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Giant cell arteritis (GCA) is the most frequent vasculitis affecting adults aged 50 years. Cardiac involvement in GCA is considered rare, and only a few cases of pericarditis have been reported. The aim of this study was to determine the characteristics and prognosis of GCA patients suffering from pericardial involvement at diagnosis.We conducted a single-centre, retrospective chart review of patients with GCA in internal medicine departments (from 2000 to 2020). Patients were identified through a centralized hospital database. We retrospectively collected demographic, clinicobiological, histological, imaging, treatment and outcome data. Patients with pericardial effusion, defined as an effusion visible on the CT-scan performed at GCA diagnosis were compared to those without pericardial involvement.Among the 250 patients with GCA, 23 patients (9.2%) had pericardial effusion on CT-scan. The comparison between the groups revealed similar distribution of age, gender, cranial symptoms and ocular ischaemic complications. Patients with pericardial effusion had a higher frequency of weight loss. They also had lower haemoglobin levels and higher platelet levels (p = 0.006 and p = 0.002, respectively), and they more frequently had positive temporal artery biopsy. There were no differences concerning the treatment, relapses, follow-up duration or deaths.This case series sheds light on GCA as a cause of unexplained pericardial effusion or symptomatic pericarditis among adults aged 50 years and elevated inflammatory biological markers. Fortunately, pericardial involvement is a benign GCA manifestation. In that context, the search for constitutional symptoms, cranial symptoms and associated signs of polymyalgia rheumatica is crucial for rapidly guiding GCA diagnosis.

Resume Introduction Le syndrome de fuite capillaire idiopathique (SFCI), ou syndrome de Clarkson, est rare et met brutalement en jeu le prognostic vital. Trois phases evolutives sont decrites. La phase prodromique est aspecifique, souvent sous la forme d’un syndrome pseudo-grippal. La phase d’etat, marquee par une fuite capillaire majeure et un etat de choc hypovolemique, fait la gravite de la maladie par la survenue rapide d’une defaillance multiviscerale (DMV). L’hypovolemie contraste avec les oedemes, et l’hemoconcentration contraste avec l’hypoalbuminemie. La phase de resolution spontanee est marquee par la restauration des defaillances d’organes. Observations Nous rapportons deux cas de SFCI pris en charge en reanimation dont l’errance diagnostique initiale a probablement greve le pronostic. La premiere patiente, âgee de 28 ans a d’abord ete prise en charge pour une « polyglobulie ». Il s’agissait pourtant d’une hemoconcentration secondaire a une hypovolemie. Elle a presente un arret cardiocirculatoire lors de la deuxieme saignee avant de developper une DMV. Des immunoglobulines polyvalentes intraveineuses ont ete prescrites. L’evolution a ete favorable en reanimation. Le second patient, âge de 57 ans, a d’abord ete pris en charge pour une « myosite » (douleurs musculaires et rhabdomyolyse). Il s’agissait pourtant d’un syndrome de loges (œdeme musculaire lie a la fuite capillaire). Un etat de choc brutal evoluant vers une DMV conduisait au deces du patient en reanimation. Conclusion La physiopathologie du SFCI est inconnue et impliquerait une dysfonction endotheliale transitoire. Devant l’impossibilite de realiser des essais controles randomises pour le traitement de cette pathologie exceptionnelle, les therapeutiques symptomatiques (expansion volemique prudente, amines vasopressives) et specifiques (aminophylline intraveineuse) restent empiriques et peu efficaces. Presentant des effets controverses voire deleteres en phase de fuite, les immunoglobulines polyvalentes sont neanmoins benefiques en prophylaxie secondaire. Le diagnostic syndromique est difficile mais sa precocite est probablement l’element clef permettant une prise en charge immediate en reanimation, avant le stade des defaillances d’organe.

Objective Life habits (LH) encompass an individual’s engagement in daily activities such as nutrition, fitness, personal care, communication, housing, and mobility, along with his/her social role (responsibility, interpersonal relationships, community life, education, employment, and recreation). This qualitative study explores the nature and context of LH restrictions in systemic lupus erythematosus (SLE) individuals across their SLE journey. Methods Narrative interviews were conducted with adult SLE patients. Interview transcripts were subjected to a thematic content analysis, using the Disability Creation Process model as a framework. Results Forty participants were interviewed. Three major themes were highlighted: (1) Temporality, capabilities, and environmental contexts: although all participants experienced LH restrictions at some point, the expression of these limitations depended on the individual’s and SLE disease characteristics as well as on temporal (time of life and lupus course) and environmental (material, social, and societal) contexts. (2) Identity issues, illness stigma, and (fear of) discriminations: LH were discussed through the lens of participants’ social roles and identities. While illness stigma can influence social relations, it is also expressed at a societal level. (3) Masking and minimizing strategies: due to illness stigma and fear of discrimination, participants developed strategies to manage their relationships, including masking and minimization. Their use was both advantageous and disadvantageous regarding LH. Conclusions For individuals with SLE, LH restrictions must be considered as an ongoing process that takes place within specific contexts. Our findings provide many opportunities for interventions that can benefit patients and their families, as well as healthcare providers.

Background A novel multisystem inflammatory syndrome in children (MIS-C) temporally associated with the coronavirus disease 2019 (COVID-19) infection has been reported, arising weeks after the peak incidence of COVID-19 infection in adults. Patients with MIS-C have been reported to have cardiac involvement and clinical features overlapping with other acute inflammatory syndromes such as Kawasaki disease, toxic shock syndrome, and macrophage activation syndrome. Multisystem inflammatory syndrome in children may follow COVID-19 infection, most of the time after its asymptomatic form, even though it can lead to serious and life-threatening illness. Case summary In this case series, we discuss two cases of young adults with no former medical history who fit with the criteria defined in MIS-C. They both developed a refractory cardiogenic shock and required intensive care treatment including mechanical circulatory support, specifically the use of venous–arterial extracorporeal membrane oxygenation. They were both treated early with intravenous immune globulin and adjunctive high-dose steroids. They recovered ad integrum in less than 2 weeks. Discussion Multisystem inflammatory syndrome in children occurs 2–4 weeks after infection with severe acute respiratory syndrome coronavirus 2. Patients with MIS-C should ideally be managed in an intensive care environment since rapid clinical deterioration may occur. It would be preferable to have a multidisciplinary care to improve outcomes. Patients should be monitored for shock. Elucidating the mechanism of this new entity may have importance for understanding COVID-19 far beyond the patients who have had MIS-C to date. The pathogenesis seems to involve post-infectious immune dysregulation so early administration intravenous immune globulin associated with corticosteroids appears appropriate. It implies early recognition of the syndrome even in young adults.

Introduction La necrose hemorragique des surrenales est la manifestation endocrinologique la plus frequente au cours du syndrome des antiphospholipides (SAPL). Il s’agit d’une complication classique mais rare puisqu’elle est retrouvee chez 0,4 % des patients ayant un SAPL. Il s’agit d’une thrombose veineuse des veines surrenaliennes dans un contexte de reseau vasculaire propice a l’ischemie hemorragique puisqu’il existe une veine de drainage unique, contrastant avec un reseau arteriel riche. Le traitement de reference reste les anti-vitamines K (AVK) mais le developpement des nouveaux anticoagulants oraux (NACO) dans d’autres pathologies, interroge sur leur place dans la prise en charge des patients ayant un SAPL. Nous rapportons un cas de necrose hemorragique bilaterale des surrenales chez un patient traite depuis 1 mois et demi par APIXABAN pour une thrombose veineuse profonde avec embolie pulmonaire, revelant un syndrome des antiphospholipides. Observation Un patient de 47 ans, sans antecedent notable, est diagnostique d’une phlebite de la jambe gauche devant une douleur persistante du mollet. Une anticoagulation efficace par APIXABAN 5 mg matin et soir est debutee. Devant la presence d’une dyspnee persistante rapportee par le patient, un angioscanner thoracique est realise a 1 mois, avec diagnostic d’embolie pulmonaire. A un mois et demi du diagnostic initial, il est hospitalise pour douleurs abdominales brutales intenses avec mise en evidence d’hematomes bilateraux des surrenales au scanner. En reprenant l’interrogatoire, on retrouve une observance stricte du traitement par APIXABAN. Cliniquement, l’abdomen est douloureux a la palpation mais depressible et on retrouve un livedo reticularis au niveau du dos. Le bilan biologique sous APIXABAN retrouve un TP a 42 %, un TCA allonge a 1,42 et l’absence de cytopenie. Le bilan immunologique retrouve une triple positivite pour les anticorps anti-phospholipides a des taux eleves : IgG anti-cardiolipine avec titre > 160GPL-U/mL (resultat negatif si 160 U/mL (titre negatif si Discussion La necrose hemorragique bilaterale des surrenales est une urgence diagnostique et therapeutique. Elle doit faire rechercher un SAPL car il s’agit d’une manifestation inaugurale dans un tiers des cas. Avec l’elargissement des indications des NACO se pose la question de leur utilisation dans le SAPL. Dans une cohorte prospective de 56 patients avec un SAPL traite par NACO, 6 recurrences d’evenements thrombotiques etaient rapportes : 4 chez des patients triple positifs et 2 en contexte de non adherence au traitement, pendant un suivi de 22 mois en moyenne (2–43 mois) [1] . L’etude controlee randomisee RASP ne retrouvait aucun evenement thrombotique chez les patients avec un SAPL traite par RIVAROXABAN (suivi 42 jours) [2] . Cependant en 2018, un essai controle randomise comparant l’efficacite du RIVAROXABAN par rapport a la WARFARINE chez des patients avec un SAPL a haut risque thrombotique, retrouvait des recidives de thromboses uniquement dans le groupe RIVAROXABAN (12 % versus 0 %) ayant justifie un arret precoce de l’essai apres l’inclusion de 120 patients [3] . Notre cas rapporte une inefficacite de l’APIXABAN en cas de SAPL a haut risque de thrombose. Un autre cas d’hemorragie bilaterale des surrenales associee a des anticorps anti-phospholipides sous RIVAROXABAN est rapporte dans la litterature, nous n’avons pas retrouve de cas rapporte sous APIXABAN. Conclusion Ce cas clinique illustre les limites d’un traitement par NACO pour la prevention des recidives thrombotiques chez les patients SAPL triple positifs. Il s’agit a ce jour, a notre connaissance, du seul cas rapporte de necrose bilaterale des surrenales sous APIXABAN en contexte de SAPL. Un essai randomise est en cours pour evaluer l’efficacite de l’APIXABAN dans le SAPL. Nous verrons si les resultats sont identiques aux resultats retrouves pour le RIVAROXABAN, comme peut le suggerer notre cas clinique.

Resume Introduction La pseudo-retinopathie de Purtscher regroupe l’ensemble des atteintes retiniennes semiologiquement similaires au syndrome initialement decrit en 1910 par Purtscher, mais survenant dans un contexte non traumatique. Observation Nous rapportons le cas d’une pseudo-retinopathie de Purtscher bilaterale survenue dans le cadre d’une poussee de maladie de Still de l’adulte chez une femme de 48 ans. Le diagnostic reposait sur l’examen du fond d’œil et l’angiographie a la fluoresceine. Sur la base d’une revue de la litterature, nous discutons les donnees actuelles disponibles sur la physiopathogenie de ce syndrome ainsi que sa signification pronostique. Le traitement en reste controverse. Conclusion Devant l’apparition de signes fonctionnels visuels au cours d’une maladie de Still de l’adulte, il faut evoquer une manifestation ophtalmique grave de cette pathologie, la pseudo-retinopathie de Purtscher et demander une expertise ophtalmologique.

Resume Introduction La syphilis est une maladie sexuellement transmissible. Tous les organes peuvent etre atteints, mais seul 0,6 % des patients atteints de syphilis ont une atteinte oculaire. Nous avons recueilli l’ensemble des cas de syphilis oculaire necessitant une hospitalisation au centre hospitalier universitaire (CHU) de Marseille en 2017. Patients et methodes Il s’agit d’une etude retrospective monocentrique. Le diagnostic de syphilis oculaire reposait sur l’association d’une inflammation oculaire et d’une serologie syphilitique positive. Pour chaque patient etaient notes le sexe, l’âge, le statut serologique VIH, les symptomes oculaires et extra oculaires, l’acuite visuelle initiale, la serologie syphilis, l’analyse du liquide cephalo-rachidien (LCR), le traitement, sa duree et la reponse clinique. Resultats Dix hommes et deux femmes, âges de 28 a 86 ans ont ete hospitalises. Deux patients etaient seropositifs. Les atteintes ophtalmologiques etaient heterogenes, mais les structures posterieures etaient majoritairement atteintes. Une patiente a presente un tableau d’uveite anterieure pure. Cinq patients avaient des signes extra oculaires cutanes et/ou muqueux. Aucun n’a presente de signe neurologique. L’analyse du LCR realisee pour 7 patients a permis le diagnostic de neurosyphilis certain pour un patient et probable pour 5 patients. Le LCR etait normal chez deux patients. Six patients ont beneficie d’un traitement par penicilline G et six par ceftriaxone. L’acuite visuelle s’est amelioree dans tous les cas. Discussion Nous assistons depuis plusieurs annees en France a une reemergence des cas de syphilis ophtalmologique. Son diagnostic doit etre evoque a tout âge et devant toute pathologie inflammatoire de l’œil meme en dehors d’une anamnese ou d’une clinique evocatrice. La recherche d’une co-infection par le VIH doit etre systematique. Enfin, notre etude montre que la ceftriaxone reste une alternative efficace a la penicilline G.

Objective To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. Methods We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer’s solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety. Results Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months’ follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of −9.2 [12.2] in the AD-SVF group vs −7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups. Conclusion This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Lysozyme amyloidosis is a non-neuropathic hereditary amyloidosis identified in 1993. About fifty cases of this rare, probably under-diagnosed disease are reported. Lysozyme amyloidosis has a very broad spectrum of clinical manifestations. Sicca syndrome is often the first symptom, preceding the diagnosis by several years. Every part of the digestive tract can be involved with different grades of severity. The hallmark of this amyloidosis is the usually life-threatening spontaneous hepatic rupture. Renal involvement is frequent and progresses towards end-stage renal failure and dialysis. Skin, lymph nodes, and spleen can also be affected. More recently, cardiac and pulmonary involvement was reported. Phenotypic heterogeneity and incomplete penetrance make the clinical diagnosis difficult. Amyloid deposits are revealed by Congo red staining with birefringence under polarized light. They can be limited or diffuse and lead to the progressive destruction of the architecture of an organ and its failure. Immunohistochemistry reveals the nature of the amyloid variant by identifying antilysozyme antibodies in the deposit. Up to know, eight pathologic mutations and one polymorphism involving exons 2, 3, and 4 of the lysozyme gene have been identified. The transmission is autosomal dominant, without any genotype-phenotype correlation. The therapeutic options are limited and based on symptomatic or supportive treatment. Renal and hepatic transplant has proved its benefits with a prolonged graft survival. A long term regular and multidisciplinary follow-up is required. (C) 2018 Societe Nationale Francaise de Medecine Interne (SNFMI). Published by Elsevier Masson SAS, L’amylose à lysozyme est une amylose héréditaire non neuropathique identifiée en 1993. Elle reste une pathologie rare avec une cinquantaine de cas rapportés, et probablement encore sous-diagnostiquée.L’amylose à lysozyme présente un très large spectre de manifestations cliniques. Le syndrome sec constitue souvent le premier symptôme précédant de plusieurs années le diagnostic. L’ensemble du tractus digestif peut être atteint avec des degrés de sévérité variable. La caractéristique de cette amylose est la rupture spontanée hépatique qui menace le plus souvent le pronostic vital. L’atteinte rénale est fréquente évoluant vers l’insuffisance rénale terminale et la mise en dialyse. Les autres atteintes sont dermatologiques, ganglionnaires et spléniques. Plus récemment une atteinte cardiaque et pulmonaire est rapportée.L’hétérogénéité phénotypique et la pénétrance incomplète rendent le diagnostic clinique difficile. Les dépôts amyloïdes sont révélés par la coloration au rouge Congo, associée à une biréfringence en lumière polarisée. Ils peuvent être limités ou diffus et conduire à la destruction progressive de l’architecture d’un organe et sa défaillance. Le typage de l’amylose repose sur l’immunohistochimie montrant la positivité des anticorps antilysozyme, ou par analyse protéomique des dépôts après microdissection au laser.L’étude du gène du lysozyme a permis d’identifier à ce jour huit variants amyloïdogènes et un poly-morphisme, touchant les exons 2, 3 et 4. La transmission est autosomique dominante, sans corrélation génotype-phénotype évidente. Les options thérapeutiques sont limitées et reposent sur des traitements symptomatiques ou de support. La transplantation rénale et hépatique a montré son intérêt du fait d’une survie prolongée du greffon. Un suivi régulier, prolongé et multidisciplinaire est nécessaire.

Neonatal immune neutropenia is observed in rare cases in newborns from mothers with idiopathic or autoimmune neutropenia, secondary to passive transfer of maternal granulocyte auto-antibodies. We performed a literature review and report four supplementary cases from the French registry of neutropenia. Only 14 cases (11 mothers, 14 newborns) have been reported. Granulocyte aggregation (GAT) and granulocyte indirect immunofluorescence test (GIFT) are the recommended laboratory procedures for antibody detection. Monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA)-confirmed antibody specificity. Antibody detection in newborns is not generally possible owing to extreme neutropenia. In half of the cases autoantibodies against neutrophils (AAN) were positive in maternal sera (7 out of 11). In some newborns tested, IgG+ AAN were also positive, with disappearance in parallel of spontaneous neutrophil count improvement. No correlation between maternal type of AAN and titer and neonatal neutropenia can be established. Neutropenia resolved spontaneously between 2 weeks and 4 months. Infections in newborns were observed in 43% of cases, with no deaths reported. Granulocyte colony-stimulating factor (G-CSF) was administered to some newborns (5 out of 14) in the case of infections. Low-dose G-CSF administered to childbearing women during pregnancy could be proposed to prevent neutropenia in newborns. From the few cases reported so far it is impossible to draw any conclusions regarding frequency, risk factors, and outcome, but the overall prognosis for newborns seems good. Because it can be associated with potentially severe neonatal infections, autoimmune neutropenia in childbearing mothers should be closely monitored in collaboration with gynecologists and pediatricians.

Objective Patients with inflammatory myopathies (IM) are known to have an increased risk of developing malignancies. Autoimmune and inflammatory diseases occur in up to 25% of patients with myelodysplastic syndrome (MDS). This study aimed to describe the rare association between IM and MDS. Methods We report here the main characteristics, treatment, and outcome of 21 patients (11 national cases and 10 additional cases from a literature review) with IM associated to MDS. Results Median age of patients at IM diagnosis was 66 years (range 26 – 78). Diagnosis of the two conditions were concomitant in most patients (n=14/21) whereas MDS diagnosis preceded IM diagnosis in 5 patients. Different types of IM were observed but dermatomyositis was the most frequent (59%). Compared to IM without MDS (IM/MDS−), patients with MDS (IM/MDS+) were older (median 66 vs 55, p=0.3), more frequently male (sex ratio M/F 1.125 vs 0.41, p=0.14) and positive for anti-TIF1γ (24% vs 4%, p=0.0039). Antisynthetase syndrome was never observed among IM/MDS+ patients (0% vs 28%, p=0.01). MDS WHO type was not univocal, but the prognostic score was of low risk in almost all cases. IM was usually steroid sensitive (82% of patients) but often steroid dependent (56% of patients). Overall survival of IM patients with MDS was worse compared to patients with IM without MDS (p=0.0002). Conclusion IM associated with MDS are mainly represented by dermatomyositis and/or anti-TIF1γ autoantibodies. Antisynthetase syndrome has not been described in association with MDS. Despite low-risk MDS, overall survival of IM patients with MDS is worse than IM patients without MDS.

International audience; Background: The detection of additional autoantibodies is of great concern in systemic sclerosis (SSc) when those included in the ACR/EULAR classification are negative. In this context, the interest of antifibrillarin (anti-U3RNP) autoantibodies (AFAs) in the routine evaluation of SSc remains unclear. We aimed to assess the relevance of AFAs and their clinical association in SSc patients. Methods: In a multicenter observational retrospective study, we collected immunological and clinical data associated with AFA positivity in SSc (n = 42) and non-SSc patients (n = 13). Patients with SSc negative for AFAs (n = 83) were considered as a control group. AFAs were detected by indirect immunofluorescence (IIF) using HEp-2 cells, EliA or immunoblot techniques. Results: We confirmed a typical nuclear IIF pattern and showed that AFAs are mostly exclusive towards SSc conventional autoantibodies. Although also observed in non-SSc patients, high levels of AFAs with the ELiA technique allowed the diagnosis of SSc. Compared to AFA-negative SSc patients, AFA-positive SSc patients more frequently exhibited visceral involvements. They more frequently suffered from the diffuse cutaneous form and had a higher global severity of the disease. Conclusions: We demonstrate the usefulness of quantifying AFAs in the immunological exploration of SSc, especially when patients are seronegative for SSc conventional autoantibodies and display a typical IIF pattern. AFAs might constitute an interesting marker of SSc severity.

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

We report the case of a 72-y-old man with concomitant autoimmune encephalitis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The patient presented with subacute cerebellar syndrome and myoclonus several days after general infectious symptoms began. Methods: Clinical examination, CT, PET, MRI, and autoantibody testing were performed. Results: The oropharyngeal swab test was positive for SARS-CoV-2. The brain MRI results were normal. Cerebrospinal fluid testing showed normal cell counts, a negative result on reverse-transcription polymerase chain reaction testing, and no oligoclonal banding. Brain 18F-FDG PET showed diffuse cortical hypometabolism associated with putaminal and cerebellum hypermetabolism, compatible with encephalitis and especially cerebellitis. The immunologic study revealed high titers of IgG autoantibodies in serum and cerebrospinal fluid directed against the nuclei of Purkinje cells, striatal neurons, and hippocampal neurons. Whole-body 18F-FDG PET and CT scans did not show neoplasia. Treatment with steroids allowed a rapid improvement in symptoms. Conclusion: This clinical case argues for a possible relationship between SARS-CoV-2 infection and autoimmune encephalitis and for the use of 18F-FDG PET in such a context.

Acute severe hepatitis is a rare complication of adult-onset Still's disease (AOSD). This condition is poorly characterized. We performed a review of the medical literature to describe clinical, biological, pathological, and treatment characteristics from AOSD patients with acute severe hepatitis. Their characteristics were compared with AOSD patients without severe hepatitis. Twenty-one cases were collected including a new case reported here. Patients with severe hepatitis were mostly young adults with a median age of 28 years (range: 20 to 55 years). Overall, patients with severe hepatitis had less arthritis, macular rash, sore throat, lymphadenopathy, or splenomegaly than patients without severe hepatitis. Cytopenia was more frequent in case of severe hepatitis. Most patients were treated with steroids, and the use of biotherapies has increased over the last decade. Despite treatment, 49% of patients required liver transplantation and 24% died. Key Points • Acute severe hepatitis in adult-onset Still's disease (AOSD) is associated with liver transplantation and/or death in, respectively, 43% and 24% of cases. • Severe hepatitis is the inaugural manifestation of AOSD in half of cases. Diagnosis is difficult when extra-hepatic clinical manifestations are lacking. • The mechanism of hepatic necrosis in AOSD with severe hepatitis is unknown. Liver biopsy is not specific and should not delay treatment initiation.

Among the antibodies described in Systemic Sclerosis (SSc), anti-Th/To antibodies (anti-Th/To) are rare and have been poorly studied. Thus, little is known about the profile of anti-Th/To positive patients. From our local Biobank (Marseille, France), we retrospectively selected data for 6 patients positive for anti-Th/To with an Immunodot assay. All of them suffered from SSc, sharing clinical and biological common features such as a limited cutaneous form of SSc, a decreased lung diffusing capacity and a speckled nuclear nucleolar immunofluorescence pattern of antinuclear antibodies screening on HEp-2 cells. In order to further characterize patients positive for anti-Th/To, we performed a thorough literature review. From 402 studied patients positive for anti-Th/To, we confirmed that these antibodies are associated with the limited cutaneous form of the disease (88% of the patients), and with an SSc related-pulmonary involvement (50%). The review analysis pointed out the rarity of the anti-Th/To with an estimated mean frequency of 3.4% of all SSc patients worldwide, their usual exclusivity with respect to the specific antibodies of scleroderma, and their high specificity (around 98%) for the diagnosis of SSc., Parmi les anticorps décrits associés à la Sclérodermie Systémique (ScS), les anticorps anti-Th/To (anti-Th/To) sont rares et ont été peu étudiés. Ainsi, nous n’avons que peu de connaissance sur le profil des patients positifs pour les anti-Th/To. À partir d’une Biobanque locale (Marseille, France), nous avons sélectionné de façon rétrospective 6 patients positifs pour les anti-Th/To, en test Immunodot. Tous souffraient de ScS et partageaient des caractéristiques cliniques et biologiques communes, comme la forme cutanée limitée de la ScS, une baisse de la diffusion alvéolocapillaire pulmonaire et un aspect moucheté nucléolaire en immunofluorescence indirecte au test de dépistage des anticorps anti-nucléaires sur cellules Hep-2. Afin de caractériser davantage les patients positifs pour les anti-Th/To, nous avons réalisé une revue de la littérature sur le sujet. À partir de l’étude de 402 patients positifs pour les anti-Th/To, nous confirmons que ces anticorps sont principalement associés à la forme cutanée limitée de la maladie (88 % de l’ensemble des patients), et à une atteinte pulmonaire de la ScS (50 % de l’ensemble des patients). Cette analyse de la littérature illustre la rareté des anti-Th/To avec une fréquence moyenne estimée de 3,4 % chez tous les patients souffrant de ScS dans le monde entier, leur caractère habituellement exclusif vis-à-vis des autres autoanticorps spécifiques de la Sclérodermie, ainsi que leur grande spécificité (environ 98 %) pour le diagnostic de la ScS.

Additional file 12. Survival analyses using Cox regression analysis adjusted for age and sex in the 5-class LCMM

Additional file 2. Number of mRSS available in patients included in LCMM.

Additional file 6. Averages of posterior probabilities of belonging to a class in the 5-class LCMM

Additional file 7. Sensitivity analysis: the 6 different LCMM with disease duration as adjustment factor

Additional file 3. The 6 different LCMM tested

Additional file 5. Averages of posterior probabilities of belonging to a class in each LCMM tested

Additional file 4. Model fit evaluation information for each LCMM tested

Additional file 8. Sensitivity analysis: model fit evaluation information for each LCMM with disease duration as adjustment factor

Additional file 9. Sensitivity analysis: averages of posterior probabilities of belonging to a class in each LCMM with disease duration as adjustment factor

Resume Introduction La leucemie lymphoide chronique (LLC) est une hemopathie maligne, associee a une proliferation de lymphocytes B matures. Elle represente une incidence de 4400 nouveaux cas par an en France. La prevalence de la maladie augmente avec l’âge, avec une mediane d’âge au diagnostic autour de 65 ans. Les atteintes renales justifiant une biopsie renale sont evaluees a 1,2 % des patients. L’histologie retrouvee reste tres variable et n’est pas toujours en lien avec la pathologie lymphoide. Nous proposons de repertorier les cas de biopsies renales obtenues chez des patients atteints de LLC au CHU de Marseille. Patients et methodes Les patients atteints d’une LLC et ayant beneficie d’une biopsie renale au CHU de Marseille entre 2000 et mars 2016 ont ete inclus. Les resultats histologiques etaient interpretes par un seul anatomopathologiste. Les donnees etaient collectees le jour de la biopsie et le suivi des patients etait recueilli. Resultats Au total, 10 patients atteints d’une LLC ont beneficie d’une biopsie renale durant la periode de l’etude. Les indications de biopsie renale etaient une insuffisance renale aigue organique ou la presence d’un syndrome nephrotique. Les atteintes retrouvees etaient une glomerulonephrite extramembraneuse (GEM) sans anticorps anti-PLA2R pour 4 patients, 1 syndrome nephrotique a lesions glomerulaires minimes, 1 glomerulonephrite membrano-proliferative associee a une cryoglobulinemie, 1 amylose AL, 1 glomerulonephrite fibrillaire non amyloide, 1 tubulopathie et 1 nephrite interstielle par infiltration lymphoide. Seul 1 patient etait traite avant la biopsie, 7 autres ont ete traites du fait de l’atteinte renale, avec des reponses variables sur le plan hematologique et renal. Conclusion Les atteintes renales associees a la LLC sont rares et de presentation variable. Elles ne sont pas integrees aux criteres classiques de la classification de Binet. Elles peuvent etre responsables d’une insuffisance renale severe ou d’un syndrome nephrotique, et conduisent cependant frequemment a initier un traitement de la LLC. La presentation la plus frequente de cette serie etait la GEM secondaire, ce qui n’etait pas le cas dans la litterature.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory condition. Primary HLH occurs early in life as a result of monogenic biallelic mutations affecting lymphocyte cytotoxicity. Secondary HLH occurs mostly in adults secondary to infection, lymphoma, or rheumatic disease. In this latter setting, lymphocyte cytotoxicity status is not known. We conducted a systematic evaluation of natural killer (NK) cell cytotoxicity in adult patients with secondary HLH. Adult patients with secondary HLH were prospectively studied ex vivo for total lymphocyte count and subtype, NK cell phenotype, perforin expression and degranulation, and natural or antibody-dependent cell cytotoxicity, in comparison with patients affected by the same underlying disease without HLH (disease controls [DCs]) and with healthy controls (HCs). Screening for variants of cytotoxity genes was systematically performed. 68 patients were included in the HLH group and 34 each in the DC and HC groups. In HLH patients, severe and transient lymphopenia, activated NK cell phenotype (eg, increased CD69, ICAM-1, HLADR, and CCR5 expression), and decreased capacity of interferon γ production were observed; mean perforin expression was normal; and degranulation tests and NK cell cytotoxicity were not different from those in DCs. A monoallelic variant of uncertain significance affecting a lymphocyte cytotoxicity gene or the perforin variant A91V was observed in almost 50% of the patients. We detected no major intrinsic cytotoxicity dysfunction in secondary HLH patients compared with DCs and no predicted pathogenic gene variant. The activated NK phenotype profile associated with decreased interferon γ production seems similar to those of other hyperinflammatory diseases such as sepsis or systemic juvenile idiopathic arthritis.

International audience; We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc). Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography. Pulmonary function tests, main manifestations and severity of the lung disease (Medsger's severity scale) were collected. KL-6 serum concentrations were significantly higher in SSc-ILD patients than in those without ILD (p < 10(-4)) and were inversely correlated with forced vital capacity, total lung capacity and diffuse lung capacity of carbon monoxide. Serum KL-6 level superior to 872 U/ml appeared as the optimal cut-off value associated with ILD. Patients with a restrictive pulmonary syndrome and dyspnoea had significant higher KL-6 serum concentrations. SSc patients with anti-topoisomerase 1 antibodies had higher KL-6 serum levels than patients with anti-centromere antibodies (p < 10(- 4)). ILD and anti-topoisomerase 1 antibodies were independent factors associated with KL-6 in multivariate analysis. Interestingly, KL-6 serum concentrations positively increased with the patient lung severity. Our study confirms that KL-6 is an accurate biomarker for the diagnosis of SSc-ILD in a French cohort of patients. High KL-6 levels should prompt physicians to assess ILD with pulmonary imaging and pulmonary functions tests. Prospective clinical studies are still required to determine whether levels of KL-6 might predict progression of ILD as well as its usefulness in the timing of therapeutic intervention.

Introduction Les inhibiteurs de check points (ICP), anticorps monoclonaux anti-PD1, PD1-L, CTLA4, ont revolutionne le domaine de l’oncologie. Mais leur mecanisme d’action « immuno-stimulant » sur les lymphocytes T n’est pas specifique de la clearance anti-tumorale. En particulier, les lymphocytes T jouent physiologiquement un role important dans la defense anti-virale. Nous proposons ici un panorama des donnees disponibles concernant l’efficacite des inhibiteurs de check point sur les infections virales a VIH, VHB, VHC et JC virus. Resultats VIH et inhibiteur de check point [1] . Le VIH est un retrovirus ayant comme cible les cellules presentant l’antigene CD4 a leur surface. En l’absence de traitement, la replication virale aboutit a une lymphopenie T CD4 a l’origine des infections opportunistes caracterisant le stade SIDA de la maladie. Plusieurs patients suivis pour un VIH (essentiellement avec des charges virales negatives) ont recu des ICP a ce jour dans le cadre de neoplasies, recenses par Cook et al. Ainsi, 5 des 6 patients a charge virale (CV) detectable ont vu leur CV decroitre sous ICP, tandis que 60 % des 35 patients pour lesquels le taux de CD4 a ete monitore ont vu ce taux augmenter. Un essai est en cours pour tester l’efficacite du pembrolizumab chez des patients VIH sans neoplasie( NCT03367754 ). VHC et inhibiteur de check point [2] . Le VHC est un virus a ARN de la famille des hepadnavirus, directement cytopathogene pour le foie, et principalement responsable d’hepatites chroniques. Un essai randomise de faible effectif publie en 2013 a teste l’efficacite du pembrolizumab chez les patients VHC, retrouvant 15 % de reduction significative de la charge virale a la posologie de 10 mg/kg. Plus recemment, une revue de l’evolution de la CV VHC chez des patients sans traitement anti-viral recevant un ICP dans un contexte neoplasique (85 patients) evalue a 38 % le taux de diminution de la CV. VHB et inhibiteur de check point [2] . Le VHB est un virus a ADN de la famille des hepadnavirus, peu cytopathogene au niveau hepatique, responsable d’hepatites aigues et chroniques, principal pourvoyeur de carcinome hepatocellulaire dans le monde. Dans la revue de Pu et al., le traitement d’un cancer par ICP a permis de reduire la CV VHB chez 10 % des patients sous traitement anti-viral (n = 67) mais n’a pas eu d’effet chez les patients non traites pour leur VHB (n = 22). Un essai est en cours pour tester l’efficacite du pembrolizumab dans le CHC lie au VHB ( NCT03419481 ). JC virus et inhibiteur de check point [3] . La leucoencephalopathie multifocale progressive (LEMP) est une infection opportuniste causee par le virus JC (JCV), letale en l’absence de restauration immunitaire. Un essai therapeutique non randomise a evalue l’efficacite du pembrolizumab dans la LEMP sur 8 patients. Une reduction de la CV JCV etait objectivee pour 5 d’entre eux, dont 3 negativations, associee a une amelioration clinique. Discussion L’utilisation des ICP comme traitement anti-viral semble pertinente sur un plan physiopathologique, et en pratique, les ICP permettent en effet une diminution des CV VHB, VHC, VIH et JCV chez une partie des patients traites. Les resultats obtenus a ce jour sont particulierement interessants dans la LEMP ou il n’existe pas de traitement de reference autre que la restitution immunitaire, mais sont a relativiser dans les autres cas du fait des therapeutiques efficaces disponibles et d’un impact malgre tout assez faible sur la CV, ne concernant qu’une partie des patients. Dans tous les cas, ces donnees semblent valider l’absence de contre-indication a l’utilisation d’un ICP dans une indication oncologique en contexte d’infection virale VHB, VIH ou VHC. Conclusion Ces resultats ne permettent clairement pas d’envisager le traitement d’une infection a VIH, VHB ou VHC par ICP seuls a l’heure actuelle, mais valident une certaine efficacite anti-virale de ces molecules, apportant ainsi une preuve de concept. D’autres etudes sont necessaires sur de plus grands effectifs afin de preciser plus particulierement les caracteristiques des patients repondeurs en vue eventuellement de determiner des criteres predictifs de reponse aux traitements.

Introduction La drepanocytose est la maladie genetique la plus frequente au niveau mondial. Sa prevalence est en augmentation en France avec pres de 20 000 patients en 2019, en lien avec le vieillissement de cette population et les nouveaux arrivants etrangers. Cette etude fait l’etat des lieux de la population suivie dans un centre de reference de la drepanocytose adulte. Patients et methodes Il s’agit d’une etude epidemiologique observationnelle descriptive retrospective monocentrique concernant les annees 2017 et 2018. Elle presente les caracteristiques epidemiologiques, les antecedents, les complications, les traitements et le suivi de ces patients. Elle compare les sous-groupes de syndromes drepanocytaires majeurs et etudie la gravite des patients en fonction de l’âge, de la prise en charge pediatrique (France ou etranger) et des parametres biologiques. Resultats 197 patients ont ete analyses : 110 femmes (55,8 %) et 87 hommes (44,2 %). L’âge moyen est de 34,7 ans, avec des âges extremes allant de 16 a 61 ans. 112 (58 %) sont HbSS, 33 (17 %) sont HbSC, 25 (13 %) sont HbSB° et 22 (12 %) sont HbSB+. 24 (28,6 %) presentent une ou deux deletions alpha-thalassemique associees. 63 patients (46,7 %) sont originaires d’Afrique sub-saharienne et 42 (31,1 %) d’Afrique du Nord. 34,7 % des patients ont ete pris en charge en France des leur enfance. Concernant les complications : 84 patients (58,7 %) ont une hyperfiltration glomerulaire, 60 (35,9 %) ont une retinopathie, 23 hommes (29,9 %) presentent un antecedent de priapisme, 46 (29,2 %) ont une hemochromatose presente ou passee, 34 (24,6 %) ont une cardiopathie, 21 patients (13,6 %) ont une insuffisance renale chronique, 42 (27,2 %) ont une osteonecrose femorale, 15 (9,54 %) ont un antecedent d’AVC, 13 (8,2 %) ont une vasculopathie cerebrale, 8 (6 %) ont une HTAP, 10 (5,7 %) ont un antecedent d’ulcere. 91 patients (54,8 %) ont presente un syndrome thoracique aigu. 50 patients presentent une allo- immunisation (RAI positive) et 7 (4,4 %) ont un antecedent d’hemolyse post-transfusionnelle retardee. Au niveau chirurgical, 79 patients (43,9 %) sont cholecystectomises et 31 (17,3 %) sont splenectomises. Les patients du groupe [HbSS + HbSB°] sont plus a risque de presenter : une splenectomie, un syndrome thoracique aigu, une hyperfiltration glomerulaire, une hemochromatose, une cholecystectomie. Les patients du groupe [HbSC + HbSB + ] sont plus a risque de presenter : un syndrome d’hyperviscosite clinique (hypoacousie, vertiges, acouphenes) ou une retinopathie. Les patients de plus de 45 ans presentent de facon attendue un nombre plus eleve d’organes atteints (p = 0,002) et sont plus graves (p = 0,004). Il y a une correlation negative entre le nombre d’organes atteints et le taux d’hemoglobine : R = 0,176, p = 0,03. Il n’y a pas de difference de gravite selon le type de mutation beta, alpha, ainsi que selon le lieu de prise en charge dans l’enfance (France ou etranger). Les patients du groupe [HbSS + HbSB°] sont 84 (70 %) et ceux du groupe [HbSC + HbSB + ] sont 11 (25 %) a etre traite par hydroxyuree (HU) OR = 2,8 ; IC95 [1,656–4,733] ; p Conclusion Cette etude fait l’etat des lieux actuel de la population drepanocytaire adulte suivie dans un centre de reference de la drepanocytose francais. Il s’agit d’une population jeune et minoritairement suivie en France depuis l’enfance. Elle presente de nombreuses complications et comorbidites, dont la prevalence varie selon le type de mutation. La majorite beneficie d’un traitement de fond. Les patients arrives en France a l’âge adulte et moins medicalises dans l’enfance ne sont ni plus ni moins severes que les autres. Le vieillissement des patients drepanocytaires et la prevention des complications, associees aux co-morbidites associees au vieillissement naturel est un enjeu majeur pour les annees futures.

Introduction Le syndrome lymphoproliferatiflie a l’X de type 2 (XLP-2), est un deficit immunitaire primitif cause par une mutation du gene XIAP, implique dans l’apoptose. Sa prevalence est inferieure a 1/1 000 000. Il est associe a un mauvais controle de l’infection a EBV et peut se compliquer de syndrome d’activation macrophagique. L’expression phenotypique est heterogene : parfois asymptomatique mais souvent associe a des symptomes evocateurs de maladies inflammatoires chroniques de l’intestin [1] , [2] . Nous rapportons un cas de leucoencephalopathie multifocale progressive (LEMP) survenu chez un patient XIAP a l’âge de 69 ans. Observation Un homme de 69 ans presente des signes deficitaires neurologiques d’aggravation lentement progressive. Il est suivi depuis plusieurs annees pour une mutation XIAP identifiee lors d’une enquete familiale autour de deux cas pediatriques (deux petits-fils). Il n’a pas de manifestation digestive et n’a jamais presente de complication infectieuse notable malgre une hypogammaglobulinemie severe (IgG 2,80 g/L). La PCR EBV est negative a plusieurs reprises durant le suivi et la serologie est positive en IgG. L’IRM cerebrale montre des lesions (hypersignaux T2 et FLAIR de la substance blanche) compatibles avec une LEMP ou un lymphome cerebral. Le phenotypage des lymphocytes B circulants montre une clonalite CD23+ FMC7+ C D22+ CD79b+ CD5− (score de Matutes = 2), et le myelogramme un envahissement medullaire lymphomateux modere. La ponction lombaire ne retrouve pas de cellules anormales, le rapport IL-6/IL-10 est normal, le bilan infectieux comprenant une PCR JC virus (sang et le LCR) est negatif. La TEP-TDM montre une hepatosplenomegalie et des adenopathies sous- et sus-diaphragmatique hypermetaboliques. Une chimiotherapie est debutee pour une presomption de lymphome cerebral sans possibilite de documentation histologique au niveau du S N C. L’etat clinique du patient s’aggrave malgre une premiere cure : une reevaluation est realisee et retrouve une positivite des PCR sang et LCR pour le JC virus. Le patient recoit alors du pembrolizumab (2 mg/kg tous les 15 jours), sans reponse clinique ou radiologique objective. Le traitement est interrompu apres deux injections. Le patient decede rapidement. Discussion Il s’agit, a notre connaissance, du premier cas rapporte de LEMP compliquant un syndrome XLP-2. La mise en place d’une immunotherapie n’a pas permis de controler l’evolution de la maladie. Conclusion La LEMP est une complication associee au syndrome XLP-2.

Objective.Cardiac involvement during systemic lupus erythematosus (SLE) may include the pericardium, myocardium, valvular tissue, and coronary arteries. The aim of this study was to describe the clinical, biological, and radiological presentation of lupus myocarditis (LM) as well as the treatment response and longterm outcomes.Methods.We conducted a multicentric retrospective study of LM from January 2000 to May 2014.Results.Twenty-nine patients (3 men and 26 women) fulfilled the inclusion criteria (median age at the diagnosis of SLE: 30 yrs, range 16–57). Myocarditis was the first sign of SLE in 17/29 cases (58.6%). Troponin was elevated in 20/25 cases. Electrocardiogram results were abnormal in 25/28 cases. Echocardiography revealed low (≤ 45%) left ventricular ejection fraction (LVEF; 19/29, 66%) and pericardium effusion (20/29, 69%). Cardiac magnetic resonance imaging revealed delayed gadolinium enhancement in 9/13 patients (69%). Patients were treated with corticosteroids (n = 28), cyclophosphamide (CYC; n = 16), intravenous immunoglobulins (n = 8), and/or mycophenolate mofetil (n = 2). The median followup was 37 months. One month after the beginning of the treatment, 10/23 patients (43%) who had undergone echocardiography had an LVEF ≥ 55%. At the end of followup, 21/26 patients (81%) exhibited an LVEF ≥ 55%. Three patients died during followup, and 2 died from LM.Conclusion.LM is a severe manifestation of SLE. It can be the first manifestation of the disease or it can occur during followup, in particular in untreated patients. However, the longterm prognosis is typically positive. Patients with less severe disease exhibited good LVEF recovery without CYC.

Patients with sickle cell disease have an increased risk of venous thromboembolism (VTE) and with a mortality 2-fold higher. The anticoagulation of VTE in a young population is an important question. Indeed, hemorrhagic complications of anticoagulation may occur more frequently than in the general population. The use of a direct oral anticoagulant (DOAC) is not recommended for VTE in patients with sickle cell disease because those patients were not included in the clinical studies. We aimed to study the safety of using DOACs in a prospective cohort of patients with sickle cell disease and VTE. We prospectively followed the cohort of all sickle cell disease patients undergoing recent DOAC treatment for VTE at a sickle cell disease reference center. Twelve patients received rivaroxaban for VTE (eight women and four men). The median age was 27 years (20-45). The sickle cell disease variants included homozygous Hb SS (

International audience

Background: IgG4-related disease (IgG4-RD) is characterized by lymphoplasmacytic infiltrates, IgG4+ plasma cells, fibrosis and frequent ectopic lymphoid structures (ELS). Excessive Th2 cytokines production and role of T follicular helper (Tfh) cells have been reported. Innate cells (ILCs), a heterogeneous population of non-B non-T lymphocytes lacking antigen-specific receptors, are able to produce type 2 cytokines (ILC2s) or to participate to ELS formation (ILC3s) and could contribute to IgG4-RD lesions. Objectives: To analyze circulating blood ILCs in IgG4-RD. Methods: IgG4-RD patients were identified according to the Comprehensive Diagnostic Criteria. Patients treated with steroids or DMARDs within 3 months or rituximab within 6 months prior inclusion were excluded. Peripheral blood mononuclear cells were isolated and analyzed by flow cytometry. ILCs were defined as lymphoid CD45+Lineage(Lin)-CD127+ cells. Among ILCs, 3 subsets were defined according to CRTH2 and CD117 expression. In some patients, transcription factor expression (T-bet, GATA3, RORγt) as well as cytokine production (IFNγ, IL-4/IL-13, IL-17/IL-22) after different stimulations were analyzed in ILC subsets. Results were compared to healthy controls (HC), correlated to clinical and biological characteristics, and compared before and after treatment. Results: Twenty patients with active untreated IgG4-RD and 30 HC were included. In IgG4-RD group, mean age was 64 years and sex ratio 4:1. Serum IgG4 levels were >1.35 g/l for 85% of patients and median eosinophil count 410/mm3. Most patients (65%) were analyzed at diagnosis. Main organs involved were lymph nodes (n=15), pancreas (n=9), salivary glands (n=8), biliary tree and kidney (n=5), lung and retroperitoneum (n=4), with ≥3 organs involved in 65%. Number of blood ILCs was not modified in IgG4-RD patients (1.2 ± 2.6 x103/ml vs 1.5 ± 1.3 x103/ml in HC, p=0.29; 0.07 ± 0.06% of CD45+ lymphocytes vs 0.09 ± 0.05% in HC, p=0.35). ILC1s, ILC2s, and ILC3s represented respectively 30%, 29% and 32% of total ILCs in HC. IgG4-RD patients presented a decrease in ILC2s (23.8% [12.4-29.3], p=0.04) and ILC3s (21.2% [8.8-28.1], p=0.002) and an increase in ILC1s (54.1% [33.8-68.7], p=0.0009) proportions. ILC2s (274/ml [152-594] vs 554/ml [62-1000], p=0.045) and ILC3s (214/ml [120-620] vs 509/ml [336-908], p=0.04) numbers were decreased in IgG4-RD patients. No correlation was found between number or proportion of total ILCs or any ILCs subsets and clinical or biological characteristics such as age, number of organ involved, IgG4-RD Responder Index or serum IgG4. No correlation was found between Tfh and ILC3s, or between eosinophils and ILC2s numbers. As human ILC3s and ILC2s can convert in vitro into IFNγ producing cells, we explore if ILC plasticity could contribute to ILCs subset distribution observed. GATA3 or RORγT expression by ILC1s was not modified (p=0.29, respectively) in IgG4-RD patients compared to HC. As previously reported, no cytokine production (IFNγ, IL-4/IL-13, IL-17/IL-22) was observed after different stimulations of blood ILCs. Analyzes before and after treatment found no difference in proportion or absolute number of total or subsets of circulating ILCs. Conclusion: Circulating ILC2s and ILC3s are decreased in IgG4-RD. Recruitment of ILC2s or ILC3s in tissues, where they could participate to Th2 cytokine production, ELS formation and fibrosis, needs further investigations. Disclosure of Interests: None declared

Background: IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect virtually every organ. Although arterial involvements have been reported, no studies have examined the occurrence of arterial or venous thrombotic events in these patients. Objectives: To explore the frequency, the characteristics, and risk factors of arterial and venous thrombotic events in IgG4-related disease patients. Methods: An observational, descriptive, retrospective study was conducted from a multicentric national case registry for IgG4-RD. Patients fulfilled the Comprehensive Diagnostic Criteria (CDC) for IgG4-RD, and all patients with arterial or venous thrombotic events confirmed by imaging during follow-up were analyzed. Clinical, radiological, biological, histological and therapeutic characteristics were retrospectively collected using a standardized online data sheet. Results obtained in patients with thrombosis were compared to those without thrombosis. Results: One hundred eighty-nine patients with IgG4-RD (135 men/54 women, median age 61 years) were included. During a 12-months median follow-up, one or more arterial thrombotic events occurred in 10 patients and venous thrombotic events in 16 (5.3 and 8.5 events/100 patient-years, respectively). Arterial complications (coronary artery disease n=5, lower limb peripheral arterial disease n=2, mesenteric ischemia, transient ischemic attack, and carotid thrombosis: n=1) occurred on average 30 months [0-140] after the first symptoms of IgG4-RD. They were inaugural in 2 patients without any cardiovascular risk factor, and associated with IgG4-RD arterial involvement in 3 (coronary aneurysms n=2, leg arteritis n=1). Among patients with arterial thrombosis, 60% had systemic involvement (≥3 organs involved), 89% elevated serum IgG4 (> 3N in 56%), and 57% CRP >10 mg/l. Only 5/10 were treated with steroids at the time of arterial complication, and 4 had never been exposed to steroid therapy. Renal involvement was associated with the occurrence of an arterial thrombotic event (p = 0.03). Venous thromboembolic complications (deep venous thrombosis (DVT) n=12, pulmonary embolism n=4) occurred on average 24 months [0-164] after the first symptoms of IgG4-RD, but were inaugural in 6 patients. Usual venous thrombosis risk factors were found in only 3/16. Seven patients had retroperitoneal fibrosis (RPF), 2 had mediastinal fibrosis, 60% had localized IgG4-RD (≤2 organs involved), serum IgG4 level was normal in 67% and CRP Conclusion: Arterial and venous thrombotic complications are common in IgG4-RD patients. While arterial events are associated with mulitorgan involvement and elevated serum IgG4, venous thrombotic complications appear to affect more likely patients with compressive localized forms of the disease, such as RPF. Mechanisms responsible for this over-risk and clinical benefit of a preventive platelet antiaggregant or anticoagulant treatment in high risk of thrombosis subgroups remain to be evaluated. Disclosure of Interests: None declared

The aim of our study was to investigate possible differences in nailfold videocapillaroscopy (NVC) features between patients with dermatomyositis (DM), overlap myositis (OM), antisynthetase syndrome (ASS), and immune-mediated necrotizing myopathy (IMNM).We performed a cross-sectional monocentric study. All patients with inflammatory myopathies (IMs) over a 6-month period were analyzed by NVC for giant and ramified capillaries, tortuosities, capillary density, disorganization, and scleroderma pattern. Clinical, biological, and pathological characteristics were retrospectively recorded. Patients were classified as having DM, OM, ASS, or IMNM for comparison. Patients were also compared with a group of patients with systemic sclerosis (SSc).NVC was analyzed in DM (n = 17), OM (n = 8), ASS (n = 12), and IMNM (n = 6). Vascular disorganization and avascular zones were observed only in DM (11.8%) and OM (62.5%). The percentage of patients with giant capillaries was higher in OM (n = 4/8) than in DM (n = 3/17) and absent in ASS and IMNM. Frequency of ramified capillaries, tortuosities, hemorrhages, or thrombosis was not different between subgroups. A scleroderma pattern was only observed in OM patients.In this limited series of patients, we observed that DM and OM NVC abnormalities are different from ASS and IMNM. We could not determine NVC specific patterns associated with myositis-specific antibody subtypes of DM because of the small number of patients.Key Points• Nailfold videocapillaroscopy abnormalities are different in subgroups of inflammatory myopathies.• Giant capillaries, disorganization, and major capillary loss are observed in overlap myositis and dermatomyositis but not in antisynthetase syndrome (ASS) or immune-mediated necrotizing myopathy.• Nailfold videocapillaroscopy abnormalities in overlap myositis (with the exclusion of ASS) are close to systemic sclerosis.

Resume Propos L’arterite a cellules geantes (ACG) est la plus frequente des vascularites du sujet âge. Afin d’evaluer l’impact de l’âge au diagnostic, nous avons compare les caracteristiques des patients âges de moins de 75 ans ( Patients et methodes Nous presentons une etude retrospective menee aupres de 164 patients ayant une ACG diagnostiquee entre 2005–2017. Tous les patients presentaient au moins 3/5 criteres de l’ACR et avaient eu un angioscanner au diagnostic. L’âge moyen etait de 73 ± 9,6 ans, 84 patients (59 femmes) etaient âges de moins 75 ans, 80 patients (53 femmes) etaient âges de 75 ans et plus. Resultats Les patients ≥ 75 ans avaient davantage d’antecedents cardiovasculaires (p = 0,026), d’hypertension arterielle (p = 0,005) et de complications ophtalmologiques (p = 0,02). Ils presentaient moins d’atteinte des gros troncs (p Conclusion Dans cette etude, les sujets ≥ 75 ans au diagnostic avaient plus de complications ophtalmologiques et a l’inverse moins d’aortite scanographique. Il n’y avait pas de difference dans la prise en charge en dehors des bolus de corticoides plus frequents chez les sujets ≥ 75 ans. Le profil evolutif n’etait pas different selon l’âge des patients au diagnostic.

Introduction La description des auto-anticorps specifiques des myopathies inflammatoires idiopathiques (ASM) est une avancee majeure pour la comprehension, le diagnostic, la classification et la prise en charge des patients atteints de ces maladies rares mais potentiellement graves. L’utilisation en routine clinique de kits commerciaux aisement disponibles bases sur de nouvelles methodes de detection multiples des ASM comme l’immunoblot a fait emerger des profils serologiques atypiques. Nous avons souhaite analyser de maniere exhaustive l’utilisation de l’immunoblot au CHU de Marseille afin d’identifier et de decrire les patients ayant presente une multipositivite de differents ASM classiquement consideres comme hetero-exclusifs. Materiels et methodes Nous avons mene une etude retrospective descriptive et analytique sur l’ensemble des prelevements adresses au laboratoire d’immunologie du CHU De Marseille pour realisation d’un immunoblot a la recherche d’ASM (Myositis profile 12 Ig Dot, Alphadia) entre le 01/01/2015 et le 19/04/2019. Les dossiers des patients avec une multipositivite des ASM ont ete analyses. Resultats 3823 prelevements sanguins ont ete analyses par immunoblot, correspondant au serum de 3142 patients d’une moyenne d’âge de 53,7 ans et composes a 60,4 % de femmes. Les specialites les plus prescriptrices etaient : la medecine interne (46 % du volume total de prescription), la neurologie (21 %), la pneumologie (7 %), la dermatologie (5 %), la rhumatologie (4 %) et la pediatrie (2 %). 243 patients (7,7 %) etaient retrouves positifs pour au moins 1 ASM : un ASM specifique des dermatomyosites (n = 127) et/ou un ASM specifique du syndrome des anti-synthetases (n = 83) et/ou un ASM specifique des myopathies necrosantes auto-immunes (n = 44). La seroprevalence des ASM variait selon la specialite du service de provenance et selon l’ASM considere (p Conclusion L’utilisation en routine de l’immunoblot a la recherche d’ASM dans la demarche diagnostique des myopathies inflammatoires fait emerger un nombre non negligeable de multipositifs. Parmi eux, on retrouve 45 % de probable fausse positivite notamment chez des patients avec antecedents d’auto-immunite. Les autres elements cliniques ainsi que les explorations musculaires permettaient de se premunir d’un surdiagnostic. Une prescription raisonnee, une collaboration entre biologistes et cliniciens ainsi qu’une interpretation critique de l’immunoblot semblent primordiales. Des efforts d’optimisation et de standardisation des nouvelles techniques de mesures des ASM en collaboration avec les fabricants semblent necessaires pour ameliorer la rentabilite de cet examen.