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Explore trial participants’ and research team members’ perceptions of the impact of the videoconference-based, supportive care program (SPIN-CHAT Program) during early COVID-19 for individuals with systemic sclerosis (SSc). Data were collected cross-sectionally. A social constructivist paradigm was adopted, and one-on-one videoconference-based, semi-structured interviews were conducted with SPIN-CHAT Trial participants and research team members. A hybrid inductive-deductive approach and reflexive thematic analysis were used. Of the 40 SPIN-CHAT Trial participants and 28 research team members approached, 30 trial participants (Mean age = 54.9; SD = 13.0 years) and 22 research team members agreed to participate. Those who took part in interviews had similar characteristics to those who declined. Five themes were identified: (1) The SPIN-CHAT Program conferred a range of positive psychological health outcomes, (2) People who don’t have SSc don’t get it: The importance of SSc-specific programming, (3) The group-based format of the SPIN-CHAT Program created a safe space to connect and meet similar others, (4) The structure and schedule of the SPIN-CHAT Program reduced feelings of boredom and contributed to enhanced psychological health, (5) The necessity of knowledge, skills, and tools to self-manage SSc and navigate COVID-19. Participants’ and research team members’ perspectives elucidated SPIN-CHAT Program benefits and how these benefits may have been realized. Results underscore the importance of social support from similar others, structure, and self-management to enhance psychological health during COVID-19. clinicaltrials.gov (NCT04335279)IMPLICATIONS FOR REHABILITATIONThe videoconference-based, supportive care SPIN-CHAT Program enhanced psychological health amongst individuals affected by systemic sclerosis.SPIN-CHAT Program participants and research team members shared that being around similar others, program structure, and self-management support were important and may have contributed to enhanced psychological health.Further efforts are required to explore experiences within supportive care programs to better understand if and how psychological health is impacted. The videoconference-based, supportive care SPIN-CHAT Program enhanced psychological health amongst individuals affected by systemic sclerosis. SPIN-CHAT Program participants and research team members shared that being around similar others, program structure, and self-management support were important and may have contributed to enhanced psychological health. Further efforts are required to explore experiences within supportive care programs to better understand if and how psychological health is impacted.

Background Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. We completed an initial feasibility trial of an online self-administered version of the Scleroderma Patient-centered Intervention Network Self-Management (SPIN-SELF) Program using the cohort multiple randomized controlled trial (RCT) design. Due to low intervention offer uptake, we will conduct a new feasibility trial with progression to full-scale trial, using a two-arm parallel, partially nested RCT design. The SPIN-SELF Program has also been revised to include facilitator-led videoconference group sessions in addition to online material. We will test the group-based intervention delivery format, then evaluate the effect of the SPIN-SELF Program on disease management self-efficacy (primary) and patient activation, social appearance anxiety, and functional health outcomes (secondary). Methods This study is a feasibility trial with progression to full-scale RCT, pending meeting pre-defined criteria, of the SPIN-SELF Program. Participants will be recruited from the ongoing SPIN Cohort (http://www.spinsclero.com/en/cohort) and via social media and partner patient organizations. Eligible participants must have SSc and low to moderate disease management self-efficacy (Self-Efficacy for Managing Chronic Disease (SEMCD) Scale score ≤ 7.0). Participants will be randomized (1:1 allocation) to the group-based SPIN-SELF Program or usual care for 3 months. The primary outcome in the full-scale trial will be disease management self-efficacy based on SEMCD Scale scores at 3 months post-randomization. Secondary outcomes include SEMCD scores 6 months post-randomization plus patient activation, social appearance anxiety, and functional health outcomes at 3 and 6 months post-randomization. We will include 40 participants to assess feasibility. At the end of the feasibility portion, stoppage criteria will be used to determine if the trial procedures or SPIN-SELF Program need important modifications, thereby requiring a re-set for the full-scale trial. Otherwise, the full-scale RCT will proceed, and outcome data from the feasibility portion will be utilized in the full-scale trial. In the full-scale RCT, 524 participants will be recruited. Discussion The SPIN-SELF Program may improve disease management self-efficacy, patient activation, social appearance anxiety, and functional health outcomes in people with SSc. SPIN works with partner patient organizations around the world to disseminate its programs free-of-charge. Trial registration ClinicalTrials.govNCT04246528. Registered on 27 January 2020

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.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.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).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.

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis, microangiopathy, and autoantibodies. We previously reported that circulating follicular helper T (cTfh) cells are increased in SSc and induce plasmablast differentiation. However, mechanisms leading to cTfh cell expansion and activation in SSc remain to be established. Tfh cells require IL-12 for their expansion and differentiation. 6-Sulfo LacNAc monocytes (slanMo), a subset of monocytes, have a higher capacity to produce IL-12 and to induce CD4+ T cell proliferation in comparison with dendritic cells (DC) or classical monocytes. The aim of this study was to perform a quantitative and functional analysis of monocytes and DC and to correlate them with cTfh cell expansion and clinical manifestations in SSc. Using flow cytometry, we analyzed different monocyte subsets including slanMo and DC from 36 SSc patients and 26 healthy controls (HC). In vitro culture experiments of sorted slanMo were performed for functional analysis and cytokine production. We observed that slanMo, intermediate and non-classical monocytes were increased in SSc in comparison with HC. Furthermore, the increase in slanMo cells was more potent in patients with diffuse SSc. We observed a significant positive correlation between slanMo and cTfh cell levels in SSc patients but not in HC. Other monocyte subsets did not correlate with cTfh cell expansion. In addition, we observed that in vitro, slanMo cells from SSc patients produced less IL-12 than slanMo from HC. SlanMo are increased in SSc and may participate in the activation of cTfh cells in SSc.

Objectives SSc is an autoimmune disease characterized by fibrosis, microangiopathy and immune dysfunctions including dysregulation of proinflammatory cytokines. Clonal haematopoiesis of indeterminate potential (CHIP) is defined by the acquisition of somatic mutations in haematopoietic stem cells leading to detectable clones in the blood. Recent data have shown a higher risk of cardiovascular disease in patients with CHIP resulting from increased production of proinflammatory cytokines and accelerated atherosclerosis. Eventual links between CHIP and autoimmune diseases are undetermined. The aim of our study was to evaluate the prevalence of CHIP in SSc patients and its association with clinical phenotype. Methods Forty-one genes frequently mutated in myeloid malignancies were sequenced in peripheral blood mononuclear cells from 90 SSc patients and 44 healthy donors. Results A total of 15 somatic variants were detected in 13/90 SSc patients (14%) and four somatic variants in 4/44 (9%) healthy donors (HD) (P = 0.58). The prevalence of CHIP was significantly higher in younger SSc patients than in HD: 25% (6/24) vs 4% (1/26) (P = 0.045) under 50 years and 17% (7/42) vs 3% (1/38) (P = 0.065) under 60 years. The prevalence of CHIP in patients over 70 years was similar in SSc patients and healthy donors. The most common mutations occurred in DNMT3A (seven variants). No major clinical differences were observed between SSc patients with or without CHIP. Conclusion Whether CHIP increases the risk to develop SSc or is a consequence of a SSc-derived modified bone marrow micro-environment remains to be explored.

SETTING: Tuberculosis (TB) is a potential trigger of haemophagocytic syndrome (HS) but little is known about the features of TB-associated HS.OBJECTIVE: To assess the risk factors associated with HS in patients with TB.DESIGN: We performed a multicentre case-control study assessing the medical records of adult patients diagnosed with proven TB with (TB/HS+) or without (TB/HS–) associated HS.RESULTS: Twenty-one patients with TB/HS+ (24% women, median age, 37 years [IQR 30–48]) were included in the study. Eleven patients (52%) were infected with human immunodeficiency virus and seven patients (33%) were immunocompromised due to other reasons. TB was disseminated in 17 patients (81%). Compared with 50 control TB patients (TB/HS–), patients with TB/HS+ were more likely to be immunocompromised (86% vs. 18%; P < 0.001) and to present with disseminated TB (80% vs. 12%; P < 0.001). The outcome was poorer in patients with TB/HS+, with a higher admission rate to intensive care (71% vs. 0%; P < 0.001) and a higher risk of death (38% vs. 7%; P = 0.005).CONCLUSION: TB/HS+ occurred more likely in immunocompromised patients and severely impaired the prognosis of TB. Further studies are needed to devise therapeutic strategies for patients with TB/HS+.

International audience; Introduction: Patients with systemic sclerosis (SSc) have an increased risk of malignancy. In this study, we aimed to analyze the prevalence of cancer, the risk factors and the impact on overall survival.Patients and methods: We analyzed clinical (history of cancer, toxic exposition, organ involvement), immunological and treatment data in a monocentric cohort of SSc patients followed between January 2004 and December 2017.Results: Two hundred and ten patients with SSc were included. During the follow-up, twenty-one patients (10 %) were diagnosed with malignancies. The underlying malignancies were breast adenocarcinoma (n=6, 28%), lung cancer (n=6, 28%), colorectal (colic adenocarcinoma, carcinoid tumor of the appendix), ovarian and cervix uteri, melanoma, kidney and papillary thyroid carcinoma (one of each). The median time between the first visit and the diagnosis of cancer was 4 [2-10] years. The overall survival in SSc patients with cancer was not significantly different from patients without cancer, with median survival during the first quartile (75%) at 12 years for patients with cancer and 11.6 years for those without cancer (P=0.9). The history of renal scleroderma crisis (HR 10.99, IC95% [1.95-62.07]; P=0.006) and the presence of anti-topoisomerase I antibodies (HR 5.5, IC95% [1.40-21.67]; P=0.01) were associated with an increased risk of cancer, whereas the presence of gastroesophageal reflux was inversely associated with the cancer occurrence (HR 0.22, IC95% [0.056-0.867]; P=0.03).Conclusion: The history of renal scleroderma crisis and the positivity of anti-topoisomerase I antibodies were associated with an increased risk of cancer in SSc patients in this monocentric study.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Systemic sclerosis (SSc) is a connective tissue disease characterized by microangiopathy. Peripheral arterial disease, increasingly studied during SSc, is responsible for digital ulcers, associated with a high risk of amputation. The aim of our study was to assess the frequency of lower limb arterial impairment in SSc patients by measuring ankle-brachial index (ABI), toe pressure (TP), and toe-brachial index (TBI).Systemic sclerosis patients were included prospectively during 1 year in Tenon and Saint-Antoine Hospitals, Paris. Clinical and biological data were recorded. For each patient, ABI, TP, and TBI were measured and an arterial duplex ultrasonography was prescribed in case of abnormal results.Eighty-six patients were included (94% women, median age 62 years). Only 24% of them had no lower limb hemodynamic vascular abnormalities; 44% had an isolated microvascular abnormality (normal ABI and TBI0.75); 31% had at least a macrovascular injury associated or not with microvascular impairment (abnormal ABI) and 12.6% had a TP50 mmHg. During follow-up, there was a trend towards association of low TBI with more major adverse event (all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, and lower limb ischemic manifestations) than normal TBI.By measuring ABI and TP, we showed that 76% of SSc patients had hemodynamic arterial lower limb abnormalities related to macro- and/or microvascular impairment and that 28% had vascular stiffness. In SSc patients, ABI is not an accurate tool to detect lower limb arterial disease, likely due to underlying micro- and macrovascular changes. Key Points • The presence of lower limb macro-and/or microvascular involvement was detected in 76% of SSc patients. • In SSc patients, ABI is not an accurate tool to detect lower limb arterial disease, likely due to underlying microvascular changes and frequent arterial stiffness.

International audience; Objective: To report the efficacy of rituximab plus belimumab in patients with refractory cryoglobulinemia vasculitis (CV).Methods: Belimumab was administered intravenously at a dose of 10 mg/kg on days 0, 14, 28 and then every month in association with rituximab in 4 patients with refractory CV. Demographic, clinical and laboratory characteristics, treatment modalities and outcomes were recorded.Results: All patients had type II IgM Kappa cryoglobulinemia, which was associated with primary Sjögren syndrome (n = 1), hepatitis C virus infection (n = 1), and essential (n = 2). Main manifestations of CV included purpura (n = 4), arthralgia and peripheral neuropathy (n = 3), and glomerulonephritis and skin ulcers (n = 1). In all cases, CV was refractory and/or relapse following rituximab. Intravenous belimumab infusion along with rituximab resulted in rapid clinical response in the four patients. Osteitis and recurrent urinary tract infections occurred in two patients.Conclusion: Belimumab along with rituximab showed promising results in refractory patients with CV.

Introduction Kikuchi-Fujimoto disease (KFD) is a self-limited histiocytic necrotizing lymphadenitis sometimes affecting the skin. “Kikuchi disease-like inflammatory pattern” (KLIP) has been described in cutaneous lesions as similar pathological features in patients without lymph node involvement and as a potential clue for the diagnosis of lupus. We aimed to describe KLIP-associated clinical and immunological features in lupus patients with a retrospective case-control study. Methods Thirteen cases of KLIP were included as well as thirty-nine age- and sex-matched control lupus patients without KLIP. At the time of KLIP diagnosis, 4/13 patients (31%) had isolated cutaneous lupus erythematosus (CLE) and 9/13 had (69%) systemic lupus erythematosus (SLE) including 6 (46%) with severe haematological, lung, cardiac or renal disease. KLIP features were observed in skin biopsies of different clinical presentations. Results Compared with our control group, KLIP patients more frequently had SLE 9/13 (69%) versus 8/39 (21%) (OR 12.9; IC95% [2.86–58.2]; p = 0.0004) and more frequently severe SLE. Two out of four CLE exhibiting KLIP lesions (50%) developed severe SLE with cardiac or renal involvement after 12 and 24 months, respectively. Treatment with thalidomide 100 mg/day allowed rapid and complete clearance of cutaneous lesions in 6/6 KLIP patients. The need to use thalidomide tended to be more frequent in KLIP patients than in controls. Conclusion Our study suggests that KLIP features in lupus skin lesions are associated with SLE and severe systemic features. Despite a limited number of isolated CLE patients with KLIP features in the skin, this observation may warrant closer follow-up on patients with a higher risk of developing SLE.

Summary Background Pain is an important and detrimental feature of systemic sclerosis but is often overlooked or deprioritised in research and clinical care. Raynaud's phenomenon, arthritis, and cutaneous ulcers are among the commonly reported disease manifestations of systemic sclerosis that could be associated with pain. We aimed to assess levels of pain intensity and interference and to evaluate disease factors associated with pain intensity and interference. Methods In this multicentre cross-sectional study, participants from the Scleroderma Patient-centered Intervention Network cohort who completed pain intensity and interference measures (Patient Reported Outcomes Information System-29 profile, version 2·0) as part of baseline assessments were included. Patients were recruited from 46 centres in Australia, Canada, France, Mexico, Spain, the UK, and the USA between April 15, 2014, and Jan 7, 2020. Eligible patients included those aged 18 years or older who met the criteria for systemic sclerosis devised by the American College of Rheumatology and the European League Against Rheumatism. Associations of pain intensity and pain interference with systemic sclerosis-related variables and overlap syndromes, controlling for sociodemographic variables, were assessed with multiple linear regression. Continuous independent variables were standardised. Findings Among 2157 participants with systemic sclerosis (268 [12%] males and 1889 [88%] females), 1870 (87%) reported mild, moderate, or severe pain (defined as ≥1 on a 0 to 10 scale), and 815 (38%) reported moderate or severe pain (defined as ≥5). Moreover, 757 (35%) participants reported moderate or severe pain interference. Greater pain intensity was independently associated with female sex (0·58 points [95% CI 0·26–0·90]), non-White race or ethnicity (0·50 points [0·21–0·79]), fewer years in formal education (0·30 points per SD [0·19–0·41]), country (reference: USA; Canada: 0·29 points [0·01–0·57] and UK: 0·58 points [0·21–0·95]), greater body-mass index (0·35 points per SD [0·24–0·45]); joint contractures (0·67 points [0·39–0·94]), digital ulcers (0·33 points [0·10–0·55]), gastrointestinal involvement (0·66 points [0·33–0·98]), skin involvement (measured using modified Rodnan skin score; 0·22 points per SD [0·10–0·35]), rheumatoid arthritis (0·96 points [0·50–1·43]), and Sjogren's syndrome (0·42 points [0·01–0·83]). Pain interference results were similar. Interpretation Pain is common among people with systemic sclerosis. Controlling for sociodemographic variables, greater pain was associated with multiple systemic sclerosis-related manifestations, including joint contractures, digital ulcers, gastrointestinal involvement, skin involvement, and the presence of overlap syndromes. Health-care providers should work with patients to address pain, including identifying and addressing systemic sclerosis manifestations associated with their pain, and supporting behavioural approaches to minimise impact on function and quality of life. Funding Canadian Institutes of Health Research, Arthritis Society, The Lady Davis Institute for Medical Research of the Jewish General Hospital, Jewish General Hospital Foundation, McGill University, Scleroderma Society of Ontario, Scleroderma Canada, Sclerodermie Quebec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, and Scleroderma Queensland.

Introduction No studies have examined factors associated with fear in any group of people vulnerable during COVID-19 due to pre-existing medical conditions. Objective To investigate factors associated with fear of consequences of COVID-19 among people living with a pre-existing medical condition, the autoimmune disease systemic sclerosis (SSc; scleroderma), including country. Methods Pre-COVID-19 data from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort were linked to COVID-19 data collected in April 2020. Multivariable linear regression was used to assess factors associated with continuous scores of the 10-item COVID-19 Fears Questionnaire for Chronic Medical Conditions, controlling for pre-COVID-19 anxiety symptoms. Results Compared to France (N = 156), COVID-19 Fear scores among participants from the United Kingdom (N = 50) were 0.12 SD (95% CI 0.03 to 0.21) higher; scores for Canada (N = 97) and the United States (N = 128) were higher, but not statistically significant. Greater interference of breathing problems was associated with higher fears due to COVID-19 (Standardized regression coefficient = 0.12, 95% CI 0.01 to 0.23). Participants with higher financial resources adequacy scores had lower COVID-19 Fear scores (Standardized coefficient = −0.18, 95% CI −0.28 to −0.09). Conclusions Fears due to COVID-19 were associated with clinical and functional vulnerabilities in this chronically ill population. This suggests that interventions may benefit from addressing specific clinical issues that apply to specific populations. Financial resources, health policies and political influences may also be important. The needs of people living with chronic illness during a pandemic may differ depending on the social and political context in which they live., Highlights • People with chronic diseases may experience high levels of fear due to COVID-19. • We examined factors associated with fears due to COVID-19 in an at-risk population. • We used the validated COVID-19 Fears Questionnaire for Chronic Medical Conditions. • Fears due to COVID-19 among people with SSc differed substantially by country. • Interference of breathing problems and financial adequacy were related to fears.

Introduction: To describe the efficacy of tocilizumab in patients with Graves' orbitopathy resistant or dependent to steroids and compare to rituximab treated patients.Patients and Methods: Graves's orbitopathy response was considered as decrease of at least 2 points of the CAS.Results: Twenty-one patients were included, 7 patients were treated with tocilizumab and 14 with rituximab. The primary was achieved in all 7 patients (100%) on tocilizumab and 9 out of 14 patients on (64%) rituximab (p = .17). Mean change in CAS was consistent with a decrease of 3.3 ± 0.5 points in patients on tocilizumab versus 2.5 ± 1.9 in patients on rituximab (p = .07). One patient on tocilizumab (14%) and 4 patients (29%) on rituximab experienced significant relapse during the follow-up. The difference in relapse-free survival was not significant in patients on tocilizumab (10.8 ± 4 months) compared with rituximab (17.88 ± 3.66).Conclusion: We showed a significant improvement in the CAS, visual acuity, diplopia, and proptosis with both tocilizumab and rituximab.

BackgroundDescription of the prevalence of diseases and resources mobilized for the management of each disease is essential to identify public health priorities. We described the prevalences of 58 health conditions and all reimbursed healthcare expenditure by health condition in France between 2012 and 2017.Methods and FindingsAll national health insurance general scheme beneficiaries (87% of the French population) with at least one reimbursed healthcare expenditure were included from the French national health database. We identified health conditions (diseases, episodes of care, chronic treatments) by algorithms using ICD-10 codes for long-term diseases or hospitalisations, medications or medical procedures. We reported crude and age and sex-standardized annual prevalences between 2012 and 2017, and total and mean (per patient) reimbursed expenditure attributed to each condition without double counting, and according to the type of expenditure.In 2017, in a population of 57.6 million people (54% of women, median age: 40 years), the most prevalent diseases were diabetes (standardized prevalence: 5.8%), chronic respiratory diseases (5.5%) and chronic coronary heart disease (2.9%). Diseases concentrating the highest expenditures were active cancers (10% of total expenditure of €140.1 billion), mental illness (10%; neurotic and mood disorders: 4%; psychotic disorders: 3%), and chronic cardiovascular diseases (8%). Between 2012 and 2017, the most marked increase in total expenditure concerned liver and pancreatic diseases (+9.3%), related to the increased drug expenditure in 2014. Conversely, the increase in the number of patients (and the prevalence) explained the majority of the increase of total expenditures for cardiovascular disease, diabetes and mental illness.ConclusionsThese results showed a regular increase of the prevalence and expenditure of certain chronic diseases, probably related to ageing of the population, and increased expenditures related to major therapeutic innovations. The Diseases and Healthcare Expenditure Mapping therefore enlightens decision-makers in charge of public health and health accounts.

Osteoarticular involvement in systemic sclerosis (SSc) is frequent and varied. Data are scarce on the prevalence and risk factors of osteoporosis (OP). We aimed to assess clinical parameters, radiological parameters, US articular involvements, and the frequency of OP and evaluate SSc-specific risk factors. In a prospective cohort of 54 patients with SSc, data of OP risk factors, SSc organ involvements, tender and swollen joint counts, DAS28-CRP, hand US sonographies, X-ray hand views, and bone mineral density (BMD) were assessed. BMD values were compared to those from a healthy female population (OFELY cohort). Nineteen patients (40%) had OP. SSc was a risk factor of lower BMD in the patient group than in the control group. OP was associated with SSc-related risk factors and not with conventional OP risk factors. Nine patients had clinical synovitis (16%), and 23 (68%) patients had at least one US synovitis. No correlation was found with articular destruction, disease severity, autoantibody profile, or other organ impairment.

Systemic sclerosis (SSc) is an autoimmune disease, characterized by fibrosis of the skin and other organs, vascular impairment and deficient immune responses. Mucosal-associated invariant T cells (MAIT) have been involved in various inflammatory and autoimmune diseases. The aims of this study were to determine the frequencies of MAIT cells in the blood of patients with systemic sclerosis (SSc) and to compare their distribution in different types of SSc. Blood samples from patients with SSc and healthy controls were examined by flow cytometer to analyse the frequencies of MAIT and γδ T cells. We demonstrate that in SSc the frequencies and absolute numbers of MAIT and γδ T cells are significantly reduced in comparison with healthy controls. MAIT and γδ T cells did not correlate with C-reactive protein, BNP, pulmonary involvement or median skin fibrosis scale, steroid amount or disease duration. In addition, MAIT and γδ T cells decrease did not stratify with gender, interstitial lung disease or active digital ulcers. Functional studies are necessary to determine the signification of MAIT cells decrease in systemic sclerosis.

Resume Introduction Le systeme national d’information inter-regime de l’Assurance Maladie (Sniiram) apporte des informations utiles sur la prise en charge des pathologies et les couts associes. Methodes Parmi les 57 millions d’assures du regime general (86 % de la population), une prise en charge pour cancer a ete retrouvee a partir d’algorithmes bases sur les diagnostics des sejours hospitaliers et/ou des affections de longue duree. Les depenses attribuables aux cancers, remboursees par l’assurance maladie, ont ete calculees (euros). Resultats En 2014, 2,491 millions de personnes, 4,4 % des assures (hommes 1,1 million, 5,1 % ; femmes 1,3 million, 4,9 %), avaient un marqueur de prise en charge pour cancer. Le taux de croissance annuel moyen de cet effectif etait de 0,8 % en 2012–2014. Les depenses attribuables au cancer etaient de 13,5 milliards : 5 milliards en soins de ville (medicaments 2,3 milliards), 7,5 milliards pour l’hopital (liste des medicaments en sus 1,3 milliard) et 900 millions en indemnites journalieres/invalidite. Le taux de croissance annuel moyen des depenses 2012–2014 etait de 4 % (medicaments +6,2 %). Les taux de patients et les depenses afferentes etaient de 1,8 % et 2,5 milliards pour le cancer du sein (femmes), 1,5 % et 1,0 milliard pour celui de la prostate (hommes), 0,9 % et 1,5 milliard pour le colon, et 0,19 % et 1,3 milliard pour le poumon. Discussion Les cancers constituent un des premiers groupes de pathologies chroniques en termes d’effectifs de personnes et de depenses. Si les effectifs restent peu evolutifs, les depenses augmentent et les medicaments constituent un poste particulierement dynamique.

Resume Introduction Le deficit en sphingomyelinase acide est une maladie de surcharge lysosomale autosomique recessive allant d’une forme neuro-viscerale severe de l’enfant, la maladie de Niemann-Pick A, a une forme chronique viscerale evoluant jusqu’a l’âge adulte, la maladie de Niemann-Pick B (NP-B). Methodes Etude retrospective multicentrique francaise de patients adultes suivis entre 1985 et mars 2015 pour une maladie de NP-B. Recueil des donnees cliniques et paracliniques a partir des dossiers medicaux. Resultats Vingt-huit patients (19 hommes, 9 femmes) ont ete analyses. Seize patients ont ete diagnostiques avant l’âge de 10 ans. Les principaux symptomes au diagnostic etaient l’hepatosplenomegalie et l’atteinte pulmonaire interstitielle. Une thrombopenie etait notee dans 24 des 28 cas (plaquettes Conclusion La maladie de NP-B associe une hepatosplenomegalie et une atteinte pulmonaire interstitielle. Un diagnostic precoce permet de reduire les complications et d’eviter les procedures inappropriees (par exemple splenectomie). A l’heure actuelle, la prise en charge repose principalement sur un traitement symptomatique, mais un essai de phase 2/3 de traitement enzymatique substitutif est en cours.

International audience; BACKGROUND:As intravenous immunoglobulins (IVIG) exhibit immunomodulatory and antifibrotic properties, they may be a relevant treatment for systemic sclerosis (SSc). The objectives of this work were thus to report on the efficacy and safety of IVIG in a population of SSc patients and to review the available literature.METHODS:46 patients from 19 French centers were retrospectively recruited. They were included if they had a diagnosis of SSc and received at least 1 IVIG infusion at a dosage >1g/kg/cycle. Relevant data collected at IVIG discontinuation were compared to those collected at IVIG initiation. A comprehensive literature review was performed.RESULTS:We observed a significant improvement of muscle pain (74% vs. 20%, p

Objective Contagious disease outbreaks and related restrictions can lead to negative psychological outcomes, particularly in vulnerable populations at risk due to pre-existing medical conditions. No randomised controlled trials (RCTs) have tested interventions to reduce mental health consequences of contagious disease outbreaks. The primary objective of the Scleroderma Patient-centered Intervention Network COVID-19 Home-isolation Activities Together (SPIN-CHAT) Trial is to evaluate the effect of a videoconference-based program on symptoms of anxiety. Secondary objectives include evaluating effects on symptoms of depression, stress, loneliness, boredom, physical activity, and social interaction. Methods The SPIN-CHAT Trial is a pragmatic RCT that will be conducted using the SPIN-COVID-19 Cohort, a sub-cohort of the SPIN Cohort. Eligible participants will be SPIN-COVID-19 Cohort participants without a positive COVID-19 test, with at least mild anxiety (PROMIS Anxiety 4a v1.0 T-score ≥ 55), not working from home, and not receiving current counselling or psychotherapy. We will randomly assign 162 participants to intervention groups of 7 to 10 participants each or waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups but not in the waitlist control. The SPIN-CHAT Program includes activity engagement, education on strategies to support mental health, and mutual participant support. Intervention participants will receive the 4-week (3 sessions per week) SPIN-CHAT Program via videoconference. The primary outcome is PROMIS Anxiety 4a score immediately post-intervention. Ethics and dissemination The SPIN-CHAT Trial will test whether a brief videoconference-based intervention will improve mental health outcomes among at-risk individuals during contagious disease outbreak., Highlights • No RCTs have tested mental health interventions in contagious disease outbreaks. • People with scleroderma face fear and isolation during COVID-19. • SPIN-CHAT is designed to improve mental health in SSc patients during COVID-19. • SPIN-CHAT provides 12 group sessions over 4 weeks. • The SPIN-CHAT trial will randomize 162 participants to intervention or waitlist.

Resume Introduction L’atteinte cardiaque au cours de la sclerodermie est frequente et peut concerner le myocarde, le tissu conductif et le pericarde. En presence d’une atteinte cardiaque, le pronostic fonctionnel et vital peut etre engage. Observation Nous rapportons l’observation d’une patiente atteinte d’une sclerodermie systemique ayant presentee une atteinte cardiaque severe, avec une pericardite compressive, une dysfonction systolique severe et des troubles de rythme supra-ventriculaire. Malgre un drainage pericardique, un traitement immunosuppresseur (corticoides et rituximab) et le traitement symptomatique de l’insuffisance cardiaque, l’evolution etait defavorable avec la persistance d’une dysfonction systolique severe (fraction d’ejection du ventricule gauche a 15 %). Un traitement par immunoglobulines intraveineuses etait introduit, permettant une evolution favorable sur le plan cardiaque, avec l’amelioration de la dyspnee, de la fraction d’ejection et de facon concomitante de l’atteinte cutanee. Conclusion Notre observation illustre un cas d’atteinte cardiaque grave au cours d’une sclerodermie systemique. Devant l’echec des differents traitements, un traitement par immunoglobulines intraveineuses a ete utilise et a permis une nette amelioration de l’atteinte cardiaque, de facon concomitante a une amelioration cutanee.

Background The aim of this study was to assess the economic burden of HIV disease in France, by analyzing structure and trends of expenditure between 2012 and 2017. Methods We identified people with HIV disease among beneficiaries of the health insurance general scheme (covering more than 57 million people, 87% of the French population), applying algorithms combining inpatient and outpatient diagnoses and claims for specific drug treatments or laboratory examinations. The individuals’ expenditure (26 different items) reimbursed for hospitalizations, ambulatory care and cash payments were included. A top-down method was used to attribute expenditure to HIV disease based on the average expenditure calculated for individuals with only HIV disease. To analyze trends, we applied the same methodology from 2012 through 2017. Results In 2017, HIV disease was identified for 131 800 individuals (0.2% of the population) and expenditure attributed to HIV disease corresponded to €1.3 billion (1% of the 140.1 billion reimbursed by the general insurance scheme). Drug treatment accounted for 85% of total expenditure reimbursed (1.2 billion). Between 2012 and 2017, the number of HIV patients identified increased steadily (+16,800 patients with an annual growth rate of 2.8%) and expenditure attributed to HIV disease increased by €8 billion. However, annual expenditure growth was variable, as a result of instability in the average annual cost per patient, ranging from 9,700€to 11,100€per year per patient. This reflects changes in practice and drug prices. Conclusions The detailed analysis of expenditures attributed to HIV disease showed that drug treatments account for the large majority of total reimbursements. Annual variation in total expenditure could therefore reflect evolution in prescription practices, such as the extension of treatment indications; or in drug prices, with the availability of combined treatments. Key messages Drug treatments account for the large majority of total reimbursements among HIV patients. Variation in total expenditure attributed to HIV disease is mainly driven by prescription practices and drug prices.

Background The purpose of this study was to assess the economic burden of cardiovascular diseases (CVDs) in France by analysing the structure and the growth of expenditure attributed to these diseases between 2012 and 2017. Methods For each year, 11 CVDs were identified from SNDS data using algorithms based on long-term disease registry and hospitalization diagnoses, applied to the population of national health insurance general scheme beneficiaries. The individuals’ expenditure (26 different items) reimbursed for hospitalisations, ambulatory care and cash payments were included. A top-down method was used to attribute expenditure to each considered groups of diseases based on the average expenditure by disease calculated for individuals with only one disease. To analyse trends, we applied the same methodology from 2012 to 2017. Results In 2017, of the €140.1 billion reimbursed, €14.0 billion (10.0%) were attributed to the care of 4.0 million people with a CVD (7.0% of the population). Short-stay hospitalisations accounted for 33% of this total expenditure. This proportion was higher for acute CVD (coronary syndrome: 64%, stroke: 56%, heart failure: 65%, pulmonary embolism: 69%) but also for valvular heart disease (50.0%). Medications represented almost 13% of the expenditure attributed to all CVDs, and up to 25% for chronic coronary heart disease. Disability pension essentially concerned sequelae of stroke (12% of the expenditure attributed to this disease). Between 2012 and 2017, the total expenditure attributed to CVDs increased by 3.3% per year, mainly due to the annual mean increase of the number of patients over the period (+3.1%). Conclusions These results demonstrate the high economic burden of CVDs in France with a detailed analysis of expenditures and their main drivers. The developed tool will help decision makers to monitor the burden of these diseases but also to provide stake holders with a better understanding of trends and regulating actions. Key messages Economic burden of CVD in France is high: 10% of healthcare expenditure. Implementation of public health policy to prevent CVD and control risk factors must be a priority.

Introduction La survenue d’un œdeme sus-claviculaire recidivant, fluctuant et lateralise a gauche doit faire evoquer le diagnostic mal connu de syndrome d’occlusion paroxystique du canal thoracique. Observations Six patients suivis dans le meme centre, tous de sexe feminin, ont ete inclus entre 2015 et 2020. L’âge median des premiers symptomes etaient de 38 ans [24–63]. Le delai median entre les premiers symptomes et le diagnostic etait de 35 mois [0–120] et la frequence variable (annuelle a mensuelle). Les symptomes etaient un œdeme non inflammatoire du creux sus-claviculaire gauche d’une duree de 3 a 5 jours. Les signes associes etaient les atteintes des sereuses avec une ascite et des douleurs abdominales (n = 5), des epanchements pleuraux (n = 4) et une pericardite (n = 1), associes a des diarrhees dans 2 cas. Les bilans biologiques etaient normaux, sans syndrome inflammatoire, d’hemodilution, de gammapathie monoclonale ou de dyslipidemie. Le dosage du C1 inhibiteur etait normal aussi. Le scanner thoracique eliminait un syndrome cave superieur et des adenopathies compressives. La lymphangio-IRM realisee pendant les crises trouvait dans tous les cas un œdeme du creux sus-claviculaire gauche sans argument pour une obstruction, une compression extrinseque ou une thrombose du confluent jugulo-sous-clavier et dans 3 cas une dilatation marquee de la portion ampullaire du canal thoracique. Le facteur declenchant etait dans 3 cas un regime alimentaire riche en graisses (« fast food », viande de sanglier). Aucun lien avec le cycle menstruel n’etait note. Les patientes ont toutes ete traitees avec un regime pauvre en graisse et deux ont egalement recu du lanreotide mensuel permettant une diminution de la frequence des crises chez une patiente et une diminution de la duree chez la seconde ; les quatre autres n’ont pas eu de recidives a ce jour. Discussion Une fois ecartees les causes d’œdeme sus-claviculaire « classiques » comme l’hypothyroidie, le syndrome cave superieur et les angiœdemes bradykiniques ou histaminiques, il faut evoquer le syndrome d’occlusion paroxystique du canal thoracique. Le diagnostic est affirme devant des œdemes paroxystiques lateralises a gauche, volontiers recidivants. L’imagerie permet d’ecarter les diagnostics differentiels tel l’occlusion endo- ou extra-luminale du canal thoracique. A ce jour, une dizaine de cas seulement ont ete decrits dans la litterature. La physiopathologique est mal connue ; un regime riche en graisse pourrait provoquer un afflux de chylomicrons depassant les capacites de transport du canal thoracique, provoquant ainsi son occlusion temporaire et paroxystique. Une anomalie constitutionnelle du canal thoracique telle qu’une ectasie pourrait etre un facteur associe favorisant l’extravasation de liquide lymphatique dans le tissu sous-cutane. La lymphoangio-IRM semble etre l’examen de premier choix pour faire le diagnostic.

Career situation of first and presenting author Student for a master or a PhD Introduction Systemic sclerosis (SSc) is an autoimmune disease characterized by widespread fibrosis, microangiopathy and autoantibodies. Follicular helper T (Tfh) cells CD4+CXCR5+PD-1+ cooperate with B lymphocytes to induce the differentiation of plasmocytes secreting Immunoglobulins (Ig). Circulating Tfh (cTfh) cells are increased in several autoimmune diseases.1 Tfh cells can infiltrate the skin of SSc patients, and induce fibrosis in vitro.2 Objectives The aim of this study was to perform a quantitative and functional analysis of cTfh cells in SSc. Methods Using flow cytometry, we analyzed cTfh cells from 52 SSc patients with no immodulotary treatment and 38 healthy controls (HC). In vitro coculture experiments of sorted cTfh and B cells from 13 SSc patients and 6 HC were performed for functional analysis. IgG and IgM production were measured by ELISA. BCL-6, Blimp-1, CXCL13 and IL-21 expression were analyzed by RTqPCR. Results We observed that cTfh cell numbers are increased in SSc patients compared with HC. Furthermore, the increase in cTfh cells was more potent in patients with severe forms of SSc such as diffuse SSc and in the presence of arterial pulmonary hypertension. cTfh cells from SSc patients present an activated Tfh phenotype, with high expression of BCL-6 and increased capacity to produce IL-21 in comparison to HC. In vitro, cTfh cells from SSc patients had higher capacity to stimulate the differentiation of CD19+CD27+CD38hi B cells and their secretion of IgG and IgM through the IL-21 pathway than cTfh cells from HC. Blocking IL-21 or using the JAK1/2 inhibitor ruxolitinib reduced the Tfh cells9 capacity to stimulate the plasmablasts and Ig production. Conclusions Circulating Tfh cells are increased in SSc and correlate with SSc severity. The IL-21 pathway or JAK1/2 blockade by ruxolitinib could be a promising strategy in the treatment of SSc. References Crotty S. T follicular helper cell differentiation, function, and roles in disease. Immunity 2014;41(4):529-42. Taylor DK, Mittereder N, Kuta E, Delaney T, Burwell T, Dacosta K, et al. T follicular helper-like cells contribute to skin fibrosis. Sci Transl Med 2018;10(431). Acknowledgements This work was supported by the Aterhit foundation and received grants from 9Groupe Francophone de Recherche sur la Sclerodermie’ (GFRS). Disclosure of Interest None declared

BACKGROUND: While different clinical manifestations of IgM and IgG monoclonal cryoglobulins have been demonstrated, little is known about the roles of IgG subclasses in the pathophysiology of these conditions. METHODS: In two cases of myeloma-associated monoclonal (type I) cryoglobulinemia with quite distinct clinical and biological features, serum samples were analyzed using an original IgG subclass-specific immunoblotting technique. RESULTS: The first case had painful arthritis of hands and feet, with skin purpura and a sharp decrease of complement C4 level, and the cryoglobulin was of IgG1 subclass. The second case displayed mostly thrombotic lesions of the limb extremities, C3 and C4 serum levels were normal, and the cryoglobulin belonged to the IgG2 subclass. CONCLUSIONS: Type I cryoglobulins of distinct IgG subclasses may result in different syndromes. In both cases, the treatment relies on eradication of the underlying plasma cell dyscrasia.

It is mandatory for all hospitals to be prepared for the occurrence of a chemical biological, radiological or nuclear (CBRN) event. This preparation requires specific investment on the part of the hospital management, as well as from the nursing teams on the frontline. Teams from Lariboisiere hospital in Paris have been working on these risks for several years. Language: fr

Objective To describe safety and efficacy of rituximab in patients with systemic sclerosis. Methods We included 13 patients with systemic sclerosis treated with rituximab and pooled with 40 additional patients from the literature. SSc rituximab untreated patients were matched to rituximab treated ones. Results Thirteen patients who received rituximab and 26 rituximab-untreated patients were included. In comparison to 26 patients who did not received rituximab, FVC changes were not significantly different, whereas DLCO improved in 13 patients who received rituximab (0 [−4; 4] vs loss of −7 [−19; 0]; p = 0.05). Considering 7 rituximab treated and 14 untreated diffuse SSc, FVC was improved during the 24 [12; 46] months of follow up in dSSc who received rituximab (gain of 12 [7.5:14] % vs loss of 1.5 [−16.8; 2.5], (p = 0.003)). Pooled analysis of 53 patients (40 literature patients and 13 from personal series) showed significant improvement of median mRSS from 18 [8; 32] at baseline to 9 [4; 18] at M6 (p = 0.007), 13 [8; 18] at M12 (p = 0.008) and 10 [4; 16] at the last follow-up (p = 0.0002). FVC increased from 71% [66; 80] at baseline to 84% [75; 90] at M12 (p = 0.001). DLCO increased from 58% [39; 65] at M0 to 63% [53; 78] at M12 (p = 0.04). Conclusion Our personal data and pooled literature analysis suggest the efficacy of rituximab in the subset of diffuse SSc in particular in skin and interstitial disease involvements. The safety of rituximab seems to be reasonable and similar to previous data in other autoimmune diseases.

Objective.Clara cell secretory protein (CC16) is a sensitive marker of bronchial epithelial cell damage. The CC16 serum level is elevated in patients with pulmonary fibrosis, but its predictive value on lung disease progression has not yet been studied. We aimed to assess the value of serum CC16 concentration in predicting lung disease deterioration in patients with systemic sclerosis (SSc).Methods.We prospectively analyzed and followed 106 patients with SSc during a 4-year period for the risk of developing combined deleterious event, defined as a 10% decrease in total lung capacity or forced vital capacity from baseline, or death, according to serum CC16 at inclusion. Receiver-operating characteristic (ROC) curve analysis was performed for prediction of events during the first 2 years after inclusion. Cumulative risks of combined events were computed by Kaplan-Meier analysis.Results.The best cutoff level of serum CC16 for prediction of a combined event was 33 ng/ml, with 76% sensitivity and 65% specificity (area under the ROC curve: 0.71, 95% CI 0.61–0.81, p < 0.0001). Progression of lung disease evaluated by a mean time-to-event differed between patients with high baseline serum CC16 (42.8 mos, 36.3–49.3) and those with low serum CC16 (56.3 mos, 50.9–61.7; log-rank test, p < 0.001). After adjustment for age, duration of disease, clinical and lung function measures, the risk of combined event occurrence in patients with high serum CC16 was significantly higher than in those with low CC16 (HR 2.9, 1.2–6.75, p < 0.05).Conclusion.High baseline serum CC16 predicts lung disease worsening in patients with SSc.

Interstitial lung disease (ILD) is becoming one of the main causes of death of patients with systemic sclerosis (SSc). The prevalence of ILD associated with SSc (SSc-ILD) varies from 33% to 100% according to diagnostic methods. Clinical features such as dyspnea on exertion, dry cough, and chest pains are not specific and usually late-appearing, implying more specific tests in the diagnostic, prognosis, and follow-up of ILD in patients with SSc. High resolution thoracic CT scanner (HRCT) is more sensitive than chest X-ray in the detection of SSc-ILD. Pulmonary function tests (PFT) are non-invasive and periodically used to assess the impacts of SSc on respiratory function. Diagnostic values of bronchoalveolar lavage and histological examination on lung biopsy are controversial. However, these techniques are essential for studying cellular and molecular mechanisms underlying the pathophysiology of SSc-ILD. Several biomarkers such as surfactant-A (SP-A), -D (SP-D), mucin-like high molecular weight glycoprotein (KL-6), and chemokine CCL-18 have been implicated in SSc-PID. Serum levels of these proteins are correlated with the severity of SSc-ILD, as assessed by HRCT and/or PFT. Finally, alveolar concentration of exhaled nitric oxide can be used to screen SSc patients with high risk of deterioration of respiratory function, in whom immunosuppressant treatment could be useful in preventing the evolution to irreversible lung fibrosis.

Reactive haemophagocytic syndrome is a life-threatening disease for which factors influencing the outcome remain unclear. We sought to identify determinants of early mortality in patients with reactive haemophagocytic syndrome by conducting a non-interventional retrospective multicentre study in three tertiary care teaching hospitals over a 6-year period. The medical files of 162 patients fulfilling our diagnostic criteria of haemophagocytic syndrome were reviewed. Patients were classified according to 30-d outcome following diagnosis. Thirty-three patients (20·4%) died within 30 d. Clinical features at diagnosis associated with 30-d death in univariate analysis were older age (P = 0·004), underlying lymphoma (P = 0·04), lower platelet count (P = 0·001) and elevated aspartate aminotransferase and lactate dehydrogenase (P = 0·04 both). The use of etoposide as a first-line treatment tended to be associated with a better outcome (P = 0·079). In multivariate analyses, increasing age, decreasing platelet count, underlying lymphoma and no etoposide in the management were associated with a poorer prognosis (P = 0·03, 0·01, 0·003 and 0·04, respectively). These prognostic factors could help to identify those patients more severely affected by reactive haemophagocytic syndrome, who should benefit from aggressive supportive care, combined with specific treatment of the precipitating factor.

Resume Introduction Les patients atteints de sclerodermie systemique ont un risque plus eleve de cancer que la population generale. Dans cette etude, nous avons analyse la survenue de cancers chez ces patients, les risques associes et l’impact sur la survie globale. Patients et methodes Dans une cohorte monocentrique de patients suivis de janvier 2004 a decembre 2017, nous avons recueilli les caracteristiques cliniques (survenue de cancer, exposition toxique, atteinte d’organe), biologiques et les traitements utilises. Resultats Deux-cent dix patients etaient inclus, et 21 patients (10 %) ont developpe un cancer solide au cours du suivi. Parmi ceux-ci, on notait des adenocarcinomes du sein (n = 6, 28 %), des cancers broncho-pulmonaires (n = 6, 28 %), digestifs (un adenocarcinome du sigmoide, une tumeur carcinoide de l’appendice), ovarien et du col uterin (n = 1 de chaque cas), un melanome, un carcinome renal a cellules claires et un cancer papillaire de la thyroide. Le delai median entre l’inclusion et le diagnostic de cancer etait de 4 [2–10] ans. La survenue de cancer n’etait pas associee a une surmortalite avec une mediane de survie au premier quartile (75 %) de 12 ans chez les patients ayant developpe un cancer et de 11,6 ans en absence de cancer associe (p = 0,9). L’antecedent de crise renale sclerodermique (HR 10,99, IC95 % [1,95–62,07] ; p = 0,006) et la presence d’anticorps anti-Scl70 (HR 5,5, IC95 % [1,40–21,67] ; p = 0,01) etaient significativement associes avec la survenue d’une neoplasie, alors que la presence d’un reflux gastro-œsophagien etait inversement correlee (HR 0,22, IC95 % [0,056–0,867] ; p = 0,03). Conclusion La survenue d’une crise renale sclerodermique et la positivite des anticorps anti-Scl70 etaient associees a la survenue d’une neoplasie chez les patients suivis pour une sclerodermie systemique dans cette etude monocentrique.

Introduction L’atteinte interstitielle pulmonaire est retrouvee chez 42 % des patients ayant une sclerodermie systemique (ScS) diffuse et a un impact majeur sur la survie [1] . Le cyclophosphamide et le mycophenolate mofetil peuvent permettre une stabilisation de l’atteinte pulmonaire [2] . Plusieurs cas rapportes et series sur un petit nombre de patients ont rapporte un effet du rituximab (RTX) dans la ScS avec une possible amelioration de l’atteinte pulmonaire [3] . Peu de donnees sont disponibles sur les facteurs associes a une reponse au RTX et sur l’efficacite a long terme dans la ScS. L’objectif etait de decrire l’efficacite et la tolerance du RTX chez les patients ayant une ScS. Patients et methodes Nous avons inclus 13 patients atteints de ScS traites par RTX et 40 patients issus de la litterature. Des patients temoins atteints de ScS non traites par RTX ont ete apparies aux patients traites par RTX. Resultats Treize patients ayant recu du RTX et 26 patients non traites par RTX ont ete inclus. En comparaison aux 26 patients n’ayant pas recu de RTX, il n’y avait pas de modification significative de la CVF alors que la variation de DLCO au cours du suivi etait significative chez les patients recevant du RTX (0 [−4 ; 4] vs une perte de −7 [−19 ; 0] ; p = 0,05). Chez les patients ayant une ScS diffuse (7 traites par RTX et 14 non-traites par RTX), la CVF s’est significativement amelioree au cours des 24 [12 ; 46] mois de suivi chez les patients ayant recu du RTX (gain de 12 [7,5 : 14] % vs perte de 1,5 [−16,8 ; 2,5], p = 0,003). L’analyse poolee de 53 patients (40 patients de la litterature et 13 de la serie personnelle) montrait une amelioration significative du mRSS median passant de 18 [8 ; 32] avant RTX a 9 [4 ; 18] a M6 (p = 0,007), a 13 [8 ; 18] a M12 (p = 0,008) et a 10 [4 ; 16] a la fin du suivi (p = 0,0002). La CVF augmentait de 71 % [66 ; 80] avant RTX a 84 % [75 ; 90] a M12 (p = 0,001). La DLCO augmentait egalement de 58 % [39 ; 65] avant RTX a 63 % [53 ; 78] a M12 (p = 0,04). Conclusion Nos donnees ainsi que l’etude des patients issus de la litterature suggerent une efficacite du RTX dans le sous-groupe de patients ayant une ScS diffuse, particulierement pour l’atteinte interstitielle pulmonaire et l’atteinte cutanee. La tolerance du RTX semble correcte, comparable aux donnees anterieures dans d’autres pathologies auto-immunes.

Introduction La sclerodermie systemique (ScS) est une connectivite ou l’atteinte microvasculaire est centrale, mais ou l’atteinte macrovasculaire peripherique est de plus en plus rapportee. L’objectif de cette etude prospective etait d’evaluer l’interet de depister systematiquement une atteinte hemodynamique arterielle des membres inferieurs (MI) chez des malades atteints de ScS, par mesure de l’index de pression systolique a la cheville (IPS), mais aussi par mesure de la pression d’orteil (PO) et calcul de l’index de pression d’orteil (IPO). Patients et methodes Les patients, suivis pour une ScS, etaient inclus prospectivement sur 1 an. Les donnees cliniques et biologiques etaient recueillies par questionnaire medical standardise. Pour chaque patient etaient realises : mesure de l’IPS, de la PO par laser-Doppler et calcul de l’IPO. Un echo-Doppler arteriel des MI etait prescrit en cas d’anomalie. L’IPS temoigne d’une atteinte macrovasculaire si 1,3 (avec rigidite arterielle dans ce dernier cas). Un IPO Resultats Quatre-vingt-six patients, dont 94 % de femmes, ont ete inclus, d’âge median 62 ans. Seuls 24 % des patients n’avaient aucune atteinte vasculaire hemodynamique des membres inferieurs ; 44 % des patients (n = 38) avaient une atteinte hemodynamique microcirculatoire isolee (IPS normaux et IPO 1,3 temoignant d’une incompressibilite arterielle. Seuls 2,3% des patients presentaient une ischemie critique (pression a la cheville Conclusion Grâce a la mesure de la PO, cette etude montre la presence d’une atteinte macro et/ou microvasculaire hemodynamique des membres inferieurs chez 76 % de patients ScS, alors que la seule mesure de l’IPS n’en aurait depiste que 31 %. L’IPS, recommande pour le depistage de l’arteriopathie, n’est pas un outil suffisant chez les patients sclerodermiques, comme chez les diabetiques, en raison de la prevalence elevee chez ces patients de rigidites arterielles et d’atteintes microcirculatoires isolees.