by the strong linkage disequilibrium in this region. We genotyped 8,572 variants in the extended HLA locus and carried out imputation and meta-analysis of 24,834 variants in 2 independent Behçet's disease cohorts from 2 ancestry groups. Genotyped SNPs were used to infer classical HLA alleles in the HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1 and HLA-DRB1 loci. Our data suggest that the robust HLA-B*51 association in Behçet's disease is explained by a variant located between the HLA-B and MICA genes (rs116799036: odds ratio (OR) = 3.88, P = 9.42 × 10(-50)). Three additional independent genetic associations within PSORS1C1 (rs12525170: OR = 3.01, P = 3.01 × 10(-26)), upstream of HLA-F-AS1 (rs114854070: OR = 1.95, P = 7.84 × 10(-14)) and with HLA-Cw*1602 (OR = 5.38, P = 6.07 × 10(-18)) were also identified and replicated.
2013
- Interleukin-6 as an inflammatory mediator and target of therapy in chronic periaortitis
[Articolo su rivista]
Vaglio, Augusto; Catanoso, Maria G; Spaggiari, Lucia; Magnani, Luca; Pipitone, Nicolò; Macchioni, Pierluigi; Pulsatelli, Lia; Nicastro, Maria; Becchi, Gabriella; Corradi, Domenico; Versari, Annibale; Boiardi, Luigi; Salvarani, Carlo
abstract
Chronic periaortitis (CP) usually responds to glucocorticoids, but some patients have glucocorticoid-refractory disease or contraindications to glucocorticoid therapy. This study was undertaken to evaluate treatment with the anti-interleukin-6 receptor (anti-IL-6R) antibody tocilizumab in 2 patients with CP, one with refractory disease and the other with contraindications to glucocorticoids, and to assess IL-6 levels in an additional cohort of patients with CP.
2013
- Is (18)F fluorodeoxyglucose positron emission tomography useful to assess activity of myositis?
[Articolo su rivista]
Pipitone, Nicolò; Versari, Annibale; Salvarani, Carlo
abstract
Letter to the editor
2013
- Is 18F-FDG PET a 'potentially hazardous' or an effective tool in evaluating patients with large-vessel vasculitis?
[Articolo su rivista]
Treglia, G; Versari, A; Giovanella, L; Pipitone, N; Salvarani, Carlo
abstract
Letter to the editor
2013
- L30. Assessment of vasculitis extent and severity
[Articolo su rivista]
Pipitone, Nicolò; Pazzola, Giulia; Muratore, Francesco; Salvarani, Carlo
abstract
Review on the assessment of vasculitis extent and severity.
2013
- Lumbar interspinous bursitis in active polymyalgia rheumatica
[Articolo su rivista]
Salvarani, Carlo; Barozzi, Libero; Boiardi, Luigi; Pipitone, Nicolò; Bajocchi, Gian Luigi; Macchioni, Pier Luigi; Catanoso, Mariagrazia; Pazzola, Giulia; Valentino, Massimo; De Luca, Carlo; Hunder, Gene G.
abstract
To evaluate the inflammatory involvement of lumbar interspinous bursae in patients with polymyalgia rheumatica (PMR) using magnetic resonance imaging (MRI).
2013
- NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica
[Articolo su rivista]
Dejaco, Christian; Duftner, Christina; Al Massad, Juman; Wagner, Annette D; Park, Joon Keun; Fessler, Johannes; Aigelsreiter, Ariane; Hafner, Franz; Vega, Sandra; Sterlacci, William; Grubeck Loebenstein, Beatrix; Tzankov, Alexander; Ness, Thomas; Boiardi, Luigi; Salvarani, Carlo; Schirmer, Michael
abstract
To investigate functional expression of NKG2D on CD4 and CD8 T-cells in patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).
2013
- Obesity and reduction of the response rate to anti-tumor necrosis factor α in rheumatoid arthritis: an approach to a personalized medicine
[Articolo su rivista]
Gremese, Elisa; Carletto, Antonio; Padovan, Melissa; Atzeni, Fabiola; Raffeiner, Bernd; Giardina, Anna Rita; Favalli, Ennio Giulio; Erre, Gian Luca; Gorla, Roberto; Galeazzi, Mauro; Foti, Rosario; Cantini, Fabrizio; Salvarani, Carlo; Olivieri, Ignazio; Lapadula, Giovanni; Ferraccioli, Gianfranco
abstract
Obesity is a mild, long-lasting inflammatory disease and, as such, could increase the inflammatory burden of rheumatoid arthritis (RA). The study aim was to determine whether obesity represents a risk factor for a poor remission rate in RA patients requiring anti-tumor necrosis factor α (anti-TNFα) therapy for progressive and active disease despite treatment with methotrexate or other disease-modifying antirheumatic drugs.
2013
- Pulmonary artery involvement in Takayasu arteritis. PET/CT versus CT angiography
[Articolo su rivista]
Addimanda, O; Spaggiari, L; Pipitone, N; Versari, A; Pattacini, P; Salvarani, Carlo
abstract
To report a patient with Takayasu arteritis in whom 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computerised tomography (CT) failed to demonstrate pulmonary artery involvement.
2013
- RESULTS OF THE CLASSIFICATION CRITERIA FOR CRYOGLOBULINEMIC VASCULITIS VALIDATION STUDY
[Abstract in Rivista]
Ferri, Clodoveo; Salvarani, Carlo
abstract
not available
2013
- Remission in ankylosing spondylitis treated with anti-TNF-α drugs: a national multicentre study
[Articolo su rivista]
Spadaro, Antonio; Lubrano, Ennio; Marchesoni, Antonio; D'Angelo, Salvatore; Ramonda, Roberta; Addimanda, Olga; Perrotta, Fabio Massimo; Olivieri, Ignazio; Punzi, Leonardo; Salvarani, Carlo
abstract
The primary objective of this retrospective study was to investigate the possibility of achieving partial remission (PR) in AS patients treated with anti-TNF-α antagonists, such as adalimumab (ADA), etanercept (ETA) and infliximab (INF), in a real clinical practice setting. Predictors of PR were also evaluated.
2013
- Role of imaging in the diagnosis of large and medium-sized vessel vasculitis
[Articolo su rivista]
Pipitone, Nicolò; Versari, Annibale; Hunder, Gene G; Salvarani, Carlo
abstract
In large-vessel vasculitis, imaging studies are useful to document temporal artery involvement and crucial to show large-vessel involvement. Color Doppler sonography, magnetic resonance, and computed tomography show early vasculitic lesions. Angiography delineates later vascular complications well. Color Doppler sonography, magnetic resonance angiography, and computed tomography angiography can also be used to show vascular luminal changes. Positron emission tomography is very sensitive in detecting large-vessel inflammation. Imaging procedures can also be used to monitor the course of large-vessel vasculitis. In medium-vessel vasculitis, imaging studies can be used to show both vascular changes and internal organ changes.
2013
- Scurvy mimicking spondyloarthritis in a young man
[Articolo su rivista]
Pazzola, Giulia; Possemato, Niccolò; Germanò, Giuseppe; Salvarani, Carlo
abstract
Clinical image
2013
- Searching for viral antibodies and genome in intraocular fluids of patients with Fuchs uveitis and non-infectious uveitis
[Articolo su rivista]
Cimino, Luca; Aldigeri, Raffaella; Parmeggiani, Maria; Belloni, Lucia; Zotti, Carlo Alberto; Fontana, Luigi; Invernizzi, Alessandro; Salvarani, Carlo; Cappuccini, Luca
abstract
To characterise the polyspecific intraocular antibody synthesis in aqueous humor of patients with Fuchs uveitis and other types of non-infectious uveitis.
2013
- Systemic sclerosis lung disease in limited (C.R.E.S.T.) and diffuse subset
[Articolo su rivista]
Bajocchi, G.; Carbonelli, C.; Zucchi, L.; Salvarani, C.
abstract
Fibrosing alveolitis and arterial pulmonary hypertension are the main cardiopulmonary findings in patients with systemic sclerosis. Clinically significant interstitial lung disease occurs in about 50% of the cases while 20% of the cases has pulmonary arterial hypertension. The onset of interstitial lung disease is characterized by cellular infiltration (alveolitis) and microvascular injury. Nonspecific interstitial pneumonia is the most common outcome of this pathological process. The extent of damage by means of high resolution CT and of disease severity by measuring the reduction of forced vital capacity with co-existing or isolated reduction of diffusing capacity, at the onset of the disease, are predictive of pulmonary fibrosis or pulmonary arterial hypertension. A case report with a limited cutaneous scleroderma leading to a fatal pre-capillary pulmonary arterial hypertension is presented.
2013
- TIR-domain-containing adaptor protein gene TIRAP S180L polymorphism is not increased in Behçet's disease patients in two ethnic cohorts
[Articolo su rivista]
Turunc, Gorkem; Coskun, Doga; Alibaz Oner, Fatma; Coit, Patrick; Duzgun, Nursen; Alpsoy, Erkan; Yentur, Sibel P; Salvarani, Carlo; Casali, Bruno; Kötter, Ina; Ergun, Tulin; Direskeneli, Haner; Sawalha, Amr H; Saruhan Direskeneli, Guher
abstract
The single nucleotide polymorphism (SNP) of TIRAP (Serine 180 leucine, S180L) that is shown to be associated with Behçet's disease (BD) in a European-derived cohort, but not in Middle Eastern patients is investigated in two other populations.
2013
- TLR-4 and VEGF polymorphisms in chronic periaortitis
[Articolo su rivista]
Atzeni, Fabiola; Boiardi, Luigi; Vaglio, Augusto; Nicoli, Davide; Farnetti, Enrico; Palmisano, Alessandra; Pipitone, Nicolò; Martorana, Davide; Moroni, Gabriella; Longhi, Selena; Bonatti, Francesco; Buzio, Carlo; Salvarani, Carlo
abstract
Chronic periaortitis (CP) is a rare disease that is characterised by fibro-inflammatory tissue surrounding the abdominal aorta and has both non-aneurysmal (idiopathic retroperitoneal fibrosis [IRF]) and aneurysmal forms (inflammatory abdominal aortic aneurysm [IAAA]). We investigated whether toll-like receptor 4 (TLR-4) and vascular endothelial growth factor (VEGF) polymorphisms were associated with susceptibility to, and the clinical features of CP.
2013
- Tocilizumab for polymyalgia rheumatica: report of two cases and review of the literature
[Articolo su rivista]
Macchioni, Pierluigi; Boiardi, Luigi; Catanoso, Mariagrazia; Pulsatelli, Lia; Pipitone, Nicolò; Meliconi, Riccardo; Salvarani, Carlo
abstract
Glucocorticoids (GC) are the mainstay of treatment of polymyalgia rheumatica (PMR). However GC-related adverse events occur frequently, particularly in patients with relapsing disease. Several studies have demonstrated that IL-6 is a key player in the pathogenesis of PMR.
2013
- Tocilizumab in glucocorticoid-naïve large-vessel vasculitis
[Articolo su rivista]
Pazzola, G; Padovano, I; Boiardi, L; Versari, A; Pipitone, N; Catanoso, M; Pulsatelli, L; Meliconi, R; Salvarani, Carlo
abstract
Glucocorticoids (GC) are the mainstay of treatment of large-vessel vasculitis (LVV), but a sizeable number of patients relapse upon tapering the GC dose or after discontinuation of GC therapy. In addition, GC cause numerous adverse events. Therefore, in patients with longstanding disease and in those at risk for GC-related adverse events, the use of alternative therapeutic agents should be considered. Interleukin-6 (IL-6) is a key player in the pathogenesis of LVV. Preliminary data suggest the efficacy of the IL-6 receptor inhibitor tocilizumab (TCZ) in patients with LVV. We report 2 treatment-naïve patients with a recent diagnosis of LVV who received monthly TCZ infusions (8 mg/kg body weight) for 6 consecutive months as monotherapy because of relative contraindications and patients' reluctance to take GC. In both cases we observed a complete clinical response and normalisation of inflammatory markers as well as a decrease in vascular FDG uptake and SUV ratio on fluorodeoxyglucose positron emission/computerised tomography. Serum IL-6 and soluble IL-6 receptor (sIL-6R) levels rose in both patients after TCZ therapy. TCZ may be an effective alternative to GC treatment for LVV patients at risk for GC-related adverse events. Larger studies are required to confirm our findings.
2013
- Ultrasonographic predictors for the development of joint damage in rheumatoid arthritis patients: a single joint prospective study
[Articolo su rivista]
Macchioni, Pierluigi; Magnani, Mirco; Mulè, Rita; Galletti, Stefano; Catanoso, Mariagrazia; Pignotti, Elettra; Boiardi, Luigi; Meliconi, Riccardo; Salvarani, Carlo
abstract
This paper aims to evaluate if any ultrasonographic aspect of metacarpo-phalangeal (MCP) joint can be predictors for the development of new joint damage, at single joint level, in rheumatoid arthritis (RA) patients.
2013
- Update on polymyalgia rheumatica
[Articolo su rivista]
Pipitone, Nicolò; Salvarani, Carlo
abstract
Polymyalgia rheumatica is an inflammatory disease of unknown etiology affecting individuals aged fifty years and older, mainly of Caucasian ethnicity. Polymyalgia rheumatica is associated with giant cell arteritis more frequently than expected by chance alone. In both conditions, females are affected two to three times more often than males. The clinical hallmark manifestations of polymyalgia rheumatica are aching and morning stiffness in the shoulder girdle and often in the pelvic girdle and neck. Serum inflammatory markers are typically elevated, while the most consistent abnormal finding on imaging studies is bursitis in the symptomatic areas. A dramatic response to glucocorticoids is characteristic of polymyalgia rheumatica. Many patients are able to discontinue glucocorticoids six months to two years after the onset of clinical symptoms, but some patients may require longstanding glucocorticoid treatment. Glucocorticoid-sparing agents may be helpful in patients with chronic relapsing courses and those at high risk of glucocorticoid-related adverse events.
2013
- Validation Study Of The International Classification Criteria For The
Cryoglobulinemic Vasculitis
[Abstract in Rivista]
Luca, Quartuccio; Miriam, Isola; Laura, Corazza; Soledad, Retamozo; Manal Abdel Moneim El, Menyawi; Elisa, Gremese; Sebastiani, Marco; Nicolo, Pipitone; Teresa, Urraro; Vincenza, Conteduca; Christos, Koutsianas; Benjamin, Terrier; Mostafa Naguib, Zoheir; Alessandra, Ghinoi; Davide, Filippini; Francesco, Saccardo; Mohamed Nabil, Salem; Salvatore, Scarpato; Paolo, Fraticelli; Antonio, Tavoni; Eleonora, Catarsi; Cesare, Mazzaro; Pietro, Pioltelli; Mervat, Matar; Patrizia, Scaini; Matija, Tomsic; Norihiro, Nishimoto; Dimitrios, Vassilopoulos; Michael, Voulgarelis; Gaafar M., Ragab; Salvarani, Carlo; Armando, Gabrielli; Patrice, Cacoub; Loic, Guillevin; Domenico, Sansonno; Anna Linda, Zignego; Gianfranco, Ferraccioli; Athanasios G., Tzioufas; Manuel Ramos, Casals; Ferri, Clodoveo; Maurizio, Pietrogrande; Giuseppe, Monti; Massimo, Galli; Stefano, Bombardieri; Salvatore De, Vita
abstract
Background/Purpose: preliminary Classification Criteria for cryoglobulinemic vasculitis (CV) have been developed in 2011 by an European cooperative study, with an adequate methodology in a large number of real cases and controls (1). The aim of this study is to validate these classification criteria for CV.
Methods: Centres from Europe, United States, Japan and Egypt, were involved. A dedicated chart included: l) a validated questionnaire for CV (1); 2) the pattern of organ involvement (4 items: constitutional, articular, vascular and neurologic involvement); 3) laboratory tests (3 items: rheumatoid factor,
complement C4 and serum monoclonal component), according to the preliminary criteria (1). New patients with CV (Group A) and controls (Group B), i.e., subjects with cryoglobulins but lacking CV based on the golden standard clinical judgment, were studied. A sample size of at least 140 patients for each group was estimated in order to obtain a sensitivity and a specificity of at least 90.5%, based on the previous results (1). Sensitivity and specificity were
calculated by comparing Group A versus Group B. Finally, not for classification purposes, but to disclose whether the Criteria may be also clinically helpful in patients lacking serum cryoglobulins, but where CV is suspected (1), Group A was also compared with Group C, including patients with diseases mimicking CV, but without serum cryoglobulins.
Results: Six hundred forty-three patients were enrolled in 22 Centres (from Italy, Spain, France, Greece, Slovenia, Japan and Egypt). MajorA comprised 268 patients with CV, Group B 182 controls with serum cryoglobulins without CV, and Group C 193 controls without serum cryoglobulins. Notably, 20 patients showed type I cryoglobulinemia, 13 in Group A, and 7 in Group B. Group C included 108/193 (55.9%) systemic vasculitides, 100/108 (92.6%) were small vessel vasculitides. The classification criteria [positivity of at least 2/3 items among questionnaire (2/3 positive questions), clinical item (3/4 clinical manifestations), laboratory (2/3 tests)] showed 89.9% (95% CI 86.1–93.6) of sensitivity and 93.5%
(95% CI 89.7–97.2) of specificity, replicating previous results (1). Sensitivity of 91.7% and specificity of 100% were observed in the subgroup of type I cryoglobulinemia. By the comparison of Group A vs. Group C, the Criteria showed a specificity 92.6% (88.8–96.5) and a sensitivity of 77.8% (72.6–83.0) when the laboratory item was positive (questionnairelaboratory item; or clinical laboratory item).
Conclusion: the International Classification Criteria for the CV have been validated in a new real cohort. High specificity and sensitivity were confirmed. Notably, in patients where CV is suspected on clinical grounds, but where cryoglobulins are negative by initial testing, or not yet available (patients who cannot be classified as CV, as positive serum cryoglobulinemia is a conditio sine qua non for classification) (1), the Criteria appear relevant to strengthen the suspicion for CV, and to optimize the follow-up.
2012
- 18F-Fluorodeoxyglucose positron emission tomography for the assessment of myositis: a case series
[Articolo su rivista]
Pipitone, Nicolo; Versari, Annibale; Zuccoli, Giulio; Levrini, Gabriele; Macchioni, Pierluigi; Bajocchi, Gianluigi; Salvarani, Carlo
abstract
To establish whether 18FFluorodeoxyglucose (FDG) positron emission computerised tomography (FDG-PET/CT) might reveal active disease in patients with myositis.
2012
- 2012 Provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative
[Articolo su rivista]
Dasgupta, Bhaskar; Cimmino, Marco A; Kremers, Hilal Maradit; Schmidt, Wolfgang A; Schirmer, Michael; Salvarani, Carlo; Bachta, Artur; Dejaco, Christian; Duftner, Christina; Jensen, Hanne Slott; Duhaut, Pierre; Poór, Gyula; Kaposi, Novák Pál; Mandl, Peter; Balint, Peter V; Schmidt, Zsuzsa; Iagnocco, Annamaria; Nannini, Carlotta; Cantini, Fabrizio; Macchioni, Pierluigi; Pipitone, Nicolò; Del Amo, Montserrat; Espígol Frigolé, Georgina; Cid, Maria C; Martínez Taboada, Víctor M; Nordborg, Elisabeth; Direskeneli, Haner; Aydin, Sibel Zehra; Ahmed, Khalid; Hazleman, Brian; Silverman, Barbara; Pease, Colin; Wakefield, Richard J; Luqmani, Raashid; Abril, Andy; Michet, Clement J; Marcus, Ralph; Gonter, Neil J; Maz, Mehrdad; Carter, Rickey E; Crowson, Cynthia S; Matteson, Eric L.
abstract
The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of rheumatoid factor and/or anti-citrullinated protein antibody (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness >45 minutes, elevated C-reactive protein and/or erythrocyte sedimentation rate, and new hip pain. These criteria are not meant for diagnostic purposes.
2012
- 2012 provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative
[Articolo su rivista]
Dasgupta, Bhaskar; Cimmino, Marco A; Maradit Kremers, Hilal; Schmidt, Wolfgang A; Schirmer, Michael; Salvarani, Carlo; Bachta, Artur; Dejaco, Christian; Duftner, Christina; Jensen, Hanne Slott; Duhaut, Pierre; Poór, Gyula; Kaposi, Novák Pál; Mandl, Peter; Balint, Peter V; Schmidt, Zsuzsa; Iagnocco, Annamaria; Nannini, Carlotta; Cantini, Fabrizio; Macchioni, Pierluigi; Pipitone, Nicolò; Amo, Montserrat Del; Espígol Frigolé, Georgina; Cid, Maria C; Martínez Taboada, Víctor M; Nordborg, Elisabeth; Direskeneli, Haner; Aydin, Sibel Zehra; Ahmed, Khalid; Hazleman, Brian; Silverman, Barbara; Pease, Colin; Wakefield, Richard J; Luqmani, Raashid; Abril, Andy; Michet, Clement J; Marcus, Ralph; Gonter, Neil J; Maz, Mehrdad; Carter, Rickey E; Crowson, Cynthia S; Matteson, Eric L.
abstract
The objective of this study was to develop EULAR/ACR classification criteria for polymyalgia rheumatica (PMR). Candidate criteria were evaluated in a 6-month prospective cohort study of 125 patients with new onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR. A scoring algorithm was developed based on morning stiffness >45 minutes (2 points), hip pain/limited range of motion (1 point), absence of RF and/or ACPA (2 points), and absence of peripheral joint pain (1 point). A score ≥4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score ≥5 had increased sensitivity to 66% and specificity to 81%. According to these provisional classification criteria, patients ≥50 years old presenting with bilateral shoulder pain, not better explained by an alternative pathology, can be classified as having PMR in the presence of morning stiffness>45 minutes, elevated CRP and/or ESR and new hip pain. These criteria are not meant for diagnostic purposes.
2012
- Adalimumab in psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Pipitone, Nicolò; Catanoso, Mariagrazia; Chiarolanza, Ilaria; Boiardi, Luigi; Caruso, Andrea; Pazzola, Giulia; Macchioni, Pierluigi; Di Lernia, Vito; Albertini, Giuseppe
abstract
Open prospective studies and randomized controlled trials (RCT) have shown the short-term efficacy of adalimumab (ADA) in psoriatic arthritis (PsA) and psoriasis. ADA effectively treated all varied musculoskeletal manifestations characteristic of PsA, including peripheral arthritis, spinal disease, enthesitis, and dactylitis. ADA significantly inhibited structural changes on radiographs, lessened disability, and improved quality of life in patients with active PsA. One study showed the efficacy of 24-week ADA therapy on bone marrow edema and erosions, as measured by magnetic resonance imaging. The clinical and radiographic efficacy of ADA demonstrated during short-term treatment was sustained during longterm treatment. ADA was generally well tolerated and its safety profile was similar to that reported in studies of ADA in rheumatoid arthritis. Overall, ADA has a favorable risk-benefit profile in PsA. The combination of ADA and cyclosporine seems to be more effective than ADA monotherapy in patients with active PsA and inadequate response to methotrexate; however, this observation must be confirmed in RCT.
2012
- Adult primary central nervous system vasculitis
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Hunder, Gene G.
abstract
Primary CNS vasculitis is an uncommon disorder of unknown cause that is restricted to brain and spinal cord. The median age of onset is 50 years. The neurological manifestations are diverse, but generally consist of headache, altered cognition, focal weakness, or stroke. Serological markers of inflammation are usually normal. Cerebrospinal fluid is abnormal in about 80-90% of patients. Diagnosis is unlikely in the presence of a normal MRI of the brain. Biopsy of CNS tissue showing vasculitis is the only definitive test; however, angiography has often been used for diagnosis even though it has only moderate sensitivity and specificity. The size of the affected vessels varies and determines outcome and response to treatment. Early recognition is important because treatment with corticosteroids with or without cytotoxic drugs can often prevent serious outcomes. The differential diagnosis includes reversible cerebral vasoconstriction syndromes and secondary cerebral vasculitis.
2012
- Adult primary central nervous system vasculitis: an update
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Hunder, Gene G.
abstract
The aim of this review was to cover the recent major advances made in the fields of clinical assessment, diagnosis and treatment of adult primary central nervous system vasculitis (PCNSV).
2012
- Antisynthetase syndrome
[Articolo su rivista]
Carbonelli, C.; Bajocchi, G.; Salvarani, C.; Zucchi, L.
abstract
We present a case of pulmonary involvement associated to idiopathic inflammatory myopathy in a relatively homogenous clinical profile known as antisynthetase syndrome. This syndrome is characterized by myositis, arthralgias/arthritis, interstitial lung disease, fever, mechanic's hands, and Raynaud's phenomenon. Autoantibodies against aminoacyl-tRNA synthetases are associated, with anti-Jo-1 being the one most commonly found. The clinical appearance of pulmonary involvement is heterogeneous, slowly progressive or acute. Myositis precedes or is concurrent with the development of lung disease in the majority of cases, but the occurrence of lung involvement before myositis occurs in more than one third of cases. Therapy of these respiratory manifestations varies with the kind of clinical onset of the disease and with the level of functional impairment and must be personalized on the basis of clinical, functional and radiological findings of the follow up.
2012
- CC chemokine receptor 5 polymorphism in Italian patients with Behcet's disease
[Articolo su rivista]
Atzeni, Fabiola; Boiardi, Luigi; Casali, Bruno; Farnetti, Enrico; Nicoli, Davide; Sarzi Puttini, Piercarlo; Pipitone, Nicolò; Olivieri, Ignazio; Cantini, Fabrizio; Salvi, Fabrizio; La Corte, Renato; Triolo, Giovanni; Filippini, Davide; Paolazzi, Giuseppe; Salvarani, Carlo
abstract
To evaluate the potential role of CC chemokine receptor 5 (CCR5)Δ32 polymorphism in the susceptibility to and clinical expression of Behçet's disease (BD) in a cohort of Italian patients.
2012
- Clinical features of polymyalgia rheumatica and giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Pipitone, Nicolò; Versari, Annibale; Hunder, Gene G.
abstract
Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are inflammatory diseases that typically affect white individuals >50 years. Women are affected ∼2-3 times more often than men. PMR and GCA occur together more frequently than expected by chance. The main symptoms of PMR are pain and stiffness in the shoulders, and often in the neck and pelvic girdle. Imaging studies reveal inflammation of joints and bursae of the affected areas. GCA is a large-vessel and medium-vessel arteritis predominantly involving the branches of the aortic arch. The typical clinical manifestations of GCA are new headache, jaw claudication and visual loss. PMR and GCA usually remit within 6 months to 2 years from disease onset. Some patients, however, have a relapsing course and might require long-standing treatment. Diagnosis of PMR and GCA is based on clinical features and elevated levels of inflammatory markers. Temporal artery biopsy remains the gold standard to support the diagnosis of GCA; imaging studies are useful to delineate large-vessel involvement in GCA. Glucocorticoids remain the cornerstone of treatment of both PMR and GCA, but patients with GCA require higher doses. Synthetic immunosuppressive drugs also have a role in disease management, whereas the role of biologic agents is currently unclear.
2012
- Efficacy of infliximab in a patient with refractory idiopathic retroperitoneal fibrosis
[Articolo su rivista]
Catanoso, Maria Grazia; Spaggiari, Lucia; Magnani, Luca; Pipitone, Nicolò; Versari, Annibale; Boiardi, Luigi; Pazzola, Giulia; Pattacini, Pierpaolo; Salvarani, Carlo
abstract
Glucocorticoids are the mainstay of treatment of idiopathic retroperitoneal fibrosis (IRF). However, relapses are frequent upon tapering of the glucocorticoid dose. A variety of traditional immunosuppressants have been proposed as steroid-sparing agents, but some patients fail to adequately respond to combined glucocorticoid and immunosuppressive therapy. We report a patient with IRF refractory to combined glucocorticoid and methotrexate therapy treated with the anti-TNF-α monoclonal antibody infliximab. Infliximab was administered at 5 mg/kg/bodyweight at week 0, 2, 6 and 8-weekly thereafter for 3 consecutive years. Drug efficacy and safety were assessed clinically and by laboratory tests at treatment onset and subsequently before each infusion. In addition, 18FFluorodeoxyglucose (FDG) positron emission computerised tomography (PET/CT) and abdominal CT scans were used to monitor disease activity and response to treatment. Infliximab therapy resulted in a satisfactory clinical and laboratory response paralleled by an improvement in imaging findings. No serious adverse events were noted. Infliximab may be an effective and safe treatment for refractory IRF. A controlled study is required to confirm our findings.
2012
- Epidemiology of psoriatic arthritis
[Articolo su rivista]
Catanoso, M; Pipitone, N; Salvarani, Carlo
abstract
Epidemiological studies on psoriatic arthritis have long been hampered by the absence of widely accepted classification criteria. The development of the CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria has recently provided the framework for conducting epidemiological studies in psoriatic arthritis using uniform recruitment criteria. However, so far, only a minority of studies have adopted such criteria. In addition to the lack of shared classification criteria, differences in study settings, designs, and ascertainment methods have contributed to yield substantial disparities in the estimates of the incidence (from 3,02 to 23,1 cases per 100,000 people) and prevalence (from 49,1 to 420 cases per 100,000 people) of psoriatic arthritis around the globe. Overall, the available data suggests that the prevalence of psoriasis in the general population is approximately 2-3%, with about a third of patients with psoriasis having arthritis. Therefore, psoriatic arthritis may affect 0,3- 1,0% of the population, a frequency not dissimilar from that of rheumatoid arthritis. Future epidemiological studies should be carried out in larger numbers of patients diagnosed using consistent criteria.
2012
- Identification of the clinical features distinguishing psoriatic arthritis and fibromyalgia
[Articolo su rivista]
Marchesoni, Antonio; Atzeni, Fabiola; Spadaro, Antonio; Lubrano, Ennio; Provenzano, Giuseppe; Cauli, Alberto; Olivieri, Ignazio; Melchiorre, Daniela; Salvarani, Carlo; Scarpa, Raffaele; Sarzi Puttini, Piercarlo; Montepaone, Monica; Porru, Giovanni; D'Angelo, Salvatore; Catanoso, Mariagrazia; Costa, Luisa; Manara, Maria; Varisco, Valentina; Rotunno, Laura; DE Lucia, Orazio; DE Marco, Gabriele
abstract
To identify the clinical features that can help to distinguish between psoriatic arthritis (PsA) and fibromyalgia (FM).
2012
- IgG4-related disease: The Rheumatologist's point of view
[Articolo su rivista]
Pipitone, N.; Vaglio, A.; Salvarani, C.
abstract
The IgG4-related disease is a rare disorder with an estimated yearly incidence of 1 case per 100000 population in Japan, characterized by the infiltration of IgG4-positive plasma cells into one or more organs. C-reactive protein and Serum IgG4 levels are often, but not invariably elevated. The most common clinical manifestation is lymphadenopathy, followed by autoimmune pancreatitis and sclerosing cholangitis. Imaging procedures are helpful to identify the affected organs and to monitor the disease course. However, biopsy is often required to secure the diagnosis. Glucocorticoids are the mainstay of therapy, but immunosuppressive agents are useful to prevent recurrences of disease in patients with a chronic relapsing course. © Georg Thieme Verlag KG Stuttgart, New York.
2012
- Is the Nail Psoriasis Severity Index reliable in the assessment of nail psoriasis by rheumatologists?
[Articolo su rivista]
Lubrano, Ennio; Scrivo, Rossana; Cantini, Fabrizio; Marchesoni, Antonio; Mathieu, Alessandro; Olivieri, Ignazio; Salvarani, Carlo; Scarpa, Raffaele; Spadaro, Antonio
abstract
To determine the agreement and reliability of the Nail Psoriasis Severity Index (NAPSI) in the assessment of nail involvement in patients with psoriatic arthritis (PsA) when performed by rheumatologists with no experience in using this instrument.
2012
- Large-vessel involvement in recent-onset giant cell arteritis: a case-control colour-Doppler sonography study
[Articolo su rivista]
Ghinoi, Alessandra; Pipitone, Nicolò; Nicolini, Alberto; Boiardi, Luigi; Silingardi, Mauro; Germanò, Giuseppe; Salvarani, Carlo
abstract
The prevalence of large-vessel vasculitis (LVV) in newly diagnosed GCA is still debated. The aim of this study was to investigate the prevalence of LVV in newly diagnosed GCA using colour-Doppler sonography (CDS) and to compare the clinical and laboratory findings of GCA patients with and without LVV.
2012
- Longterm retention of tumor necrosis factor-α inhibitor therapy in a large italian cohort of patients with rheumatoid arthritis from the GISEA registry: an appraisal of predictors
[Articolo su rivista]
Iannone, Florenzo; Gremese, Elisa; Atzeni, Fabiola; Biasi, Domenico; Botsios, Costantino; Cipriani, Paola; Ferri, Clodoveo; Foschi, Valentina; Galeazzi, Mauro; Gerli, Roberto; Giardina, Annarita; Marchesoni, Antonio; Salaffi, Fausto; Ziglioli, Tamara; Lapadula, Giovanni; Bambara, Ml; Cantini, F; Ferraccioli, G; Foti, R; Giacomelli, R; Gorla, R; Grassi, W; Mathieu, A; Olivieri, I; Passiu, G; Punzi, L; Salvarani, Carlo; Sarzi Puttini, P; Scarpa, R; Triolo, G; Trotta, F.
abstract
OBJECTIVE: To evaluate 4-year retention rates of tumor necrosis factor-α (TNF-α) inhibitors adalimumab, etanercept, and infliximab among patients with longstanding rheumatoid arthritis (RA), as derived from an Italian national registry.METHODS: The clinical records of 853 adult patients with RA in the GISEA (Gruppo Italiano Studio Early Arthritis) registry were prospectively analyzed to compare drug survival rates and the baseline factors that may predict adherence to therapy.RESULTS: In 2003 and 2004, 324 patients started treatment with adalimumab, 311 with etanercept, and 218 with infliximab. After 4 years, the global retention rate of anti-TNF-α therapy was 42%. Etanercept survival (51.4%) was significantly better than that of infliximab (37.6%) or adalimumab (36.4%; p < 0.0001). Accordingly, the mean duration of therapy was significantly longer for etanercept (3.1 ± 2 yrs) than for adalimumab (2.6 ± 2 yrs) or infliximab (2.7 ± 2 yrs; p < 0.05). The use of concomitant disease-modifying antirheumatic drugs, mainly methotrexate, and the presence of comorbidities significantly predicted drug continuation (p < 0.01), whereas a high Disease Activity Score did not.CONCLUSION: The 4-year global drug survival of adalimumab, etanercept, and infliximab was lower than 50%, with etanercept having the best retention rate. The main positive predictor of adherence to anti-TNF-α therapy was the concomitant use of methotrexate. Our study provides further evidence that the real-life treatment of patients with RA may be different from that of randomized clinical trials.
2012
- Myocardial positron emission tomography/computed tomography scan revealing right coronary artery involvement in large vessel vasculitis
[Articolo su rivista]
Piga, Matteo; Ruffini, Livia; Salvarani, Carlo; Mathieu, Alessandro
abstract
Description of coronary artery involvement in a patient with Takayasu arteritis detected using a PET/CT perfusion scan in a symptomatic patient with normal coronary angiography.
2012
- Patient-reported outcomes in polymyalgia rheumatica
[Articolo su rivista]
Matteson, Eric L; Maradit Kremers, Hilal; Cimmino, Marco A; Schmidt, Wolfgang A; Schirmer, Michael; Salvarani, Carlo; Bachta, Artur; Dejaco, Christian; Duftner, Christina; Slott Jensen, Hanne; Poór, Gyula; Kaposi, Novák Pál; Mandl, Peter; Balint, Peter V; Schmidt, Zsuzsa; Iagnocco, Annamaria; Cantini, Fabrizio; Nannini, Carlotta; Macchioni, Pierluigi; Pipitone, Nicolò; Del Amo, Montserrat; Espígol Frigolé, Georgina; Cid, Maria C; Martínez Taboada, Víctor M; Nordborg, Elisabeth; Direskeneli, Haner; Aydin, Sibel Zehra; Ahmed, Khalid; Hazelman, Brian; Pease, Colin; Wakefield, Richard J; Luqmani, Raashid; Abril, Andy; Marcus, Ralph; Gonter, Neil J; Maz, Mehrdad; Crowson, Cynthia S; Dasgupta, Bhaskar
abstract
To prospectively evaluate the disease course and the performance of clinical, patient-reported outcome (PRO) and musculoskeletal ultrasound measures in patients with polymyalgia rheumatica (PMR).
2012
- Primary central nervous system vasculitis: pathology and mechanisms
[Articolo su rivista]
Giannini, Caterina; Salvarani, Carlo; Hunder, Gene; Brown, Robert D.
abstract
Primary vasculitis of the central nervous system (PCNSV) is a rare and diagnostically challenging form of vasculitis limited to the brain and/or spinal cord. It is a complex and often severe disease with multifaceted clinical and pathological appearances, suggesting multiple disease subtypes and the potential existence of multiple etiologic pathways. We describe in detail the clinical, imaging, and neuropathological findings of PCNSV summarizing literature data and our observations from a cohort of 131 patients diagnosed at Mayo Clinic over a 25-year period (1983-2007). Unlike systemic vasculitis, little is known regarding PCNSV pathogenesis and the involved immunological mechanisms. Increased recognition of the disease spectrum and in-depth characterization of its histopathologic and immunological phenotype will be critical to eventually understanding the underlying derangements and mechanisms driving PCNSV. Improved understanding of the pathogenetic mechanisms of the disease may also help determine whether the different histologic patterns and clinical subsets represent more than one disease and ultimately may permit development of novel diagnostic and therapeutic strategies for it.
2012
- Quantitative ultrasound criteria for risk stratification in clinical practice: a comparative assessment
[Articolo su rivista]
Accardi, A; Angeli, A; Baglio, S; Baldoncini, A; Ballardini, P; Bancheri, C; Beghe, F; Bernini, L; Bevilacqua, M; Bianchi, G; Bonomi, G; Bottai, M; Brogi, G; Candioto, G; Candiotto, S; Cecchetti, R; Serqua, R; Cervelli, S; Coaccioli, S; Coin, F; Colella, C; Costi, D; Cravero, M; D'Auria, S; D'Avola, G; De Gennaro, N; Del Forno, L; D'Elia, A; Di Munno, O; Di Virgilio, R; Favazzi, F; Ferraris, M; Filippini, P; Francucci, Cm; Frediani, B; Gandolini, G; Gasparini, R; Gatti, R; Gatto, S; Gemini, E; Gismondi, T; Gonnelli, S; Grassi, S; Iolascon, G; Isaia, Gc; Izzo, T; La Montagna, G; La forgia, R; Lapadula, G; Martina, Gl; Lombardi, P; Lovato, R; Maglitto, R; Magnani, F; Malavolta, N; Mancini, G; Masellis, G; Maugeri, D; Micale, C; Mora, R; Muratore, M; Occhipinti, R; Oliva, G; Palummeri, E; Panzavecchia, D; Parello, S; Pellerito, R; Pisanu, G; Policicchio, D; Pozone, M; Pucci, G; Respizzi, S; Roberti, G; Rossini, M; Rossitto, S; Sabadini, L; Salvarani, Carlo; Salvini, S; Santeufemia, G; Santi, I; Sartori, L; Sfrappini, M; Silveri, F; Sinigaglia, L; Vibo, Ms; Spinazzè, R; Stancati, G; Tartarelli, G; Topini, D; Trotta, F; Varcasia, G; Zanatta, A.
abstract
This study aimed to compare two different classifications of the risk of fracture/osteoporosis (OP) based on quantitative ultrasound (QUS). Analyses were based on data from the Epidemiological Study on the Prevalence of Osteoporosis, a cross-sectional study conducted in 2000 aimed at assessing the risk of OP in a representative sample of the Italian population. Subjects were classified into 5 groups considering the cross-classification found in previous studies; logistic regression models were defined separately for women and men to study the fracture risk attributable to groups defined by the cross-classification, adjusting for traditional risk factors. Eight-thousand six-hundred eighty-one subjects were considered in the analyses. Logistic regression models revealed that the two classifications seem to be able to identify a common core of individuals at low and at high risk of fractures, and the importance of a multidimensional assessment in older patients to evaluate clinical risk factors together with a simple, inexpensive, radiation-free device such as QUS.
2012
- Recommendations of the Italian Society of Rheumatology for the treatment of the primary large-vessel vasculitis with biological agents
[Articolo su rivista]
Pipitone, Nicolò; Olivieri, Ignazio; Salvarani, Carlo
abstract
To provide recommendations on behalf of the Italian Society for Rheumatology for the off-label use of biologic agents in the treatment of large-vessel vasculitis.
2012
- Rescue treatment with tocilizumab for Takayasu arteritis resistant to TNF-α blockers
[Articolo su rivista]
Salvarani, Carlo; Magnani, Luca; Catanoso, Maria Grazia; Pipitone, Nicolò; Versari, Annibale; Dardani, Lucia; Pulsatelli, Lia; Meliconi, Riccardo; Boiardi, Luigi
abstract
Anti-TNF-α therapy has successfully been used to treat Takayasu arteritis (TA) refractory to conventional immunosuppressive treatment. However, some patients fail to respond even to TNF-α blockers. Interleukin-6 (IL-6) is a key player in the pathogenesis of TA. Preliminary data also suggest efficacy of the IL-6 receptor inhibitor tocilizumab in patients with large-vessel vasculitis. We report a patient with TA refractory to multiple conventional immunosuppressive agents and two TNF-α blockers successfully treated with monthly tocilizumab infusions (8 mg/kg body weight) for 6 consecutive months. Clinical indices of disease activity, inflammatory markers, and 18Ffluorodeoxyglucose positron emission/computerised tomography findings normalised, while the prednisone dosage could be tapered. Serum IL-6 and soluble IL-6 receptor (sIL-6R) levels raised during tocilizumab treatment consistent with the mode of action of tocilizumab. Tocilizumab holds promise for patients with refractory TA. Larger studies are required to confirm our findings.
2012
- Retroperitoneal fibrosis
[Articolo su rivista]
Pipitone, Nicolò; Vaglio, Augusto; Salvarani, Carlo
abstract
Retroperitoneal fibrosis is a rare syndrome hallmarked by a fibrosclerotic tissue in the retroperitoneum, often leading to encasement of the ureters. About two-thirds of cases of retroperitoneal fibrosis are idiopathic, while the remaining cases are secondary to a variety of different causes, including drugs, tumors and infections. Idiopathic retroperitoneal fibrosis may be associated with abdominal aorta aneurysms, with vasculitis of the thoracic aorta and of epi-aortic vessels, or both. Most patients present with abdominal and/or low back pain. Serum markers of inflammation are usually, but not invariably, elevated. The diagnosis is secured by computed tomography or magnetic resonance imaging, which typically show an enhancing retroperitoneal mass medially dislodging the ureters. Positron emission tomography can be useful to document the extent and metabolic activity of the inflammatory process. Treatment rests on glucocorticoids with a tapering scheme variably combined with immunosuppressive agents. In cases of ureter obstruction, relief of obstruction by stenting or ureterolysis is required.
2012
- Small-vessel vasculitis surrounding an uninflamed temporal artery and isolated vasa vasorum vasculitis of the temporal artery: two subsets of giant cell arteritis
[Articolo su rivista]
Restuccia, Giovanna; Cavazza, Alberto; Boiardi, Luigi; Pipitone, Nicolò; Macchioni, Pierluigi; Bajocchi, Gianluigi; Catanoso, Maria Grazia; Muratore, Francesco; Ghinoi, Alessandra; Magnani, Luca; Cimino, Luca; Salvarani, Carlo
abstract
To evaluate the frequency and clinical characteristics of periadventitial small-vessel vasculitis (SVV) and isolated vasa vasorum vasculitis (VVV).
2012
- The impact of 18F-FDG PET on the management of patients with suspected large vessel vasculitis
[Articolo su rivista]
Fuchs, Martin; Briel, Matthias; Daikeler, Thomas; Walker, Ulrich A; Rasch, Helmut; Berg, Scott; Ng, Quinn K. T; Raatz, Heike; Jayne, David; Kötter, Ina; Blockmans, Daniel; Cid, Maria C; Prieto González, Sergio; Lamprecht, Peter; Salvarani, Carlo; Karageorgaki, Zaharenia; Watts, Richard; Luqmani, Raashid; Müller Brand, Jan; Tyndall, Alan; Walter, Martin A.
abstract
We aimed to assess the impact of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the management of patients with suspected large vessel vasculitis.
2012
- Tocilizumab: a novel therapy for patients with large-vessel vasculitis
[Articolo su rivista]
Salvarani, Carlo; Magnani, Luca; Catanoso, Mariagrazia; Pipitone, Nicolò; Versari, Annibale; Dardani, Lucia; Pulsatelli, Lia; Meliconi, Riccardo; Boiardi, Luigi
abstract
Treatment of large-vessel vasculitis (LVV) remains challenging. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose or after GC withdrawal. In addition, GCs are fraught with numerous adverse events. The aim of this study was to assess the efficacy and safety of the anti-IL-6 receptor (IL-6R) antibody tocilizumab (TCZ) in patients with LVV.
2012
- [18F]fluorodeoxyglucose positron emission tomography imaging in a case of relapsing polychondritis
[Articolo su rivista]
Cassone, Giulia; Lo Gullo, Alberto; Bajocchi, Gianluigi; Salvarani, Carlo
abstract
Clinical image: [18F]fluorodeoxyglucose positron emission tomography imaging in a case of relapsing polychondritis
2011
- A putative functional variant within the UBAC2 gene is associated with increased risk of Behçet's disease
[Articolo su rivista]
Sawalha, Amr H; Hughes, Travis; Nadig, Ajay; Yılmaz, Vuslat; Aksu, Kenan; Keser, Gokhan; Cefle, Ayse; Yazıcı, Ayten; Ergen, Andaç; Alarcón Riquelme, Marta E; Salvarani, Carlo; Casali, Bruno; Direskeneli, Haner; Saruhan Direskeneli, Güher
abstract
Using a genome-wide association scan and DNA pooling, we previously identified 5 novel genetic susceptibility loci for Behçet's disease. We undertook this study to establish the genetic effect within the UBAC2 gene, in the course of which we replicated this genetic association and identified a functional variant within this locus.
2011
- Aortitis and periaortitis in ankylosing spondylitis
[Articolo su rivista]
Palazzi, Carlo; Salvarani, Carlo; D'Angelo, Salvatore; Olivieri, Ignazio
abstract
Aortic involvement is a potential life-threatening complication of ankylosing spondylitis, usually occurring late in the course of this frequent disease. Inflammatory lesions evolving to fibrosis are primarily localized in the aortic root causing regurgitation, but this process can extend into the left atrium (subaortic bump) involving the mitral valve and the heart conduction system. First, second and third degree atrioventricular blocks are the most common conduction alterations described and they can be temporary. Chronic periaortitis has been described in ankylosing spondylitis patients. This disease is characterized by inflammation evolving to fibrosis and it is localized in the periaortic and peri-iliac retroperitoneum. It causes compressive effects on ureters and venous, arterial and lymphatic vessels. Its treatment employs endoscopic and/or surgical procedures and administration of corticosteroids, even in association with immunosuppressive agents. Both aortitis (with conduction system alterations) and periaortitis should be kept in mind by the physicians because they can significantly influence the prognosis of ankylosing spondylitis patients and they can need a rapid treatment.
2011
- Aortitis and periaortitis in ankylosing spondylitis
[Articolo su rivista]
Palazzi, C.; Salvarani, C.; D'Angelo, S.; Olivieri, I.
abstract
2011
- CC chemokine receptor 5 polymorphism in chronic periaortitis
[Articolo su rivista]
Boiardi, Luigi; Vaglio, Augusto; Nicoli, Davide; Farnetti, Enrico; Palmisano, Alessandra; Pipitone, Nicolò; Maritati, Federica; Casali, Bruno; Martorana, Davide; Moroni, Gabriella; Gallelli, Beniamina; Buzio, Carlo; Salvarani, Carlo
abstract
Chronic periaortitis (CP) is a rare disease characterized by a fibro-inflammatory tissue surrounding the abdominal aorta, and includes non-aneurysmal [idiopathic retroperitoneal fibrosis (IRF)] and aneurysmal forms [inflammatory abdominal aortic aneurysm (IAAA)]. We investigated whether CC chemokine receptor 5 (CCR5)Δ32 polymorphism confers susceptibility to CP.
2011
- Chronic periaortitis: a large-vessel vasculitis?
[Articolo su rivista]
Vaglio, Augusto; Pipitone, Nicolò; Salvarani, Carlo
abstract
Chronic periaortitis is characterized by a fibro-inflammatory process spreading from the abdominal aorta and the iliac arteries. Originally, chronic periaortitis was considered a localized inflammatory response to severe aortic atherosclerosis. However, subsequent studies have shown that chronic periaortitis may also involve other arteries and present with features of auto-immune diseases. This article reviews the issue of large-vessel involvement in chronic periaortitis and its implications in the pathogenesis and nosography of the disease.
2011
- Current Opinion in Rheumatology: Editorial introductions
[Articolo su rivista]
Hoffman, G. S.; Salvarani, C.
abstract
2011
- Definition of remission and relapse in polymyalgia rheumatica: data from a literature search compared with a Delphi-based expert consensus
[Articolo su rivista]
Dejaco, Christian; Duftner, Christina; Cimmino, Marco A; Dasgupta, Bhaskar; Salvarani, Carlo; Crowson, Cynthia S; Maradit Kremers, Hilal; Hutchings, Andrew; Matteson, Eric L; Schirmer, Michael
abstract
To compare current definitions of remission and relapse in polymyalgia rheumatica (PMR) with items resulting from a Delphi-based expert consensus.
2011
- Does Ultrasonography Guidance Increase the Yeld of Temporal Artery Biopsy in Patients with Giant Cell Arteritis? Preliminary Results From a Single-Blinded Randomized Study
[Articolo su rivista]
Germano, G; Pipitone, N; Boiardi, L; Chiarolanza, I; Cimino, L; Catanoso, Mg; Caruso, A; Salvarani, C
abstract
2011
- Etanercept in spondyloarthopathies. Part II: safety and pharmacoeconomic issues
[Articolo su rivista]
D'Angelo, Salvatore; Palazzi, Carlo; Cantini, Fabrizio; Lubrano, Ennio; Marchesoni, Antonio; Mathieu, Alessandro; Salvarani, Carlo; Scarpa, Raffaele; Spadaro, Antonio; Olivieri, Ignazio
abstract
Etanercept (ETN) and other anti-TNF-α agents have revolutionised the management of spondyloarthropathies (SpA). With the increasingly widespread and prolonged use of these drugs an assessment of their long-term safety is extremely important. An additional concern regarding biological agents is their higher costs compared with conventional drugs. We examined safety data regarding ETN from clinical reports, clinical trials, review articles, databases and registries. In addition, evidence was reviewed about the cost effectiveness of ETN in the treatment of patients with SpA. Our review suggests that ETN is well tolerated as long-term, continuous treatment of SpA with a favourable risk-benefit ratio maintained from 4 to 5 years. Diversity in structure and mode of action could explain some differences in the safety profile of ETN with respect to the other anti-TNF agents. In particular, ETN is less immunogenic and is less likely to induce tuberculosis re-activation than the other TNF-α antagonists. Although ETN is considerably more expensive than conventional therapy, it reduces direct and indirect costs associated to SpA by improving disease activity and quality of life. Recent pharmacoeconomic studies have demonstrated its cost-effectiveness in the treatment of SpA.
2011
- Etanercept in spondyloarthropathies. Part I: current evidence of efficacy
[Articolo su rivista]
Palazzi, Carlo; D'Angelo, Salvatore; Cantini, Fabrizio; Lubrano, Ennio; Marchesoni, Antonio; Mathieu, Alessandro; Salvarani, Carlo; Scarpa, Raffaele; Spadaro, Antonio; Olivieri, Ignazio
abstract
Etanercept is a recombinant soluble tumour necrosis factor alpha receptor administered subcutaneously at the dose of 50 mg weekly (or 25 mg/twice weekly) for the treatment of the main chronic arthritides: rheumatoid arthritis and spondyloarthropathies. It shows high qualities in terms of efficacy and manageability. Favourable results were reported in all localisations of spondyloarthropathies: axial disease, peripheral arthritis, and enthesitis. In particular, several studies demonstrated its efficacy on the clinical and functional indicators of ankylosing spondylitis. Similar data were also reported for psoriatic arthritis in which, in addition, a significant reduction in the progression of erosive damages was widely described. Furthermore, although only a few studies are available, very interesting results have been obtained in patients suffering from undifferentiated spondyloarthropathies and severe enthesitis.
2011
- Expression of interleukin-32 in the inflamed arteries of patients with giant cell arteritis
[Articolo su rivista]
Ciccia, Francesco; Alessandro, Riccardo; Rizzo, Aroldo; Principe, Simona; Raiata, Francesca; Cavazza, Alberto; Guggino, Giuliana; Accardo Palumbo, Antonina; Boiardi, Luigi; Ferrante, Angelo; Principato, Alfonso; Giardina, Annarita; De Leo, Giacomo; Salvarani, Carlo; Triolo, Giovanni
abstract
Giant cell (temporal) arteritis (GCA) is a vasculitis that mainly affects the large and medium arteries, especially the branches of the proximal aorta. Interleukin-32 (IL-32) is a recently described Th1 proinflammatory cytokine, and is mainly induced by interferon-γ (IFNγ), IL-1β, and tumor necrosis factor α (TNFα). This study was undertaken to investigate the expression and tissue distribution of IL-32 in artery biopsy specimens from patients with GCA.
2011
- Idiopathic aortitis: an underrecognized vasculitis
[Articolo su rivista]
Pipitone, Nicolò; Salvarani, Carlo
abstract
Aortitis is a general term denoting inflammation of the aortic wall. Various infectious and non-infectious diseases can be complicated by aortitis; in addition, isolated idiopathic aortitis has also been described. In a 12-year nationwide Danish population-based study, the prevalence of aortitis among 1,210 resected thoracic aorta samples was 6.1%, with nearly three-quarters of cases being idiopathic. Identified risk factors for aortitis included advanced age, a history of connective tissue disease, diabetes mellitus, and heart valve pathology. As in virtually all pathological studies, this study has a bias toward reporting the most severe cases of aortitis requiring surgical repair.
2011
- IgG4-associated sclerosing mesenteritis
[Articolo su rivista]
Salvarani, Carlo; Valli, Riccardo; Boiardi, Luigi; Pipitone, Nicolò; Nicoli, Franco; Muratore, Francesco
abstract
Clinical image: IgG4-associated sclerosing mesenteritis
2011
- Imaging findings in primary central nervous system vasculitis
[Articolo su rivista]
Zuccoli, Giulio; Pipitone, Nicolo; Haldipur, Anshul; Brown, Robert D; Hunder, Gene; Salvarani, Carlo
abstract
Primary central nervous system vasculitis (PCNSV) is a rare primary vasculitis limited to the brain and spinal cord. It can affect any age group, but has a predilection for subjects aged 40 to 60 years without clear gender predominance. Clinical manifestations are nonspecific, including headache, non-focal neurological features and, less frequently, focal neurological signs. Brain biopsy is the diagnostic gold standard, but may be falsely negative when unaffected tissue is sampled. In addition, brain biopsy carries a small but significant risk of serious complications. Imaging procedures are a key part of the workup of PCNSV patients. They can be used to document the extent and type of lesions, to gauge response to treatment, and sometimes as surrogates for brain biopsy. Magnetic resonance is extremely sensitive but non-specific. The most common findings are multiple bilateral ischaemic lesions often involving white and grey matter. Conventional or magnetic resonance angiography (MRA) typically shows segmental narrowing and dilation in multiple cerebral arteries. However, atypical findings have also been described both with magnetic resonance and angiography. This review discusses the state-of-the-art of current imaging techniques in the workup of PCNSV patients and highlights future prospects.
2011
- Inhibition of joint damage and improved clinical outcomes with rituximab plus methotrexate in early active rheumatoid arthritis: the IMAGE trial.
[Articolo su rivista]
Tak, Pp; Rigby, Wf; Rubbert Roth, A; Peterfy, Cg; van Vollenhoven, Rf; Stohl, W; Hessey, E; Chen, A; Tyrrell, H; Shaw, Tm; Aelion J, IMAGE I. n. v. e. s. t. i. g. a. t. o. r. s.; Afif, N; Ahmadi, F; Aires, F; Alanis, E; Alonso, Cs; Alten, Rh; Alvaro Gracia, Jm; Ashrafzadeh, A; Ballina, J; Bambara, Lm; Bao, C; Bell, M; Berney, S; Bessette, L; Birbara, C; Boling, E; Bourgeois, P; Braun, J; Briones, H; Brzezicki, J; Burgos Vargos, R; Burmester, G; Burnett, M; Busch, H; Cabello, E; Calvo, A; Cantagrel, A; Cantini, F; Zea, Ac; Carreño Perez, L; Chavez, J; Shim, Sc; Chindalore, V; Chiriac, R; Codding, C; Danda, D; Del Guidice, J; De Vita, S; Digiovanni, R; Dikranian, A; Eider, W; Fantini, F; Ferraccioli, G; Fietchner, J; Filipowicz Sosnowska, A; Finnanger, B; Fiocco, G; Fleck, M; Fleischmann, R; Fraser, A; Gaudin, P; Gauler, G; Gaylis, N; Gerlag, Dm; Godde, J; Gomez Reino, Jj; Gornisiewicz, M; Gough, W; Greenwald, M; Guerra, G; Hackshaw, K; Haentzschel, Hm; Hammond, T; Hazleman, Bl; Heilig, B; Herenius, Mm; Hilliquin, P; Holt, D; Huang, F; Huff, J; Huizinga, T; Isaacs, J; Jaffer, A; Amante, Ej; Jeka, S; Jimenez, R; Jones, G; Jones, R; Kaine, J; Kashif, A; Kaufmann, C; Kay, J; Khraishi, M; Kivitz, A; Klinkhoff, A; Kraag, G; Krystufkova, O; Kucharz, E; Lawson, J; Leirisalo Repo, M; Levin, R; Liang, G; Liang, P; Limonta, M; Lowenstein, M; Rodriguez Lozano, C; Lue, C; Mahowald, M; Maradiaga, M; Maricic, M; Mariette, X; Martin, L; Massarotti, E; Matucci Cerinic, M; Montecucco, Cm; Mazurov, V; Mcnally, J; Mehta, D; Meyer, O; Misra, R; Moreland, Lw; Mueller Ladner, U; Myerson, G; Nasonov, E; Navarra, S; Navarro, F; Neal, N; Olech, E; Olsen, N; Pablos, Jl; Pacheco, C; Pal, S; Palomo, Er; Pandith, V; Penserga, Eg; Prupas, H; Radominski, S; Ramos Remus, C; Reid, D; Riordan, K; Rosenberg, D; Ruiz, A; Saadeh, C; Salvarani, Carlo; Samuels, A; Sanmarti, R; Sarzi Puttini, P; Saxe, P; Schechtman, J; Scoville, C; Sedlackova, M; Sedrish, M; Sejer Hansen, M; Sibilia, J; Siebert, S; Specker, C; Stern, S; Szechinski, J; Tahir, H; Taylor, A; Thompson, Pw; Tony, Hp; Tornero, J; Trapp, R; Tremblay, Jl; Valesini, G; Van Den Bosch, F; Wanchu, A; Wassenberg, S; Ximenes, Ac; Kim, Hy; Zanetakis, E; Zazueta, B; Zerbini, C.
abstract
Rituximab is an effective treatment in patients with established rheumatoid arthritis (RA). The objective of the IMAGE study was to determine the efficacy of rituximab in the prevention of joint damage and its safety in combination with methotrexate (MTX) in patients initiating treatment with MTX.
2011
- Isolated vasculitis of the lower extremities in a patient with polymyalgia rheumatica and giant cell arteritis
[Articolo su rivista]
Germanò, Giuseppe; Versari, Annibale; Muratore, Francesco; Pipitone, Nicolo'; Bajocchi, Gian Luigi; Catanoso, Maria Grazia; Salvarani, Carlo
abstract
Case report: Isolated vasculitis of the lower extremities in a patient with polymyalgia rheumatica and giant cell arteritis
2011
- New indications for biological therapies
[Articolo su rivista]
Catanoso, Mariagrazia; Pipitone, Nicolò; Magnani, Luca; Boiardi, Luigi; Salvarani, Carlo
abstract
Biological agents have originally been developed to treat refractory arthritis, but evidence has been accruing, supporting their use in vasculitis as well. In the large-vessel vasculitides giant cell arteritis and Takayasu arteritis, TNF-α inhibitors have shown some efficacy in patients with relapsing disease. In contrast, in patients with recent onset of giant cell arteritis, TNF-α inhibitors failed to provide a significant benefit over and above that conferred by glucocorticoids alone. More recent, preliminary data suggest a role for the interleukin-6 receptor antagonist tocilizumab in both resistant and treatment-naïve giant cell arteritis and Takayasu arteritis. Biological agents have also been proposed to treat difficult anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. Uncontrolled observations suggest that the TNF-α inhibitor infliximab might be beneficial in resistant cases. On the contrary, a randomized controlled trial did not show superiority of the recombinant human soluble TNF-α p75 receptor fusion protein etanercept over placebo in maintaining remission in granulomatosis with polyangiitis. Two randomized controlled trials have demonstrated that the anti-CD20 monoclonal antibody rituximab was as effective as the standard-of-care agent cyclophosphamide in inducing remission. In addition, rituximab appeared to be superior to cyclophosphamide in inducing remission in the subset of patients with relapsing disease. These findings prove that biological therapy has a role in vasculitis. Research is investigating novel therapies as well as focusing on how to best use the available drugs.
2011
- PLA1/A2 polymorphism of the platelet glycoprotein receptors IIIA in Behçet's disease
[Articolo su rivista]
Atzeni, Fabiola; Boiardi, Luigi; Nicoli, Davide; Farnetti, Enrico; Casali, Bruno; Sarzi Puttini, Piercarlo; Pipitone, Nicolò; Olivieri, Ignazio; Cantini, Fabrizio; Salvi, Fabrizio; La Corte, Renato; Triolo, Giovanni; Filippini, Davide; Paolazzi, Giuseppe; Salvarani, Carlo
abstract
To investigate potential associations between the PlA1/A2 polymorphism of the platelet glycoprotein receptor IIIA (GpIIIa) gene and venous thrombosis and other clinical manifestations in Italian patients with Behçet's disease (BD).
2011
- Patient global assessment in psoriatic arthritis: a multicenter GRAPPA and OMERACT study
[Articolo su rivista]
Cauli, Alberto; Gladman, Dafna D; Mathieu, Alessandro; Olivieri, Ignazio; Porru, Giovanni; Tak, Paul P; Sardu, Claudia; Ujfalussy, Ilona; Scarpa, Raffaele; Marchesoni, Antonio; Taylor, William J; Spadaro, Antonio; Fernàndez Sueiro, Jose L; Salvarani, Carlo; Kalden, Joachim R; Lubrano, Ennio; Carneiro, Sueli; Desiati, Francesca; Flynn, John A; D'Angelo, Salvatore; Vacca, Alessandra; VAN Kuijk, Arno W. R; Catanoso, Maria Grazia; Gruenke, Mathias; Peluso, Rosario; Parsons, Wendy J; Ferrara, Nicola; Contu, Paolo; Helliwell, Philip S; Mease, Philip J.
abstract
During OMERACT 8, delegates selected patient global assessment (PGA) of disease as a domain to be evaluated in randomized controlled trials in psoriatic arthritis (PsA). This study assessed the reliability of the PGA, measured by means of 0-100 mm visual analog scale (VAS), and the additional utility of separate VAS scales for joints (PJA) and skin (PSA).
2011
- Possible left endoventricular myxoma in a patient with deep vein thrombosis of the lower limbs: A case report
[Articolo su rivista]
Galimberti, D.; Navazio, A.; Salvarani, C.; Bajocchi, G.; Dolzani, P.; Assirelli, E.; Casali, A. M.; Leone, M. C.; Pizzini, A. M.; Silingardi, M.; Arioli, D.; Morini, L.; Favali, D.; Iori, I.
abstract
Introduction: We describe an unusual case of left ventricular myxoma associated with deep vein thrombosis (DVT). Materials and methods: A 79-year-old woman was admitted with bilateral proximal DVT that developed while she was on warfarin. The anticoagulant therapy had been started (after 2 weeks of low-molecular weight heparin) 1 month earlier in a Cardiologic Unit, where the patient had been treated for "left ventricular thrombosis associated with acute pericarditis". After discharge, the patient continued to experience malaise, recurrent dizziness, dyspnea, flushing, and progressively severe leg swelling despite transthoracic echocardiography (TTE) findings of normal left ventricular function. She was finally admitted to our Unit for ultrasound studies for possible DVT. On admission the INR was in the therapeutic range with increased C-reactive protein (CRP), thrombocytopenia, mild anemia, anti-PF4 antibodies, lupus anticoagulant (LAC), a positive direct Coombs test, and mildly increased anti-platelet and anticardiolipin antibody levels. Malignancy, SLE, and inherited thrombophilia were excluded by a broad-spectrum instrumental and laboratory investigation. Since heparin-induced-thrombocytopenia could not be excluded, the warfarin was replaced with fondaparinux (7.5 mg/day). Given the persistence on TTE of a "small floating mass" at the left ventricular apex, we suspected the previously diagnosed thrombosis was actually an unusually located myxoma, and this diagnosis was confirmed by CT and MRI. The patient also had markedly increased serum levels of interleukin 6 (IL-6), regarded by many as a marker of cardiac myxoma and the source of the constitutional symptoms and immunologic features ("activity") of these lesions. The patient is now well except for recurrent flushing episodes. The IL-6 level is still high although the ESR, CRP, LAC have normalized. Since isolated IL-6 increases are associated with recurrence in PMR patients, we consider our patient at risk for relapse of systemic illness. Results: Three cases of cardiac myxoma associated with DVT have been reported. Myxoma production of IL-6 could explain the extracardiac symptoms and the inflammatory/autoimmune activation that caused the DVT. Discussion: Although histologic confirmation is lacking, the features of this case strongly suggest an atypical-site myxoma, in particular the concordant findings generated by the various diagnostic exams and unchanging nature of the ventricular lesion during follow-up. © 2011 Elsevier Srl. All rights reserved.
2011
- Prednisone versus tamoxifen in patients with idiopathic retroperitoneal fibrosis: an open-label randomised controlled trial
[Articolo su rivista]
Vaglio, Augusto; Palmisano, Alessandra; Alberici, Federico; Maggiore, Umberto; Ferretti, Stefania; Cobelli, Rocco; Ferrozzi, Francesco; Corradi, Domenico; Salvarani, Carlo; Buzio, Carlo
abstract
Glucocorticoids are the mainstay of treatment of idiopathic retroperitoneal fibrosis, but they often have substantial toxic effects. Several reports have suggested tamoxifen as an alternative to glucocorticoids. We compared the efficacy of prednisone with that of tamoxifen in maintainance of remission in patients with idiopathic retroperitoneal fibrosis.
2011
- Primary central nervous system vasculitis presenting with intracranial hemorrhage
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Calamia, Kenneth T; Christianson, Teresa J. H; Huston, John; Meschia, James F; Giannini, Caterina; Miller, Dylan V; Hunder, Gene G.
abstract
To describe a subset of cases in a large retrospectively identified cohort of patients with primary central nervous system vasculitis (PCNSV) who present with intracranial hemorrhage.
2011
- Rapidly progressive primary central nervous system vasculitis
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Calamia, Kenneth T; Christianson, Teresa J. H; Huston, John; Meschia, James F; Giannini, Caterina; Miller, Dylan V; Hunder, Gene G.
abstract
To describe a subset of cases in a large cohort of patients with primary CNS vasculitis (PCNSV) who appear to have a rapidly progressive clinical course.
2011
- Recommendations for the use of biologic therapy in rheumatoid arthritis: update from the Italian Society for Rheumatology I. Efficacy
[Articolo su rivista]
Caporali, Roberto; Conti, Fabrizio; Alivernini, Stefano; Atzeni, Fabiola; Seriolo, Bruno; Cutolo, Maurizio; Valesini, Guido; Ferraccioli, Gianfranco; Sarzi Puttini, Piercarlo; Salvarani, Carlo; Guiducci, Serena; Zampogna, Giuseppe; Gremese, Elisa; Pipitone, Nicolo'; Scrivo, Rossana; Bugatti, Serena; Montecucco, Carlomaurizio; Matucci Cerinic, Marco
abstract
Given the availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), various national scientific societies have developed specific recommendations in order to assist rheumatologists in prescribing these drugs. The Italian Society for Rheumatology (Società Italiana di Reumatologia, SIR) decided to update its recommendations and, to this end, a systematic literature review was carried out and the evidence derived from it was discussed and summarised as expert opinions. Levels of evidence, strength of recommendations and levels of agreement were reported. The recommendations reported are intended to help prescribing rheumatologists to optimise the use of biologic agents in patients with RA seen in everyday practice; they are not to be considered as a regulatory rule.
2011
- Recommendations for the use of biologic therapy in the treatment of psoriatic arthritis: update from the Italian Society for Rheumatology
[Articolo su rivista]
Salvarani, Carlo; Pipitone, Nicolò; Marchesoni, Antonio; Cantini, Fabrizio; Cauli, Alberto; Lubrano, Ennio; Punzi, Leonardo; Scarpa, Raffaele; Spadaro, Antonio; Matucci Cerinic, Marco; Olivieri, Ignazio
abstract
To update the 2006 Italian Society for Rheumatology recommendations for the use of biologic (TNF-α blocking) agents in the treatment of psoriatic arthritis (PsA).
2011
- Role of 18F-fluorodeoxyglucose positron emission tomography in the workup of retroperitoneal fibrosis
[Articolo su rivista]
Pipitone, Nicolo; Versari, Annibale; Vaglio, Augusto; Salvarani, Carlo
abstract
Retroperitoneal fibrosis is a syndrome characterised by the presence of fibrosclerotic tissue in the retroperitoneum, often encasing the ureters. In most cases, retroperitoneal fibrosis is idiopathic, but may also be associated with large vessel vasculitis at distant sites, with the so-called IgG4-related sclerosing disease, as well as with exposure to some medications, infections, malignancies, surgery, or radiation. 18-Fluorodeoxyglucose (FDG) positron emission tomography (PET) is a nuclear medicine technique which is able to accurately identify in vivo areas characterised by elevated glucose metabolism, such as inflammatory, infective, and neoplastic lesions. There is mounting evidence suggesting that FDG-PET may have a role in assessing disease activity in idiopathic retroperitoneal fibrosis, but the role of FDG-PET in secondary retroperitoneal fibrosis is less established. Herein, we present four patients with retroperitoneal fibrosis of different etiology (isolated idiopathic, associated with large-vessel involvement, associated with carcinoid tumour, and secondary to pergolide) who underwent FDG-PET as part of their workup. The implications of FGD-PET results in the diagnosis and treatment of retroperitoneal fibrosis of different etiology are discussed.
2011
- The effectiveness of a biologic agent on axial manifestations of psoriatic arthritis. A twelve months observational study in a group of patients treated with etanercept
[Articolo su rivista]
Lubrano, Ennio; Spadaro, Antonio; Marchesoni, Antonio; Olivieri, Ignazio; Scarpa, Raffaele; D'Angelo, Salvatore; Salvarani, Carlo; Mathieu, Alessandro; Cauli, Alberto; Ferrara, Nicola; Helliwell, Philip
abstract
To investigate the effectiveness of etanercept on axial manifestations of a group of patients with established psoriatic arthritis (PsA).
2011
- Treatment of large-vessel vasculitis: where do we stand?
[Articolo su rivista]
Salvarani, Carlo; Pipitone, Nicolo'
abstract
Editorial on the new strategies for the treatment of large vessels vasculitis.
2011
- Vasculitis of the gastrointestinal tract in chronic periaortitis
[Articolo su rivista]
Salvarani, Carlo; Calamia, Kenneth T; Matteson, Eric L; Hunder, Gene G; Pipitone, Nicolò; Miller, Dylan V; Warrington, Kenneth J.
abstract
The term "chronic periaortitis" (CP), proposed by Mitchinson in 1984, comprises 3 main entities: idiopathic retroperitoneal fibrosis (IRF), inflammatory abdominal aortic aneurysms (IAAAs), and perianeurysmal retroperitoneal fibrosis (PRF).The presence of constitutional symptoms, high acute-phase reactants, positive autoantibodies, and associated autoimmune diseases suggests a systemic inflammatory process. Histopathologic findings show vasculitis with fibrinoid necrosis involving the aortic vasa vasorum as well as the small and medium retroperitoneal vessels.We reviewed the medical records of 608 patients with a diagnosis of vasculitis involving the gastrointestinal (GI) tract at the Mayo Clinic between January 1996 and December 2007. Only patients with biopsy-proven or typical angiographic findings of vasculitis localized to the GI tract were included.Five patients were identified with evidence of CP (1 patient with PRF, 1 with IRF, and 3 with IAAAs). Three patients were men, and the median age at diagnosis was 49 years. The diagnosis of GI vasculitis and CP was made simultaneously in 4 patients. At the time of onset, all patients had abdominal pain and constitutional manifestations; the median erythrocyte sedimentation rate was 62.5 mm/1 h (range, 20-86 mm/1 h). All patients had evidence of mesenteric vasculitis at angiography. Three patients also had associated renal artery stenoses. Abdominal computed tomography showed spleen infarcts in 2 patients, bowel wall thickening in 1, and liver infarction in 1. Two patients underwent surgical intervention for acute abdomen; there was histologic evidence of small bowel infarcts and infarction of the spleen and liver in 1. Oral prednisone was administered to all 5 patients (median starting dose, 60 mg/d; range, 25-80 mg/d). Three patients also received immunosuppressive agents, 1 tamoxifen, and 1 anti-tumor necrosis factor therapy. All patients had at least 1 relapse or recurrence of vasculitis, but at last visit, GI vasculitis and CP were in remission in all 5 patients.This study provides evidence that GI manifestations due to mesenteric vasculitis may be associated with CP. Vasculitic involvement of the renal arteries is also frequently present in these patients. Aggressive immunosuppressive treatment should be promptly initiated to forestall abdominal complications. These findings reinforce the hypothesis that a vasculitic process plays an important role in the pathogenesis of CP.
2011
- [Disease activity assessment in large vessel vasculitis]
[Articolo su rivista]
Magnani, L; Versari, A; Salvo, D; Casali, M; Germanò, G; Meliconi, R; Pulsatelli, L; Formisano, D; Bajocchi, G; Pipitone, N; Boiardi, L; Salvarani, Carlo
abstract
Disease activity assessment in large vessel vasculitis (LVV) is often challenging for physicians. In this study, we compared the assessment of disease activity based on inflammatory markers, clinical indices (Indian Takayasu Activity Score [ITAS] and the Kerr/National Institute of Health indices [Kerr/NIH]), and 18F-Fluorodesossiglucose (FGD) vascular uptake at positron emission tomography (Pet). We found that Pet results did not statistically correlate with the clinical indices ITAS and Kerr/NIH, because FDG uptake was increased (grade>2 on a 0-3 scale in at least one evaluated vascular segment) in many patients with inactive disease according to clinical and laboratory parameters (i.e., negative ITAS and Kerr/NIH indices as well as normal erythrocyte sedimentation rate (ESR) and C-reactive protein (PCR)). Similarly, interleukin- 6 and its soluble receptor did not statistically correlate with disease activity. In contrast, clinical indices showed a significant correlation between each other and with inflammatory markers (VES and PCR). These data suggest that while clinical indices and inflammatory markers may be useful to assess disease activity, Pet may be more sensitive.
2010
- An Italian shared dermatological and rheumatological proposal for the use of biological agents in psoriatic disease
[Articolo su rivista]
Marchesoni, A; Altomare, G; Matucci Cerinic, M; Balato, N; Olivieri, I; Salvarani, Carlo; Lotti, T; Scarpa, R; Vena, G. A; Valesini, G; Giannetti, Alberto
abstract
As psoriatic disease (PD) is a condition characterized by the combination of inflammatory skin (psoriasis) and osteo-articular manifestations (psoriatic arthritis), its treatment should cover both its clinical components.
2010
- Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis involving the central nervous system: case report and review of the literature
[Articolo su rivista]
Ghinoi, A; Zuccoli, G; Pipitone, N; Salvarani, Carlo
abstract
To report a case of biopsy-proven, ANCA-associated vasculitis (AAV) involving the central nervous system (CNS) and to review the relevant literature.
2010
- Chronic periaortitis
[Articolo su rivista]
Pipitone, N; Salvarani, Carlo; Peter, H. H.
abstract
Chronic periaortitis is a rare fibroinflammatory disorder which affects the abdominal aorta and may spread into the retroperitoneum, often encasing the ureters. An aneurysma of the abdominal aorta and vasculitis of the thoracic aorta and of supra-aortic vessels may also coexist. Chronic periaortitis can be idiopathic or secondary to different triggers such as drugs, tumors and infections. Abdominal and/or low back pain is the hallmark symptom. Laboratory markers of inflammation are usually increased. The diagnosis rests on computerized tomography or magnetic resonance imaging, which typically show a retroperitoneal mass displacing the aorta anteriorly and the ureters medially. Positron-emission tomography may assist in defining disease activity and extension. Chronic periaortitis should be differentiated from other fibrosing disorders of various origins. Histology is required in atypical cases to secure the diagnosis. Treatment is based on high-dose steroids with a tapering scheme combined with immunosuppressive agents in refractory or relapsing disease. In case of ureter obstruction early DJ-catheter placement is required. Operative interventions to relieve ureter obstruction are rarely necessary provided immunosuppressive treatment is timely instituted.
2010
- Comment on: Longitudinal examination with shoulder ultrasound in patients with polymyalgia rheumatica: Reply
[Articolo su rivista]
Macchioni, P.; Boiardi, L.; Salvarani, C.
abstract
2010
- Differential effects of anti-TNF-alpha drugs on fibroblast-like synoviocyte apoptosis
[Articolo su rivista]
Pattacini, Laura; Boiardi, Luigi; Casali, Bruno; Salvarani, Carlo
abstract
Novel drugs targeting TNF-alpha are available for treatment of RA. Fibroblast-like synoviocytes (FLSs) play a fundamental role in RA progression, through their expansion caused in part by resistance to cell death induction. The aim of our study was to determine the effects of different anti-TNF-alpha agents on FLS apoptosis.
2010
- EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis
[Articolo su rivista]
Basu, Neil; Watts, Richard; Bajema, Ingeborg; Baslund, Bo; Bley, Thorsten; Boers, Maarten; Brogan, Paul; Calabrese, Len; Cid, Maria C; Cohen Tervaert, Jan Willem; Flores Suarez, Luis Felipe; Fujimoto, Shouichi; de Groot, Kirsten; Guillevin, Loic; Hatemi, Gulen; Hauser, Thomas; Jayne, David; Jennette, Charles; Kallenberg, Cees G. M; Kobayashi, Shigeto; Little, Mark A; Mahr, Alfred; Mclaren, John; Merkel, Peter A; Ozen, Seza; Puechal, Xavier; Rasmussen, Niels; Salama, Alan; Salvarani, Carlo; Savage, Caroline; Scott, David G. I; Segelmark, Mårten; Specks, Ulrich; Sunderköetter, Cord; Suzuki, Kazuo; Tesar, Vladimir; Wiik, Allan; Yazici, Hasan; Luqmani, Raashid
abstract
The systemic vasculitides are multiorgan diseases where early diagnosis and treatment can significantly improve outcomes. Robust nomenclature reduces diagnostic delay. However, key aspects of current nomenclature are widely perceived to be out of date, these include disease definitions, classification and diagnostic criteria. Therefore, the aim of the present work was to identify deficiencies and provide contemporary points to consider for the development of future definitions and criteria in systemic vasculitis.
2010
- Efficacy and safety of various repeat treatment dosing regimens of rituximab in patients with active rheumatoid arthritis: results of a Phase III randomized study (MIRROR)
[Articolo su rivista]
Rubbert Roth, Andrea; Tak, Paul P; Zerbini, Cristiano; Tremblay, Jean Luc; Carreño, Luis; Armstrong, Gillian; Collinson, Neil; Shaw, Tim M; MIRROR Trial, Investigators; Nash, P; Bagga, H; Hall, S; Littlejohn, G; Manolios, N; Van Den Bosch, F; Ximenes, Ac; Mccarthy, T; Atkins, C; Thorne, Jc; Offer, R; Pope, J; Keystone, E; Huang, F; Wu, D; Karjalainen, A; Schaeverbeke, T; Euller Ziegler, L; Jorgensen, C; Nguyen, M; Puechal, X; Wassenberg, S; Heilig, B; Mueller Ladner, U; Wollenhaupt, J; Braun, J; Gauler, G; Szekanecz, Z; Nagy, K; Galeazzi, M; Trotta, F; Bombardieri, S; Salvarani, Carlo; Pellerito, R; Seriolo, B; Adami, S; Bianchi, G; Giacomelli, R; Arioli, G; Cantini, F; Ching, D; Gilchrist, N; Singh, J; Lukac, J; Rovensky, J; Macejova, Z; Kalla, A; Tikly, M; Ally, Mm; Marenco, Jl; Tinture, T; Juanola, J; Alvaro Gracia, Jm; Rodriguez Heredia, Jm; Sandoval, Tp; Cheng, Tt; Luo, Sf; Lan, Jl; Osiri, M; Nilganuwong, S; Asavatanabodee, P; Nanagara, R; Louthrenoo, W; Hazleman, Bl; Jubb, R; George, E; Hakim, A; Grennan, D; Gardiner, P; Taylor, J; Mcnally, J; Hutchinson, D; Plant, M.
abstract
To evaluate the efficacy and safety of three dosing and repeat treatment regimens of rituximab (RTX) plus MTX in patients with active RA.
2010
- G/R 241 polymorphism of intercellular adhesion molecule 1 (ICAM-1) is associated with Fuchs uveitis
[Articolo su rivista]
Cimino, Luca; Boiardi, Luigi; Aldigeri, Raffaella; Casali, Bruno; Nicoli, Davide; Farnetti, Enrico; SALVARANI, CARLO; Cirone, Daniele; De Martino, Liberatina; Pupino, Alessandro; Cappuccini, Luca
abstract
To investigate potential associations of the ICAM-1 gene polymorphisms and Fuchs uveitis in a cohort of Italian patients.
2010
- Localized vasculitis of the gastrointestinal tract: a case series
[Articolo su rivista]
Salvarani, Carlo; Calamia, Kenneth T; Crowson, Cynthia S; Miller, Dylan V; Broadwell, Aaron W; Hunder, Gene G; Matteson, Eric L; Warrington, Kenneth J.
abstract
To describe the clinical features and outcomes of patients with localized vasculitis of the gastrointestinal tract (LVGT).
2010
- Patient preferences in the choice of anti-TNF therapies in rheumatoid arthritis. Results from a questionnaire survey (RIVIERA study).
[Articolo su rivista]
S., Scarpato; M., Antivalle; E. G., Favalli; F., Nacci; S., Frigelli; F., Bartoli; L., Bazzichi; G., Minisola; M., Matucci Cerinic; Salvarani, Carlo; Altucci, P; Bombardieri, S; Battaglia, E; Ferri, Clodoveo; Pozzi, Mr; Afeltra, A; Bersi, M; Tartarelli, G; Montecucco, Cm; Altomare, E; Bambara, Lm; Bucci, R; Colombelli, Pl; Corsaro, S; Rinaldi, F; Sinigaglia, L; Trotta, F; Carrabba, M; Migliore, A; Bianchi, G; Grassi, W; Rocchetta, Pa; Altomonte, L; Coaccioli, S; Danieli Armando, G; Perpignano, G; Broggini, M; Morassi, P; Peronato, G; Canesi, B; Delsante, G; Di Giuseppe, P; Di Rosa, So; Gorla, R; Malavolta, N; Solinas, F; Todesco, S; Varcasia, G; Versace, F; Sabadini, L; Del Giacco, S; Marasini, B; Bagnato, G; Gerli, R; Modena, V; Di Piazza, V.
abstract
OBJECTIVE: To identify the determinants of anti-TNF-naive patients' preferences for the route of administration of anti-TNF agents.METHODS: The study was carried out in 50 Italian rheumatology centres (802 patients). All patients completed a 31-item questionnaire addressing their perceptions of current treatment and the preferences for treatment with anti-TNF agents. Statistical methods included analysis of variance (ANOVA), t-test and chi-square test.RESULTS: The response rate to the questionnaire was 97.6%. At the time of the survey, 310 (39.9%) patients were dissatisfied with current treatments, owing to inefficacy, side effects and inconvenience of administration. The i.v. and s.c. routes of administration were preferred by 50.2 and 49.8%, respectively. No significant difference was found in patients by gender, age, RA duration or number of drugs used. Reasons for the choice of i.v. administration were the safety of treatment at the hospital and the reassuring effect of physician presence. The s.c. administration was chosen for the convenience of treatment and in particular for home treatment. Patients dissatisfied with current therapy due to side effects preferred s.c. administration (P = 0.029), whereas patients choosing the i.v. route had slightly higher scores on 'today pain' (P = 0.047) and 'articular pain' (P = 0.023) of the Rheumatoid Arthritis Disease Activity Index (RADAI).CONCLUSIONS: Both i.v. and s.c. treatments were well accepted by patients. However, treatment choice has to be discussed with patients, as individual preference seems to be determined by personal attitudes towards safety and convenience, by past experience and by the perception of current disease status.
2010
- Primary central nervous system vasculitis: Is it a single disease?
[Articolo su rivista]
Hunder, Gene G; Salvarani, Carlo; Brown, Robert D.
abstract
Editorial on primary central nervous system vasculitis.
2010
- Psoriatic disease: concepts and implications
[Articolo su rivista]
Scarpa, R; Altomare, G; Marchesoni, A; Balato, N; Matucci Cerinic, M; Lotti, T; Olivieri, I; Vena, G. A; Salvarani, Carlo; Valesini, G; Giannetti, Alberto
abstract
The term Psoriatic disease was recently introduced in an attempt to provide a new perspective on psoriasis and related disorders. This concept emerged from a better understanding of the pathogenesis of psoriasis and of its extra-cutaneous manifestations. Beginning with a historical perspective, this manuscript reviews the evolution which led, over the last 30 years, to the development of this new concept.
2010
- Reelin levels are increased in synovial fluid of patients with rheumatoid arthritis
[Articolo su rivista]
Magnani, A; Pattacini, L; Boiardi, L; Casali, B; Salvarani, Carlo
abstract
To evaluate the presence and the glycosylation pattern of reelin in synovial fluid and serum of patients affected by different rheumatic pathologies.
2010
- Serum levels of long pentraxin PTX3 in patients with polymyalgia rheumatica
[Articolo su rivista]
Pulsatelli, L; Peri, G; Macchioni, P; Boiardi, L; Salvarani, Carlo; Cantini, F; Mantovani, A; Meliconi, R.
abstract
To evaluate PTX3 feasibility to provide a prognostic tool in PMR clinical practice.
2010
- Switching from infliximab or etanercept to adalimumab in resistant or intolerant patients with spondyloarthritis: a 4-year study
[Articolo su rivista]
Spadaro, Antonio; Punzi, Leonardo; Marchesoni, Antonio; Lubrano, Ennio; Mathieu, Alessandro; Cantini, Fabrizio; Olivieri, Ignazio; Salvarani, Carlo; Scarpa, Raffaele; Scrivo, Rossana; Ramonda, Roberta; Porru, Giovanni; D'Angelo, Salvatore; Catanoso, Mariagrazia; Atteno, Mariangela; Valesini, Guido
abstract
TNF-alpha antagonists, infliximab (INF), etanercept (ETA) and adalimumab (ADA), have been demonstrated to be effective in controlling symptoms in SpAs. The aim of this study was to investigate the possibility of using ADA as a second or third choice.
2010
- Terapia delle manifestazioni oculari associate a malattie reumatiche infiammatorie
[Capitolo/Saggio]
Pipitone, N; Salvarani, C; Cimino, L
abstract
2010
- The causes of uveitis in a referral centre of Northern Italy
[Articolo su rivista]
Cimino, L; Aldigeri, R; Salvarani, Carlo; Zotti, C. A; Boiardi, L; Parmeggiani, M; Casali, B; Cappuccini, L.
abstract
Uveitis is a complex intraocular inflammatory disease resulting from several aetiological entities that are linked to geographical, genetic and socioeconomic variables. The purpose of this study was to provide an overview of the distribution patterns of uveitis as seen in a nationwide referral centre at a community hospital in Reggio Emilia, northern Italy, and to compare our data with those reported in previously published international series. The records of 1064 patients of Italian origin with uveitis referred to the Immunology Ocular Unit of the Arcispedale S. Maria Nuova Hospital in Reggio Emilia from 2002 to 2008 were classified and analysed. Data regarding sex, race, residence, age at presentation and at onset of uveitis, ocular involvement, clinical characteristics, ocular condition, and systemic disease associations were collected. The mean age at onset of uveitis was 41 years (range: 1-94), and the male-to-female ratio was 1:1.2. Anterior uveitis was the most common location (51.2%), followed by posterior uveitis (23.4%), panuveitis (19.6%), and intermediate uveitis (5.8%). The most frequent entities included Fuchs uveitis (22.7%), herpetic anterior uveitis (9.9%), toxoplasmosis (6.9%), HLA-B27-associated anterior uveitis (5.3%), and Behçet's disease (5.3%). The distribution we observed of the most common disease entities conformed to previous international series. In our series, Fuchs uveitis represented the most common diagnosis (22.7%, 45% of anterior uveitis). The high percentage of specific diagnosis (74%) can be explained by the establishment of new disease categories over time as well as by a systematic multi-disciplinary diagnostic approach.
2009
- Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial
[Articolo su rivista]
Van der Heijde, D; Schiff, M. H; Sieper, J; Kivitz, A. J; Wong, R. L; Kupper, H; Dijkmans, B. A. C; Mease, P. J; Davis, J. C; Atlas, ; Salvarani, Carlo
abstract
To determine the long-term effect of adalimumab on patients with ankylosing spondylitis (AS) who participated in the Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS (ATLAS), a randomised, double-blind, placebo controlled, 24-week trial.
2009
- Biopsy findings in primary angiitis of the central nervous system
[Articolo su rivista]
Miller, Dylan V; Salvarani, Carlo; Hunder, Gene G; Brown, Robert D; Parisi, Joseph E; Christianson, Teresa J; Giannini, Caterina
abstract
Primary angiitis of the central nervous system (PACNS) is a form of vasculitis restricted to the brain and spinal cord, with protean clinical manifestations and often slowly progressive course. Outcomes vary, ranging from spontaneous resolution to rapid decline and death. Diagnosis of PACNS is based on angiography and/or biopsy. We reviewed surgical biopsies from 46 patients (53 biopsies) with PACNS, including 25 men and 21 women (median age 46, range: 25 to 84 y) and correlated the findings with relevant clinical parameters. Biopsies (51 brain, 2 spinal) were diagnostic of vasculitis in 29 (63%) patients. Three morphologic patterns of vasculitis were observed: acute necrotizing (n=4, 14%); purely lymphocytic (n=8, 28%); and granulomatous (n=17, 58%), 8 associated with deposition of beta-A4 amyloid. Biopsies not diagnostic of PACNS (n=17, 37%) showed nonspecific gliosis (53%), mild perivascular mononuclear inflammation (18%), and parenchymal ischemic damage/infarct (18%). All positive biopsies were among those directed to an imaging abnormality (targeted biopsies) and biopsies including leptomeninges were more often positive than those that did not. Thus, where possible, a targeted biopsy that includes leptomeninges is recommended to maximize diagnostic potential. No statistically significant differences in outcome were noted among the 3 histopathologic groups or when comparing biopsy positive versus biopsy negative PACNS groups. Overall the outcomes were relatively favorable, with only 14% mortality or severe morbidity at 1.14 years (mean) after biopsy.
2009
- Clinical features and epidemiology of spondyloarthritides associated with inflammatory bowel disease
[Articolo su rivista]
Salvarani, Carlo; Fries, Walter
abstract
Inflammation of axial and/or peripheral joints is one of the most frequent extra-intestinal manifestations complicating the clinical course and therapeutic approach in inflammatory bowel diseases (IBD). The frequency of these complications seems to be similar for both diseases, Crohn's disease and ulcerative colitis. Arthritis associated with IBD belongs to the category of spondyloarthropathies. Axial involvement ranges from isolated inflammatory back pain to ankylosing spondylitis, whereas peripheral arthritis is noted in pauciarticular and in polyarticular disease. Asymptomatic radiological involvement of the sacroiliac joints is reported to occur in up to 50% of patients. Other musculoskeletal manifestations such as buttock pain, dactylitis, calcaneal enthesitis, and thoracic pain are frequently underdiagnosed and, consequently, are not treated appropriately. Several diagnostic approaches and criteria have been proposed over the past 40 years in an attempt to correctly classify and diagnose such manifestations. The correct recognition of spondylarthropathies needs an integrated multidisciplinary approach in order to identify common therapeutic strategies, especially in the era of the new biologic therapies.
2009
- Comment on: Risk factors for severe cranial ischaemic events in an Italian population-based cohort of patients with giant cell arteritis: Reply
[Articolo su rivista]
Salvarani, C.; Boiardi, L.; Pipitone, N.
abstract
2009
- Criteria, frequency, and duration of clinical remission in psoriatic arthritis patients with peripheral involvement requiring second-line drugs
[Articolo su rivista]
Cantini, Fabrizio; Niccoli, Laura; Nannini, Carlotta; Cassarà, Emanuele; Pasquetti, Paolo; Olivieri, Ignazio; Salvarani, Carlo
abstract
This article outlines our case-control, prospective, 6-year followup study to evaluate the frequency of clinical remission and duration of remission episodes in patients with peripheral psoriatic arthritis (PsA). All case patients were consecutive new outpatients with peripheral PsA requiring second-line drugs. Controls were consecutive new outpatients with rheumatoid arthritis (RA). Modified American College of Rheumatology criteria for RA were used to assess the remission in patients with PsA. One or more episodes of remission occurred in 57/236 (24.1%) PsA patients and in 20/268 (7.5%) controls (p < 0.001). No significant difference was recorded for duration of remissions between the group receiving traditional disease modifying antirheumatic drug (DMARD) and the anti-tumor necrosis factor (TNF) group: 11 +/- 7.2 and 13.3 +/- 8.1 months, respectively (p = NS). The duration of remission after interruption of therapy was 12 +/- 2.4 months for the PsA group and 3 +/- 1.5 months for patients with RA (p < 0.001). No predictor of remission at diagnosis could be determined by multivariate analysis. Based on our findings, remission is possible in up to 24% of patients with peripheral PsA. It is significantly more frequent, but not longer, in patients receiving anti-TNF drugs compared to those treated with traditional DMARD.
2009
- EULAR recommendations for the management of large vessel vasculitis
[Articolo su rivista]
Mukhtyar, C; Guillevin, L; Cid, M. C; Dasgupta, B; de Groot, K; Gross, W; Hauser, T; Hellmich, B; Jayne, D; Kallenberg, C. G. M; Merkel, P. A; Raspe, H; Salvarani, Carlo; Scott, D. G. I; Stegeman, C; Watts, R; Westman, K; Witter, J; Yazici, H; Luqmani, R.
abstract
To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis.
2009
- EULAR recommendations for the management of primary small and medium vessel vasculitis
[Articolo su rivista]
Mukhtyar, C; Guillevin, L; Cid, M. C; Dasgupta, B; de Groot, K; Gross, W; Hauser, T; Hellmich, B; Jayne, D; Kallenberg, C. G. M; Merkel, P. A; Raspe, H; Salvarani, Carlo; Scott, D. G. I; Stegeman, C; Watts, R; Westman, K; Witter, J; Yazici, H; Luqmani, R.
abstract
To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis.
2009
- Etanercept in the longterm treatment of patients with ankylosing spondylitis
[Articolo su rivista]
Dijkmans, Ben; Emery, Paul; Hakala, Markku; Leirisalo Repo, Marjatta; Mola, Emilio Martin; Paolozzi, Laurence; Salvarani, Carlo; Sanmarti, Raimon; Sibilia, Jean; Sieper, Joachim; Van Den Bosch, Filip; van der Heijde, Désirée; van der Linden, Sjef; Wajdula, Joseph
abstract
To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis (AS).
2009
- Giant cell arteritis and polymyalgia rheumatica
[Capitolo/Saggio]
Stone, J. R.; Pless, M.; Salvarani, C.; Pipitone, N.; Lessell, S.; Stone, J. H.
abstract
Giant cell arteritis (GCA) is a form a large-to medium-vessel vasculitis that involves the aorta and its branches. Polymyalgia rheumatica (PMR), a syndrome of muscle pain and stiffness in the neck, shoulders, and hips, often occurs with GCA but can occur independently. GCA predominantly affects the second-to fifth-order aortic branches, often in the extracranial arteries of the head. The mean age at diagnosis of GCA is approximately 72. The diagnosis of GCA is made usually by biopsy of the temporal artery. GCA associated with granulomatous inflammation within the blood vessel wall, but granulomatous changes are not always evident early in the disease. Giant cells occur in a slight majority of cases of positive temporal artery biopsies. Estimates of the frequency of giant cells in temporal artery biopsy tissues are on the order of 50-80%. In GCA, clinical symptoms of local vascular inflam-mation and vascular insufficiency are usually accompanied or preceded by a systemic inflammatory process. Visual loss is the most feared complication of GCA. Visual loss may occur through the syndrome of anterior ischemic optic neuropathy, caused by narrowing of the posterior ciliary artery, as well as through other arterial insufficiency syndromes. Glucocorticoids are the cornerstone of treatment for GCA and PMR. PMR occurring in the absence of GCA requires a lower dose of prednisone for disease control. © 2010 Springer-Verlag London.
2009
- International multicenter psoriasis and psoriatic arthritis reliability trial for the assessment of skin, joints, nails, and dactylitis
[Articolo su rivista]
Chandran, Vinod; Gottlieb, Alice; Cook, Richard J; Duffin, Kristina Callis; Garg, Amit; Helliwell, Philip; Kavanaugh, Arthur; Krueger, Gerald G; Langley, Richard G; Lynde, Charles; Mchugh, Neil; Mease, Philip; Olivieri, Ignazio; Rahman, Proton; Rosen, Cheryl F; Salvarani, Carlo; Thaci, Diamant; Toloza, Sergio M. A; Wong, Maxine Yat Wing; Zhou, Qian M; Gladman, Dafna D.
abstract
Clinical trials in psoriasis and psoriatic arthritis (PsA) involve assessment of the skin and joints. This study aimed to determine whether assessment of the skin and joints in patients with PsA by rheumatologists and dermatologists is reproducible.
2009
- Late-onset rheumatoid arthritis and late-onset spondyloarthritis
[Articolo su rivista]
Olivieri, I; Pipitone, N; D' Angelo, S; Padula, A; Salvarani, Carlo
abstract
Both rheumatoid arthritis and spondyloarthritis may have a late onset. Elderly-onset rheumatoid arthritis is usually defined as rheumatoid arthritis with onset at age 60 or over. It appears to be a heterogeneous disease, with a seropositive subset resembling adult-onset rheumatoid arthritis, and a less severe seronegative subset which sometimes exhibits features overlapping with those of polymyalgia rheumatica. The spondyloarthritis complex includes definite entities as well as undifferentiated forms. Each of these may have a late-onset. Late-onset undifferentiated spondyloarthritis appears to be relatively more frequent than late-onset ankylosing spondylitis. Its clinical spectrum seems to be as broad as that observed in young and middle-aged adults with the exception of distal inflammatory swelling with pitting oedema. A special aspect of the differential diagnosis is the discrimination from other elderly-onset diseases showing the inflammatory swelling with pitting oedema over the dorsum of feet or hands. Psoriatic arthritis frequently begins in the elderly and shows some differences from the younger onset disease. Regarding the management, patients with late-onset rheumatoid arthritis and spondyloarthritis are treated similarly to younger patients taking into account age-related changes in the pharmacokinetics and pharmacodynamics of drugs and the presence of conditions able to reduce medication adherence.
2009
- Longitudinal examination with shoulder ultrasound of patients with polymyalgia rheumatica
[Articolo su rivista]
Macchioni, Pierluigi; Catanoso, Maria Grazia; Pipitone, Nicolò; Boiardi, Luigi; Salvarani, Carlo
abstract
To determine if ultrasonography (US) and power Doppler (PD) may be useful in identifying polymyalgia rheumatica (PMR) patients with relapsing disease.
2009
- Management of Behçet disease: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for the management of Behçet disease
[Articolo su rivista]
Hatemi, G; Silman, A; Bang, D; Bodaghi, B; Chamberlain, A. M; Gul, A; Houman, M. H; Kötter, I; Olivieri, I; Salvarani, Carlo; Sfikakis, P. P; Siva, A; Stanford, M. R; Stübiger, N; Yurdakul, S; Yazici, H.
abstract
To present and analyse the literature sources regarding the management of Behçet disease (BD) identified during the systematic literature research, which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for the management of BD.
2009
- Multidisciplinary focus on cyclosporin A
[Articolo su rivista]
Salvarani, Carlo; Boiardi, Luigi; Macchioni, Pierluigi; Pipitone, Nicolò; Catanoso, Mariagrazia; Pigatto, Paolo
abstract
Cyclosporin A (CsA) has been proved to be effective in the treatment of severe cutaneous psoriasis and psoriatic arthritis (PsA). In psoriasis, CsA therapy can be used as: (1) intermittent short-course therapy; (2) continuous long-term therapy; (3) crisis intervention; and (4) a combination of sequential and rotational therapy. Several open prospective studies have shown the short-term efficacy of CsA in PsA. While there were no randomized controlled trials (RCT) comparing CsA to placebo, 3 published controlled trials compared CsA to other disease modifying antirheumatic drugs (DMARD). These studies support the efficacy of CsA in patients with PsA and peripheral arthritis. However, no conclusions can be drawn on the efficacy of CsA for dactylitis and axial disease. Long-term studies have shown the persistent efficacy and safety of CsA in PsA. The beneficial effects of CsA in angiogenesis-related diseases such as PsA and cutaneous psoriasis may also be mediated by its ability to block the angiogenic effects induced by vascular endothelial growth factor.
2009
- Protein Z G79A and A-13G gene polymorphisms in Italian patients with Behçet's disease
[Articolo su rivista]
Ghinoi, A; Boiardi, L; Atzeni, F; Casali, B; Farnetti, E; Nicoli, D; Pipitone, N; Olivieri, I; Cantini, F; Salvi, F; La Corte, R; Triolo, G; Filippini, D; Paolazzi, G; Salvarani, Carlo
abstract
To investigate potential associations between A-13G and G79A polymorphisms of the protein Z gene and venous thrombosis and other clinical manifestations in Italian patients with Behçet's disease (BD).
2009
- Psoriatic arthritis spondylitis radiology index: a modified index for radiologic assessment of axial involvement in psoriatic arthritis
[Articolo su rivista]
Lubrano, Ennio; Marchesoni, Antonio; Olivieri, Ignazio; D'Angelo, Salvatore; Spadaro, Antonio; Parsons, Wendy J; Cauli, Alberto; Salvarani, Carlo; Mathieu, Antonio; Porter, Guy; Helliwell, Philip S.
abstract
To develop and validate a modified index for assessing the radiologic axial involvement in psoriatic arthritis (PsA) in a group of patients with established disease.
2009
- Risk factors for severe cranial ischaemic events in an Italian population-based cohort of patients with giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Della Bella, C; Cimino, L; Macchioni, P; Formisano, D; Bajocchi, G; Pipitone, N; Catanoso, M. G; Restuccia, G; Ghinoi, A; Boiardi, L.
abstract
To evaluate the impact of traditional cardiovascular risk factors, carotid atherosclerosis and the effect of anti-platelet/anti-coagulant therapy on the occurrence of severe cranial ischaemic events (CIEs) in GCA.
2009
- Single-center series and systematic review of randomized controlled trials of malignancies in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis receiving anti-tumor necrosis factor alpha therapy: is there a need for more comprehensive screening procedures?
[Articolo su rivista]
Nannini, Carlotta; Cantini, Fabrizio; Niccoli, Laura; Cassarà, Emanuele; Salvarani, Carlo; Olivieri, Ignazio; Lally, Edward V.
abstract
To systematically review the occurrence of malignancies among patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) treated with anti-tumor necrosis factor alpha (anti-TNFalpha) therapy in randomized controlled trials (RCTs), and to report a retrospective personal case series evaluating the frequency of malignancies in patients with RA, PsA, and AS requiring anti-TNF therapy selected with more comprehensive cancer screening procedures compared with patients screened according to previously published procedures.
2009
- The radiological assessment of axial involvement in psoriatic arthritis: a validation study of the BASRI total and the modified SASSS scoring methods
[Articolo su rivista]
Lubrano, E; Marchesoni, A; Olivieri, I; D'Angelo, S; Spadaro, A; Parsons, W. J; Cauli, A; Salvarani, Carlo; Mathieu, A; Zaccara, E; Ferrara, N; Helliwell, P. S.
abstract
To assess the validity of the BASRI and m-SASSS scores for the radiological axial involvement in psoriatic arthritis (PsA). Secondary end-points were to report on clinical, functional and radiographic characteristics of axial involvement.
2009
- Toll-like receptor 4 (TLR4) gene polymorphisms in Italian patients with Behçet's disease
[Articolo su rivista]
Boiardi, L; Atzeni, F; Casali, B; Farnetti, E; Nicoli, D; Pipitone, N; Catanoso, M. G; Olivieri, I; Cantini, F; Salvi, F; La Corte, R; Triolo, G; Filippini, D; Paolazzi, G; Salvarani, Carlo
abstract
To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, clinical features, and severity of Behçet's disease (BD).
2009
- Toll-like receptor 4 (TLR4) gene polymorphisms in giant cell arteritis
[Articolo su rivista]
Boiardi, L; Casali, B; Farnetti, E; Pipitone, N; Nicoli, D; Macchioni, P; Cimino, L; Bajocchi, G. L; Catanoso, M. G; Pattacini, L; Ghinoi, A; Restuccia, G; Salvarani, Carlo
abstract
To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, and clinical features of giant cell arteritis (GCA).
2009
- Tuberculous uveitis, a resurgent and underdiagnosed disease
[Articolo su rivista]
Cimino, Luca; Herbort, Carl P; Aldigeri, Raffaella; Salvarani, Carlo; Boiardi, Luigi
abstract
Over the last decade ocular involvement due to tuberculosis has re-emerged. In non-endemic areas the low frequency of active tuberculosis is at the origin of an underestimation of the disease. The purpose of this study is to report a group of patients with presumed tuberculous uveitis and to analyse the pre-diagnostic course, the diagnostic delay and the evolution of ocular inflammation after diagnosis and anti-tuberculous treatment.
2008
- -463 G/A myeloperoxidase promoter polymorphism in giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Casali, B; Farnetti, E; Pipitone, N; Nicoli, D; Macchioni, P. L; Cimino, L; Bajocchi, G. L; Catanoso, M. G; Pattacini, L; Ghinoi, A; Restuccia, G; Boiardi, L.
abstract
To investigate potential associations between-463 G/A myeloperoxidase (MPO) promoter polymorphism and susceptibility to, and clinical features of giant cell arteritis (GCA).
2008
- 1T magnetic resonance imaging in the diagnosis of giant cell arteritis: comparison with ultrasonography and physical examination of temporal arteries
[Articolo su rivista]
Ghinoi, A; Zuccoli, G; Nicolini, A; Pipitone, N; Macchioni, L; Bajocchi, G. L; Nicoli, F; Silingardi, M; Catanoso, M. G; Boiardi, L; Salvarani, Carlo
abstract
To assess the usefulness of 1T magnetic resonance imaging (MRI) of temporal arteries and to compare 1T MRI with duplex ultrasonography (US) and physical examination of temporal arteries for the diagnosis of giant cell arteritis (GCA) in patients with suspected GCA.
2008
- Adalimumab reduces pain, fatigue, and stiffness in patients with ankylosing spondylitis: results from the adalimumab trial evaluating long-term safety and efficacy for ankylosing spondylitis (ATLAS).
[Articolo su rivista]
Revicki, Dennis A; Luo, Michelle P; Wordsworth, Paul; Wong, Robert L; Chen, Naijun; Davis, John C; Atlas, ; Salvarani, Carlo
abstract
To evaluate the effect of adalimumab on pain, fatigue, and stiffness in patients with active ankylosing spondylitis (AS).
2008
- Angiography-negative primary central nervous system vasculitis: a syndrome involving small cerebral vessels
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Calamia, Kenneth T; Christianson, Teresa J. H; Huston, John; Meschia, James F; Giannini, Caterina; Miller, Dylan V; Hunder, Gene G.
abstract
Primary central nervous system vasculitis (PCNSV) is a rare and poorly understood syndrome. We describe the clinical findings in 8 patients who appear to have a distinct subset of PCNSV. We identified 101 consecutive patients with PCNSV who were seen between January 1, 1983, and December 31, 2003. The diagnosis was based on conventional angiography in 70 patients and on central nervous system biopsy in 31 patients. Six of the 31 patients also had angiograms showing changes of vasculitis. Thus, 76 patients of the cohort had abnormal angiograms. Eight of the 101 patients had normal angiograms ("angiography-negative") but had brain biopsies that showed vasculitis. We compared the clinical and laboratory findings and outcomes of the 8 patients with angiography-negative PCNSV with those of the 76 patients with PCNSV whose angiograms showed evidence of vasculitis ("angiography-positive"). In comparison with the 76 patients with angiography-positive PCNSV, the 8 patients with angiography-negative PCNSV more commonly had 1) a cognitive disorder (87.5% vs. 43.4%; p =.024); 2) cerebrospinal fluid abnormalities (a protein level >or=700 mg/L or a white blood cell count >or=10 x 10(6)/L) (100% vs. 35.5%; p =.034); and 3) meningeal or parenchymal enhancing lesions on magnetic resonance imaging (75.0% vs. 23.9%; p =.007). Other differences between the 2 groups were observed but were not significantly different. All patients with angiography-negative PCNSV responded to treatment and none died. Angiography-negative PCNSV appears to be a distinct subtype of cerebral vasculitis with small vessel involvement beyond the resolution of conventional angiography and is associated with a favorable outcome.
2008
- Cervical interspinous bursitis in active polymyalgia rheumatica
[Articolo su rivista]
Salvarani, Carlo; Barozzi, L; Cantini, F; Niccoli, L; Boiardi, L; Valentino, M; Pipitone, N; Bajocchi, G; Macchioni, P; Catanoso, M. G; Olivieri, I; Hunder, G. G.
abstract
To evaluate the inflammatory involvement of cervical interspinous bursae in patients with polymyalgia rheumatica (PMR) using MRI.
2008
- Cranial giant cell arteritis evolving into early large-vessel vasculitis
[Articolo su rivista]
Ghinoi, A; Pipitone, N; Nicolini, A; Salvarani, Carlo
abstract
Case report: Cranial giant cell arteritis evolving into early large-vessel vasculitis
2008
- Developing classification criteria for polymyalgia rheumatica: comparison of views from an expert panel and wider survey
[Articolo su rivista]
Dasgupta, Bhaskar; Salvarani, Carlo; Schirmer, Michael; Crowson, Cynthia S; Maradit Kremers, Hilal; Hutchings, Andrew; Matteson, Eric L.
abstract
This report summarizes the findings from a consensus process to identify potential classification criteria for polymyalgia rheumatica (PMR).
2008
- Diagnosis and treatment of giant cell arteritis
[Articolo su rivista]
Cantini, Fabrizio; Niccoli, Laura; Nannini, Carlotta; Bertoni, Michele; Salvarani, Carlo
abstract
Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of unknown aetiology occurring in the elderly. It affects the cranial branches of the arteries originating from the aortic arch and is usually associated with markedly elevated acute-phase reactants. In 10-15% of cases the extra-cranial branches of the aortic arch are involved. GCA is closely related to polymyalgia rheumatica (PMR), although the relationship between the two disorders is still unclear. New-onset headache, scalp tenderness, jaw claudication, temporal artery abnormalities on physical examination, visual symptoms and associated PMR represent the most typical and frequent features of the disease. Systemic manifestations, including fever, anorexia and weight loss, are observed in 50% of cases. Less frequent manifestations are related to the central or peripheral nervous systems, the respiratory tract and extra-cranial large-vessel involvement. As GCA is characterized by a wide spectrum of clinical manifestations, it is important to recognize the different onset patterns of the disease and related diagnostic steps. The diagnosis is relatively straightforward in the presence of typical cranial manifestations, but it may be challenging in the case of a normal erythrocyte sedimentation rate, occult GCA or in patients with isolated extra-cranial features. Temporal artery biopsy still represents the gold standard for diagnosis, while the role of ultrasonography, high-resolution magnetic resonance imaging and positron emission tomography should be better addressed. Corticosteroids remain the therapy of choice. Data supporting the usefulness of antiplatelet agents and anticoagulants combined with corticosteroids to prevent ischaemic complications as well as the corticosteroid-sparing effect of methotrexate and anti-tumour necrosis factor-alpha drugs are limited and non-conclusive.
2008
- Do we need treatment with tumour necrosis factor blockers for giant cell arteritis?
[Articolo su rivista]
Salvarani, Carlo; Pipitone, Nicolò; Boiardi, Luigi; Hunder, Gene G.
abstract
Editorial on tumour necrosis factor blockers for giant cell arteritis.
2008
- EULAR recommendations for the management of Behçet disease
[Articolo su rivista]
Hatemi, G; Silman, A; Bang, D; Bodaghi, B; Chamberlain, A. M; Gul, A; Houman, M. H; Kötter, I; Olivieri, I; Salvarani, Carlo; Sfikakis, P. P; Siva, A; Stanford, M. R; Stübiger, N; Yurdakul, S; Yazici, H.
abstract
To develop evidence-based European League Against Rheumatism (EULAR) recommendations for the management of Behçet disease (BD) supplemented where necessary by expert opinion.
2008
- Editorial
[Articolo su rivista]
Salvarani, C.
abstract
2008
- Efficacy of tumor necrosis factor alpha blockade in primary central nervous system vasculitis resistant to immunosuppressive treatment
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Calamia, Kenneth T; Huston, John; Meschia, James F; Giannini, Caterina; Miller, Dylan V; Hunder, Gene G.
abstract
We report 2 patients with PCNSV who did not respond to treatment with corticosteroids and immunosuppressive medication. They were treated with tumor necrosis factor (TNF) blockers in an attempt to control the disease.
2008
- Fast spin echo-T2-weighted sequences with fat saturation in toe dactylitis of spondyloarthritis
[Articolo su rivista]
Olivieri, Ignazio; Scarano, Enrico; Padula, Angela; D'Angelo, Salvatore; Salvarani, Carlo; Cantini, Fabrizio; Niccoli, Laura; Barozzi, Libero
abstract
We aimed to establish by using fast spin echo (FSE)-T2-weighted sequences with fat saturation if flexor tendon enthesitis is the primary lesion in spondyloarthritis (SpA) toe dactylitis. Consecutive patients showing toe dactylitis and meeting Amor criteria for the classification of SpA were enrolled. Dactylitic toes and their corresponding normal contralateral digits were studied by FSE-T2-weighted sequences with fat saturation. Twelve dactylitic toes belonging to ten SpA patients were studied. All dactylitic toes showed mild-to-moderate fluid collection in the synovial sheaths of flexor digitorum brevis and longus. Involvement of joint cavity was simultaneously seen in at least one joint of eight (66.6%) out of the 12 toes. A mild-to-severe peritendinous soft tissue edema was observed in all but one of the affected toes. In no dactylitic toe was bone edema observed either near the insertions of the flexor digitorum brevis and longus tendons or in other sites of the phalanges. No lesions were observed in the 12 contralateral clinically normal toes. In SpA toe dactylitis there is no evidence of enthesitis of the flexor digitorum brevis and longus tendons and joint capsules.
2008
- Focal myositis of the calf muscles
[Articolo su rivista]
Pipitone, N; Macchioni, P; Zuccoli, G; Salvarani, Carlo
abstract
Case report of a patient with focal myositis of the calf muscles.
2008
- Frequency and duration of clinical remission in patients with peripheral psoriatic arthritis requiring second-line drugs
[Articolo su rivista]
Cantini, F; Niccoli, L; Nannini, C; Cassarà, E; Pasquetti, P; Olivieri, I; Salvarani, Carlo
abstract
To evaluate the frequency and duration of clinical remission in patients with PsA.
2008
- Images in cardiovascular medicine. Chronic periaortitis
[Articolo su rivista]
Pipitone, Nicolò; Ghinoi, Alessandra; Versari, Annibale; Vaglio, Augusto; Palmisano, Alessandra; Salvarani, Carlo
abstract
Images in cardiovascular medicine. Chronic periaortitis
2008
- Improving therapeutic options for patients with giant cell arteritis
[Articolo su rivista]
Pipitone, Nicolò; Salvarani, Carlo
abstract
Glucocorticoids remain the mainstay of treatment of giant cell arteritis. The aim of this review is to establish the optimal schedule of glucocorticoid administration, and to ascertain which other treatments may be used as glucocorticoid-sparing agents.
2008
- Infliximab for the treatment of Neuro-Behçet's disease: a case series and review of the literature
[Articolo su rivista]
Pipitone, Nicolò; Olivieri, Ignazio; Padula, Angela; D'Angelo, Salvatore; Nigro, Angelo; Zuccoli, Giulio; Boiardi, Luigi; Salvarani, Carlo
abstract
Behçet's disease (BD) is a vasculitis in which the hallmark lesions are oral and often genital ulcers. Involvement of parenchymal central nervous system (neuro-Behçet's) is a serious complication commonly characterized by brainstem and/or basal ganglia lesions. To date, treatment of neuro-Behçet's remains largely empirical, and may not adequately control the disease.
Serum tumor necrosis factor α (TNFα) levels are increased in active BD, suggesting a role for TNFα in disease pathogenesis. Clinically, significant improvement of various BD manifestations has been reported with TNFα blockade. However, evidence for the efficacy of TNFα blockers in the treatment of neuro-Behçet's is scant. We present 8 patients with neuro-Behçet's who responded favorably to infliximab therapy and review the relevant literature.
2008
- Initiative for quality in psoriasis and psoriatic arthritis
[Articolo su rivista]
Boehncke, Wolf Henning; Adebajo, Ade; Cauli, Alberto; Nash, Peter; Salvarani, Carlo; Kavanaugh, Arthur F.
abstract
Psoriasis is a common and severe skin disease. Up to 30% of psoriasis patients develop psoriatic arthritis (PsA), another severe disease that contributes significantly to the burden of psoriatic disease in patients. The treatment of patients with both psoriasis and PsA is particularly challenging, because different strategies are often followed, and considerable resources are needed for these chronic inflammatory diseases. Of note, psoriasis patients tend to be undertreated. Efforts to improve the management of psoriasis and PsA are urgently needed, to incorporate improvement of patient outcomes by promotion of best practice from both the medical and the pharmacoeconomic perspective. These are the goals of the Quality Movement in the USA and of quality management in general. The need for evidence-based guidance on safety, efficacy, overall outcome, and cost-effectiveness is being addressed by numerous initiatives striving to generate practice guidelines, control costs, and optimize cost-effectiveness of treatments. The 2007 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis's (GRAPPA) Initiative for Quality aims to secure and improve management of psoriasis and PsA, elaborating on these evidence-based guidelines by defining major domains of quality and creating a checklist that identifies physicians who can administer state-of-the-art medical services to patients who need their services.
2008
- Italian evidence-based recommendations for the management of ankylosing spondylitis: the 3E Initiative in Rheumatology
[Articolo su rivista]
D' Angelo, S; Padula, A; Nigro, A; Cantini, F; Matucci Cerinic, M; Modena, V; Punzi, L; Salvarani, Carlo; Scarpa, R; Olivieri, I.
abstract
The 3E (Evidence, Expertise, Exchange) Initiative is a multinational effort of rheumatologists aimed at developing evidence-based recommendations addressing specific questions relevant to clinical practice. The objective of the Italian part of the 3E Initiative was to develop new recommendations designed to help Italian rheumatologists in everyday clinical practice management of patients suffering from ankylosing spondylitis (AS).
2008
- Long-term follow-up of polymyalgia rheumatica patients treated with methotrexate and steroids
[Articolo su rivista]
Cimmino, M. A; Salvarani, Carlo; Macchioni, P; Gerli, R; Bartoloni Bocci, E; Montecucco, C; Caporali, R.
abstract
A series of patients with polymyalgia rheumatica (PMR) who received the steroid-sparing combination therapy, prednisone and methotrexate (MTX), underwent a long-term follow-up study at five years to investigate possible reductions of steroid-related side effects. Additional end-points were the number of patients still in need of steroid treatment, the cumulative steroid dose, and the number of flare-ups of PMR.
2008
- Pericarditis heralding Erdheim-Chester disease
[Articolo su rivista]
Vaglio, Augusto; Corradi, Domenico; Maestri, Roberta; Callegari, Sergio; Buzio, Carlo; Salvarani, Carlo
abstract
Images in Cardiovascular Medicine: Pericarditis Heralding Erdheim-Chester Disease
2008
- Peripheral inflammatory arthritis in patients with chronic periaortitis: report of five cases and review of the literature
[Articolo su rivista]
Vaglio, A; Palmisano, A; Ferretti, S; Alberici, F; Casazza, I; Salvarani, Carlo; Buzio, C.
abstract
Chronic periaortitis (CP) is a rare disease with a potentially immune-mediated pathogenesis. The study aims to report the frequency and the clinical characteristics of peripheral inflammatory arthritis in a cohort of CP patients, and to review the literature regarding the association between arthritis and CP.
2008
- Polymyalgia rheumatica and giant-cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Cantini, Fabrizio; Hunder, Gene G.
abstract
Polymyalgia rheumatica and giant-cell arteritis are closely related disorders that affect people of middle age and older. They frequently occur together. Both are syndromes of unknown cause, but genetic and environmental factors might have a role in their pathogenesis. The symptoms of polymyalgia rheumatica seem to be related to synovitis of proximal joints and extra-articular synovial structures. Giant-cell arteritis primarily affects the aorta and its extracranial branches. The clinical findings in giant-cell arteritis are broad, but commonly include visual loss, headache, scalp tenderness, jaw claudication, cerebrovascular accidents, aortic arch syndrome, thoracic aorta aneurysm, and dissection. Glucocorticosteroids are the cornerstone of treatment of both polymyalgia rheumatica and giant-cell arteritis. Some patients have a chronic course and might need glucocorticosteroids for several years. Adverse events of glucocorticosteroids affect more than 50% of patients. Trials of steroid-sparing drugs have yielded conflicting results. A greater understanding of the molecular mechanisms involved in the pathogenesis should provide new targets for therapy.
2008
- Pre-pregnancy counselling of patients with vasculitis
[Articolo su rivista]
Doria, A; Bajocchi, G; Tonon, M; Salvarani, Carlo
abstract
The knowledge about the risk of pregnancy in vasculitides mostly derives from single case reports or at best from retrospective studies with all the caveats that these observations include. Primary systemic vasculitides are uncommon, encompassing a broad spectrum of severity, from mild to life-threatening manifestations and with different natural histories, from self-limiting to relapsing or chronic active disease. The treatments require a cautious use of immunosuppressants tailored to each specific condition. Furthermore, most of the cytotoxic drugs necessary to treat vasculitis act by modifying the cell cycle and cell differentiation, biological effects that are particularly hazardous for the foetus. In order to have an uncomplicated pregnancy, conception should be planned when the disease is inactive. Moreover, organ failure or damage, due to previous disease activity, must also be taken into account since it can lead to adverse obstetrical and fetal outcomes.
2008
- Primary CNS vasculitis with spinal cord involvement
[Articolo su rivista]
Salvarani, Carlo; Brown, R. D; Calamia, K. T; Christianson, T. J. H; Huston, J; Meschia, J. F; Giannini, C; Miller, D. V; Hunder, G. G.
abstract
Primary CNS vasculitis (PCNSV) is an uncommon disease in which lesions are limited to the brain and spinal cord. Our objective was to evaluate the frequency, clinical features, and outcome of spinal cord involvement in PCNSV.
2008
- Primary central nervous system vasculitis with prominent leptomeningeal enhancement: a subset with a benign outcome
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Calamia, Kenneth T; Christianson, Teresa J. H; Huston, John; Meschia, James F; Giannini, Caterina; Miller, Dylan V; Hunder, Gene G.
abstract
Primary central nervous system vasculitis (PCNSV) is an uncommon condition that affects the brain and spinal cord. This study was undertaken to evaluate the clinical features and outcomes among patients with PCNSV who presented with prominent gadolinium meningeal enhancement on magnetic resonance imaging (MRI).
2008
- Primary central nervous system vasculitis: comparison of patients with and without cerebral amyloid angiopathy
[Articolo su rivista]
Salvarani, Carlo; Brown, R. D; Calamia, K. T; Christianson, T. J. H; Huston, J; Meschia, J. F; Giannini, C; Miller, D. V; Hunder, G. G.
abstract
To describe the clinical features and outcomes of patients with primary central nervous system vasculitis (PCNSV) and cerebral amyloid angiopathy (CAA) from a large cohort of consecutive patients with PCNSV treated at a single institution.
2008
- Primary pathologic role of interleukin-6 in rheumatoid arthritis
[Articolo su rivista]
Bajocchi, G. L.; Pipitone, N.; Boiardi, P. L.; Salvarani, C.
abstract
BACKGROUND: Interleukin-6 (IL-6) is a polyfunctional cytokine that regulates a very large number of cellular activities. Its implication in acute-phase reactant production by hepatocytes is of particular interest, as is its involvement in chronic inflammatory diseases, mainly rheumatoid arthritis, Crohn's disease, and Castleman's disease. Transgenic mice lacking IL-6 expression were completely protected against collagen-induced arthritis, and Tumor Necrosis Factor (TNF-alpha) induces synovial cells to produce IL-6 and their proliferation. However, there is still some controversies regarding the unique proinflammatory activity of IL-6. Some studies have demonstrated that IL-6 and TNF-alpha may have an opposite effect in synovial cultured cells since IL-6 could represent a negative loop for TNF-alpha induced synovitis. However, phase III studies of rheumatoid arthritis patients treated with anti IL-6 receptor (tocilizumab) indicate an acceptable safety profile relative to the clinical benefit. AIM OF THE STUDY: In this review, we summarized the rationale and the main evidence regarding the therapeutic benefit of blocking IL-6 activity in rheumatoid arthritis. © 2008 Elsevier Srl.
2008
- Prominent perivascular enhancement in primary central nervous system vasculitis
[Articolo su rivista]
Salvarani, Carlo; Brown, R. D; Huston, J; Hunder, G. G.
abstract
Clinical images: prominent perivascular enhancement in primary central nervous system vasculitis
2008
- Reply
[Articolo su rivista]
Salvarani, C.; Brown, Jr. R. D.; Hunder, G. G.
abstract
2008
- Risk factors for severe cranial ischemic events in giant cell arteritis
[Articolo su rivista]
Salvarani, C; Della Bella, C; Restuccia, G; Pipitone, N; Ghinoi, A; Catanoso, Mg; Bajocchi, G; Macchioni, P; Cimino, L; Boiardi, L
abstract
2008
- Role of imaging in vasculitis and connective tissue diseases
[Articolo su rivista]
Pipitone, Nicolò; Salvarani, Carlo
abstract
Imaging techniques play a pivotal role in securing the diagnosis of large vessel vasculitis, and in demonstrating internal organ involvement in connective tissue diseases. In large vessel vasculitis, angiography is useful in demonstrating vessel stenoses or aneurysms. However, angiography is unable to reveal initial lesions such as vessel wall oedema and thickening, and is thus not useful to make an early diagnosis. In contrast, colour Doppler ultrasonography, computerized tomography angiography, and magnetic resonance imaging/angiography are able to delineate both the vessel wall and the lumen. Therefore, they may show vessel wall alterations when the lumen is still unaffected on angiography. 18fluorodeoxyglucose positron emission tomography does not visualize the vessel wall, but is very sensitive in revealing inflamed vessels. All of these investigations have also been used to follow up patients over time and to monitor response to treatment. In connective tissue diseases, imaging techniques are particularly useful to study internal organs, especially the brain and lung. Magnetic resonance imaging is the investigation of choice to detect and monitor brain disease, while computerized tomography is the best procedure for lung disease. However, since most imaging findings are not entirely specific for any given condition, it is important to interpret the results of imaging in the broader clinical context.
2008
- Role of imaging studies in the diagnosis and follow-up of large-vessel vasculitis: an update
[Articolo su rivista]
Pipitone, N; Versari, A; Salvarani, Carlo
abstract
Imaging studies play a central role in diagnosing and monitoring giant-cell and Takayasu arteritis. Deep, large vessels can be examined by CT or MRI, while colour Doppler ultrasound and MRI have been used with promising results to investigate the temporal arteries. Positron emission tomography is very sensitive in detecting large-vessel inflammation, although it does not delineate the vessel wall. Imaging procedures can also be used to monitor the disease course. However, imaging signs of inflammation may sometimes persist despite clinical remission and, conversely, seemingly unaffected vessels may develop alterations later on.
2008
- Serum interleukin-6 receptor in polymyalgia rheumatica: a potential marker of relapse/recurrence risk
[Articolo su rivista]
Pulsatelli, Lia; Boiardi, Luigi; Pignotti, Elettra; Dolzani, Paolo; Silvestri, Tania; Macchioni, Pierluigi; Cantini, Fabrizio; Salvarani, Carlo; Facchini, Andrea; Meliconi, Riccardo
abstract
To investigate the modulation of systemic levels of soluble interleukin-6 receptor (sIL-6R) and soluble gp130 (sgp130) in untreated and treated polymyalgia rheumatica (PMR) patients during a followup period of at least 24 months in order to evaluate the relationship of these molecules with clinical outcome and their feasibility to provide a prognostic tool in clinical practice.
2008
- The psoriatic arthritis cost evaluation study: a cost-of-illness study on tumour necrosis factor inhibitors in psoriatic arthritis patients with inadequate response to conventional therapy
[Articolo su rivista]
Olivieri, I; de Portu, S; Salvarani, Carlo; Cauli, A; Lubrano, E; Spadaro, A; Cantini, F; Cutro, M. S; Mathieu, A; Matucci Cerinic, M; Pappone, N; Punzi, L; Scarpa, R; Mantovani, L. G.
abstract
To evaluate costs, benefits and cost-effectiveness of anti-TNF agents in PsA patients with inadequate response to conventional treatment.
2008
- The role of infectious agents in the pathogenesis of vasculitis
[Articolo su rivista]
Pipitone, Nicolò; Salvarani, Carlo
abstract
Numerous human studies and animal models have implicated various infectious agents in the pathogenesis of vasculitis in susceptible hosts. However, the link between infection and vasculitis is very complex and only incompletely understood. In fact, different agents can induce the same type of vasculitis, as the case of leukocytoclastic vasculitis exemplifies. Conversely, the same agent can give rise to a panoply of host responses ranging from a clinically silent infection or localized organ involvement to devastating, widespread vasculitis.
2008
- Treatment of psoriatic arthritis and rheumatoid arthritis with disease modifying drugs -- comparison of drugs and adverse reactions
[Articolo su rivista]
Helliwell, ; Philip, S; Taylor, ; William J., Lassere M; Rappo, J; Mielants, H; Van de Berghe, M; Zmierczak, Hg; de Vlam, K; Russell, A; Gladman, D; Schentag, C; Fournie, B; Dougados, M; Dernis, E; Gossec, L; Zerkak, D; Veale, D; Fitzgerald, O; O'Rourke, M; Hajjaj Hassouni, N; Bentalha, Nl; Taylor, W; Healy, P; Marchesoni, A; Salvarani, Carlo; Macchioni, P; Emilia, R; Lubrano, E; Olivieri, I; Kalla, Aa; Potts, J; Modi, G; Patel, N; Torre Alonso, Jc; Svensson, B; Lindqvist, U; Holmstrom, G; Theander, E; Dahlqvist, Sr; Alenius, Gm; Ek, K; Isdale, A; Mcgonagle, D; Holdsworth, J; Sharlala, H; Adebajo, A; Kay, L; Mchugh, N; Lewis, J; Owen, P; Barkham, N; Bejarano, V; Henry, J; Henshaw, K; Emery, P; Helliwell, P; Ibrahim, G; Ritchlin, C; Durham, R; Espinoza, Lr; Candia, L; Mease, P; Wang, L; Gunter, L.
abstract
Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory diseases of the musculoskeletal system. Although it seems likely that these conditions have a different pathogenesis, the drugs used to treat them are the same. Our study used a cross-sectional clinical database to compare drug use and side-effect profile in these 2 diseases.
2008
- Tumor necrosis factor blocking agents in polymyalgia rheumatica and giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Hunder, Gene G.
abstract
Letter to the editor on the efficacy of Tumor Necrosis Factor–Blocking Agents in Polymyalgia Rheumatica and Giant Cell Arteritis
2008
- Vasculitides E. miscellaneous vasculitis (Behçet's Disease, Primary Angiitis of the Central Nervous System, Cogan's Syndrome, and Erythema Elevatum Diutinum)
[Capitolo/Saggio]
Calamia, K. T.; Salvarani, C.
abstract
The prevalence of Behçet's disease is highest in countries of the eastern Mediterranean, the Middle East, and East Asia. Aphthous oral ulcers are usually the first and most persistent clinical feature of Behçet's disease. Aphthous ulcers also occur frequently on the genitals (e.g., the scrotum or vulva). Uveitis-either anterior or posterior-is common in Behçet's disease and a source of major morbidity. Many forms of central nervous system disease may occur in Behçet's disease. These include aseptic meningitis and white matter lesions in the brainstem. Human leukocyte antigen (HLA)-B51 is a strong risk factor for Behçet's disease. The diagnosis of primary angiitis of the central nervous system is predicated upon either biopsy evidence of vasculitis or angiographic findings suggestive of vasculitis in the setting of other compelling features, for example, strokes demonstrated by magnetic resonance imaging or the findings of a cerebrospinal fluid pleocytosis. The diagnosis of primary angiitis of the central nervous system should never be made on the basis of an angiogram alone. Patients with benign angiopathy of the central nervous system are predominantly female, tend to present acutely with headache (with or without focal symptoms), and have normal or near normal cerebrospinal fluid. Cogan's syndrome refers to the association of inflammation in both the eyes and ears: specifically, the occurrence of nonsyphilitic interstitial keratitis and immune-mediated inner ear disease, resulting in audiovestibular dysfunction. Any type of ocular inflammation may occur in Cogan's syndrome (e.g., scleritis, uveitis, orbital pseudotumor). The inner ear disease associated with this condition often leads to deafness. In erythema elevatum diutinum, skin lesions consist of purple, red, or brown plaques and often have an annular or nodular appearance. The skin lesions have a predilection for the extensor surfaces of the distal extremities and often overlie joints, but may be generalized. © 2008 Springer Science+Business Media, LLC. © 2008 Springer-Verlag New York.
2008
- Wegener granulomatosis with spleen infarction: case report and review of the literature
[Articolo su rivista]
Ghinoi, Alessandra; Pipitone, Nicolò; Cavazza, Alberto; Boiardi, Luigi; Salvarani, Carlo
abstract
To report a case of biopsy-verified Wegener granulomatosis (WG) with positive c-antineutrophil cytoplasmic antibodies who had evidence of spleen infarction and to review the relevant literature on spleen involvement in WG.
2007
- Angiotensin II protects fibroblast-like synoviocytes from apoptosis via the AT1-NF-kappaB pathway
[Articolo su rivista]
Pattacini, L; Casali, B; Boiardi, L; Pipitone, N; Albertazzi, L; Salvarani, Carlo
abstract
To evaluate the effects of angiotensin II (Ang II) treatment on apoptosis of fibroblast-like synoviocytes (FLS) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA).
2007
- Circulating RANKL/OPG in polymyalgia rheumatica
[Articolo su rivista]
Pulsatelli, L; Dolzani, P; Silvestri, T; Boiardi, L; Salvarani, Carlo; Macchioni, P; Facchini, A; Meliconi, R.
abstract
To evaluate whether RANKL/OPG balance is modified in PMR patients, either in the active phase of the disease or during corticosteroid treatment.
2007
- Clinical assessment in psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Pipitone, N; Catanoso, M. G.
abstract
Due to the heterogeneous clinical picture, with a possible combination in any individual patient of axial disease, peripheral arthritis, enthesitis and dactylitis, psoriatic arthritis (PsA) is difficult to assess. Validated assessment tools for PsA are lacking. Recently, international study groups have a special interest in developing and validating standardized tools to assess PsA. We will review the existing assessment modalities of PsA focusing on axial disease, peripheral arthritis, enthesitis and dactylitis. Measures of function and disability recommended for PsA will be also reviewed.
2007
- Epidemiology and clinical course of Behçet's disease in the Reggio Emilia area of Northern Italy: a seventeen-year population-based study
[Articolo su rivista]
Salvarani, Carlo; Pipitone, Nicolò; Catanoso, Maria Grazia; Cimino, Luca; Tumiati, Bruno; Macchioni, Pierluigi; Bajocchi, Gianluigi; Olivieri, Ignazio; Boiardi, Luigi
abstract
To investigate the epidemiology and clinical course of Behçet's disease (BD) over a 17-year period in a defined area of northern Italy.
2007
- Established and new treatments of the idiopathic inflammatory myopathies: dermatomyositis and polymyositis
[Articolo su rivista]
Pipitone, N; Salvarani, Carlo
abstract
The aim of this article was to critically review and summarize the evidence on established and novel treatments for adult-onset DM and PM derived from randomized controlled trials (RCT). In the absence of evidence from such trials, data from open studies and case reports have been reported. Abstract data 2002 through 2006, American College of Rheumatology and 2002 through 2007 European League against Rheumatism have been included if relevant, if sufficient information could be extracted with regard to diagnosis ascertainment, treatment modalities, and outcome measures, and if the reported data had not been published as a full paper.
2007
- Giant-cell arteritis of the female genital tract associated with occult temporal arteritis and FDG-PET evidence of large-vessel vasculitis
[Articolo su rivista]
Bajocchi, G; Zamorani, G; Cavazza, A; Pipitone, N; Versari, A; Boiardi, L; Salvarani, Carlo
abstract
We describe a case of giant cell arteritis (GCA) of the female genital tract. Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and CT-scan showed evidence of large-vessel vasculitis involving the thoracic aorta and its branches, while temporal artery biopsy showed arteritis despite the absence of clinical manifestations suggestive of GCA. We review the literature and discuss the relationship between "cranial" GCA, large-vessel GCA and female genital GCA.
2007
- Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis: a randomized trial
[Articolo su rivista]
Hoffman, Gary S; Cid, Maria C; Rendt Zagar, Karen E; Merkel, Peter A; Weyand, Cornelia M; Stone, John H; Salvarani, Carlo; Xu, Weichun; Visvanathan, Sudha; Rahman, Mahboob U.
abstract
To evaluate the efficacy of infliximab, an anti-tumor necrosis factor-alpha agent, in giant cell arteritis.
DESIGN:
Randomized, controlled trial.
SETTING:
22 sites in the United States, the United Kingdom, Belgium, Italy, and Spain.
PATIENTS:
44 patients with newly diagnosed giant cell arteritis that was in glucocorticosteroid-induced remission.
INTERVENTION:
Participants were randomly assigned in a 2:1 ratio to receive infliximab (5 mg/kg of body weight) or placebo. Sixteen patients were assigned to glucocorticosteroid plus placebo, and 28 patients to glucocorticosteroid plus infliximab.
MEASUREMENTS:
End points were measured through week 22, when an interim analysis resulted in early stopping of the planned 54-week trial. Primary end points were the number of patients who remained free of relapse through week 22 and adverse events. Secondary end points were time to first relapse, biomarkers, cumulative glucocorticosteroid dose, and the number of patients who remained relapse-free while the glucocorticosteroid dosage was tapered to 10 mg/d.
RESULTS:
Infliximab therapy did not increase the proportion of patients without relapse at week 22 compared with placebo (43% vs. 50%, respectively; difference, -7 percentage points [95% CI, -38 to 23 percentage points; P = 0.65), nor did it increase the proportion of patients whose glucocorticosteroid dosages were tapered to 10 mg/d without relapse (61% vs. 75%, respectively; difference, -14 percentage points [CI, -42 to 14 percentage points]; P = 0.31). The incidence of infection was 71% with infliximab and 56% with placebo (difference, 15 percentage points [CI, -14 to 45 percentage points]).
LIMITATIONS:
The sample was too small to rule out modest effects of infliximab and included only patients with a new diagnosis. Only one dose of infliximab was evaluated, and the study was terminated early.
CONCLUSIONS:
This trial is too small to draw definitive conclusions, but it provides evidence that using infliximab as maintenance therapy in patients in glucocorticoid-induced remission of newly diagnosed giant cell arteritis is of no benefit and may be harmful. If infliximab has benefit, it is unlikely to be great.
2007
- Infliximab plus prednisone or placebo plus prednisone for the initial treatment of polymyalgia rheumatica: a randomized trial
[Articolo su rivista]
Salvarani, Carlo; Macchioni, Pierluigi; Manzini, Carlo; Paolazzi, Giuseppe; Trotta, Aldo; Manganelli, Paolo; Cimmino, Marco; Gerli, Roberto; Catanoso, Maria Grazia; Boiardi, Luigi; Cantini, Fabrizio; Klersy, Catherine; Hunder, Gene G.
abstract
To compare the efficacy of prednisone plus infliximab with that of prednisone plus placebo in patients with newly diagnosed polymyalgia rheumatica.
DESIGN:
Randomized, placebo-controlled trial.
SETTING:
7 rheumatology clinics in Italy.
PATIENTS:
51 patients with newly diagnosed polymyalgia rheumatica. Patients with associated giant cell arteritis and those who had been previously treated with steroids or biological or immunosuppressive agents were excluded.
INTERVENTION:
Initial therapy with oral prednisone tapered from 15 mg/d to 0 mg/d over 16 weeks according to a standard protocol, plus infusions of placebo or infliximab, 3 mg/kg of body weight, at weeks 0, 2, 6, 14, and 22.
MEASUREMENTS:
The primary efficacy end point was the proportion of patients without relapse or recurrence through week 52. Secondary outcomes were the proportion of patients no longer taking prednisone, the number of relapses and recurrences, the duration of prednisone therapy, and the cumulative prednisone dose.
RESULTS:
Four patients (3 in the infliximab group and 1 in the placebo group) did not complete the trial. The proportion of patients who were free of relapse and recurrence at 52 weeks did not differ between groups (6 of 20 patients [30%] in the infliximab group vs. 10 of 27 patients [37%] in the placebo group; adjusted risk difference, -3 percentage points [95% CI, -31 to 24 percentage points]; P = 0.80). In a sensitivity analysis that included dropouts, the best-case scenario yielded a difference of 5 percentage points (CI, -21 to 31 percentage points) between the groups. The secondary outcomes at weeks 22 and 52 did not differ between the groups.
LIMITATIONS:
The study had a small sample and a short follow-up. A low dosage of infliximab was used, and the prednisone dosage was rapidly tapered.
CONCLUSIONS:
Although too small to be definitive, the trial provides evidence that adding infliximab to prednisone for treating newly diagnosed polymyalgia rheumatica is of no benefit and may be harmful. If there is benefit, it is unlikely to be large.
2007
- Isolated knee monoarthritis heralding resectable non-small-cell lung cancer. A paraneoplastic syndrome not previously described
[Articolo su rivista]
Cantini, Fabrizio; Niccoli, Laura; Nannini, Carlotta; Chindamo, Daniela; Bertoni, Michele; Cassarà, Emanuele; Salvarani, Carlo
abstract
To describe isolated knee monoarthritis as a paraneoplastic syndrome heralding non-small cell lung cancer (NSCLC), and to discuss its clinical characteristics.
2007
- Lack of association of the -463 G/A myeloperoxidase promoter polymorphism with Behcet's disease in Italian patients
[Articolo su rivista]
Atzeni, F; Boiardi, L; Casali, B; Farnetti, E; Sarzi Puttini, P; Pipitone, N; Olivieri, I; Cantini, F; Salvi, F; La Corte, R; Triolo, G; Filippini, D; Paolazzi, G; Salvarani, Carlo
abstract
To investigate potential associations between the -463 G/A myeloperoxidase (MPO) promoter polymorphism and susceptibility to, and clinical expression of, Behçet's disease (BD).
2007
- Late onset undifferentiated spondyloarthritis presenting with polymyalgia rheumatica features: description of seven cases
[Articolo su rivista]
Olivieri, Ignazio; Garcia Porrua, Carlos; Padula, Angela; Cantini, Fabrizio; Salvarani, Carlo; Gonzalez Gay, Miguel A.
abstract
To underline the importance of considering a diagnosis of undifferentiated spondyloarthritis (uSpA) in patients presenting polymyalgia rheumatica (PMR) features. All patients with late onset uSpA meeting criteria for PMR at the onset of their disease seen in the Rheumatology Division of Xeral-Calde Hospital of Lugo, Spain during a 5 year period, and in the Rheumatology Department of Lucania, Italy in a two and a half year period, were studied. Six patients with late onset uSpA showing PMR symptoms at the onset were seen during the study periods in the two centres. Another patient had previously been observed in Lugo in a study dealing with the spectrum of conditions mimicking PMR. Of the seven patients, five had manifestations of SpA at the beginning of the disease and two developed these in the following 6 months. All seven met the Amor and/or the ESSG criteria for classifying and diagnosing SpA. The possibility that late onset uSpA may have PMR-like features at the beginning of the disease should be taken into account. The diagnosis is not difficult if the entire clinical spectrum of SpA is considered.
2007
- Long-term efficacy of infliximab in refractory posterior uveitis of Behcet's disease: a 24-month follow-up study
[Articolo su rivista]
Niccoli, L; Nannini, C; Benucci, M; Chindamo, D; Cassarà, E; Salvarani, Carlo; Cimino, L; Gini, G; Lenzetti, I; Cantini, F.
abstract
To evaluate the long-term efficacy and safety of infliximab in patients with Behçet's disease (BD) and refractory bilateral posterior uveitis, and to assess the proportion of relapse-free subjects through months 12 and 24.
2007
- PlA1/A2 polymorphism of the platelet glycoprotein receptor IIIA and risk of cranial ischemic complications in giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Casali, Bruno; Farnetti, Enrico; Pipitone, Nicolò; Formisano, Debora; Nicoli, Davide; Macchioni, Pierluigi; Cimino, Luca; Bajocchi, Gianluigi; Grazia Catanoso, Maria; Restuccia, Giovanna; Ghinoi, Alessandra; Boiardi, Luigi
abstract
To investigate potential associations of the PlA1/A2 polymorphism of the platelet glycoprotein IIIa (GPIIIa) gene with susceptibility to, and clinical expression of, giant cell arteritis (GCA).
2007
- Primary Sjogren's syndrome associated with chronic periaortitis
[Articolo su rivista]
Ghinoi, A; Pipitone, N; Boiardi, L; Pizzini, A; Salvarani, Carlo
abstract
We describe the first case of primary Sjögren's syndrome in a patient with an inflammatory abdominal aortic aneurysm.
2007
- Primary central nervous system vasculitis: analysis of 101 patients
[Articolo su rivista]
Salvarani, Carlo; Brown, Robert D; Calamia, Kenneth T; Christianson, Teresa J. H; Weigand, Stephen D; Miller, Dylan V; Giannini, Caterina; Meschia, James F; Huston, John; Hunder, Gene G.
abstract
To analyze the clinical findings, response to therapy, outcome, and incidence of primary central nervous system vasculitis (PCNSV) in a large cohort from a single center.
2007
- Retroperitoneal fibrosis: evolving concepts
[Articolo su rivista]
Vaglio, Augusto; Palmisano, Alessandra; Corradi, Domenico; Salvarani, Carlo; Buzio, Carlo
abstract
Retroperitoneal fibrosis (RPF) is a rare fibro-inflammatory condition that is idiopathic in most cases, but may be secondary to various causes. Although the cause and pathogenesis of the idiopathic form are unknown, immunogenetic factors and immunopathologic/autoimmune mechanisms are probably involved. Idiopathic RPF usually develops around the abdominal aorta and iliac arteries but in some cases may also involve the thoracic aorta and the origin of its major branches, with a pattern similar to that of other forms of large-vessel vasculitis. In addition, the disease is frequently associated with autoimmune conditions affecting other organs. Glucocorticoids alone or in combination with immunosuppressive agents are usually effective treatment options, but the disease frequently has a chronic relapsing course.
2007
- Sensitivity and specificity of plain radiographic features of peripheral enthesopathy at major sites in psoriatic arthritis
[Articolo su rivista]
Helliwell, P. S.; Porter, G.; Lassere, M.; Rappo, J.; Mielants, H.; Van De Berghe, M.; Zmierczak, H. G.; De Vlam, K.; Russell, A.; Gladman, D.; Schentag, C.; Fournie, B.; Dougados, M.; Dernis, E.; Gossec, L.; Zerkak, D.; Veale, D.; Fitzgerald, O.; O'Rourke, M.; Hajjaj-Hassouni, N.; Lazrak Bentalha, N.; Taylor, W.; Healy, P.; Marchesoni, A.; Salvarani, C.; Macchioni, P.; Lubrano, E.; Olivieri, I.; Ali Kalla, A.; Potts, J.; Modi, G.; Patel, N.; Torre Alonso, J. C.; Svensson, B.; Lindqvist, U.; Holmstrom, G.; Theander, E.; Dahlqvist, S. R.; Alenius, G. M.; Ek, K.; Isdale, A.; McGonagle, D.; Holdsworth, J.; Sharlala, H.; Adebajo, A.; K, L.; McHugh, N.; Lewis, J.; Owen, P.; Barkham, N.; Bejarano, V.; Henry, J.; Emery, P.; Helliwell, P.; Ibrahim, G.; Ritchlin, C.; Durham, R.; Espinoza, L. R.; Candia, L.; Mease, P.; Wang, L.; Gunter, L.; Helliwell, P.; Porter, G.
abstract
Background: It has been proposed that the defining difference between rheumatoid arthritis and spondyloarthropathy (including psoriatic arthritis) is the initial pathological lesion where the emphasis in psoriatic arthritis is on the enthesis and in rheumatoid arthritis on the synovium. Classical radiological descriptions of seronegative spondyloarthropathy include enthesopathy at major entheseal insertions characterised by erosions and exuberant new bone formation. In this study, the plain radiographic features of spondyloarthropathy are compared between psoriatic arthritis, other spondyloarthropathies and rheumatoid arthritis. Methods: The CASPAR study collected clinical, radiological and laboratory data on 588 patients with physician diagnosed psoriatic arthritis and 525 controls with other inflammatory arthritis, 70% of which had rheumatoid arthritis. Plain radiographs of the pelvis and heels were part of the study protocol, although radiographs of other potential entheseal sites such as the knee, elbow and shoulder, were interpreted if available. All radiographs were read blind by two observers working in tandem. Results: Significant differences in entheseal erosion and entheseal new bone formation were found between psoriatic arthritis, ankylosing spondylitis, undifferentiated spondyloarthropathy, rheumatoid arthritis and other diagnoses (entheseal erosion, chi-squared 20.8, p = 0.008; entheseal new bone formation, chi-squared 24.5, p = 0.001). These differences were mainly due to a higher proportion of these features in ankylosing spondylitis. No differences in the plain radiographic features of enthesopathy were found between psoriatic arthritis and rheumatoid arthritis except in the case of entheseal new bone formation at sites of attachment of inguinal ligament, sartorius and rectus femoris muscles to the ilium (OR 3.01, 95% CI 1.13-8.02). Very few subjects with symptomatic heel involvement had radiographic changes and minimal differences were found between those with and without symptoms in terms of new bone formation and erosion at either calcaneal site. Conclusions: New bone formation and erosion at major entheseal sites is most commonly seen in ankylosing spondylitis. Plain radiographic features of major enthesopathy are poor discriminators between psoriatic arthritis and rheumatoid arthritis. © 2007 ISS.
2007
- The codon 72 polymorphic variants of p53 in Italian rheumatoid arthritis patients
[Articolo su rivista]
Macchioni, P; Nicoli, D; Casali, B; Catanoso, M; Farnetti, E; Boiardi, L; Salvarani, Carlo
abstract
The p53 tumor suppressor protein plays an important role in cell apoptosis. The wild type p53 protein presents a common polymorphism at position 72 resulting in either a proline or an arginine residue at this position, leading to differences between the two variants in the induction of apoptosis. We examined the possible associations of this polymorphism with the occurrence of rheumatoid arthritis (RA) and its severity in a series of RA patients of Italian origin.
2007
- Treatment of refractory polymyalgia rheumatica with etanercept: an open pilot study
[Articolo su rivista]
Catanoso, Maria Grazia; Macchioni, Pierluigi; Boiardi, Luigi; Pipitone, Nicolò; Salvarani, Carlo
abstract
To investigate whether etanercept has a steroid-sparing effect in the treatment of patients with relapsing polymyalgia rheumatica (PMR).
2007
- XIII international vasculitis and ANCA workshop
[Articolo su rivista]
Flores-Suarez, L. F.; Gross, W. L.; Guillevin, L.; Salvarani, C.
abstract
2006
- A case of arthritis and vasculitis associated with the refractory anemia with excess of blasts syndrome resistant to glucocorticoid treatment that responded favorably to TNF-alpha blockade
[Articolo su rivista]
Pipitone, N; Masini, L; Salvarani, Carlo
abstract
To describe a case of arthritis and vasculitis associated with the refractory anemia with excess of blasts syndrome resistant to glucocorticoid treatment that responded favorably to TNF-alpha blockade.
2006
- Chronic periaortitis and HLA-DRB1*03: another clue to an autoimmune origin
[Articolo su rivista]
Martorana, Davide; Vaglio, Augusto; Greco, Paolo; Zanetti, Adele; Moroni, Gabriella; Salvarani, Carlo; Savi, Mario; Buzio, Carlo; Neri, Tauro M.
abstract
Patients with chronic periaortitis (CP) often show clinical and laboratory findings of a systemic autoimmune disorder. The aim of the present study was to investigate the role of the HLA system in CP.
2006
- Giant cell arteritis: Involvement of intracranial arteries
[Articolo su rivista]
Salvarani, Carlo; Giannini, Caterina; Miller, Dylan V; Hunder, Gene
abstract
To determine the occurrence and frequency of central nervous system (CNS) vasculitis in GCA, we reviewed the medical records of all patients with a diagnosis of CNS vasculitis or angiitis at the Mayo Clinic (Rochester, MN) over a 17-year period and identified those with both biopsy-proven GCA and pathologic and/or angiographic evidence of intracranial vasculitis.
2006
- Interleukin-10 promoter polymorphisms in giant cell arteritis
[Articolo su rivista]
Boiardi, Luigi; Casali, Bruno; Farnetti, Enrico; Pipitone, Nicolò; Nicoli, Davide; Macchioni, Pierluigi; Cimino, Luca; Bajocchi, Gianluigi; Catanoso, Maria Grazia; Pattacini, Laura; Salvarani, Carlo
abstract
To investigate potential associations between interleukin-10 (IL-10) promoter polymorphisms and susceptibility to, and clinical features of, giant cell arteritis (GCA).
2006
- Long-term outcome of giant cell arteritis
[Articolo su rivista]
Pipitone, N; Boiardi, L; Bajocchi, G; Salvarani, Carlo
abstract
Giant cell arteritis is usually a self-limiting disease with a variable duration of months to years. However, in a subset of patients the disease may follow a protracted course, requiring long-term treatment with glucocorticoids. To date, glucocorticoids are the only agents whose efficacy has been unquestionably proven. More specifically, they can both improve the clinical symptoms of giant cell arteritis and also prevent its complications, including visual loss. Glucocorticoids therapy is notoriously fraught with numerous side effects, therefore it is sensible to taper glucocorticoids as quickly as possible. Flares are not uncommon and tend often to occur upon tapering of glucocorticoids dosage or on withdrawal of glucocorticoids therapy. However, in most cases flares are mild and appear to respond favorably to an increase in glucocorticoids dosage or reintroduction of glucocorticoids therapy, respectively. Mortality rates of giant cell arteritis patients are comparable to those of the general population, but there is evidence for an increased frequency of potentially life-threatening ischemic events, such as myocardial infarction and cerebro-vascular accidents, especially early on in the disease course. The risk conferred by the disease appears to decrease with time, presumably as a consequence of glucocorticoids treatment, whereas it can remain significantly elevated in patients whose disease activity is not sufficiently controlled by the treatment. By contrast, there is no evidence that giant cell arteritis is associated with an increased prevalence of malignancies or that it may represent a paraneoplastic syndrome.
2006
- New approaches in the treatment of Adamantiades-Behçet's disease
[Articolo su rivista]
Pipitone, Nicolò; Olivieri, Ignazio; Cantini, Fabrizio; Triolo, Giovanni; Salvarani, Carlo
abstract
To update clinicians on the recent advances in the treatment of Adamantiades-Behçet's disease.
2006
- Psoriasis and psoriatic arthritis: immunological aspects and therapeutic guidelines
[Articolo su rivista]
Griffiths, C. E. M; Iaccarino, L; Naldi, L; Olivieri, I; Pipitone, N; Salvarani, Carlo; Doria, A.
abstract
Psoriasis is an inflammatory skin disease that affects 1-3% of the European population. Chronic plaque psoriasis, the commonest form of the condition - affecting the majority of patients - usually manifests as red, heavily scaled plaques on elbows, knees, scalp and lower back, but any skin surface may be affected. Psoriasis is associated with an inflammatory sero-negative arthritis, namely "psoriatic arthritis", in approximately 15%of patients with psoriasis and occurs more commonly in people with inflammatory bowel disease such as patients with Crohn's disease. Several studies have demonstrated the role of genetic predisposition, innate and adaptive immunity in the pathogenesis of psoriasis. There is considerable evidence that innate immunity and specifically a dysregulation of the innate immune response is central to the development of psoriasis. The role of TNFalpha is particularly intriguing. The evidence includes further observations that a variety of anti-TNF approaches such as monoclonal antibodies and fusion proteins of soluble TNF receptors are effective therapies both in psoriasis and psoriatic arthritis. In this review, in addition to pathogenetic aspects, some preliminary guidelines for the use of anti-TNFalpha therapy in patients with psoriasis and psoriatic arthritis will be discussed.
2006
- Recommendations of the Italian Society for Rheumatology for the use of biologic (TNF-alpha blocking) agents in the treatment of psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Olivieri, I; Pipitone, N; Cantini, F; Marchesoni, A; Punzi, L; Scarpa, R; Matucci Cerinic, M.
abstract
To propose recommendations for the use of biologic (TNF-alpha blocking) agents in the treatment of psoriatic arthritis (PsA).
2006
- Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica
[Articolo su rivista]
Boiardi, Luigi; Casali, Bruno; Farnetti, Enrico; Pipitone, Nicolò; Nicoli, Davide; Cantini, Fabrizio; Macchioni, Pierluigi; Bajocchi, Gianluigi; Catanoso, Maria Grazia; Pulsatelli, Lia; Consonni, Dario; Salvarani, Carlo
abstract
To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively.
2006
- Relationship between visual symptoms and PIA2 polymorphism of the platelet glycoprotein receptor IIIa in giant cell arteritis
[Articolo su rivista]
Boiardi, L; Casali, B; Nicoli, D; Farnetti, E; Cimino, L; Restuccia, G; Frigelli, S; Ghinoi, A; Catanoso, M; Macchioni, P; Bajocchi, G; Pipitone, N; Salvarani, C
abstract
2006
- Retroperitoneal fibrosis
[Articolo su rivista]
Vaglio, Augusto; Salvarani, Carlo; Buzio, Carlo
abstract
Retroperitoneal fibrosis encompasses a range of diseases characterised by the presence of a fibro-inflammatory tissue, which usually surrounds the abdominal aorta and the iliac arteries and extends into the retroperitoneum to envelop neighbouring structures--eg, ureters. Retroperitoneal fibrosis is generally idiopathic, but can also be secondary to the use of certain drugs, malignant diseases, infections, and surgery. Idiopathic disease was thought to result from a local inflammatory reaction to antigens in the atherosclerotic plaques of the abdominal aorta, but clinicolaboratory findings--namely, the presence of constitutional symptoms and the high concentrations of acute-phase reactants--and the frequent association of the disease with autoimmune diseases that involve other organs suggest that it might be a manifestation of a systemic autoimmune or inflammatory disease. Steroids are normally used to treat idiopathic retroperitoneal fibrosis, although other options--eg, immunosuppressants, tamoxifen--are available. The outlook is usually good, but, if not appropriately diagnosed or treated, the disease can cause severe complications, such as end-stage renal failure. Here, we review the different aspects of retroperitoneal fibrosis, focusing on idiopathic retroperitoneal fibrosis and on the differential diagnosis associated with the secondary forms.
2006
- Switching from infliximab to once-weekly administration of 50 mg etanercept in resistant or intolerant patients with ankylosing spondylitis: results of a fifty-four-week study
[Articolo su rivista]
Cantini, Fabrizio; Niccoli, Laura; Benucci, Maurizio; Chindamo, Daniela; Nannini, Carlotta; Olivieri, Ignazio; Padula, Angela; Salvarani, Carlo
abstract
We conducted a 54-week, open-label, prospective, followup study to evaluate the efficacy and tolerability of etanercept administered at 50 mg once weekly in patients with active AS who were resistant or intolerant to previous therapy with infliximab.
2006
- Synovial expression of vasoactive intestinal peptide in polymyalgia rheumatica
[Articolo su rivista]
Pulsatelli, L; Dolzani, P; Silvestri, T; De Giorgio, R; Salvarani, Carlo; Macchioni, P; Frizziero, L; Meliconi, R.
abstract
Polymyalgia rheumatica (PMR) is an inflammatory disease that typically affects elderly people. Its clinical hallmark is the severity of pain in the shoulder and pelvic girdle. Mild to moderate synovitis and/or bursitis of the joints involved has been described. Neuropeptides are involved in nociception and modulation of inflammatory reaction. To evaluate whether neuropeptides have a role in PMR pathophysiology, we studied the expression of substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and somatostatin (SOM) in shoulder synovial tissues of PMR patients.
2006
- Systemic vasculitis: state of the art and emerging concepts
[Articolo su rivista]
Pipitone, Nicolò; Salvarani, Carlo
abstract
Systemic vasculitis: state of the art and emerging concepts
2006
- Tumor necrosis factor-alpha protects synovial cells from nitric oxide induced apoptosis through phosphoinositide 3-kinase Akt signal transduction
[Articolo su rivista]
Chen, Qingquan; Casali, Bruno; Pattacini, Laura; Boiardi, Luigi; Salvarani, Carlo
abstract
To investigate the anti-apoptotic role of tumor necrosis factor-a (TNF-a) and its signaling pathways in cultured human fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis.
2005
- (18)F-fluorodeoxyglucose positron emission tomography in the diagnosis and followup of idiopathic retroperitoneal fibrosis
[Articolo su rivista]
Vaglio, Augusto; Versari, Annibale; Fraternali, Alessandro; Ferrozzi, Francesco; Salvarani, Carlo; Buzio, Carlo
abstract
We describe the case of a patient with IRF who was studied by means of 18F-FDG–PET and discuss the potential role of this technique in assessing disease activity and clinically managing IRF patients.
2005
- Acute-phase reactants and the risk of relapse/recurrence in polymyalgia rheumatica: a prospective followup study
[Articolo su rivista]
Salvarani, Carlo; Cantini, Fabrizio; Niccoli, Laura; Macchioni, Pierluigi; Consonni, Dario; Bajocchi, Gianluigi; Vinceti, Marco; Catanoso, Maria Grazia; Pulsatelli, Lia; Meliconi, Riccardo; Boiardi, Luigi
abstract
Objective. To determine laboratory parameters that may be useful in identifying polymyalgia rheumatica (PMR) patients who require long-term corticosteroid therapy. Methods. A prospective followup study of 94 consecutive untreated patients with PMR were assessed for relapse/recurrence for a mean of 39 months. This cohort represented all the patients diagnosed over a 4-year period in 2 Italian secondary referral centers. Patients were monitored for clinical signs and symptoms, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum interleukin-6 (IL-6). IL-6 levels were also measured in 43 controls matched to the patients for age and sex. Results The ESR was elevated in 91.5% of the patients prior to therapy initiation, as were CRP in 98.9% and serum IL-6 in 92.6%. Forty-seven (50.0%) patients had at least 1 relapse/recurrence during the followup period and 24 (25.5%) had at lease 2. After 4 weeks of prednisone therapy, ESR was elevated in 13.2% patients, CRP in 41.9%, and serum IL-6 in 37.2%. IL-6 levels remained persistently elevated in 9.9% and CRP in 8.7% of patients during the first year of followup, whereas no patient had persistently elevated ESR. Persistently elevated CRP and IL-6 levels were significantly associated with an increased risk of relapse/recurrence. In particular, patients with persistently elevated levels of IL-6 during the first year of therapy had the highest relative risk. Conclusion. Despite the control of clinical symptoms, corticosteroids do not adequately control the inflammatory process in a subset of patients with PMR who have persistently elevated levels of CRP and IL-6 and who have a higher risk of relapsing.
2005
- Are steroids alone sufficient for the treatment of giant cell arteritis?
[Articolo su rivista]
Pipitone, Nicolò; Boiardi, Luigi; Salvarani, Carlo
abstract
Glucocorticosteroids are the cornerstone of treatment of giant cell arteritis. An initial dose of prednisone or its equivalent of at least 40-60mg per day as single or divided dose is usually adequate. Glucocorticosteroids may prevent, but usually do not reverse, visual loss. A treatment course of 1-2 years is often required. Some patients, however, have a more chronic-relapsing course and may require low doses of glucocorticosteroids for several years. Glucocorticosteroid-related adverse events are common. In studies on immunosuppressant agents, methotrexate has been used as a glucocorticosteroid-sparing drug with conflicting results. This drug may, however, be given to patients who need high doses of glucocorticosteroids to control active disease and who have serious side effects. A recent pilot study found that infliximab was efficacious in patients with glucocorticosteroid-resistant giant cell arteritis. However, randomized controlled trials are required to define the role of anti-tumor necrosis factor-alpha agents in the treatment of giant cell arteritis. Finally, low-dose aspirin has been shown in a recent retrospective study to decrease the rate of cranial ischemic complications secondary to giant cell arteritis. It is conceivable that the definition of different patterns of inflammation in giant cell arteritis in the future might facilitate the design of differentiated therapeutic approaches.
2005
- Behçet's disease and cardiovascular involvement
[Articolo su rivista]
Atzeni, F; Sarzi Puttini, P; Doria, A; Boiardi, L; Pipitone, N; Salvarani, Carlo
abstract
Behcet's disease (BD) is a multisystem disease of unknown etiology characterized by chronic relapsing orogenital ulcers, uveitis and systemic involvement including articular, gastrointestinal, cardiopulmonary, neurological and vascular pathology. The incidence and nature of cardiac involvement are not clearly elucidated. Cardiovascular manifestations have been reported in 7-46% of patients and mortality occurs in up to 20% of those patients with marked vascular involvement. Sporadic cases of endocarditis, myocarditis, pericarditis, acute myocardial infarction, aortic aneurysm, ventricular thrombosis, congestive cardiomyopathy and valvular dysfunction have been reported. This review discusses the general aspects of the pathogenic mechanisms and clinical features cardiovascular involvement in BD, and provides the data of cardiovascular involvement in a cohort of Italian BD patients.
2005
- Editorial introductions
[Articolo su rivista]
Weyand, C. M.; Salvarani, C.; Erkan, D.; Paget, S. A.
abstract
2005
- IL-10 promoter polymorphism at position-592 in giant cell arteritis
[Articolo su rivista]
Boiardi, L; Casali, B; Nicoli, D; Farnetti, E; Pipitone, N; Macchioni, P; Cimino, L; Bajocchi, G; Catanoso, M; Frigelli, S; Salvarani, C
abstract
2005
- Inflammatory changes of hip synovial structures in polymyalgia rheumatica
[Articolo su rivista]
Cantini, F; Niccoli, L; Nannini, C; Padula, A; Olivieri, I; Boiardi, L; Salvarani, Carlo
abstract
To investigate the hip inflammatory lesions and to evaluate the accuracy of clinical examination compared to magnetic resonance imaging (MRI) in patients with polymyalgia rheumatica (PMR) with pelvic girdle symptoms. Secondary end-point was to evaluate the sensitivity and specificity of ultrasonography (US) compared to MRI in the assessment of hip lesions.
2005
- Interleukin-6 promoter polymorphism at position -174 in giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Casali, Bruno; Farnetti, Enrico; Pipitone, Nicolò; Nicoli, Davide; Macchioni, Pierluigi; Cimino, Luca; Bajocchi, Gianluigi; Catanoso, Maria Grazia; Boiardi, Luigi
abstract
To investigate potential associations between the -174 G/C interleukin-6 (IL-6) promoter polymorphism and susceptibility to and clinical features of giant cell arteritis (GCA), particularly in patients with or without polymyalgia rheumatica (PMR) and with or without ischemic complications.
2005
- Positron emission tomography (PET): evaluation of chronic periaortitis
[Articolo su rivista]
Salvarani, Carlo; Pipitone, Nicolò; Versari, Annibale; Vaglio, Augusto; Serafini, Desiderio; Bajocchi, Gianluigi; Salvo, Diana; Buzio, Carlo; Greco, Paolo; Boiardi, Luigi
abstract
To evaluate the presence and extent of large-vessel inflammation in patients with chronic periaortitis (CP) using (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET).
2005
- Post-treatment residual tissue in idiopathic retroperitoneal fibrosis: active residual disease or silent "scar" ? A study using 18F-fluorodeoxyglucose positron emission tomography
[Articolo su rivista]
Vaglio, A; Greco, P; Versari, A; Filice, A; Cobelli, R; Manenti, L; Salvarani, Carlo; Buzio, C.
abstract
Medical treatment is often effective in idiopathic retroperitoneal fibrosis (IRF) but frequently leads to residual retroperitoneal masses that may represent active disease or simply consist of inactive fibrotic tissue. 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is a functional imaging modality that reliably assesses disease activity in a number of inflammatory diseases including IRF. We used 18F-FDG PET to evaluate the metabolic activity of residual masses in a series of IRF patients.
2005
- Risk factors for visual loss in an Italian population-based cohort of patients with giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Cimino, Luca; Macchioni, Pierluigi; Consonni, Dario; Cantini, Fabrizio; Bajocchi, Gianluigi; Pipitone, Nicolò; Catanoso, Maria Grazia; Boiardi, Luigi
abstract
To evaluate the frequency of visual manifestations at presentation in an Italian population-based cohort of patients with biopsy-proven giant cell arteritis (GCA), and to investigate predictors for the development of permanent visual loss.
2005
- Systemic lupus erythematosus (SLE) in Italy: an Italian prevalence study based on a two-step strategy in an area of Florence (Scandicci-Le Signe)
[Articolo su rivista]
Benucci, Maurizio; Del Rosso, Angela; Li Gobbi, Francesca; Manfredi, Mariangela; Cerinic, Marco Matucci; Salvarani, Carlo
abstract
The goal was to ascertain the prevalence of SLE in the population over 18 years of age in the Scandicci-Le Signe area of Florence, Italy, based on the records of general practitioners (GPs).
2005
- Takayasu's arteritis: A study of 104 Italian patients
[Articolo su rivista]
Vanoli, M; Daina, E; Salvarani, Carlo; Sabbadini, M. G; Rossi, C; Bacchiani, G; Schieppati, A; Baldissera, E; Bertolini, G.
abstract
Takayasu's arteritis (TA) is a rare vasculitis. The Italian Takayasu's Arteritis study group was established with the aim to describe a large cohort of patients.
2004
- Are polymyalgia rheumatica and giant cell arteritis the same disease?
[Articolo su rivista]
Cantini, Fabrizio; Niccoli, Laura; Storri, Lara; Nannini, Carlotta; Olivieri, Ignazio; Padula, Angela; Boiardi, Luigi; Salvarani, Carlo
abstract
To summarize the evidence about the relationship between polymyalgia rheumatica (PMR) and giant cell arteritis (GCA).
2004
- Clinical manifestations of Behçet's disease in 137 Italian patients: results of a multicenter study
[Articolo su rivista]
Pipitone, N; Boiardi, L; Olivieri, I; Cantini, F; Salvi, F; Malatesta, R; La Corte, R; Triolo, G; Ferrante, A; Filippini, D; Paolazzi, G; Sarzi Puttini, P; Restuccia, G; Salvarani, Carlo
abstract
To determine the type and frequency of clinical features of Behçet's disease in a population of Italian patients.
2004
- Factor V Leiden and prothrombin gene G20210A mutations in Italian patients with Behçet's disease and deep vein thrombosis
[Articolo su rivista]
Silingardi, Mauro; Salvarani, Carlo; Boiardi, Luigi; Accardo, Pietro; Iorio, Alfonso; Olivieri, Ignazio; Cantini, Fabrizio; Salvi, Fabrizio; La Corte, Renato; Triolo, Giovanni; Ciccia, Francesco; Ghirarduzzi, Angelo; Filippini, Davide; Paolazzi, Giuseppe; Iori, Ido
abstract
To evaluate the frequency and type of vascular lesions and to study the association of factor V gene G1691A (Leiden) and prothrombin gene G20210A polymorphisms with venous thrombosis in Italian patients with Behçet's disease (BD).
2004
- Fat suppression magnetic resonance imaging in shoulders of patients with polymyalgia rheumatica
[Articolo su rivista]
Cantini, Fabrizio; Salvarani, Carlo; Niccoli, Laura; Nannini, Carlotta; Boiardi, Luigi; Padula, Angela; Olivieri, Ignazio; Valentino, Massimo; Barozzi, Libero
abstract
To evaluate the sites of inflammatory process in the shoulders of patients with polymyalgia rheumatica (PMR) using fat suppressed magnetic resonance imaging (MRI).
2004
- Geographical and genetic factors do not account for significant differences in the clinical spectrum of giant cell arteritis in southern europe
[Articolo su rivista]
Gonzalez Gay, Miguel A; Boiardi, Luigi; Garcia Porrua, Carlos; Macchioni, Pierluigi; Amor Dorado, Juan C; Salvarani, Carlo
abstract
To investigate whether genetic and geographical differences may influence the clinical spectrum of giant cell arteritis (GCA), we compared the demographic and clinical features of patients with biopsy-proven GCA from Reggio Emilia (Northern Italy) and Lugo (Northwest Spain) during a 15-year period.
2004
- Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis
[Articolo su rivista]
Calin, A; Dijkmans, B. A. C; Emery, P; Hakala, M; Kalden, J; Leirisalo Repo, M; Mola, E. M; Salvarani, Carlo; Sanmartí, R; Sany, J; Sibilia, J; Sieper, J; van der Linden, S; Veys, E; Appel, A. M; Fatenejad, S.
abstract
A double blind, randomised, placebo controlled study to evaluate the safety and efficacy of etanercept to treat adult patients with ankylosing spondylitis (AS).
2004
- Polymyalgia rheumatica
[Articolo su rivista]
Salvarani, Carlo; Cantini, Fabrizio; Boiardi, Luigi; Hunder, Gene G.
abstract
Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by aching and stiffness in the shoulder and in the pelvic girdles and neck. In the past, PMR was considered a manifestation of giant cell arteritis (GCA) or a variant of elderly-onset rheumatoid arthritis (EORA). The current diagnostic criteria for PMR were empirically formulated by clinical experts who had studied the disease extensively. Arthroscopic, radioisotopic and magnetic resonance imaging studies all have indicated the presence of a synovitis in proximal joints and periarticular structures. The synovitis is probably responsible for the musculoskeletal symptoms in PMR. The prominence assigned to the proximal symptoms has probably overshadowed the less well recognized and more variable distal musculoskeletal manifestations which are present in about half of the cases. A normal erythrocyte sedimentation rate does not exclude a diagnosis of PMR. C-reactive protein and interleukin-6 seem to be more sensitive indicators of disease activity both at diagnosis and during relapse/recurrence. Corticosteroids are the drugs of choice for treating PMR. A course of treatment of 1-2 years is often required. However, some patients have a chronic, relapsing course and require low doses of corticosteroids for several years. Large, multicenter, double-blind, placebo-controlled studies are required to define the role of methotrexate and anti-TNF-alpha agents as corticosteroid-sparing drugs in PMR.
2004
- Prednisone plus methotrexate for polymyalgia rheumatica: a randomized, double-blind, placebo-controlled trial
[Articolo su rivista]
Caporali, Roberto; Cimmino, Marco A; Ferraccioli, Gianfranco; Gerli, Roberto; Klersy, Catherine; Salvarani, Carlo; Montecucco, Carlomaurizio
abstract
Steroids are the standard treatment for polymyalgia rheumatica. The efficacy of the candidate drug methotrexate has not yet been demonstrated in controlled studies.
2004
- Pulse steroid treatment of polymyalgia rheumatica
[Articolo su rivista]
Cimmino, M. A; Macchioni, P; Boiardi, L; Cantini, F; Pulsatelli, L; Salvarani, Carlo
abstract
Pulse steroid treatment of polymyalgia rheumatica.
2004
- Reappraisal of the epidemiology of giant cell arteritis in Olmsted County, Minnesota, over a fifty-year period
[Articolo su rivista]
Salvarani, Carlo; Crowson, Cynthia S; O'Fallon, W. Michael; Hunder, Gene G; Gabriel, Sherine E.
abstract
To investigate time trends in the incidence and survival of giant cell arteritis (GCA) over a 50-year period in Olmsted County, Minnesota.
2004
- Soluble receptor activator of nuclear factor- kappaB Ligand (sRANKL)/osteoprotegerin balance in ageing and age-associated diseases
[Articolo su rivista]
Pulsatelli, Lia; Dolzani, Paolo; Silvestri, Tania; Caraceni, Paolo; Facchini, Andrea; Ravaglia, Giovanni; Salvarani, Carlo; Meliconi, Riccardo; Mariani, Erminia
abstract
Recently, novel members of the TNF/TNF receptor superfamily, receptor activator of nuclear factor- kappa B ligand (RANKL), its receptor RANK, and the decoy receptor osteoprotegerin (OPG), have been identified as paracrine mediators of both the immune system and bone functions. The balance of RANK/RANK-L and OPG is critical for osteoclastogenesis modulation and physiological bone remodeling. In order to evaluate whether RANKL/OPG balance is modified by ageing, we analyzed, by imunoassay, systemic levels of OPG and sRANKL in healthy elderly subjects (age range from 70 to over 90 years) and in patients affected by two age-related diseases, osteoarthritis (OA) and polymyalgia rheumatica (PMR), characterized by bone metabolism alteration and involvement of the immune system. We demonstrated that (a) plasma concentrations of OPG increased significantly with age; (b) conversely, sRANKL significantly declined in the group of subjects aged between 81 and 90 years, being similar to the young controls in the other age groups; (c) in OA and PMR, circulating OPG did not differ from plasma levels found in age-matched control groups, while sRANKL concentration was significantly increased compared to controls. Hence, in ageing, the sRANKL/OPG system appears to be modified, with prominent changes in circulating OPG levels; in OA and PMR, the sRANKL/OPG balance alteration was shown to be mainly due to the increase of plasma sRANKL concentration.
2004
- Thalidomide, deep venous thrombosis and vasculitis
[Articolo su rivista]
Silingardi, M; Iotti, M; Trenti, C; Salvarani, Carlo; Iori, I.
abstract
We describe a case of proximal DVT in a patient with SLE treated with thalidomide for cutaneous vasculitis.
2004
- Vascular endothelial growth factor gene polymorphisms in Behçet's disease
[Articolo su rivista]
Salvarani, Carlo; Boiardi, Luigi; Casali, Bruno; Olivieri, Ignazio; Cantini, Fabrizio; Salvi, Fabrizio; Malatesta, Renato; La Corte, Renato; Triolo, Giovanni; Ferrante, Angelo; Filippini, Davide; Paolazzi, Giuseppe; Sarzi Puttini, Piercarlo; Nicoli, Davide; Farnetti, Enrico; Chen, Qingquan; Pulsatelli, Lia
abstract
To evaluate potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with Behçet's disease (BD) and disease expression.
2004
- Visual manifestations in an Italian population-based cohort of patients with giant cell arteritis
[Articolo su rivista]
Salvarani, C; Cimino, L; Macchioni, P; Catanoso, Mg; Restuccia, G; Pipotone, N; Bajocchi, G; Cantini, F; Boiardi, L
abstract
2004
- Workshop report: clinical diagnosis and imaging of sacroiliitis, Innsbruck, Austria, October 9, 2003
[Articolo su rivista]
Klauser, Andrea; Bollow, Matthias; Calin, Andrei; Frauscher, Ferdinand; Kainberger, Franz; Moncayo, Roy; Salvarani, Carlo; Sieper, Joachim; zur Nedden, Dieter; Schirmer, Michael
abstract
Confirmation of sacroiliitis in clinical practice is based on various imaging techniques. Sacroiliitis detected by radiography, magnetic resonance imaging (MRI), or computerized tomography (CT) in the presence of clinical manifestations is diagnostic of ankylosing spondylitis (AS). The cooperation between rheumatologists, radiologists, and nuclear medicine specialists can be crucial for future developments. The techniques currently used in the diagnosis of sacroiliitis are discussed in this review and an algorithm is proposed for the use
in clinical practice.
2004
- [Recommendations for the appropriate use of anti-TNFalpha therapy in patients with psoriatic arthritis. Italian Rheumatology Society]
[Articolo su rivista]
Salvarani, Carlo; Olivieri, I; Cantini, F; Marchesoni, A; Punzi, L; Scarpa, R; Matucci Cerinic, M.
abstract
Recommendations for the appropriate use of anti-TNFα therapy in patients with psoriatic arthritis
2003
- 18F-fluorodeoxyglucose-positron emission tomography: a new explorative perspective
[Articolo su rivista]
Schirmer, M; Calamia, K. T; Wenger, M; Klauser, A; Salvarani, Carlo; Moncayo, R.
abstract
18F-Fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) is a new functional imaging technique available for clinical and experimental use. 18F-FDG-PET studies can be used for screening, localization and follow-up of hypermetabolic processes including malignancies, infections and autoimmune processes. For several years it has been applied in oncological, cardiological and neurological patients, but nowadays an increasing number of studies favours its use in patients with autoimmune diseases including large vessel arteritis. From the experimental view, this technique has even become more important since the introduction of a small PET scanner for the use in animal models. This review focuses on technical aspects, clinical experiences and experimental and future perspectives of 18F-FDG-PET, with a special emphasis on large vessel vasculitis and other autoimmune diseases.
2003
- Cutaneous vasculitis: a diagnostic approach
[Articolo su rivista]
Gonzalez Gay, M. A; Garcia Porrua, C; Salvarani, Carlo; Lo Scocco, G; Pujol, R. M.
abstract
Cutaneous vasculitis: a diagnostic approach.
2003
- Do we need 18F-FDG-positron emission tomography as a functional imaging technique for diagnosing large vessel arteritis?
[Articolo su rivista]
Wenger, M; Calamia, K. T; Salvarani, Carlo; Moncayo, R; Schirmer, M.
abstract
To discuss the role of 18F-FDG-positron emission tomography as a functional imaging technique for diagnosing large vessel arteritis
2003
- Duplex Ultrasonography in Temporal Arteritis [2] (multiple letters)
[Articolo su rivista]
Schmidt, W. A.; Gromnica-Ihle, E.; Salvarani, C.; Ghirarduzzi, A.; Boiardi, L.
abstract
2003
- Efficacy of infliximab in resistant psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Cantini, Fabrizio; Olivieri, Ignazio; Macchioni, Pierluigi; Padula, Angela; Niccoli, Laura; Catanoso, Maria Grazia; Scocco, Giovanni Lo; Boiardi, Luigi
abstract
To evaluate the efficacy and safety of the anti-tumor necrosis factor alpha monoclonal antibody infliximab in the treatment of active psoriatic arthritis (PsA) resistant to previous symptom modifying antirheumatic drugs.
2003
- Endothelial nitric oxide synthase gene polymorphisms in giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Casali, Bruno; Nicoli, Davide; Farnetti, Enrico; Macchioni, Pierluigi; Catanoso, Maria Grazia; Chen, Qingquan; Bajocchi, Gianluigi; Boiardi, Luigi
abstract
To examine potential associations of the Glu/Asp(298) polymorphism in exon 7 and the 4a/b polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene with susceptibility to and clinical expression of giant cell arteritis (GCA), particularly in patients with versus those without ischemic complications.
2003
- Giant-cell arteritis [4] (multiple letters)
[Articolo su rivista]
Vedrine, L.; Algayres, J. -P.; Coutant, G.; Salvarani, C.; Boiardi, L.; Hunder, G. G.
abstract
2003
- Laboratory investigations useful in giant cell arteritis and Takayasu's arteritis
[Articolo su rivista]
Salvarani, Carlo; Cantini, F; Boiardi, L; Hunder, G. G.
abstract
A raised erythrocyte sedimentation rate (ESR) is considered a hallmark for the diagnosis of giant cell arteritis (GCA). The American College of Rheumatology 1990 criteria for GCA include ESR greater than or equal to 50 mm/h as one of the five criteria. Although the presence of a normal ESR made GCA less likely, the results of a population-based study showed that the occurrence of a low/normal value in GCA at diagnosis is not rare. Pre-treatment ESR may be a prognostic indicator for duration of treatment. C-reactive protein (CRP) and interleukin-6 (IL-6) may be more sensitive indicators of disease activity than ESR in GCA patients. However, it is unclear whether the use in clinical practice of CRP and IL-6 has some apparent advantage over ESR. ESR is the most often used tool to assess disease activity in Takayasu's arteritis (TA). However, some studies have found that ESR and CRP are not able to differentiate patients with clinically active and inactive TA. Furthermore, histopathological studies have shown that over 40% of patients thought to be in clinical remission with normal acute phase reactants have active arteritis. IL-6 could be a promising marker of disease activity in TA; however, further studies are required to confirm its usefulness in clinical practice. Other laboratory investigations could be useful in the diagnosis or follow-up of GCA and TA, but more studies are required.
2003
- Large vessel vasculitis
[Articolo su rivista]
Salvarani, Carlo
abstract
Review on large vessels vasculitis
2003
- Persistent efficacy of tumor necrosis factor alpha blockage therapy in SAPHO syndrome: comment on the article by Wagner et al
[Articolo su rivista]
Olivieri, Ignazio; Padula, Angela; Ciancìo, Giovanni; Salvarani, Carlo; Niccoli, Laura; Cantini, Fabrizio
abstract
Comment on the article by Wagner et al. on the efficacy of tumor necrosis factor alpha blockage in SAPHO syndrome.
2003
- Pulmonary involvement in ankylosing spondylitis
[Articolo su rivista]
Olivieri, I.; Palazzi, C.; Padula, A.; Salvarani, C.; Cantini, F.; Niccoli, L.; Petricca, A.
abstract
Two kinds of respiratory alterations can be found in patients with ankylosing spondylitis. The first consists in reduction of chest expansion due to the skeletal involvement. The second one is characterized by intrinsic lung disorders. Progressive stiffening of thoracic joints does not usually induce symptomatic dyspnea because of increased compensatory diaphragmatic function. As a consequence, vital capacity and total lung capacity are moderately reduced. Intrinsic lung damages consist in a fibro-bullous apical disease, described for the first time in the 1940s and now well recognized, and interstitial lung disease, recently found in studies using high-resolution computed tomography. Pulmonary cavities may be colonized by germs, especially mycetes.
2003
- Treatment of refractory polymyalgia rheumatica with infliximab: a pilot study
[Articolo su rivista]
Salvarani, Carlo; Cantini, Fabrizio; Niccoli, Laura; Catanoso, Maria Grazia; Macchioni, Pierluigi; Pulsatelli, Lia; Padula, Angela; Olivieri, Ignazio; Boiardi, Luigi
abstract
To investigate whether infliximab has a steroid-sparing effect in the treatment of patients with polymyalgia rheumatica (PMR) who are resistant to corticosteroid (CS) therapy and have had CS-related side effects.
2003
- Vascular endothelial growth factor gene polymorphisms in giant cell arteritis
[Articolo su rivista]
Boiardi, Luigi; Casali, Bruno; Nicoli, Davide; Farnetti, Enrico; Chen, Qingquan; Macchioni, Pierluigi; Catanoso, Maria Grazia; Pulsatelli, Lia; Meliconi, Riccardo; Salvarani, Carlo
abstract
To examine potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with giant cell arteritis (GCA) and disease expression, in particular in patients with and without ischemic complications.
2003
- [Recommendations for starting anti TNF-alpha in patients with ankylosing spondylitis]
[Articolo su rivista]
Olivieri, I; Salvarani, Carlo; Cantini, F; Punzi, L; Matucci Cerinic, M.
abstract
Recommendations for starting anti TNF-alpha in patients with ankylosing spondylitis
2002
- Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6
[Articolo su rivista]
Cutolo, Maurizio; Straub, Rainer H; Foppiani, Luca; Prete, Camilla; Pulsatelli, Lia; Sulli, Alberto; Boiardi, Luigi; Macchioni, Pierluigi; Giusti, Massimo; Pizzorni, Carmen; Seriolo, Bruno; Salvarani, Carlo
abstract
To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment.
2002
- Ankylosing spondylitis: a difficult diagnosis in patients on long-term renal replacement therapy
[Articolo su rivista]
Piccoli, Giorgina B; Quaglia, Marco; Mezza, Elisabetta; Burdese, Manuel; Lacuzzo, Candida; Bechis, Francesca; Biancone, Luigi; Anania, Patrizia; Maddalena, Emanuela; Jeantet, Alberto; Segoloni, Giuseppe P; Salvarani, Carlo
abstract
We report the case of a 48-year-old male, whose musculoskeletal manifestations, previously related to long-term renal replacement therapy (RRT), were diagnosed as ankylosing spondylitis when symptoms changed their pattern on daily hemodialysis (DHD). The patient started RRT in 1981; in 1985 he received a cadaver graft, which failed in 1987. Secondary hyperparathyroidism, amyloid geoids, bilateral carpal tunnel syndrome and high aluminium levels were present. Musculoskeletal pain, reported since 1986, involved feet, heels, hips, shoulders, hands, spine. Symptoms impairing daily life did not improve after parathyroidectomy. He developed chronic hypotension and recurrent atrial fibrillation. In 1994 and 1998, because of thoracic pain, coronarography was performed (normal on both occasions). In June 2000, DHD was started. Equivalent renal clearance increased from 9-12 to 15-17 mL/min. Well-being remarkably improved. In September 2000, musculoskeletal pain worsened and bilateral Achilles tendinitis occurred. The worsening of musculoskeletal symptoms despite the improvements in well-being and other dialysis related symptoms prompted a re-evaluation of the case. The diagnosis of ankylosing spondylitis was based on: history of plantar fasciitis, bilateral Achilles tendinitis, inflammatory spinal pain with limitation of lumbar spine mobility (positive Schober test), radiological evidence of grade 2 bilateral sacroiliitis, presence of HLA-B27. This diagnosis cast light on the episodes of chest pain, explained by enthesopathy at the costosternal and manubriosternal joints and atrial fibrillation, due to HLA-B27 associated impairment in heart conduction. This case exemplifies the difficulty of differential diagnosis of multisystem illness in patients with long RRT follow-up.
2002
- Cortisol, dehydroepiandrosterone sulfate, and androstenedione levels in patients with polymyalgia rheumatica during twelve months of glucocorticoid therapy
[Articolo su rivista]
Cutolo, M; Sulli, A; Pizzorni, C; Craviotto, C; Prete, C; Foppiani, L; Salvarani, Carlo; Straub, R. H; Seriolo, B.
abstract
This paper aims to evaluate adrenal gland hormone levels in patients with polymyalgia rheumatica (PMR) during glucocorticoid (GC) therapy. A lower than expected basal production of cortisol was found in active and glucocorticoid-untreated PMR patients, particularly females. The abrupt onset of PMR with clinical features similar to those of the steroid-withdrawal syndrome or adrenal insufficiency, as well as the clinical response to GC therapy in elderly people already age-disposed to an inadequate adrenal and anti-inflammatory response, might represent the most significant pathophysiological basis of the disease.
2002
- Detection of parvovirus B19 DNA by polymerase chain reaction in giant cell arteritis: a case-control study
[Articolo su rivista]
Salvarani, Carlo; Farnetti, Enrico; Casali, Bruno; Nicoli, Davide; Wenlan, Liu; Bajocchi, Gianluigi; Macchioni, Pierluigi; Lo Scocco, Giovanni; Grazia Catanoso, Maria; Boiardi, Luigi; Cantini, Fabrizio
abstract
The aim of this study was to evaluate whether B19 DNA was more likely to be present in the temporal arteries of patients with biopsy-proven GCA or “pure” PMR than in the arteries of control subjects.
2002
- Disease-modifying antirheumatic drug therapy for psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Cantini, F; Olivieri, I.
abstract
As erosive and deforming arthritis is present in 40% of patients with psoriatic arthritis (PsA), early and aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) may be as effective in controlling the progression of the disease as it is for rheumatoid arthritis (RA). Methotrexate (MTX), sulfasalazine (SSZ), and cyclosporine (CsA) are the most widely used DMARDs in the treatment of PsA and are safe and effective in patients with active peripheral arthritis, although they do not appear to be effective on axial manifestations. No controlled study has evaluated the efficacy of these drugs on the progression of radiological damage. It has recently been demonstrated that leflunomide and anti-tumor necrosis factor (TNF) agents are effective in PsA and psoriasis. The symptomatic improvement has been important and sustained and side effects minimal. In particular, inhibitors of TNF appear to have excellent potential to treat PsA. These agents are able to slow joint damage in rheumatoid arthritis and they are effective on spinal symptoms in ankylosing spondylitis. Hopefully, these findings will prove true in PsA as well.
2002
- Endothelial nitric oxide synthase gene polymorphisms in Behçet's disease
[Articolo su rivista]
Salvarani, Carlo; Boiardi, Luigi; Casali, Bruno; Olivieri, Ignazio; Ciancio, Giovanni; Cantini, Fabrizio; Salvi, Fabrizio; Malatesta, Renato; Govoni, Marcello; Trotta, Francesco; Filippini, Davide; Paolazzi, Giuseppe; Nicoli, Davide; Farnetti, Enrico; Macchioni, Pierluigi
abstract
To analyze potential associations of Glu-Asp298 polymorphism in exon 7 and 4 a/b polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene with susceptibility for Behçet's disease (BD).
2002
- Fast spin echo-T2-weighted sequences with fat saturation in dactylitis of spondylarthritis. No evidence of entheseal involvement of the flexor digitorum tendons
[Articolo su rivista]
Olivieri, Ignazio; Salvarani, Carlo; Cantini, Fabrizio; Scarano, Enrico; Padula, Angela; Niccoli, Laura; Ciancio, Giovanni; Barozzi, Libero
abstract
To establish by means of fast spin echo (FSE)-T2-weighted sequences with fat saturation if enthesitis of the flexor digitorum superficialis and profundus tendons is the primary lesion in spondylarthritis (SpA) finger dactylitis.
2002
- Is duplex ultrasonography useful for the diagnosis of giant-cell arteritis?
[Articolo su rivista]
Salvarani, Carlo; M., Silingardi; A., Ghirarduzzi; G., Lo Scocco; P., Macchioni; G., Bajocchi; Vinceti, Marco; F., Cantini; I., Iori; L., Boiardi
abstract
Background: Evidence of a dark halo on ultrasonography has been considered a specific sign of giant-cell arteritis and may replace temporal artery biopsy for the diagnosis of giant-cell arteritis in patients with typical clinical manifestations. Objective: To assess the usefulness of temporal artery duplex Ultrasonography and to compare this mode of ultrasonography with physical examination of temporal arteries for the diagnosis of giant-cell arteritis in patients with suspected giant-cell arteritis or polymyalgia rheumatica. Design: Diagnostic test study. Setting: Several divisions of Reggio Emilia Hospital, Reggio Emilia, Italy. Patients: 86 consecutive patients with a suspected diagnosis of giant-cell arteritis or polymyalgia rheumatica identified over a 22-month period. Measurements: The temporal arteries were examined in all 86 patients. Duplex ultrasonography of the temporal arteries was then performed by two ultrasonographers who were unaware of the clinical diagnosis. Before corticosteroid therapy was started; temporal artery biopsies were performed in all patients at the site targeted by the ultrasonographer. Results: A hypoechoic halo around the lumen of the temporal arteries had a sensitivity of only 40% (95% Cl, 16% to 68%) and a specificity of 79% (Cl, 68% to 88%) for the diagnosis of biopsy-proven giant-cell arteritis. The negative likelihood ratio was 0.8 (Cl, 0.5 to 1.2), and the positive likelihood ratio was 1.9 (Cl, 0.9 to 4.1). When the thickness of the halo was at least 1 mm, specificity increased to 93% (Cl, 84% to 98%) and the positive likelihood ratio increased to 5.7 (Cl, 2.0 to 16.2); however, sensitivity remained low at 40% (Cl, 16% to 68%). On physical examination, temporal artery abnormalities had a higher sensitivity of 67% (Cl, 38% to 88%), a higher specificity of 99% (Cl, 92% to 100%), and a higher positive likelihood ratio of 47.3 (Cl, 6.5 to 342.4) than did ultrasonographic findings. None of the patients with giant-cell arteritis had a normal temporal artery inspection and a hypoechoic halo on ultrasonography. Conclusion: Evidence on ultrasonography of a halo around temporal arteries, either any halo or a halo 1 mm or greater in thickness, only modestly increased the probability of biopsy-proven giant-cell arteritis but did not improve the diagnostic accuracy of a careful physical examination.
2002
- Late onset undifferentiated spondyloarthritis
[Articolo su rivista]
Olivieri, I.; Salvarani, C.; Cantini, F.; Ciancio, G.; Padula, A.
abstract
2002
- Local injections in polymyalgia rheumatica [1] (multiple letters)
[Articolo su rivista]
Akgun, K.; Aydingoz, O.; Salvarani, C.; Cantini, F.; Olivieri, I.
abstract
2002
- Polymyalgia rheumatica and giant-cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Cantini, Fabrizio; Boiardi, Luigi; Hunder, Gene G.
abstract
Polymyalgia rheumatica is an inflammatory disorder manifested principally by stiffness of the neck, shoulder girdle, and pelvic girdle; giant-cell (or temporal) arteritis affects the cranial branches of arteries arising from the aortic arch. The two conditions are believed to be linked and may occur together. Giant-cell arteritis is a serious disorder that can cause blindness as a result of ischemia of the optic nerve or retina. Both disorders respond to corticosteroid therapy. This comprehensive article reviews the clinical manifestations, pathophysiology, and treatment of these disorders.
2002
- Renal cell carcinoma mimicking polymyalgia rheumatica. Clues for a correct diagnosis
[Articolo su rivista]
Niccoli, Laura; Salvarani, Carlo; Baroncelli, Giovanna; Padula, Angela; Olivieri, Ignazio; Cantini, Fabrizio
abstract
Proximal musculoskeletal symptoms mimicking the clinical picture of polymyalgia rheumatica may herald the onset of solid malignancies. We report on three patients presenting with polymyalgia-like symptoms, who had renal cell carcinoma. The review of the literature and our cases suggest that the absence of prolonged morning stiffness, the atypical clinical findings, the inefficacy of corticosteroids, and the absence of shoulder sonographic pathologic findings may help to facilitate the proper diagnosis.
2002
- Rheumatoid arthritis or psoriatic symmetric polyarthritis? A difficult differential diagnosis
[Articolo su rivista]
Palazzi, C; Olivieri, I; Petricca, A; Salvarani, Carlo
abstract
Focus on the differential diagnosis between rheumatoid arthritis and psoriatic symmetric polyarthritis.
2002
- Seronegative spondyloarthritides
[Articolo su rivista]
Olivieri, Ignazio; van Tubergen, Astrid; Salvarani, Carlo; van der Linden, Sjef
abstract
Epidemiological studies on the spondyloarthritides have been hindered in the past by the lack of adequate classification criteria for the whole group of these diseases. Using the Amor and the European Spondyloathropathy Study Group (ESSG) criteria the total prevalence of such diseases has been found to be higher than estimated in the past. The prevalence of ankylosing spondylitis varies across populations, but closely parallels the frequency of HLA B27-associated subtypes. The lack of well established criteria for reactive arthritis and the varying expression of its clinical manifestations are the principal reasons for the under-reporting of the true prevalence and incidence of this type of spondyloarthritis. Few data exist on the prevalence and incidence of psoriatic arthritis. A recent European study on an inception cohort of patients having inflammatory bowel disease has evaluated the prevalence of spondyloarthritis using the ESSG criteria. Of the patients studied, 18% met these criteria. Undifferentiated spondyloarthritis is one of the most frequent spondyloarthritides. It also includes a number of different subtypes.
2002
- Successful treatment of SAPHO syndrome with infliximab: report of two cases
[Articolo su rivista]
Olivieri, I; Padula, A; Ciancio, G; Salvarani, Carlo; Niccoli, L; Cantini, F.
abstract
To report two cases of successful treatment of SAPHO syndrome with infliximab
2002
- [Reactive arthritis: advances in diagnosis and treatment]
[Articolo su rivista]
Palazzi, C; Olivieri, I; Salvarani, Carlo; D'Amico, E; Alleva, G; Vitullo, P; Petricca, A.
abstract
Reactive Arthritis (ReA) is an aseptic synovitis developing after a primary infection distant from the joint, mainly localized in the gastrointestinal (Enteroarthritis) or genitourinary tract (Uroarthritis). Because of either the asymmetric joint involvement, the possibility of involvement of the spine and enthesis, and the HLA-B27 association ReA is considered one of the spondylarthropathies. Recently, bacterial components or viable bacteria were found in joints during ReA. For this reason, the limits between ReA itself and infectious arthritis are now less definite. Generally accepted diagnostic and classification criteria are still lacking but the improvement in techniques for detection of bacteria increase the possibility to identify the triggering agents. Several studies have examined the role of antimicrobial drugs in ameliorating the natural course of ReA, with some positive results for Uroarthritis only. However, more conventional treatments based on NSAIDs, sulfasalazine and steroids are effective in many cases.
2001
- A comparison of cyclosporine, sulfasalazine, and symptomatic therapy in the treatment of psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Olivieri, I; Marchesoni, A; Cutolo, M; Ferraccioli, G; Cantini, F; Salaffi, F; Padula, A; Lovino, C; Dovigo, L; Bordin, G; Davoli, C; Pasero, G; Alberighi, O. D.
abstract
To compare the efficacy and tolerability of cyclosporine (CSA) with that of symptomatic therapy (ST) alone and sulfasalazine (SSZ) in the treatment of psoriatic arthritis (PsA).
2001
- Ankylosing spondylitis and undifferentiated spondyloarthropathies: a clinical review and description of a disease subset with older age at onset
[Articolo su rivista]
Olivieri, I; Salvarani, Carlo; Cantini, F; Ciancio, G; Padula, A.
abstract
The onset of ankylosing spondylitis, as defined by the currently used criteria, after the age of 50 years is uncommon. Late-onset undifferentiated spondyloarthropathy is relatively more frequent. Its clinical spectrum seems to be as wide as it is in children and young and middle-aged adults. Most patients have two or more manifestations of spondyloarthropathy and meet the Amor criteria or the European Spondylarthropathy Study Group criteria. Some patients show only one manifestation of the B27-associated disease process for years and need more sensitive criteria. A subset of patients shows distal inflammatory swelling with pitting edema on the dorsum of feet or hands together with peripheral arthritis and peripheral enthesitis. In these cases spondyloarthropathy must be differentiated from other inflammatory rheumatic diseases with elderly onset showing the same distal inflammatory swelling with pitting edema.
2001
- Association of MICA alleles and HLA-B51 in Italian patients with Behçet's disease
[Articolo su rivista]
Salvarani, Carlo; Boiardi, L; Mantovani, V; Olivieri, I; Ciancio, G; Cantini, F; Salvi, F; Malatesta, R; Molinotti, C; Govoni, M; Trotta, F; Filippini, D; Paolazzi, G; Viggiani, M.
abstract
To evaluate the distribution of the MHC class I chain related gene A transmembrane (MICA-TM) alleles in Italian patients with Behçet's disease (BD), and to investigate the relative contribution of MICA alleles and HLA-B51 in the susceptibility and specific clinical features of BD.
2001
- Distal extremity swelling with pitting edema in psoriatic arthritis: a case-control study
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I; Macchioni, L; Niccoli, L; Padula, A; Falcone, C; Boiardi, L; Bozza, A; Barozzi, L; Pavlica, P.
abstract
To evaluate the frequency and the clinical characteristics of distal extremity swelling with pitting edema in patients with psoriatic arthritis (PsA).
2001
- Erythema nodosum: a clinical approach
[Articolo su rivista]
González Gay, M. A; García Porrúa, C; Pujol, R. M; Salvarani, Carlo
abstract
Clinical approach to erythema nodosum.
2001
- Giant cell arteritis with low erythrocyte sedimentation rate: frequency of occurence in a population-based study
[Articolo su rivista]
Salvarani, Carlo; Hunder, G. G.
abstract
To determine the frequency of a low erythrocyte sedimentation rate (ESR) in patients with giant cell arteritis (GCA) and evaluate their clinical features in a defined population.
2001
- Inflamed shoulder structures in polymyalgia rheumatica with normal erythrocyte sedimentation rate
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I; Niccoli, L; Macchioni, P; Boiardi, L; Mastrorosato, M; Ciancio, G; Padula, A; Bozza, A; Rubini, F.
abstract
To investigate the inflammatory involvement of shoulder articular and extraarticular structures in polymyalgia rheumatica (PMR) patients with a normal erythrocyte sedimentation rate (ESR) at diagnosis.
2001
- Intercellular adhesion molecule-1 gene polymorphisms in Behçet's Disease
[Articolo su rivista]
Boiardi, L; Salvarani, Carlo; Casali, B; Olivieri, I; Ciancio, G; Cantini, F; Salvi, F; Malatesta, R; Govoni, M; Trotta, F; Filippini, D; Paolazzi, G; Nicoli, D; Farnetti, E; Macchioni, L.
abstract
Intercellular adhesion molecule 1 (ICAM-1) is strongly expressed in vascular endothelial cells and perivascular inflammatory infiltrates in immunopathologic studies of Behçet's disease (BD) lesions. ICAM-1 genes may contribute to the inflammatory events responsible for the vessel damage in BD. We examined potential associations of ICAM-1 gene polymorphisms with BD susceptibility.
2001
- Magnetic resonance imaging and polymyalgia rheumatica
[Articolo su rivista]
Maria Nuova, A. S.; Emilia, R.; Ospedale di Prato, P.; Ospedale, S. C.; Salvarani, C.; Cantini, F.; Olivieri, I.; Hunder, G. G.; McGonagle, D.; Pease, C.; Marzo-Ortega, H.; O'Connor, P.; Emery, P.
abstract
2001
- Muscoloskeletal manifestations in inflammatory bowel disease
[Articolo su rivista]
Fornaciari, G; Salvarani, Carlo; Beltrami, M; Macchioni, P; Stockbrügger, R. W; Russel, M. G.
abstract
Muscoloskeletal manifestations are the most common extraintestinal complications of inflammatory bowel disease. Wide ranges in prevalence have been reported, depending on the criteria used to define spondylarthropathy. In 1991, the European Spondylarthropathy Study Group developed classification criteria that included previously neglected cases of undifferentiated spondylarthropathies, which had been ignored in most of the oldest epidemiological studies on inflammatory bowel disease. The spectrum of muscoloskeletal manifestations in inflammatory bowel disease patients includes all of the clinical features of spondylarthropathies: peripheral arthritis, inflammatory spinal pain, dactylitis, enthesitis (Achilles tendinitis and plantar fasciitis), buttock pain and anterior chest wall pain. Radiological evidence of sacroiliitis is common but not obligatory. The articular manifestations begin either concomitantly or subsequent to the bowel disease; however, the onset of spinal disease often precedes the diagnosis of inflammatory bowel disease. The prevalence of the different muscoloskeletal manifestations is similar in ulcerative colitis and Crohn's disease. Symptoms usually disappear after proctocolectomy. The pathogenetic mechanisms that produce the muscoloskeletal manifestations in inflammatory bowel disease are unclear. Several arguments favour an important role of the intestinal mucosa in the development of spondylarthropathy. The natural history is characterized by periods of flares and remission; therefore, the efficacy of treatment is difficult to establish. Most patients respond to rest, physical therapy and nonsteroidal anti-inflammatory drugs, but these drugs may activate bowel disease. Sulphasalazine may be recommended in some patients. There is no indication for the systemic use of steroids.
2001
- Musculoskeletal manifestations in a population-based cohort of inflammatory bowel disease patients
[Articolo su rivista]
Salvarani, Carlo; Vlachonikolis, I. G; van der Heijde, D. M; Fornaciari, G; Macchioni, P; Beltrami, M; Olivieri, I; Di Gennaro, F; Politi, P; Stockbrügger, R. W; Russel, M. G.
abstract
Musculoskeletal disorders are the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). Wide ranges of prevalence have been reported depending on the criteria used to define spondylarthropathy and on the selection of patients. We aimed to evaluate the prevalence and clinical spectrum of musculoskeletal manifestations in an inception cohort of European IBD patients.
2001
- Retrocalcaneal bursitis in polymyalgia rheumatica
[Articolo su rivista]
Olivieri, I; Padula, A; Salvarani, Carlo; Cantini, F; Barozzi, L.
abstract
We recently observed the case of a patient with PMR showing retrocalcaneal bursitis, which we describe briefly here.
2001
- Shoulder ultrasonography in the diagnosis of polymyalgia rheumatica: a case-control study
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I; Niccoli, L; Padula, A; Macchioni, L; Boiardi, L; Ciancio, G; Mastrorosato, M; Rubini, F; Bozza, A; Zanfranceschi, G.
abstract
Magnetic resonance imaging (MRI) showed that subacromial/subdeltoid bursitis is the most frequent shoulder lesion in polymyalgia rheumatica (PMR). We evaluated whether shoulder ultrasonography (US) was as effective as MRI in the detection of this lesion and assessed the sensitivity and specificity of bilateral subacromial/subdeltoid bursitis in the diagnosis of PMR.
2001
- Treatment of longstanding active giant cell arteritis with infliximab: report of four cases
[Articolo su rivista]
Cantini, F; Niccoli, L; Salvarani, Carlo; Padula, A; Olivieri, I.
abstract
To report four cases of longstanding active giant cell arteritis successfully treated with infliximab
2001
- [Left atrial thrombosis in patients with antiphospholipid antibody syndrome and mesenchymal abnormal septum]
[Articolo su rivista]
Ghirarduzzi, A; Galimberti, D; Silingardi, M; Cerioli, G. C; Parravicini, R; Salvarani, Carlo; Iori, I.
abstract
Antiphospholipid antibodies are a heterogeneous family of immunoglobulins that includes lupus anticoagulant and anticardiolipin antibodies. They are strongly associated with a clinical syndrome characterized by venous and arterial thrombosis and spontaneous fetal losses. This syndrome may be primary or else secondary to autoimmune or neoplastic diseases. The cardiovascular system is frequently involved with mitral or aortic insufficiency, juvenile myocardial infarction, and primitive pulmonary hypertension. However, the occurrence of intracardiac thrombi is rare. We describe a case of an intracardiac right atrial thrombus in a 19-year-old asymptomatic woman who was admitted in December 1998 to the Thrombosis Center owing to the finding, during routine work-up, of a prolonged activated partial thromboplastin time (71 s) and thrombocytopenia (71 x 1000/mm3), a positive antinuclear antibody test (1/320), positivity for lupus anticoagulant, and increased IgG (92 GPL-U/ml) and IgM (27 MPL-U/ml) anticardiolipin antibodies. Six months later, the patient presented with headache, edema and cyanosis of the face and jugular swelling. Transthoracic and transesophageal echocardiography revealed a right atrial mass which was clearly distinguishable from the tricuspid valve and extended to the superior vena cava. The patient was successfully submitted to surgical excision of the thrombus. Histology revealed that the mass was adherent to an abnormal septum consisting of mesenchymal tissue. Although the American Rheumatology Association criteria for the diagnosis of systemic lupus erythematosus were not fulfilled, the positivity of antinuclear antibody test is in favor of a lupus-like syndrome. The decision to opt for surgical excision of the thrombus was determined by the unclear nature of the atrial mass. It may be necessary that such patients be submitted to anticoagulant therapy for the rest of their lives or temporarily (6-12 months). This underscores the importance of the anatomical abnormality as a promoting factor. Transthoracic echocardiography (as well as transesophageal echocardiography in selected cases) must be considered as an essential component of the initial diagnostic work-up in patients presenting with antiphospholipid antibodies.
2000
- Absence of the association with CC chemokine receptor 5 polymorphism in polymyalgia rheumatica
[Articolo su rivista]
Salvarani, Carlo; Boiardi, L; Timms, J. M; Silvestri, T; Ranzi, A; Macchioni, P. L; Pulsatelli, L; di Giovine, F. S.
abstract
Elevated RANTES serum levels are present in polymyalgia rheumatica (PMR) patients with active disease. Chemokines may contribute to the inflammatory PMR process through their binding to CC chemokine receptor 5 (CCR5). The aim of this study was to examine if the 32 base pair deletion allele in CCR5 (CCR5 delta 32 allele) might be associated with PMR susceptibility and influence the disease outcome.
2000
- Corticosteroid injections in polymyalgia rheumatica: a double-blind, prospective, randomized, placebo controlled study
[Articolo su rivista]
Salvarani, Carlo; Cantini, F; Olivieri, I; Barozzi, L; Macchioni, L; Boiardi, L; Niccoli, L; Padula, A; Pulsatelli, L; Meliconi, R.
abstract
To determine the efficacy and safety of shoulder corticosteroid injections in polymyalgia rheumatica (PMR).
2000
- Cutaneous vasculitis and cancer: a clinical approach
[Articolo su rivista]
González Gay, M. A; García Porrúa, C; Salvarani, Carlo; Hunder, G. G.
abstract
Focus on clinical approach in cutaneous vasculitis and cancer.
2000
- Distal musculoskeletal manifestations in polymyalgia rheumatica
[Articolo su rivista]
Salvarani, Carlo; Cantini, F; Olivieri, I.
abstract
In polymyalgia rheumatica (PMR) the marked and distinctive symptoms of proximal aching and stiffness have tended to draw attention away from the distal musculoskeletal manifestations which also occur in this syndrome. Peripheral manifestations are present in about half of all cases of PMR and include joint synovitis, diffuse swelling of the distal extremities with or without pitting edema, tenosynovitis and carpal tunnel syndrome. Awareness of these findings will help to facilitate the proper diagnosis and institution of appropriate therapy for this disease.
2000
- Erythrocyte sedimentation rate and C-reactive protein in the evaluation of disease activity and severity in polymyalgia rheumatica: a prospective follow-up study
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I; Macchioni, L; Ranzi, A; Niccoli, L; Padula, A; Boiardi, L.
abstract
To determine the frequency and clinical features of patients with polymyalgia rheumatica (PMR) and normal erythrocyte sedimentation rate (ESR) at diagnosis or during relapse/recurrence. To evaluate the usefulness of C-reactive protein (CRP) and ESR in the assessment of PMR activity.
2000
- Extra-articular manifestations in 587 Italian patients with rheumatoid arthritis
[Articolo su rivista]
Cimmino, M. A; Salvarani, Carlo; Macchioni, P; Montecucco, C; Fossaluzza, V; Mascia, Maria Teresa; Punzi, L; Davoli, C; Filippini, D; Numo, R.
abstract
The aim of the study was to evaluate the frequency of extra-articular manifestations (EAMs) of rheumatoid arthritis (RA) in a series of patients from nine Italian rheumatology clinics. A total of 587 patients underwent direct questioning, complete physical evaluation, and review of medical records and laboratory data. The relationships between EAMs and the eosinophilic count, IgM rheumatoid factor (RF), and antinuclear antibodies (ANA) were studied. EAMs were present in 240/587 (40.9%) patients. The most common features were sicca syndrome (17.5%) and rheumatoid nodules (16.7%). EAMs were significantly more frequent in male patients (OR = 1.68), patients with ANA positivity (OR = 2.82), high anatomical class (OR = 2.3), and rheumatoid factor seropositivity (OR = 2.22). EAMs were more common in patients from southern Italy than in those from northern Italy (P < 0.001). EAMs seem to be rarer in Italy than in the Anglo-Saxon populations of northern Europe and the USA. Differences in prevalence of EAMs can exist even within the same country.
2000
- First international conference on polymyalgia rheumatica and giant cell arteritis, Prato, Italy. May 25-26, 1999
[Relazione in Atti di Convegno]
Schirmer, M; Calamia, K. T; Salvarani, Carlo
abstract
First international conference on polymyalgia rheumatica and giant cell arteritis, Prato, Italy. May 25-26, 1999.
2000
- Intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in Italian patients with rheumatoid arthritis
[Articolo su rivista]
Macchioni, P; Boiardi, L; Casali, B; Nicoli, D; Farnetti, E; Salvarani, Carlo
abstract
Rheumatoid arthritis (RA) has a wide range of clinical expressions which probably reflects different genetic backgrounds. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the inflammatory synovial activity in RA. The aim of this study was to examine the potential associations of ICAM-1 gene polymorphisms with RA and its severity.
2000
- Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: association with disease risk and severity
[Articolo su rivista]
Salvarani, Carlo; Casali, B; Boiardi, L; Ranzi, A; Macchioni, P; Nicoli, D; Farnetti, E; Brini, M; Portioli, I.
abstract
Intercellular adhesion molecule 1 (ICAM-1) is widely distributed in shoulder synovial membrane of active polymyalgia rheumatica (PMR) and strongly expressed in granulomatous inflammatory infiltrate of the temporal artery in giant cell arteritis (GCA). ICAM-1 genes may contribute to the inflammatory PMR/GCA processes. We examined potential associations of ICAM-1 gene polymorphisms with PMR/GCA susceptibility and severity.
2000
- Interleukin-1 cluster and tumor necrosis factor-alpha gene polymorphisms in polymyalgia rheumatica
[Articolo su rivista]
Boiardi, L; Salvarani, Carlo; Timms, J. M; Silvestri, T; Macchioni, P. L; di Giovine, F. S.
abstract
To investigate whether polymorphisms in the interleukin (IL)-1 locus (human chrom. 2q13) and TNF-alpha gene are associated with susceptibility to or severity of polymyalgia rheumatica (PMR).
2000
- Magnetic resonance imaging in the diagnosis of PMR
[Articolo su rivista]
Pavlica, P; Barozzi, L; Salvarani, Carlo; Cantini, F; Olivieri, I.
abstract
The cause of musculoskeletal symptoms in polymyalgia rheumatica (PMR) is not clearly defined because joint synovitis may only partially explain the diffuse discomfort. MRI imaging of the shoulders, hip and extremities of patients with PMR has been analyzed. MRI showed that subacromial and subdeltoid bursitis of the shoulders and iliopectineal bursitis and hip synovitis are the predominant and most frequently observed lesions in active PMR. The inflammation of the bursae associated with glenohumeral synovitis, bicipital tenosynovitis and hip synovitis may explain the diffuse discomfort and morning stiffness.
2000
- Musculoskeletal manifestations in inflammatory bowel disease
[Articolo su rivista]
Salvarani, Carlo; Fornaciari, G; Beltrami, M; Macchioni, Pl
abstract
Musculoskeletal manifestations are the most common extra-intestinal complication of inflammatory bowel disease (IBD). They are part of the clinical spectrum of spondylarthropathies and include different articular manifestations. In addition to axial symptoms, peripheral findings such as seronegative oligoarthritis, dactylitis, and enthesopathy commonly occur, sometimes representing the only manifestation. Wide ranges of prevalence have been reported, depending on the criteria used to define spondyloarthropathy and on the selection of patients. In an inceptional cohort of newly diagnosed IBD patients, we observed musculoskeletal manifestations in 30.7% of the patients. The clinician should, therefore, carefully evaluate any rheumatological findings in order to provide an accurate and early diagnosis, and to establish an adequate therapy. In this article, epidemiological, clinical, and diagnostic aspects are discussed. Furthermore, the contribution of intestinal bacteria and immunogenetic factors to the pathogenesis of arthritis is briefly reviewed. Finally, we summarize the available therapeutic options.
2000
- Polymyalgia manifestations in different conditions mimicking polymyalgia rheumatica
[Articolo su rivista]
González Gay, M. A; García Porrúa, C; Salvarani, Carlo; Olivieri, I; Hunder, G. G.
abstract
Polymyalgia rheumatica (PMR) is a generally benign syndrome involving the neck, shoulder, and hip girdles in the elderly. However, none of the clinical and laboratory findings are specific for this syndrome. Different diseases may present with features suggesting PMR. The consideration of other conditions which in some cases resemble PMR is very important, as their therapy and prognosis differ completely from that of PMR. Four patients presenting with typical PMR manifestations, who were finally diagnosed as having conditions very different from PMR, are described. The importance of the differential diagnosis in patients presenting with polymyalgia symptoms is underlined.
2000
- RS3PE syndrome: an overview
[Articolo su rivista]
Olivieri, I; Salvarani, Carlo; Cantini, F.
abstract
More than ten years ago McCarty et al. described the RS3PE syndrome based on their study of 23 patients. Numerous additional cases have since been reported. In addition to the isolated or "pure" type which probably forms part of the clinical spectrum of polymyalgia rheumatica, inflammatory swelling with pitting edema of the dorsum of the hands and/or feet can be observed in different inflammatory rheumatic diseases as well as in haematological and solid malignancies.
2000
- Rationale opf the cyclosporine and methotrexate combination to control aggressive rheumatoid arthritis
[Articolo su rivista]
Ferraccioli, G.; Marchesoni, A.; Ostuni, P.; Govoni, M.; Salvarani, C.; Valesini, G.; Valentini, G.; Della Casa Alberighi, O.
abstract
The therapy of rheumatoid arthritis (RA) has undergone profound changes over the last five years. What was once an approach based on clinical practice without any strong biological or pharmacological roots has now become directed towards questions of the cell populations and molecules involved in the various phases of joint and bone damage. This has led to the introduction of innovative therapeutic combinations based on a pivotal drug such as methotrexate (MTX), which is effective on activated T cells and macrophagic-monocytic cytokines, and drugs that act another targets such as cyclosporine (CsA). CsA is an immunosuppressant of the genes of interleukin 2 (Il2) and interferon g that is also capable of depressing other phlogosis-mediating genes by blocking the nuclear migratuon of NF-AT, a crucial transcription factor. The domonstrated efficacy of CsA (and MTX) on the progression of erosions make it one of the most attactive therapeutic combinations. This paper discusses the characteristics of the patients for whom the CsA + MTX combination is most suited as well as its medium-term safety profile.
2000
- The spectrum of conditions mimicking polymyalgia rheumatica in Northwestern Spain
[Articolo su rivista]
Gonzalez Gay, M. A; Garcia Porrua, C; Salvarani, Carlo; Olivieri, I; Hunder, G. G.
abstract
To examine the spectrum and the main clinical data of patients presenting with polymyalgia symptoms who have conditions other than polymyalgia rheumatica (PMR) or PMR associated with giant cell arteritis (GCA) during a 10 year period in Northwestern Spain.
2000
- Thrombosis associated with the prothrombin G-->A20210 mutation in Behçet's disease
[Articolo su rivista]
Salvarani, Carlo; Calamia, K; Silingardi, M; Ghirarduzzi, A; Olivieri, I.
abstract
We describe 2 cases of Behcet's disease (BD) and thrombosis who were heterozygous for the prothrombin G-->A20210 mutation. In one case, progressive uncontrolled thromboses led to death. Case-control studies are needed to support the hypothesis of the role of the prothrombin A20210 allele as a risk factor for venous thrombosis in some patients with BD.
2000
- Vascular endothelial growth factor production in polymyalgia rheumatica
[Articolo su rivista]
Meliconi, R; Pulsatelli, L; Dolzani, P; Boiardi, L; Macchioni, P; Salvarani, Carlo; Silvestri, T; Frizziero, L; Facchini, A.
abstract
To evaluate peripheral production and synovial expression of vascular endothelial growth factor (VEGF) in polymyalgia rheumatica (PMR).
1999
- Achilles tendinitis in spondyloarthropathy [4] (multiple letters)
[Articolo su rivista]
Mcgonagle, D.; Emery, P.; Olivieri, I.; Barozzi, L.; Pavlica, P.; Padula, A.; Salvarani, C.; Cantini, F.; Canoso, J. J.
abstract
1999
- Diagnostic approach in a patient presenting with polymyalgia
[Articolo su rivista]
Gonzalez Gay, M. A; Garcia Porrua, C; Salvarani, Carlo; Hunder, G. G.
abstract
Focus on the diagnostic approach in patients presenting with polymyalgia rheumatica.
1999
- Distal extremity swelling with pitting edema in psoriatic arthritis: evidence of 2 pathological mechanisms
[Articolo su rivista]
Salvarani, Carlo; Cantini, F; Olivieri, I; Niccoli, L; Senesi, C; Macchioni, L; Boiardi, L; Padula, A.
abstract
Distal extremity swelling with pitting edema due to altered lymphatic drainage has been reported in some patients with psoriatic arthritis (PsA). The edema usually affected the upper limbs in an asymmetric pattern and was resistant to therapy. We describe 2 additional cases. The distal swelling and pitting edema responded promptly and completely to corticosteroids in the first patient but persisted in the second. Lymphoscintigraphy and magnetic resonance imaging (MRI) revealed a predominant tenosynovitis in the hand without lymphedema in the first patient, and impaired lymphatic drainage without tenosynovial sheath involvement in the second. We conclude that 2 different mechanisms, characterized by a different response to therapy, may be associated with the same clinical picture of distal swelling with pitting edema in patients with psoriatic arthritis. Lymphoscintigraphy and MRI are useful in defining the structures involved and in predicting the prognosis.
1999
- HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy: correlation with disease severity
[Articolo su rivista]
Salvarani, Carlo; Boiardi, L; Mantovani, V; Ranzi, A; Cantini, F; Olivieri, I; Bragliani, M; Collina, E; Macchioni, P.
abstract
To examine the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) in a Mediterranean country and to explore the role of HLA-DRB1 genes in determining disease severity.
1999
- HLA-DRB1, DQA1, and DQB1 alleles associated with giant cell arteritis in northern Italy
[Articolo su rivista]
Salvarani, Carlo; Boiardi, L; Mantovani, V; Ranzi, A; Cantini, F; Olivieri, I; Viggiani, M; Bragliani, M; Macchioni, P.
abstract
To evaluate by molecular typing the possible associations of HLA-DRB1, DQA1, and DQB1 alleles with biopsy proven giant cell arteritis (GCA) in a Mediterranean country, and to examine possible relationships between these alleles and GCA clinical subsets.
1999
- Hip bursitis in active polymyalgia rheumatica: report of a case
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I; Niccoli, L; Padula, A; Bozza, A.
abstract
To report a case of hip bursitis in active polymyalgia rheumatica
1999
- Involvement of transitional lumbosacral joints in spondyloarthritis
[Articolo su rivista]
Padula, A; Barozzi, L; Ciancio, G; Cantini, F; Salvarani, Carlo; Olivieri, I.
abstract
To describe the involvement of transitional lumbosacral joints in spondyloarthritis.
1999
- Isolated tenosynovitis associated with psoriasis triggered by physical injury
[Articolo su rivista]
Padula, A; Belsito, F; Barozzi, L; Cantini, F; Salvarani, Carlo; Pavlica, P; Olivieri, I.
abstract
A 60-year-old man who had been suffering from psoriasis for 20 years developed finger dactylitis and inflammatory swelling with pitting edema over the dorsum of the hand one week after a contusive trauma to the left hand. These were not followed by any other clinical manifestations of PsA.
1999
- Musculoskeletal manifestations in a population-based cohort of patients with giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Hunder, G. G.
abstract
To define musculoskeletal manifestations occurring in a population-based cohort of patients with giant cell (temporal) arteritis (GCA).
1999
- Paraneoplastic remitting seronegative symmetrical synovitis with pitting edema
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I.
abstract
Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a syndrome that may be associated with many conditions, including malignancy. Three further cases of paraneoplastic RS3PE are described and the literature is reviewed. Paraneoplastic RS3PE is more frequently associated with solid tumors, in particular adenocarcinoma. The two clinical characteristics suggestive of paraneoplastic RS3PE are systemic sign/symptoms and the poor response to corticosteroid therapy.
1999
- Polymyalgia rheumatica: a disorder of extraarticular synovial structures?
[Articolo su rivista]
Salvarani, Carlo; Cantini, F; Olivieri, I; Hunder, G. S.
abstract
To describe the extraarticular synovial structures involvement in polymyalgia rheumatica
1999
- RS3PE: Six years later [5] (multiple letters)
[Articolo su rivista]
Guma, M.; Casado, E.; Tena, X.; Olive, A.; Cantini, F.; Salvarani, C.; Olivieri, I.
abstract
1999
- Relationship between serum RANTES levels and radiological progression in rheumatoid arthritis patients treated with methotrexate
[Articolo su rivista]
Boiardi, L; Macchioni, P; Meliconi, R; Pulsatelli, L; Facchini, A; Salvarani, Carlo
abstract
The aim of this study was to evaluate the relationship between serum chemokines and the clinical and radiological response to a one-year course of methotrexate (MTX) in patients suffering from rheumatoid arthritis (RA).
1999
- Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome: a prospective follow up and magnetic resonance imaging study
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I; Barozzi, L; Macchioni, L; Niccoli, L; Padula, A; Pavlica, P; Boiardi, L.
abstract
To determine the clinical characteristics of patients with "pure" remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome, and to investigate its relation with polymyalgia rheumatica (PMR). Magnetic resonance imaging (MRI) was used to describe the anatomical structures affected by inflammation in pure RS3PE syndrome.
1999
- Shoulder sonographic findings in polymyalgia rheumatica
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I.
abstract
To describe shoulder sonographic findings in polymyalgia rheumatica
1999
- The pathophysiology of polymyalgia rheumatica [3] (multiple letters)
[Articolo su rivista]
Docken, W. P.; Salvarani, C.; Cantini, F.; Olivieri, I.; Hunder, G. G.
abstract
1999
- Treatment of thrombophlebitis of Behçet's disease with low dose cyclosporin A
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Niccoli, L; Padula, A; Arena, A. I; Bellandi, F; Macchioni, P; Olivieri, I.
abstract
To describe the treatment of thrombophlebitis with low dose cyclosporin A in patients with Behçet's disease.
1998
- Behçet's disease with unusual cutaneous lesions
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Niccoli, L; Senesi, C; Truglia, M. C; Padula, A; Olivieri, I.
abstract
A variety of cutaneous lesions may occur in Behçet's disease (BD) both at presentation and over the course of the disease. Skin involvement of the hands and feet has been infrequently observed. We describe a patient with BD with recurrent, multiple, papulonodular cutaneous lesions affecting the palm and fingers of both hands, occurring simultaneously with aphthous stomatitis. The lesions consisted of roundish, erythematous, painful, bluish-red nodules, 0.5-1 cm in diameter, with a "pernio-like" aspect. Histologic examination revealed perivascular neutrophilic infiltrates. We suggest that cutaneous lesions with a pernio-like aspect as observed in our patient may be included in the spectrum of the cutaneous manifestations of Behçet's disease.
1998
- Classification of inflammatory arthritis
[Articolo su rivista]
Salvarani, Carlo; Olivieri, I; Cantini, F; Hunder, G. G.
abstract
Letter to the editor on classification of inflammatory arthritis
1998
- Dactylitis also involving the synovial sheaths in the palm of the hand: two more cases studied by magnetic resonance imaging
[Articolo su rivista]
Padula, A; Salvarani, Carlo; Barozzi, L; De Matteis, M; Pavlica, P; Cantini, F; Olivieri, I.
abstract
To report two cases of dactylitis involving the synovial sheaths in the palm of the hand studied by magnetic resonance imaging
1998
- Diagnosis and management of polymyalgia rheumatica/giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Macchioni, L; Olivieri, I; Cantini, F; Boiardi, L.
abstract
There are no standardised diagnostic criteria for polymyalgia rheumatica. The combination of persistent pain (at least 1 month) with marked morning stiffness in at least 2 of the neck, shoulder or pelvic girdle is characteristic of polymyalgia rheumatica. The other criteria are age >50 years, erythrocyte sedimentation rate (ESR) >40 mm/hour, rapid response to corticosteroids and an absence of other diseases capable of causing the musculoskeletal symptoms. A normal ESR does not exclude a diagnosis of polymyalgia rheumatica. Diagnostic temporal artery biopsy is recommended in all patients suspected of having giant cell arteritis. The segment of temporal artery with abnormality on physical examination should be biopsied. The drugs of choice in the treatment of polymyalgia rheumatica/giant cell arteritis are corticosteroids. An initial prednisone dosage of 40 to 60 mg/day is adequate in almost all cases of giant cell arteritis. Higher dosages and/or intravenous pulse methylprednisolone can be tried on patients with partial response or with recent visual loss. Polymyalgia rheumatica in the absence of giant cell arteritis requires an initial dose of prednisone 10 to 20 mg/day. In some cases of mild polymyalgia rheumatica, a short course of nonsteroidal anti-inflammatory drugs may be tried. Long term corticosteroid therapy in polymyalgia rheumatica and giant cell arteritis is complicated by serious adverse effects in between 48 and 65% of patients. Vertebral fractures and infections are among the most dangerous and frequent complications. Although there are limited data on the use of cytotoxic or immunosuppressive drugs, such as methotrexate, azathioprine and cyclosporin, in these indications, they might be effective either in sparing corticosteroids or in treating patients who do not respond to treatment with corticosteroids.
1998
- Distal musculoskeletal manifestations in polymyalgia rheumatica: a prospective followup study
[Articolo su rivista]
Salvarani, Carlo; Cantini, F; Macchioni, P; Olivieri, I; Niccoli, L; Padula, A; Boiardi, L.
abstract
To determine the frequency and the characteristics of distal musculoskeletal manifestations in polymyalgia rheumatica (PMR).
1998
- Elevated serum concentrations of the chemokine RANTES in patients with polymyalgia rheumatica
[Articolo su rivista]
Pulsatelli, L; Meliconi, R; Boiardi, L; Macchioni, P; Salvarani, Carlo; Facchini, A.
abstract
Evaluation of serum concentrations of chemotactic cytokines (chemokines) in patients with polymyalgia rheumatica at disease diagnosis and during a six-month period of corticosteroid treatment.
1998
- Erythrocyte sedimentation rate and C-reactive protein in the diagnosis of polymyalgia rheumatica
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I.
abstract
To determine if C-reactive protein, a direct measure of acute phase response, could be a more sensitive marker of disease activity than ESR in patients with polymyalgia rheumatica.
1998
- HLA-DRB1 alleles associated with rheumatoid arthritis in Northern Italy: correlation with disease severity
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P. L; Mantovani, W; Bragliani, M; Collina, E; Cremonesi, T; Battistel, B; Boiardi, L.
abstract
The aim of the study was to evaluate the relationship between the presence of the 'rheumatoid epitope', defined by a sequence motif in the HLA-DRB1 alleles, rheumatoid factor and disease severity in Northern Italian patients with rheumatoid arthritis (RA). Twenty-nine DR4-positive and 57 DR4-negative RA patients were studied. Each DR4-positive patient was matched with two DR4-negative controls of similar disease duration and sex. HLA-DRB1 alleles were determined in the 86 patients and 351 controls from the same geographical area. The patients were retrospectively evaluated for extra-articular features (EAF) and radiographic damage. The rheumatoid epitope was expressed in 45% of patients. No significant differences in the presence of rheumatoid factor, EAF and articular damage were observed between patients with no, one or two doses of epitope. However, the patients encoding the epitope by an HLA-DR4 allele had a higher number of eroded joints and a higher Larsen score compared to those without the epitope. No differences were present between patients expressing HLA-DRB1*01 alleles and those lacking the rheumatoid epitope. Even in the absence of expression of the rheumatoid epitope, seropositive patients had more EAF and more erosive disease compared to those who were seronegative. Even if most Northern Italian RA patients do not express the rheumatoid epitope, the radiological severity of disease is associated with HLA-DRB1*04 alleles.
1998
- More on remitting seronegative symmetrical synovitis with pitting edema as paraneoplastic syndrome
[Articolo su rivista]
Cantini, F; Olivieri, I; Salvarani, Carlo
abstract
Focus on remitting seronegative symmetrical synovitis with pitting edema as paraneoplastic syndrome
1998
- Possible association between eosinophilic fasciitis and subcutaneous heparin use
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I; Padula, A; Senesi, C; Bellandi, F; Truglia, M. C; Niccoli, L; Palchetti, R.
abstract
The association between the onset of eosinophilic fasciitis and exposure to a drug or a toxin has occasionally been reported. We describe 3 patients who developed eosinophilic fasciitis a few months after they received subcutaneous calcium heparin. In 2 patients, clinical manifestations and eosinophilia improved after interruption of the therapy. Although spontaneous occurrence of eosinophilic fasciitis cannot be excluded in our patients, the temporal relationship with the beginning of subcutaneous heparin therapy raises the possibility that the syndrome might be precipitated by the drug.
1998
- Psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Olivieri, I; Cantini, F; Macchioni, L; Boiardi, L.
abstract
Recent population-based studies have examined the incidence, prevalence, and survival rates of patients with psoriatic arthritis (PsA). Although there are still no completely satisfactory diagnostic criteria for PsA, Moll and Wright's criteria--although not a true classification/diagnostic scheme--are the most used. The sensitivity of these criteria is low (61%), as are the sensitivities of the European Spondyloarthropathy Study Group and Amor classification criteria for the whole spectrum of spondyloarthropathy. In some patients, PsA can occur only with peripheral enthesitis, particularly Achilles tendinitis or dactylitis. These patients may represent a subset of PsA that is not defined by the Moll and Wright or European. Spondyloarthropathy Study Group criteria and is, therefore, poorly recognized as such. Recent studies have analyzed the expression of adhesion molecules, cytokines, and chemokines in the synovial fluid and synovial membrane of patients with PsA. The therapeutic approach to PsA must be multidisciplinary, involving dermatologists and rheumatologists. Currently the most widely used second-line drugs are methotrexate, sulfasalazine, and cyclosporine. Used in combination, these drugs will probably become a well-established therapy for PsA.
1998
- Pulmonary involvement in ankylosing spondylitis
[Articolo su rivista]
Olivieri, I.; Palazzi, C.; Padula, A.; Salvarani, C.; Niccoli, L.; Cantini, F.; Sbragia, P.; Falaschi, F.
abstract
Respiratory problems in patients with ankylosing spondylitis may be due to the reduction of chest wall expansion and to intrinsic lung involvement. The inability to expand the chest due to the fusion of the thoracic joints does not usually result in ventilatory insufficiency by reason of increased diaphragmatic function. Vital capacity and total lung capacity are not markedly reduced and are correlated with reduction of chest expansion intrinsic lung disease consists in a fibro-bullous apical disease, described for the first time in the 1940s and now well recognized, and interstitial lung disease recently found in studies using high-resolution CT.
1998
- Retrocalcaneal bursitis in spondyloarthropathy: assessment by ultrasonography and magnetic resonance imaging
[Articolo su rivista]
Olivieri, I; Barozzi, L; Padula, A; De Matteis, M; Pierro, A; Cantini, F; Salvarani, Carlo; Pavlica, P.
abstract
To establish by magnetic resonance imaging (MRI) and ultrasonography (US) the frequency of retrocalcaneal bursa involvement in Achilles enthesitis of spondyloarthropathy (SpA) and to compare the results of the 2 examinations.
1998
- Serum chemokines in patients with psoriatic arthritis treated with cyclosporin A
[Articolo su rivista]
Macchioni, P; Boiardi, L; Meliconi, R; Pulsatelli, L; Maldini, M. C; Ruggeri, R; Facchini, A; Salvarani, Carlo
abstract
To evaluate the levels of serum chemokines in patients with psoriatic arthritis (PsA) before and during cyclosporin A (CyA) treatment.
1998
- The relationship between serum-soluble interleukin-2 receptor and radiological evolution in psoriatic arthritis patients treated with cyclosporin-A
[Articolo su rivista]
Macchioni, P; Boiardi, L; Cremonesi, T; Battistel, B; Casadei Maldini, M; Beltrandi, E; Mancini, R; Salvarani, Carlo
abstract
Aims of the study to evaluate the radiologically detected progression of joint damage in patients with psoriatic arthritis (PA) treated with cyclosporin-A (CsA) and to look for clinical and/or immunological parameters that might predict outcome. Twenty-four out-patients suffering from active PA entered a 2-year open prospective study on low-dose CsA (starting dose 3 mg/kg/day). Fifteen patients completed the study. Plain radiographs of hands and feet at study entry and at the end of follow-up were compared for the number of eroded joints. Serum-soluble IL-2 receptor (sIL-2R) levels were available in 13/15 patients before CsA therapy, after 6 months and after 2 years. The mean number of eroded joints per patient increased significantly during the study period (P = 0.017). Nine patients had less than two new eroded joints (responders) while the remaining six patients had five or more new eroded joints (non-responders). Serum sIL-2R levels were in the normal range after 6 months and 2 years of CsA treatment in all the responder patients and were above the 95th percentile of the control population in the six non-responders. We did not find any other demographical, clinical, radiological or laboratory parameter predictive of outcome in conclusion. (1) CsA seems to be able to control the 2-year progression of the radiologically measured damage in peripheral joints in 60% of PA patients. (2) A normal serum sIL-2R level after 6 months of therapy seems to have a prognostic value for a good outcome in PA patients treated with CsA.
1998
- Tuberculous spondylitis as a cause of inflammatory spinal pain: a report of 4 cases
[Articolo su rivista]
Cantini, F; Salvarani, Carlo; Olivieri, I; Niccoli, L; Padula, A; Bellandi, F; Palchetti, R.
abstract
Patients are said to have inflammatory spinal pain if they fulfill at presentation 4 of the following 5 criteria: duration of spinal discomfort for at least 3 months, spinal morning stiffness, age less than 40, insidious onset of symptoms, and no relief from pain with rest, but improvement with exercise. Inflammatory spinal pain is typical of the spondylarthropathies. Only in a minority of the cases it is found in other rheumatic disorders such as rheumatoid arthritis, fibromyalgia or infectious spondyilitis. Tuberculous spondylitis is rarely mentioned as a possible cause of inflammatory spinal pain. We describe 4 patients with tuberculous spondylitis seen over a 3-year period who met the clinical criteria for inflammatory spinal pain at presentation. We conclude that inflammatory spinal pain may be a presenting feature, albeit rare, of tuberculous spondylitis. Awareness of this finding should help facilitate the proper diagnosis and the institution of appropriate therapy.
1997
- Adverse outcomes of antiinflammatory therapy among patients with polymyalgia rheumatica
[Articolo su rivista]
Gabriel, S. E; Sunku, J; Salvarani, Carlo; O'Fallon, W. M; Hunder, G. G.
abstract
To evaluate the incidence and risks of adverse events associated with therapy (both corticosteroids [CS] and nonsteroidal antiinflammatory drugs [NSAIDs]) among a previously identified, population-based cohort of patients first diagnosed with polymyalgia rheumatica (PMR) between 1970 and 1991 who were followed up over the long term.
1997
- Diagnostic and classification criteria, clinical and functional assessment, and therapeutic advances for spondyloarthropathies
[Articolo su rivista]
Olivieri, I; Cantini, F; Salvarani, Carlo
abstract
Two sets of criteria have been proposed and widely accepted in the last few years for the classification of the whole spectrum of spondyloarthropathy, including the undifferentiated forms. These classification criteria--the Amor criteria and the European Spondyloarthropathy Study Group criteria--are not, however, particularly helpful for diagnosis because they do not include the milder and monosymptomatic forms. Outcomes research in spondyloarthritis is growing, and new instruments have been suggested. An international study group of experts is working to propose a core set of measures to be included in future clinical trials on ankylosing spondylitis. Intrasynovial corticosteroid injections in the sacroiliac joints may represent a valid alternative for patients with inflammatory low back pain that is unresponsive to nonsteroidal anti-inflammatory drugs. Sulfasalazine is an effective therapy for the psoriatic arthritis and peripheral arthritis of ankylosing spondylitis. A recent study has suggested its efficacy in reactive arthritis as well. In reactive arthritis, the use of long-term antibiotic therapy has been proposed and is under study.
1997
- Distal extremity swelling with pitting edema in polymyalgia rheumatica [6] (multiple letters)
[Articolo su rivista]
Caliani, L.; Paira, S.; Salvarani, C.; Gabriel, S.; Hunder, G.
abstract
1997
- Distal extremity swelling with pitting edema in polymyalgia rheumatica: a case studied with MRI
[Articolo su rivista]
Olivieri, I; Salvarani, Carlo; Cantini, F; Barozzi, L; Macchioni, L; Pavlica, P.
abstract
To report a case of distal extremity swelling with pitting edema in polymyalgia rheumatica studied with MRI
1997
- Is Behçet's disease part of the spondyloarthritis complex?
[Articolo su rivista]
Olivieri, I; Salvarani, Carlo; Cantini, F.
abstract
Focus on Behçet's disease as possible part of the spondyloarthritis spectrum
1997
- Isolated peripheral enthesitis and/or dactylitis: a subset of psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Cantini, F; Olivieri, I; Macchioni, P; Niccoli, L; Padula, A; Ferri, S; Portioli, I.
abstract
To identify isolated peripheral enthesitis and/or dactylitis as a subset of psoriatic arthritis (PsA) and to define the clinical characteristics of these patients.
1997
- Lack of association between chronic hepatitis C virus infection and Behçet's disease
[Articolo su rivista]
Cantini, F; Emmi, L; Niccoli, L; Padula, A; Salvarani, Carlo; Olivieri, I.
abstract
To investigate the association between chronic hepatitis C virus infection and Behçet's disease.
1997
- Neurological manifestations of vasculitis
[Articolo su rivista]
Guidetti, D.; Salvarani, C.
abstract
Primary vasculitis syndromes are diseases characterized by inflammation and necrosis of blood vessel, resulting in vessel occlusion and secondary ischemia of involved tissues. The presentation and clinical manifestations of the vasculitides are extremely variables, and an accurate diagnosis is often difficult. Because neurologic symptoms may be the presenting, the first and in some cases the only manifestations of the underlying disease process, a systematic diagnostic and therapeutic approach to the vasculitic syndromes is essential for the neurologist. Furthemore, a wide variety of clinical manifestations, particularly neurological, of connective tissue disorders may also be related to vasculitis. This review focuses on the neurological manifestations of the late primary vasculitis and of the vasculitis associated with connective tissue disorders. An early diagnosis and the begun of appropiate therapy will prevent the development or progression of central nervous system and peripheral nervous system manifestations.
1997
- Polymyalgia rheumatica
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Boiardi, L.
abstract
Polymyalgia rheumatica is a clinical syndrome of unknown aetiology characterised by aching and stiffness in the shoulder girdle, pelvic girdle, and neck that occurs in people aged over 50 years. Polymyalgia rheumatica is generally associated with giant-cell arteritis, frequently occurring in the same patient. However, the nature of the association is not known. The first description of polymyalgia rheumatica was made by Bruce in 1888, who defined typical polymyalgia rheumatica clinical findings in five patients as senile rheumatic gout. Only 60 years later Bagratuni described a group of patients with polymyalgia rheumatica articular manifestations as having “anarthritic rheumatoid disease”. Bagratuni followed the clinical course of these patients for more than 10 years, and did not observe any progression in erosive arthritis; he judged this disease to be a mild form of rheumatoid arthritis. The term polymyalgia rheumatica for this disorder was suggested by Barber in 1957. During the 1960s, polymyalgia rheumatica was generally accepted as a different disease from rheumatoid arthritis and giant-cell arteritis. However, Scandinavian clinicians deem polymyalgia rheumatica to be a manifestation of a generalised arteritis and generally use the term giant-cell arteritis to define polymyalgia rheumatica/giant-cell arteritis as a whole.
1997
- Proximal bursitis in active polymyalgia rheumatica
[Articolo su rivista]
Salvarani, Carlo; Cantini, F; Olivieri, I; Barozzi, L; Macchioni, L; Niccoli, L; Padula, A; De Matteis, M; Pavlica, P.
abstract
To determine the involvement of the synovial structures of the shoulder girdle of patients who have active symptoms of polymyalgia rheumatica.
DESIGN:
Case-control study.
SETTING:
2 secondary referral centers of rheumatology.
PATIENTS:
13 case-patients who had active symptoms of polymyalgia rheumatica seen during a 6-month period, 9 control-patients who had early symptoms of elderly-onset rheumatoid arthritis, and 10 age-matched healthy controls.
MEASUREMENTS:
Magnetic resonance imaging of the shoulder was done on the 13 case-patients, 9 control-patients, and 10 healthy controls.
RESULTS:
The frequency of subacromial and subdeltoid bursitis was significantly higher in the case-patients (who had polymyalgia rheumatica) than in the control-patients (who had elderly-onset rheumatoid arthritis). The frequencies of synovitis of the joints and tenosynovitis of the biceps did not significantly differ between the 13 case-patients and the 9 control-patients. None of the healthy controls showed evidence of fluid accumulation in the joints, bursae, or sheaths of the long head of the biceps.
CONCLUSIONS:
Inflammation of subacromial and subdeltoid bursae in association with synovitis of the glenohumeral joints and tenosynovitis of the biceps may contribute to the diffuse discomfort in the shoulder girdle observed in patients with polymyalgia rheumatica.
1997
- Remitting distal extremity swelling with pitting edema: a distinct syndrome or a clinical feature of different inflammatory rheumatic diseases?
[Articolo su rivista]
Olivieri, I; Salvarani, Carlo; Cantini, F.
abstract
Focus on Remitting distal extremity swelling with pitting edema
1997
- Remitting distal lower extremity swelling with pitting oedema in acute sarcoidosis
[Articolo su rivista]
Cantini, F; Niccoli, L; Olivieri, I; Barozzi, L; Pavlica, P; Bozza, A; Macchioni, P. L; Padula, A. A; Salvarani, Carlo
abstract
We describe five patients with acute sarcoidosis who presented as first manifestation of the disease an impressive distal lower extremity swelling with pitting oedema of the dorsum of both feet.
1997
- Synovial expression of cell adhesion molecules in polymyalgia rheumatica
[Articolo su rivista]
Meliconi, R; Pulsatelli, L; Melchiorri, C; Frizziero, L; Salvarani, Carlo; Macchioni, P; Uguccioni, M; Focherini, M. C; Facchini, A.
abstract
Polymyalgia rheumatica (PMR) is a common disorder of the elderly: the pathogenesis of the syndrome is still debated, though active synovitis of the shoulder has recently been confirmed. To investigate the pathogenesis of this synovitis we evaluated cell adhesion molecule (CAM) expression in shoulder synovial tissue from patients with PMR, correlated synovial expression with the serum levels of soluble forms, and assessed the changes associated with corticosteroid treatment. Arthroscopic synovial biopsies were obtained from 12 untreated and seven corticosteroid (CS)-treated cases. CAM expression was evaluated by MoAb staining on frozen sections and computerized image analysis. Soluble CAM were quantified by ELISA. Endothelial cells expressed intercellular adhesion molecule-1 (ICAM-1), E- and P-selectins. Infiltrating cells were ICAM-1 and beta1-integrin-positive, while L-selectin expression was limited to intravascular leucocytes. Synovial lining cells strongly expressed vascular cell adhesion molecule-1 (VCAM-1), and less intensely ICAM-1. Only the soluble form of ICAM-1 (sICAM-1) was elevated in untreated patients. CS treatment was associated with a decrease in ICAM-1, VCAM-1 and E- and P-selectin expression. sICAM-1 levels were in the normal range in treated patients. VLA-5 and 6 expression was widely distributed among cell types, and was not CS-sensitive. Active shoulder synovitis is associated with different CAM expression in PMR. ICAM-1 expression is widely distributed and correlates with elevated levels of the soluble form; it is significantly lower in CS-treated asymptomatic cases.
1997
- Therapy with cyclosporine in psoriatic arthritis
[Articolo su rivista]
Olivieri, I; Salvarani, Carlo; Cantini, F; Macchioni, L; Padula, A; Niccoli, L; Boiardi, L; Portioli, I.
abstract
To evaluate the efficacy and toxicity of cyclosporin A (CsA) in the treatment of patients with psoriatic arthritis (PsA).
1996
- CD8 lymphocyte subsets in active polymyalgia rheumatica: comparison with elderly-onset and adult rheumatoid arthritis and influence of prednisone therapy
[Articolo su rivista]
Boiardi, L; Salvarani, Carlo; Macchioni, P; Casadei Maldini, M; Mancini, R; Beltrandi, E; Portioli, I.
abstract
The aim of this study was to evaluate CD8 lymphocyte subsets in active polymyalgia rheumatica (PMR), to determine whether low percentages of CD8+ cells could be used to differentiate PMR from elderly-onset (EORA) and adult rheumatoid arthritis (RA), and to investigate the effects of prednisone on CD8 lymphocyte subsets. A significant reduction of percentages and absolute numbers of CD8bright+ cells was observed in patients with active PMR. Both CD8bright+, CD57- and CD8bright+, CD57+ subsets were significantly reduced. Reduced percentages of CD8+ cells were observed in 55% of patients with active PMR/giant cell arteritis (GCA), in 23% with EORA and in 44% with adult RA. Prednisone therapy in PMR patients, after only 1 week, increased the lymphocyte count and the absolute numbers of lymphocyte subsets significantly. However, the percentages of CD8bright+ cells remained persistently low for the 2 yr study period in 80% of the patients with low pre-treatment levels. Our results demonstrate that CD8 cell percentage is a poor epidemiological discriminator for PMR diagnosis. Notwithstanding the rise in absolute numbers of CD8 cell subsets induced by prednisone, the persistently low percentages of CD8+ cells in a group of PMR patients indicate an abnormality connected with the disease.
1996
- Distal extremity swelling with pitting edema in polymyalgia rheumatica. Report on nineteen cases
[Articolo su rivista]
Salvarani, Carlo; Gabriel, S; Hunder, G. G.
abstract
To determine the frequency and clinical characteristics of diffuse distal extremity swelling with pitting edema occurring in polymyalgia rheumatica (PMR).
1996
- Effects of desferrioxamine therapy on chronic disease anemia associated with rheumatoid arthritis
[Articolo su rivista]
Salvarani, Carlo; Baricchi, R; Lasagni, D; Boiardi, L; Piccinini, R; Brunati, C; Macchioni, P; Portioli, I.
abstract
To investigate the effects of desferrioxamine (DFO) infusion on chronic disease anemia (CDA) of rheumatoid arthritis (RA) by evaluating interleukin-6 (IL-6) and erythropoietin (EPO) production.
1996
- Erratum: The value of CD8 assessment in distinguishing polymyalgia rheumatica from early elderly onset rheumatoid arthritis (letter). (J. Rheumatol 1996;23:570-1)
[Articolo su rivista]
Salvarani, C.; Boiardi, L.; Macchioni, P.
abstract
1996
- Leukocyte infiltration in synovial tissue from the shoulder of patients with polymyalgia rheumatica. Quantitative analysis and influence of corticosteroid treatment
[Articolo su rivista]
Meliconi, R; Pulsatelli, L; Uguccioni, M; Salvarani, Carlo; Macchioni, P; Melchiorri, C; Focherini, M. C; Frizziero, L; Facchini, A.
abstract
To investigate the immunologic features of synovitis in patients with polymyalgia rheumatica (PMR) and to assess the modifications induced by corticosteroids.
1996
- Polyarteritis nodosa and HIV infection: no evidence of a direct pathogenic role of HIV
[Articolo su rivista]
Massari, M; Salvarani, Carlo; Portioli, I; Ramazzotti, E; Gabbi, E; Bonazzi, L.
abstract
A case of polyarteritis nodosa identified by the American College of Rheumatology (ACR) 1990 criteria in a 44-year-old HIV-infected man is described. The search for cytomegalovirus, HBV and B19 parvovirus infections was negative. In situ hybridization did not reveal proviral HIV-1 DNA in a skin sample. A zidovudine-associated vasculitis was excluded. Corticosteroid therapy resolved vasculitis manifestations and was well tolerated without opportunistic infections during the 10-month follow-up period. An indirect pathogenetic role of HIV as a possible cause of vascular damage cannot be excluded in our patient.
1996
- Polymyalgia rheumatica
[Articolo su rivista]
Salvarani, Carlo; Boiardi, L; Macchioni, L; Olivieri, I; Portioli, I.
abstract
To report a population-based study in which we confirmed the presence of a subset of polymyalgia patients with normal ESR.
1996
- The value of CD8 assessment in distinguishing polymyalgia rheumatica from early elderly onset rheumatoid arthritis [corrected]
[Articolo su rivista]
Salvarani, Carlo; Boiardi, L; Macchioni, P.
abstract
Correction. Erratum in J Rheumatol 1996 May;23(5):950.
1995
- Epidemiology of polymyalgia rheumatica in Olmsted County, Minnesota, 1970-1991
[Articolo su rivista]
Salvarani, Carlo; Gabriel, S. E; O'Fallon, W. M; Hunder, G. G.
abstract
To determine the incidence, prevalence, and survival of polymyalgia rheumatica (PMR) over a 22-year period in Olmsted County, Minnesota.
1995
- Immunohistochemical analysis of an additional case of focal myositis
[Articolo su rivista]
Macchioni, P; Boiardi, L; Meliconi, R; Salvarani, Carlo; Pulsatelli, L; Mancini, R; Prandi, S; Facchini, A; Portioli, I.
abstract
We present an additional case of focal myositis which, after surgical excision of the muscular mass, did not evolve to generalized polymyositis. To our knowledge immunological evaluations of this disease have never before been carried out. Immunohistochemical analysis of the muscular mass showed the presence of activated endothelial cells, CD4 and macrophage cells in the perivascular and endomysial areas, suggesting an immune-mediated mechanism of muscular damage. At the same time the normal distribution of the peripheral blood lymphocyte subpopulations and the normal levels of serum IL-1 beta, IL-6, TNF-alpha, soluble IL-2R and soluble CD8 underline the non-systemic nature of the disease.
1995
- On the utility of CD8 level assessment in the diagnosis of polymyalgia rheumatica/giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Boiardi, L; Macchioni, P. L; Portioli, I.
abstract
Focus on the utility of CD8 level assessment in the diagnosis of polymyalgia rheumatica/giant cell arteritis
1995
- Polymyalgia rheumatica and giant cell arteritis
[Articolo su rivista]
Cimmino, M. A; Salvarani, Carlo
abstract
The original descriptions of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in the medical literature date back to 1888 and 1890, respectively. Classification criteria for PMR and GCA are not standardized since most authors used subjective criteria based on their personal experience. Only one study has evaluated criteria for PMR and has found seven variables with high discriminant value. Criteria for GCA are less varied because a positive biopsy of the temporal artery is diagnostic. However, combinations of different clinical and laboratory features have been used for diagnosis when biopsy is negative or missing. Assessment of PMR/GCA is based on the serial determination of markers of acute phase such as ESR, CRP, or plasma viscosity. However, their value in predicting recurrence of the diseases is poor. New immunological factors including soluble interleukin-2 receptors, interleukin-6, serum soluble CD8, and serum soluble intercellular adhesion molecule-1 are presently under investigation.
1995
- Prevalence of psoriatic arthritis in Italian psoriatic patients
[Articolo su rivista]
Salvarani, Carlo; Lo Scocco, G; Macchioni, P; Cremonesi, T; Rossi, F; Mantovani, W; Battistel, B; Bisighini, G; Portioli, I.
abstract
To evaluate the prevalence of psoriatic arthritis (PsA) in Italian patients with psoriasis and to compare the Moll and Wright criteria, the European Spondylarthropathy Study Group (ESSG) criteria, and Amor criteria when applied to this patient population.
1995
- Role of peripheral CD8 lymphocytes and soluble IL-2 receptor in predicting the duration of corticosteroid treatment in polymyalgia rheumatica and giant cell arteritis
[Articolo su rivista]
Salvarani, Carlo; Boiardi, L; Macchioni, P; Rossi, F; Tartoni, P; Casadei Maldini, M; Mancini, R; Beltrandi, E; Portioli, I.
abstract
To determine if the presence of low percentages of CD8 positive cells or high levels of soluble interleukin-2 receptors (sIL-2R) define a subgroup of patients with more severe polymyalgia rheumatica and giant cell arteritis (PMR/GCA).
1995
- The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern
[Articolo su rivista]
Salvarani, Carlo; Gabriel, S. E; O'Fallon, W. M; Hunder, G. G.
abstract
To investigate trends in the incidence of giant cell arteritis over a 42-year period in Olmsted County, Minnesota.DESIGN:
Population-based incidence study.
SETTING:
Olmsted County, Minnesota.
METHODS:
All incidence cases of giant cell arteritis first diagnosed between 1950 and 1991 were identified using the unified record system at Mayo Clinic. Age- and sex-specific incidence rates were calculated using the number of incidence cases as the numerator and population estimates as the denominator. Overall rates were age- and sex-adjusted to the 1980 United States white population. The annual incidence rates were graphically illustrated using a 3-year centered moving average.
RESULTS:
Between 1950 and 1991, 125 Olmsted County residents (103 women and 22 men) were diagnosed with giant cell arteritis. The age- and sex-adjusted incidence per 100,000 persons 50 years of age or older was 17.8 (95% CI, 14.7 to 21.0); incidence was significantly higher in women (24.2 [CI, 19.5 to 28.9]) than in men (8.2 [CI, 4.8 to 11.6]). Age-specific incidence rates increased with age (P < 0.0001). The annual incidence rates increased significantly over the study period (P = 0.002) and appear to have clustered in five peak periods, which occurred about every 7 years. A significant calendar-time effect was identified; it predicted an increase in incidence of 2.6% (CI, 0.9% to 4.3%) every 5 years.
CONCLUSIONS:
Our observation of a regular cyclic pattern in incidence rates over time supports the hypothesis of an infectious cause for giant cell arteritis. Similar studies in other populations are needed to confirm our findings.
1995
- Upper limb lymphedema in inflammatory arthropathy
[Articolo su rivista]
Salvarani, Carlo
abstract
Upper limb lymphedema in inflammatory arthropathy
1994
- Elevated soluble intercellular adhesion molecule 1 in the serum of patients with polymyalgia rheumatica: influence of steroid treatment
[Articolo su rivista]
Macchioni, P; Boiardi, L; Meliconi, R; Salvarani, Carlo; Grazia Uguccioni, M; Rossi, F; Pulsatelli, L; Facchini, A.
abstract
To determine the levels of serum soluble intercellular adhesion molecule 1 (sICAM-1) in patients with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA) prior and during steroid therapy.
1994
- Primary systemic amyloidosis presenting as giant cell arteritis and polymyalgia rheumatica
[Articolo su rivista]
Salvarani, Carlo; Gabriel, S. E; Gertz, M. A; Bjornsson, J; Li, C. Y; Hunder, G. G.
abstract
Primary systemic amyloidosis may present with features suggesting a vasculitis, including giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). In this report, we describe the clinical characteristics, temporal artery biopsy findings, and the response of vascular and musculoskeletal symptoms to corticosteroid therapy in 4 patients with primary systemic amyloidosis who presented with manifestations of GCA or PMR.
1994
- Rheumatoid arthritis in the elderly: Frequency of side effects of parenteral and oral chrysotherapy
[Articolo su rivista]
Nurchis, P.; Salvarani, C.; Zizzi, F.; Garau, P.; Passiu, G.; Portioli, I.; Frizziero, L.; Ferraccioli, G.; Pala, R.; Mathieu, A.
abstract
The clinical history of 362 patients affected by Rheumatoid Arthritis (RA) who were followed-up for a period of 1-10 years has been analyzed to evaluate the Side Effects (SE) induced by the drug treatment. The patients studied were taking the conventional therapy with gold salts: oral gold salts (OGS: Auranofin 6 mg/day) or parenteral chrysotherapy (PGS: aurothomalate 50 mg/week). The side effects (SE) induced by the drugs considered in this study were haematological, mucocutaneous and renal ones. Patients less than 60 years old (Group 1) have been analyzed separately in comparison with older patients (Group 2). 31.5% of patients in Group 1 and 32.3% in Group 2 experienced gold-dependent SE. Subjects with multiple SE were 5.7% among younger patients and 8% in the older cohort. Treatment withdrawal was decided in 18.2% of patients of Group l and in 19.1% of those of Group 2. No significant difference was found in the frequence and distribution of SE in these two groups. The analysis of the SE frequence according to the kind of treatment (oral or parenteral) and the age of the patients did not show any significant difference for the frequence of the single SE observed (mucocutaneous, hematologic, renal), occurrence of multiple SE and treatment withdrawal.
1994
- Serum soluble CD4 and CD8 levels in polymyalgia rheumatica
[Articolo su rivista]
Salvarani, Carlo; Boiardi, L; Macchioni, P; Casadei Maldini, M; Mancini, R; Beltrandi, E; Rossi, F; Portioli, I.
abstract
Soluble CD4 (sCD4) and sCD8 were measured in the sera of 19 patients with active polymyalgia rheumatica (PMR). METHODS:
We correlated the results obtained with lymphocyte subpopulations, soluble interleukin 2 receptors (sIL-2R), and clinical and laboratory variables at diagnosis. In addition 15 patients were prospectively studied during a 6 month period of prednisone therapy. Assays of the sCD4 and sCD8 molecules and of the sIL-2R were performed using an enzyme-linked immunosorbent kit.
RESULTS:
Serum sCD8 and sIL-2R levels were significantly elevated in patients with active disease compared to normal controls, while serum sCD4 and the relative percentage of CD8+ T cell levels decreased. In the 15 patients prospectively studied sCD8 levels fell significantly after 1 week of therapy along with the remission of clinical disease and normalization of erythrocyte sedimentation rate. At the end of the study period, sCD8 values did not differ from normal controls and they were significantly reduced compared to baseline values. CD8+ lymphopenia persisted at the end of the study. sCD4 levels remained significantly lower during the study period. sIL-2R levels fell significantly at the end of the study period. However, the 6-month levels of sIL-2R remained significantly higher compared to controls.
CONCLUSION:
The rise of serum sCD8 levels observed in patients with PMR with active disease suggests an early activation of CD8 T cells. The therapeutic effect of steroid in PMR may be partially mediated by its effect on CD8 activated cells.
1994
- Serum soluble interleukin-2 receptor levels in rheumatoid arthritis: correlation with clinical and immunological parameters and with the response to auranofin treatment
[Articolo su rivista]
Boiardi, L; Macchioni, P; Salvarani, Carlo; Rossi, F; Casadei Maldini, M; Mancini, R; Beltrandi, E; Portioli, I.
abstract
38 untreated patients suffering from rheumatoid arthritis (RA) were studied to evaluate the relationship between serum sIL-2R levels and laboratory and clinical indexes of disease activity and circulating lymphocyte subpopulations. Furthermore, we serially analyzed the correlation between the clinical response to oral gold (Auranofin) treatment and serum sIL-2R levels in 28 RA patients.
1993
- High dose immunoglobulin therapy in a case of inclusion body myositis: clinical and immunologic aspects
[Articolo su rivista]
Salvarani, Carlo; Boiardi, L; Maldini, M. C; Mancini, R; Rinaldi, M; Macchioni, P; Portioli, I.
abstract
To report clinical and immunologic aspects of a case with inclusion body myositis successfully treated with high dose immunoglobulin therapy.
1993
- Incidence of stroke in young adults in the Reggio Emilia area, northern Italy
[Articolo su rivista]
Guidetti, D; Baratti, M; Zucco, R. G; Greco, G; Terenziani, S; Vescovini, E; Sabadini, R; Bondavalli, M; Masini, L; Salvarani, Carlo
abstract
A retrospective epidemiological study on the first episode of stroke in young adults aged 15-44 years was carried out in the territory of the Local Health Unit No. 9 in Reggio Emilia (46,491 km2), Italy, from 1987 to 1989. 29 patients were identified: 17 were affected with cerebral infarction and 12 with hemorrhage. All young patients were discharged with diagnostic codes 430-438 according to the International Classification of Disease, i.e. the criteria of the World Health Organisation for stroke definition. All patients had computed tomography or necropsy. The average annual incidence rate per 100,000 population aged 15-44 for all strokes was 13.6 and the 95% confidence interval (CI 95%) was 9.1-19.6. The general population of the same age on January 1, 1987, was 69,845 and 71,920 on December 31, 1989; the incidence rate of stroke was 14.0 for males (CI 95% 7.9-2.3) and 13.2 (CI 95% 7.1-22.2) for females. The average annual incidence rates were 8.0 (CI 95% 4.7-12.2) for cerebral infarction (8.4, CI 95% 3.9-16 for males, 7.6, CI 95% 3.3-14.9 for females), 5.6 (CI 95% 2.9-9.9) for cerebral hemorrhage and 2.8 (CI 95% 1.0-6.1) for both subarachnoid (SAH) and intracerebral hemorrhage (ICH). Based on angiography or necropsy findings, aneurysms or arteriovenous malformations were present in 83% of the patients with SAH and in 66% of the patients with ICH. The 1-month fatality ratio was 0 for cerebral infarction, 50% for SAH and 33% for ICH.(ABSTRACT TRUNCATED AT 250 WORDS)
1993
- Low molecular weight IgM in primary Sjögren's syndrome
[Articolo su rivista]
Salvarani, Carlo; Casali, B; Boiardi, L; Macchioni, P. L; Rivasi, P; Portioli, I.
abstract
Low molecular weight IgM (LMW IgM), the monomeric subunit of pentameric IgM, was measured in the serum of 27 patients with primary Sjögren's syndrome. LMW IgM was also measured in a control group consisting of 24 patients with psoriatic arthritis (PA) and 8 patients with active rheumatoid arthritis (RA). LMW IgM was found in the majority of patients with primary SS (63%) and those patients had a longer disease duration than those without SS (80.7 +/- 43.9 months vs 37 +/- 18.3, p = 0.01). Although the differences were not significant, SS patients with LMW IgM showed higher rates of: seropositive disease (71% vs 50%), anti-Ro (59% vs 30%) and anti-La antibodies (12% vs 0%), extraglandular involvement (76% vs 60%) and raised gammaglobulins levels (47% vs 30%) compared to those without LMW IgM. Our only two patients with active RA and vasculitis had LMW IgM. None of the patients with PA showed LMW IgM, regardless of their Kammer subgroup classification, disease activity or radiological evidence of erosions. The presence of LMW IgM in a high percentage of patients with primary SS appears to be the expression of a dysregulation of B cell state that may predispose these patients to developing malignant lymphoproliferation.
1993
- Lymphocyte subpopulations analysis in peripheral blood in polymyalgia rheumatica/giant cell arteritis
[Articolo su rivista]
Macchioni, P; Boiardi, L; Salvarani, Carlo; Rossi, F; Casadei Maldini, M; Mancini, R; Beltrandi, E; Portioli, I.
abstract
The phenotypic characteristics of peripheral blood lymphocytes were investigated in 22 patients suffering from active polymyalgia rheumatica/giant cell arteritis (PMR/GCA) prior to steroid treatment. We observed a significant reduction in the absolute number and the relative percentage of CD4-, CD8+ and CD3+, CD16+ and/or CD56+ cells compared to controls. Fifteen patients were investigated prospectively over a 6-month period of prednisone therapy. At the end of the study CD4-CD8+ cells had increased significantly compared to baselines, CD3+ CD16+ and/or CD56+ cells remained significantly lower when compared to controls. We did not observe any abnormalities in the absolute number and percentage of HLA-DR+ T lymphocytes, CD5+ B cells and NK cell phenotypes before or during steroid treatment. Our study confirms that there was significant increase in the absolute number of CD8+ T cells during steroid treatment in the PMR/GCA patients, but indicates the persistence of an immunological alteration despite the control of disease manifestations.
1993
- Polymyalgia rheumatica and seronegative rheumatoid arthritis: some considerations based on a northern Italian population
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Mantovani, W; Portioli, I.
abstract
To report some considerations on polymyalgia rheumatica and seronegative rheumatoid arthritis based on a northern Italian population
1992
- Anticardiolipin antibodies in northern Italian population with PMR/GCA
[Articolo su rivista]
Salvarani, Carlo; Baricchi, R; Macchioni, P; Carbognani, R; Morelli, A; Lodi, L; Portioli, I.
abstract
To report the frequency of anticardiolipin antibodies in northern Italian population with PMR/GCA
1992
- Chronic neutrophilic leukemia (CNL) with karyotypic abnormalities associated with plasma cell dyscrasia: a case report
[Articolo su rivista]
Masini, L; Salvarani, Carlo; Macchioni, P; Baldi, G; Rossi, F; Croci, G; Prandi, S; Davoli, C; Portioli, I; Gobbi, F.
abstract
A case of chronic neutrophilic leukemia (CNL), a rare myeloproliferative syndrome associated with monoclonal gammopathy of uncertain significance (MGUS-Type IgGk), is reported. Karyotypic study, carried out on bone marrow, excluded Philadelphia-pos. chronic myeloid leukemia (CML) and showed Y loss (45 XO). Only a few cases of CNL with paraproteinemia have been reported, but no case of associated karyotypic abnormalities and paraproteinemia has so far been described.
1992
- Endocrine abortion in assisted reproduction technologies (ART)
[Articolo su rivista]
Coppola, F.; Tridenti, G.; Barletta, C.; Bertoli, M.; Trentadue, R.; Barusi, L.; Ferrari, B.; Avanzini, A. M.; Salvarani, C.
abstract
Luteal function, endometrial receptivity, endometrial prolactin and glycoprotein secretions, blastocyst-secreted immunomodulant factors and embryo quality are nowadays considered the main determinants involved in embryo implantation control. The endometrial factors are progesterone-dependent. Out of 128 cycles of ART (AIH-IU, GIFT, IVF-ET), performed in 67 women at the Dept. of Obstetrics and Gynaecology of Parma during the period 1986-1991, 31 conceptions were obtained (pregnancy rate: 24.21%), 7 of which miscarried (abortion rate: 22.58%). According to these data, ART high abortion rate is possibly connected with poor luteo-endometrial function and poor embryo quality. Controlled ovarian hyperstimulation is thought to inhibit embryo implantation after IVF-ET by decreasing endometrial receptivity. Such a situation can be treated either by exogenous progesterone administration or by tubal techniques (GIFT, TET) performed in non-tubal infertility. Both strategies showed to better endometrial receptivity. A delayed intrauterine embryo transfer at blastocyst stage, when cocultures allow to, is supposed to raise the implantation rate in tubal infertility by enhancing embryo selection and endometrial receptivity. This paper also reports preliminarily on the predictive value of beta-HGC and estradiol levels, as well as of endometrial thickness, on early pregnancy outcome.
1992
- Extraarticular manifestations of rheumatoid arthritis and HLA antigens in northern Italy
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Mantovani, W; Rossi, F; Veneziani, M; Boiardi, L; Lodi, L; Portioli, I.
abstract
We performed retrospective analysis of 141 Northern Italian patients with rheumatoid arthritis (RA). This series represents all the patients seen as in and/or outpatients at the rheumatologic unit of Reggio Emilia Hospital during a 2 year period (1987-88). We observed a low frequency of nodules (16%) and vasculitis (2.1%). Thus, RA seems to be milder in our population compared to Caucasian patients with RA originating from North America or England. We observed a weak association with DR4 (RR = 2.4) in the total group of patients with RA. A low frequency of DR4 was observed in patients and controls (29 vs 14.5%, p = 0.001). When compared with controls the frequency of DR4 was significantly higher in seropositive (p = 0.001), but not in seronegative patients. We found that DR4 was significantly associated with nodules (RR = 6.4), with extraarticular features (EAF) (RR = 4) and with erosions (RR = 3) compared with controls. The subgroups with nodules and EAF had a DR4 frequency (respectively, of 52 and 40%) which was significantly higher than that observed in remaining patients (respectively, 25 and 24%). No significant difference was observed in the DR4 frequency between the patients with erosions and those without (34 vs 18%). Thus, DR4 in our population seems to be predominantly associated with a subgroup of patients characterized by seropositivity and EAF.
1992
- Giant cell arteritis in Mediterranean countries: Comment on the article by Salvarani et al
[Articolo su rivista]
Gonzalez-Gay, M. A.; Alonso, M. D.; Aguero, J. J.; Bal, M.; Fernandez-Camblor, B.; Sanchez-Andrade, A.; Salvarani, C.; Macchioni, P.; Boiardi, L.; Lodi, L.; Portioli, I.
abstract
1992
- Immunologic effects in patients with psoriatic arthritis treated with cyclosporine A
[Articolo su rivista]
Boiardi, L; Salvarani, Carlo; Macchioni, P; Casadei Maldini, M; Mancini, R; Beltrandi, E; Rossi, F; Lodi, L; Portioli, I.
abstract
Twelve patients with psoriatic arthritis (PsA) and very active articular disease resistant to conventional second line therapy entered into a 6-month open study of cyclosporine A (CsA) at a starting dosage of 3 mg/kg/day. Comparisons of phenotypic characteristics of lymphocytes and response to mitogens of peripheral blood mononuclear cells (PBMC) were made between these patients with PsA before CsA therapy, 7 patients without prior 2nd line therapy, 14 untreated patients with psoriasis alone, and 61 healthy controls. We confirmed a significant reduction of the basal percentage of CD8+ cells and an increase in the CD4/CD8 ratio in patients with PsA before CsA therapy compared to controls. These abnormalities were not present in patients with PsA without prior 2nd line therapy and in patients with psoriasis alone. Peripheral blood activated T cells (CD3+, HLA-DR+), natural killer (NK) (CD3-, CD16+ and/or CD56+), total B and CD5+ B cells were decreased only in patients with PsA before CsA therapy. The reduction of non-MHC restricted cytotoxicity T (CD3+, CD16+ and/or CD56+) was observed in all the 3 groups of patients compared to controls. After the 6 months of CsA therapy we observed a significant increase of CD3+, HLA-DR+, CD3+, CD16+ and/or CD56+, total B, and CD20+, CD5+ cells in the 11 patients with PsA compared to pretreatment values. Contrary to azathioprine, CsA does not impair the NK cell population which has a protective role against cancer and viral infections.
1992
- Low dose cyclosporine A in psoriatic arthritis: relation between soluble interleukin 2 receptors and response to therapy
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Boiardi, L; Rossi, F; Casadei Maldini, M; Mancini, R; Beltrandi, E; Lodi, L; Bisighini, G; Portioli, I.
abstract
Twelve patients with psoriatic arthritis (PsA) were treated with low doses of cyclosporine A (CsA) (the initial dose was 3 mg/kg daily) and were entered into an open 6-month study. At the end of the study arthritis was improved in 7 patients (number of patients achieving a 50% or more reduction in the number of swollen or tender joints) and unchanged in 4 patients. Cutaneous psoriasis also improved significantly as shown by psoriasis area and severity index score. Only one patient withdrew from the study after one month because of severe nephrotoxicity. Serum creatinine fell to baseline value 6 weeks after the discontinuation of CsA. Three patients had minor side effects. CsA maintained articular improvement also in the 9 patients who are still taking this drug (mean duration of therapy of 12 +/- 0.8 months). There was no significant reduction of erythrocyte sedimentation rate during the study period. We assayed levels of soluble interleukin 2 receptors (sIL-2R) in serial serum samples obtained from 10 patients during the study period. Concentrations of sIL-2R were significantly increased in patients with PsA compared to controls. In 6 responder patients we observed a parallel decrease in joint pain/tenderness score and serum sIL-2R values. This finding was not observed in 4 nonresponders. Our results suggest that low dose CsA is a short term effective and safe therapy in patients with PsA and that serial sIL-2R levels are a useful means of measuring changes in disease activity.
1992
- Soluble interleukin 2 receptors in polymyalgia rheumatica/giant cell arteritis. Clinical and laboratory correlations
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Boiardi, L; Rossi, F; Casadei Maldini, M; Mancini, R; Beltrandi, E; Spacca, C; Lodi, L; Portioli, I.
abstract
Serum levels of soluble interleukin 2 receptors (sIL-2R) were measured in 21 patients with polymyalgia rheumatica (PMR)/giant cell arteritis (GCA) prior to steroid treatment. These levels were significantly elevated in patients with PMR/GCA compared with healthy controls (p = 0.002). A significantly longer duration of morning stiffness (p = 0.005) was observed in patients with a high concentration of sIL-2R. A significant correlation was observed at diagnosis between sIL-2R and erythrocyte sedimentation rate (ESR) (p = 0.01) and between ESR and C-reactive protein (CRP) (p = 0.005). We investigated prospectively a group of 10 patients over a period of 6 months of prednisone therapy. At the end of the study sIL-2R levels fell significantly compared to pretreatment values (p = 0.02), but remained significantly higher compared to controls (p = 0.02). ESR and CRP values also fell significantly compared to pretreatment levels (p = 0.0001 in both cases). We observed a significant correlation between the decrease in ESR values and the decrease in sIL-2R and CRP levels after 6 weeks (p = 0.01 in both cases) and after 6 months of therapy (p = 0.002 and p = 0.05). sIL-2R may be considered a useful serologic marker for monitoring response to steroid therapy in patients with PMR/GCA. This laboratory variable correlated more closely with ESR than with CRP. The presence of elevated levels of sIL-2R is likely to reflect T cell activation occurring in PMR/GCA. T lymphocyte activation persisted after 6 months of steroid therapy, despite rapid and continuous control of disease manifestations.
1992
- Synovitis in polymyalgia rheumatica: an immunogenetic study
[Articolo su rivista]
Salvarani, Carlo; Rossi, F; Macchioni, P; Mantovani, W; Veneziani, M; Boiardi, L; Lodi, L; Portioli, I.
abstract
Immunogenetic study on synovitis in polymyalgia rheumatica
1992
- The cervical spine in patients with psoriatic arthritis: a clinical, radiological and immunogenetic study
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Cremonesi, T; Mantovani, W; Battistel, B; Rossi, F; Capozzoli, N; Baricchi, R; Portioli, I.
abstract
The radiological changes of the cervical spine were evaluated in 57 patients with psoriatic arthritis and were correlated with clinical, radiological, and immunogenetic features of the disease. Forty patients (70%) showed radiological evidence of the cervical spine being affected by the disease. Two patterns of cervical spine abnormalities were noted. Fifteen patients (26%) had erosive and/or subluxing cervical rheumatoid like lesions; 25 patients (44%) had a more frequently reported pattern similar to ankylosing spondylitis. Although subaxial subluxations were the most frequently observed cervical abnormalities (53%) in the inflammatory subgroup, none of the patients studied had cord compression. Ankylosing cervical spine disease was the only form of axial involvement in nine (36%) of 25 patients with the ankylosing form of psoriatic arthritis. All of these patients had peripheral disease and were B27 negative. Predictors of cervical spine disease patterns were considered using clinical, demographic, and radiological features and HLA antigens. The results of a multivariate analysis showed that the best predictors of inflammatory cervical spine disease are the presence of HLA-B39 and HLA-DR4 antigens, radiocarpal erosions, and the absence of the HLA-DR5 antigen.
1991
- Clinical and pathologic study on eleven cases of systemic vasculitis
[Articolo su rivista]
Soliani, F; Salvarani, Carlo; Ambrosetti, F; Lindner, G; Lusenti, T; Prandi, S; Manicardi, E; Portioli, I; Borgatti, P.
abstract
To report clinical and pathologic study on eleven cases of systemic vasculitis
1991
- Epidemiologic and immunogenetic aspects of polymyalgia rheumatica and giant cell arteritis in northern Italy
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Zizzi, F; Mantovani, W; Rossi, F; Castri, C; Capozzoli, N; Baricchi, R; Boiardi, L; Chiaravalloti, F.
abstract
We studied the epidemiology of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) in a Mediterranean population. Ninety-nine patients with PMR and/or GCA were identified over a 9-year period (1980-1988) in Reggio Emilia, Italy. The average annual incidence of PMR and GCA was 12.7/100,000 and 6.9/100,000, respectively, in a population aged 50 years or older. Frequencies of HLA antigens were determined in 49 patients with PMR and/or GCA who were followed by staff at our rheumatology unit during the 1980-1988 period. When compared with HLA findings in 242 healthy controls, DR4 was not found to be significantly associated with PMR (24% in PMR patients versus 14% in controls). Patients with GCA also showed an increased frequency of DR4 compared with controls (36% versus 14%), but this difference was also not statistically significant. The immunogenetic features of PMR and GCA and the relationship between the immunogenetic and epidemiologic patterns in different populations are discussed.
1991
- Incidence of stroke in young adults in Reggio Emilia, Italy (1987-1989)
[Articolo su rivista]
Guidetti, D.; Baratti, M.; Zucco, G.; Greco, G.; Terenziani, S.; Vescovini, E.; Sabadini, R.; Bondavalli, M.; Masini, L.; Salvarani, C.; Dall'Ara, P.; Zannoni, P.; Paderni, F.; Solime, F.
abstract
1991
- Low incidence of toxicity from gold thiomalate in Hong Kong chinese patients with rheumatoid arthritis [3]
[Articolo su rivista]
Cohen, M. G.; Ng, P. Y.; Chan, K. L.; Li, E. K.; Salvarani, C.; Macchioni, P.; Zizzi, F.; Rossi, F.; Frizziero, L.; Portioli, I.
abstract
1991
- Recombinant human erythropoietin therapy in patients with rheumatoid arthritis with the anemia of chronic disease
[Articolo su rivista]
Salvarani, Carlo; Lasagni, D; Casali, B; Macchioni, P; Boiardi, L; Rossi, F; Rivasi, P; Portioli, I.
abstract
We treated 5 patients with rheumatoid arthritis (RA) with anemia of chronic disease with recombinant human erythropoietin (rHuEPO) for 11 weeks. An increase in hematocrit (Hct) greater than 5 was seen in 4 patients after 4 weeks of therapy. The 5th patient had a significant rise in Hct when the dosage of rHuEPO was increased to 150 units/kg from the 4th to 7th week. The subcutaneous administration of rHuEPO dose, reduced by one third with respect to initial dose, maintained an effective Hct value in all the 5 patients during the last 4 weeks of therapy. There was no change in disease activity. In one patient Hct normalization completely resolved symptoms of angina pectoris and permitted hip replacement surgery in another. No side effects occurred during rHuEPO therapy. We conclude that HuEPO is an effective, safe and well tolerated therapy for RA patients with severe anemia of chronic disease.
1991
- Relationship between plasma profiles of oxytocin and adrenocorticotropic hormone during suckling or breast stimulation in women
[Articolo su rivista]
Chiodera, P; Salvarani, Carlo; Bacchi Modena, A; Spallanzani, R; Cigarini, C; Alboni, A; Gardini, E; Coiro, V.
abstract
Oxytocin (OT) administration has been shown to inhibit adrenocorticotropic hormone (ACTH)/cortisol secretion in several experimental conditions. In the present study, the plasma OT responses to suckling in 7 lactating women or to mechanical breast stimulation in 6 normally menstruating women (experimental tests) or to sham stimuli in the same subjects (control tests) were measured and correlated with the simultaneous changes in plasma ACTH/cortisol levels. All women showed similar basal levels of OT, ACTH and cortisol, which remained unmodified after sham stimulation. In contrast, both suckling and breast stimulation produced a significant increase in plasma OT levels and a significant decrease in plasma ACTH concentrations. When OT and ACTH data were considered together, a significant negative correlation was found between the OT increase and the simultaneous ACTH decline. Plasma cortisol levels were lower during suckling or breast stimulation than in control conditions. These data show an inverse relationship between plasma OT and ACTH levels during suckling and breast stimulation in humans, suggesting an inhibitory influence of OT on ACTH/cortisol secretion in a physiological condition.
1991
- Sjögren's syndrome in human immunodeficiency virus (HIV) infection: association with HLA-DR3 and CD8 lymphocytosis in an Italian patient
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Lodi, L; Iori, I; Boiardi, L; Bertorelli, G; Rossi, F; Panciroli, G; Portioli, I.
abstract
To report the association with HLA-DR3 and CD8 lymphocytosis in an Italian patient with Sjögren's syndrome and human immunodeficiency virus (HIV) infection.
1991
- The role of interleukin 1, erythropoietin and red cell bound immunoglobulins in the anaemia of rheumatoid arthritis
[Articolo su rivista]
Salvarani, Carlo; Casali, B; Salvo, D; Brunati, C; Macchioni, P. L; Massai, G; Lasagni, D; Rivasi, P; Portioli, I.
abstract
Since interleukin 1 (IL-1) and erythropoietin (Epo) are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) anaemia we measured IL-1 alpha and Epo concentrations in 10 RA patients with chronic disease anaemia (CDA) and in 14 RA patients without anaemia. Anaemic RA patients had significantly higher IL-1 alpha concentrations than patients without anaemia. IL-1 alpha correlated negatively with haemoglobin and correlated positively with ESR. The results of a multivariate analysis showed that the best predictors of the presence and absence of anaemia were IL-1 alpha and ESR. No clinical parameters permitted a distinction between these two groups of patients. Epo levels were not different in anaemic and non-anaemic RA patients. No correlation was found between Hb and Epo, indicating the presence of an impaired Epo response in RA patients with CDA. We completed our study with the determination of the mean red cell lifespan and with the quantification of IgG and IgM bound to the surfaces of red blood cells (RBC-IgG and RBC-IgM) using a sensitive ELISA method. We observed a modest reduction in red cell survival in anaemic RA patients compared to normal controls. We did not find any correlation between Hb and red cell lifespan and between Hb and RBC-IgG. RBC-IgG and RBC-IgM were not found to be more elevated in anaemic RA than in non-anaemic patients.
1990
- Low incidence of proteinuria in RA after gold thiosulfate treatment
[Articolo su rivista]
Salvarani, C.; Macchioni, P.; Zizzi, F.; Rossi, F.; Baricchi, R.; Mantovani, W.; Ghirelli, L.; Capozzoli, N.; Frizziero, L.; Portioli, I.
abstract
1990
- Psychosocial problems and work disability in rheumatoid arthritis: A study in Reggio Emilia area
[Articolo su rivista]
Sottilotta, P.; Salvarani, C.; Veneziani, M.; Giovinazzo, M.; Macchioni, P. L.; Rossi, F.; Portioli, I.
abstract
1990
- Upper limb lymphedema in psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P. L; Veneziani, M; Rossi, F; Lodi, L; Baricchi, R; Boiardi, L; Portioli, I.
abstract
To report a case of upper limb lymphedema in psoriatic arthritis
1989
- Autoimmune disease in hairy-cell leukemia: systemic vasculitis and anticardiolipin syndrome
[Articolo su rivista]
Salvarani, Carlo; Capozzoli, N; Baricchi, R; Macchioni, P. L; Rossi, F; Ghirelli, L; Bellelli, A; Tumiati, B; Portioli, I.
abstract
To report a case of systemic vasculitis and anticardiolipin syndrome in hairy-cell leukemia
1989
- Bartter's syndrome and chondrocalcinosis: a possible role for hypomagnesemia in the deposition of calcium pyrophosphate dihydrate (CPPD) crystals
[Articolo su rivista]
Salvarani, Carlo; Rossi, F; Macchioni, P. L; Baricchi, R; Capozzoli, N; Castellani, S; Ghirelli, L; Veneziani, M; Scarti, L; Portioli, I.
abstract
A new case of association between Bartter's syndrome and chondrocalcinosis is reported. The patient was shown to have marked hypomagnesemia. Indomethacin and magnesium therapy was started and resulted in increased magnesemia, even if it did not reach normal levels. There was complete remission of articular symptoms and no progression on the radiological picture after 2 years of continuous magnesium and indomethacin therapy. The 7 available family members were studied to assess the possible presence of a familial form of chondrocalcinosis and/or hypomagnesemia. The literature is reviewed and reports of previously described associations between Bartter's syndrome and chondrocalcinosis are summarized. The possible role of hypomagnesemia in predisposing to deposition of calcium pyrophosphate dihydrate crystal in cartilagine is also discussed.
1989
- Cerebellar syndrome associated with hypothyroidism
[Articolo su rivista]
Guidetti, D.; Greco, G.; Zucco, R.; Marbini, A.; Salvarani, C.; Valcavi, R.
abstract
1989
- Clinical response to auranofin in patients with psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Zizzi, F; Macchioni, P; Mantovani, W; Rossi, F; Baricchi, R; Bellelli, A; Capozzoli, N; Frizziero, L; Portioli, I.
abstract
Fifty-two patients with psoriatic arthritis (PA), treated with auranofin (AF), were entered into a one year prospective, open study. The total group showed a significant increase in frequency of HLA antigens A1 and B38, and a reduction of B5 when compared to healthy controls. There was a remission or an important improvement of disease in the 51% of 45 patients who completed the study. The rate of withdrawal due to side effects was low (8.8%) and the toxicity was mild in nature (diarrhoea and mucocutaneous rash). We prospectively sought predictors of response using HLA antigens, and clinical and laboratory parameters at the beginning of therapy. The only 3 factors found to be related to outcome were duration of psoriasis, physician and patient assessment of disease activity. No laboratory data or HLA specificities could be associated with substantial response to AF therapy.
1989
- Clinical subgroups and HLA antigens in Italian patients with psoriatic arthritis
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P. L; Zizzi, F; Mantovani, W; Rossi, F; Baricchi, R; Ghirelli, L; Frizziero, L; Portioli, I.
abstract
The frequencies of HLA antigens were studied in 101 Italian patients with psoriatic arthritis. The total group showed a significant increase in frequency of A1 and B38, and a reduction of B5 when compared to healthy controls. No association between DR and/or DQw antigens and PA were demonstrated. The comparisons between the clinical subgroups and normal controls revealed a significant association of B38 with asymmetric peripheral arthritis, B27 and B39 with spondylitis (with or without peripheral involvement). When intergroup comparison were made, the patients with spondylitis had an increase in frequency of B27 and DQw3 as compared to those with symmetric and asymmetric peripheral disease. DR4 and DRw53 were associated with earlier age of onset of arthritis. There were also significant associations between DQw3 and severe disease, and between A9, B5 and presence of erosions and joint space narrowing. No association with DR4 was showed in a subgroup of patients with symmetric polyarthritis without DIP involvement.
1988
- Hypothyroidism simulating polymyositis. Report of two cases
[Articolo su rivista]
Salvarani, Carlo; Marcello, N; Macchioni, P; Guidetti, D; Rossi, F; Iori, I; Baricchi, R; Ghirelli, L; Portioli, I.
abstract
To report two cases of hypothyroidism simulating polymyositis.
1987
- Anticardiolipin antibodies in a case of neuro-Behçet with superior vena caval occlusion
[Articolo su rivista]
Salvarani, Carlo; Massai, G; Macchioni, P; Monti, M; Rossi, F; Baricchi, R.
abstract
The patient, a 55-year-old man with neuro-Behçet, developed superior vena caval occlusion. Antibodies to cardiolipin were detected in high titres in his serum and a decreased fibrinolysis was also found. It is suggested that anticardiolipin antibodies, perhaps decreasing fibrinolysis, may play an important pathogenic role in some patients with Behçet's disease.
1987
- Polymyalgia rheumatica and giant cell arteritis: a 5-year epidemiologic and clinical study in Reggio Emilia, Italy
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P. L; Tartoni, P. L; Rossi, F; Baricchi, R; Castri, C; Chiaravalloti, F; Portioli, I.
abstract
Among the population of Reggio Emilia, Italy, 56 patients with polymyalgia rheumatica (PR) and giant cell arteritis (GCA) were identified during the 5-year period 1981-85. The average annual incidence rates of PR and GCA were 12.8 and 8.8 respectively per 100,000 population aged 50 years or older. Forty-nine patients were followed up and the mean duration of follow-up was 32 months. All the patients received steroid therapy. We have evaluated the cumulative probability of requiring continued steroid therapy between patients with PR only, GCA only, and PR associated with GCA using life-table methods with permanent discontinuation of therapy as an end point. The different duration of steroid therapy between these 3 groups did not achieve statistical significance by the method of Lee and Desu. We identified a 5 variable discriminant function that correctly predicted whether the duration of therapy would be longer or shorter than 16 months (median duration of therapy) in 80% of our patients followed up for at least 24 months. The presence of synovitis in PR is also discussed.
1987
- Synovitis in polymyalgia rheumatica: a 5-year followup study in Reggio Emilia, Italy
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Rossi, F; Baricchi, R; Ghirelli, L; Portioli, I.
abstract
Synovitis in polymyalgia rheumatica: a 5-year followup study in Reggio Emilia, Italy
1986
- HLA typing, platelet associated immunoglobulins and anticardiolipin antibody
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Ross, F; Baricchi, R; Filippi, G; Iori, I; Massai, G; Monti, M.
abstract
To investigate the associations between HLA typing, platelet associated immunoglobulins and anticardiolipin antibody
1985
- Gold induced severe aplastic anemia: medullary autologous reconstitution after immunosuppression
[Articolo su rivista]
Salvarani, Carlo; Iori, I; Prandi, S; Rossi, F; Filippi, G.
abstract
To report a case of gold induced severe aplastic anemia with medullary autologous reconstitution after immunosuppression
1985
- Nephrotic syndrome induced by tiopronin: association with the HLA-DR3 antigen
[Articolo su rivista]
Salvarani, Carlo; Macchioni, P; Rossi, F; Iori, I; Filippi, G.
abstract
To report a case of nephrotic syndrome induced by tiopronin and the association with the HLA-DR3 antigen.
1985
- [Gold-induced severe aplastic anemia: medullary autologous reconstitution after immunosuppressive treatment. An observation]
[Articolo su rivista]
Iori, I; Salvarani, Carlo; Prandi, S; Macchioni, P; Filippi, G; Del Din, G.
abstract
Gold-induced severe aplastic anemia: medullary autologous reconstitution after immunosuppressive treatment. An observation
1984
- Neurologic involvement as first sign of Behcet's syndrome
[Articolo su rivista]
Salvarani, Carlo; Iori, I; Rossi, F; Del Din, G; Filippi, G; Macchioni, P.
abstract
To describe a case of neurologic involvement as first sign of Behcet's syndrome
1984
- [Acute myelosclerosis. Evolution in acute lymphoblastic leukemia]
[Articolo su rivista]
Iori, I; Salvarani, Carlo; Fantesini, C; Prandi, S; Dall'Aglio, E.
abstract
To describe a case of acute myelosclerosis evolved in acute lymphoblastic leukemia
1982
- [Kaposi's sarcoma during corticoid therapy. Description of a clinical case]
[Articolo su rivista]
Bellelli, A; Azzarito, C; Salvarani, Carlo; Baricchi, R; Portioli, I.
abstract
To describe a case of Kaposi's sarcoma during corticoid therapy.
1982
- [Malignant myelofibrosis. Evolution toward acute lymphoblastic leukemia]
[Articolo su rivista]
Fantesini, C; Prandi, S; Iori, I; Salvarani, Carlo
abstract
To report a case of malignant myelofibrosis evolved toward acute lymphoblastic leukemia
1981
- [The Reynolds syndrome. Clinical case and review of the literature. Analogy with graft-versus-host disease]
[Articolo su rivista]
Bellelli, A; Tumiati, B; Rossi, F; Salvarani, Carlo; Portioli, I.
abstract
The Reynolds syndrome. Clinical case and review of the literature.
1976
- [The preparation and characterization of steroid antisera (author's transl)]
[Articolo su rivista]
Vadora, E; Dagradi, G; Bacchi Modena, A; Salvarani, Carlo; Coppola, F.
abstract
The steroids, as compounds of low molecular weight, are not immunogenic; however, certain small molecules (haptens) when covalently linked to proteins become antigenic i.e., they provoke the production of unique antibody. If a steroid were covalently copuled to a protein, an artifical antigen would be produced capable of eliciting the formation of antibody with specificity not only for the protein carrier but also for the particular haptenic steroid. The results would be an in vivo production of a tailor made binding sites for any steroid that can be attached as a hapten to a protein by covalent bonds and thus become antigenic. This procedure allow the preparation of steroid specific antisera suitable for clinical use in radioimmunoassay, methods. The Authors report the techniques of preparation of steroid-derivative antigens of Androstenedion, Testosteron, and Progesteron. The three derivative steroid antigens have shown a good antigenic property by eliciting the formation of specifical antisera in 5 out of 6 rabbits used for the immunization. After 10 weeks from the beginning of immunization antisera useful in radioimmunoassay at the diluition 1/300; 1/1600; 1/2000 respectively for Progesteron, Testosteron and Androstenedion were obtained. The standard curves show a good sensitivity suitable for clinical use.