Publications by authors named "Giulia Cassone"

41 Publications

Interstitial Lung Disease and Anti-Myeloperoxidase Antibodies: Not a Simple Association.

J Clin Med 2021 Jun 9;10(12). Epub 2021 Jun 9.

Rheumatology Unit, Azienda Ospedaliera Policlinico di Modena, University of Modena and Reggio Emilia, 41121 Modena, Italy.

Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). However, their role remains unclear, and only 7-23% of these patients develops clinically overt vasculitis. We aimed to investigate the clinical, serological, and radiological features and prognosis of anti-MPO-positive interstitial lung disease (ILD) patients. Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clinical data, lung function testing, chest high-resolution computed tomography (HRCT) pattern, and survival were recorded. Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the patients' survival. In fact, while the 52-week survival of the overall population was 71.4 ± 7.5%, significantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7 and 41.5% of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. A careful clinical history and evaluation should always be performed in ILD patients with anti-MPO antibodies to quickly identify patients who are developing a systemic rheumatic disease.
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http://dx.doi.org/10.3390/jcm10122548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227546PMC
June 2021

Fibrosing interstitial lung disease in primary Sjogren syndrome.

Joint Bone Spine 2021 Jun 9;88(6):105237. Epub 2021 Jun 9.

Rheumatology Unit, University of Modena and Reggio-Emilia, Modena, Italy.

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.
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http://dx.doi.org/10.1016/j.jbspin.2021.105237DOI Listing
June 2021

Usefulness of digital velcro crackles detection in identification of interstitial lung disease in patients with connective tissue diseases.

Arch Rheumatol 2021 Mar 25;36(1):19-25. Epub 2020 Jun 25.

Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy.

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.
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http://dx.doi.org/10.46497/ArchRheumatol.2021.7975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140864PMC
March 2021

The impact of chest CT body composition parameters on clinical outcomes in COVID-19 patients.

PLoS One 2021 14;16(5):e0251768. Epub 2021 May 14.

Epidemiology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251768PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121324PMC
May 2021

Tofacitinib for the Treatment of Severe Interstitial Lung Disease Related to Rheumatoid Arthritis.

Case Rep Med 2021 22;2021:6652845. Epub 2021 Apr 22.

Rheumatology Unit, University of Modena and Reggio Emilia, Via Del Pozzo 71, Modena 41125, Italy.

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.
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http://dx.doi.org/10.1155/2021/6652845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084679PMC
April 2021

Rheumatoid arthritis related interstitial lung disease.

Expert Rev Clin Immunol 2021 May 23;17(5):485-497. Epub 2021 Apr 23.

Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico Di , Modena, Italy.

Introduction: Interstitial lung disease (ILD) represents a frequent extra-articular manifestation of rheumatoid arthritis (RA) deeply impacting both quality of life and overall prognosis. 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.  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.
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http://dx.doi.org/10.1080/1744666X.2021.1905524DOI Listing
May 2021

Reply to the comment on: Hypereosinophilic bronchiolitis in ANCA-associated vasculitis: where does it stand? by Bilgin et al.

Clin Exp Rheumatol 2021 Mar-Apr;39 Suppl 129(2):197. Epub 2021 Mar 25.

Department of Medicine and Surgery, University of Milan-Bicocca, Respiratory Unit, San Gerardo Hospital, Monza, Italy.

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July 2021

High-dose glucocorticoids pulse-therapy for beta-coronaviridae pneumonia: a systematic literature review and case-series of Coronavirus disease-2019.

Clin Exp Rheumatol 2021 Feb 26. Epub 2021 Feb 26.

Rheumatology Unit, IRCCS Arcispedale Santa Maria Nuova, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, and Rheumatology Unit, University of Modena and Reggio Emilia, Modena, Italy.

Objectives: 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.

Conclusions: 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.
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February 2021

Human Dental Pulp Stem Cells Modulate Cytokine Production by Peripheral Blood Mononuclear Cells From Coronavirus Disease 2019 Patients.

Front Cell Dev Biol 2020 5;8:609204. Epub 2021 Feb 5.

Department of Surgery, Medicine Dentistry and Morphological Sciences with Interest in Transplant, University of Modena and Reggio Emilia, Modena, Italy.

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 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.
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http://dx.doi.org/10.3389/fcell.2020.609204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901970PMC
February 2021

Efficacy and safety of mycophenolate mofetil in the treatment of rheumatic disease-related interstitial lung disease: a narrative review.

Drugs Context 2021 15;10. Epub 2021 Jan 15.

Chair and Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy.

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.
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http://dx.doi.org/10.7573/dic.2020-8-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813435PMC
January 2021

Efficacy and safety of rituximab in the treatment of connective tissue disease-related interstitial lung disease.

Drugs Context 2021 15;10. Epub 2021 Jan 15.

Chair and Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy.

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.
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http://dx.doi.org/10.7573/dic.2020-8-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813433PMC
January 2021

Interstitial Pneumonia with Autoimmune Features: Why Rheumatologist-Pulmonologist Collaboration Is Essential.

Biomedicines 2020 Dec 26;9(1). Epub 2020 Dec 26.

Respiratory Unit, San Gerardo Hospital, Department of Medicine and Surgery, University of Milan-Bicocca, 20900 Monza, Italy.

In 2015 the European Respiratory Society (ERS) and the American Thoracic Society (ATS) "Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease" proposed classification criteria for a new research category defined as "Interstitial Pneumonia with Autoimmune Features" (IPAF), to uniformly define 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 involvement. 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.
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http://dx.doi.org/10.3390/biomedicines9010017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824155PMC
December 2020

Significance of PR3-ANCA positivity in eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

Rheumatology (Oxford) 2020 Dec 21. Epub 2020 Dec 21.

Department of Internal Medicine, Cochin Hospital, National Referral Center for Rare Systemic Autoimmune Diseases, Paris University, Paris, France.

Objectives: 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.

Methods: We set up a retrospective European multicentre cohort including 845 patients. Baseline characteristics and outcomes were analysed and compared according to ANCA status.

Results: ANCA status was available for 734 patients: 508 (69.2%) ANCA-negative, 210 (28.6%) MPO-ANCA and 16 (2.2%) PR3-ANCA. At baseline, PR3-ANCA patients, compared with those with MPO-ANCA and ANCA-negative, less frequently had active asthma (69% vs 91% and 93%, P = 0.003, respectively) and peripheral neuropathy (31% vs 71% and 47%, P < 0.0001), more frequently had cutaneous manifestations (63% vs 38% and 34%, P = 0.03) and pulmonary nodules (25% vs 10% and 8%, P = 0.046), and lower median eosinophil count (1450 vs 5400 and 3224/mm3, P < 0.0001). Vasculitis relapse-free survival was shorter for PR3-ANCA (hazard ratio 6.05, P = 0.005) and MPO-ANCA patients (hazard ratio 1.88, P = 0.0002) compared with ANCA-negative patients.

Conclusion: PR3-ANCA EGPA patients differ from those with MPO-ANCA and negative ANCA, and share clinical features with granulomatosis with polyangiitis. This suggests that PR3-ANCA EGPA could be a particular form of PR3-ANCA-associated vasculitis.
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http://dx.doi.org/10.1093/rheumatology/keaa805DOI Listing
December 2020

Acute-phase reactants during tocilizumab therapy for severe COVID-19 pneumonia.

Clin Exp Rheumatol 2020 Nov-Dec;38(6):1215-1222. Epub 2020 Dec 3.

University of Modena and Reggio Emilia, Modena, and Rheumatology Unit, Azienda USL-IRCCS di Reggio Emilia, Italy.

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.
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December 2020

Erratum to acute exacerbation of interstitial lung diseases secondary to systemic rheumatic diseases: a prospective study and review of the literature.

J Thorac Dis 2020 Oct;12(10):6411

Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy.

[This corrects the article DOI: 10.21037/jtd.2019.03.28.].
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http://dx.doi.org/10.21037/jtd-2020-64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656429PMC
October 2020

Factors Predicting Early Failure of Etanercept in Rheumatoid Arthritis: An Analysis From the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis) Registry.

Arch Rheumatol 2020 Jun 7;35(2):163-169. Epub 2020 Feb 7.

Department of Medicine, Rheumatology Unit, University of Bari, Interdisciplinary Bari, Italy.

Objectives: This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry.

Patients And Methods: This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model.

Results: Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis.

Conclusion: Although ETA demonstrated a high persistence in biologic-naïve RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug.
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http://dx.doi.org/10.46497/ArchRheumatol.2020.7499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406167PMC
June 2020

Susceptibility to COVID-19 in Patients Treated With Antimalarials: A Population-Based Study in Emilia-Romagna, Northern Italy.

Arthritis Rheumatol 2021 01 27;73(1):48-52. Epub 2020 Nov 27.

Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

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.
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http://dx.doi.org/10.1002/art.41475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436811PMC
January 2021

Epidemiology and management of interstitial lung disease in ANCA-associated vasculitis.

Clin Exp Rheumatol 2020 Mar-Apr;38 Suppl 124(2):221-231. Epub 2020 Apr 22.

Department of Medicine and Surgery, University of Milan Bicocca, Respiratory Unit, San Gerardo Hospital, ASST Monza, Italy.

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.
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September 2020

Pirfenidone for the treatment of interstitial lung disease associated to rheumatoid arthritis: a new scenario is coming?

Respir Med Case Rep 2020 4;30:101051. Epub 2020 Apr 4.

Chair and Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Via Del Pozzo, 71, 41100, Modena, Italy.

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.
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http://dx.doi.org/10.1016/j.rmcr.2020.101051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7150508PMC
April 2020

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows.

J Clin Med 2020 Apr 10;9(4). Epub 2020 Apr 10.

Chair and Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41124 Modena, Italy.

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.
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http://dx.doi.org/10.3390/jcm9041082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230307PMC
April 2020

Combination Therapy with Nintedanib and Sarilumab for the Management of Rheumatoid Arthritis Related Interstitial Lung Disease.

Case Rep Med 2020 9;2020:6390749. Epub 2020 Mar 9.

Rheumatology Unit, Azienda Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italy.

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.
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http://dx.doi.org/10.1155/2020/6390749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085352PMC
March 2020

Therapeutic Options for the Treatment of Interstitial Lung Disease Related to Connective Tissue Diseases. A Narrative Review.

J Clin Med 2020 Feb 3;9(2). Epub 2020 Feb 3.

Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41121 Modena, Italy.

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.
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http://dx.doi.org/10.3390/jcm9020407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073957PMC
February 2020

Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study.

J Clin Med 2020 Jan 19;9(1). Epub 2020 Jan 19.

Chair and Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, 41121 Modena, Italy.

Background: 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).

Methods: All RA-ILD patients treated with ABA for at least six months were retrospectively evaluated. Serology, previous and concurrent therapies, chest high-resolution computer tomography (HRCT), forced vital capacity (FVC), and lung diffusion of carbon monoxide (CO, DLCO) were collected.

Results: Forty-four patients were included; HRCT, FVC, and DLCO were analyzed at baseline, at one year, and at the end of follow-up. A remission or a low disease activity of RA was reached in 41/44 patients. Overall, FVC and DLCO remained stable or increased in 86.1% and 91.7% of patients, respectively, while HRCT was stable or improved in 81.4% of them. Previous and concurrent treatments, in particular, methotrexate, serology, age, sex, joint and lung disease duration were not associated with the outcome at univariate analysis.

Conclusion: The management of RA-ILD patients remains a critical unmet medical need. Waiting for prospective controlled studies, ABA has shown a good safety profile in our cohort of Italian RA-ILD patients.
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http://dx.doi.org/10.3390/jcm9010277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019755PMC
January 2020

Interstitial pneumonia with autoimmune features: A single center prospective follow-up study.

Autoimmun Rev 2020 Feb 12;19(2):102451. Epub 2019 Dec 12.

Chair and Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy.

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.
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http://dx.doi.org/10.1016/j.autrev.2019.102451DOI Listing
February 2020

Tocilizumab therapy in rheumatoid arthritis with interstitial lung disease: a multicentre retrospective study.

Intern Med J 2020 09;50(9):1085-1090

Rheumatology Unit, University of Modena and Reggio Emilia, Univeritary Hospital Policlinico of Modena, Modena, Italy.

Background: 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.

Aims: To analyse the evolution of ILD in a population of RA patients treated with tocilizumab (TCZ).

Methods: In this national multicentre study, we retrospectively collected patients with RA-ILD treated with at least one dose of TCZ. For each patient, disease activity and serological data were evaluated. Moreover, we analysed the evolution of high-resolution computed tomography (HRCT) and pulmonary function tests, including forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO).

Results: Twenty-eight RA-ILD patients were identified (females/males 18/10, mean age 61.6 years), with a mean follow up for TCZ therapy of 30 months. At the end of follow up, FVC remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%). DLCO remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%), even though in 3 patients DLCO and FVC showed an opposite trend. HRCT remained stable in the majority (25) of cases, worsened in two patients with a usual interstitial pneumonia pattern and improved in only one case with a non-specific interstitial pneumonia pattern.

Conclusions: The management of RA-ILD patients remains a critical unmet need. TCZ demonstrated a good safety profile in patients with RA-ILD and a potential effect on the stabilisation of lung involvement.
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http://dx.doi.org/10.1111/imj.14670DOI Listing
September 2020

Acute exacerbation of interstitial lung diseases secondary to systemic rheumatic diseases: a prospective study and review of the literature.

J Thorac Dis 2019 Apr;11(4):1621-1628

Rheumatology Unit, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy.

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.
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http://dx.doi.org/10.21037/jtd.2019.03.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531687PMC
April 2019

Rituximab therapy for primary central nervous system vasculitis: A 6 patient experience and review of the literature.

Autoimmun Rev 2019 04 10;18(4):399-405. Epub 2019 Feb 10.

Division of Rheumatology, Mayo Clinic, Rochester, MN, United States.

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.
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http://dx.doi.org/10.1016/j.autrev.2018.12.002DOI Listing
April 2019

Nailfold Capillaroscopy Characteristics of Antisynthetase Syndrome and Possible Clinical Associations: Results of a Multicenter International Study.

J Rheumatol 2019 03 15;46(3):279-284. Epub 2018 Nov 15.

From the Rheumatology Unit, Azienda Policlinico of Modena, University of Modena and Reggio Emilia, Modena, Italy; ACURA Rheumatology Center, Bad Kreuznach, Germany; Rheumatology Division, Hospital Universitario Marqués de Valdecilla, IDiVAL, University of Cantabria, Santander, Spain; Rheumatology Division, University Hospital of Frankfurt, Frankfurt, Germany; Interstitial Lung Disease and Rheumatology Unit, Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas, Mexico City, Mexico; Servicio de Reumatología, Hospital Universitario La Paz, Madrid, Spain; Interdisciplinary Department of Medicine (DIM), Rheumatology Unit, University of Bari, Bari, Italy; Rheumatology Department, Hospital Universitario de la Princesa, Instituto de Investigación Sanitaria (IIS) Princesa, Madrid; Unidad de Enfermedades Autoinmunes Sistémicas, Servicio de Medicina Interna, Universidad Autonoma de Barcelona, on behalf of the GEAS group, Barcelona, Spain; Department of Experimental and Clinical Medicine, and Department of Medical and Surgical Critical Care, Section of Dermatology, University of Florence, Florence; Unità Operativa Complessa (UOC) Reumatologia, Ospedale San Camillo-Forlanini, Rome; ACURA Centre for Rheumatic Diseases, Baden-Baden, Germany; Rheumatology Department, Città Della Salute e della Scienza, Torino; Division of Rheumatology, University and Institute for Research and Health Care (IRCCS) Policlinico S. Matteo Foundation, Pavia, Italy; Servicio de Reumatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Dermatology Clinic, University Hospital of Trieste; Department of Pneumology and Respiratory Intermediate Care Unit, University Hospital of Cattinara, Trieste; Rheumatology Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Trieste, Trieste, Italy; Medizinische Klinik A, Klinikum der Stadt, Ludwigshafen, Germany; Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, San Martino Polyclinic Hospital IRCCS Genoa, Genoa, Italy; Interstitial and Rare Lung Disease Unit, Ruhrlandklinik University Hospital, University of Duisburg-Essen, Essen, Germany; UOC Reumatologia, Azienda Ospedaliero Universitaria S. Anna, University of Ferrara, Italy; Department for Rheumatology and Clinical Immunology, St. Josef Krankenhaus, University Clinic, Essen, Germany; Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa; Department of Internal Medicine, Rheumatology and Clinical Immunology, University Hospital Johannes-Gutenberg, Mainz, Germany; University of Ghent, Ghent University Hospital, Ghent, Belgium.

Objective: To describe nailfold videocapillaroscopy (NVC) features of patients with antisynthetase syndrome (AS) and to investigate possible correlations with clinical and serological features of the disease.

Methods: We retrospectively analyzed NVC images of 190 patients with AS [females/males 3.63, mean age 49.7 ± 12.8 yrs, median disease duration 53.7 mos (interquartile range 82), 133 anti-Jo1 and 57 non-anti-Jo1-positive patients]. For each patient, we examined number of capillaries, giant capillaries, microhemorrhages, avascular areas, ramified capillaries, and the presence of systemic sclerosis (SSc)-like pattern. Finally, we correlated NVC features with clinical and serological findings of patients with AS. Concomitantly, a historical cohort of 75 patients with antinuclear antibody-negative primary Raynaud phenomenon (RP) and longterm followup was used as a control group (female/male ratio 4.13/1, mean age 53.9 ± 17.6 yrs) for NVC measures.

Results: NVC abnormalities were observed in 62.1% of AS patients compared with 29.3% of primary RP group (p < 0.001). An SSc-like pattern was detected in 67 patients (35.3%) and it was associated with anti-Jo1 antibodies (p = 0.002) and also with a longer disease duration (p = 0.004). Interestingly, there was no significant correlation between the presence of SSc-like pattern and RP, and only 47% of patients with SSc-like pattern had RP.

Conclusion: NVC abnormalities are commonly observed in AS, independently from the occurrence of RP. The presence of an SSc-like pattern could allow identification of a more defined AS subtype, and prospective studies could confirm the association with clinical and serological features of AS.
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http://dx.doi.org/10.3899/jrheum.180355DOI Listing
March 2019

Analysis of pulmonary sounds for the diagnosis of interstitial lung diseases secondary to rheumatoid arthritis.

Comput Biol Med 2018 05 9;96:91-97. Epub 2018 Mar 9.

Department of Medical and Surgical Sciences of the University of Modena and Reggio Emilia, Modena, Italy; Rheumatology Unit at Azienda Ospedaliera Universitaria Policlinico di Modena, Modena, Italy. Electronic address:

The diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis is fundamental to improving their survival rate. In particular, the average survival time of patients affected by rheumatoid arthritis with pulmonary implications is approximately 3 years. The gold standard for confirming the diagnosis of this disease is computer tomography. However, it is very difficult to raise diagnosis suspicion because the symptoms of the disease are extremely common in elderly people. The detection of the so-called velcro crackle in lung sounds can effectively raise the suspicion of an interstitial disease and speed up diagnosis. However, this task largely relies on the experience of physicians and has not yet been standardized in clinical practice. The diagnosis of interstitial lung diseases based on thorax auscultation still represents an underexplored field in the study of rheumatoid arthritis. In this study, we investigate the problem of the automatic detection of velcro crackle in lung sounds. In practice, the patient is auscultated using a digital stethoscope and the lung sounds are saved to a file. The acquired digital data are then analysed using a suitably developed algorithm. In particular, the proposed solution relies on the empirical observation that the audio bandwidth associated with velcro crackle is larger than that associated with healthy breath sounds. Experimental results from a database of 70 patients affected by rheumatoid arthritis demonstrate that the developed tool can outperform specialized physicians in terms of diagnosing pulmonary disorders. The overall accuracy of the proposed solution is 90.0%, with negative and positive predictive values of 95.0% and 83.3%, respectively, whereas the reliability of physician diagnosis is in the range of 60-70%. The devised algorithm represents an enabling technology for a novel approach to the diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis.
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http://dx.doi.org/10.1016/j.compbiomed.2018.03.006DOI Listing
May 2018
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