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Background: Takayasu arteritis (TA) is a large vessel vasculitis that may complicate with cerebrovascular ischemic events. The objective was to describe clinical and vascular features of TA patients with cerebrovascular ischemic events and to identify risk factors for these events. Methods: We analyzed the prevalence and type of stroke/transient ischemic attack (TIA), factors associated with cerebrovascular ischemic events, and stroke-free survival in a large cohort fulfilling the American College of Rheumatology or Ishikawa criteria of TA. Results: Among 320 patients with TA (median age at diagnosis, 36 [25–47] years; 261 [86%] women), 63 (20%) had a stroke (n=41; 65%) or TIA (n=22; 35%). Ischemic event localized in the carotid territory for 55 (87%) patients and the vertebral artery territory in 8 (13%) patients. Multiple stenosis were observed in 33 (52%) patients with a median number of stenosis of 2 (minimum, 0 to maximum, 11), and aneurysms were observed in 10 (16%) patients. A history of stroke or TIA before TA diagnosis (hazard ratio [HR], 4.50 [2.45–8.17]; P P =0.05), myocardial infarction history (HR, 0.21 [0.05–0.89]; P =0.039), thoracic aorta involvement (HR, 2.05 [1.30–3.75]; P =0.023), time from first symptoms to diagnosis >1 year (HR, 2.22 [1.30–3.80]; P =0.005), and aspirin treatment (HR, 1.82 [1.04–3.19]; P =0.035) were associated with cerebrovascular ischemic event. In multivariate analysis, time from first symptoms to TA diagnosis >1 year (HR, 2.16 [1.27–3.70]; P =0.007) was independently associated with cerebrovascular ischemic events in patients with TA. The HR for cerebrovascular ischemic event in patients who already experienced a stroke/TIA was 5.11 (2.91–8.99; P Conclusions: Carotid stroke/TIA is frequent in TA. We identified factors associated with cerebrovascular ischemic events.

International audience; Hepatitis C virus (HCV) has been shown to induce many B-cell lymphoproliferative disorders. B lymphocytes are specialized in producing immunoglobulins, and within chronic HCV infection they can cause a range that goes from polyclonal hypergammaglobulinemia without clinical repercussions, passing by mixed cryoglobulinemic vasculitis and eventually reaching B-cell non-Hodgkin lymphoma. This spectrum is supported by substantial epidemiological, pathophysiological and therapeutic data. Many, although not all, pathogenic pathways leading from one extreme to another have been decrypted. Chronic viral antigen stimulation of B lymphocytes has a central role until the last steps towards overt malignancy. This has direct implications in treatment strategies, which always include the use of direct-acting antiviral agents sometimes associated with immunosuppressants. The role of direct-acting antiviral agents has been well established in patients with cryoglobulinemia vasculitis. Its positive impact on B cell non-Hodgkin lymphoma needs to be confirmed in larger studies with longer follow-up.

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

OBJECTIVE Our aim was to compare transcriptome and phenotype profiles of CD4+ T cells and CD19+ B cells in patients with Takayasu arteritis (TAK), patients with giant cell arteritis (GCA), and healthy donors. METHODS Gene expression analyses, flow cytometry immunophenotyping, T cell receptor (TCR) gene sequencing, and functional assessments of cells from peripheral blood and arterial lesions from TAK patients, GCA patients, and healthy donors were performed. RESULTS Among the most significantly dysregulated genes in CD4+ T cells of TAK patients compared to GCA patients (n = 720 genes) and in CD4+ T cells of TAK patients compared to healthy donors (n = 1,447 genes), we identified a follicular helper T (Tfh) cell signature, which included CXCR5, CCR6, and CCL20 genes, that was transcriptionally up-regulated in TAK patients. Phenotypically, there was an increase in CD4+CXCR5+CCR6+CXCR3- Tfh17 cells in TAK patients that was associated with a significant enrichment of CD19+ B cell activation. Functionally, Tfh cells helped B cells to proliferate, differentiate into memory cells, and secrete IgG antibodies. Maturation of B cells was inhibited by JAK inhibitors. Locally, in areas of arterial inflammation, we found a higher proportion of tertiary lymphoid structures comprised CD4+, CXCR5+, programmed death 1+, and CD20+ cells in TAK patients compared to GCA patients. CD4+CXCR5+ T cells in the aortas of TAK patients had an oligoclonal α/β TCR repertoire. CONCLUSION We established the presence of a specific Tfh cell signature in both circulating and aorta-infiltrating CD4+ T cells from TAK patients. The cooperation of Tfh cells and B cells might be critical in the occurrence of vascular inflammation in patients with TAK.

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.

To determine whether giant cell arteritis and polymyalgia rheumatica (GCA/PMR) represent independent risk factors for worse outcomes in COVID-19.Observational, national, French, multicenter cohort (NCT04353609) comprising patients aged ≥18 years with confirmed diagnoses of either GCA, PMR or rheumatoid arthritis (RA) having presented COVID-19; those under rituximab were excluded. Primary endpoint was COVID-19 severity in GCA/PMR patients as compared to RA. We also aimed to describe the evolution of GCA/PMR patients following COVID-19. Multinomial logistic regression models were performed, with and without adjustment on pre-specified confounding factors (i.e., age, sex, body mass index, arterial hypertension, diabetes and cardiovascular disease). Unadjusted and adjusted multinomial odds-ratio (OR/aOR) and their 95% confidence intervals (CIs) were calculated as effect size using RA as reference group.Between April 15, 2020, and August 20, 2021, 674 patients [45 (6.6%) GCA, 47 (7.0%) PMR, 582 (86.4%) RA; 62.8 years, 73.2% female] were included. Compared to RA patients, those with GCA/PMR were older and more frequently presented hypertension, diabetes and cardiovascular disease. Severe COVID-19 and death occurred in 24 (26.1%) and 16 (17.8%) patients with GCA/PMR, respectively. Unadjusted analyses revealed higher odds of severe COVID-19 [OR = 3.32 (95% CI 1.89-5.83; p 0.001)] and death [OR = 3.20 (95%CI 1.67-6.13; p 0.001)] for GCA/PMR compared to RA. After model adjustment, these odds were attenuated.Patients with GCA/PMR were more likely to have severe COVID-19 and higher mortality compared to those with RA. This worse prognosis is mostly due to well known risk factors for the general population rather than vasculitis per se.

International audience; Takayasu arteritis (TAK) is a chronic inflammatory vasculitis of unknown origin affecting large vessels, predominantly the aorta and its main branches. TAK usually affects young women and the management of pregnancy during this vasculitis may be a challenging situation. After a review of the literature, we analysed the data of 505 pregnancies in 373 TAK patients. We discuss main results to clarify if the pregnancy outcome is affected by TAK, especially during disease clinical onset or disease activity. We also discuss the potential impact of pregnancy on TAK prognosis. Disease activity of TAK appears independently associated with a poor pregnancy outcome. More than 5% of pregnant women with TAK develop a life-threatening maternal cardiovascular complication. A good control of TAK disease activity and arterial hypertension before conception and during pregnancy is critical to improve both maternal and foetal outcomes. Pregnancies in the setting of TAK should be considered high-risk, requiring a close collaboration between specialists involved in the care of TAK and obstetricians.

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.

Objective To report the long term mortality in Takayasu arteritis (TA) and to identify prognosis factors. Methods We analyzed the causes of death and the factors associated with mortality in a cohort of 318 patients [median age at diagnosis was 36 [25–47] years and 276 (86%) patients were women] fulfilling American College of Rheumatology and/or Ishikawa criteria of TA. A prognostic score for death and vascular complications was elaborated based on a multivariate model. Results Among 318 TA patients, 16 (5%) died after a median [IQR] follow-up of 6.1 [2.8–13.0] years. The median age at death was 38 [25–47] years with 88% of women. Main causes of death included mesenteric ischemia (n = 4, 25%) and aortic aneurysm rupture (n = 4, 25%). The mortality rate at 5 and 10 years was of 1.9% and 3.9%, respectively. Caucasians (p = 0.049) and smokers (p = 0.002) TA patients were more likely to die. There was an increased mortality in TA (SMR with 95% confidence interval, 2.73 [1.69–4.22]) as compared to age and sex matched healthy controls. We defined high risk patients for death and vascular complications according to the presence of two of the following factors (i.e a progressive clinical course, thoracic aorta involvement and/or retinopathy). In the high risk TA group, the 5-year incidence of death and vascular complication was 48.5% compared to 21.6% (p = 0.001) in those with low risk. Conclusion The overall mortality in our Takayasu cohort was 5% after a median follow-up of 6.1 years. We identified specific characteristics that distinguish TA patients at highest risk for death and vascular complications.

International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.

ObjectiveTo assess the spectrum and long-term outcome of patients with noninfectious aortitis.MethodsWe performed a retrospective multicenter study of 353 patients (median age at diagnosis was 62 [IQR 46–71] yrs and 242 [68.6%] patients were women) with noninfectious aortitis. Factors associated with vascular complications were assessed in multivariate analysis.ResultsWe included 136 patients with giant cell arteritis (GCA), 96 with Takayasu arteritis (TA), 73 with clinically isolated aortitis (CIA), and 48 with aortitis secondary to inflammatory diseases (including Behçet disease, relapsing polychondritis, IgG4-related disease, Cogan syndrome, ankylosing spondylitis). After a median follow-up of 52 months, vascular complications were observed in 32.3%, revascularizations in 30% of patients, and death in 7.6%. The 5-year cumulative incidence of vascular complications was 58% (95% CI 41–71), 20% (95% CI 13–29), and 19% (95% CI 11–28) in CIA, GCA, and TA, respectively. In multivariate analysis, male sex (HR 2.10, 95% CI 1.45–3.05, P < 0.0001) and CIA (HR 1.76, 95% CI 1.11–2.81, P = 0.02) were independently associated with vascular complications.ConclusionNoninfectious aortitis accounts for significant morbidity and mortality. CIA seems to carry the highest rate of vascular complications.

International audience; Background: Takayasu arteritis (TAK) is a large vessel vasculitis resulting in artery wall remodeling with segmental stenosis and/or aneurysm formation. Mast cells (MCs) are instrumental in bridging cell injury and inflammatory response.Objectives: This study sought to investigate the contribution of MCs on vessel permeability, angiogenesis, and fibrosis in patients with TAK. Methods: MC activation and their tissue expression were assessed in sera and in aorta from patients with TAK and from healthy donors (HDs). In vivo permeability was assessed using a modified Miles assay. Subconfluent cultured human umbilic vein endothelial cells and fibroblasts were used in vitro to investigate the effects of MC mediators on angiogenesis and fibrogenesis.Results: This study found increased levels of MC activation markers (histamine and indoleamine 2,3-dioxygenase) in sera of patients with TAK compared with in sera of HDs. Marked expression of MCs was shown in aortic lesions of patients with TAK compared with in those of noninflammatory aorta controls. Using Miles assay, this study showed that sera of patients with TAK significantly increased vascular permeability in vivo as compared with that of HDs. Vessel permeability was abrogated in MC-deficient mice. MCs stimulated by sera of patients with TAK supported neoangiogenesis (increased human umbilic vein endothelial cell proliferation and branches) and fibrosis by inducing increased production of fibronectin, type 1 collagen, and a-smooth muscle actin by fibroblasts as compared to MCs stimulated by sera of HD.Conclusions: MCs are a key regulator of vascular lesions in patients with TAK and may represent a new therapeutic target in large vessel vasculitis.

Introduction La maladie de Takayasu est une vascularite des gros vaisseaux d’etiologie inconnue, touchant l’aorte et ses branches. Les accidents ischemiques cerebraux peuvent compliquer l’evolution de cette maladie. L’objectif etait de decrire les atteintes clinique et vasculaire des patients avec maladie de Takayasu et presentant des evenements vasculaires cerebraux ischemiques. Patients et methodes Nous avons analyses dans une cohorte francaise la prevalence et les caracteristiques des accidents vasculaires cerebraux (AVC) et accidents ischemiques transitoires (AIT) chez les patients suivis pour une maladie de Takayasu ainsi que les facteurs de risque associes a ces evenements et a la survie sans evenement. Resultats Parmi 320 patients avec maladie de Takayasu, 261 (86 %) etaient des femmes et l’âge median au diagnostic etait de 36 [25-47] ans. Nous avons identifie 63 patients avec accident ichemique, incluant 41 (65 %) AVC et 22 (35 %) AIT. Les accidents ischemiques survenaient dans le territoire carotidien chez 55 (87 %) patients et dans le territoire de l’artere vertebrale chez 8 (13 %) patients. L’analyse vasculaire en imagerie retrouvait de multiples stenoses vasculaires chez 33 (52 %) patients avec un nombre median de stenose de 2 [min0-max 11] et des anevrismes chez 10 (16 %) patients. Un antecedent d’AVC/AIT avant le diagnostic de maladie de Takayasu (HR 5,11 [2,91-8,99], p 1an (HR 2,15 [1,25-3,72], p = 0,006), la retinopathie (HR 2,32 [1,09-4,92], p = 0,029), et le syndrome inflammatoire (HR 0,38 [0,18-0,80], p = 0,011 etaient associes aux evenements ischemiques neurologiques. En analyse multivariee, un delai entre les premiers symptomes et le diagnostic > 1 an (HR 2,12 [1,13-3,97], p = 0,018) et la carotidodynie (HR 2,33 [1,12-4,84], p = 0,023) etaient independamment associes aux evenements ischemiques neurologiques. Le risque relatif d’un nouvel evenement neurologique cerebral ischemique chez les patients ayant deja eu un evenement etait de 5,11 [2,91-8,99] (p Conclusion Les AVC et AIT sont frequents au cours de la maladie de Takayasu, touchant essentiellement le territoire carotidien. Nous avons identifie des facteurs de risque de ces evenements au cours de la maladie.

Introduction La maladie de Behcet est une maladie inflammatoire idiopathique survenant habituellement avant l’âge de 50 ans chez des patients originaires du pourtour mediterraneen, Moyen Orient ou Extreme Orient [1] . L’atteinte neurologique, observee dans 5 a 59 % des cas, correspond le plus souvent a un tableau de meningoencephalite avec des lesions parenchymateuses inflammatoires mais des lesions pseudotumorales sont egalement rapportees [2] . Observation Une patiente senegalaise de 36 ans, sans antecedent, a ete adressee en medecine interne pour cephalees avec hemiparesie et paralysie faciale gauches apparues en 24 heures. L’IRM cerebrale montrait une volumineuse lesion capsulo-lenticulo-thalamique et du pedoncule cerebral a droite, en hypersignal FLAIR et rehaussee au gadolinium, avec compression du ventricule lateral droit. La ponction lombaire retrouvait une meningite lymphocytaire. Devant la presence d’ulcerations orales et genitales, de synovites interphalangiennes et d’une reaction de pathergie, et apres elimination d’un processus infectieux, le diagnostic de maladie de Behcet a ete retenu. Une corticotherapie par bolus intraveineux puis relais oral a ete initiee en association a du cyclophosphamide mensuel (1000 mg) et de l’aspirine. Apres 6 cures, on observait une regression des signes neurologiques et d’imagerie conduisant a un espacement des perfusions. Au moment de la 9e cure, la patiente presentait des troubles de la vigilance et une aphasie, avec une nouvelle lesion inflammatoire atteignant le pedoncule cerebral et le noyau lenticulaire gauches et comprimant le 3e ventricule a l’IRM, et de nouveau une meningite lymphocytaire. La biopsie cerebrale etant jugee trop dangereuse, la prise en charge a consiste en un nouveau traitement d’attaque par corticoides, associe a de l’infliximab et de la colchicine. L’evolution etait favorable jusqu’a une rupture de traitement par la patiente, et dix-huit mois plus tard une readmission pour ralentissement psychomoteur. Il existait alors une hypothermie (32 °C), une bradycardie (54/min) et une hypotension arterielle (100/52 mmHg), une absence de signe de localisation neurologique, et une thrombopenie a 55 000/mm3. La ponction lombaire et l’electro-encephalogramme etaient normaux et l’IRM cerebrale ne montrait que des anomalies sequellaires. Le PET-scanner cerebral retrouvait un hypometabolisme dans les regions hippocampiques et cingulaires. Apres elimination d’autres causes (hypothyroidie, insuffisance surrenalienne), l’hypothermie a ete rapportee a de probables sequelles cerebrales du neuro-Behcet impliquant le systeme limbique. L’utilisation d’une couverture chauffante et l’introduction de clonidine a permis une resolution durable de l’hypothermie avec normalisation de l’etat neurologique et des plaquettes. La colchicine et l’aspirine ont ete reintroduits pour le traitement au long cours de la maladie de Behcet. Discussion Les formes pseudotumorales de neuro-Behcet sont rares, et ont une expression clinique plus aigue et severe. Le traitement de premiere intention est souvent le cyclophosphamide associe a la corticotherapie, mais les anti-TNF alpha presentent un interet dans les formes refractaires [2] . L’atteinte IRM du neuro-Behcet concerne plutot le tronc cerebral pour les formes encephalitiques, et les regions capsulo-thalamiques pour les formes pseudotumorales, mais une etude a observe la presence d’un hypometabolisme significatif dans les regions parahippocampiques et cingulaires chez ces patients, par rapport a des sujets sains et des cas non neurologiques de Behcet, malgre l’absence de lesion observee a l’IRM [3] . La thermoregulation repose sur l’hypothalamus mais egalement sur le systeme limbique dont l’atteinte peut etre responsable d’hypothermie paroxystique. Par analogie avec le syndrome de Shapiro, l’introduction de clonidine a montre un benefice chez notre patiente. Conclusion Nous rapportons un cas rare de neuro-Behcet pseudotumoral responsable d’une hypothermie paroxystique sequellaire.

ObjectiveTakayasu’s arteritis (TAK) is a large vessel vasculitis with important infiltration of proinflammatory T cells in the aorta and its main branches, but its aetiology is still unknown. Our work aims to explore the involvement of Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) signalling pathway in proinflammatory T cells differentiation and disease activity of TAK.MethodsWe analysed transcriptome and interferons gene signatures of fluorescence-activated cell sorting (FACS-sorted) CD4+ and CD8+ T cells from healthy donors (HD) and in 25 TAK (median age of 37.6 years including 21 active TAK with National Institutes of Health (NIH) score >1). Then we tested, in vitro and in vivo, the effects of JAK inhibitors (JAKinibs) in TAK.ResultsTranscriptome analysis showed 248 and 432 significantly dysregulated genes for CD4+ and CD8+ samples between HD and TAK, respectively. Among dysregulated genes, we highlighted a great enrichment for pathways linked to type I and type II interferons, JAK/STAT and cytokines/chemokines-related signalling in TAK. We confirmed by Real Time Reverse Transcription Polymerase Chain Reaction (RT-qPCR) the upregulation of type I interferons gene signature in TAK as compared with HD. JAKinibs induced both in vitro and in vivo a significant reduction of CD25 expression by CD4+ and CD8+ T cells, a significant decrease of type 1 helper T cells (Th1) and Th17 cells and an increase of Tregs cells in TAK. JAKinibs also decreased C reactive protein level, NIH score and corticosteroid dose in TAK patients.ConclusionsJAK/STAT signalling pathway is critical in the pathogenesis of TAK and JAKinibs may be a promising therapy.

The mechanisms regulating inflammation in large vessels vasculitis (LVV) are poorly understood. Interleukin 33 (IL-33) has been shown to license innate and adaptive immunity by enhancing Th2 cytokines production. We aimed to examine the role of IL-33 in the immunomodulation of T cell activation in LVV. T cell homeostasis and cytokines production were determined in peripheral blood from 52 patients with giant cell arteritis (GCA) and 50 healthy donors (HD), using Luminex assay, flow cytometry, quantitative RT-PCR and by immunofluorescence analysis in inflammatory aorta lesions. We found increased level of IL-33 and its receptor ST2/IL-1R4 in the serum of patient with LVV. Endothelial cells were the main source of IL-33, whereas Th2 cells, Tregs and mast cells (MC) express ST2 in LVV vessels. IL-33 had a direct immunomodulatory impact by increasing Th2 and Tregs. IL-33 and MC further enhanced Th2 and regulatory responses by inducing a 6.1 fold increased proportion of Tregs (p = 0.008). Stimulation of MC by IL-33 increased indoleamine 2 3-dioxygenase (IDO) activity and IL-2 secretion. IL-33 mRNA expression was significantly correlated with the expression of IL-10 and TGF-β within aorta inflammatory lesions. To conclude, our findings suggest that IL-33 may exert a critical immunoregulatory role in promoting Tregs and Th2 cells in LVV.

Objective The objective of this study was to describe large-vessel vasculitis (LVV) in patients with human immunodeficiency virus (HIV) infection. It is a retrospective single-center study conducted between 2000 and 2015 through a university hospital of 11 HIV-infected patients with LVV. Methods The characteristics and outcome of 11 HIV-infected patients with LVV (7 patients fulfilled international criteria for Takayasu arteritis, 5 patients had histologic findings of vasculitis, and 5 patients had imaging features of aortitis) were analyzed and compared with those of 82 patients with LVV but without HIV infection. Results Concerning the HIV-infected patients with LVV (n = 11), the mean age was 40 years (range, 36-56 years), and 55% of patients were female. At diagnosis of LLV, the mean initial CD4 cell count was 455 cells/mm 3 (range, 166-837 cells/mm 3 ), and the median HIV viral load was 9241 copies. Vascular lesions were located in the aorta (n = 7), in supra-aortic trunks (n = 7), and in digestive arteries (n = 3). Inflammatory aorta infiltrates showed a strong expression of interferon-γ and interleukin 6. In HIV-negative LVV patients (n = 82), the median age was 42 years, and 88% of the patients were women. Thirty patients had an inflammatory syndrome. Seventy patients had been treated with glucocorticosteroids and 57 with immunosuppressive treatments. Compared with their negative counterparts, HIV-positive patients with LVV were more frequently male ( P = .014), had more vascular complications (ie, Ishikawa score; P = .017), and had more frequent revascularization ( P = .047). After a mean follow-up of 96 months, four relapses of vasculitis were reported, and one patient died. Regardless of the HIV virologic response, antiretroviral therapy improved LVV in only one case. Conclusions LVV in HIV-infected patients is a rare and severe entity.

Introduction La maladie de Behcet (MB) est une affection inflammatoire et systemique chronique evoluant par poussees. Elle est caracterisee par l’atteinte de plusieurs organes dont les muqueuses (aphtes) et la peau (pseudo-folliculites). La physiopathologie de la MB est en grande partie inconnue. Le role de l’immunite innee semble preponderant avec notamment une activation des polynucleaires neutrophiles. La voie NF-κB, engagee des le contact d’un ligand sur le recepteur 1 du facteur de necrose tumorale (TNFR1), joue un role critique dans l’engagement du processus inflammatoire car elle produit des cytokines majeures comme l’interleukine 1 (IL-1), l’IL-6 et le facteur de necrose tumorale α (TNF- α). Sa regulation negative est essentielle a l’arret du processus inflammatoire et depend du niveau d’ubiquitination des proteines associees au TNFR1 et d’autres composes intermediaires. A20 et OTULINE sont des proteines qui modifient cette ubiquitination et leur defaut resulte en une activation de la voie NF-κB avec production excessive de cytokines proinflammatoires. L’haploinsuffisance de A20 partage avec la maladie de Behcet l’aphtose bipolaire et l’uveite, mais elle s’en distingue par sa transmission dominante, un debut des symptomes plus precoce, et une atteinte digestive severe au premier plan. Des lymphocytes T CD8+ (LT CD8 + ) secretant de l’interferon-γ (IFN-γ) et du TNF-α. ainsi que des mediateurs de cytotoxicite ont ete retrouve dans le sang peripherique et l’humeur aqueuse des patients atteints de MB, indiquant qu’ils pourraient ainsi participer a la physiopathologie de la MB. La phosphodiesterase 4 (PDE4) une enzyme du systeme immunitaire qui, en degradant l’adenosine monophosphate cyclique (AMPc), augmente la secretion de mediateurs de l’inflammation. Sachant que l’AMPc induit l’inhibition de la voie NF-κB, sa degradation entraine une augmentation de cette importante voie de l’inflammation. L’Apremilast est une molecule administree oralement qui inhibe la PDE4. Bien que ses mecanismes d’action precis ne soient pas connus dans la MB, l’Apremilast s’est revele efficace dans le traitement des manifestations cutaneo-articulaires de la MB. Resultats Methodes et resultats: Trente-cinq patients atteints de MB et 34 temoins apparies sur l’âge et le sexe ont ete inclus. L’analyse du transcriptome des LT CD8+ a permis de montrer qu’il existait un enrichissement des voies de signalisation NF-κB, de l’immunite innee et de l’inflammation dans les LT CD8+ de patients compares aux temoins. Nous avons confirme par cytometrie en flux la surexpression de pNF-κB dans les LT CD8+ de patients (4,4 ± 0,9 vs. 1,8 ± 0,2 en MFI, p = 0,001). L’analyse transcriptomique de LT CD8+ a egalement montre un enrichissement des isoformes de PDE4 (A, B, C et D) chez les patients atteints de MB par rapport aux temoins. L’analyse en immunohistochimique a confirme cette surexpression de PDE4 dans les lesions cutanees de patients. Nous avons ensuite evalue l’effet in vitro par cytometrie en flux du Roflumilast (un inhibiteur de PDE4) sur les LT CD8+ de patients et de temoins. Les LT CD8+ de patients exprimaient davantage de marqueurs d’activation de surface (CD11c, CD11b, CD25 et CD69), intracellulaires (IFN-γ et TNF-α), de cytotoxicite (Perforine et Granzyme B) et de proliferation par rapport aux LT CD8+ de temoins. Le traitement par Roflumilast abrogeait specifiquement l’expression de ces differents marqueurs d’activation et de fonctionnalite. Enfin nous avons confirme ces resultats in vivo. Les LT CD8+ de 10 patients traites par Apremilast (30 mg 2 fois par jour) ont ete analyse avant et apres 12 semaines de traitement. Les marqueurs d’activation de surface (CD11c, CD11b, CD25 et CD69), intracellulaires (IFN-γ, TNF-a), de cytotoxicite (Perforine et Granzyme B) et de proliferation diminuaient significativement apres 12 semaines de traitement. Conclusion Nous avons mis en evidence in vitro et in vivo l’implication de la voie NF-κB dans l’activation des LT CD8+ de patients atteints de MB. Nous avons egalement pu montrer qu’elle etait, au moins en partie, mediee par PDE4 et qu’elle etait pharmacologiquement reversible.

Introduction La sarcoidose est une pathologie inflammatoire systemique d’etiologie inconnue et de presentation heterogene, dont le diagnostic repose sur un faisceau d’arguments du fait de l’absence de test specifique. L’objectif de cette etude etait d’evaluer la valeur du dosage du recepteur soluble de l’interleukine 2 (sIL2R), marqueur de l’activation lymphocytaire T, pour le diagnostic et l’evolutivite de la sarcoidose. Patients et methodes Cette etude prospective concernait tous les patients admis dans le service de medecine interne de l’Hopital Lariboisiere (APHP) avec une suspicion de sarcoidose ou une sarcoidose averee, entre novembre 2019 et decembre 2020. Les donnees recueillies etaient celles permettant le diagnostic de sarcoidose : atteintes cliniques, donnees biologiques incluant l’enzyme de conversion de l’angiotensine (ECA), donnees histologiques (presence d’un granulome sans necrose) ; ainsi que la presence de traitement. La maladie etait consideree active au diagnostic ou en presence de manifestations cliniques et paracliniques justifiant une adaptation therapeutique au decours du bilan. Le dosage du sIL2R etait realise au Centre Hospitalier Lyon Sud, avec un seuil de positivite a 1425 pg/mL. L’analyse statistique reposait sur la mesure de la sensibilite et de la specificite du dosage, et sur des tests statistiques univaries (Chi2). Resultats Cinquante-sept patients ont ete inclus dans l’etude, dont 32 femmes (56,1 %) avec un âge moyen de 46,4 ans (ecart-type 15,8 ans). Dans 28 sur 51 cas (49,1 %), il y avait un granulome objective sur biopsie. Un diagnostic de sarcoidose etait effectif chez 27 patients (47,4 %). Les principales manifestations etaient ganglionnaires (22 cas, 81,5 %) et pulmonaires (17 cas, 63 %), et 88,9 % presentaient du granulome (24 cas). Neuf patients (33,3 %) faisaient l’objet d’un diagnostic initial de sarcoidose, et la plupart des patients (16 soit 59,3 %) avaient une maladie active au moment du bilan. Quatorze patients etaient sous traitement (51,3 %) dont douze sous corticotherapie. Trente patients avaient un diagnostic differentiel : uveite idiopathique (n = 10), tuberculose (n = 6), lymphome (n = 2), autres (n = 12). Le taux moyen de sIL2R etait de 2494,9 pg/mL (ecart-type 3233,4 pg/mL), avec 51,9 % de positivite, chez les patients atteint de sarcoidose, contre 1679,4 pg/mL (ecart-type 1088,7 pg/mL) avec 50 % de positivite dans les autres diagnostics, sans difference significative (p = 0,9). Pour l’ECA, les taux moyens etaient respectivement de 77,7 UI/L (ecart-type 48,5 UI/L) et 36,3 UI/L (ecart-type 23,5 UI/L), les taux de positivite de 48,1 % et 8,7 % (p = 0,002). La specificite de l’ECA etait meilleure (91,3 % versus 50 %). Les taux seriques de sIL2R et d’ECA etaient plus souvent eleves en presence qu’en l’absence d’un granulome, quel qu’en soit le diagnostic (60,7 % versus 30,4 % ; p = 0,03 ; 48,1 % versus 10,5 % ; p = 0,007, respectivement). Chez les patients sarcoidosiques, le taux serique de sIL2R etait plus eleve chez les patients ayant une sarcoidose active que chez ceux ayant une sarcoidose quiescente (3424,9 versus 1142,1 pg/mL) de meme que le taux de positivite (75 % versus 18,2 % ; p = 0,004). Le taux de positivite de l’ECA etait de 62,5 % chez les patients ayant une sarcoidose active contre 27,3 % chez ceux ayant une sarcoidose quiescente (p = 0,07), avec des taux seriques respectivement de 91,8 UI/L et 57,2 UI/L. Pour les 16 patients atteints d’uveite, dont 6 atteints de sarcoidose (37,5 %), la sensibilite du dosage du sIL2R et de l’ECA etait respectivement a 66,7 % et 50 %. Discussion Dans notre serie, le dosage du sIL2R presentait une sensibilite faible pour le diagnostic de sarcoidose tout comme l’ECA meme si ce dernier presentait une meilleure specificite. Dans la litterature, les chiffres de sensibilite et specificite du sIL2R sont tres variables (respectivement 63-82 % et 57-100 %), et il pourrait y avoir une meilleure sensibilite dans le contexte d’uveite (82-98 %) [1] , tout comme dans notre etude. Chez les patients ayant une sarcoidose, les taux seriques de sIL2R sont significativement associes au degre d’activite, avec une meilleure correlation que l’ECA, comme cela est rapporte dans d’autres etudes [1] , [2] . Conclusion Le sIL2R ne semble pas etre suffisamment discriminant comme test diagnostique de sarcoidose mais semble etre un meilleur biomarqueur d’activite que l’ECA.

Background: Because of the wide variation in the course of Takayasu arteritis (TA), predicting outcome is challenging. We assess long-term outcome and prognosis factors for vascular complications in patients with TA. Methods: A retrospective multicenter study of characteristics and outcomes of 318 patients with TA fulfilling American College of Rheumatology and Ishikawa criteria was analyzed. Factors associated with event-free survival, relapse-free survival, and incidences of vascular complications were assessed. Risk factors for vascular complications were identified in a multivariable model. Results: The median age at TA diagnosis was 36 [25–47] years, and 276 patients (86.8%) were women. After a median follow-up of 6.1 years, relapses were observed in 43%, vascular complications in 38%, and death in 5%. Progressive clinical course was observed in 45%, carotidodynia in 10%, and retinopathy in 4%. The 5- and 10-year event-free survival, relapse-free survival, and complication-free survival were 48.2% (42.2; 54.9) and 36.4% (30.3; 43.9), 58.6% (52.7; 65.1) and 47.7% (41.2; 55.1), and 69.9% (64.3; 76.0) and 53.7% (46.8; 61.7), respectively. Progressive disease course ( P =0.018) and carotidynia ( P =0.036) were independently associated with event-free survival. Male sex ( P =0.048), elevated C-reactive protein ( P =0.013), and carotidynia ( P =0.003) were associated with relapse-free survival. Progressive disease course ( P =0.017), thoracic aorta involvement ( P =0.009), and retinopathy ( P =0.002) were associated with complication-free survival. Conclusions: This nationwide study shows that 50% of patients with TA will relapse and experience a vascular complication ≤10 years from diagnosis. We identified specific characteristics that identified those at highest risk for subsequent vascular complications.

Introduction: Treatment of systemic vasculitis is based on glucocorticoids (GC) in association with immunosuppressive therapy. There are still unmet needs, including earlier onset of response, more targeted therapies, reduction of relapse-risk and decrease of long-term GC and classic immunosuppressants toxicities.Areas covered: In this review, we discuss investigational drugs in early phase clinical trials for induction of remission in vasculitis. We focus on ANCA-associated vasculitis, Behcet’s disease, giant cell arteritis, Takayasu arteritis, and cryoglobulinemic vasculitis. We performed a comprehensive review of articles published on pubmed and a review of clinical trials registered online (https://clinicaltrials.gov) for each vasculitis.Expert opinion: Recent progress in the pathogenesis identifies new therapeutic targets. Some of these therapies are promising in GC sparing effects, in reducing relapse rate, and for their safety profile. These results need to be confirmed in large-scale phase...

International audience; Myocarditis is a major cause of heart disease in young patients and a common precursor of heart failure due to dilated cardiomyopathy. Some auto-immune and/or auto-inflammatory diseases may be accompanied by myocarditis, such as sarcoidosis, Behçet's disease, eosinophilic granulomatosis with polyangiitis, myositis, and systemic lupus erythematosus. However, data concerning myocarditis in such auto-immune and/or auto-inflammatory diseases are sparse. New therapeutic strategies should better target the modulation of the immune system, depending on the phase of the disease and the type of underlying auto-immune and/or auto-inflammatory disease.

Takayasu disease is a large-vessels vasculitis involving the aorta and its main branches. The main symptoms are constitutionals signs and those in relation to vascular damage. Acute phase reactants can be discordant with the disease activity and imaging tools are crucial to determine the affected arterial sites and the vascular complications. The active inflammatory nature of arterial lesions can be difficult to determine, and the value of functional imaging such as FDG PET should be discussed. The treatment includes the immunosuppressive treatment in case of active disease, cardiovascular risk prevention and management of adverse events related to immunosuppressive drugs. The arterial revascularization should also be considered if necessary and regular monitoring is mandatory., La maladie de Takayasu est une vascularite des gros vaisseaux touchant l’aorte et ses branches principales. Les signes principaux sont les signes généraux et les signes en rapport avec l’atteinte vasculaire. Le syndrome inflammatoire peut être discordant avec l’activité de la maladie et l’imagerie est primordiale pour déterminer les sites artériels touchés et les complications éventuelles. Le caractère inflammatoire des lésions artérielles peut être difficile à déterminer, et la place des méthodes d’imagerie fonctionnelle telle que la TEP-FDG peut se discuter. La prise en charge comprend le traitement immunosuppresseur si la maladie est active, les traitements symptomatiques à visée cardiovasculaire et en prévention des effets secondaires des immunosuppresseurs, ainsi qu’en cas de nécessité la revascularisation artérielle. La surveillance régulière est nécessaire pour dépister une progression artérielle et les complications vasculaires.

Graphical abstract, Hepatitis C virus (HCV) infected patients are known to be exposed to major liver complications i.e. cirrhosis and hepatocellular carcinoma. In addition, many extrahepatic manifestations including rheumatologic disorders have been reported in up to two-third of HCV infected patients. These manifestations include frank auto-immune and rheumatic diseases (such as arthralgia, myalgia, arthritis, sicca syndrome and vasculitis) which may dominate the course of infection. Until recently, the standard of care of HCV has been the use of interferon-alpha based regimens, which not only had limited effectiveness in HCV cure but were poorly tolerated. In patients with rheumatic diseases interferon-based regimens may be problematic given their association with a wide variety of autoimmune toxicities. Recent therapeutic advances with new direct anti-HCV therapies (interferon-free) which are more effective and better tolerated, make screening for this comorbidity in patients with rheumatic disorders more important than ever. This review aimed to outline main HCV extrahepatic with a special focus on rheumatologic manifestations.

La maladie de Takayasu (TAKA) est une vascularite inflammatoire chronique d’etiologie inconnue, touchant preferentiellement l’aorte et ses principales branches. L’inflammation vasculaire peut conduire a des stenoses, des occlusions, voire des anevrysmes arteriels entrainant ou non des symptomes cliniques. Ses manifestations cliniques sont tres variees et dependent du type de vaisseaux touches et du type de lesions (stenose ou occlusion), notamment au niveau de la crosse aortique, de l’aorte thoracique descendante, de l’aorte abdominale, des arteres renales, des arteres coronaires, voire des arteres pulmonaires et des lesions ischemiques secondaires. Du fait de la grande variabilite des lesions arterielles et de leur evolutivite, la recherche de facteurs predictifs d’evolution defavorable revet un caractere particulierement important. Peu d’etudes ont analyse les facteurs pronostiques defavorables et ont ete releves sur des etudes de petite taille ou avec un recul peu important : hypertension arterielle, retinopathie ischemique, insuffisance aortique, anevrysme arteriel, evolution progressive de la maladie, type V de la maladie. Patients et methodes Pour essayer de mieux cerner le pronostic a long terme et les facteurs pronostiques defavorables, nous avons mene une etude collaborative nationale francaise qui a permis d’inclure 318 patients ayant une maladie de Takayasu, d’âge median au diagnostic 36 ans, 87 % de femmes avec un suivi median de 6,1 ans, d’origine caucasienne (37 % des cas), d’Afrique du Nord (31 %), d’Afrique subsaharienne (24 %). Les principaux types de lesions arterielles etaient des stenoses (77 %), des epaississements (62 %), des anevrysmes (24 %) ou des occlusions arterielles (19 %). Resultats Au total, 178/318 (56 %) patients ont eu au moins un evenement « qualifiant » (complications vasculaires et/ou rechute et/ou deces). La survie globale sans evenement etait, a 1 an, 5 ans et 10 ans, de 75,6 %, 48,2 % et 36,4 % respectivement. La survie sans rechute etait, a 1 an, 5 ans et 10 ans, de 81,1 %, 58,6 % et 47,7 %. La survie sans complication vasculaire etait, a 1 an, 5 ans et 10 ans, de 90 %, 69,9 % et 53,7 %. En analyse multivariee, les facteurs significativement associes a une rechute etaient la presence d’une carotidodynie (HR : 2,36) et une elevation de la CRP (HR : 2,09). Les facteurs associes a une complication ischemique etaient l’evolution progressive de la maladie (HR : 2,03), une atteinte de l’aorte thoracique (HR : 2,74) et la presence d’une retinopathie (HR : 3,4). Ces donnees ont permis de definir un score clinique pronostique permettant de mieux identifier les patients a haut risque de complications (deces et/ou de complications vasculaires) si au moins deux des facteurs suivants etaient presents : maladie d’evolution progressive, atteinte de l’aorte thoracique et retinopathie. Pour la mortalite, les risques a 10 ans dans cette etude etaient de 5 % (versus 7 a 24 % dans la litterature). Un sur-risque de mortalite a ete retrouve chez les patients blancs, fumeurs et de sexe feminin. Quelle strategie therapeutique medicale Les donnees experimentales et une meilleure comprehension des mecanismes physio-pathogeniques sous-jacents ont revele un role important de l’activation des cellules dendritiques, amenant a une activation des cellules T et notamment une polarisation des lymphocytes Th1 et Th17. La voie Th1 mediee par l’IL12, l’IL18 et l’interferon Gamma, permet un recrutement des monocytes amenant a la production de cytokines pro-inflammatoires telles que TNF-Alpha, IL6, IL1-beta et aboutissant aux symptomes systemiques de la vascularite. La voie Th17 mediee par l’IL6, l’IL23, l’IL1-beta a egalement un role important, notamment pour le remodelage vasculaire, l’hyperplasie intimale et les stenoses ou occlusions vasculaires amenant aux symptomes ischemiques. L’utilisation d’une corticotherapie apparait encore indispensable (0,5 a 1 mg/kg/jour). L’association a un immunosuppresseur est fortement conseillee, meme si les donnees reposent essentiellement sur des etudes de petit effectif, avec des limites methodologiques importantes et des suivis peu prolonges. Les meta-analyses suggerent que l’ajout d’un immunosuppresseur conventionnel (methotrexate, azathioprine, cyclophosphamide, mycophenolate) a une corticotherapie permet d’augmenter d’environ 40 % les chances de mise en remission, et de diminuer d’environ 45 % le risque de rechute. Les donnees plus recentes collaboratives francaises suggerent que certaines biotherapies (anti-TNF, anti-IL6) amenent un benefice encore superieur puisque, comparees aux immunosuppresseurs conventionnels, le risque de rechute a 6 ans etait respectivement de 10 % versus 65 %. Dans une meta-analyse recente, les biotherapies etaient associees a une augmentation d’environ 36 % des chances de mise en remission et une diminution d’environ 70 % du risque de rechute. Enfin, la seule etude controlee randomisee japonaise comparant le tocilizumab (anti-IL6) a un placebo chez 36 patients a montre, apres un suivi de 3 ans, une diminution du risque de rechute (50 % versus 20 % ; HR : 0,41). En conclusion, la maladie de Takayasu est caracterisee par une morbidite importante. Un score pronostique permet de predire le risque de complications (retinopathie, forme progressive de la maladie, atteinte de l’aorte thoracique). Sur le plan therapeutique, a cote de la corticotherapie et des immunosuppresseurs conventionnels, plusieurs etudes recentes ont montre l’interet des biotherapies, notamment anti-TNF et anti-IL6. D’autres etudes en cours devraient permettre d’ameliorer encore le pronostic de cette vascularite systemique qui reste encore redoutable.

Introduction L’arterite gigantocellulaire (AGC) et la maladie de Takayasu (TAK) sont les 2 principales formes de vascularite des gros vaisseaux. Peu de donnees sur les facteurs pronostics des vascularites des gros vaisseaux et sur la comparaison de l’evolution a long terme de ces 2 vascularites sont disponibles. Le but de cette etude etait de determiner les facteurs pronostics des vascularites des gros vaisseaux et de comparer l’evolution a long terme de l’AGC et de la maladie de Takayasu. Patients et methodes Nous avons conduit une etude multicentrique retrospective chez 417 patients presentant une vascularite des gros vaisseaux, dont 299 TAK et 118 AGC remplissant respectivement les criteres d’Ishikawa et de l’ACR et presentant une atteinte des gros vaisseaux. Les caracteristiques cliniques, biologique et radiologique et le pronostic des atteintes des gros vaisseaux (complications ischemiques et anevrysmales, rechutes et revascularisations) ont ete analyses. Resultats Dans le groupe AGC, les patients etaient significativement plus âges, de sexe masculin et caucasien, comparativement au groupe TAK. La proteine C reactive etait significativement plus elevee dans le groupe AGC comparativement au groupe TAK (79,5 [43,8–141] et 23 [7–67,5], p Parmi l’ensemble des vascularites des gros vaisseaux, le tabagisme [hazard ratio (HR) : 1,82 (IC95 % : 1,1–3), p = 0,019], les accidents cerebraux ischemiques [HR : 3,24 (1,64–6,42), p = 0,0008], les arthralgies [HR : 0,54 (0,3–0,98), p = 0,041] et l’atteinte des arteres cerebrales [HR : 3,09 (1,47–6,47), p = 0,003] etaient associees aux complications vasculaires ischemiques et anevrysmales (survie sans evenement) en analyse univariee. En analyse multivariee, les accidents cerebraux ischemiques [HR : 3,72 (1,65–8,39), p = 0,002] etaient independamment associees a un plus mauvais pronostic alors que la claudication des membres etait associe a un meilleur pronostic [0,51 (0,29–0,9), p = 0,019]. L’âge et les traitements n’etaient pas associe a la survie sans evenement en analyse uni et multivariee. La survie sans evenement et la survie sans ischemie n’etait pas significativement differente entre les 2 groupes. La survie sans anevrysmes a 5 et 10 ans etait significativement plus basse dans le groupe AGC (84 % [75–94] et 67 % [48–93]) comparativement aux patients TAK (93 % [89–96] et 89 % [84–95]), p = 0,02. La survie sans rechute etait significativement plus basse chez les patients AGC (47 % [37–60] et 0 %) comparativement au groupe TAK (69 % [63–75] et 26 % [20–34]), p Les principales causes de deces, dans les 2 groupes, etaient liees aux complication vasculaires anevrysmales (26 %) ou ischemiques (26 %). Conclusion Cette large etude de cohorte de vascularite des gros vaisseaux montre que la survenue d’un accident vasculaire cerebrale est un facteur de mauvais pronostic. L’AGC et la maladie de Takayasu ont des profils evolutifs differents en termes de complication vasculaire a long terme, de rechute et de revascularisation.

Introduction Jusqu’a une periode recente, les cryoglobulinemies mixtes (CM) (type II et type III) etaient associees dans 70–90 % des cas a une infection chronique par le virus de l’hepatite C (VHC). L’avenement des agents antiviraux directs (AAD) disponibles en France depuis plusieurs annees a completement revolutionne la prise en charge de l’hepatite C chronique. L’objectif de cette etude est de decrire l’incidence, les principales etiologies, les manifestations cliniques et les parametres biologiques des CM a l’ere des AAD. Patients et methodes Nous avons mene une etude longitudinale retrospective monocentrique sur la periode 2011–2018, a partir de 15 970 patients testes a l’hopital de La Pitie-Salpetriere pour une recherche de CM. Parmi ces patients, 679 (4,3 %) presentaient une CM > 0,05 g/L sur au moins deux prelevements et ont fait l’objet de l’analyse. Les variables qualitatives sont presentees avec les effectifs assortis des pourcentages. Les variables quantitatives sont presentees sous la forme suivante : effectif/mediane (ecart interquartile). Une valeur p Resultats Parmi les 679 patients inclus (âge median 55 ans, 54,6 % femmes), 373 (54,9 %) avaient une cryoglobulinemie de type II et 306 (45,1 %) de type III. Cent trente-neuf patients (21,5 %) etaient symptomatiques avec des manifestations de vascularite systemique (purpura [54,7 %], neuropathie peripherique [49,6 %], glomerulonephrite membranoproliferative [21,6 %] et arthrite [10,1 %]). Pour les cryoglobulinemies de type II, le composant monoclonal etait une IgM kappa (46,2 %), IgG kappa (13,4 %) et IgM lambda (11,3 %). Sur la periode de l’etude la cause la plus frequente de CM etait l’infection par le VHC (56 %). Les autres causes etaient le lupus systemique (28,9 %), le syndrome de Sjogren (10,7 %), les lymphomes non-Hodgkiniens (5,4 %), le VIH (4,4 %) et la macroglobulinemie de Waldenstrom (4,0 %). La CM etait consideree comme essentielle dans 23,8 % des cas. Les patients avec une CM associee au VHC comparativement a ceux d’autre cause etaient plus frequemment des hommes (51,7 % vs 37,2 %, p Conclusion Depuis l’avenement des AAD les caracteristiques cliniques et biologiques de la CM sont en train de changer. Dans notre cohorte, l’infection par le VHC ne represente plus que la seconde cause de CM, derriere les maladies auto-immunes. Compte tenu des reponses virologiques soutenues apres AAD ( > 95 %), l’incidence de la CM associee au VHC devrait encore diminuer.

Introduction Les aortites non infectieuses peuvent survenir au cours de differentes maladies systemiques comme l’arterite a cellules geantes (ACG) ou l’arterite de Takayasu (AT), ou de facon isolee sans autre signe systemique. Dans cette etude, nous avons analyse la survie globale, la survie sans evenements et les facteurs pronostiques des aortites isolees (AI) comparativement aux aortites au cours de l’ACG ou l’AT. Patients et methodes Cette etude francaise retrospective inclue des patients avec une aortite non infectieuse isolee ou dans le cadre d’une ACG ou d’une AT. Une aortite etait definie par un epaississement de la paroi aortique > 2 mm a l’imagerie et/ou une preuve histologique. Les patients avec une ACG ou une AT repondaient aux criteres de la classification ACR. L’AI etait definie par la presence d’une vascularite isolee sur un segment aortique sans criteres pour une ACG ou une AT ou une autre maladies systemiques. La survenue d’evenements tels que le deces, une revascularisation chirurgicale, un anevrysme, une dissection, un faux anevrysme ou une ulceration ont ete analyse en tant que donnees de survie. Resultats Parmi les 353 aortites non infectieuses identifiees, 73 (21 %) etaient des aortites isolees, 96 (27 %) survenaient au cours de l’AT, 136 (39 %) au cours de l’ACG et 48 (14 %) au cours d’une autre maladie systemique. L’âge median au diagnostic d’aortite etait de 70 (64 ; 76) ans pour les aortites d’ACG, 64 (54 ; 71) ans pour les aortites isolees et 39 (25 ; 49) ans pour les aortites d’AT (p Conclusion Apres 5 ans de suivi dans cette etude, plus de 50 % des aortites isolees necessitaient un geste de revascularisation et presque 60 % avaient une complication vasculaire. Parmi les aortites non infectieuses, les aortites isolees en comparaison aux aortites de l’ACG et de l’AT sont associees a un moins bon pronostic. Le sexe masculin est egalement un facteur de moins bon pronostic.

Background: Takayasu’s arteritis (TA) and giant cell arteritis (GCA), the two most common types of large vessel vasculitis (LVV), are characterized by an arterial inflammatory granulomatous infiltrate mainly located in the media and the adventitia. However, distinct histological features of the immune response are poorly known. Objectives: To investigate distinct pathological mechanisms of the immune response in patients with GCA and TA. Methods: We performed comparative immunohistochemistry analysis of aorta of GCA and TA patients. We performed microarray gene analysis of purified CD4+ T cells of TA and GCA patients. Reverse transcriptase PCR, flow cytometry analysis and cell culture were used to investigate T and B cells subpopulations in 54 patients with TA, 52 with GCA and 60 controls. Results: We found higher proportion of tertiary lymphoid structures composed of CXCR5+, CD4+, PD-1+ and CD-20+ cells in inflammatory aortic lesions in TA as compared to GCA. We demonstrated increased proportion of aortic B cells in TA. We next evaluated differentiation of circulating CD4+ T cells in both diseases. Among sixty-seven genes differentially expressed in CD4+ T cells of TA compared to GCA patients, we identified a specific “T follicular helper” (Tfh) signature in TA patients. We also found a specific Tfh 17 signature in TA patients. Flow cytometry analysis confirmed increased circulating Tfh, defined as CXCR5+ CD4+ T cells, in TA patients as compared to GCA and healthy donors (HD) [median of 15.4 (10;30.8)% versus 5.3 (1.4; 12.2)% and 9.7 (5.6; 12.5)% (p Functionally, CXCR5+ CD4+ T cells of TA patients helped B cells to differentiate into memory cells, to proliferate and to secrete type G immunoglobulins. We sequenced the TCR repertoire α/β in CD3+CD4+CXCR5- and CD3+CD4+CXCR5+ cells, in aortic and blood samples from 2 patients. In both patients, we identified oligoclonal profile of TCR repertoire only for aortic CXCR5+ cells, suggesting antigenic selection of CXCR5+ CD4+ T cells. Conclusion: We provide evidence of the presence of tertiary lymphoid structures composed of Tfh and B cells in TA aorta. We identified a specific Tfh signature in circulating CD4+ T cells that distinguishes TA and GCA patients. The key cooperation of Tfh and B cells in TA and the oligoclonal repertoire of CXCR5+ CD4+ T cells strongly suggest the role of antigenic trigger. Disclosure of Interests: Anne-Claire DESBOIS Speakers bureau: SOBI en 2015, Anna Maciejewski-Duval: None declared, Paul Regnier: None declared, Valentin QUINIOU: None declared, Cloe Comarmond: None declared, Helene Vallet: None declared, Patrick Bruneval: None declared, Pierre Fouret: None declared, Michele Rosenzwajg: None declared, David Klatzmann: None declared, Fabien Koskas: None declared, Marlene Garrido: None declared, Guillaume Darrasse-Jeze: None declared, Patrice cacoub Consultant for: d’Abbvie, Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Glaxo Smith Kline, Janssen, Merck Sharp Dohme, Pfizer, Roche, Servier, and Vifor., Speakers bureau: d’Abbvie, Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Glaxo Smith Kline, Janssen, Merck Sharp Dohme, Pfizer, Roche, Servier, and Vifor., David Saadoun Grant/research support from: Roche, Abbvie, Consultant for: Janssen, Celgene, Abbvie, Roche

International audience; Hepatitis C virus (HCV) infection has been demonstrated to result in several adverse hepatic outcomes and has been associated with a number of important extrahepatic manifestations. The scope of extrahepatic clinical possibilities includes systemic diseases such as vasculitis and lymphoproliferative disorders, cardiovascular disease, myalgia, arthritis, and sicca syndrome. These end-organ effects of HCV may dominate the clinical course beyond the hepatic complications and significantly worsen the long-term prognosis of infected patients. Until several years ago, the standard of care for the treatment of HCV infection had been interferon-alpha-based regimens, which not only had limited effectiveness in achieving a cure but were often poorly tolerated, especially in patients with kidney disease. In those HCV-infected patients with significant systemic manifestations, the interferon-based regimens were problematic given their association with a wide variety of toxicities. The development of highly effective direct-acting antiviral agents to treat HCV infection presented an opportunity to improve the HCV care cascade with the eradication of HCV in most infected patients and by reducing the burden of both hepatic and extrahepatic complications.

Introduction Analyser l’efficacite et la tolerance des biotherapies (TNFa et tocilizumab) chez les patients avec une maladie de TAKAYASU. Patients et methodes Etude retrospective europeenne de 2017-2019, incluant les patients ayant au moins 3 mois de biotherapie. La reponse au traitement etait definie en cas de NIH Resultats Deux cents trois patients ont ete inclus, avec un âge 29 ans [7–62], et 180 (89 %) de sexe feminin. Selon NUMANO, 20 patients (10 %) etait de type I, 68 (33 %) de type II, 14 (7 %) de type III, 8 (4 %) IV et 90 (44 %) de type V. Les biotherapies etaient des anti-TNF-α (n = 130 ; 63 % avec au total 173 lignes de differents types anti-TNF-α) ou tocilizumab (n = 75 ; 37 % avec 122 lignes de tocilizumab SC ou IV). Des anti-TNF-α etaient l’infliximab (n = 109), l’adalimumab (n = 45), l’etanercept (n = 5), golimumab (n = 8), certolizumab (n = 5) et parmi les 122 lignes de tocilizumab, IV dans 96 et SC dans 26 cas. Une reponse complete (NIH Conclusion Cette serie europeenne permet de decrire les profils de reponse et de tolerance des differentes biotherapies au cours de la maladie de TAKAYASU.

Introduction Les ulceres buccaux (UB) et genitaux (UG) recurrents representent la pierre angulaire de la maladie de Behcet (MB) et peuvent etre tres douloureux, affectant considerablement la qualite de vie. La colchicine ne permet pas de controler efficacement l’ensemble des patients. Un grand nombre de medicaments topiques et immunomodulateurs peuvent etre utilises dans ce contexte [1] , mais un niveau de preuve reste limite. L’efficacite de l’apremilast, un inhibiteur de la phosphodiesterase-4, a ete demontree dans des essais randomises dans les ulcerations muqueuses de la MB [2] , et de petites cohortes ont confirme cet effet [3] , [4] . Cependant, la prevalence et l’impact des effets secondaires dans des phases IV n’ont pas ete evalues dans des echantillons plus importants. De plus, l’efficacite de l’apremilast sur d’autres manifestations de la MB, notamment articulaires, fait toujours defaut. Resultats Pour tenter de repondre a ces questions, nous avons recueilli les donnees de 49 patients (55 % etaient de sexe feminin, avec un âge moyen de 42,4 ans (± 13) et un suivi median de 9 mois [3–14]) atteints de MB dans sept centres francais. Les patients etaient auparavant refractaires a la colchicine (n = 48), aux DMARD conventionnels synthetiques (n = 21) et/ou biologiques (n = 9; anti-TNF = 5). Le nombre median de lignes therapeutiques avant le debut de l’apremilast etait de 2 [2] , [3] . Six patients n’ont pas tolere le traitement des la premiere semaine et n’ont donc pas pu etre evalues pour la reponse therapeutique. Parmi les 43 patients restants, 22 (51 %) ont presente une reponse complete definie par la resolution totale du tableau clinique, tandis que 18 (42 %) ont eu une reponse partielle, definie par l’amelioration d’au moins 50 % des symptomes. En evaluant separement chaque manifestation de la maladie a la fin du suivi, les reponses completes et partielles etaient de 58 % et 34 % pour les ulceres buccaux (n = 41), 71 % et 17 % pour les ulceres genitaux (n = 24), 53 % et 42 % pour les manifestations cutanees (n = 17), et 48 % et 22 % pour les manifestations articulaires (n = 27). La mediane de l’echelle d’activite du syndrome de Behcet (BSAS) est passee de 50 [40–60] au debut de l’etude a 20 [5–40] a la fin du suivi. En parallele, pour les 15 patients sous corticoides, le dosage median a diminue de 8 [8–15] a 5 [5–8,5] au cours du suivi. 31 patients (63 %) de l’ensemble de la cohorte ont subi au moins un effet indesirable au cours du suivi, et 15 (30 %) d’entre eux ont definitivement interrompu le traitement en raison d’effets secondaires. Le temps median avant l’apparition des effets secondaires etait d’une semaine [0,4–4]. La diarrhee a ete observe chez 18 (36 %) patients, etant l’effet secondaire le plus frequent, suivie par les nausees (35 %) et les maux de tete (32 %). Conclusion Cette etude rapporte la plus grande cohorte de vie reelle de patients atteints de la MB sous apremilast. Bien que le taux global d’effets indesirables rapporte soit plus faible que celui des essais cliniques [2] , l’arret du traitement du a ces effets semble etre significativement plus eleve dans la vie reelle.

Introduction Les vascularites des gros vaisseaux dont la maladie de Takayasu sont des pathologies inflammatoires responsables d’un remodelage de la paroi arterielle conduisant a la formation de stenose ou d’anevrysmes. Les mecanismes physiopathologiques impliques dans ce remodelage ne sont pas connus. Les mastocytes sont des cellules cles dans le remodelage vasculaire comme cela a ete montre dans diverses pathologies telles que l’anevrysme de l’aorte abdominale, l’infarctus du myocarde et l’atherosclerose. L’objectif de cette etude etait d’etudier le role des mastocytes dans la remodelage vasculaire des patients atteints de maladie de Takayasu. Resultats Methodes et Resultats Trente patients atteints de maladie de Takayasu et 20 temoins apparies sur l’âge et le sexe ont ete inclus. Nous avons tout d’abord montre que les patients avaient des taux d’histamines seriques plus eleves que les temoins [11,23 ± 1,3 vs 7,15 ± 0,5 nM, p = 0,008] et que le serum des patients activait de facon plus importante des mastocytes humains (lignees cellulaire ROSAKIT WT) [11,19 ± 7,5 vs 3,2 μM ± 0,2, p Conclusion Nos resultats montrent que les mastocytes jouent un role essentiel dans la regulation de la permeabilite vasculaire, de l’angiogenese et de la fibrogenese dans la maladie de Takayasu. Des therapeutiques ciblant les mastocytes pourraient ainsi favorablement modifier le remodelage vasculaire dans cette vascularite.

COVID-19, caused by the SARS-CoV-2, is an unprecedented global pandemic. Advanced age and cardiovascular diseases are recognised as major comorbidities associated with severe forms of COVID-19. Patients with large vessels vasculitis (LVV) could be considered at-risk for severe COVID-19 due to frequent age over 65 years in patients with giant cell arteritis (GCA), severe hypertension in patients with Takayasu arteritis (TAK) and current use of immunomodulating therapies in both LVV. Data on prevalence, clinical presentation and outcome of SARS-CoV-2 infection among patients with LVV are lacking.1–3 Tomelleri et al reported their experience in a single tertiary centre in Lombardy, the Italian region with the highest proportion of infected subjects.2 Their incidence rate of confirmed COVID-19 infection by nasopharyngeal PCR was 2.5% (4/162). Two patients required hospitalisation for COVID-19 interstitial pneumonia and no death was observed. We report our experience on clinical presentation and outcome of COVID-19 among patients with LVV in Paris-Ile de France, another region particularly affected during the same period. A phone survey was conducted between 04 and 20 May 2020, 8 weeks after lockdown started in France, among patients with LVV followed in Pitie-Salpetriere Hospital (Paris, France). Patients with positive nasopharyngeal PCR and/or thoracic CT scan suggestive of …

Background:Takayasu’s arteritis (TAK) is a large vessel vasculitis (LVV) in which the aorta and its main branches are greatly inflamed, leading to wall thickening, fibrosis, stenosis and to artery occlusion(1). The disease is more common in women mostly between 20 and 30 years old. TAK has a high morbidity rate: 50% of patients will relapse within 10 years after diagnosis(2, 3). This inflammation is essentially mediated by infiltration with macrophages and pro-inflammatory Th1/Th17 effector subsets(4–8). But the mechanisms behind these phenomena are essentially unknown. TAK is mainly treated with non-specific steroids(1) which are associated with potential side effects when used for a long-time course.Objectives:Our work aims to explore the involvement of JAK/STAT signaling pathway and its downstream biological cascades in pro-inflammatory T cells differentiation and disease activity of TAK. Plus, our work allows to consider targeting the JAK/STAT pathway in TAK using JAK inhibitors (JAKinibs).Methods:We analyzed transcriptome of FACS-sorted CD4+ and CD8+ T cells from healthy donors (HD) and TAK, using differential gene, pathway and network analysis. Then, we assessed in vitro and in vivo effects of JAKinibs in TAK by flow cytometry (FC).Results:Transcriptome analysis showed hundreds of significantly dysregulated genes/pathways for CD4+ and CD8+ samples between HD and TAK. Among these, we noticed in TAK a great enrichment for pathways linked to type I and II interferons (IFN), JAK/STAT and cytokines/chemokines-related signaling. We confirmed by RT-qPCR the upregulation of a type I IFN-specific gene signature in TAK T cells as compared to HD. Using genes coming from the previous pathways, we constructed networks connecting them according to their respective protein interactions. This representation showed for both CD4+ and CD8+ T cells that JAK and STAT genes were densely connected, thus representing core genes/proteins in the TAK physiopathology.We then performed in vitro cell cultures of PBMCs from HD or TAK supplemented with Ruxolitinib (JAK1/2 inhibitor) or PBS. We observed by FC that JAKinibs significantly induced in TAK CD4+ and CD8+ T cells reduction of CD25 expression, decrease of Th1/Th17 pro-inflammatory cells and increase of Tregs.Next, we followed by FC 3 TAK (refractory to conventional treatments) treated with JAKinibs. We also observed in their PBMCs a reduction of CD25 expression by CD4+ T cells, a decrease of Th1 and Th17 cells and an increase of Tregs, accompanied by an increase of the Tregs/Teffs ratio. JAKinibs also decreased C-Reactive Protein level, NIH score and co-administered steroids doses (present before JAKinibs introduction) in these 3 in vivo-treated TAK.Conclusion:JAK/STAT signaling pathway is critical in the pathogenesis of TAK and JAKinibs may be promising in its treatment.References:[1]F. Numano, M. Okawara, H. Inomata, Y. Kobayashi, The Lancet. 356, 1023–1025 (2000).[2]C. Comarmond et al., Circulation. 136, 1114–1122 (2017).[3]A. Mirouse et al., J. Autoimmun. 96, 35–39 (2019).[4]C. M. Weyand, J. J. Goronzy, Nat. Rev. Rheumatol. 9, 731–740 (2013).[5]C. M. Weyand et al., Clin. Immunol. 206, 33–41 (2019).[6]D. Saadoun et al., Arthritis Rheumatol. 67, 1353–1360 (2015).[7]T. Mirault, H. Guillet, E. Messas, Presse Médicale. 46, e189–e196 (2017).[8]D. P. Misra, S. Chaurasia, R. Misra, Autoimmune Dis. 2016, 1–8 (2016).Disclosure of Interests:Paul Régnier: None declared, Alexandre Le Joncour: None declared, Anna Maciejewski-Duval: None declared, Anne-Claire DESBOIS: None declared, Cloé Comarmond: None declared, Michelle Rosenzwajg: None declared, David Klatzmann Consultant of: ILTOO Pharma, Patrice cacoub: None declared, David Saadoun: None declared

Background:Aortitis is a group of disorders characterized by the inflammation of the aorta. The most common causes of aortitis are the large-vessel vasculitis i.e. giant cell arteritis (GCA) and Takayasu arteritis (TA). However, aortitis may be isolated. Because of the wide variation in the course of aortitis, predicting outcome is challenging. The optimal management strategy of isolated aortitis (IA) is still unclear as IA is poorly defined, with data consisting of small retrospective and case control studies.Objectives:To assess the long-term outcome and prognosis factors for vascular complications in patients with isolated aortitis.Methods:Retrospective multicenter study of 353 patients with non-infectious aortitis including 136 giant cell arteritis (GCA), 96 Takayasu arteritis (TA) and 73 isolated aortitis (IA). Factors associated with event-free survival, vascular event-free survival and revascularization-free survival were assessed. Risk factors for vascular complications were identified in multivariate analysis.Results:After a median follow up of 52 months, vascular complications were observed in 32.3 %, revascularization in 30 % and death in 7.6%. The 5-year cumulative incidence of vascular complications was 58% (41; 71), 20% (13; 29), and 19 % (11; 28) in IA, GCA and TA, respectively. In multivariate analysis, IA [HR, 1.85 (1.19 to 2.88), p=0.017] and male gender [1.77 (1.26 to 2.49), pConclusion:IA has a worse vascular prognosis than GCA and TA. Sixty percent of IA patients will experience a vascular complication within 5 years from diagnosis.Disclosure of Interests:None declared

Background:Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are the two main forms of large vessels vasculitis (LVV). Vessel inflammation leads to aneurysms, wall thickening, stenosis, and, in some cases, complete occlusion of the artery. Due to the wide variation in the course of LVV, predicting outcome is challenging. To our knowledge, data regarding prognosis factors of LVI in LVV patients and comparison of outcome of LVI in GCA and TAK are lacking. An early identification of patients with higher mortality could help to prevent deaths and vascular complications.Objectives:To assess prognosis factors and outcome of large vessel involvement (LVI) in large vessels vasculitis (LVV) patients.Methods:Retrospective multicenter study of characteristics and outcomes of 417 patients with LVI including 299 Takayasu arteritis (TAK) and 118 Giant cell arteritis (GCA-LVI) were analyzed. Logistic regression analysis assessed prognosis factors in LVV patients. Outcome of LVI among TAK and GCA-LVI patients (ischemic complications, aneurysms complications, relapses and revascularization) were assessed.Results:In multivariable analysis, stroke/transient ischemic attack [HR: 3.63 (1.46 - 9.04), p=0.006] was independently associated with vascular complications in LVV. The 10-years aneurysm free survival was significantly lower [67% (48 – 93) vs 89% (84 – 95), p=0.02] in GCA-LVI compare to TAK patients. The 5-years relapse free survival was significantly lower [47% (37 – 60) vs 69% (63 – 75), pConclusion:This large nationwide cohort of LVI provided prognosis factors of vascular complications in LVV patients. TAK and GCA-LVI have different long-term outcome in term of aneurysm development, relapse and revascularization.Disclosure of Interests:None declared