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Connective tissue diseases are known to be one of the causes of organising pneumonia (OP). However, this association is rare and signs of OP usually occur in the context of an already diagnosed disease. We report three cases of OP preceding the articular symptoms of the underlying connective tissue disease by 3–6 months in two cases of rheumatoid arthritis and by 36 months in one patient with primary Sjögren's syndrome. The diagnosis of post-infectious OP had initially been suspected in the three cases and the patients had not been followed up further. The occurrence of OP preceding articular or any other extrapulmonary involvement of connective tissue disease had been reported in only four cases in the literature and, to our knowledge, no case preceding Sjögren's syndrome had ever been reported. These observations suggest that exhaustive investigations should be considered when OP is diagnosed, including antinuclear auto-antibodies and investigations for Sjögren's syndrome, even when there are no clinical signs suggesting an underlying connective tissue disease. These investigations should also be repeated during the course of the disease, especially in the case of OP continuing to progress under treatment and, of course, if signs of connective tissue disease appear.

Introduction & Objectives: This study aimed to characterize the whole phenotype of Systemic sclerosis (SSc) patients with sicca symptoms, using major salivary glands Ultrasound (SGUS) parameters, minor salivary glands biopsies (mSGB) and clinical findings, and to compare these characteristics with those from patients with Sjogren's Disease (SjD), and patients with sicca manifestations from other causes., Methods: Sixty SSc patients fulfilling the 2013 ACR/EULAR classification criteria and with subjective self-declared sicca symptoms were consecutively recruited and had SGUS and mSGB. Fifteen SSc patients without subjective sicca symptoms and 65 patients with sicca symptoms from other causes (including 37 SjD with no SSc)., Results: SSc patients with subjective sicca symptoms had frequent objective clinical (up to 83 %), histological (44 % of Focus score≥1/ mm2) and US anomalies (63 % of OMERACT ≥2). 53 % patients without subjective clinical complaint also had abnormal objective tests, suggesting the existence of a sub clinical involvement of salivary glands in SSc. SjD-SSc patients had more severe glandular involvement as compared to patients with isolated SjD and isolated Sicca-SSc patients (70%, 48,6 % and 38% of patients with OMERACT ≥2 respectively) suggesting additive impact of both diseases on glandular physiology and structure., Conclusion: SjD-SSc overlap have more severe sicca features as compared to isolated sicca-SSc and isolated SjD, suggesting a specific impact of SSc on salivary gland physiology. Further translational studies are needed to identify the underlying pathways that could serve as therapeutic targets., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Antoinette PERLAT declares 1 Oral presentation , with paiement on Behçet disease 04.24 ( AMGEN) Dr Nicolas BELHOMME declares for past 36 months consulting fees (AstraZeneca) and payment or honoraria for lectures (Astrazeneca, CHUGAI Pharma GSK and LeoPharma), (Copyright © 2024 Elsevier Inc. All rights reserved.)

Because Systemic Lupus Erythematosus (SLE) is a rare disease, and due to the significant prognostic impact of early management, a diagnosis confirmed by a physician with experience in SLE is recommended, for example from an expert center. Once the diagnosis is confirmed, existing manifestations should be identified in particular, renal involvement by an assessment of proteinuria, disease activity and severity should be determined, potential complications anticipated, associated diseases searched for, and the patient's socioprofessional and family context noted. Therapeutic management of SLE includes patient education on recognizing symptoms, understanding disease progression as well as when they should seek medical advice. Patients are informed about routine checkups, treatment side effects, and the need for regular vaccinations, especially if they are receiving immunosuppressive treatment. They are also advised on lifestyle factors such as the risks of smoking, sun exposure, and dietary adjustments, especially when they are receiving corticosteroids. The importance of contraception, particularly when teratogenic medications are being used, and regular cancer screening are emphasized. Support networks can help relieve a patient's isolation. The first-line medical treatment of SLE is hydroxychloroquine (HCQ), possibly combined with an immunosuppressant and/or low-dose corticosteroid therapy. The treatment of flares depends on their severity, and typically involves HCQ and NSAIDs, but may be escalated to corticosteroid therapy with immunosuppressants or biologic therapies in moderate to severe cases. Because there is no curative treatment, the goals of therapy are patient comfort, preventing progression and flares, and preserving overall long-term health and fertility. The frequency of follow-up visits depends on disease severity and any new symptoms. Regular specialized assessments are necessary, especially when treatment changes, but a frequency of every 3 to 6 months is recommended during periods of remission and monthly during active or severe disease, especially in children. These assessments include both clinical and laboratory tests to monitor complications and disease activity, with specific attention to proteinuria., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to identify associated risk factors, and to describe its therapeutic management., Methods: This multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type., Results: We included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 [95 % CI: 1.11-10.01, p = 0.03]), but not with cardiovascular risk factors (OR=0.70 [95 % CI: 0.23-2.21, p = 0.60]), or AAV relapse (OR=2.01 [95 % CI: 0.70-5.88, p = 0.16]). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %)., Conclusion: Regardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: High-resolution computed tomography (HRCT) may lack sensitivity for the early detection of interstitial lung disease associated with systemic sclerosis (SSc-ILD). Lung ultrasound is an emerging technique for the diagnosis of SSc-ILD. This cross-sectional study aimed to describe the prevalence of ultrasound interstitial syndrome in SSc patients with normal HRCT and pulmonary function tests (PFT). Methods: Thirty SSc patients with normal HRCT, FVC > 80% predicted and DLCO > 70% predicted were included. Echocardiography and PFT including impulse oscillometry and cardiopulmonary exercise testing were performed. Lung ultrasound was analyzed by two blinded operators. Patients were classified into two groups, according to the presence or absence of ultrasound interstitial syndrome, defined as the sum of B-lines in all thoracic areas ≥10 and/or pleural line thickness >3 mm on at least one thoracic area and/or a pleural line irregularity score >16%. Results: Ultrasound interstitial syndrome was present in 12 patients (40%). Inter-reader agreement for the diagnosis of ultrasound interstitial syndrome defined by the Kappa coefficient was 0.93 (95%CI 0.79-1.00). Patients with ultrasound interstitial syndrome were younger (37 years vs. 53 years, p = 0.009), more often had pitting scars ( n = 7/12 vs. 3/18, p = 0.045) and had lower FVC (102 vs. 110% pred, p = 0.009), TLC (114 vs. 122% pred, p = 0.042) and low-frequency respiratory system reactance (Xrs5 Z-score 0.16 vs. 1.02, p = 0.018), while pulmonary gas exchange was similar. Conclusions: Ultrasound interstitial syndrome was detected in 12/30 SSc patients with normal HRCT and PFT. Patients with ultrasound interstitial syndrome had differences in lung function consistent with reduced respiratory compliance, suggesting minimal and/or early suspected SSc-ILD.

Background: Vascular phenotype is associated with a poor prognosis in systemic sclerosis (SSc). The identification of its risk factors could facilitate its early detection., Objectives: To explore risk factors for a vascular phenotype of SSc, among them a history of pre-eclampsia., Methods: This observational multicentre case-control study enrolled adult women fulfilling European Alliance of Associations for Rheumatology 2013 diagnosis criteria for SSc and having a pregnancy history≥6 months before SSc diagnosis in 14 French hospital-based recruiting centres from July 2020 to July 2022. Cases had specific vascular complications of SSc defined as history of digital ischaemic ulcers, pulmonary arterial hypertension, specific cardiac involvement or renal crisis. Women with SSc were included during their annual follow-up visit and filled in a self-administered questionnaire about pregnancy. A case report form was completed by their physician, reporting data on medical history, physical examination, clinical investigations and current medication. The main outcome was the presence/absence of a personal history of pre-eclampsia before SSc diagnosis, according to the validated pre-eclampsia questionnaire., Results: 378 women were included: 129 cases with a vascular phenotype and 249 matched controls. A history of pre-eclampsia was reported in 5 (3.9%) cases and 12 (4.8%) controls and was not associated with a vascular phenotype (OR=0.96, 95% CI 0.28 to 3.34, p=0.9). Besides, Rodnan skin score and disease duration≥5 years were risk factors for vascular phenotype., Conclusions: In women with SSc and a pregnancy history≥6 months before SSc, a history of pre-eclampsia is not associated with a vascular phenotype., Competing Interests: Competing interests: M-ET declared consulting fees from AbbVie, Boehringer and UCB, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Lilly and UCB and support for attending meetings and/or travel from AbbVie and Novartis. CA declared payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Boehringer Ingelheim, Roche-Chugai and Janssen and support for attending meetings and/or travel from Boehringer Ingelheim, Roche-Chugai and Janssen. NB declared grants or contracts from GSK, Astra Zeneca, LEO Pharma and Roche., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series., Methods: We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day., Results: Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9-34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004)., Conclusions: Benralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows GC-sparing. However, its efficacy was lower after prior failure of mepolizumab., Competing Interests: Competing interests: The authors declare no financial support. MG reports personal fees from GlaxoSmithKline and AstraZeneca outside the submitted work. CT reports personal fees from AstraZeneca, Sanofi, GlaxoSmithKline, Chiesi and Novartis outside the submitted work. CDupin reports personal fees from AstraZeneca and GlaxoSmithKline outside the submitted work. HY reports personal fees from GlaxoSmithKline outside the submitted work. Other authors has nothing to disclose., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Heart involvement is one of the leading causes of death in systemic sclerosis (SSc). The prevalence of SSc-related cardiac involvement is poorly known. Our objective was to investigate the prevalence and prognosis burden of different heart diseases in a nationwide cohort of patients with SSc., Methods: We used data from a multicentric prospective study using the French SSc national database. Focusing on SSc-related cardiac involvement, we aimed to determine its incidence and risk factors., Results: Over the 3528 patients with SSc 312 (10.9%) had SSc-related cardiac involvement at baseline. They tended to have a diffuse SSc subtype more frequently, more severe clinical features, and presented more cardiovascular risk factors. From the 1646 patients available for follow-up analysis, SSc-related cardiac involvement was associated with an increased risk of death. There was no significant difference in overall survival between SSc-related cardiac involvement, ischaemic heart disease or pulmonary arterial hypertension. Regarding survival analysis, 98 patients developed SSc-related cardiac involvement at five years (5-year event rate: 11.15%). Regarding reduced LVEF < 50% and left ventricular diastolic dysfunction, the 5-year event rate was 2.49% and 5.84% respectively. Pericarditis cumulative incidence at five years was 3%. Diffuse SSc subtype was a risk factor for SSc-related cardiac involvement and pericarditis. Female sex was associated with less left ventricular diastolic dysfunction incidence., Conclusions: Our results describe the incidence and prognostic burden of SSc-related cardiac involvement at a large scale, with gender and diffuse SSc subtype as risk factors. Further analyses should assess the potential impact of treatment on these various cardiac outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Few studies have evaluated mouth opening (MO) in systemic sclerosis (SSc). None have studied MO trajectories., Objective: To study MO trajectories in SSc., Methods: This multicentre study included patients enrolled in the French national SSc cohort with at least one MO assessment, described patients based on MO baseline measure, modeled MO trajectories, and associated MO measures with SSc prognosis., Results: We included 1101 patients. Baseline MO was associated with disease severity. On Kaplan-Meier analysis, MO < 30 mm was associated with worse 30-year-survival (p<0.01) and risk of pulmonary arterial hypertension (p<0.05). Individual MO trajectories were heterogenous among patients. The best model of MO trajectories according to latent-process mixed modeling showed that 88.8% patients had a stable MO trajectory and clustered patients into 3 groups that predicted SSc survival (p<0.05) and interstitial lung disease (ILD) occurrence (p<0.05). The model highlighted a cluster of 9.5% patients with diffuse cutaneous SSc (dcSSc) (p<0.05) and high but decreasing MO over 1 year (p<0.0001) who were at increased risk of poor survival and ILD., Conclusion: MO, which is a simple and reliable measure, could be used to predict disease severity and survival in SSc. Although MO remained stable in most SSc patients, dcSSc patients with high but decreasing MO were at risk of poor survival and ILD. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

Background: Adverse pregnancy outcomes in women with primary Sjögren's syndrome have only been evaluated retrospectively using heterogeneous methods and with contradictory results. We aimed to describe adverse pregnancy, delivery, and birth outcome risks in pregnant women with primary Sjögren's syndrome compared with those of a matched general population in France, and to identify factors predictive of disease flares or adverse pregnancy outcomes., Methods: We conducted a multicentre, prospective, cohort study in France using the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) registry. Women from the GR2 study were eligible if they had conceived before March, 2021, had primary Sjögren's syndrome according to the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) 2016 classification criteria, and had an ongoing pregnancy at 12 weeks of gestation. In women who entered in the registry with pregnancies before 18 weeks of gestation, we sought to identify factors associated with primary Sjögren's syndrome flare (≥3-point increase in EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI] score) or adverse pregnancy outcomes (fetal or neonatal death, placental insufficiency leading to a preterm delivery [<37 weeks of gestation], or small-for-gestational-age birthweight). A matched controlled study compared adverse pregnancy, delivery, and birth outcome rates between pregnant women with primary Sjögren's syndrome from the GR2 registry and matched controls from the general population included in the last French perinatal survey (Enquête Nationale Périnatale 2016)., Findings: 1944 pregnancies were identified in the GR2 cohort, of which 106 pregnancies in 96 women with primary Sjögren's syndrome were included in this analysis. The median age at pregnancy onset was 33 years (IQR 31-36). 87 (83%) of 105 pregnancies (with ethnicity data) were in White women, 18 (17%) were in Black women; 92 (90%) of 102 had previous systemic activity (ESSDAI score of ≥1; data missing in four pregnancies), and 48 (45%) of 106 had systemic activity at inclusion. Of 93 pregnancies included at week 18 of gestation or earlier, primary Sjögren's syndrome flares occurred in 12 (13%). No baseline parameters were associated with primary Sjögren's syndrome flare. Four twin pregnancies and one medical termination were excluded from the adverse pregnancy outcome analysis; of the remaining 88, adverse pregnancy outcomes occurred in six (7%). Among pregnancies in women with data for antiphospholipid antibodies (n=55), antiphospholipid antibody positivity was more frequent among pregnancies with adverse outcomes (two [50%] of four pregnancies) compared with those without adverse outcomes (two [4%] of 51 pregnancies; p=0·023). Anti-RNP antibody positivity was also more frequent among pregnancies with adverse outcomes than those without, although this was not statistically significant. In the matched controlled study, adverse pregnancy outcomes occurred in nine (9%) of 105 pregnancies in women with primary Sjögren's syndrome and 28 (7%) of the 420 matched control pregnancies; adverse pregnancy outcomes were not significantly associated with primary Sjögren's syndrome (odds ratio 1·31, 95% CI 0·53-2·98; p=0·52)., Interpretation: Pregnancies in women with primary Sjögren's syndrome had very good prognoses for mothers and fetuses, with no overall increase in adverse pregnancy outcome risk compared with the general population. Women with antiphospholipid antibodies or anti-RNP antibodies require close monitoring, because these factors might be associated with a higher risk of adverse pregnancy outcomes., Funding: Lupus France, Association des Sclérodermiques de France, Association Gougerot Sjögren, Association Francophone Contre la Polychondrite Chronique Atrophiante, AFM-Telethon, Société Nationale Française de Médecine Interne, Société Française de Rhumatologie, Cochin Hospital, French Health Ministry, Fondation for Research in Rheumatology, Association Prix Véronique Roualet, Union Chimique Belge., Competing Interests: Declaration of interests NC-C reports an unrestricted research grant from UCB to her institution. GN reports grants from la Société Française de Rhumatologie and Arthritis Foundation; consulting fees from Biogen, Pfizer, Novartis, Lilly, and Amgen; support for attending meetings and travel from Amgen; and is an advisory board member for Boehringer Ingelheim. AM reports an unrestricted research grant from Pfizer to her institution; consulting fees from Janssen and Gilead; and honoraria for presentations or speaker bureaus from AbbVie, Bristol Myers Squibb, Biogen, Pfizer, UCB, and Lilly; support from AbbVie, Janssen, Bristol Myers Squibb, and Pfizer for attending meetings or travel; and is an advisory board member for Janssen and UCB. CR reports consulting fees from Novartis and UCB. MM received grants from GSK and received support for travel and attending meetings from Novartis and LFB. LR reports support for attending meetings from Novartis and Otsuka. XM reports consulting fees from AstraZeneca, Bristol Myers Squibb, Galapagos, GlaxoSmithKline, Novartis, and Pfizer. VLG reports honoraria for presentations or speaker bureaus from Bristol Myers Squibb; consulting fees from Novartis; and support from AstraZeneca–MedImmune for attending meetings and travel. RS reports consulting fees from GlaxoSmithKline, Bristol Myers Squibb, Boehringer Ingelheim, and Janssen; honoraria for presentations or speaker bureaus from GlaxoSmithKline, Bristol Myers Squibb, Fresenius Kabi, Boehringer Ingelheim, Janssen, Pfizer, and Roche; and support for attending meetings and travel from Amgen and GlaxoSmithKline. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To determine whether a single session of botulinum toxin type A (BTA) injections into both hands more effectively decreases the frequency of systemic sclerosis-associated Raynaud's phenomenon (SSc-RP) episodes than placebo., Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group phase III trial in patients with SSc-RP assessed the effect of 50-unit BTA or placebo injections into the palms of both hands around each neurovascular bundle during 1 session in winter. The primary end point was the between-group difference in the median change in the number of RP episodes from baseline (day 0) to 4 weeks postinjection. Values between the groups were compared with the Wilcoxon rank-sum test., Results: The intent-to-treat analysis included 46 BTA-treated patients and 44 placebo recipients. At 4 weeks after assigned treatment injections, the median number of daily RP episodes decreased comparably in the BTA and placebo groups (median change -1 episode/day [interquartile range (IQR) -1.5, 0 episodes/day] and -1 episode/day [IQR -2.5, 0 episodes/day], respectively) (P = 0.77 versus placebo). Moreover, change in Raynaud's Condition Score, quality of life assessed by Health Assessment Questionnaire disability index, and hand function assessed by shortened Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Cochin Hand Function Scale from baseline to follow-up weeks 4, 12, and 24 did not differ significantly between groups. The BTA group experienced transient hand muscle weakness significantly more frequently (P = 0.003)., Conclusion: Neither the primary nor secondary end points were reached, and our results do not support any beneficial effect of palmar BTA injections to treat SSc-RP., (© 2022 American College of Rheumatology.)

SSc is an auto-immune disease characterized by life-threatening manifestations such as lung fibrosis or pulmonary arterial hypertension. Symptoms with a detrimental impact on quality of life are also reported and sicca syndrome (xerostomia, xeropthalmia) is present in up to 80% of patients with SSc. Sicca syndrome can occur in the absence of overlap with Sjögren's disease and recent studies highlight that fibrosis of minor and major salivary glands, directly linked to the pathogenesis of SSc, could be a major contributor of xerostomia in SSc. This narrative review provides an overview of the clinical presentation, diagnostic strategies, management and future perspectives on sicca syndrome in patients with SSc., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Immunoglobulin A vasculitis (IgAV) usually occurs following viral respiratory tract infection. In the context of the global coronavirus disease 2019 (COVID-19) pandemic, we describe a case series of patients who developed IgAV following SARS-CoV-2 infection., Methods: This national multicenter retrospective study included patients with IgAV following SARS-CoV-2 infection from January 1, 2020, to January 1, 2022. Patients had histologically proven IgAV and reverse transcription PCR (RT-PCR)-proven SARS-CoV-2 infection. The interval between infection and vasculitis onset had to be < 4 weeks., Results: We included 5 patients, 4 of whom were women with a mean age of 45 years. Four patients had paucisymptomatic infections and 1 required a 48-hour low-flow oxygen treatment. All 5 patients had purpuric skin involvement. Arthritis was observed in 2 patients, 3 had IgA glomerulonephritis, and 2 had digestive involvement. Three renal biopsies were performed and showed mesangial IgA deposits without any extracapillary proliferation. Median C-reactive protein was 180 (range 15.1-225) mg/L, median serum creatinine level was 65 (range 41-169) µmol/L, and 2 patients had a glomerular filtration rate < 60 mL/min. Four patients received first-line treatment with glucocorticoids. All patients had a favorable progression and 2 patients experienced minor skin relapses, one after COVID-19 vaccination., Conclusion: This series describes the emergence of IgAV closely following COVID-19; we were not able to eliminate an incidental link between these events. Their disease outcomes were favorable. In most of our patients, the SARS-CoV-2 infection was paucisymptomatic, and we recommend RT-PCR tests to look for COVID-19 in patients without any evident triggers for IgAV., (Copyright © 2022 by the Journal of Rheumatology.)

Background: Identification of underlying diseases is crucial for secondary hyperhidrosis management, but data are lacking to guide appropriate investigation. Objective: To describe aetiologies of recurrent sweating in a hospital setting and the diagnostic performance parameters of their respective clinical/biological features. Patients and Methods: We performed a monocentric evaluative study in a tertiary care centre. Patients with recurrent generalised sweating were selected via the Clinical Data Warehouse (CDW) by screening all electronic hospital documents from the year 2018 using a keyword-based algorithm. All in and out-patients aged ≥ 18 years having reported recurrent sweating for at least 2 weeks in 2018 were included, with a minimum one-year follow-up after symptoms' onset. Results: A total of 420 patients were included. Over 130 different aetiologies were identified; 70 patients (16.7%) remained without diagnosis. Solid organ cancers (14.3% with 13 lung cancers), haematologic malignancies (14.0% with 35 non-Hodgkin's lymphomas) and Infectious Diseases (10.5% including 13 tuberculosis) were the most frequent diagnoses. Other aetiologies were gathered into inflammatory (16.9%) and non-inflammatory (27.6%) conditions. To distinguish non-inflammatory and undiagnosed hyperhidrosis from other causes, fever had a specificity of 94%, impaired general condition a sensitivity of 78%, and C-reactive protein (CRP) > 5.6 mg/l a positive predictive value of 0.86. Symptoms' duration over 1 year was in favour of non-infectious and non-malignant causes (94% specificity). Conclusions: We identified fever, impaired general condition, duration, and CRP as helpful orientation parameters to assess the need for complementary explorations for hyperhidrosis. The study provides a diagnostic algorithm for the investigation of recurrent sweating.KEY MESSAGESIn a hospital setting, malignancies and infections are the most frequently associated diseases, but 1/5 remain without diagnosis.Fever is a specific but not sensitive sign to distinguish inflammatory conditions.Over 1 year duration of symptoms significantly reduce the probability of malignancy or infection as the underlying diagnosis.

Background: Prospective data about the risks of thrombotic and severe haemorrhagic complications during pregnancy and post partum are unavailable for women with antiphospholipid syndrome. We aimed to assess thrombotic and haemorrhagic events in a prospective cohort of pregnant women with antiphospholipid syndrome., Methods: This multicentre, prospective, observational study was done at 76 centres in France. To be eligible for this study, women had to have diagnosis of antiphospholipid syndrome; have conceived before April 17, 2020; have an ongoing pregnancy that had reached 12 weeks of gestation; and be included in the study before 18 weeks of gestation. Exclusion criteria were active systemic lupus erythematosus nephropathy, or a multifetal pregnancy. Severe haemorrhage was defined as the need for red blood cell transfusion or maternal intensive care unit admission because of bleeding or invasive procedures, defined as interventional radiology or surgery, to control bleeding. The GR2 study is registered with ClinicalTrials.gov, NCT02450396., Findings: Between May 26, 2014, and April 17, 2020, 168 pregnancies in 27 centres met the inclusion criteria for the study. 89 (53%) of 168 women had a history of thrombosis. The median term at inclusion was 8 weeks gestation. 16 (10%) of 168 women (95%CI 5-15) had a thrombotic (six [4%] women; 95% CI 1-8) or severe haemorrhagic event (12 [7%] women; 95% CI 4-12). There were no deaths during the study. The main risk factors for thrombotic events were lupus anticoagulant positivity at inclusion (six [100%] of six women with thrombosis vs 78 [51%] of 152 of those with no thrombosis; p=0·030) and placental insufficiency (four [67%] of six women vs 28 [17%] of 162 women; p=0·013). The main risk factors for severe haemorrhagic events were pre-existing maternal hypertension (four [33%] of 12 women vs 11 [7%] of 156 women; p=0·014), lupus anticoagulant positivity at inclusion (12 [100%] of 12 women vs 72 [49%] of 146 women; p<0·0001) and during antiphospholipid history (12 [100%] of 12 women vs 104 [67%] of 156 women; p=0·019), triple antiphospholipid antibody positivity (eight [67%] of 12 women vs 36 [24%] of 147 women; p=0·0040), placental insufficiency (five [42%] of 12 women vs 27 [17%] of 156 women; p=0·038), and preterm delivery at 34 weeks or earlier (five [45%] of 11 women vs 12 [8%] of 145 women; p=0·0030)., Interpretation: Despite treatment adhering to international recommendations, a proportion of women with antiphospholipid syndrome developed a thrombotic or severe haemorrhagic complication related to pregnancy, most frequently in the post-partum period. Lupus anticoagulant and placental insufficiency were risk factors for these life-threatening complications. These complications are difficult to prevent, but knowledge of the antenatal characteristics associated with them should increase awareness and help physicians manage these high-risk pregnancies., Funding: Lupus France, association des Sclérodermiques de France, association Gougerot Sjögren, Association Francophone contre la Polychondrite chronique atrophiante, AFM-Telethon, the French Society of Internal Medicine and Rheumatology, Cochin Hospital, the French Health Ministry, FOREUM, the Association Prix Veronique Roualet, and UCB., Competing Interests: Declaration of interests NC-C has received an unrestricted research grant from UCB to her institution. NB has received honoraria for presentations or speaker bureaus from GSK, Astra Zeneca, and Leo, and was supported by Boehringer Ingelheim for attending meetings or travel. CL has received honoraria for lectures about interstitial pneumopathies from Boehringer Ingelheim. VLG has received honoraria for presentations or speaker bureaus from Bristol Myers Squibb and consulting fees from Novartis, and was supported by AstraZeneca-MedImmune for attending meetings and travel. NL has received consulting fees from Amgen. AMo has received an unrestricted research grant from Pfizer to her institution, consulting fees from Janssen and Gilead, and honoraria for presentations or speaker bureaus from Abbvie, Bristol Myers Squibb, Biogen, Pfizer, UCB, and Lilly, was supported by Abbvie, Janssen, BMS, and Pfizer for attending meetings or travel, and is an advisory board member for Janssen and UCB. LM received unrestricted research grants from LFB Biotechnologies, CSL Behring, and Roche to her institution and honoraria for presentations or speaker bureaus from Boehringer Ingelheim and CSL Behring, and was supported by LFB Biotechnologies and Abbvie for attending meetings or travel. NS has received honoraria for presentations from CSL Behring and Eusapharma and from Takeda for participation on an advisory board. LS reports consulting fees from Ferring Pharmaceuticals and payment or honoraria for lectures from Ferring Pharmaceuticals. GU reports research support from Philippe Foundation for their postdoctoral research and has received honoraria for lectures from Sanofi. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: There is currently no evidence of the possible benefit of plasma cell-targeting therapies (PCTT) in immunoglobulin A (IgA) monoclonal gammopathy (MG) associated with IgA vasculitis (IgAV). We report the outcome of different PCTT regimens in a cohort of MG-IgAV., Methods: We used a French network to retrospectively describe the outcome of MG-IgAV patients treated with PCTT., Results: Five patients were included (mean age 65 years). All patients had severe baseline presentation including extensive necrotic purpura (n = 5), gastrointestinal involvement (n = 2), peripheral neuropathies (n = 2), and glomerulonephritis (n = 1). Two patients had IgA indolent multiple myeloma and three had IgA "MG of undetermined significance." Monotypic IgA deposition in the skin vessels wall was highlighted using an immunofluorescence assay. Cases of vasculitis in three patients (n = 3) were refractory to multiple line therapies, including cyclophosphamide (n = 3) or rituximab. Finally, PCTT including bortezomib plus cyclophosphamide and dexamethasone, bortezomib plus melphalan and prednisone, or bortezomib plus lenalidomide and dexamethasone were proposed, allowing complete remission in 4/5 patients without major adverse drug events., Conclusion: This study suggests that the MG-IgAV phenotype might be distinctive of usual IgAV (severe and refractory to conventional immunosuppressive regimens) and supports the benefit of PCTT. This study sheds new light on the overall biology of IgAV, strengthening the pathogenic role of the monoclonal IgA component in IgAV., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objectives: The specific roles of remission status, lupus low disease activity state (LLDAS), and damage accrual on the prognosis of pregnancies in women with SLE are unknown. We analysed their impact on maternal flares and adverse pregnancy outcomes (APOs)., Methods: We evaluated all women (≥18 years) with SLE enrolled in the prospective GR2 study with an ongoing singleton pregnancy at 12 weeks (one pregnancy/woman). Several sets of criteria were used to define remission, disease activity and damage. APOs included: foetal/neonatal death, placental insufficiency with preterm delivery and small-for-gestational-age birth weight. First trimester maternal and disease features were tested as predictors of maternal flares and APOs., Results: The study included 238 women (98.3% on hydroxychloroquine (HCQ)) with 230 live births. Thirty-five (14.7%) patients had at least one flare during the second/third trimester. At least one APOs occurred in 34 (14.3%) women. Hypocomplementemia in the first trimester was the only factor associated with maternal flares later in pregnancy (P=0.02), while several factors were associated with APOs. In the logistic regression models, damage by SLICC-Damage Index [odds ratio (OR) 1.8, 95% CI: 1.1, 2.9 for model 1 and OR 1.7, 95% CI: 1.1, 2.8 for model 2] and lupus anticoagulant (LA, OR 4.2, 95% CI: 1.8, 9.7 for model 1; OR 3.7, 95% CI: 1.6, 8.7 for model 2) were significantly associated with APOs., Conclusion: LA and damage at conception were predictors of APOs, and hypocomplementemia in the first trimester was associated with maternal flares later in pregnancy in this cohort of pregnant patients mostly with well-controlled SLE treated with HCQ., Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02450396., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: The aim of this study was to describe the efficacy and safety of rituximab and MTX (RTX/MTX) combination therapy in ANCA-associated vasculitides (AAV)., Methods: A retrospective French nationwide study was conducted in patients with AAV who received RTX/MTX combination therapy for persistently active disease., Results: Seventeen patients were included. All patients had granulomatosis with polyangiitis (GPA), with positive ANCA in 76% of them, mainly with PR3-ANCA specificity. Sixteen patients (94%) had priorly failed to achieve remission with RTX and 11 (65%) with CYC. Patients had experienced a median of 3 (2-4) flares. Manifestations requiring RTX/MTX combination therapy were subglottic or bronchial stenosis in 6 patients (35%), orbital mass in 6 (35%), disabling ENT involvement in 2 (12%), and epiduritis and pachymeningitis in 1 case (6%) each. The median follow-up duration for the RTX/MTX combination therapy was 11 months (11-26 months). At 6 months, global response had been achieved in 15 patients (88%), including partial response in 11 (65%) and complete response in 4 (24%). At last evaluation, global response had been achieved in 16 patients (94%). Seven patients (41%) experienced severe adverse events (grade 3 or 4), including infections in 4 (24%) and hepatitis in 2 (12%). Combination therapy was withdrawn in 4 patients (24%), but never for safety concerns. In contrast, the MTX dose was decreased in 2 patients (12%) because of adverse events. One patient died of an unknown cause., Conclusion: RTX/MTX combination therapy could be an effective salvage therapy to treat persistently active GPA with granulomatous manifestations, with an acceptable safety profile., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by skin fibrosis, vasculopathy, and dysimmunity. Data regarding osteitis in SSc are scarce., Methods: We performed a nationwide multicenter, retrospective, case-control study including patients with SSc, according to the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification, with a diagnosis of osteitis. The objectives of the study were to describe, to characterize, and to identify associated factors for osteitis in patients with SSc., Results: Forty-eight patients were included. Twenty-six patients (54.1%) had osteitis beneath digital tip ulcers. Physical symptoms included pain (36 of 48, 75%), erythema (35 of 48, 73%), and local warmth (35 of 48, 73%). Thirty-one (65%) patients had median (interquartile range) C-reactive protein levels >2 mg/liter of 8 (2.7-44.3) mg/liter. On radiography, computed tomography, or magnetic resonance imaging, osteitis was characterized by swelling or abscess of soft tissues, with acro-osteolysis or lysis in 28 patients (58%). Microbiological sampling was performed in 45 (94%) patients. Most pathogens were Staphylococcus aureus (43.8%), anaerobes and Enterobacteriaceae (29.1%), and Pseudomonas aeruginosa (10.4%). Management comprised antibiotics in 37 (77.1%) patients and/or surgery in 26 (54.2%). Fluoroquinolones were used in 22 (45.8%) patients, and amoxicillin plus β-lactamase inhibitor in 7 (14.6%). Six (12.6%) patients relapsed, 6 (12.6%) patients had osteitis recurrence, 15 (32%) sequelae, and 2 patients had septic shock and died., Conclusion: This study confirmed digital tip ulcers as an associated factor for osteitis and revealed a high rate of functional sequelae. Antimicrobial therapy with oral fluoroquinolone or intravenous amoxicillin and β-lactamase inhibitor are used as first-line antibiotic therapy in SSc patients with osteitis., (© 2020 American College of Rheumatology.)

Background: Although male sex is associated with poor prognosis in systemic sclerosis (SSc), it is unclear whether this association is independent of confounding factors such as occupational exposure to toxicants., Research Question: What is the respective impact of sex and occupational exposure on characteristics of patients with SSc with a focus on lung function decline?, Study Design and Methods: Patients with SSc (n = 210; 55 men) underwent standardized quantitative assessment of occupational exposure through a cumulative exposure score (CES) in a multicenter recruitment retrospective cohort. Association of the CES with patients' characteristics was assessed. Mixed linear, logistic, and Cox regression models were used to identify predictors of time variation of FVC and the diffusing capacity of the lungs for CO 2 corrected for hemoglobin (Dlcoc)., Results: Male sex was associated strongly with occupational exposure (OR, 10.3; P < .0001). The CES was correlated inversely (r = -0.20) and associated independently with decline in FVC over time and with occurrence of FVC decline of ≥ 10% from baseline (P < .05). By contrast, the CES was not associated with decline in Dlcoc or Dlcoc decline of ≥ 15%. No independent association was found between sex and decline in FVC or Dlcoc. The prevalence of interstitial lung disease was similar across sex or occupational exposure., Interpretation: Occupational exposure to toxicants seems to predict decline of FVC in patients with SSc independently, regardless of sex. Assessment of occupational exposure may be useful for SSc prognostication., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Glucocorticoids (GCs) plus rituximab (RTX) represent the first-line treatment of nonviral mixed cryoglobulinemia vasculitis (CryoVas). However, data on therapeutic management and outcome of patients refractory to RTX are lacking., Methods: We conducted a European collaborative retrospective multicenter study of patients with nonviral mixed CryoVas refractory to RTX and performed a literature review., Results: Twenty-six original cases and 7 additional patients from the literature were included. All patients but one had type 2 cryoglobulinemia, and causes were autoimmune disease (51%), malignant hemopathy (12%) or essential CryoVas (42%). CryoVas was primary refractory to RTX in 42%, while 58% had an initial response to RTX before immune escape. After RTX failure, patients received a median of 1 (IQR, 1-3) line of treatment, representing 65 treatment periods during follow-up. Main treatments used were GCs in 92%, alkylating agents in 43%, RTX in combination with other treatments in 46%, and belimumab in 17%. Combination of anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents provided the highest rates of clinical response in 100% 82% and 73%, respectively, but showed poor immunological response, in 50%, 30% and 38%, respectively. Rates of severe infection were 57%, 9% and 0% in patients receiving anti-CD20 plus belimumab, alkylating agents alone and anti-CD20 plus alkylating agents, respectively., Conclusion: In patients with nonviral mixed CryoVas refractory to RTX, anti-CD20 plus belimumab, and alkylating agents associated or not with anti-CD20, provide the highest rates of clinical response. However, anti-CD20 plus belimumab was frequently associated with severe infections., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD). Data on use of prostanoids in this particular subset of patients are lacking. We aimed to describe the characteristics of patients with PAH-CTD treated with prostanoids and the outcomes under treatment., Methods: In this multicenter retrospective study, all patients treated with prostanoids since 2006 were included. Data on PAH and CTD were collected at the time of prostanoid introduction and under treatment., Results: Twenty-one patients were included, of whom 20 (95%) had limited cutaneous systemic sclerosis. Nineteen patients were treated with oral monotherapy or combination before addition of prostanoid. Treprostinil was the most used molecule (57% of patients). At the time of prostanoid introduction, 90% of patients were considered at high risk for death. Among patients who had right heart catheterization during follow-up, there was no significant difference in haemodynamics. No extrarespiratory worsening of the CTD was reported. The 1-year survival under prostanoid was 62%. In univariate analysis, NYHA functional class was associated with survival under treatment., Conclusion: This study provides original data on use of prostanoids in a cohort consisting mainly of systemic sclerosis. It underlines the difficulty to achieve a standardized assessment in this subset of patients. Safety profile was comparable with data reported in idiopathic PAH., (Copyright © 2021. Published by Elsevier Masson SAS.)

The neonatal Fc receptor (FcRn) is a ubiquitously expressed protein historically involved in IgG and albumin recycling. Recent data suggest an involvement in the pathophysiology of antibody-mediated autoimmune diseases. Among them, systemic lupus erythematosus (SLE) implies clinical and biological abnormalities of innate and adaptive circulating immune cells, potentially involving newly described functions of FcRn. In this study, FcRn expression was assessed by flow cytometry in peripheral blood leukocytes of 41 SLE patients with either active or inactive disease and 32 healthy donors. FcRn expression in B cells, natural killer cells, and T cells of SLE patients was statistically lower as compared to healthy donors. Conversely, FcRn level was statistically higher in non-classical monocyte subpopulations (CD14+CD16+ monocytes) of SLE patients versus healthy donors providing an interesting perspective to further explore its role in SLE pathophysiology.

Objectives: Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV., Methods: We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: <36, 36 ≤ age < 52; 52 ≤ age < 63 and ≥63 years. Comparison of presentation and outcome were performed according to age of disease onset., Results: Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P < 0.0001) and gastrointestinal involvement (P = 0.001). In contrast, the oldest patients had more severe purpura with necrotic lesions (P = 0.001) and more frequent renal involvement (P < 0.0001), with more frequent haematuria, renal failure, higher urine protein excretion and more frequent tubulointerstitial lesions. Patients were treated similarly in all groups of age, and clinical response and relapse rates were similar between groups. In the 127 treated patients with follow-up data for >6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1-38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age., Conclusion: Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Systemic sclerosis (SSc) is a generalized disease of the connective tissue, arterioles, and microvessels, characterized by the appearance of fibrosis and vascular obliteration. There are two main phenotypical forms of SSc: a diffuse cutaneous form that extends towards the proximal region of the limbs and/or torso, and a limited cutaneous form where the cutaneous sclerosis only affects the extremities of the limbs (without passing beyond the elbows and knees). There also exists in less than 10% of cases forms that never involve the skin. This is called SSc sine scleroderma. The prognosis depends essentially on the occurrence of visceral damage and more particularly interstitial lung disease (which is sometimes severe), pulmonary arterial hypertension, or primary cardiac damage, which represent the three commonest causes of mortality in SSc. Another type of involvement with poor prognosis, scleroderma renal crisis, is rare (less than 5% of cases). Cutaneous extension is also an important parameter, with the diffuse cutaneous forms having less favorable prognosis., (© 2021. The Author(s).)

Background: Gastrointestinal (GI) involvement was described to be a poor prognostic factor in systemic necrotizing vasculitis. Its prognostic significance may vary according to clinical presentation and vasculitis subtype., Aims: This study investigated risk-factors associated to poor outcome in GI-involvement of vasculitis., Methods: Patients with systemic vasculitis as defined by the 2012 Chapel Hill Consensus Conference and presenting with GI involvement were retrospectively included. Baseline characteristics, treatments and outcome were recorded. Primary endpoint was a composite of admission to intensive care unit (ICU), emergency surgical procedure, or death., Results: Two hundred and thirteen patients were included. Vasculitis were distributed as follows: 41% IgA vasculitis, 27% ANCA-associated vasculitis, 17% polyarteritis nodosa (PAN), and 15% other vasculitis. Eighty-three (39%) patients fulfilled the composite primary endpoint within 6 months. Predictive factors associated with the primary endpoint included PAN subtype (OR 3.08, 95% CI 1.29-7.34), performance status (OR 1.40, 1.05-1.87), use of morphine (OR 2.51, 0.87-7.24), abdominal guarding (OR 3.08, 1.01-9.37), ileus (OR 2.29, 0.98-5.32), melena (OR 2.74, 1.17-6.42), increased leukocytes (per G/L, OR 1.05, 1.00-1.10), low hemoglobin (per g/dL, OR 0.80, 0.71-0.91) and increased CRP (log mg/L, OR 1.21, 0.94-1.56). A risk prediction model for the achievement of primary endpoint had a very good performance [C-statistics 0.853 (0.810 to 0.895], and for overall survival as well., Conclusions: Vasculitis presenting with GI involvement have a poor outcome in more than one third of cases. An easy-to-use risk prediction model had a very good performance to predict the admission to ICU, emergency surgical procedure, or death., Competing Interests: Declarations of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To report on a large series of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and bronchiectasis, with a specific focus on the timeline of occurrence of both features., Methods: Retrospective nationwide multicenter study of patients diagnosed with both AAV and bronchiectasis., Results: Sixty-one patients were included, among whom 27 (44.25%) had microscopic polyangiitis (MPA), 27 (44.25%) had granulomatosis with polyangiitis (GPA), and 7 (11.5%) had eosinophilic GPA. Thirty-nine (64%) had myeloperoxidase (MPO)-ANCA and 13 (21%) had proteinase 3-ANCA. The diagnosis of bronchiectasis either preceded (n = 25; median time between both diagnoses: 16 yrs, IQR 4-54 yrs), was concomitant to (n = 12), or followed (n = 24; median time between both diagnoses: 1, IQR 0-6 yrs) that of AAV. Patients in whom bronchiectasis precedes the onset of AAV (B-AAV group) have more frequent mononeuritis multiplex, MPA, MPO-ANCA, and a 5-fold increase of death. The occurrence of an AAV relapse tended to be protective against bronchiectasis worsening (HR 0.6, 95% CI 0.4-0.99, P = 0.049), while a diagnosis of bronchiectasis before AAV (HR 5.8, 95% CI 1.2-28.7, P = 0.03) or MPA (HR 18.1, 95% CI 2.2-146.3, P = 0.01) were associated with shorter survival during AAV follow-up., Conclusion: The association of bronchiectasis with AAV is likely not accidental and is mostly associated with MPO-ANCA. Patients in whom bronchiectasis precedes the onset of AAV tend to have distinct clinical and biological features and could carry a worse prognosis.

Objective: Systemic sclerosis mainly affects the microvascular network. However, macrovascular manifestations have been reported. We aimed to investigate the characteristics of systemic sclerosis patients with an amputation of a lower limb segment., Methods: We designed a retrospective, case-control, multicentric study on systemic sclerosis patients with amputation of a lower limb segment secondary to critical ischemia via the French Research Group on Systemic Sclerosis. For each case, a control (systemic sclerosis patient without lower limb symptom) was matched with sex, age (±5 years), and cutaneous subset of systemic sclerosis., Results: In total, 26 systemic sclerosis patients (mean age of 67.2 ± 10.9 years, 20 females, 21 limited cutaneous forms) with a lower limb amputation and 26 matched controls (mean age of 67.3 ± 11.2 years, 20 females, 22 limited cutaneous forms) were included. At the time of amputation, the mean disease duration was 12.8 (±8.6) years. In comparison to controls, systemic sclerosis patients with amputation had more digital ulcers (p = 0.048), history of digital ulcers (p = 0.026), and a higher prevalence of pulmonary arterial hypertension (p = 0.024). Systemic sclerosis patients with amputation were more often smokers (p = 0.008) and under corticosteroids (p = 0.015). In the multivariate model, pulmonary arterial hypertension, smoking status, and corticosteroids were independent markers associated with lower limb amputation in systemic sclerosis. In the follow-up, 10 patients (38.5%) had recurrent ischemia requiring a new limb amputation, and five patients (19.2%) had an amputation of the contralateral limb., Conclusion: This study identifies some markers associated with lower limb amputation in systemic sclerosis such as digital ulcers and pulmonary arterial hypertension and points out the high risk associated with tobacco consumption and corticosteroid use., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Objectives: The predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease., Methods: To characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5-; n = 190/201) based on selected variables, collected retrospectively, without any missing data., Results: Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; p < 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia; 82.6%; p < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; p < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; p < 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5- patients with myositis., Conclusion: Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist., (© 2020 American Academy of Neurology.)

Background: Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival., Methods: From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes., Results: A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1-6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2-5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5., Conclusions: Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.

Objective : To compare the clinical presentation and outcome of giant cell arteritis (GCA)-related aortitis according to the results of temporal artery biopsy (TAB). Method : Patients with GCA-related aortitis diagnosed between 2000 and 2017, who underwent TAB, were retrospectively included from a French multicentre database. They all met at least three American College of Rheumatology criteria for the diagnosis of GCA. Aortitis was defined by aortic wall thickening > 2 mm on computed tomography scan and/or an aortic aneurysm, associated with an inflammatory syndrome. Patients were divided into two groups [positive and negative TAB (TAB+, TAB-)], which were compared regarding aortic imaging characteristics and aortic events, at aortitis diagnosis and during follow-up. Results : We included 56 patients with TAB+ (70%) and 24 with TAB- (30%). At aortitis diagnosis, patients with TAB- were significantly younger than those with TAB+ (67.7 ± 9 vs 72.3 ± 7 years, p = 0.022). Initial clinical signs of GCA, inflammatory parameters, and glucocorticoid therapy were similar in both groups. Coronary artery disease and/or lower limb peripheral arterial disease was more frequent in TAB- patients (25% vs 5.3%, p = 0.018). Aortic wall thickness and type of aortic involvement were not significantly different between groups. Diffuse arterial involvement from the aortic arch was more frequent in TAB- patients (29.1 vs 8.9%, p = 0.03). There were no differences between the groups regarding overall, aneurism-free, relapse-free, and aortic event-free survival. Conclusion : Among patients with GCA-related aortitis, those with TAB- are characterized by younger age and increased frequency of diffuse arterial involvement from the aortic arch compared to those with TAB+, without significant differences in terms of prognosis.

Objective: To evaluate the performance of salivary gland ultrasonography for the diagnosis of primary and secondary Sjögren's syndromes (pSS and sSS)., Method: Multicenter cross-sectional study on 97 patients with clinical sicca symptoms. The pSS (n = 22) met the American-European Consensus Group (AECG) classification criteria. The control patients (n = 36) with sicca symptoms did not fulfill the AECG criteria. Four scores were used to evaluate the 4 major salivary gland echostructure: the Salaffi score (0-16), Jousse-Joulin score (0-4), Hocevar score (0-48) and Milic score (0-12)., Results: The medians of ultrasonographic (US) scores were higher in the pSS and sSS groups than in the control group (P < 0.001). The receiver-operating characteristic (ROC) curves and the positive likelihood ratio (LR+) of the four scores showed a good diagnostic performance for the US diagnosis of pSS and sSS. Respectively, for pSS and sSS, the AUC were 0.891 (95%CI 0.812-0.970) and 0.824 (95%CI 0.695-0.954) for Hocevar score, 0.885 (95%CI 0.804-0.965) and 0.808 (95%CI 0.673-0.943) for Milic score, 0.915 (95%CI 0.848-0.982) and 0.844 (95%CI 0.724-0.965) for Salaffi score, 0.897 (95%CI 0.821-0.973) and 0.851 (95%CI 0.735-0.968) for Jousse-Joulin score. This study showed an interesting inter-observer reproducibility (kappa = 0.714 ± 0.131) of the US evaluation with 85.7% agreement between reader to determine the pathological character of the salivary glands., Conclusion: Salivary gland US is a simple, non-invasive and performant imaging procedure for the diagnosis of pSS and sSS, with Salaffi, Milic and Jousse-Joulin scores., (Copyright © 2018. Published by Elsevier Masson SAS.)

Objectives: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs)., Methods: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV)., Results: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%., Conclusions: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years., Trial Registration Number: NCT02339441., Competing Interests: Competing interests: ALH has done consultancy work for Actelion, served on a Data Safety Monitoring Board for Apricus, received research funding and speaker’s fees from Actelion, and speaker’s fees from GSK. JHWD has consultancy relationships and/or has received research funding from Actelion, BMS, Celgene, Bayer Pharma, Boehringer Ingelheim, JB Therapeutics, Sanofi-Aventis, Novartis, UCB, GSK, Array BioPharma, Active Biotech, Galapagos, Inventiva, Medac, Pfizer, Anamar and RuiYi, and is stock owner of 4D Science. OD has received consultancy fees from 4D Science, Actelion, Active Biotech, Bayer, Biogenidec, BMS, Boehringer Ingelheim, EpiPharm, Ergonex, espeRare Foundation, Genentech/Roche, GSK, Inventiva, Lilly, Medac, Medimmune, Pharmacyclics, Pfizer, Serodapharm, Sinoxa and UCB, and received research grants from Actelion, Bayer, Boehringer Ingelheim, Ergonex, Pfizer and Sanofi, and has a patent mir-29 for the treatment of systemic sclerosis licensed. WJG has received teaching fees from Pfizer. CA has served as a consultant for AbbVie, Pfizer, Roche, UCB, MSD, BMS and Novartis, and has received research funding and speaker fees from AbbVie, Pfizer, Roche, UCB, MSD, BMS and Novartis. FCH has received research funding from Actelion. MEA has undertaken advisory board work and received honoraria from Actelion, and received speaker’s fees from Bristol-Myers Squibb. NSD has done consultancy for AbbVie, Pfizer, Roche and MSD, and received speaker’s fees from AbbVie, Boehringer-Ingelheim, Pfizer, Richter Gedeon, Roche and MSD. HG has done consultancy work and received honoraria from Actelion. UM-L is funded in part by EUSTAR, EULAR and the European Community (Desscipher programme). JMvL has received honoraria from Eli Lilly, Pfizer, Roche, MSD and BMS. SP has received research grants from Actelion Pharmaceuticals Australia, Bayer, GlaxoSmithKline Australia and Pfizer, and speaker fees from Actelion. AR receives funding from AstraZeneca. CPD has done consultancy for GSK, Actelion, Bayer, Inventiva and Merck-Serono, received research grant funding from GSK, Actelion, CSL Behring and Inventiva, received speaker’s fees from Bayer and given trial advice to Merck-Serono., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features., Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined., Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001)., Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objective: In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN)., Methods: All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24., Results: Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms., Conclusion: Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate., (© 2017, American College of Rheumatology.)

Objectives: A single-center case-control study was carried out to investigate the relationship between occupational and environmental exposure and organizing pneumonia (OP)., Methods: Thirty-seven cases of OP, including 25 cases of cryptogenic OP, and 111 controls were included. Occupational exposure was assessed retrospectively by an industrial hygienist and an occupational physician, through semi-quantitative estimates of exposure. An exposure score was calculated for each subject, based on probability, intensity, daily frequency, and duration of exposure for each period of employment. The final cumulative exposure score was obtained by summing exposure scores for all periods of employment., Results: Significant associations with all-cause OP were observed for exposure to tetrachloroethylene (OR 13.33, CI 95% 1.44-123.5) and silica (OR 6.61, CI 95% 1.16-37.71). A significant association with cryptogenic OP was observed only for tetrachloroethylene (OR 31.6, CI 95% 1.64-610.8). No associations were found for environmental exposure., Conclusion: Despite its low statistical power, this work suggests that occupational risk factors could be involved in OP.

The objective of the study was to assess the quality of life (QOL) of patients with giant cell arteritis (GCA), following high dose of corticosteroids (CS). Thirty patients with GCA who had stopped CS or who were under long-term low dose of CS were included and matched to 60 controls. QOL was measured by the SF-36 score and a specific questionnaire. GCA patients had no impairment of QOL compared to controls according to SF-36. Most of them (57%) estimated that their general condition was improved following treatment. Patients with GCA complications or CS therapy side effects had no significant impairment of their QOL compared with patients without complications or adverse effects. Only the patients who had gained weight had a lower score on the domain "Vitality" (VT; p = 0.013). Walking difficulties were the most frequent complaints. They were associated with impaired scores on the physical summary score (p = 0.0340) and on the "General Health" (GH; p = 0.005) and "Physical Functioning" (PF, p = 0.0298) domains. Falls among GCA patients were associated with altered scores on the domain VT (p = 0.0058) and on the mental summary score if they had fallen at least three times (p = 0.0460). GCA patients following high dose of CS or under long-term low doses of CS have no significant impairment of their QOL compared to controls. GCA complications, including visual impairment, do not seem to have any major impact on QOL.

Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches., Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival., Results: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months., Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed., Trial Registration Number: NCT02339441., Competing Interests: Competing interests: ALH has done consultancy work for Actelion, served on a Data Safety Monitoring Board for Apricus, received research funding and speaker's fees from Actelion, and speaker's fees from GSK. JHWD has consultancy relationships and/or has received research funding from Actelion, BMS, Celgene, Bayer Pharma, Boehringer Ingelheim, JB Therapeutics, Sanofi-Aventis, Novartis, UCB, GSK, Array Biopharma, Active Biotech, Galapagos, Inventiva, Medac, Pfizer, Anamar and RuiYi and is stock owner of 4D Science GmbH. OD has received consultancy fees from 4D Science, Actelion, Active Biotech, Bayer, Biogenidec, BMS, Boehringer Ingelheim, EpiPharm, Ergonex, espeRare Foundation, Genentech/Roche, GSK, Inventiva, Lilly, Medac, Medimmune, Pharmacyclics, Pfizer, Serodapharm, and Sinoxa and received research grants from Actelion, Bayer, Boehringer Ingelheim, Ergonex, Pfizer and Sanofi, and has a patent mir-29 for the treatment of systemic sclerosis licenced. WG has received teaching fees from Pfizer. FH has received research funding from Actelion. MEA has undertaken advisory board work and received honoraria from Actelion, and received speaker's fees from Bristol-Myers Squibb. LC has done advisory board work for Gilead and served Data Safety Monitoring Boards for Cytori and Reata. HG has done consultancy work and received honoraria from Actelion. UM-L is funded in part bu EUSTAR/EULAR. JMvL has received honoraria from Eli Lilly, Pfizer, Roche, MSD and BMS. AR receives funding from AstraZeneca. CPD has done consultancy for GSK, Actelion, Bayer, Inventiva and Merck-Serono, received research grant funding from GSK, Actelion, CSL Behring and Inventiva, received speaker's fees from Bayer and given trial advice to Merck-Serono., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: Ischemic digital ulcers (DU) represent a major complication of systemic sclerosis (SSc). We investigated the impact of controlling the ulcerative disease on disability, pain, and quality of life in SSc patients receiving bosentan., Methods: ECLIPSE (Study AC-052-517) is a 2-year prospective, multicenter, and observational study. Patients with SSc who experienced at least 1 DU in the previous year and received bosentan were included between October 2009 and March 2011. Disability scores [Cochin Hand Function Scale (CHFS) and Health Assessment Questionnaire Disability Index (HAQ-DI)], pain scores (visual analog scale), and quality-of-life scores (SF-36) were collected at inclusion and 1 year later (primary endpoint). A controlled ulcerative disease was defined by the absence of ongoing/new DU episode between inclusion and 1-year follow-up., Results: Data were available at 1 year for 120 patients out of 190 included. During follow-up, 46 (38.3%) patients experienced a new DU episode. The number of DU per patient decreased from 1.4 ± 1.8 at inclusion to 0.6 ± 1.6 (p < 0.0001) at 1 year. Disability scores decreased from 1.0 ± 0.7 to 0.9 ± 0.7 (p = 0.04) for the HAQ-DI and from 29 ± 20 to 25 ± 20 (p = 0.005) for the CHFS; the pain score decreased from 4.3 ± 3.1 to 2.9 ± 2.8 (p < 0.0001). This improvement was attributed to patients with a controlled ulcerative disease (48.3%), who significantly improved HAQ-DI (p = 0.04), CHFS (p = 0.04), and pain score (p = 0.046)., Conclusions: In patients with SSc, control of the ulcerative disease for 1 year was associated with significant attenuation of hand disability., (Copyright © 2017 Elsevier Inc. All rights reserved.)