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Les myosites à éosinophiles appartiennent au groupe des myopathies inflammatoires idiopathiques et sont définies par un infiltrat inflammatoire musculaire composé de polynucléaires éosinophiles. Il n’existe pas à ce jour de consensus concernant le diagnostic et le traitement de ces patients. Grâce à une revue exhaustive de la littérature, les principales caractéristiques cliniques et histologiques, ainsi que le traitement et l’évolution des patients, ont été résumés dans cette synthèse. Cette revue a permis de distinguer trois sous-groupes de myosites à éosinophiles : la forme focale, la forme diffuse et les périmyosites à éosinophiles. Un algorithme de traitement et de prise en charge est proposé, et les principaux diagnostics différentiels sont discutés.

Objective Among specific autoantibodies in DM, the anti–small ubiquitin-like modifier activating enzyme (SAE) antibody is rare. We aim to describe the clinical characteristics, cancer prevalence, and muscle pathology of anti-SAE–positive DM. Methods Patients with a diagnosis of DM and sera positive for the anti-SAE antibody were recruited from 19 centres in this retrospective observational study. The available muscular biopsies were reviewed. We conducted a comparison with anti-SAE–negative DM and a review of the literature. Results Of the patients in the study (n = 49), 84% were women. Skin involvement was typical in 96% of patients, with 10% having calcinosis, 18% ulceration and 12% necrosis; 35% presented with a widespread skin rash. Muscular disease affected 84% of patients, with mild weakness [Medical Research Council (MRC) scale 4 (3, 5)], although 39% of patients had dysphagia. Muscular biopsies showed typical DM lesions. Interstitial lung disease was found in 21% of patients, mainly with organizing pneumonia pattern, and 26% of patients showed dyspnoea. Cancer-associated myositis was diagnosed in 16% of patients and was responsible for the majority of deaths, its prevalence being five times that of the general population. IVIG therapy was administered to 51% of the patients during the course of the disease. Comparison with anti-SAE–negative DM (n = 85) showed less and milder muscle weakness (P = 0.02 and P = 0.006, respectively), lower creatinine kinase levels (P Conclusion Anti-SAE positive DM is a rare subgroup associated with typical skin features but a potentially diffuse rash, a mild myopathy. Interstitial lung disease defines an organizing pneumonia pattern. Cancer associated DM prevalence is five times that of the general population. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT04637672.

BackgroundIdiopathic inflammatory myopathies (IIMs) are a group of rare acquired muscular diseases. In healthy muscle, myofibers do not express major histocompatibility complex (MHC) class I and II. It was established that MHC-I positive immunostaining, although non-specific, is a marker for IIM diagnosis, while the significance of MHC-II immunostaining remains unclear. The present study investigates the expression of MCH-II in myofibers and capillaries of IIM muscles, taking into account the current IIM classification.Patients & MethodsA historical cohort was designed, including dermatomyositis (DM), inclusion body myositis (IBM), anti-synthetase syndrome (ASyS), immune-mediated necrotizing myopathy (IMNM), or overlap myositis (OM). MHC-II immunostaining was performed on patient muscle sections and was analyzed in a standardized and blind manner.ResultsMuscle sections from biopsies of 72 IIM patients were included: 23 DM, 17 IBM, 12 IMNM, 9 ASyS, and 11 OM. Overall, abnormal MHC-II immunostaining was found in myofibers and/or capillaries in 67 (93%) patients. Myofiber MHC-II immunostaining patterns differed according to the IIM subgroup: the immunostaining was diffuse in IBM (100%), negative in IMNM (75%), perifascicular in ASyS (67%), and either diffuse heterogeneous, clustered, or perifascicular in OM (27%, 27%, and 18%, respectively). MHC-II expression was found in 50% of DM (n=11/22).While all IIM subgroups presented quantitative and qualitative abnormalities of MHC-II immunostaining in capillaries, some subgroups displayed specificities. Most IBM and IMNM muscles presented frequent dilated capillaries (88% and 67%, respectively). DM, ASyS, and OM exhibited high frequencies of capillary lesions, including capillary dropout, leaky capillaries, and dilated capillaries.ConclusionWhile recent expert opinion (EURO-NMD pathology working group) recommended that MHC-II immunostaining of muscle biopsy remains optional, the present work demonstrates that the expression pattern of MHC-II allows to distinguish between several IIM subgroups. Our data argue for the inclusion of MHC-II immunostaining in the routine histological diagnosis for IIMs.

Objectives Idiopathic inflammatory myopathies are mainly defined by inflammatory infiltrates within the muscle (lymphocytes and macrophages). Eosinophil muscle infiltration has been described in idiopathic eosinophilic myositis (IEM) and rarely in EF. This study aimed to further delineate the nosological frame of idiopathic eosinophil muscle infiltration through the exhaustive analysis of IEM and EF patients. Methods This multicentre retrospective case series included IEM patients diagnosed between 2000 and 2022. IEM inclusion criteria were eosinophilic muscle infiltration with myositis pathological features, after the exclusion of differential diagnoses. An additional group of EF patients diagnosed between 2016 and 2022 was constituted. Inclusion criteria were an EF diagnosis and fascia thickening with inflammatory infiltrate. Results A total of 20 IEM cases and 10 EF cases were included. The median (interquartile range) age at diagnosis was 65 (49–70) years; there were 18 males. Data analysis delineated four subgroups: focal EM (FEM, n = 3), diffuse EM (DEM, n = 6), eosinophilic myofasciitis (EMF, n = 11) and EF (n = 10). FEM represented a limited and benign form of myositis. DEM cases presented objective muscle impairment with eosinophilic muscle infiltration. EMF patients presented subjective muscle impairment (myalgia, 55%), fasciitis (on histology and/or imaging), eosinophilic muscle infiltration and frequent hypereosinophilia (55%). EF patients presented myalgia (50%), muscle lesions on histology with fascia-restricted inflammatory infiltrates with (60%) or without (40%) eosinophils. Conclusions The analysis of IEM and EF patient characteristics delineates four subgroups (FEM, DEM, EMF and EF) in terms of clinical, laboratory, imaging, pathological and outcome specificities, and proposes an adapted diagnostic and care management approach.

Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and severe manifestation of anti-MDA5 dermatomyositis (MDA5-DM) associated with poor outcome. The optimal treatment regimen for MDA5-DM RP-ILD is yet to be determined. Specifically, the value of adding plasma exchange (PLEX) to corticosteroids and immunosuppressants remains unclear. We aimed to evaluate the effect of PLEX on the outcome of patients with MDA5-DM RP-ILD.This French nationwide multicentre retrospective study included all MDA5-DM RP-ILD patients from 2012 to 2021 admitted to 18 centres. The primary endpoint was one-year transplant-free survival.51 patients with MDA5-DM RP-ILD (female 67%; mean age at disease onset: 51 ± 11.6 years) were included. Thirty-two (63%) patients required mechanical ventilation and twenty-five (49%) received PLEX. One-year mortality or lung transplant occurred in 63% cases after a median follow-up of 77 [38-264] days. The Cox proportional hazards multivariable model only retained mechanical ventilation but not PLEX (p = 0.7) as independent predictor of the primary endpoint. One-year transplant-free survival rates in PLEX + vs. PLEX-were 20% vs. 54% (p = 0.01), respectively. The Kaplan-Meier estimated probabilities of one-year transplant-free survival was statistically higher in PLEX-compared to PLEX + patients (p = 0.05). PLEX + compared to PLEX-patients more frequently received mechanical ventilation and immunosuppressants suggesting PLEX + patients had a more severe disease.MDA5-DM RP-ILD is associated with poor rate of one-year transplant-free survival. The use of PLEX was not associated with a better outcome albeit they were mainly given to more severe patients. While our study reports the largest series of MDA5-DM RP-ILD given PLEX, these results needs to be interpreted with caution owing the numerous selection, indication and interpretation bias. Further studies are needed to evaluate their efficacy in this setting.

Anti-synthetase syndrome (ASyS)-associated myositis is a major subgroup of the idiopathic inflammatory myopathies (IIM) and is characterized by disease chronicity with musculoskeletal, dermatological and pulmonary manifestations. One of eight autoantibodies against the aminoacyl-transferase RNA synthetases (ARS) is detectable in the serum of affected patients. However, disease-specific therapeutic approaches have not yet been established.To obtain a deeper understanding of the underlying pathogenesis and to identify putative therapeutic targets, we comparatively investigated the most common forms of ASyS associated with anti-PL-7, anti-PL-12 and anti-Jo-1. Our cohort consisted of 80 ASyS patients as well as healthy controls (n = 40), diseased controls (n = 40) and non-diseased controls (n = 20). We detected a reduced extent of necrosis and regeneration in muscle biopsies from PL-12+ patients compared to Jo-1+ patients, while PL-7+ patients had higher capillary dropout in biopsies of skeletal muscle. Aside from these subtle alterations, no significant differences between ASyS subgroups were observed. Interestingly, a tissue-specific subpopulation of CD138+ plasma cells and CXCL12+/CXCL13+CD20+ B cells common to ASyS myositis were identified. These cells were localized in the endomysium associated with alkaline phosphatase+ activated mesenchymal fibroblasts and CD68+MHC-II+CD169+ macrophages. An MHC-I+ and MHC-II+ MxA negative type II interferon-driven milieu of myofiber activation, topographically restricted to the perifascicular area and the adjacent perimysium, as well as perimysial clusters of T follicular helper cells defined an extra-medullary immunological niche for plasma cells and activated B cells. Consistent with this, proteomic analyses of muscle tissues from ASyS patients demonstrated alterations in antigen processing and presentation. In-depth immunological analyses of peripheral blood supported a B-cell/plasma-cell-driven pathology with a shift towards immature B cells, an increase of B-cell-related cytokines and chemokines, and activation of the complement system. We hypothesize that a B-cell-driven pathology with the presence and persistence of a specific subtype of plasma cells in the skeletal muscle is crucially involved in the self-perpetuating chronicity of ASyS myositis. This work provides the conceptual framework for the application of plasma-cell-targeting therapies in ASyS myositis.

The present review describes the interferon (IFN)-signature currently emerging as a tool for the diagnosis of idiopathic inflammatory myopathies (IIMs), and aims at presenting the interests and limitations of this recent tool for the clinics and the research.Recent in-vivo and in-vitro transcriptomic studies have evidenced the involvement of IFNs in the pathogenesis of IIMs. A correlation between the IFN-signature and the clinical severity of IIMs has been established. Moreover, studies pointed out differences in the IFN-signature regarding the IIM subgroup (dermatomyositis, polymyositis, inclusion body myositis, anti-synthetase syndrome, immuno-mediated necrotizing myopathies), raising the hypothesis of several pathogenic processes in IIMs.IIM pathogenesis remains partially understood. IFN-signature represents one of the main recent advances in the field. IFN-signature was identified thanks to transcriptomic analyses of tissues or cells from IIM patients (muscle, skin, blood cells, muscle cells) and should allow to establish new diagnosis and better monitoring of IIM patients. It also provides a tool for investigation of IIM pathogenesis. Nevertheless, IFN-signature still requires accurate definition in order to standardize its use, notably in the clinical practice.

International audience

Eosinophilic myositis belong to the idiopathic inflammatory myopathies and are defined by an inflammatory infiltrate composed of eosinophils within the muscle. To date, no consensus exists for diagnosis and care of such patients. The aim of this review was to describe clinical and histological presentation, treatment, and outcome of eosinophilic myositis based on a systematic review of all published histologically proven cases of eosinophilic myositis. A total of 453 records were identified in MEDLINE until November 2020. A total of 69 published cases were identified. The analysis of these allowed the distinction of the 3 previously described pathological subtypes: focal eosinophilic myositis (n=17); diffuse eosinophilic myositis (n=36); and eosinophilic perimyositis (n=16). We propose a simple algorithm for diagnosis and treatment strategy for the care of patient with muscular symptoms and blood eosinophilia. This work also highlights eosinophilic myositis pathogenesis and the need for careful investigations in order to rule out differential diagnoses.

Objective To assess the effectiveness of corticosteroids among older adults with coronavirus disease 2019 (COVID-19) pneumonia requiring oxygen. Methods We used routine care data from 36 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids with at least 0.4 mg/kg/day equivalent prednisone (treatment group) versus standard of care (control group). Participants were adults aged 80 years or older with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or CT scan images typical of COVID-19 pneumonia, requiring oxygen ≥3 L/min, and with an inflammatory syndrome (C-reactive protein ≥40 mg/L). The primary outcome was overall survival at day 14. In our main analysis, characteristics of patients at baseline (i.e. time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. Results Among the 267 patients included in the analysis, 98 were assigned to the treatment group. Their median age was 86 years (interquartile range 83–90 years) and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. In total, 43/98 (43.9%) patients in the treatment group and 84/166 (50.6%) in the control group died before day 14 (weighted hazard ratio 0.67, 95% CI 0.46–0.99). The treatment and control groups did not differ significantly for the proportion of patients discharged to home/rehabilitation at day 14 (weighted relative risk 1.12, 95% CI 0.68–1.82). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events, but only 11 (6.4%) from the control group. Conclusions Corticosteroids were associated with a significant increase in the overall survival at day 14 of patients aged 80 years and older hospitalized for severe COVID-19.

OBJECTIVE: To assess the effectiveness of corticosteroids on outcomes of patients with COVID-19 pneumonia requiring oxygen without mechanical ventilation. METHODS: We used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) versus standard of care (no-CTC group) among adults 18 to 80 years old with confirmed COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death by day 28. In our main analysis, characteristics of patients at baseline (i.e., time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting. RESULTS: Among the 891 patients included in the analysis, 203 were assigned to the CTC group. Use of corticosteroids was not significantly associated with risk of intubation or death by day 28 (weighted hazard ratio [wHR] 0.92, 95% CI 0.61 to 1.39) or cumulative death rate (wHR 1.03, 95% CI 0.54 to 1.98). However, use of corticosteroids was associated with reduced risk of intubation or death by day 28 in the prespecified subgroups of patients requiring oxygen ≥ 3 L/min (wHR 0.50, 95% CI 0.30 to 0.85) or C-reactive protein level ≥ 100 mg/L (wHR 0.44, 95%CI 0.23 to 0.85). Number of hyperglycaemia events was higher for patients with than without corticosteroids, but number of infections was similar. CONCLUSIONS: We found no association between the use of corticosteroids and intubation or death in the broad population of patients 18 to 80 years old with COVID-19 hospitalized in non-intensive care unit settings. However, the treatment was associated with reduced risk of intubation or death for patients with ≥ 3 L/min oxygen or C-reactive protein level ≥ 100 mg/L at baseline. Further research need to confirm the right timing of corticosteroids for patients with COVID-19 requiring oxygen only.

To assess the effectiveness of corticosteroids among older adults with coronavirus disease 2019 (COVID-19) pneumonia requiring oxygen.We used routine care data from 36 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids with at least 0.4 mg/kg/day equivalent prednisone (treatment group) versus standard of care (control group). Participants were adults aged 80 years or older with PCR-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or CT scan images typical of COVID-19 pneumonia, requiring oxygen ≥3 L/min, and with an inflammatory syndrome (C-reactive protein ≥40 mg/L). The primary outcome was overall survival at day 14. In our main analysis, characteristics of patients at baseline (i.e. time when patients met all inclusion criteria) were balanced by using propensity-score inverse probability of treatment weighting.Among the 267 patients included in the analysis, 98 were assigned to the treatment group. Their median age was 86 years (interquartile range 83-90 years) and 95% had a SARS-CoV-2 PCR-confirmed diagnosis. In total, 43/98 (43.9%) patients in the treatment group and 84/166 (50.6%) in the control group died before day 14 (weighted hazard ratio 0.67, 95% CI 0.46-0.99). The treatment and control groups did not differ significantly for the proportion of patients discharged to home/rehabilitation at day 14 (weighted relative risk 1.12, 95% CI 0.68-1.82). Twenty-two (16.7%) patients receiving corticosteroids developed adverse events, but only 11 (6.4%) from the control group.Corticosteroids were associated with a significant increase in the overall survival at day 14 of patients aged 80 years and older hospitalized for severe COVID-19.

International audience

International audience; For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.

ObjectiveTo assess the effectiveness of corticosteroids on outcomes of patients with mild COVID-19 pneumonia.MethodsWe used routine care data from 51 hospitals in France and Luxembourg to assess the effectiveness of corticosteroids at 0.8 mg/kg/day eq. prednisone (CTC group) vs standard of care (no-CTC group) among patients ≤ 80 years old with COVID-19 pneumonia requiring oxygen without mechanical ventilation. The primary outcome was intubation or death at Day 28. Baseline characteristics of patients were balanced using propensity score inverse probability of treatment weighting.ResultsAmong the 891 patients included in the analysis, 203 were assigned to the CTC group. At day 28, corticosteroids did not reduce the rate of the primary outcome (wHR 0.92, 95% CI 0.61 to 1.39) nor the cumulative death rate (wHR 1.03, 95% CI 0.54 to 1.98). Corticosteroids significantly reduced the rate of the primary outcome for patients requiring oxygen ≥ at 3L/min (wHR 0.50, 95% CI 0.30 to 0.85) or C-Reactive Protein (CRP) ≥ 100mg/L (wHR 0.44, 95%CI 0.23 to 0.85). We found a higher number of hyperglycaemia events among patients who received corticosteroids, but number of infections were similar across the two groups.ConclusionsWe found no association between the use of corticosteroids and intubation or death in the broad population of patients ≤80 years old with COVID-19 hospitalized in non-ICU settings. However, the treatment was beneficial for patients with ≥ 3L/min oxygen or CRP ≥ 100mg/L at baseline. These data support the need to confirm the right timing of corticosteroids for patients with mild COVID.Short summaryWe assessed the effectiveness of corticosteroids among patients ≤ 80 years old with COVID-19, in non-ICU settings. Our results support the use of corticosteroids for patients receiving oxygen at ≥3L/min or with a C-reactive protein ≥ 100mg/L at baseline.

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

ObjectiveTo better define in a cohort study the clinical and pathologic features of focal myositis (FM).MethodsWith the use of the usual clinicopathologic definition, each confirmed case of FM in the Lyon University Hospital's myopathologic database between 2000 and 2016 was retrieved. Clinical, pathologic, imaging, serologic, and therapeutic data were collected. When data were missing but feasible, appropriate pathologic analyses were performed.ResultsOf the 924 patients included in the database, 37 (4%) had confirmed FM (14 female, 23 male patients). The main symptoms were pain (n = 30, 81%), muscular mass (n = 16, 43%), erythema at the site of FM (n = 12, 32%), and fever (n = 9, 24%). Serum creatine kinase was normal in most patients (81%); serum immune abnormalities were frequent (inflammatory syndrome in sera [39%], dysglobulinemia [52%], and anti-nuclear antibody positivity [29%]). In addition to confirming previously reported findings, pathologic analyses found significant rates of vasculitis (68%) and fasciitis (73%). Here, FM appeared frequently to be associated with other diseases such as immune-mediated inflammatory disease (IMID; 32%), neoplasia (24%), and radiculopathy (11%). Regarding outcomes, 64% of the cases had received immunosuppressive drugs, and the relapse rate was 41%.ConclusionThe present study suggests that FM is not as innocuous as previously believed, particularly considering the associated disorders. Notably, patients with FM should receive careful IMID and neoplasia screening.

Myalgia or muscle weakness is frequently observed during HIV infection (1), and 15% of HIV patients may have an increased serum creatine kinase (CK) level.1 Case reports or case series have suggested that HIV-associated myopathies represent a large spectrum of disease.2 To date, data on muscle involvement during HIV infection remain sparse and we aimed to describe the clinical characteristics and evolution of biopsy-proven HIV-associated myopathies. All HIV-positive patients who had a muscle biopsy performed at the Pitie-Salpetriere University Hospital between 2001 and 2012 were identified. Medical records were retrospectively reviewed to assess muscle disease features and HIV infection characteristics. Patients were classified histologically as polymyositis (PM), non-specific myositis (NSM), immune-mediated necrotizing myopathy (IMNM), or inclusion body myositis (IBM) according to the European Neuromuscular Center (ENMC) criteria.3 4 Isolated mitochondrial abnormality (IMA) was defined as presence of cytochrome c oxidase negative fibres and/or succinate dehydrogenase positive staining without inflammatory cell infiltrate or rimmed vacuoles. PM or NSM evolution towards IBM was evaluated at follow-up. Uncontrolled viral load was defined as >40 copies/mL. Categorical variables are reported herein as numbers and/or percentages and were compared using a χ2 or Fisher’s exact test. Quantitative variables are reported as median (IQR1–IQR3) and compared using non-parametric one-way one-way analysis of variance (ANOVA). For all statistical analyses, p

Patients with systemic rheumatic disease (SRD) share the risks of multi-organ flare-up, cardiovascular diseases, and immunosuppression. Such situations can lead to an acute critical illness. The present study describes the clinical features of SRD patients admitted to the intensive care unit (ICU) and their short- and long- term mortality.We performed a multicentre retrospective study in 10 French ICU in Lyon, France. Inclusion criteria were SRD diagnosis and admission for an acute organ failure. The primary endpoint was ICU mortality.A total of 271 patients were included. SRD included systemic lupus erythematosus (23.2% of included patients), vasculitis (10.7%), systemic sclerosis (10.7%), idiopathic inflammatory myopathy (6.3%), and other connective tissue disorders (rheumatoid arthritis, Sjogren and Sharp syndromes; 50.9%). Initial organ failure(s) were shock (43.5% of included patients), acute kidney injury (30.5%), and acute respiratory failure (23.2%). The cause(s) of ICU admission included sepsis (61.6%), cardiovascular events (33.9%), SRD-flare up (32.8%), and decompensations related to comorbidities (28%). The ICU mortality reached 14.3%. The factors associated with ICU mortality were chronic cardiac failure, invasive ventilation and admission in ICU for another reason than sepsis or SRD flare-up. The median follow-up after ICU discharge was 33.6 months. During follow-up, 109 patients died. The factors associated with long-term mortality included age, Charlson comorbidity index, and ICU admission for sepsis or SRD flare-up.The ICU mortality of patients with SRD was low. Sepsis was the first cause of admission. Cardiovascular events and comorbidities negatively impacted ICU mortality. Admission for sepsis or SRD flare-up exerted a negative effect on the long-term outcome.

Amongst the heterogeneous group of inflammatory myopathies, focal myositis stands as a rare and benign dysimmune disease. Although it can be associated with root and/or nerve lesions, traumatic muscle lesions and autoimmune diseases, its triggering factors remain poorly understood. Defined as an isolated inflammatory pseudotumour usually restricted to one skeletal muscle, clinical presentation of focal myositis is that of a rapidly growing solitary mass within a single muscle, usually in the lower limbs. Electromyography shows spontaneous activity associated with a myopathic pattern. MRI reveals a contrast enhanced enlarged muscle appearing hyper-intense on FAT-SAT T2 weighted images. Adjacent structures are spared and there are no calcifications. Serum creatine kinase (CK) levels are usually moderately augmented and biological markers of systemic inflammation are absent in most cases. Pathological histological features include marked variation in fibre size, inflammatory infiltrates mostly composed of T CD4+ lymphocytes and macrophages, degenerating/regenerating fibres and interstitial fibrosis. Differential diagnoses are numerous and include myositis of other origin with focal onset. Steroid treatment should be reserved for patients who present with major pain, nerve lesions, associated autoimmune disease, or elevated C reactive protein or CK.

Pompe disease is an inherited lysosomal disease in which there is a decrease or absence of acid alpha-glucosidase activity. This enzyme defect induces glycogen storage in different tissues, especially muscle and heart, resulting in muscle weakness, respiratory failure and heart disease. Substitutive enzyme replacement therapy (ERT) dispensed every two weeks is the only treatment that has shown benefits. However, this treatment induces hypersensitivity for half of the treated patients. Reactions range from mild to severe, sometimes requiring ERT suspension and anti-anaphylaxis drug administration. Understandably, high amount of acid alpha-glucosidase infusion seems to be identified by the immune system as a danger associated molecular pattern, and induce an immune reaction, involving sometimes, but not always, immunoglobulin E (IgE) production and activating mast and basophil polynuclear cells. Considering the lack of therapeutic alternatives and the proved benefit of ERT, desensitization finds its place here. We hereby report the case of a patient for whom a simplified desensitization protocol ("SWORD": Start With One Regular Drop) was successfully achieved, allowing ERT to be pursued, resulting eventually in clinical improvement.

International audience; Objective: Anti-transcription intermediary factor 1γ (anti-TIF1γ) antibodies are the main predictors of cancer in dermatomyositis (DM). Yet, a substantial proportion of anti-TIF1γ-positive DM patients do not develop cancer. This study was undertaken to identify biomarkers to better evaluate the risk of cancer and mortality in DM.Methods: This multicenter study was conducted in adult anti-TIF1γ-positive DM patients from August 2013 to August 2017. Anti-TIF1γ autoantibody levels and IgG subclasses were identified using a newly developed quantitative immunoassay. Age, sex, DM signs and activity, malignancy, and creatine kinase (CK) level were recorded. Risk factors were determined by univariate and multivariate analysis according to a Cox proportional hazards regression model.Results: Among the 51 adult patients enrolled (mean ± SD age 61 ± 17 years; ratio of men to women 0.65), 40 (78%) had cancer and 21 (41%) died, with a mean ± SD survival time of 10 ± 6 months. Detection of anti-TIF1γ IgG2 was significantly associated with mortality (P = 0.0011) and occurrence of cancer during follow-up (P < 0.0001), with a 100% positive predictive value for cancer when the mean fluorescence intensity of anti-TIF1γ IgG2 was >385. None of the patients developed cancer after 24 months of follow-up. Univariate survival analyses showed that mortality was also associated with age >60 years (P = 0.0003), active DM (P = 0.0042), cancer (P = 0.0031), male sex (P = 0.011), and CK level >1,084 units/liter (P = 0.005). Multivariate analysis revealed that age >60 years (P = 0.015) and the presence of anti-TIF1γ IgG2 (P = 0.048) were independently associated with mortality.Conclusion: Our findings indicate that anti-TIF1γ IgG2 is a potential new biomarker of cancer that should be helpful in identifying the risk of mortality in anti-TIF1γ-positive DM patients.

Background Myositis is recognized as a manifestation of primary Sjogren’s syndrome (pSS). Grading muscle involvement using the EULAR Sjogren Syndrome Disease Activity index (ESSDAI) does not require biopsy-proven active myositis or extensive immunological investigations. However, several studies have reported that a high proportion of pSS-associated myositis is either inclusion body myositis (IBM) or an overlap with idiopathic inflammatory myopathies. Objectives The objective of our study was to investigate the nature of inflammatory muscle involvement in a large sample of patients with pSS and concurrent myositis. Methods We conducted a French nation-wide survey among reference centers known for their experience in the field of systemic auto-immune diseases. Patients with physician-based diagnosis of pSS and inflammatory muscle involvement were included. They were categorized and subsequently described and compared according to the identification of an associated condition likely to explain inflammatory muscle involvement. Results 60 cases of myositis in patients with pSS were identified. Patients were mostly female (52/60) and pSS classification criteria were met in 43/60. Muscle biopsy was performed in 50/60 patients and showed inflammatory lesions in 80% of cases. An associated condition likely to explain myositis was identified in 31 patients: typical dermatomyositis rash (n=8), MCTD-specific antibodies (n=11), myositis specific antibodies (n=10), and systemic lupus erythematosus, scleroderma or ANCA associated vasculitis specific antibodies in favor of an overlap syndrome (n=7). Among the 29 patients without associated condition likely to explain myositis, 17 had a biopsy proven inflammatory muscle disease, showing histopathologic features consistent with IBM in 5 cases. 4 of the 5 patients with IBM histological features received corticosteroids and/or other immunosuppressive agents to treat muscle disease. Worsening of muscular involvement despite treatment was reported in these 4 patients. Comparative analysis showed a lower ESSDAI (p = 0.001) among patients without identified associated condition likely to explain myositis. Conclusion In most cases of concurrent pSS and myositis, inflammatory muscle involvement is explained by a context of overlap syndrome or has a histological pattern consistent with IBM. Extensive immunological investigations and muscle biopsy appear to be necessary in pSS patients with suspected inflammatory muscle involvement, in order to avoid misclassification and/or overtreatment. Disclosure of Interests Camille Houssais: None declared, Jean-baptiste Noury: None declared, Yves Allenbach: None declared, Laure Gallay: None declared, Florence Assan: None declared, Olivier Benveniste: None declared, Jonathan Broner: None declared, Pierre Duffau: None declared, Alexandra Espitia-Thibault: None declared, Anne Grasland: None declared, Sebastien SANGES: None declared, Gilles Hayem: None declared, Veronique LE GUERN: None declared, Nihal Martis: None declared, Kuberaka Marianpillai: None declared, Denis Mulleman Speakers bureau: Pfizer, Novartis, Grifols, Gaetane Nocturne: None declared, alain meyer: None declared, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Divi Cornec: None declared, Dewi Guellec: None declared

Introduction Les dermatomyosites a anticorps anti-MDA5 (DM MDA5+) ont des atteintes extramusculaires au premier plan (lesions cutanees severes, arthralgies/arthrite, fievre) pouvant engager le pronostic vital (atteinte pulmonaire), alors que l’atteinte musculaire est peu marquee. Leur pronostic est sombre (25 % de mortalite) et il est important de definir des facteurs de risque de mortalite pour mieux definir la strategie therapeutique. L’objectif de cette etude est d’identifier des facteurs pronostiques chez les DM MDA5+. Materiels et methodes Nous avons realise une etude nationale multicentrique retrospective grâce au Reseau francais des myosites pour les DM MDA5+. Les criteres d’inclusion etaient : – un diagnostic de DM (definie selon les criteres de l’ENMC en 2004 : un debut progressif subaigu, une faiblesse musculaire plutot proximale, une atteinte cutanee typique comme un erytheme lilace des paupieres, des papules de Gottron ou un erytheme du decollete et une atrophie perifasciculaire a la biopsie musculaire) ; – la positivite des anticorps anti-MDA5. Les recueils des donnees cliniques, paracliniques et evolutives ont ete realises a partir des dossiers des patients. Resultats Quarante et un patients ont ete identifies. L’âge moyen etait de 44 ans (± 16,5) avec un sex-ratio femme/homme de 1,4. Au diagnostic 92 % patients presentaient une atteinte pulmonaire et 87 % une atteinte cutanee. Un tiers (31 %) des patients ont presente une atteinte pulmonaire rapidement progressive (RPILD definie par une aggravation des lesions au scanner thoracique ou une aggravation des EFR pendant une duree inferieure ou egale a 3 mois). Les atteintes articulaires et musculaires (deficit moteur ou elevation des CK) etaient observees respectivement dans 75 % et 51 % des cas. La duree moyenne de suivi etait de 41,2 mois (± 61,3). La plupart des patients ont beneficie de corticosteroides (98 %) et d’immunosuppresseurs (83 %, dont 24 % du cyclophosphamide et 15 % des inhibiteurs des calcineurines) ou de rituximab (7 %), plus ou moins associes a des echanges plasmatiques (20 %) et/ou des immunoglobulines intraveineuses (15 %) selon leur severite. Le taux de mortalite etait de 22 %, avec des 44 % des deces survenus dans les 3 mois suivants le diagnostic. Les deces etaient dus a l’atteinte respiratoire dans 67 % des cas. Parmi les patients vivants, 52 % ont presente au moins une rechute, avec le plus frequemment une rechute pulmonaire (45 % des patients rechuteurs). L’analyse univariee identifie 3 variables liees au deces. Comme attendu les signes de gravite immediate respiratoire ont ete identifies avec une hypoxie severe (paO2 Conclusion Comme attendu, la severite initiale de l’atteinte pulmonaire (RPILD et hypoxie profonde) est un facteur pronostique pejoratif. Cette etude suggere pour la premiere fois que le sexe feminin et l’existence d’une atteinte articulaire seraient des elements de bon pronostic a prendre en compte dans la strategie therapeutique chez les patients sans signe de gravite pulmonaire immediate.

Sporadic inclusion-body myositis (sIBM) is the most frequent myopathy after 50 years of age. As the clinical presentation may often be typical, pathological confirmation by muscle biopsy appears necessary, but sometimes difficult. Further delineation of the framework of this particular disease, especially during its early-onset stage, appears to be challenging. New classification of diagnostic criteria as well as the identification of new diagnostic hallmarks appear to be the two main tools towards to achieve this purpose. sIBM pathophysiology has long been discussed and remains yet controversial. Since its initial description, there have been two major pathogenic hypotheses: inflammatory and degenerative. To date, the debate is still ongoing, as recent works support both pathophysiological mechanisms, although the inflammatory process seems to be slightly more preeminent in the recent literature. Treatment remains the most disappointing aspect of the disease as, despite various therapeutic attempts, no significant efficacy has been reported thus far. Nevertheless, advances in our pathophysiological understanding of the disease are paving the way for further therapeutic perspectives that might arise in the years to come. The objective of the present work was to summarize the most significant data published on sIBM during the past 2 years.

Antisynthetase syndrome (ASyS) is an acquired myopathy characterized by the presence of myositis-specific autoantibodies directed against tRNA-synthetases. ASyS is potentially life threatening due to lung involvement and treatment remains a challenge to date. With symptoms not limited to muscles but also involving lung, skin and joints, ASyS appears specific and has a particular pathogenesis, different from the other inflammatory myopathies. This review is intended to discuss the current understanding of ASyS pathogenesis, pointing its current knowledge and also the crucial prospects that may lead to critical improvement of ASyS care.Regarding ASyS pathogenesis, initiation of the disease seems to arise in a multifactorial context, with first lesions occurring within the lungs. This may lead to aberrant self-antigen exposure and tolerance breakdown. The consequences are abnormal activation of both innate and adaptive immunity, resulting in the patients with favourable genetic background to autoimmune-mediated organ lesions. Immune and nonimmune roles of the antigen, as well as antigen presentation leading to specific T-cell and B-cell activation and to the production of specific autoantibodies belong to the disease process.This work aims to detail ASyS pathogenesis understanding, from initiation to the disease propagation and target tissue lesions, in order to considering future treatment directions.

Introduction La dermatomyosite a anticorps anti-MDA5 (Melanoma differentiation-associated gene 5) (DM MDA5 + ) est une maladie systemique touchant la peau, les articulations et le poumon. L’atteinte pulmonaire peut etre rapidement progressive et fatale. L’anticorps anti-MDA5 cible un recepteur reconnaissant les ADN/ARN viraux. La frequence de l’atteinte respiratoire (> 80 % des cas) et la nature de la cible auto-antigenique suggerent un facteur declenchant viral de la maladie. Pour explorer cette question nous avons fait l’hypothese que le debut de la maladie etait rythme par les infections virales saisonnieres a tropisme respiratoire. Ce travail avait pour objectif de determiner si le debut des symptomes etait saisonnier. Materiels et methodes Nous avons realise une etude observationnelle, retrospective et multicentrique (n = 37) sur une cohorte francaise de patients atteinte de DM MDA5 + . Les donnees cliniques, biologiques et radiographiques ont ete etudiees, ainsi que la date d’apparition des premiers symptomes respiratoires (definis par le mois d’apparition des premiers symptomes reportes dans le premier compte rendu). Apres une analyse de la serie temporelle (stationnaire, autocorrelation) la modelisation des resultats (SARIMA) a pu etre appliquee. Les resultats ont ete compares a ceux de la declaration des cas de grippe recueillis par l’institut de veille sanitaire (INVS). Resultats Les patients inclus (n = 121) etaient majoritairement des femmes (diagnostic 2002–2017) d’âge moyen 49 ans. La majorite des patients presentaient des lesions cutanees (87,5 %), une pneumopathie interstitielle (77 %) et des arthralgies (69 %). Un tiers des patients etait febrile au diagnostic. L’atteinte pulmonaire etait rapidement progressive dans un tiers des cas. Un quart des patients sont decedes. La survenue des symptomes a ete classee par trimestre. Dans un premier temps, l’analyse de la repartition des premiers symptomes par trimestre montre qu’ils surviennent plus frequemment en periode hivernale (p = 0,05). Dans un second temps, la modelisation a permis de montrer que la repartition des premiers symptomes etait saisonniere (periodique) (p Conclusion Cette etude a permis de mettre en evidence que le debut des symptomes etait saisonnier avec un pic hivernal comparable a celui des cas declares de grippe. Ensemble, ces donnees suggerent indirectement l’implication d’un virus dans la physiopathologie de la maladie.

Extracellular vesicles (EVs) are composed of microvesicles and exosomes. Exosomes are small membrane vesicles (40-120 nm sized) of endosomal origin released in the extracellular medium from cells when multivesicular bodies fuse with the plasma membrane, whereas microvesicles (i.e., shedding vesicles, 100 nm to 1 μm sized) bud from the plasma membrane. Exosomes and microvesicles carry functional proteins and nucleic acids (especially mRNAs and microRNAs) that can be transferred to surrounding cells and tissues and can impact multiple dimensions of the cellular life. Most of the cells, if not all, from neuronal to immune cells, release exosomes and microvesicles in the extracellular medium, and all biological fluids including blood (serum/plasma), urine, cerebrospinal fluid, and saliva contain EVs.Prion-infected cultured cells are known to secrete infectivity into their environment. We characterized this cell-free form of prions and showed that infectivity was associated with exosomes. Since exosomes are produced by a variety of cells, including cells that actively accumulate prions, they could be a vehicle for infectivity in body fluids and could participate to the dissemination of prions in the organism. In addition, such infectious exosomes also represent a natural, simple, biological material to get key information on the abnormal PrP forms associated with infectivity.In this chapter, we describe first a method that allows exosomes and microvesicles isolation from prion-infected cell cultures and in a second time the strategies to characterize the prions containing exosomes and their ability to disseminate the prion agent.

Focal myositis are inflammatory muscle diseases of unknown origin. At the opposite from the other idiopathic inflammatory myopathies, they are restricted to a single muscle or to a muscle group. They are not associated with extramuscular manifestations, and they have a good prognosis without any treatment. They are characterized by a localized swelling affecting mostly lower limbs. The pseudo-tumor can be painful, but is not associated with a muscle weakness. Creatine kinase level is normal. Muscle MRI shows an inflammation restricted to a muscle or a muscle group. Muscle biopsy and pathological analysis remain necessary for the diagnosis, showing inflammatory infiltrates composed by macrophages and lymphocytes without any specific distribution within the muscle. Focal overexpression of HLA-1 by the muscle fibers is frequently observed. The muscle biopsy permits to rule out differential diagnosis such a malignancy (sarcoma). Spontaneous remission occurs within weeks or months after the first symptoms, relapse is unusual., Les myosites focales sont des maladies musculaires inflammatoires de cause inconnue. Elles se distinguent des autres myopathies auto-immunes par leur caractère limité à un muscle ou à un groupe musculaire, par l’absence de signe extramusculaire associé et par leur pronostic favorable en l’absence de traitement. Elles touchent le plus souvent le membre inférieur, et se présentent typiquement comme une masse plus ou moins douloureuse, sans déficit moteur associée. Le taux d’enzymes musculaires n’est pas élevé. L’IRM musculaire est l’élément diagnostique clef qui permet de voir une inflammation musculaire focale, touchant un seul muscle ou un groupe musculaire. Seule la biopsie musculaire permet d’affirmer le diagnostic, montrant des infiltrats inflammatoires sans topographie particulière constitués de lymphocytes et de macrophages associés le plus souvent à une expression focale de HLA-1 par les fibres musculaires. Elle permet surtout d’écarter des diagnostics différentiels comme un sarcome. Le pronostic est favorable avec une régression spontanée de la lésion en quelques semaines ou mois après les premiers symptômes. Les récidives sont possibles mais peu fréquentes.

Introduction La myosite focale (MF) est une maladie rare. Elle a ete decrite dans des cases reports, de petites series, et une large serie centree sur la description anatomopathologique. La litterature sur la FM reste pauvre, notamment concernant les questions majeures que sont le cadre nosologique, les maladies associees, la presentation clinique et la prise en charge therapeutique. Le but de ce travail est de decrire pour la premiere fois une large cohorte, en analysant les donnees cliniques, paracliniques ainsi que l’evolution et la therapeutique. Patients et methodes En partant de la base de donnees « Myosite » du CHU de Lyon, regroupant les patients avec un diagnostic anatomopathologique de myosite entre 2000 et 2016, une cohorte retrospective de 37 MF a ete individualisee. Les donnees cliniques, biologiques, morphologiques, anatomopathologiques et therapeutiques etaient analysees. Resultats Parmi les 924 patients inclus dans la base de donnee lyonnaise « myosite », 37 (soit 4 %) avaient une FM (23 hommes, 14 femmes, âge moyen = 44 ans). Les symptomes les plus frequents etaient la douleur (81 %), la fievre (24 %) et un erytheme localise en regard de la lesion (32 %). Les creatine phospho-kinases etaient normales dans la majorite des cas (81 %), en revanche, les investigations biologiques retrouvaient des stigmates de dysimmunite chez la moitie des patients. L’analyse anatomopathologique etait en accord avec les descriptions retrouvees dans la litterature, mais identifiait neanmoins deux nouveaux elements frequemment retrouves : la presence de lesions de vascularite intramusculaire, non necrosante, (68 %) ainsi que des lesions de fasciite (73 %). Sur le plan pathogenique, les FM etait frequemment associees a d’autres pathologies. En effet, les patients presentaient de maniere synchrone ou dans un delai d’apparition rapide : une maladie dysimmunitaire ou inflammatoire (32 %), une neoplasie (tumeur solide ou hemopathie, 24 %), une radiculopathie (11 %). Considerant l’evolution, la majorite des patients ont beneficie de traitements immunosuppresseurs (64 %), et les recidives etaient frequentes (41 %). Conclusion Contrairement aux considerations usuelles de pathologie peu grave, se resolvant spontanement, les resultats de cette etude soulignent l’importance de considerer serieusement la survenue de la MF. Notamment, il semble important de realiser chez les patients presentant une FM un bilan exhaustif visant a la recherche d’une neoplasie, d’une maladie dysimmunitaire ou d’une radiculopathie.

Introduction Dans la dermatomyosite (DM), la balance necrose/regeneration de la fibre musculaire apparait comme negative, avec une lesion musculaire chronique, dictant l’evolution clinique de la maladie. Les mecanismes lesionnels ont ete largement investigues, notamment ceux lies a l’immunite acquise, et ont conduit a la decouverte d’autoanticorps, sans que ne se degagent d’avancees notables sur la prise en charge. Cependant, les capacites de regeneration ont ete tres peu documentees. Dans un muscle normal, une lesion musculaire enclenche le processus de regeneration, qui est une reparation ad integrum des fibres musculaires. La regeneration est possible grâce au processus de myogenese adulte, incluant la sortie de quiescence des cellules souches musculaires (CSM), leur proliferation, puis leur differenciation myogenique terminale et enfin leur fusion en myotubes puis en fibres musculaires. L’hypothese de travail est que dans un contexte de lesion chronique comme la DM, les proprietes de regeneration musculaire des CSM pourraient etre alterees du fait de la presence continue de signaux de regeneration et de signaux inflammatoires environnants. Materiels et methodes L’analyse detaillee de la myogenese est realisee sur des CSM issues de patients DM (total n = 8) et comparee a un groupe de controles (n = 5) apparies sur le sexe et l’âge. Les cas de DM sont definis comme leger, modere et severe a l’aide d’une classification anatomopathologique s’appuyant sur la classification des DM juveniles (Wedderburn et al., 2007). Les echantillons de patients et controles sont obtenus a la biobanque TissuTumoroteque Est (CRB-HCL hospices civils de Lyon BB-0033-00046). Les CSM sont cultivees in vitro selon plusieurs protocoles qui permettent d’analyser specifiquement les differentes etapes de la myogenese par des techniques d’immunofluorescence. La proliferation des cellules est evaluee par inclusion d’un analogue a la thymidine marque identifiant les cellules en cycle (protocole Click-it EDU). La differenciation myogenique terminale des cellules est evaluee par leur expression de la myogenine, qui est un facteur de transcription indispensable a la differenciation myogenique. Enfin, la fusion des cellules est quantifiee par le nombre de noyaux dans les cellules differenciees plurinucleees qui resultent d’une fusion cellulaire (myotubes). Une analyse quantitative des differentes etapes a ete realisee apres numerisation des images a l’aide du logiciel Image J. Resultats La proliferation des CSM n’etait pas significativement differente entre les groupes patients et controles cultivees dans les memes conditions. En revanche, l’analyse de la myogenese a montre une alteration tres importante chez les 3 cas DM severes etudies a ce jour, compares aux controles. Concernant la differenciation myogenique, on observe que le nombre de cellules engagees dans la differenciation terminale (exprimant la myogenine) etait significativement plus faible dans les DM compare aux controles (26 % vs 70 %). Concernant la fusion, l’index de fusion (ratio du nombre de noyaux presents dans des myotubes/nombre total de noyaux) etait egalement fortement altere chez les DM versus controles (28 % vs 76 %). La repartition des myotubes en differentes classes en fonction de leur nombre de noyaux montre des profils differents entre les controles et les DM. Conclusion Ces premiers resultats montrent une alteration importante des capacites regeneratives des CSM issues de muscle de patients DM avec notamment une incapacite a enclencher la differenciation terminale. Les analyses a venir permettront d’un part de dissequer precisement quelle etape de la myogenese est alteree (regulation du programme myogenique versus fusion per se) et d’autre part d’etablir un lien entre capacites regeneratives des CSM et gravite clinique de la DM. Ces resultats supportent l’hypothese d’une modification intrinseque des proprietes myogeniques des CSM des patients DM. Une diminution des capacites regeneratives du muscle dans la DM pourrait constituer un nouvel element dans la pathogenie de cette maladie, en lien avec sa chronicisation.

Introduction La myosite a inclusions (IBM pour Inclusion Body Myositis) est la myopathie inflammatoire la plus frequente apres 50 ans. L’atteinte clinique, composee d’une atteinte proximale aux membres inferieurs et distale aux membres superieurs, s’associe a un pattern histologique particulier avec la presence d’un infiltrat inflammatoire et de vacuoles bordees. La maladie cœliaque est une enteropathie immune liee a la presence d’auto anticorps (anti-gliadine, anti-transglutaminase, anti-endomysium). Durant cette pathologie, l’ingestion de gluten entraine une inflammation de la muqueuse duodeno-jejunale. Nous rapportons un cas ayant presente cette association particuliere et discutons l’intrication de ces 2 pathologies dysimmunitaires. Observation Cas report : un patient de 44 ans presentait depuis un an un amaigrissement de 10 kg, une faiblesse musculaire avec une atteinte distale des membres superieurs et proximale des membres inferieurs, ainsi que des troubles de deglutition et des douleurs abdominales. Il n’y avait pas de syndrome inflammatoire, les CPK etaient a 625 U/L. L’ensemble du bilan immunologique (anticorps anti-nucleaire, anti-SSA/B, Sm, Scl70, centromere, ribosome, Mi2, Ku, PmSCL, ainsi que le DOT myosite et les anti-SRP et HMGCoA) etait negatif. L’IRM musculaire mettait en evidence une amyotrophie bilaterale des vastes, associee a un infiltrat graisseux. Une biopsie musculaire etait realisee et mettait en evidence un infiltrat inflammatoire et des vacuoles bordees, permettant de poser le diagnostic d’IBM en accord avec les criteres usuels [1] . Cependant, devant l’âge jeune du patient, et la perte de poids massive, un bilan complementaire etait realise. Un scanner thoraco-abdomino-pelvien mettait en evidence de multiples adenopathies mesenteriques supra-centimetriques. Un PET scanner etait alors realise et montrait un hyper-metabolisme des anses digestives jejunales, et a un moindre degre pyloro-duodenales. Une gastroscopie etait realisee, retrouvant une atrophie marquee des segments D1-D2, dont l’analyse anatomo-pathologique retrouvait une franche atrophie villositaire avec inflammation. Les anticorps anti-transglutaminase etaient positifs. Un complement de bilan nutritionnel mettait en evidence des carences en vitamines E et B12, et par ailleurs un fer et une vitamine D normaux. Discussion La myosite a inclusions est une myopathie inflammatoire dont la pathogenese est encore discutee. Son association a d’autres pathologies dysimmunes a ete rapportee a de multiples reprises, parmi lesquelles la maladie cœliaque. Cependant, il s’agit du premier cas avec une positivite des anticorps anti-transglutaminase. Chez notre patient, l’atteinte precoce, ainsi que l’amaigrissement massif etaient des elements inhabituels qui ont mene au complement de bilan permettant le diagnostic de la pathologie digestive. Concernant la physiopathologie, dans leur etude des enzymes TGase (transglutaminase), Kim et al. [2] discutaient un lien entre l’expression des TGase et la formation des agregats retrouves dans les inclusions des fibres musculaires. Ce resultat etait appuye par la co-localisation histologique des TGases et des agregats, et la mise en jeu dans les deux processus de cytokines identiques (notamment IFNγ et TNFα). Par ailleurs, il est interessant de noter que les infiltrats musculaire et digestif sont composes majoritairement de lymphocytes T CD8. Un cas de patient presentant une myopathie inflammatoire « IBM-like » reversible dans le cadre d’une maladie cœliaque compliquee d’une carence severe en vitamine E a ete rapporte [3] . De maniere interessante, notre patient presentait lui aussi une carence en vitamine E, qui a ete supplementee. Des myopathies liees a des carences en vitamine E ont d’autre part ete rapportees, mais n’avaient pas le phenotype particulier de la myosite a inclusion. Enfin, l’intrication hypovitaminose E et atteinte musculaire pourra etre discutee, notamment en fonction de l’evolution clinique du patient, en considerant la correction de la carence vitaminique. Conclusion L’association IBM et maladie cœliaque est tres peu decrite. Elle fait discuter l’implication de processus dysimmunitaire commun dans la pathogenese de ces deux pathologies, et pose de question du role de la vitamine E.

Introduction La myosite a inclusions est la myopathie inflammatoire la plus frequente apres 50 ans. Si sa physiopathologie reste discutee, deux phenomenes pathologiques sont identifies : l’inflammation et la degenerescence. L’objectif de ce travail etait l’identification des marqueurs immunologiques seriques dans une large cohorte de patients atteints de myosite a inclusions (IBM). Patients et methodes Nous avons inclus tous les patients repertories dans la base de donnees « Myosites » (960 patients, reference CNIL 1739552) en septembre 2014 associant les criteres d’IBM selon Benveniste [1] ( n = 228) et ayant beneficie d’un bilan immunologique large ( n = 89). Resultats Il s’agissait de 46 hommes, 43 femmes, l’âge moyen etait de 69,4 ans [44–88]. Cinquante-sept patients (64 %) presentaient a au moins une reprise des anticorps antinucleaires (ANA) positifs (≥ 1/80). La repartition des titres d’ANA etait la suivante : 1/80 = 38,6 %, 1/160 = 28,1 %, 1/320 = 15,8 %, 1/640 3,5 %, superieur ou egal a 1/1280 = 14 %. L’aspect de l’immunofluorescence etait majoritairement mouchetee ( n = 43, 75,4 %), ou parfois nucleolaire ( n = 7, 12,3 %). Isolement, d’autres aspects etaient notes : granuleux, filamenteux, golgien, ou de type NOR90. Parmi tous les anticorps anti-antigene soluble du noyau testes, seuls les anti-SSA ont ete retrouves positifs chez 12 patients. Dans une moindre mesure, differentes specificites etaient egalement rencontrees : anticorps anti-gangliosides ( n = 11, 19,3 %), antithyroidiens ( n = 7, 12, » %), anti-Actine et pANCA (atypiques) dans 1 cas chacun (1,1 %). Une cryoglobulinemie a ete retrouve dans 2 cas, dont un en association a une hepatite C tres replicante. Par ailleurs, 44 patients presentaient une anomalie dans les gammaglobulines (77,2 %). Il s’agissait d’une gammapathie monoclonale de signification indeterminee ( n = 14, 24,6 % des 89 patients de la cohorte), d’hypogammaglobulinemies ( n = 4, 7 % de la cohorte), ou hypergammaglobulinemies polyclonales ( n = 27, 47,4 % de la cohorte). Conclusion Des stigmates biologiques d’auto-immunite ont ete retrouves chez 2/3 des patients de cette cohorte. Cette proportion est plus importante qu’attendue dans la population generale de plus de 70 ans (19,2 %) [2] . Par ailleurs, nous observons une frequence plus elevee de gammapathies monoclonales chez les patients IBM que dans la population generale de la meme tranche d’âge (24,6 % vs 3,7 %). Cette etude suggere donc une participation immunologique a la physiopathologie de la maladie et plaide pour la recherche d’auto-anticorps specifiques des IBM comme les anti-5′-nucleotidase cytosolique recemment decrits.

An 82-year-old woman, treated for severe rheumatoid polyarthritis by tumour necrosis factor inhibitors (2003–2008), rituximab (2008), abatacept (2008–2011) and long-term steroid therapy, also received prolonged bisphosphonate therapy to prevent bone mass loss. In 2009, a bilateral bisphosphonate severe osteonecrosis of the jaw (BONJ) was discovered along with evidence of left chronic mandible infection in early 2012, as mucosal disruption and suppurative sinus tract occurred (figure 1A,B). Bisphosphonate was stopped and mild surgical debridement was performed. Despite administration of antimicrobial therapy including high dose of amoxicillin and fluconazole, the suppurative sinus tract persisted. As a left mandibular fracture …