Publications by authors named "Giacomo Emmi"

203 Publications

Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis (EGPA): a European multicenter observational study.

Arthritis Rheumatol 2021 Aug 4. Epub 2021 Aug 4.

Nephrology and Dialysis Unit (ERKnet Member)-CMID, Center of Research of Immunopathology and Rare Diseases, San Giovanni Bosco Hospital and University of Turin, Turin, Italy.

Objective: 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.

Methods: We included all EGPA patients treated with mepolizumab at the recruiting centres in 2015-2020. Treatment response was evaluated from month 3 through 24 (T3-T24) after mepolizumab starting. Complete response (CR) was defined as no disease activity (Birmingham Vasculitis Activity Score, BVAS=0) and a prednisone dose ≤4mg/day. Respiratory outcomes included asthma and ear-nose-throat (ENT) exacerbations.

Results: We included 203 patients, of whom 191 at stable dosage (158 mepolizumab 100mg/4 weeks, 33 300mg/4 weeks). At T3, 25 patients (12.3%) had a CR. CR rates increased to 30.4% and 35.7% at T12 and T24 and were comparable between mepolizumab 100 and 300mg/4 weeks. Mepolizumab led to a significant reduction in BVAS, prednisone dose, eosinophil counts from T3 through T24, with no significant differences between 100 and 300 mg/4weeks. Eighty-two patients (40.4%) experienced asthma exacerbations [57/158 (36%) on 100mg/4 weeks; 17/33 (52%) on 300mg/4 weeks]. Thirty-one (15.3%) experienced ENT exacerbations. Forty-four patients (21.7%) experienced adverse events, most being non-serious (38/44).

Conclusion: Mepolizumab both at 100 and 300mg/4 weeks is effective for EGPA. The two dosages should be compared in the setting of a controlled trial.
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http://dx.doi.org/10.1002/art.41943DOI Listing
August 2021

Biotechnological Agents for Patients With Tumor Necrosis Factor Receptor Associated Periodic Syndrome-Therapeutic Outcome and Predictors of Response: Real-Life Data From the AIDA Network.

Front Med (Lausanne) 2021 8;8:668173. Epub 2021 Jul 8.

Department of Medical Sciences, Surgery and Neurosciences, Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease and Rheumatology-Ophthalmology Collaborative Uveitis Center, University of Siena, Siena, Italy.

To describe the role of biotechnological therapies in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) and to identify any predictor of complete response. Clinical, laboratory, and therapeutic data from 44 Caucasian TRAPS patients treated with biologic agents were retrospectively collected in 16 Italian tertiary Centers. A total of 55 biological courses with anakinra ( = 26), canakinumab ( = 16), anti-TNF-α agents ( = 10), and tocilizumab ( = 3) were analyzed. A complete response was observed in 41 (74.5%) cases, a partial response in 9 (16.4%) cases and a treatment failure in 5 (9.1%) cases. The frequency of TRAPS exacerbations was 458.2 flare/100 patients-year during the 12 months prior to the start of biologic treatment and 65.7 flare/100 patients-years during the first 12 months of therapy ( < 0.0001). The median duration of attacks was 5.00 (IQR = 10.50) days at the start of biologics and 1.00 (IQR = 0.00) days at the 12-month assessment ( < 0.0001). Likewise, a significant reduction was observed in the Autoinflammatory Disease Activity Index during the study period ( < 0.0001). A significant corticosteroid sparing effect was observed as early as the first 12 months of treatment both in the number of patients requiring corticosteroids ( = 0.025) and in the dosages employed ( < 0.0001). A significant reduction was identified in the erythrocyte sedimentation rate ( < 0.0001), C reactive protein ( < 0.0001), serum amyloid A ( < 0.0001), and in the 24-h proteinuria dosage during follow-up ( = 0.001). A relapsing-remitting disease course (OR = 0.027, C.I. 0.001-0.841, = 0.040) and the frequency of relapses at the start of biologics (OR = 0.363, C.I. 0.301-0.953, = 0.034) were significantly associated with a complete response. No serious adverse events were observed. Treatment with biologic agents is highly effective in controlling clinical and laboratory TRAPS manifestations. Patients with a relapsing-remitting course and a lower frequency of flares at the start of treatment show more likely a complete response to biologic agents.
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http://dx.doi.org/10.3389/fmed.2021.668173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295690PMC
July 2021

IgG4-related disease: not just a matter of IgG4.

Rheumatology (Oxford) 2021 Jun;60(Supplement_3):iii35-iii38

Department of Biomedical Experimental and Clinical Sciences 'Mario Serio', University of Firenze, and Nephrology Unit, Meyer Children's Hospital, Firenze, Italy.

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http://dx.doi.org/10.1093/rheumatology/keab039DOI Listing
June 2021

Prevalence and clinical course of SARS-CoV-2 infection in patients with Behçet's syndrome.

Clin Exp Rheumatol 2021 Jun 9. Epub 2021 Jun 9.

Department of Experimental and Clinical Medicine, University of Florence, Italy.

Objectives: We aimed to assess the prevalence of SARS-CoV-2 infection among Behçet's syndrome (BS) patients, evaluating the possible association between demographic and clinical features and the risk of infection. Moreover, we aimed to evaluate the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection.

Methods: A survey was conducted on BS patients followed at the Behçet's Centre of the Careggi University Hospital, Florence, Italy. We further evaluated the possible association between BS disease activity and treatment, and the risk of SARS-CoV-2 infection.

Results: Out of 335 BS patients contacted, fourteen cases of SARS-CoV-2 were identified between April 1st, 2020 and February 9th, 2021, suggesting a prevalence of SARS-CoV-2 infection among BS patients of 4.2%, in line with the data of the general population in Italy (4.4%). When comparing clinical features between SARS-CoV-2 cases and matched SARS-CoV-2 negative BS patients, we found that the presence of different disease manifestations did not significantly differ between the two groups. SARS-CoV-2 cases and controls were also comparable in terms of immunosuppressive therapy, with the only exception of corticosteroids (71.4% vs. 35.7%, p=0.030), whose daily dose was significantly higher in cases than controls [5mg/day (IQR 0-10,) vs. 0 mg/day (IQR 0-5), p=0.005], suggesting that the right timing of usage and the more appropriate dosage of corticosteroid are a key question for the better management of these patients.

Conclusions: Based on our results, patients with BS do not seem to be at a greater risk of SARS-CoV-2 infection or severe complications compared with the general population.
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June 2021

Sjögren's syndrome: a systemic autoimmune disease.

Clin Exp Med 2021 Jun 7. Epub 2021 Jun 7.

Department of Internal Medicine, University of Genoa, 16132, Genoa, Italy.

Sjögren's syndrome is a chronic autoimmune disease characterized by ocular and oral dryness resulting from lacrimal and salivary gland dysfunction. Besides, a variety of systemic manifestations may occur, involving virtually any organ system. As a result, the disease is characterized by pleomorphic clinical manifestations whose characteristics and severity may vary greatly from one patient to another. Sjögren's syndrome can be defined as primary or secondary, depending on whether it occurs alone or in association with other systemic autoimmune diseases, respectively. The pathogenesis of Sjögren's syndrome is still elusive, nevertheless, different, not mutually exclusive, models involving genetic and environmental factors have been proposed to explain its development. Anyhow, the emergence of aberrant autoreactive B-lymphocytes, conducting to autoantibody production and immune complex formation, seems to be crucial in the development of the disease. The diagnosis of Sjögren's syndrome is based on characteristic clinical signs and symptoms, as well as on specific tests including salivary gland histopathology and autoantibodies. Recently, new classification criteria and disease activity scores have been developed primarily for research purposes and they can also be useful tools in everyday clinical practice. Treatment of Sjögren's syndrome ranges from local and symptomatic therapies aimed to control dryness to systemic medications, including disease-modifying agents and biological drugs. The objective of this review paper is to summarize the recent literature on Sjögren's syndrome, starting from its pathogenesis to current therapeutic options.
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http://dx.doi.org/10.1007/s10238-021-00728-6DOI Listing
June 2021

An Insight into Giant Cell Arteritis Pathogenesis: Evidence for Oxidative Stress and SIRT1 Downregulation.

Antioxidants (Basel) 2021 May 31;10(6). Epub 2021 May 31.

Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Firenze, 50134 Firenze, Italy.

Giant cell arteritis (GCA), medium and large vessel granulomatous vasculitis affecting the elderly, is characterized by a multitude of vascular complications, including venous thrombosis, myocardial infraction and stroke. The formation of granulomatous infiltrates and the enhanced accumulation of proinflammatory cytokines are typical features of this condition. The GCA pathogenesis remains largely unknown, but recent studies have suggested the involvement of oxidative stress, mainly sustained by an enhanced reactive oxygen species (ROS) production by immature neutrophils. On this basis, in the present study, we intended to evaluate, in GCA patients, the presence of systemic oxidative stress and possible alterations in the expression level of nuclear sirtuins, enzymes involved in the inhibition of inflammation and oxidative stress. Thirty GCA patients were included in the study and compared to 30 healthy controls in terms of leukocyte ROS production, oxidative stress and SIRT1 expression. Our results clearly indicated a significant increase ( < 0.05) both in the ROS levels in the leukocyte fractions and plasma oxidative stress markers (lipid peroxidation and total antioxidant capacity) in the GCA patients compared to the healthy controls. In PBMCs from the GCA patients, a significant decrease in SIRT1 expression ( < 0.05) but not in SIRT6 and SIRT7 expression was found. Taken together, our preliminary findings indicate that, in GCA patients, plasma oxidative stress is paralleled by a reduced SIRT1 expression in PBMC. Further studies are needed to highlight if and how these alterations contribute to GCA pathogenesis.
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http://dx.doi.org/10.3390/antiox10060885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229481PMC
May 2021

Prognostic Factors and Long-Term Outcome with ANCA-Associated Kidney Vasculitis in Childhood.

Clin J Am Soc Nephrol 2021 May 26. Epub 2021 May 26.

G Montini, Department of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico , Milan, Italy.

Background And Objectives: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is extremely rare in children. We report the clinico-pathological features, long-term outcomes, and prognostic factors of a large paediatric cohort of patients with ANCA-associated kidney vasculitis.

Design, Setting, Participants, And Measurements: This retrospective study included 85 consecutive patients with kidney biopsy-proven ANCA-associated vasculitis followed at tertiary referral centres in Italy and Canada. Kidney biopsies were categorised as focal, crescentic, sclerotic or mixed following Berden's classification. The prognostic significance of baseline clinical, laboratory and histological findings was analysed with respect to kidney failure or chronic kidney disease (CKD) 3-5/kidney failure.

Results: Fifty-three patients had microscopic polyangiitis (62%) and 32 granulomatosis with polyangiitis (38%). Rapidly progressive glomerulonephritis was the most frequent presentation (39%); one third of the patients also had nephrotic-range proteinuria. Kidney biopsies were classified as focal in 21% of the patients, crescentic in 51%, sclerotic in 15% and mixed in 13%. Remission-induction therapies included cyclophosphamide in 78% of cases. Twenty-five patients (29%) reached kidney failure. The median time to kidney failure or last follow-up was 35 months (6-89) in the whole cohort, and 73 months (24-109) among the patients who did not reach this outcome. Cases with sclerotic histology showed significantly shorter kidney survival [HR 11.80 (95% CI 2.49-55.99)] and CKD 3-5-free survival [HR 8.88 (95% CI 2.43-32.48)] as compared with focal/mixed ones. Baseline eGFR, low serum albumin, hypertension, central nervous system complications and sclerotic histology, which reflected severe kidney involvement, were associated with both kidney failure or CKD stage 3-5/kidney failure at unadjusted analysis; no independent prognostic factors emerged at multivariate analysis.

Conclusions: Children with ANCA-associated kidney vasculitis often have aggressive presentation; one-third of them progress to kidney failure and usually do so early during the follow-up. A severe renal presentation is associated with the development of CKD or kidney failure.
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http://dx.doi.org/10.2215/CJN.19181220DOI Listing
May 2021

Treatment of Behçet's Disease: An Algorithmic Multidisciplinary Approach.

Front Med (Lausanne) 2021 28;8:624795. Epub 2021 Apr 28.

Ophthalmology Center, Aishin Memorial Hospital, Sapporo, Japan.

Behçet's disease (BD) is a chronic, relapsing inflammatory, multisystem disease of unknown etiology. The disease has a wide clinical spectrum of mucocutaneous lesions and ocular, vascular, articular, neurologic, gastrointestinal and cardiac involvement. Although the number of effective drugs used in the disease's treatment has increased in recent years, BD is still associated with severe morbidity because of mainly mucocutaneous, articular and ocular symptoms and an increased mortality because of large vessel, neurological, gastrointestinal and cardiac involvement. Many factors are associated with a more serious course, such as male gender and a younger age of onset. While the severity of the disease is more pronounced in the first years of the disease, it decreases in most patients after the age of forties. The primary goal of treatment should be the prevention of irreversible organ damage. Therefore, early diagnosis and appropriate treatment and close follow-up are mandatory to reduce the morbidity and mortality of the disease. Treatment varies depending on the organ involved and the severity of the involvement. For all these reasons, the treatment should be personalized and arranged with a multidisciplinary approach according to the organs involved. Treatment is mainly based on suppression of the inflammatory attacks of the disease using local and systemic immunomodulatory and immunosuppressive drugs. In this review, based on the mainly controlled studies and personal experience in clinical practice and basic research in this field, we propose a stepwise, symptom-based, algorithmic approach for the management of BD with a holistic perspective.
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http://dx.doi.org/10.3389/fmed.2021.624795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115406PMC
April 2021

Drug survival of anakinra and canakinumab in monogenic autoinflammatory diseases: observational study from the International AIDA Registry.

Rheumatology (Oxford) 2021 May 7. Epub 2021 May 7.

Research Center of Systemic Auto inflammatory Diseases and Behçet's Disease and Rheumatology-Ophthalmology Collaborative Uveitis Center, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.

Objectives: To investigate survival of interleukin (IL)-1 inhibitors in monogenic autoinflammatory disorders (mAID) through drug retention rate (DRR) and identify potential predictive factors of drug survival from a real-life perspective.

Patients And Methods: Multicentre retrospective study analyzing patients affected by the most common mAID treated with anakinra or canakinumab. Survival curves were analyzed with the Kaplan-Meier method. Statistical analysis included a Cox-proportional hazard model to detect factors responsible for drug discontinuation.

Results: Seventy-eight patients for a total of 102 treatment regimens were enrolled. The mean treatment duration was 29.59 months. The estimated DRR of IL-1 inhibitors at 12, 24, and 48 months of follow-up was 75.8%, 69.7% and 51.1%, respectively. Patients experiencing an adverse event had a significantly lower DRR (p = 0.019). In contrast, no significant differences were observed between biologic-naïve patients and those previously treated with biologic drugs (p = 0.985) Patients carrying high-penetrance mutations exhibited a significantly higher DRR compared with those with low-penetrance variants (p = 0.015). Adverse events were the only variable associated with a higher hazard of treatment withdrawal (HR 2.573 [CI: 1.223-5.411], p = 0.013) on regression analysis. A significant glucorticoid-sparing effect was observed (p < 0.0001).

Conclusions: IL-1 inhibitors display an excellent long-term effectiveness in terms of DRR, and their survival is not influenced by the biologic line of treatment. They display a favorable safety profile, that deserves however a close monitoring given its impact on treatment continuation. Special attention should be paid to molecular diagnosis and mutation penetrance, as patients carrying low-penetrance variants are more likely to interrupt treatment.
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http://dx.doi.org/10.1093/rheumatology/keab419DOI Listing
May 2021

Baseline characteristics of systemic lupus erythematosus patients included in the Lupus Italian Registry of the Italian Society for Rheumatology.

Lupus 2021 Jul 22;30(8):1233-1243. Epub 2021 Apr 22.

Rheumatology Unit, University of Padova, Padova, Italy.

Objective: To report baseline data of SLE patients enrolled in the Lupus Italian Registry (LIRE).

Methods: Patients affected by SLE aged ≥ 16 years were consecutively recruited in a multicenter prospective study comparing two cohorts: patients starting biologic immunosuppressants (BC) and patients starting non-biologic immunosuppresants (NBC).

Results: 308 patients were enrolled, 179 in NBC and 129 in BC. Mean age at disease onset and at diagnosis was significantly higher in NBC (p = 0.023, p = 0.045, respectively). Disease duration was longer in BC (p = 0.022). Patients in BC presented arthritis more frequently (p = 0.024), those in NBC nephropathy (p = 0.03). Quality of life was worse in BC (p = 0.031). Anti-dsDNA, low C3, were significantly more frequent in BC (p < 0.001, p = 0.009, respectively). Mycophenolate, methotrexate and azathioprine were the drugs more frequently prescribed in NBC, Belimumab and Rituximab in BC.

Conclusion: The predominant organ involvement was different in the two cohorts: kidney involvement predominated in NBC, joint involvement in BC. Despite the younger age at disease onset, patients of the BC had a longer disease duration and more frequently had taken a cumulative prednisone dosage greater than 10 g. Even the pattern of clinical manifestations inducing to prescribe biological rather than conventional immunosuppressants was quite different.Keywords: Autoantibody(ies), autoimmune disease, belimumab, cohort studies, glucocorticoids, immunosuppressants, rituximab, systemic lupus erythematosus.
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http://dx.doi.org/10.1177/09612033211012470DOI Listing
July 2021

Microarray evaluation of allergen-specific IgE in eosinophilic granulomatosis with polyangiitis.

Ann Rheum Dis 2021 Apr 21. Epub 2021 Apr 21.

Biomedical Experimental and Clinical Sciences, University of Florence, Firenze, Italy

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http://dx.doi.org/10.1136/annrheumdis-2021-220111DOI Listing
April 2021

Clinical profile and evolution of patients with juvenile-onset Behçet's syndrome over a 25-year period: insights from the AIDA network.

Intern Emerg Med 2021 Apr 9. Epub 2021 Apr 9.

Research Center of Systemic Auto Inflammatory Diseases, Behçet's Disease and Rheumatology-Ophthalmology Collaborative Uveitis Center, Rheumatology Unit, Policlinico "Le Scotte", Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Viale Bracci 16, 53100, Siena, Italy.

Behçet's syndrome (BS) represents an understudied topic in pediatrics: the main aims of our study were to characterize demographic and clinical features of a cohort of BS patients with juvenile-onset managed in three tertiary referral centers in Italy, evaluate their evolution in the long-term, and detect any potential differences with BS patients having an adult-onset. Medical records of 64 juvenile-onset and 332 adult-onset BS followed-up over a 2-year period were retrospectively analyzed and compared. Mean age ± SD of first symptom-appearance was 10.92 ± 4.34 years with a female-to-male ratio of 1.06:1. Mucocutaneous signs were the most frequent initial manifestations, followed by uveitis. Throughout the disease course, genital aphthae (76.56%) and pseudofolliculitis (40.63%) prevailed among the mucocutaneous signs, while major organ involvement was represented by gastrointestinal and ocular involvement (43.75 and 34.38%, respectively). No significant differences emerged for both mucocutaneous signs and specific major organ involvement between juvenile-onset and adult BS patients. After excluding nonspecific abdominal pain, juvenile-onset BS patients were less frequently characterized by the development of major organ involvement (p = 0.027). Logistic regression detected the juvenile-onset as a variable associated with reduced risk of long-term major organ involvement (OR 0.495 [0.263-0.932], p = 0.029). In our cohort, juvenile-onset BS resembled the clinical spectrum of adult-onset patients. Pediatric patients with a full-blown disease at onset showed a more frequent mucocutaneous involvement. In addition, patients with juvenile-onset seemed to develop less frequently major organ involvement and had an overall less severe disease course.
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http://dx.doi.org/10.1007/s11739-021-02725-9DOI Listing
April 2021

Neutrophil Extracellular Traps in the Autoimmunity Context.

Front Med (Lausanne) 2021 22;8:614829. Epub 2021 Mar 22.

Laboratory of Molecular Nephrology, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

The formation of neutrophil extracellular traps (NETs) is a strategy utilized by neutrophils for capturing infective agents. Extracellular traps consist in a physical net made of DNA and intracellular proteins externalized from neutrophils, where bacteria and viruses are entrapped and killed by proteolysis. A complex series of events contributes to achieving NET formation: signaling from infectious triggers comes first, followed by decondensation of chromatin and extrusion of the nucleosome components (DNA, histones) from the nucleus and, after cell membrane breakdown, outside the cell. NETs are composed of either DNA or nucleosome proteins and hundreds of cytoplasm proteins, a part of which undergo post-translational modification during the steps leading to NETs. There is a thin balance between the production and the removal of circulating NETs from blood where digestion of DNA by circulating DNases 1 and IL3 has a critical role. A delay in NET removal may have consequences for autoimmunity. Recent studies have shown that circulating NET levels are increased in systemic lupus erythematosus (SLE) for a functional block of NET removal mediated by anti-DNase antibodies or, in rare cases, by DNase IL3 mutations. In SLE, the persistence in circulation of NETs signifies elevated concentrations of either free DNA/nucleosome components and oxidized proteins that, in some cases, are recognized as non-self and presented to B-cells by Toll-like receptor 9 (TLR9). In this way, it is activated as an immunologic response, leading to the formation of IgG2 auto-antibody. Monitoring serum NET levels represents a potential new way to herald the development of renal lesions and has clinical implications. Modulating the balance between NET formation and removal is one of the objectives of basic research that are aimed to design new drugs for SLE. The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).
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http://dx.doi.org/10.3389/fmed.2021.614829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019736PMC
March 2021

Occupational Exposures and Smoking in Eosinophilic Granulomatosis With Polyangiitis: A Case-Control Study.

Arthritis Rheumatol 2021 Mar 22. Epub 2021 Mar 22.

University of Florence,, Florence, Italy.

Objective: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Environmental agents and occupational exposures may confer susceptibility to EGPA, but data are scarce. This study was undertaken to investigate the association between occupational exposures (e.g., silica, farming, asbestos, and organic solvents) and other environmental agents (e.g., smoking) and the risk of EGPA.

Methods: Patients with newly diagnosed EGPA (n = 111) and general population controls (n = 333) who were matched for age, sex, and geographic area of origin were recruited at a national referral center for EGPA. Exposures were assessed using a dedicated questionnaire administered by a specialist in occupational medicine, under blinded conditions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results: Exposures to silica (OR 2.79 [95% CI 1.55-5.01], P = 0.001), organic solvents (OR 3.19 [95% CI 1.91-5.34], P < 0.001), and farming (OR 2.71 [95% CI 1.71-4.29], P < 0.001) were associated with an increased risk of EGPA. Co-exposure to silica and farming yielded an OR of 9.12 (95% CI 3.06-27.19, P < 0.001), suggesting a multiplicative effect between these 2 exposures. Smoking (current and former smokers combined) was significantly less frequent among patients with EGPA compared to controls (OR 0.49 [95% CI 0.29-0.70], P < 0.001). The pack-year index was also lower among patients with EGPA (OR 0.96 [95% CI 0.94-0.98], P < 0.001). The association of silica and farming was primarily aligned with ANCA-positive EGPA, while the association of smoking status and organic solvents was primarily aligned with ANCA-negative EGPA.

Conclusion: The environment can influence susceptibility to EGPA. Exposure to silica, farming, or organic solvents is associated with an increased risk of EGPA, while smoking is associated with a lower risk. These exposures seem to have distinct effects on different EGPA subsets.
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http://dx.doi.org/10.1002/art.41722DOI Listing
March 2021

Eosinophilic Granulomatosis With Polyangiitis: Dissecting the Pathophysiology.

Front Med (Lausanne) 2021 24;8:627776. Epub 2021 Feb 24.

Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare multisystemic disease classified both amongst hypereosinophilic disorders and ANCA-associated vasculitis. Vessel inflammation and eosinophilic proliferation are the hallmarks of the disease and main effectors of organ damage. Two distinct disease phenotypes have classically been described according to ANCA-status: the ANCA-negative subset with eosinophil-driven manifestation and the ANCA-positive one with vasculitic manifestations. An analogous dichotomization has also been backed by histological findings and a distinct genetic background. EGPA is typically consider a Th2-mediated disease and blood and tissue eosinophilia represent the cornerstone of diagnosis. Besides, ANCA are known for inducing endothelial injury and vascular inflammation by activating the circulating neutrophils. Thus, the pathogenesis of EGPA seems to be mediated by two coexisting mechanisms. However, the verbatim application of this strict dualism cannot always be translated into routine clinical practice. In the present review we describe the current knowledge on the eosinophilic and ANCA-mediated aspects of EGPA pathogenesis. Finally, we review the rationale of the currently proposed EGPA dichotomy and future research perspectives.
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http://dx.doi.org/10.3389/fmed.2021.627776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943470PMC
February 2021

Direct oral anticoagulant for venous thrombosis in Behçet's syndrome.

Autoimmun Rev 2021 Apr 17;20(4):102783. Epub 2021 Feb 17.

Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR S 959, Immunology-Immunopathology- Immunotherapy (I3), F-75005, Paris, France; Immunology-Immunopathology-Immunotherapy (i3) Laboratory, INSERM UMR-S 959, Sorbonne Université, 75005 Paris, France; Biotherapy Unit (CIC-BTi), Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP), 75013 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2021.102783DOI Listing
April 2021

Epidemiology of systemic sclerosis: a multi-database population-based study in Tuscany (Italy).

Orphanet J Rare Dis 2021 02 17;16(1):90. Epub 2021 Feb 17.

Institute of Clinical Physiology, National Research Council, Via Moruzzi 1, Pisa, Italy.

Background: Systemic Sclerosis (SSc) is a chronic autoimmune disease with a complex pathogenesis that includes vascular injury, abnormal immune activation, and tissue fibrosis. We provided a complete epidemiological characterization of SSc in the Tuscany region (Italy), considering prevalence and incidence, survival, comorbidities and drug prescriptions, by using a multi-database population-based approach. Cases of SSc diagnosed between 1st January 2003 and 31st December 2017 among residents in Tuscany were collected from the population-based Rare Diseases Registry of Tuscany. All cases were linked to regional health and demographic databases to obtain information about vital statistics, principal causes of hospitalization, complications and comorbidities, and drug prescriptions.

Results: The prevalence of SSc in Tuscany population resulted to be 22.2 per 100,000, with the highest prevalence observed for the cases aged ≥ 65 years (33.2 per 100,000, CI 95% 29.6-37.3). In females, SSc was predominant (86.7% on the total) with an overall sex ratio F/M of 6.5. Nevertheless, males presented a more severe disease, with a lower survival and significant differences in respiratory complications and metabolic comorbidities. Complications and comorbidities such as pulmonary involvement (HR = 1.66, CI 95% 1.17-2.35), congestive heart failure (HR = 2.76, CI 95% 1.80-4.25), subarachnoid and intracerebral haemorrhage (HR = 2.33, CI 95% 1.21-4.48) and malignant neoplasms (HR = 1.63, CI 95% 1.06-2.52), were significantly associated to a lower survival, also after adjustment for age, sex and other SSc-related complications. Disease-modifying antirheumatic drugs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors were the drugs with the more increasing prevalence of use in the 2008-2017 period.

Conclusions: The multi-database approach is important in the investigation of rare diseases where it is often difficult to provide accurate epidemiological indicators. A population-based registry can be exploited in synergy with health databases, to provide evidence related to disease outcomes and therapies and to assess the burden of disease, relying on a large cohort of cases. Building an integrated archive of data from multiple databases linking a cohort of patients to their comorbidities, clinical outcomes and survival, is important both in terms of treatment and prevention.
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http://dx.doi.org/10.1186/s13023-021-01733-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890847PMC
February 2021

Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome.

Clin Kidney J 2021 Jan 6;14(1):332-340. Epub 2020 Sep 6.

Department of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Firenze, and Nephrology Unit, Meyer Children's Hospital, Firenze, Italy.

Background: Although rapidly progressive glomerulonephritis is the main renal phenotype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), slow renal disease progression is sometimes observed. These forms have been rarely discussed; we analysed their prevalence, clinico-pathological characteristics and outcome.

Methods: We screened patients with microscopic  polyangiitis (MPA) and granulomatosis with polyangiitis followed at seven referral centres and selected those with estimated glomerular filtration rate (eGFR) reduction <50% over a 6-month period preceding diagnosis. Data regarding patient features and response to treatment were retrieved.

Results: Of 856 patients, 41 (5%) had slowly progressive renal AAV. All had MPA and all but one was P-ANCA/myeloperoxidase (MPO) ANCA-positive. At diagnosis, the median age was 70 years [interquartile range (IQR) 64-78] and extra-renal manifestations were absent or subclinical (interstitial lung lesions in 10, 24%). The median (IQR) eGFR was 23 mL/min/1.73 m (15-35); six patients (15%) had started renal replacement therapy (RRT). All had proteinuria (median 1180 mg/24 h, IQR 670-2600) and micro-haematuria. Main histologic findings were extracapillary proliferation at chronic stages and glomerulosclerosis; following Berden's classification, 6/28 biopsies (21%) were 'focal', 1/28 (4%) 'crescentic', 9/28 (32%) 'mixed' and 12/28 (43%) 'sclerotic'. At last follow-up (median 32 months, IQR 12-52), 20/34 patients (59%) treated with immunosuppression had eGFR improvement >25% as compared with diagnosis, while 4/34 (12%) had started RRT.

Conclusions: AAV may present with slow renal disease progression; this subset is hallmarked by advanced age at diagnosis, positive MPO-ANCA, subclinical interstitial lung lesions and chronic damage at kidney biopsy. Partial renal recovery may occur following immunosuppression.
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http://dx.doi.org/10.1093/ckj/sfaa139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857823PMC
January 2021

Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases.

Autoimmun Rev 2021 Mar 20;20(3):102763. Epub 2021 Jan 20.

Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA. Electronic address:

The interleukin (IL)-1 family member IL-1α is a ubiquitous and pivotal pro-inflammatory cytokine. The IL-1α precursor is constitutively present in nearly all cell types in health, but is released upon necrotic cell death as a bioactive mediator. IL-1α is also expressed by infiltrating myeloid cells within injured tissues. The cytokine binds the IL-1 receptor 1 (IL-1R1), as does IL-1β, and induces the same pro-inflammatory effects. Being a bioactive precursor released upon tissue damage and necrotic cell death, IL-1α is central to the pathogenesis of numerous conditions characterized by organ or tissue inflammation. These include conditions affecting the lung and respiratory tract, dermatoses and inflammatory skin disorders, systemic sclerosis, myocarditis, pericarditis, myocardial infarction, coronary artery disease, inflammatory thrombosis, as well as complex multifactorial conditions such as COVID-19, vasculitis and Kawasaki disease, Behcet's syndrome, Sjogren Syndrome, and cancer. This review illustrates the clinical relevance of IL-1α to the pathogenesis of inflammatory diseases, as well as the rationale for the targeted inhibition of this cytokine for treatment of these conditions. Three biologics are available to reduce the activities of IL-1α; the monoclonal antibody bermekimab, the IL-1 soluble receptor rilonacept, and the IL-1 receptor antagonist anakinra. These advances in mechanistic understanding and therapeutic management make it incumbent on physicians to be aware of IL-1α and of the opportunity for therapeutic inhibition of this cytokine in a broad spectrum of diseases.
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http://dx.doi.org/10.1016/j.autrev.2021.102763DOI Listing
March 2021

Comparison of treatments for the prevention of fetal growth restriction in obstetric antiphospholipid syndrome: a systematic review and network meta-analysis.

Intern Emerg Med 2021 Aug 21;16(5):1357-1367. Epub 2021 Jan 21.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Women with criteria and non-criteria obstetric antiphospholipid syndrome (APS) carry an increased risk of pregnancy complications, including fetal growth restriction (FGR). The management of obstetric APS traditionally involves clinicians, obstetricians and gynaecologists; however, the most appropriate prophylactic treatment strategy for FGR prevention in APS is still debated. We performed a systematic review and network meta-analysis (NetMA) to summarize current evidence on pharmacological treatments for the prevention of FGR in APS. We searched PubMed and Embase from inception until July 2020, for randomized controlled trials and prospective studies on pregnant women with criteria or non-criteria obstetric APS. NetMA using a frequentist framework were conducted for the primary outcome (FGR) and for secondary outcomes (fetal or neonatal death and preterm birth). Adverse events were narratively summarised. Out of 1124 citations, we included eight studies on 395 pregnant patients with obstetric APS treated with low-dose aspirin (LDA) + unfractionated heparin (UFH) (n = 132 patients), LDA (n = 115), LDA + low molecular weight heparin (n = 100), LDA + corticosteroids (n = 29), LDA + UFH + intravenous immunoglobulin (n = 7), or untreated (n = 12). No difference among treatments emerged in terms of FGR prevention, but estimates were largely imprecise, and most studies were at high/unclear risk of bias. An increased risk of fetal or neonatal death was found for LDA monotherapy as compared to LDA + heparin, and for no treatment as compared to LDA + corticosteroids. The risk of preterm birth was higher for LDA + UFH + IVIg as compared to LDA or LDA + heparin, and for LDA + corticosteroids as compared to LDA or LDA + LMWH. No treatment was associated with an increased risk of bleeding, thrombocytopenia or osteopenia.
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http://dx.doi.org/10.1007/s11739-020-02609-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310508PMC
August 2021

Pharmacological Interventions for the Prevention of Fetal Growth Restriction: A Systematic Review and Network Meta-Analysis.

Clin Pharmacol Ther 2021 07 26;110(1):189-199. Epub 2021 Feb 26.

Department of Neurosciences, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy.

The prevention of fetal growth restriction (FGR) is challenging in clinical practice. To date, no meta-analysis summarized evidence on the relative benefits and harms of pharmacological interventions for FGR prevention. We performed a systematic review and network meta-analysis (NetMA), searching PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception until November 2019. We included clinical trials and observational studies on singleton gestating women evaluating antiplatelet, anticoagulant, or other treatments, compared between each other or with controls (placebo or no treatment), and considering the pregnancy outcome FGR (primary outcome of the NetMA). Secondary efficacy outcomes included preterm birth, placental abruption, and fetal or neonatal death. Safety outcomes included bleeding and thrombocytopenia. Network meta-analyses using a frequentist framework were conducted to derive odds ratios (ORs) and 95% confidence intervals (CIs). Of 18,780 citations, we included 30 studies on 4,326 patients. Low molecular weight heparin (LMWH), alone or associated with low-dose aspirin (LDA), appeared more efficacious than controls in preventing FGR (OR 2.00, 95% CI 1.27-3.16 and OR 2.67, 95% CI 1.21-5.89 for controls vs. LMWH and LDA + LMWH, respectively). No difference between active treatments emerged in terms of FGR prevention, but estimates for treatments other than LMWH +/- LDA were imprecise. Only the confidence in the evidence regarding LMWH vs. controls was judged as moderate, according to the Confidence in Network Meta-Analysis framework. No treatment was associated with an increased risk of bleeding, although estimates were precise enough only for LMWH. These results should inform clinicians on the benefits of active pharmacological prophylaxis for FGR prevention.
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http://dx.doi.org/10.1002/cpt.2164DOI Listing
July 2021

Dissecting the clinical heterogeneity of adult-onset Still's disease, results from a multi-dimensional characterisation and stratification.

Rheumatology (Oxford) 2021 Jan 6. Epub 2021 Jan 6.

Department of Biotechnological and Applied Clinical Sciences, Rheumatology Unit, University of L'Aquila, L'Aquila, Italy.

Objectives: To stratify adult-onset Still's disease (AOSD) patients in distinct clinical subsets to be differently managed, by using a multi-dimensional characterisation.

Methods: AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, laboratory markers systemic score, and outcomes. The squared Euclidean distances between each pair of patients were calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusters were descriptively analysed for any possible difference.

Results: Four AOSD patients clusters have been identified. Disease onset in cluster 1 was characterised by fever (100%), skin rash (92%), and arthritis (83%) with the highest ferritin levels (14724 ± 6837 ng/ml). In cluster 2 the onset was characterised by fever (100%), arthritis (100%), and liver involvement (90%) together with the highest CRP levels (288.10 ± 46.01 mg/l). The patients in cluster 3 presented with fever (100%), myalgia (96%), and sore throat (92%). The highest systemic score values (8.88 ± 1.70) and the highest mortality rate (54.2%) defined cluster 3. Fever (100%) and arthritis (90%) were the symptoms at the onset in cluster 4, which was characterized by the lowest ferritin and CRP levels (1457 ± 1298 ng/ml; 54.98 ± 48.67 mg/l).

Conclusion: Four distinct phenotypic subgroups in AOSD could be suggested possibly associated with different genetic background and pathogenic mechanisms. Our results could provide the basis for a precision medicine approach in AOSD, trying to find a clinical and laboratory multidimensional stratification and characterisation, which would drive a tailored therapeutic approach in these patients.
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http://dx.doi.org/10.1093/rheumatology/keaa904DOI Listing
January 2021

Serum IgG2 antibody multicomposition in systemic lupus erythematosus and lupus nephritis (Part 1): cross-sectional analysis.

Rheumatology (Oxford) 2021 Jul;60(7):3176-3188

Division of Nephrology and Dialysis, University of Brescia and Ospedale di Montichiari, Brescia.

Objectives: Serum anti-dsDNA and anti-nucleosome IgGs have been proposed as signatures for SLE and LN in limited numbers of patients. We sought to show higher sensitivity and specificity of the same antibodies with the IgG2 isotype and included IgG2 antibodies vs specific intracellular antigens in the analysis.

Methods: A total of 1052 SLE patients with (n = 479) and without (n = 573) LN, recruited at different times from the beginning of symptoms, were included in the study. Patients with primary APS (PAPS, n = 24), RA (RA, n = 24) and UCTD (UCTD, n = 96) were analysed for comparison. Anti-nucleosome (dsDNA, Histone2A, Histone3), anti-intracellular antigens (ENO1), anti-annexin A1 and anti-C1q IgG2 were determined by non-commercial techniques.

Results: The presence in the serum of the IgG2 panel was highly discriminatory for SLE/LN vs healthy subjects. Serum levels of anti-dsDNA and anti-C1q IgG2 were more sensitive than those of IgGs (Farr radioimmunoassay/commercial assays) in identifying SLE patients at low-medium increments. Of more importance, serum positivity for anti-ENO1 and anti-H2A IgG2 discriminated between LN and SLE (ROC T0-12 months), and high levels at T0-1 month were detected in 63% and 67%, respectively, of LN, vs 3% and 3%, respectively, of SLE patients; serum positivity for each of these was correlated with high SLEDAI values. Minor differences existed between LN/SLE and the other rheumatologic conditions.

Conclusion: Nephritogenic IgG2 antibodies represent a specific signature of SLE/LN, with a few overlaps with other rheumatologic conditions. High levels of anti-ENO1 and anti-H2A IgG2 correlated with SLE activity indexes and were discriminatory between SLE patients limited to the renal complication and other SLE patients.

Trial Registration: The Zeus study was registered at https://clinicaltrials.gov, NCT02403115.
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http://dx.doi.org/10.1093/rheumatology/keaa767DOI Listing
July 2021

Cardiac involvement in eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome): Prospective evaluation at a tertiary referral centre.

Eur J Intern Med 2021 Mar 23;85:68-79. Epub 2020 Dec 23.

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis. Cardiac specific involvement (CSI) is caused by coronary artery vasculitis, but also by myocardial eosinophilic infiltration. To date, the prevalence of CSI associated with EGPA is unresolved. Aim of this study was to systematically assess the prevalence and clinical impact of CSI in a consecutive outpatient EGPA population.

Methods: Between October 2018 and July 2019, we prospectively enrolled 52 consecutive EGPA patients. All underwent comprehensive evaluation including a standardized questionnaire, physical examination, 12-lead-ECG, echocardiography. Cardiac magnetic resonance and 24 h-Holter were performed as deemed clinically appropriate. Cardiac abnormalities were defined as CSI based on the likelihood of their relation to EGPA vasculitis, after exclusion of alternative diagnoses.

Results: 52 enrolled patients, mean age 59±1 years. Thirteen of the 52 patients (25%) were classified as CSI+. CSI was characterized by myocarditis in four patients, non-scar-related regional wall motions abnormalities (RWMA) in three, apical thrombosis in two (one also had RWMA), pericarditis in three and non-atherosclerotic coronary disease (Prinzmetal angina and coronaritis) in 2. Five (38%) of the 13 CSI+ patients, presented an apical aneurysm. Peak eosinophil count at diagnosis was higher in CSI+: 8000 /μl vs CSI-: 3000 /μl, p = 0.017. Overall, 2 patients had severe LV dysfunction, 5 required urgent hospitalization and 8 required long-term cardioactive therapy.

Conclusions: CSI was present in one-quarter of patients, often associated with high peak eosinophils. Myocarditis, RWMA and apical aneurysms were the most common manifestations. Although rarely severe and life-threatening, CSI often required long-term cardioactive treatment.
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http://dx.doi.org/10.1016/j.ejim.2020.12.008DOI Listing
March 2021

Serum IgG2 antibody multi-composition in systemic lupus erythematosus and in lupus nephritis (Part 2): prospective study.

Rheumatology (Oxford) 2021 Jul;60(7):3388-3397

Nephrology and Dialysis Unit, University of Messina and G Martino Hospital, Messina, Italy.

Objectives: Circulating anti-ENO1 and anti-H2A IgG2 have been identified as specific signatures of LN in a cross-over approach. We sought to show whether the same antibodies identify selected population of patients with LN with potentially different clinical outcomes.

Methods: Here we report the prospective analysis over 36 months of circulating IgG2 levels in patients with newly diagnosed LN (n=91) and SLE (n=31) and in other patients with SLE recruited within 2 years from diagnosis (n=99). Anti-podocyte (ENO1), anti-nucleosome (DNA, histone 2 A, histone 3) and anti-circulating proteins (C1q, AnnexinA1-ANXA1) IgG2 antibodies were determined by home-made techniques.

Results: LN patients were the main focus of the study. Anti-ENO1, anti-H2A and anti-ANXA1 IgG2 decreased in parallel to proteinuria and normalized within 12 months in the majority of patients while anti-dsDNA IgG2 remained high over the 36 months. Anti-ENO1 and anti-H2A had the highest association with proteinuria (Heat Map) and identified the highest number of patients with high proteinuria (68% and 71% respectively) and/or with reduced estimated glomerula filtration rate (eGFR) (58% for both antibodies) compared with 23% and 17% of anti-dsDNA (agreement analysis). Anti-ENO1 positive LN patients had higher proteinuria than negative patients at T0 and presented the maximal decrement within 12 months.

Conclusions: Anti-ENO1, anti-H2A and anti-ANXA1 antibodies were associated with high proteinuria in LN patients and Anti-ENO1 also presented the maximal reduction within 12 months that paralleled the decrease of proteinuria. Anti-dsDNA were not associated with renal outcome parameters. New IgG2 antibody signatures should be utilized as tracers of personalized therapies in LN.

Trial Registration: The Zeus study was registered at https://clinicaltrials.gov (study number: NCT02403115).
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http://dx.doi.org/10.1093/rheumatology/keaa793DOI Listing
July 2021

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

Occurrence and predictive factors of high blood pressure, type 2 diabetes, and metabolic syndrome in rheumatoid arthritis: findings from a 3-year, multicentre, prospective, observational study.

Clin Exp Rheumatol 2020 Dec 4. Epub 2020 Dec 4.

Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Italy.

Objectives: In rheumatoid arthritis (RA), "traditional" cardiovascular (CV) risk factors continue to be underdiagnosed and undertreated, thus increasing the risk of developing atherosclerosis. In this work, we evaluated the occurrence and predictive factors of "traditional" cardiovascular risk factors, with a focus on high blood pressure (HBP), type 2 diabetes (T2D), and metabolic syndrome (MetS), in participants with RA, in a 3-year, multicentre, prospective, observational study.

Methods: To assess the occurrence and predictive factors of HBP, T2D, and MetS, consecutive participants with RA, admitted to Italian Rheumatology Units, were evaluated in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort, a 3-year, multicentre, prospective, observational study.

Results: In the present evaluation, 841 participants, who were fully followed up with 3-year of prospective follow-up were assessed. At the end of follow-up, a significant increased incidence of HBP, T2D, and MetS was recorded. Assessing predictive factors, the mean values of C-reactive protein during the follow-up were independent predictors of occurrence of those comorbidities, whereas participants maintaining remission showed a significant lower risk. Furthermore, therapy with hydroxychloroquine (HCQ) reduced the risk of occurrence of T2D and MetS.

Conclusions: An increased incidence of HBP, T2D, and MetS was observed in assessed participants, prospectively followed-up. Furthermore, the analysis of predictive factors suggested that the rheumatoid pro-inflammatory process could increase the occurrence of these comorbidities. Conversely, metabolic and cardiovascular benefits of maintaining remission as well as of therapy with HCQ were reported.
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December 2020

Editorial: "Toward Precision Medicine in Vasculitis".

Front Immunol 2020 17;11:616221. Epub 2020 Nov 17.

Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria.

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http://dx.doi.org/10.3389/fimmu.2020.616221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705214PMC
June 2021
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