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A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome').To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome.One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded.The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis.VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

International audience; Introduction: Infections are responsible for a part of the overall mortality in primary Sjögren's syndrome patients (pSS). Our retrospective monocentric study aimed at describing infections reported in a population of pSS hospitalized patients, along with the characteristics of their disease.Methods: Patients with SS have been randomly selected from our hospital database claim, between 2009 and 2018. After careful analysis of their medical chart, only patients with pSS and fulfilling ACR/EULAR 2016 diagnosis criteria were included. We collected main clinical, biological and pathological characteristics of SS, along with all the reported infections during the follow-up. The characteristics of the disease were compared according to the presence of an infection in hospitalization.Results: In total, 109 pSS patients were included (93% of women, mean age 53.6±14.3 years, mean follow-up 8.2±8.4 years). Fifty-one percent had been exposed to hydroxychloroquine (HCQ). Seventy-eight infections were recorded in 47 (43%) patients. Twenty-five infections were recorded in hospitalization (5 in critical care) in 20 (18%) patients, whom leading causes were urinary tract (28%), pulmonary (24%), ENT (16%), and intestinal (12%) infections. pSS patients with infections in hospitalization were older, exhibited more hypocomplementemia, and were less exposed to HCQ. We found no difference in immunosuppressive treatments exposure.Conclusions: The impact of HCQ exposure on infectious risk needs further investigations. Broad vaccination campaign and tight control of sicca syndrome could lead to a better control of infection risk.

International audience

Infections are responsible for a part of the overall mortality in primary Sjögren's syndrome patients (pSS). Our retrospective monocentric study aimed at describing infections reported in a population of pSS hospitalized patients, along with the characteristics of their disease.Patients with SS have been randomly selected from our hospital database claim, between 2009 and 2018. After careful analysis of their medical chart, only patients with pSS and fulfilling ACR/EULAR 2016 diagnosis criteria were included. We collected main clinical, biological and pathological characteristics of SS, along with all the reported infections during the follow-up. The characteristics of the disease were compared according to the presence of an infection in hospitalization.In total, 109 pSS patients were included (93% of women, mean age 53.6±14.3 years, mean follow-up 8.2±8.4 years). Fifty-one percent had been exposed to hydroxychloroquine (HCQ). Seventy-eight infections were recorded in 47 (43%) patients. Twenty-five infections were recorded in hospitalization (5 in critical care) in 20 (18%) patients, whom leading causes were urinary tract (28%), pulmonary (24%), ENT (16%), and intestinal (12%) infections. pSS patients with infections in hospitalization were older, exhibited more hypocomplementemia, and were less exposed to HCQ. We found no difference in immunosuppressive treatments exposure.The impact of HCQ exposure on infectious risk needs further investigations. Broad vaccination campaign and tight control of sicca syndrome could lead to a better control of infection risk.

International audience; The evolution of the nitrogen concentration and isotopic composition during the degassing of Earth's magma ocean, and thus in the primitive atmosphere, is key to understanding how habitable conditions developed on Earth. To constrain nitrogen degassing from the magma ocean, we determined the variations of the N content at N 2 gas saturation, N speciation, and N isotopic composition of a magma ocean analogue (basaltic komatiite) at oxygen fugacities (fO2) from IW−4.2 to IW (where IW is the logarithmic difference between experimental fO2 and that at Fe-FeO equilibrium). We performed a series of N degassing experiments in a piston cylinder at 1.5 GPa and 1550°C in pure forsterite capsules. N concentrations in the mafic silicate melts decreased from 13,481 ± 735 ppm under the most reducing conditions to 798 ± 4 ppm at IW, controlled by N speciation (as determined by Raman spectroscopy), which changed from nitride (±N-H complexes) to molecular N 2 with increasing fO2. Nitrogen occurs solely as N2 in the degassed gas, regardless of fO2. Nitrogen isotopic compositions (as determined by secondary ion mass spectroscopy) became significantly lighter in the degassed melt (quenched glass), down to −41 ± 13 ‰ relative to the initial composition (measured in an undegassed sample), following open system degassing trends (variable with fO2 conditions), indicative of Rayleigh fractionation. These findings imply that an atmosphere in equilibrium with a reduced magma ocean would be N-depleted, whereas with increasing magma ocean fO2 conditions, the primitive atmosphere would have become more enriched in N2 gas.

BackgroundSystemic diseases of pediatric onset are more frequent in Afro-Caribbean population, especially Pediatric systemic lupus (pSLE).ObjectivesOur work is a retrospective study of patients followed in French overseas departments of America for systemic disease or auto-inflammatory syndrome of pediatric onset. It describes their clinical and biological specificities at diagnosis, during childhood and early adulthood.MethodsOur retrospective study was conducted between 01/01/2000 and 01/09/2021. Listings of adult patients with pediatric onset and pediatric patients were obtained in each center through computerized hospital archives, list of patients followed by referent pediatricians and adult specialists in internal medicine and the French National Registry for rare disease. Data were then gathered by going through their medical files. The spectrum of diseases studied included pSLE, Sjogren syndrome, antiphospholipid syndrome (APS), connectivitis, systemic scleroderma, dermatomyositis, Systemic juvenile idiopathic arthritis (sJIA), unclassified auto-inflammatory syndrome.Results2148 patients were identified on a 21 year-period, and 135 patients were included. Most patients diagnosed with a systemic pathology (102) suffered from pSLE (53%), followed by dermatomyositis (17%). Average follow up was 8.3 years (0.3 - 25 years), median age at last follow up was 21.2 (14 - 36.7). We found an increase in the number of new diagnoses throughout the years. For pSLE, sex repartition was 4/1 girl/boy and did not vary according to age (p= 0,31). At onset, patients had 10 Sclicc criteria (4-12) and median EULAR/ACR 2019 score was 38 (12 - 54). The combination of typical skin involvement, arthritis and fever was found for 87%. At onset, a third of patients had renal involvement, 15% had Neurolupus and 41% cardiac involvement. All patients had a positive ANA and Anti-DNA antibodies, followed by anti-Ssa/Ssb antibodies (78%), Anti-Sm (78%) and anti RNP (52%). During childhood, 54% had renal involvement and 26% suffered from Neurolupus. Patients suffered in median from 3 flares and 26% suffered from more than 5 flares during childhood. Pre-pubertal patients (26%) had worst outcomes, 93% had renal and / or neurological involvement, they had more flares (median at 5 p = 0,02) and needed an average of 4 background therapies (p = 0,04). Boys seemed to have better disease control at transition to adult care but gender was not an independent predictor of severity during childhood (p = 0,21). 17 patients had dermatomyositis, 29% of them had respiratory involvement during childhood. 33 patients had auto-inflammatory syndromes mostly sJIA (67%), 50% of them had hemophagocytic syndrome during childhood and their disease was controlled by steroids for 64%, 36% needed biotherapy. The overall mortality was 3%.ConclusionThis is a large cohort of patients of Afro-Caribbean origin with a higher frequency of pSLE. Although the outcomes for these patients were similar to western countries, they had loud symptoms at onset, not corelated to delay at diagnosis. Compared to ethnic studies of North America or Africa, the French health care system being universal and free, the bias related to socio-economic status was lower. This work will continue with the exploration by transcriptomic and genetic tests for early and severe forms to identify the extra-environmental causes. The environmental factors specific to these regions should be explored in additional prospective studies.Figure 1.Clinical and biological characteristics of patients with pediatric onset systemic lupus. Orange: clinical signs at onset, Green: immunological profile, Blue: evolutive profile and proportion of organ involvement during childhood. ANA: anti-nuclear antibody.Disclosure of InterestsNone declared

BackgroundLupus nephritis (LN) is a frequent complication of systemic lupus erythematosus (SLE). Severe (proliferative) forms of LN are treated with an induction immunosuppressive therapy (IST), followed by a maintenance IST, to target remission and avoid relapses. The optimal duration of maintenance IST for proliferative LN is unknown.ObjectivesThe WIN-Lupus trial tested whether IST discontinuation after 2-3 years in proliferative LN was non-inferior to IST continuation for 2 more years.MethodsWIN-Lupus is an investigator-initiated academic randomized controlled trial, conducted in 28 French centers. Patients on maintenance IST with azathioprine or mycophenolate mofetil for a minimum of 2 years and a maximum of 3 years, and who were taking Hydroxychloroquine, were randomized (1:1) between 2 groups: IST continuation and IST discontinuation. The primary endpoint was the relapse rate of proliferative LN at 24 months. Secondary endpoints were the rate of severe SLE flares, survival without renal relapse or severe flare, adverse events, kidney function, disease activity, corticosteroid exposure, patient-reported outcome and medico-economic impact.ResultsBetween 2011 and 2016, 125 patients were screened and 96 were randomized in the trial: 48 in the IST continuation group, 48 in the IST discontinuation group. In the per-protocol population, a relapse of proliferative LN occurred in 5/40 (10.4%) patients with IST continuation, and in 12/44 (25%) patients with IST discontinuation (difference 14.8%, 95%CI [-1.9; 31.5]). Non-inferiority was not demonstrated for relapse rate. Time to renal relapse did not differ between groups (p=0.092). Severe SLE flares (renal or extra-renal) were less frequent in patients with IST continuation compared to IST discontinuation (5/40 vs 14/44 patients, p=0.035). IST discontinuation was associated with lower health-related costs. Adverse events did not differ between groups.ConclusionNon-inferiority of maintenance IST discontinuation after 2 to 3 years was not demonstrated for renal relapse. IST discontinuation was associated with a higher risk of severe SLE flare.References[1]Moroni G et al. When and how is it possible to stop therapy in patients with lupus nephritis? Clin J Am Soc Nephrol. 2021. CJN.04830421. doi: 10.2215/CJN.04830421.[2]Fanouriakis A et al. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020;79(6):713-723.[3]Jourde-Chiche N et al. Proliferative lupus nephritis treatment: practice survey in nephrology and internal medicine in France. Nephrol Ther. 2014;10(3):170-6.[4]Zen M et al. Immunosuppressive therapy withdrawal after remission achievement in patients with lupus nephritis. Rheumatology (Oxford). 2021;keab373. doi: 10.1093/rheumatology/keab373.[5]Malvar A et al. Kidney biopsy-based management of maintenance immunosuppression is safe and may ameliorate flare rate in lupus nephritis. Kidney Int. 2020;97(1):156-162.AcknowledgementsGroupe Coopératif sur le Lupus Rénal (GCLR)Disclosure of InterestsNoemie JOURDE-CHICHE Speakers bureau: Vifor Pharma, Grant/research support from: Fresenius Medical Care: grant paid to my institution (AP-HM) for the CINEVAS study in ANCA-associated vasculitis, Nathalie Costedoat-Chalumeau Grant/research support from: AP-HP received a research support from ROCHE for the OBILUP trial, Karine Baumstarck: None declared, LAURENCE BOUILLET Speakers bureau: GSK, novartis, biocryst, takeda, behring, Paid instructor for: takeda, novartis, Consultant of: GSK, novartis, biocryst, takeda, behring, blueprint, Grant/research support from: takeda, gsk, sanofi, biocryst, novartis, Stéphane Burtey: None declared, Valerie Caudwell: None declared, Laurent Chiche Speakers bureau: BMS, Paid instructor for: BMS, Lionel Couzi Speakers bureau: Astellas, Chiesi, Novartis, Sandoz, Ostuka, GSK, Biotest, Consultant of: Biotest, Hansa, Novartis, Grant/research support from: Novartis, Astellas, Christophe DELIGNY: None declared, Bertrand Dussol Speakers bureau: Genzyme, Novonordisk, Grant/research support from: Shire, Stanislas Faguer Speakers bureau: Asahi, Vifor Pharma, Sanofi, Consultant of: Abyonyx Pharma, Pierre Gobert: None declared, Guillaume Gondran Speakers bureau: Pfizer, Novartis, Consultant of: Genzyme, Antoine Huart Speakers bureau: Janssen, Paid instructor for: Pfizer, Aurélie Hummel: None declared, Emilie Kalbacher: None declared, Alexandre Karras Speakers bureau: Vifor, GSK, Astra-Zeneca, Roche, Paid instructor for: Vifor, Sanofi, Alexion, Consultant of: Novartis, GSK, Bohringer-Ingelheim, Marc Lambert Speakers bureau: CHUGAI-ROCHE, BAYER, PFIZER, LEOPHARMA, Paid instructor for: CHUGAI-ROCHE, Consultant of: CHUGAI-ROCHE, BAYER, PFIZER, LEOPHARMA, Grant/research support from: CHUGAI-ROCHE, Véronique LE GUERN: None declared, Sandrine Loubiere: None declared, Helene Maillard: None declared, Francois Maurier: None declared, Micheline Pha: None declared, Viviane Queyrel Paid instructor for: GSK, Consultant of: Boehringer Ingelheim, Francoise Sarrot-Reynauld: None declared, David Verhelst: None declared, Eric Hachulla Speakers bureau: Johnson & Johnson, GSK, Roche-Chugai, Consultant of: Johnson & Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, Sanofi-Genzyme, Grant/research support from: CSL Behring, GSK, Roche-Chugai and Johnson & Johnson, Zahir Amoura Speakers bureau: GSK, CSL Behring, Consultant of: GSK, Grant/research support from: GSK, Eric Daugas Speakers bureau: GSK, Amgen, Paid instructor for: GSK, Astra Zeneca, Consultant of: GSK, Astra Zeneca, Amgen, Grant/research support from: ROCHE for the OBILUP trial (AP-HP)

BackgroundMortality and morbidity related to rheumatoid arthritis (RA) has remarkably improved over the last twenty years since using biologics DMARDs1. However, their effectiveness remains questionable in Afro-descendants (AD) due to their large under-representation in RA clinical trials2,3. Martinique is a French Caribbean region with a majority of AD population4, with free access to healthcare, including biotherapies, and a unique university hospital and rheumatology unit.ObjectivesTo evaluate effectiveness of Tocilizumab (TCZ), an interleukin-6 inhibitor, in an afro descendant RA population.MethodsRetrospective cohort of 171 patients who received at least 1 infusion of Tocilizumab (IV TCZ) at Martinique University Hospital Center between 2008 and 2019. Inclusion Criteria: Patients over 18 y/o meeting RA 2010 ACR/EULAR criteria, having received at least 4 courses of IV TCZ starting at 8mg/kg every 4 weeks, with available baseline clinical/biological data. Exclusion criteria: Patients having received subcutaneous TCZ (SC TCZ) prior to IV TCZ, not living in Martinique. Primary endpoint was proportion of patients in remission (R) and low disease activity (LDA) according to DAS28 CRP at 12, 24, 36 weeks. Secondary endpoint was proportion of patients achieving good (GR) and moderate (MR) EULAR response criteria 5 at 12, 24 and 36 weeks, and TCZ retention at 1 year defined as the proportion of patient receiving TCZ at 1 year follow up.ResultsOut of 171 patients receiving IV TCZ, we identified 138 RA and 80 patients met inclusion criteria: 90% were women, mean age was 56.8 (± 11.8) y/o, mean duration of RA was 11.6 (± 8.9) years, ACPA and Rheumatoid Factor were positive in 72.1% and 73% of cases, 69.6% of patients had erosions and 77.8% had received at least 1 biologic prior to IV TCZ. At baseline, 8 patients were in R, 8 had LDA but presented steroid dependency over 10 mg per day of prednisone and mean dose of prednisone was 6.9 (+/- 6.7) mg per day.At 12, 24, 36 weeks, R was achieved in 44.8%, 55.2% and 51.2% of patients and LDA in 37.3%, 17.2% and 20.9%, respectively (Figure 1). At 12, 24, 36 weeks, GR was achieved in 44.8 %, 60.3% and 48.8% of patients respectively, MR was achieved in 20.9%, 20.7% and 27.9% of patients respectively (Figure 1) and mean dose of prednisone per day was 5.1 (± 4.9) mg, 4.9 (± 5.6) mg and 3.3 (± 5.1) mg respectively. At 1 year, 78.8% of patients were still on TCZ. During follow up: 15 patients experienced 19 infectious events; 6 patients liver cytolysis; 12 patients neutropenia. No patient died.ConclusionThis is the first study evaluating efficacy and safety of TCZ in an AD RA cohort. TCZ is safe and effective in our AD population with comparable data observed in other ethnicities6,7.References[1]Lacaille, D., Avina-Zubieta, J. A., Sayre, E. C. & Abrahamowicz, M. Improvement in 5-year mortality in incident rheumatoid arthritis compared with the general population—closing the mortality gap. Ann. Rheum. Dis.76, 1057–1063 (2017).[2]Strait, A. et al. Demographic Characteristics of Participants in Rheumatoid Arthritis Randomized Clinical Trials: A Systematic Review. JAMA Netw. Open2, e1914745 (2019).[3]Dunbar-Jacob, J. et al. Factors associated with attrition of African Americans during the recruitment phase of a clinical trial examining adherence among individuals with rheumatoid arthritis: Attrition of African Americans. Arthritis Care Res.51, 422–428 (2004).[4]Levinson, D. Ethnic Groups Worldwide : a ready handbook. (1998).[5]Fransen, J. & van Riel, P. L. C. M. The Disease Activity Score and the EULAR Response Criteria. Rheum. Dis. Clin. N. Am.35, 745–757 (2009).[6]Gottenberg, J.-E. et al. Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study. BMJ l67 (2019) doi:10.1136/bmj.l67.[7]Mori, S. et al. Retention of tocilizumab with and without methotrexate during maintenance therapy for rheumatoid arthritis: the ACTRA-RI cohort study. Rheumatology58, 1274–1284 (2019).Disclosure of InterestsNone declared

European member states are increasingly vying with one another to recruit patients for clinical trials (CTs). The French national agency for medicines (ANSM) now receives an ever-growing number of CTs, extending response times. The aim of the new methodology presented herein is to reduce assessment times below the national mandatory timeframe of 60 days and to improve patient safety. Based on an analysis of the criteria defining CTs, 4 key points were identified (safety, fragile population, loss of opportunity, design complexity) to build a criticality score which would determine evaluation type. This score also determines the resources needed (complete evaluation, multidisciplinary advice, ad hoc evaluation) and the timeframe required for appropriate analysis. All post-phase I CTs were analysed from the implementation of the new assessment method, on 01/02/2018 through to 31/12/2019. 447 CTs were analysed (63% industry and 37% academic sponsors). Based on a criticality scale, 27% of the CTs received a type A evaluation (complete), 37% a type B (multidisciplinary evaluation), 23% a type C evaluation (ad hoc evaluation) and 13% a type D evaluation (fast evaluation). From 2014 to 2017, 37% of the CTs were analysed within the mandatory timeframe, with a mean of 68 days, reaching a maximum of 102 days in 2017. Using this new assessment method, 92% of CTs respected the mandatory timeframe in 2019; the mean time in 2018–2019 was 34 days; Grounds for Non-Acceptance (GNA) were raised for 66% of the CTs (69% from academic sponsors and 65% from industrial firms). 3 CTs were refused. Here, we demonstrate the feasibility of risk analysis and multidisciplinarity method, which resulted in a dramatic improvement of assessment times.

Resume Du 24 juin au 6 juillet 2005, neuf hommes se sont presentes successivement aux urgences de l’hopital de Fort-de-France (Martinique, Antilles francaise) avec une symptomatologie pulmonaire plus ou moins marquee associee dans deux cas a la presence de lesions cutanees. Ces neuf hommes avaient tous realise des travaux dans une maison abandonnee trois semaines auparavant. Le diagnostic d’histoplasmose a pu etre etabli grâce aux examens mycologiques realises sur les prelevements pulmonaires (l’examen direct et la culture), la biologie moleculaire et les serologies. L’interrogatoire et l’enquete environnementale sur la zone presumee de l’exposition aux spores d’ H . capsulatum var. capsulatum a permis de confirmer les lieux et les modalites de contamination.

Evolution of serum cytokine profile after hematopoietic stem cell transplantation in systemic sclerosis patients

Some studies suggest that thrombotic thrombocytopenic purpura (TTP) occurs more often in African Americans. However there is low evidence for this in the literature. The aim of our study was to describe the clinical and biological characteristics of TTP in the Afro-Caribbean population of Martinique.We retrospectively analysed all patients with TTP diagnosed at the Fort-de-France hospital between 2008, January 1st and 2015, December 31st. Diagnosis was confirmed if ADAMTS-13 activity was10 %.Ten patients were included, corresponding to an average annual incidence of 3.2 cases/year/million individuals. None of the patient presented with the association of the five characteristic features of TTP. Microangiopathic haemolytic anaemia and severe peripheral thrombocytopenia (median: 13G/L) was the main presentation leading to diagnosis. There was no kidney involvement in 90 % of all patients, but severe neurological manifestations occurred in 70 %. Classical management including corticosteroids and plasma exchanges allowed clinical remission in 6 out of the 10 cases. If necessary, rituximab or cyclophosphamide was used. The overall survival rate was 90 %.In Martinique, the incidence of TTP is twice that reported in similar studies in France. Clinical manifestations seem to differ by more common and more severe neurological involvement. Mortality is low, in part, due to optimal care.

Between the 24th of June and the 6th of July 2005, nine men came to Fort-de-France emergency department (Martinique, French West Indies) with more or less pronounced pulmonary symptoms associated in two cases with skin lesions. Three weeks before these nine men performed work in a deserted house. The diagnosis of histoplasmosis was based on pulmonary sample mycological analysis (direct examination and culture), molecular biology and serological tests. Interrogatory and environmental investigations on the presumed place of exposition to H. capsulatum var. capsulatum spores allowed confirming how and where contamination took place.

Wells's cellulitis is a rare eosinophilic dermatose characterized by an inflammatory erythematous eruption, often associated with eosinophilia, and suggestive histologic features. The differential diagnosis with other eosinophilic dermatitis is problematic. The treatment is typically based on systemic steroids.We report a 63-year-old patient with an extensive pruritic maculo-papular eruption of the limbs and the trunk, forming large indurated and painful erythematous patches. Blood analysis revealed eosinophilia. Histologic examination showed perivascular eosinophilic inflammatory infiltration, also disposed around collagen fibers. The symptoms disappeared with topical corticosteroids.The diagnosis of Well's cellulitis is difficult because of the lack of specific sign; it is based on suggestive clinical, biological and histological features. Topical corticosteroids are efficient and well-tolerated, and should be used as first treatment.

Introduction Epidemiological and clinical characteristics of pulmonary artery hypertension (PAH) have never been described in Afro-Caribbean populations. Objective To describe the demographic, clinical, and hemodynamic characteristics of all patients with PAH followed in the dedicated Rare Diseases Centre for Pulmonary Hypertension of Martinique, and to compare them with those of the overall French Cohort. Methods A retrospective analysis of clinical and demographic data of all the adult patients referred for pulmonary hypertension in the Centre of Rare Diseases of the University Hospital of Martinique from January 2007 to November 2015. Results During this 9 years period, 107 patients were diagnosed with pulmonary hypertension. Sixty-three of them had a pulmonary artery hypertension. Most of them were also women. Mean age at diagnosis was 56 years, and 71% of the patients were in III-IV WHO functional class. Mean pulmonary artery pressure and cardiac index at right heart catheterism were 43 mmHg and 2.7 L/min/m 2 , respectively. The most frequent causes were idiopathic pulmonary hypertension (28.8%), pulmonary artery hypertension associated with connective disease (16.7%), congenital cardiac diseases. The estimated prevalence was 113 per million inhabitants, 7,5 times higher than that of overall France. One-year survival was 84.1%. Compared to the French overall cohort, our patients were more likely to be women (sex ratio 3.9 versus 1.9, P = 0.005) and older than 70 years at diagnosis (33.3% vs. 9.1%, P P = 0.07) was observed. Conclusion This first study of the epidemiological characteristics of pulmonary hypertension in an Afro-Caribbean region shows a high prevalence of disease, a diagnosis uncharacteristically done often in late stages of life, and a high frequency of connective tissue disorders.

Myelofibrosis is associated with numerous causes other than hematologic malignant neoplasms, including autoimmune diseases. We describe a 44-year-old woman who suffered bone lytic lesions with extramedullary haematopoiesis in the setting of myelofibrosis associated with systemic lupus erythematosus.

We report a case of pyoderma gangrenosum (PG) associated with a complication comprising ascending aortic dissection (neutrophilic aortitis) in a setting of rheumatoid arthritis (RA).A 79-year-old female patient was hospitalized in late 2009 for vegetating PG. Treatment with general steroids followed by colchicine and topical steroids resulted in complete healing of skin lesions. During hospitalization, the patient presented dissection of the ascending part of the aorta, for which emergency surgery proved effective. Histological examination of the excised tissue revealed diffuse neutrophilic aortitis. Diagnoses of Takayashu's disease and of lupus were ruled out. A chest CT scan showed interstitial lung disease with mild lymphocytosis in the bronchoalveolar fluid, but with no isolated pathogenic organisms. Relapse of skin lesions occurred 3 and 4 years later, associated with the development of RA, and worsening of the interstitial lung disease was noted in a scan carried out it in 2013, following which stabilization was observed in April 2014. There was no recurrence of the PG lesions.To our knowledge, no other cases involving association of neutrophilic aortitis with PG and RA has been published to date. The literature describes the emergence of the concept of systemic neutrophilic dermatoses, and this notion is reinforced by the presence of a cutaneous and aortic site of the neutrophilic disease in a single patient.

To evaluate in France the annual direct medical cost of adult patients with active systemic lupus erythematosus (SLE) on medication and estimate the cost of a flare.A two-year, observational, retrospective, multicenter study, carried out between December 2010 and February 2011. Patients' characteristics, SLE disease activity and severity, rate of flares, healthcare consumption (medications, hospitalisations, etc.) were evaluated. Medical costs were assessed from the national Health Insurance perspective. Cost predictors were estimated using multivariate regression models.Eight centres specialized in SLE management included 93 eligible patients (including 50.5% severe). The mean age was 39.9 (11.9) years and 93.5% were women. At baseline, the mean SLE duration was 9.8 (6.6) years. The mean scores of the SELENA-SLEDAI instrument and the SLICC/ACR index were higher in severe patients (9.8 vs 5.6, and 1.2 vs 0.4 respectively; P0.001). Over the study period, 51% of patients received the combination containing at least corticosteroids or immunosuppressants. The mean annual direct medical cost of severe patients was €4660 versus €3560 for non-severe patients (non-significant difference). The cost of medications (61.8% of the annual cost) was higher in severe patients (€3214 vs €1856; P0.05). Immunosuppressants and biologics represented 26.5% and 4.6% of the annual total cost respectively. Patients experienced on average 1.10 (0.59) flares/year, of which 0.50 were severe flare. The occurrence of a new severe flare incremented the annual cost of €1330 (P0.05).Medications represented the major component of the annual direct medical cost. Severe flares increase significantly the cost of SLE care management.

Diabetic muscular infarction is an exceptional complication of diabetes mellitus. Patients with macro- and microvascular manifestations are mostly concerned. Muscular pain with swelling of the thigh is the main manifestation, sometimes associated with fever.We report here five cases of diabetic muscular infarction in three Afro-carribean patients with atypical clinical features. The surgical biopsy procedure allowed the diagnosis and ruled out pyomyositis, a more common bacterial disease on tropical condition.This report of three cases of this exceptional disease in a small population seems more related to the high prevalence of diabetes mellitus in the French West Indies than to their ethnic origin.

Background Chick is an epidemic disease due to an arthropod-borne virus ( Alphavirus ) transmitted by Aedes mosquitoes. CHIKV causes an acute illness with a febrile phase, followed by a period of severe polyarthritis that can persist for long time. There is no specific treatment, the best prevention is mosquito control and avoidance of bites. Martinique (French West Indies) is currently experiencing an outbreak of CHIK with 170 000 reported cases (Dec 1st). Objectives No data is available regarding the prognosis of Chikungunya in patients under biologics. We have observed 22 patients with Chik infection while on biotherapy and DMARDS for rheumatic diseases, between January and May 2014. Methods Physicians prescribing biologics were asked to declare patients under biologics experiencing Chik. For each patient we collected diseases characteristics and course, current treatment (steroids, immunosuppressant, biologics…), changes in the treatment during infection, and outcome. 22 patients were included, all with a diagnosis confirmed by PCR (20/22) or serology. Results Among these patients were 19 women and 3 men, 3 Caucasians and 19 Afro-Caribbean9s. There were 5 spondyloarthritis (3 associated with Crohn), 1 psoriatic rheumatism, 2 systemic lupus, 1 antisynthetase syndrome and 13 RA. 17 had methotrexate (mean dose 21.6 mg), 3 Plaquenil, 2 Imuran, 1 cellcept, 2 cyclophosphamide. 11/22 were under steroids (mean dose of 8.6 mg/d). All experienced fever (mean duration 1.7 day), skin rash (15/22, mean duration 1.3 d), and acute disabling polyarthritis (mean pain VAS 8.4, mean SJC 9.6, mean TJC 6.8) for a mean 11.5 days duration. Nine had back pain and 4 tenosynovitis. None of them showed any organ failure, one single episode of transient thrombopenia was noted. None of them was hospitalized for Chik. Analgesic treatment (alone 4/22), associated with NSAIDs (17/22) or prednisone (1/22) and rest were sufficient to overcome the crisis. All but one patient maintained their previous treatment (DMARDS, Biologic, steroids…) without specific complication. All patients were able to differentiate between Chik related complains and those related to their preexisting condition. Mean clinical disease scores before and after Chik (DAS, BASDAI, SLEDAI) remained unchanged. Conclusions This is the first report of the occurrence of Chik in patients under biologics. Patients under biologics are at increased risk for serious infections either viral or bacterial, but no data has been published regarding Chik. This study was not conducted to discover all cases of Chik among patients under biologic. Chik does not seem to be deleterious in patients under biologics who do not exhibit more severe or prolonged disease than common forms. Chik does not seem to aggravate pre-existing disease. It does not seem necessary to modify the basic treatment of rheumatism in the announcement of a Chik as the clinical pictures observed in these patients are quite benign. NSAIDs and best rest are mostly effective. Chik does not seem harmful in patients receiving biological and this issue should be given to travellers. Disclosure of Interest None declared

To review epidemiological and clinical aspects of systemic lupus erythematosus (SLE) in Martinique, French West Indies.Cases of SLE were identified by attending physicians. Patients who presented with at least four of the criteria defined by the American College of Rheumatology were included. Determination of incidence and prevalence included the new cases arising during the 1990-1999 period and 1999 population census results. Probability of survival was based on the use of the Kaplan-Meier estimator.Two hundred and eighty-six patients were studied, including 265 females (92.7%). The average annual incidence was 4.7 cases per 100,000 inhabitants (95% confidence interval [CI]: 2.5-6.9). The prevalence for 1999 was 64.2 cases per 100,000 inhabitants (CI: 56.2-72.2). The mean age at onset was 30 years. Eleven percent of all patients had at least one parent with SLE. Renal disease was present in 139 patients (48.6%), and neurological disorders were diagnosed in 70 patients (24.5%). Patients tested positive for the following antibodies: anti-Sm (37.1%), anti-RNP (58.7%), anti-SSA (47.2%). Mean survival time was: 96.4% (CI: 94.1-98.7) at 5 years, 91.8% (CI: 87.9-95.7) at 10 years. Survival was significantly reduced in patients with end-stage renal disease (n = 40, chi 2 = 6.96, P0.01).The high incidence of SLE in Martinique and the immunological characteristics of patients were found to be similar to those described in other populations of African descent. The frequency of renal disease and survival rates were identical to those reported in Caucasians.

Risk factors for peripartum cardiomyopathy (PPCM) are controversial. PPCM seems to be more prevalent in women of African descent, the highest observed incidence is in Haiti (1 per 300 live births). Our retrospective study conducted in Martinique showed an incidence of 1 per 5500 live births. This incidence is significantly lower than in Haiti. Women from Martinique and Haiti do not differ for most classical risk factors: African descent, age, pregnancy-associated hypertension, multiple pregnancy and pre-eclampsia. However, the parity rate and the socioeconomic level are different. Thus, African descent could be confounded by high parity rate and socioeconomic status.

Bilateral deep brain stimulation (DBS) in the subthalamic nucleus (STN) is a widely used surgical option for patients with severe levodopa-responsive Parkinson disease (PD).1,2 Hardware-related infection is one of the most burdensome complications of such treatment.3 Despite antiobiotherapy, the hardware usually needs to be removed, and the device with new leads cannot be reimplanted for several months. During this period, patients lose the clinical benefit of DBS and often have increased disability despite the adjustment of drug treatment. We report a patient in whom we performed a bilateral subthalamotomy in 2 steps through the DBS electrodes before removing them because of infection. ### Methods. Bilateral DBS electrodes were implanted in the STN of a 60-year-old man with a 19-year history of PD with severe disability despite optimized drug treatment (table). After adjustment of the DBS parameters and a progressive reduction of drug treatment, there was a clear improvement of PD symptoms with almost no residual motor fluctuations or dyskinesias (table). The patient complained only of a mild dysarthria. View this table: Table Clinical evolution of the patient before DBS, with DBS, and after bilateral subthalamotomy Forty days after lead implantation, he was readmitted with delirium and pyrexia (39°C). The CT scan revealed an abscess (diameter ∼0.6 …

Introduction Des patients developpent une dystonie atypique secondaire a un traumatisme peripherique mineur. Des etudes neurologiques fonctionnelles sont realisees afin d’etayer une hypothese organique et comprendre la physiopathologie. Objectifs L’origine de la symptomatologie reste incomprise. La semiologie clinique tres atypique evoque une origine psychogene. La recherche d’une atteinte neurologique objective remettrait en cause cette hypothese. Methodes Des patients presentant une dystonie respectant les criteres de Jankovic (traumatisme avec retentissement local, dystonie survenue dans l’annee et sur le site du traumatisme) sont rapportes. Leur description semiologique, l’evolution, la therapeutique et l’imagerie cerebrale et cervicale (si torticolis) sont presentees. L’integrite des voies sensitivo-motrices peripheriques et centrales (EMG, potentiels evoques) puis leur excitabilite corticale (periode de silence, inhibition et facilitation intracorticale) sont testees. Resultats Six patients sont selectionnes. Leur presentation clinique est heterogene et atypique avec une attitude fixee et douloureuse fixee d’apparition rapide, des troubles neurovegetatifs. Le terrain psychiatrique est sans particularite. Les traitements usuels (antalgiques, antidystoniques, biphosphonates, toxine botulique) sont inefficaces. Les voies sensitivo-motrices peripheriques et centrales sont integres alors que sur le plan fonctionnel, l’inhibition et la facilitation sont absentes dans la moitie des cas. Discussion La dystonie focale survenant apres un traumatisme peripherique s’integre au groupe des dystonies secondaires par sa presentation clinique atypique. L’hypothese serait une integration sensitivo-motrice centrale des informations peripheriques defectueuse. Ces alterations entretiendraient la symptomatologie. L’origine de cette pathologie reste cependant indeterminee. La part psychogene reste a considerer. Conclusion La dystonie dans les suites d’un traumatisme peripherique mineur est une entite clinique heterogene. Une atteinte de l’excitabilite corticale apporte des hypotheses physiopathologiques sans definir son origine exacte.

Objectifs Decrire une nouvelle technique non invasive pour l’exploration des fistules durales intracrâniennes. Materiels et methodes Nous presentons 10 patients porteurs d’une fistule durale intracrânienne : 6 femmes et 4 hommes âges de 44 a 74 ans. Ils ont tous beneficie d’une angiographie cerebrale et d’une angioMR-Dynamique (ARMD) dans un delai de 24 heures a 2 mois. L’ARMD a ete effectuee en sequence echo de gradient Tl 3D apres injection de Gadolinium, avec une image acquise toutes les 1,77 a 4 secondes en fonction de la machine utilisee. L’epaisseur du volume etait de 80 mm. L’existence d’un shunt etait notee. La visualisation des arteres afferentes et l’existence d’un retour veineux cortical etaient precisees. Resultats L’angioMR-Dynamique retrouvait le shunt dans tous les cas avec opacification precoce du sinus lateral ou de la loge caverneuse avant le sinus sagittal superieur et notait le retour veineux cortical quand il existait (3 cas). L’artere afferente principale etait toujours visualisee. Conclusion L’angioMR-Dynamique est une nouvelle technique diagnostique des fistules durales intracrâniennes. Cette etude revele sa bonne sensibilite. L’ARMD pourrait ainsi permettre de selectionner les patients qui doivent beneficier d’une angiographie cerebrale lorsqu’une fistule durale est suspectee ou de realiser un controle non invasif chez les patients embolises.

Between December 7, 1985 and September 17, 1986, eleven terrorist bomb explosions took place in Paris. Thirteen people died immediately, 255 others were injured. Forty were treated on-site and were not hospitalized, 205 were subjected to triage and stabilization and were then hospitalized. These latter 205 patients are analyzed in this study. None of them died during transportation, and seven eventually died in hospitals. Forty-seven per cent of all victims suffered from multiple injuries. All deaths except one occurred in the polytraumatized group. The policy of subjecting victims of terrorist bomb explosions to triage and stabilization before hospitalization is compared to the so-called "scoop and run" technique, more generally applied in mass casualty situations. Its limitations and advantages are discussed.

mai 2013; National audience; A venir