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This prospective population-based study estimated the incidence of giant cell arteritis (GCA) in northeastern Paris. GCA cases diagnosed between 2015 and 2017 were obtained from local hospital and community-based physicians and the national health insurance system database. Criteria for inclusion were living in the study area at that time and fulfilling the 1990 American College of Rheumatology classification criteria and/or its expanded version. Cranial and large-vessel GCA cases were defined by the presence or absence of cranial signs and/or symptoms, respectively. Annual incidence was calculated by dividing the number of incident cases by the size of the study population ≥ 50 years old. Completeness of case ascertainment was assessed by a three-source capture-recapture analysis. Among the 62 included cases, 42 (68%) were women, mean (± SD) age 77.3 ± 9.1 years. The annual incidence of GCA in northeastern Paris and completeness of case ascertainment were estimated at 7.6 (95% CI 5.9-9.8) per 100,000 inhabitants ≥ 50 years old and 66% (95% CI 52-92%), respectively. Incidence increased with age, peaked at age 80-89 years, and was almost twice as high in women versus men. Large-vessel GCA cases, mean (± SD) age 68.6 ± 11.5 years, accounted for 8% of all GCA cases. In this study, GCA epidemiology was mainly driven by cases with cranial GCA signs or symptoms and incidence results were consistent with recent European and past French studies.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies raised against nuclear antigens and whose production is promoted by autoreactive T follicular helper (TFH) cells. Basophils, by accumulating in secondary lymphoid organs (SLO), amplify autoantibody production and disease progression through mechanisms to be defined. Here, we demonstrate that a functional relationship between TFH cells and basophils occurs in SLO during lupus pathogenesis. On SLE patient blood basophils, PD-L1 expression was upregulated and associated with TFH and TFH2 cell expansions and with disease activity. In two distinct lupus-like mouse models, TFH cell pathogenic accumulation, maintenance and function, and disease activity were dependent on basophils and their expressions of PD-L1 and IL-4. Our study establishes a direct link between basophils and TFH cells in the SLE context that promotes autoreactive IgG production and lupus nephritis pathogenesis. Altering the basophil/TFH cell axis in the SLE context may represent a promising innovative intervention strategy in SLE.

Susac syndrome is a rare disease affecting mainly young women, characterized by a microangiopathy limited to the cerebral, retinal, and cochlear vessels. Although the pathophysiology of Susac syndrome is not yet fully elucidated, recent advances favour a primitive vasculitis affecting the cerebral, retinal and cochlear small vessels. Susac syndrome must be recognized in the presence of the pathognomonic clinical triad associating: 1/subacute encephalopathy with unusual headache and pseudopsychiatric features associated with diffuse white matter, grey matter nuclei and specifically corpus callosum lesions on brain MRI; 2/eye involvement that may be pauci-symptomatic, with occlusions of the branches of the central artery of the retina at fundoscopy and arterial wall hyperfluorescence on fluorescein angiography; and 3/cochleo-vestibular damage with hearing loss predominating at low frequencies on the audiogram. Relapses are frequent during an active period lasting approximately 2 years. Eventually, the disease resolves but isolated retinal arterial wall hyperfluorescence without new occlusions may recur, which should not lead to treatment intensification. First-line treatment consists of a combination of anti-aggregants and high dose corticosteroids. In refractory patients or in case of relapse, immunomodulatory molecules such as intravenous immunoglobulins or immunosuppressive drugs such as mycophenolate mofetil, cyclophosphamide or rituximab should be started. Unfortunately, sequelae-mostly hearing loss- remain frequent in these young patients.

Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

ObjectiveWe analysed the incidence of, the specific outcomes and factors associated with COVID-19-associated organ failure (AOF) in patients with systemic lupus erythematosus (SLE) in France.MethodsWe performed a cohort study using the French national medical/administrative hospital database for the January 2011–November 2020 period. Each patient with SLE diagnosed in a French hospital with a COVID-19-AOF until November 2020 was randomly matched with five non-SLE patients with COVID-19-AOF. We performed an exact matching procedure taking age ±2 years, gender and comorbidities as matching variables. COVID-19-AOF was defined as the combination of at least one code of COVID-19 diagnosis with one code referring to an organ failure diagnosis.ResultsFrom March to November 2020, 127 380 hospital stays in France matched the definition of COVID-19-AOF, out of which 196 corresponded with patients diagnosed with SLE. Based on the presence of comorbidities, we matched 908 non-SLE patients with COVID-19-AOF with 190 SLE patients with COVID-19-AOF. On day 30, 43 in-hospital deaths (22.6%) occurred in SLE patients with COVID-19-AOF vs 198 (21.8%) in matched non-SLE patients with COVID-19-AOF: HR 0.98 (0.71–1.34). Seventy-five patients in the SLE COVID-19-AOF group and 299 in the matched control group were followed up from day 30 to day 90. During this period, 19 in-hospital deaths occurred in the SLE group (25.3%) vs 46 (15.4%) in the matched control group; the HR associated with death occurring after COVID-19-AOF among patients with SLE was 1.83 (1.05–3.20).ConclusionsCOVID-19-AOF is associated with a poor late-onset prognosis among patients with SLE.

Objective The detection of somatic mutations among the genes of myeloid cells in asymptomatic patients—defining clonal haematopoiesis of indeterminate potential (CHIP)—is associated with a predisposition to cardiovascular events (CVEs) in the general population. We aimed to determine whether CHIP was associated with CVEs in SLE patients. Methods The study is an ancillary study of the randomized, double-blind, placebo-controlled, multicentre PLUS trial conducted from June 2007 through August 2010 at 37 centres in France, involving 573 SLE patients. The search for somatic mutations by high-throughput sequencing of 53 genes involved in clonal haematopoiesis was performed on genomic DNA collected at PLUS inclusion. CHIP prevalence was assessed in SLE and in a retrospective cohort of 479 patients free of haematological malignancy. The primary outcome was an incident CVE in SLE. Results Screening for CHIP was performed in 438 SLE patients [38 (29–47) years, 91.8% female]. Overall, 63 somatic mutations were identified in 47 patients, defining a CHIP prevalence of 10.7% in SLE. Most SLE patients (78.7%) carried a single mutation. Most variants (62.5%) were located in the DNMT3A gene. CHIP frequency was related to age and to age at SLE diagnosis, and was associated with a lower frequency of aPLs. CHIP occurred >20 years earlier (P Conclusion The prevalence of CHIP is relatively high in SLE for a given age, but was not found to be associated with incident CVEs. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT05146414.

Quality indicators (QIs) for systemic lupus erythematosus (SLE) management based on the 2019 update of European League Against Rheumatism (EULAR) recommendations have been recently proposed. We aimed to determine whether adherence to QIs was associated with patient reported outcome (PRO).Adherence to a set of 18 EULAR-based QIs and correlation with PRO assessed by Lupus Impact Tracker (LIT) was tested in a cohort of 162 SLE patients.On average, SLE patients received 41% (33; 52.5) of recommended care. Higher adherence to monitoring-related QIs was associated with an older age, a shorter SLE disease duration and a more severe disease (i.e. Class III/IV/V nephritis). LIT demonstrated that the average impact of lupus on patients' life was of 30% (12.5;47.5). In multivariable analysis, patients of female gender (OR 0.25, 95% 0.05-0.94; p = 0.05), with lupus CNS (OR 0.33, 95%CI 0.08-1.05; p = 0.08) and skin involvements (OR 0.49, 95%CI 0.23-1.04; p = 0.07) had higher odds of experiencing a negative impact of the lupus on their life. No association were found between adherences to QIs by physicians and reported quality of life in lupus patients.Our study confirms a variable degree of clinicians' adherence to QIs for SLE and shows no clear association between QIs adherence and patient reported outcome. Adherence to QIs by physicians are not enough to impact the quality of life of patients.

International audience

Introduction Script concordance tests (SCTs) have been developed to assess clinical reasoning in uncertain situations. Their reliability for the evaluation of undergraduate medical students has not been evaluated. Methods Twenty internal medicine SCT cases were implemented in undergraduate students of two programs. The results obtained on the SCTs were compared to those obtained by the same students on clinical-based classical multiple-choice questions (MCQs). Results A total of 551/883 students (62%) answered the SCTs. The mean aggregate score (based on a total 20 points) was 11.54 (3.29). The success rate and mean score for each question did not differ depending on the modal response but the discrimination rate did. The results obtained by the students on the SCT test correlated with their scores on the MCQ tests. Among students, 446/517 (86%) considered the SCTs to be more difficult than classical MCQs, although the mean score did not differ between the SCT and MCQ tests. Conclusion The use of SCTs is a feasible option for the evaluation of undergraduate students. The SCT scores correlated with those obtained on classical MCQ tests.

Skeletal tuberculosis (TB) is rare. We aimed to report on diagnostic strategy and treatment of skeletal TB.In this multidisciplinary single-center medical records review study, all adult patients admitted between January 2009 and December 2019 with microbiologically proven skeletal TB were included. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records.Among 184 patients identified with TB, 21 (16 women, 42 years [27, 48 years]) had skeletal involvement. Skeletal TB included spondylitis (n = 11), lytic bone lesions (n = 7), sacroiliitis (n = 5), arthritis (n = 3), osteitis (n = 2), and diffuse muscle abscesses without bone lesion (n = 1). Lytic lesions involved both axial and peripheral skeleton at multiple sites in most cases. 18F-fluorodeoxyglucose positron emission tomography was performed in 13 patients and helped to detect multifocal asymptomatic lesions and to target biopsy. All patients were treated with anti-TB therapy for 7 to 18 months. Fifteen patients (71.4%) received steroids as an adjunct therapy. Eleven patients needed an orthopedic immobilization corset, and 3 patients underwent surgery. All patients clinically improved under treatment, but 2 relapsed over a median follow-up of 24 months (12-30 months). No patient died or suffered long-term disabilities.Our study emphasizes the diversity of skeletal involvement in TB. 18F-fluorodeoxyglucose positron emission tomography scanner at diagnosis is key to assess the extension of skeletal involvement and guide extraskeletal biopsy. Neurological complications might be prevented by adding corticosteroids to anti-TB therapy.

Background Myocardial Tuberculosis (MT) is exceedingly rare. We aimed to report on myocardial involvement in tuberculosis (TB). Methods All adult patients admitted in a department of Internal Medicine over an 8-year period with microbiologically proven MT were retrospectively reviewed. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records. Results Six patients (4 women, 37.6 [21.3–62.1] years) with MT were identified. MT included cardiac mass (n = 1), coronaritis (n = 1), left ventricle spontaneous rupture (n = 1) and myocarditis (n = 3). Pericardial effusion was associated with myocardial involvement in 2 cases. Four patients presented with acute heart failure. CRP serum level was high in all cases. The mean delay between the first symptoms and TB diagnosis was of 6 [1–44] months. The time from admission to diagnosis was of 18 (9–28) days. No patient had human immunodeficiency virus infection. Fluorodeoxyglucose - positron emission tomography (FDG-PET) detected extra-cardiac asymptomatic Mycobacterium tuberculosis infection localization and guided biopsy in 5 cases. As compared to TB patients without cardiac involvement, patients with MT were younger and more frequently women. All patients received antituberculosis therapy for 7.5 to 12 months associated with steroids for at least 6 weeks. Cardiac surgery was required in all but one patient. No patient died over a median follow-up of 1.2 [0.2–4.4] years. Conclusion Our study emphasizes the clinical spectrum of life-threatening MT. Early diagnosis using FDG-PET imaging to target biopsy in extra-cardiac tissues and combined treatment strategy associating antituberculosis therapy, corticosteroids and surgery prevent complications and death.

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.

To evaluate the specific response of SLE patients to BNT162b2 vaccination and its impact on autoimmunity defined as in vivo production of interferon-alpha (IFNα) by plasmacytoid dendritic cells (pDCs) and autoreactive immune responses.Our prospective study included SLE patients and healthy volunteers (HV) who received 2 doses of BNT162b2 vaccine 4 weeks apart. Subjects under immunosuppressive drugs or with evidence of prior COVID-19 were excluded. IgG anti-Spike SARS-CoV-2 (anti-S) antibodies, anti-S specific-B cells, anti-S specific T cells, in vivo INF-α production by pDCs, activation marker expression by pDCs and autoreactive anti-nuclear T cells were quantified before first injection, before second injection, and 3 and 6 months after first injection.Vaccinated SLE patients produced significantly lower IgG antibodies and specific B cells against SARS-CoV-2 as compared to HV. In contrast, anti-S T cell response did not significantly differ between SLE patients and HV. Following vaccination, the surface expression of HLA-DR and CD86 and the in vivo production of IFNα by pDCs significantly increased in SLE patients. The boosted expression of HLA-DR on pDCs induced by BNT162b2 vaccine correlated with the overall immune responses against SARS-CoV-2 (anti-S antibodies: r = 0.27 [0.05-0.46], p = 0.02; anti-S B cells: r = 0.19 [-0.03-0.39], p = 0.09); anti-S T cells: r = 0.28 [0.05-0.47], p = 0.016). Eventually, anti-SARS-CoV-2 vaccination was associated with an overall decrease of autoreactive T cells (slope = - 0.00067, p = 0.015).BNT162b2 vaccine induces a transient in vivo activation of pDCs in SLE that contributes to the immune responses against SARS-CoV-2. Unexpectedly BNT162b2 vaccine also dampens the pool of circulating autoreactive T cells, suggesting that vaccination may have a beneficial impact on SLE disease.

Objective Cardiovascular disease (CVD) is the leading cause of death in systemic lupus erythematosus (SLE). B cells play a key role in the pathogenesis of lupus, and anti-BAFF therapy has been approved for use in SLE. Since mature B cells also promote atherosclerosis, we undertook this study to evaluate, in a mouse model and in SLE patients, whether BAFF neutralization has an atheroprotective effect in SLE. Methods The effect of BAFF on atherosclerosis associated with lupus was investigated in the atherosclerosis/lupus-prone apolipoprotein E-knockout D227K mouse model and in a cohort of SLE patients. Mice were treated with a blocking anti-BAFF monoclonal antibody (mAb), while fed a standard chow diet. Carotid plaque and carotid intima-media thickness were assessed by ultrasound at baseline and during follow-up in SLE patients who were asymptomatic for CVD. Results Anti-BAFF mAb in ApoE-/- D227K mice induced B cell depletion, efficiently treated lupus, and improved atherosclerosis lesions (21% decrease; P = 0.007) in mice with low plasma cholesterol levels but worsened the lesions (17% increase; P = 0.06) in mice with high cholesterol levels. The atheroprotective effect of the BAFF-BAFF receptor signaling inhibition on B cells was counterbalanced by the proatherogenic effect of the BAFF-TACI signaling inhibition on macrophages. In SLE patients, blood BAFF levels were associated with subclinical atherosclerosis (r = 0.26, P = 0.03). Anti-BAFF mAb treatment had a differential effect on the intima-media thickness progression in SLE patients depending on body mass index. Conclusion Depending on the balance between lipid- and B cell-induced proatherogenic conditions, anti-BAFF could be detrimental or beneficial, respectively, to atherosclerosis development in SLE.

Resume Introduction L'unite de soins de suite et readaptation de Medecine Interne Bichat (Paris) est une structure dediee a la prise en charge des patients polypathologiques de moins de 75 ans. Nous presentons les caracteristiques et le devenir des patients pris en charge dans cette unite pilote au sein de l'assistance publique hopitaux de Paris. Methodes Les sejours des patients hospitalises entre le 1er Mai 2017 et le 1er Mai 2018 ont ete analyses de facon retrospective. Resultats L'analyse a porte sur 61 patients âges en mediane de 61 (24 a 75) ans, hospitalises pour une duree mediane de 108 jours (13 a 974). A l'admission, le nombre de pathologies chroniques graves par patient etait de 5 (1 a 9) pour un score de Charlson a 6 (0 a 12). La majorite des patients etaient sans emploi (83,6 %) avec des revenus inferieurs au SMIC (65,6 %). A la sortie, les problemes medicaux et sociaux ayant motive l'admission etaient resolus chez 65,6 % des patients et 85,4 % des patients regagnaient leur domicile. Le nombre de readmissions pour chaque patient sur le site etait plus faible dans l'annee suivant (vs l'annee precedant, p Conclusion Les patients admis en SSR de Medecine Interne sont jeunes, polypathologiques, et en situation de grande vulnerabilite sociale. Pour la majorite, le sejour en SSR a permis la resolution des problemes medicaux et sociaux, un retour au domicile dans des conditions optimisees et un moindre recours hospitalier dans l'annee suivant la sortie d'hospitalisation.

Resume Introduction L'endometriose thoracique est une forme rare d'endometriose extra-pelvienne survenant chez la femme en âge de procreer et dont les manifestations les plus frequentes sont le pneumothorax et l'hemothorax catameniaux. La chirurgie thoracique par videothoracoscopie permet le diagnostic histologique. Les recidives sont frequentes malgre un traitement medico-chirurgical. Observation Nous rapportons l'observation d'une femme de 36 ans atteinte d'endometriose thoracique dont le diagnostic a ete porte devant un tableau d'hemothorax droit recidivant. Nous effectuons une mise au point diagnostique, physiopathologique et therapeutique de cette entite rare. Conclusion Le diagnostic d'endometriose pleurale doit etre evoque devant un hemothorax spontane chez une femme en âge de procreer.

International audience; Background and objective: Data regarding interstitial lung disease (ILD) in the setting of systemic lupus erythematosus (SLE) are limited. We used a nationwide database to determine the incidence and the prevalence of ILD in SLE. Methods: Characteristics of all SLE inpatients admitted between 2011 and 2012 in France were analysed through the French medico-administrative database. Features associated with the presence of ILD were studied. Cox hazard model was used to measure the impact of ILD on survival from the first stay to 2020. The incidence of ILD in SLE was estimated by analysing the onset of ILD from 2013 to 2020 in SLE patients who had no evidence of ILD in 2013. Results: Between 2011 and 2012, 10,460 SLE patients had at least one hospital stay and could be traced until 2020. Among them, 134 (1.2%) had an ILD diagnosed at baseline. The frequency of ILD in SLE was higher in patients who had an associated autoimmune disease such as Sjögren's syndrome or systemic sclerosis (29.9% vs. 5.9%, p < 0.0001). ILD was associated with an increased risk of death in SLE in the multivariable analysis (hazard ratio [95% CI] 1.992 [1.420–2.794]; p < 0.0001). Among the 31,029 SLE patients with no evidence of ILD at baseline, ILD occurred in 795 (2.6%) between 2013 and 2020. The incidence rate of ILD in SLE was 10.26 for 1000 patient-years [95% CI: 10.24–10.28]. Conclusion: In SLE, ILD is exceedingly rare, often associated with another systemic autoimmune disorder and appears as a major risk factor for death. © 2022 Asian Pacific Society of Respirology.

Objective Identification of biological markers able to better stratify cardiovascular risks in SLE patients is needed. We aimed to determine whether serum cardiac troponin T (cTnT) levels measured with a highly sensitive assay [high sensitivity cTnT (HS-cTnT)] may predict cardiovascular events (CVEs) in SLE. Method All SLE patients included between 2007 and 2010 in the randomized, double-blind, placebo-controlled, multicentre PLUS trial were screened. Patients with no past history of CVE at inclusion and a follow-up period of >20 months were analysed. HS-cTnT concentration was measured using the electrochemiluminescence method on serum collected at PLUS inclusion. The primary outcome was the incident CVE. Factors associated with the primary outcome were identified and multivariate analysis was performed. Results Overall, 442 SLE patients (of the 573 included in the PLUS study) were analysed for the primary outcome with a median follow up of 110 (interquartile range: 99–120) months. Among them, 29 (6.6%) experienced at least one CVE that occurred at a median of 67 (interquartile range: 31–91) months after inclusion. Six out of 29 patients had more than one CVE. In the multivariate analysis, dyslipidaemia, age and HS-cTnT were associated with the occurrence of CVE. Kaplan–Meier analysis showed that a concentration of HS-cTnT > 4.27 ng/l at inclusion increased by 2.7 [hazard ratio 2.7 (95% CI: 1.3, 5.6), P =0.0083] the risk of CVE in SLE. Conclusion HS-cTnT measured in serum is the first identified biomarker independently associated with incident CVE in SLE patients.

In non-human immunodeficiency virus (HIV)-infected patients, tuberculosis (TB) immune reconstitution inflammatory syndrome (IRIS) is unusual. The management of corticosteroids-refractory IRIS is unclear. We report on infliximab efficacy for treatment of corticosteroid-resistant TB-IRIS occurring in an immunocompetent patient.

Objective HCQ is an essential medication in SLE, proven to lengthen survival and reduce flares. Its use, however, is limited by its rare but severe ophthalmological complications. Here, we aimed to analyse factors associated with HCQ retinopathy including HCQ blood levels. Methods This case–control study compared SLE patients with and without HCQ retinopathy, defined by abnormal results for at least two of the following ophthalmological tests: automated visual fields, spectral-domain optical coherence tomography (SD-OCT), multifocal electroretinogram (mfERG) and fundus autofluorescence. We compared clinical and laboratory findings to assess risk factors for HCQ retinopathy. Results The study included 23 patients with confirmed retinopathy (cases) and 547 controls. In the univariate analysis, age (P Conclusion SLE patients on HCQ should be closely monitored for retinopathy, especially those from the West Indies or sub-Saharan Africa, or with renal insufficiency, longer HCQ intake or a high cumulative dose. Although reducing the daily dose of HCQ in patients with persistently high HCQ blood levels seems logical, these concentrations were not associated with retinopathy in this study with controls adherent to treatment.

Acute myocarditis (AM) may be the heralding manifestation of autoimmune and inflammatory disorders (AIID). We aimed to describe the clinical presentation and outcome of patients with AM revealing AIID.All consecutive adult patients with AM admitted in a department of Cardiology (Bichat Hospital, Paris, France) from January 2011 to January 2019 were included. Diagnosis of AM was based on clinical manifestations, elevated Troponin, myocardial inflammation on CMR and no evidence for coronary artery disease. AIID were classified using international criteria.Two-hundred and eighteen (35.3 [26.4-47.1] years, 75.2% males) patients with AM were included. Overall, AM revealed AIID in 15 (6.9%), including systemic lupus erythematosus (n = 3), adult onset Still's disease (n = 3), sarcoidosis (n = 2), mixed connective tissue disease (n = 1), anti-Jo1 syndrome (n = 1), eosinophilic granulomatosis with polyangiitis (n = 1), antiphospholipid syndrome (n = 1), reactive arthritis (n = 1), Graves' disease (n = 1) and Crohn's colitis (n = 1). Left ventricular ejection fraction (LVEF) at onset was30% in 5 (33.3%) patients with AIID. All but 2 patients with AIID were treated with steroids, immunosuppressive and/or immunomodulatory drugs and LVEF normalized in all by the end of follow-up. By comparing patients with AIID to patients with idiopathic AM (n = 203), multivariable analysis showed that pericardial effusion, lack of chest pain and high CRP level at onset were independently associated with AIID.Acute myocarditis revealing AIID may be life-threatening at the acute phase but has an overall good prognosis under specific treatment. Pericardial effusion and CRP level at admission suggest an AIID as the cause for AM.

BACKGROUND Susac syndrome (SuS) is a rare occlusive microvessel disease of the brain, retina and inner ear. We aimed to determine whether brain lesion load at the acute phase predicts poor outcomes in SuS. METHODS A prospective national cohort study was conducted from December 2012 to December 2019 in 20 centres in France. Patients included at the principal investigator's center with available brain magnetic resonance imaging (MRI) at diagnosis were analyzed. MRI was reviewed by an experienced neuroradiologist blinded to clinical status. The size, topography and number of hyperintense lesions on diffusion-weighted imaging (DWI-HL) were analyzed at diagnosis and during follow-up. Outcomes involved descriptive characteristics of patients at onset and last follow-up. RESULTS Twenty-three patients (38.1 [18.8-56.5] years, 16 females) were prospectively studied. The triad (i.e., brain, eye and ear involvement) was complete at onset in 17 patients. Brain MRI was performed 1.1 (0.1-3.4) months after the first symptom. All patients had DWI-HL at the acute phase. Patients were separated into two groups according to the number of DWI-HL on first MRI: a first group of patients (n=15) displaying low brain lesion load (

ObjectivesBehçet’s disease (BD) is a chronic systemic vasculitis. Thrombosis is a frequent and life-threatening complication. The pathogenesis of BD is poorly understood and evidence supporting a role for primed neutrophils in BD-associated thrombotic risk is scant. To respond to inflammatory insults, neutrophils release web-like structures, known as neutrophil extracellular traps (NETs), which are prothrombotic. We evaluated the role of NETs and markers of NETs in BD.MethodsBlood samples were collected from patients with BD, according to the International Study Group Criteria for Behçet's disease, and healthy donors (HD). NET components, including cell-free DNA (CfDNA) and neutrophil enzymes myeloperoxidase (MPO), were assessed in serum or in purified neutrophils from patients with BD and HD.ResultsPatients with active BD had elevated serum cfDNA levels and MPO-DNA complexes compared with patients with inactive BD and to HD. In addition, levels of cfDNA and MPO-DNA complexes were significantly higher in patients with BD with vascular involvement compared with those without vascular symptoms. Purified neutrophils from patients with BD exhibited spontaneous NETosis compared with HD. Thrombin generation in BD plasma was significantly increased and positively correlated with the levels of MPO-DNA complexes and cfDNA. Importantly, DNAse treatment significantly decreased thrombin generation in BD plasma but not in HD plasma. In addition, biopsy materials obtained from patients with BD showed NETs production in areas of vasculitic inflammation and thrombosis.ConclusionsOur data show that NETs and markers of NETS levels are elevated in patients with BD and contribute to the procoagulant state. Targeting NETs may represent a potential therapeutic target for the reduction or prevention of BD-associated thrombotic risk.