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International audience; Immunoglobulin G4-related disease (IgG4-RD) is a recently described rare systemic fibroinflammatory disease with an estimated incidence of less than 1 in 100,000 persons per year. The disease can affect virtually any organ and is characterized by unifying histopathological findings. Recently, four subgroups of patients have been characterized: hepatobiliary, head and neck, Mikulicz syndrome and retroperitoneal fibrosis, who illustrate the mainly abdominal and ENT tropism of the disease. Yet, thoracic involvement is not uncommon. It can be detected in up to 30% of patients with systemic IgG4-RD and is the exclusive manifestation of the disease in about 10% of cases. Clinical symptoms are nonspecific and may include dyspnoea, cough or chest pain. Chest CT findings are heterogeneous and primarily include peribronchovascular thickening, nodules, ground-glass opacities and lymphadenopathy. There is no specific diagnostic test for IgG4-RD thoracic involvement, which may mimic malignancy or vasculitis. Therefore, a cautious approach is needed to make an accurate diagnosis: a search for extra-thoracic manifestations, elevated serum IgG4 levels, circulating levels of plasmablasts and pathologic evidence of disease is warranted. Although very suggestive, neither the presence of a polyclonal IgG4 lymphoplasmacytic infiltrate, storiform fibrosis or obliterative phlebitis are sufficient to confirm the histological diagnosis. Steroids are recommended as first-line therapy. Rituximab or disease-modifying antirheumatic drugs may be used in relapsed or rare cases of steroid-refractory disease. In this review, we summarize current knowledge regarding the pathophysiology, epidemiology, diagnostic modalities (clinical-biological-imaging-histopathology) and treatment of IgG4-RD thoracic involvement.

International audience; OBJECTIVES: Severe COVID-19 is associated with exaggerated complement activation. We assessed the efficacy and safety of avdoralimab (an anti-C5aR1 mAb) in severe COVID-19. DESIGN: FOR COVID Elimination (FORCE) was a double-blind, placebo-controlled study. SETTING: Twelve clinical sites in France (ICU and general hospitals). PATIENTS: Patients receiving greater than or equal to 5 L oxygen/min to maintain Spo 2 greater than 93% (World Health Organization scale ≥ 5). Patients received conventional oxygen therapy or high-flow oxygen (HFO)/noninvasive ventilation (NIV) in cohort 1; HFO, NIV, or invasive mechanical ventilation (IMV) in cohort 2; and IMV in cohort 3. INTERVENTIONS: Patients were randomly assigned, in a 1:1 ratio, to receive avdoralimab or placebo. The primary outcome was clinical status on the World Health Organization ordinal scale at days 14 and 28 for cohorts 1 and 3, and the number of ventilator-free days at day 28 (VFD28) for cohort 2. MEASUREMENTS AND MAIN RESULTS: We randomized 207 patients: 99 in cohort 1, 49 in cohort 2, and 59 in cohort 3. During hospitalization, 95% of patients received glucocorticoids. Avdoralimab did not improve World Health Organization clinical scale score on days 14 and 28 (between-group difference on day 28 of-0.26 (95% CI,-1.2 to 0.7; p = 0.7) in cohort 1 and-0.28 (95% CI,-1.8 to 1.2; p = 0.6) in cohort 3). Avdoralimab did not improve VFD28 in cohort 2 (between-group difference of-6.3 (95% CI,-13.2 to 0.7; p = 0.96) or secondary outcomes in any cohort. No subgroup of interest was identified. CONCLUSIONS: In this randomized trial in hospitalized patients with severe COVID-19 pneumonia, avdoralimab did not significantly improve clinical status at days 14 and 28 (funded by Innate Pharma, ClinicalTrials.gov number, NCT04371367).

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.

Allogeneic hematopoietic stem cell transplantation (alloSCT) is curative for severe inborn errors of immunity (IEIs), with recent data suggesting alloSCT in adulthood is safe and effective in selected patients. However, questions remain regarding the indications for and optimal timing of transplant. We retrospectively compared outcomes of transplanted vs matched nontransplanted adults with severe IEIs. Seventy-nine patients (aged ≥ 15 years) underwent alloSCT between 2008 and 2018 for IEIs such as chronic granulomatous disease (n = 20) and various combined immune deficiencies (n = 59). A cohort of nontransplanted patients from the French Centre de Référence Déficits Immunitaires Héréditaires registry was identified blindly for case-control analysis, with ≤3 matched controls per index patient, without replacement. The nontransplanted patients were matched for birth decade, age at last review greater than index patient age at alloSCT, chronic granulomatous disease or combined immune deficiencies, and autoimmune/lymphoproliferative complications. A total of 281 patients were included (79 transplanted, 202 nontransplanted). Median age at transplant was 21 years. Transplant indications were mainly lymphoproliferative disease (n = 23) or colitis (n = 15). Median follow-up was 4.8 years (interquartile range, 2.5-7.2). One-year transplant-related mortality rate was 13%. Estimated disease-free survival at 5 years was higher in transplanted patients (58% vs 33%; P = .007). Nontransplanted patients had an ongoing risk of severe events, with an increased mean cumulative number of recurrent events compared with transplanted patients. Sensitivity analyses removing patients with common variable immune deficiency and their matched transplanted patients confirm these results. AlloSCT prevents progressive morbidity associated with IEIs in adults, which may outweigh the negative impact of transplant-related mortality.

Acquired factor V inhibitor (AFVI) is an extremely rare disorder that may cause severe bleeding. To identify factors associated with bleeding risk in AFVI patients, a national, multicentre, retrospective study was made including all AFVI patients followed in 21 centres in France between 1988 and 2015. All patients had an isolated factor V (FV) deficiency50% associated with inhibitor activity. Patients with constitutional FV deficiency and other causes of acquired coagulation FV deficiencies were excluded. The primary outcome was incident bleeding and factors associated with the primary outcome were identified. Thirty-eight (74 [36-100] years, 42·1% females) patients with AFVI were analysed. Bleeding was reported in 18 (47·4%) patients at diagnosis and in three (7·9%) during follow-up (7 [0·2-48.7] months). At diagnosis, FV was10% in 31 (81·6%) patients. Bleeding at diagnosis was associated with a prolonged prothrombin time that strongly correlated with the AFVI level measured in plasma {r = 0·63, 95% confidence interval (CI) [0·36-0·80], P 0·05}. Bleeding onset during follow-up was associated with a slow AFVI clearance (P 0·001). The corresponding receiver operating characteristics curve showed that AFVI clearance was predictive of bleeding onset with an AFVI clearance of seven months with a sensitivity of 100% (95% CI: 29-100) and a specificity of 86% (95% CI: 57-98, P = 0·02). Kaplan-Meier analysis showed that AFVI clearance7 months increased the risk of bleeding by 8 (95% CI: [0·67-97], P = 0·075). Prothrombin time at diagnosis and time for clearance of FV inhibitor during follow-up are both associated with bleeding in patients with AFVI.

Resume Introduction Le purpura thrombopenique immunologique (PTI) est a l’origine d’une alteration majeure de la qualite de vie. L’education therapeutique du patient (ETP) est une modalite d’accompagnement des patients qui pourrait limiter son retentissement : elle vise a faire emerger des competences d’auto-soin et psychosociales pour etre plus autonome face a sa maladie et mieux vivre avec. L’objectif de cette etude etait d’evaluer les attentes respectives des soignants et des patients vis-a-vis d’un programme d’ETP dans le PTI. Methode Etude observationnelle qualitative et quantitative a partir d’un questionnaire diffuse numeriquement et anonymement aupres de patients atteints de PTI et de soignants. Le questionnaire demandait quels themes aborder au cours d’un programme d’ETP specifique au PTI. Un codage en double insu des reponses a ete effectue par deux medecins, puis confronte jusqu’a l’obtention d’un consensus. Resultats Trente-huit patients atteints de PTI ont ete inclus : 68 % avaient moins de 50 ans et 84 % etaient au stade de PTI chronique. Vingt-cinq soignants ont ete inclus. Les soignants evoquaient plus d’idees se rapportant au domaine cognitif que les patients, centrees en premier lieu sur des thematiques securitaires. Les domaines psychoaffectifs et motivationnels tendaient a etre plus representes dans les reponses des patients. Seulement 53 % des themes etaient evoques a la fois par les patients et les soignants. Conclusion Les discordances observees soulignent les differences entre les attentes respectives des patients et des soignants vis-a-vis d’un programme d’ETP dans le PTI, et donc l’interet d’une co-construction patients-soignants d’un tel type de programme.

Resume Le concept de maladie associee aux IgG4 (MAG4) est relativement recent. Il a ete individualise au debut des annees 2000, mais les cadres nosologiques concernes sont anciens. Il s'agit d'une affection inflammatoire non maligne, fibrosante, caracterisee par un type d'inflammation histologique particulier pouvant toucher de nombreux organes, ainsi que des anomalies immunologiques singulieres. Des criteres dits « diagnostiques » ont ete proposes et ont rapidement evolue, avec l'apparition de criteres dits « generaux » et de criteres specifiques d'organes. Un groupe de travail international et multidisciplinaire a recemment propose des criteres de classification sous l'egide de l'American College of Rheumatology (ACR) et de l'European League Against Rheumatism (EULAR). L'objectif de cette mise au point est de decrire l'evolution de ces differents criteres « diagnostiques » puis de classification, en discutant leurs avantages mais egalement leurs limites respectives. L'utilisation des criteres de classification ACR/EULAR 2019 devrait permettre de mieux definir des groupes plus homogenes de patients et d'encadrer les futurs travaux de recherche clinique, epidemiologique et translationnelle dans le domaine de la MAG4.

Resume Objectif Decrire la presentation clinique, la distribution des lesions, le traitement et les resultats de la sarcoidose osseuse. Methodes Il s’agit d’une etude retrospective francaise multicentrique de patients atteints de sarcoidose confirmee par une biopsie a analyse des patients presentant un granulome confirme par une biopsie sans necrose caseeuse et, soit des manifestations cliniques d’atteintes osseuses, soit des anomalies osseuses a l’imagerie. Les patients presentant une sarcoidose avec atteinte osseuse (cas) ont ete compares a 264 patients atteints de sarcoidose sans manifestations osseuses apparies selon l’âge et le sexe (temoins). Resultats Dans le groupe sarcoidose osseuse (n = 88), 42 patients (48 %) presentaient des symptomes osseux touchant le squelette axial (69 %) et/ou appendiculaire (58 %). Les os les plus frequemment touches sur l’imagerie etaient le rachis (52 %), le pelvis (42 %), les mains (22 %) et le femur (19 %). Par rapport aux temoins, les cas avaient des taux plus eleves d’atteinte mediastinale (93 % contre 47 %), des ganglions lymphatiques extra-thoraciques (66 % contre 21 %), pulmonaire (90 % contre 65 %) et cutanee (44 % contre 23 %) (toutes les valeurs p Conclusion Le rachis et le pelvis etaient les os les plus frequemment touches chez les patients presentant une sarcoidose osseuse. Par rapport aux temoins, les patients atteints de sarcoidose osseuse avaient des taux plus eleves d’atteinte des ganglions lymphatiques thoraciques et extra-thoraciques, pulmonaire et cutanee et d’hypercalcemie. La reponse aux glucocorticoides combines avec le methotrexate ou l’hydroxychloroquine etait bonne chez la majorite des patients.

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.

Background: Tumor necrosis factor (TNF) antagonists have been reported as an efficient third-line therapy for sarcoidosis but there is no data regarding patients who do not respond to this treatment. Objective: To report the characteristics, the outcome and the response to therapy of patients with sarcoidosis resistant to TNF antagonists. Methods: Patients from the French STAT (Sarcoidosis Treatment with Anti-TNF) registry who were classified as non-responders and who were followed-up for >1 year were included. The response to further therapies was classified as complete response, or partial response, and the others were classified as non-responders. Results: Among the 132 patients from the registry, 14 were considered as non-responders to anti-TNF. Nine patients (66% of women; mean age 48 years) were analyzed. The mean number of organs involved was 4.2. Seven patients were previously treated with more than 2 immunosuppressive treatments. The mean duration of the anti-TNF treatment was 9 months (range, 3-24). After a mean follow-up duration of 58 months (median, 35; range, 19-128) a complete response was observed in 2/9 cases, a partial response in 5/9 cases, and 2/9 cases were considered as non-responders. In all but one patient, the immunosuppressant that allowed the clinical response had previously been used. Furthermore, the dosage was not necessarily increased to gain efficacy. Non-responders were treated by corticosteroids only because of their comorbidities or noncompliance. Conclusion: In patients who do not respond to TNF antagonists, previously used immunosuppressants may be useful. Excluding a differential diagnosis, assessing compliance and testing for anti-drug antibodies should be systematic. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 371-375)

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.

International audience

Objective To assess the safety and the efficacy of TNF-α antagonists and tocilizumab in patients with Takayasu arteritis (TAK). Methods A total of 209 patients with TAK [median age 29 years (interquartile range 7–62)], 186 (89%) females] were included. They received either TNF-α antagonists [n = 132 (63%) with 172 lines; infliximab (n = 109), adalimumab (n = 45), golimumab (n = 8), certolizumab (n = 6) and etanercept (n = 5)] or tocilizumab [n = 77 (37%) with 121 lines; i.v. and s.c. in 95 and 26 cases, respectively]. Results A complete response at 6 months was evidenced in 101/152 (66%) patients on TNF-α antagonists and 75/107 (70%) patients on tocilizumab. Age ≥30 years [odds ratio 2.09 (95% CI 1.09, 3.99)] was associated with complete response, whereas vascular signs [OR 0.26 (95% CI 0.1, 0.65)], baseline prednisone ≥20 mg/day [OR 0.51 (95% CI 0.28, 0.93)] were negatively associated with the complete response to TNF-α antagonists or tocilizumab. During a median follow-up of 36 months, 103 relapses were noted. Supra-aortic branches and thoracic aorta involvement [HR 2.44 (95% CI 1.06, 5.65) and 3.66 (1.18, 11.4), respectively] and systemic signs at baseline [HR 2.01 (95% CI 1.30, 3.11)] were significantly associated with relapse. The cumulative incidence of treatment discontinuation and relapse were similar in TNF-α antagonists and tocilizumab. Fifty-eight (20%) adverse effects occurred on biologic targeted therapies [37 (21%) on TNF-α antagonists and 21 (17%) on tocilizumab (P = 0.4), respectively]. Conclusion This large multicentre study shows high efficacy of biologic targeted treatments in refractory TAK. Efficacy, relapse and drug retention rate were equivalent with TNF-α antagonists and tocilizumab.

Systemic sclerosis (SSc) is a rare immune disease leading to fibrosis of the skin and internal organs. Microvasculopathy is a hallmark of SSc. However, some patients have severe macrovascular complications as affecting cerebral, cardiac or peripheral vessels. To date, macrovascular involvement in SSc remains a matter of debate. Many studies have shown an increased prevalence of macrovascular involvement in SSc in comparison with controlled subjects with similar cardiovascular risk factors. Various methods were used: ankle brachial pressure index, intima media thickness, imagery, coronary calcium score, pulse wave velocity, or flow mediated dilation. The pathophysiology of macrovascular involvement remains unknown and is probably multifactorial: accelerated atherosclerosis, endothelial dysfunction, or reflected wave of microvessel obliteration. The aim of this study was to perform a comprehensible review of the literature, through the study of different types of involved vessels. Results of the main studies are summarized in tables according to the method of investigation used.

International audience; No abstract available

Noninfectious manifestations-allergy, autoimmunity/inflammation, lymphoproliferation, and malignancies-are known to exist in many primary immunodeficiency diseases (PID) and to participate in prognosis.To obtain a global view on their occurrence, we retrieved data from a retrospective cohort of 1375 patients included in the French National Reference Center for Primary Immune Deficiencies (CEREDIH) for whom we had a 10-year follow-up since inclusion in the registry.These patients were followed for 10 years (2009-2018) by specialized centers in university hospitals. This study showed that 20.1% of patients without prior curative therapy (n = 1163) developed at least 1 manifestation (event) encompassing 277 events.Autoimmune/inflammatory events (n = 138) and malignancies (n = 85) affected all age classes and virtually all PID diagnostic groups. They were associated with a risk of death that occurred in 195 patients (14.2%) and were found to be causal in 43% of cases. Malignancies (odds ratio, 5.62; 95% confidence interval, 3.66-8.62) and autoimmunity (odds ratio, 1.9; 95% confidence interval, 1.27-2.84) were clearly identified as risk factors for lethality. Patients who underwent curative therapy (mostly allogeneic hematopoietic stem cell transplantation, with a few cases of gene therapy or thymus transplantation) before the 10-year study period (n = 212) had comparatively reduced but still detectable clinical manifestations (n = 16) leading to death in 9.4% of them.This study points to the frequency and severity of noninfectious manifestations in various PID groups across all age groups. These results warrant further prospective analysis to better assess their consequences and to adapt therapy, notably indication of curative therapy.

To describe the clinical presentation, distribution of lesions, treatment, and outcomes of osseous sarcoidosis.A French retrospective multicenter study of patients with biopsy-proven sarcoidosis analyzed patients with 1) a biopsy-proven granuloma without caseous necrosis, and either 2) osseous clinical manifestations, or 3) abnormal osseous imaging. Sarcoidosis patients with osseous involvement (cases) were compared with 264 age- and sex-matched sarcoidosis patients with no osseous manifestations (controls).In the osseous sarcoidosis group (n=88), forty-two (48%) patients had osseous-related symptoms involving the axial (69%) and/or appendicular (58%) skeleton. On imaging, the most commonly affected bones were in the spine (52%), pelvis (42%), hands (22%) and femur (19%). Compared with controls, cases had higher rates of mediastinal (93% vs. 47%) and extra-thoracic lymph node involvement (66% vs. 21%), pulmonary (90% vs. 65%) and cutaneous involvement (44% vs. 23%) (all P0.0001), and hypercalcemia (8.5% vs. 2%, P=0.014). Spleen/liver and gastrointestinal involvement were less frequent in the osseous sarcoidosis group (29% vs. 45%, and 1% vs. 17%, respectively, P0.0001). Response rates to with glucocorticoids alone, glucocorticoids plus methotrexate or glucocorticoids plus hydroxychloroquine were 23/44 (52%), 9/13 (69%) and 4/6 (67%), respectively.In patients with osseous sarcoidosis the spine and pelvis were the most commonly affected bones. Compared with controls, cases with osseous sarcoidosis have higher rates of thoracic and extra-thoracic lymph node involvement, pulmonary and cutaneous involvement, and hypercalcemia. Most patients with osseous sarcoidosis had a good response to glucocorticoids in combination with methotrexate or hydroxychloroquine.

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.

Introduction La maladie associee aux IgG4 (MAG4) est une pathologie localisee ou systemique de presentation habituellement pseudo-tumorale par infiltration tissulaire lymphoplasmocytaire polyclonale d’evolution fibrosante. Elle est definie par un faisceau d’arguments cliniques, biologiques et histologiques. Les glandes salivaires, le pancreas et les ganglions sont les principales atteintes mais elle peut toucher virtuellement tous les organes [1] . Nous rapportons ici le cas d’un jeune patient ayant presente un infarctus du myocarde, revelant une vascularite coronarienne associee aux IgG4. Observation Un homme de 22 ans, asthmatique, tabagique et fumeur de cannabis sans autre facteur de risque cardiovasculaire, se presente aux urgences pour douleur thoracique d’apparition brutale. L’ECG, la troponinemie et l’echographie cardiaque trans-thoracique confirment un infarctus du myocarde dans le territoire inferieur. La coronarographie objective une occlusion thrombotique coronaire droite (CD) desobtruee par thrombo-aspiration ainsi qu’un anevrysme sacciforme de la bifurcation interventriculaire anterieure (IVA)-diagonale (Dg). Un bilan met alors en evidence: elevation des IgE totales, elevation des IgG4 seriques (3 g/L, N La coronarographie revele une nouvelle thrombose de la CD, traitee par angioplastie, une ectasie sacciforme de la circonflexe (Cx), tandis que l’anevrysme IVA-Dg est stable. Une echographie endocoronaire objective au sein de la CD deux lesions superposees; l’une en croissant peri-stent d’allure fibrotique ancienne, l’autre circonferentielle epaisse evocatrice d’un processus inflammatoire. En regard de la Cx, ce meme aspect circonferentiel deborde l’adventice. Un coroscanner confirme l’epaississement perivasculaire CD, l’anevrysme de l’IVA siege d’un thrombus parietal ainsi qu’un epaississement perivasculaire de plusieurs arteres du reseau coronaire gauche. Le bilan biologique de reevaluation est sans anomalies hormis: eosinophiles 620/mm3, IgG4 8 g/L, IgE totales 446 UI/mL (n 90 %). Une corticotherapie a 0,5 mg/kg/j associe a du rituximab (1 gramme J1 et J15) est debutee, entrainant une regression de l’infiltration tissulaire peri-coronarienne et des hypermetabolismes au PET-TDM. Discussion Nous decrivons ici le cas d’un patient presentant une arterite coronaire associee aux IgG4, remplissant les criteres CDC et ACR/EULAR de la MAG4. Cette maladie coronaire associait ici des lesions stenosantes et anevrysmales, et la survenue de deux accidents thrombotiques probablement favorises par la consommation de toxique. Ceci et le jeune âge a rendu le diagnostic complexe, d’autant plus qu’il n’existe pas, a notre connaissance, de description d’atteinte coronaire associee aux IgG4 avant 50 ans . L’arterite (peri-)coronaire est une atteinte vasculaire rare, peu frequente mais bien etablie de la MAG4. Elle est responsable d’epaississements inflammatoires de la paroi vasculaire, parfois stenosants, pouvant se compliquer d’anevrysmes et d’occlusions thrombotiques. Cette atteinte s’inscrit dans un contexte systemique dans la majorite des cas [2] , [3] . Notre cas illustre la necessite d’imageries complementaires a la coronarographie en cas d’evenement coronaire atypique ou de lesions inhabituelles telles des anevrysmes sacciformes. L’atteinte coronaire repond aux traitements immunosuppresseurs qui reduisent le risque de complications evolutives graves [3] . Ceci justifie une recherche de MAG4 en cas d’arterite coronaire et en contexte d’accident coronaire atypique. Conclusion Un syndrome coronaire aigu en contexte epidemiologique, clinique ou lesionnel atypique doit faire rechercher une arterite coronaire, et notamment une maladie associee aux IgG4.

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.