Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with systemic inflammatory or autoimmune diseases in 10-20 % of cases. Among them, immune thrombocytopenia (ITP) has been reported but large studies assessing this association are missing. Whether such patients have a particular phenotype and require particular management is unclear. This study analyzes the clinical spectrum, outcome and therapeutic management of patients with ITP associated with MDS or CMML, in comparison (i) to patients with primary ITP without MDS/CMML and (ii) to patients with MDS/CMML without ITP. Forty-one MDS/CMML-associated ITP patients were included, with chronic ITP in 26 (63%) patients, low-risk myelodysplasia in 30 (73%) patients and CMML in 24 (59%) patients. An associated autoimmune disease was noted in 10 (24%) patients. In comparison to primary ITP patients, MDS/CMML-associated ITP patients had a higher occurrence of severe bleeding despite similar platelet counts at diagnosis. First-line treatment consisted of glucocorticoids (98%) and intravenous immunoglobulin (IVIg) (56%). Response achievement with IVIg was more frequent in primary ITP than in MDS/CMML-associated ITP patients. Response rates to second-line therapies were not statistically different between primary ITP and MDS/CMMLassociated ITP patients. Ten percent (n=4) of patients with MDS/CMML-associated ITP had multirefractory ITP versus none in primary ITP controls. After a median follow-up of 60 months, there was no difference in overall survival between MDS/CMML-associated ITP and primary ITP patients. Leukemia-free-survival was significantly better in MDS/CMMLassociated ITP patients than in MDS/CMML without ITP MDS/CMML-associated ITP have a particular outcome with more severe bleeding and multirefractory profile than primary ITP, similar response profile to primary ITP therapy except for IVIg, and less progression toward acute myeloid leukemia than MDS/CMML without ITP.

Introduction: Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) can be associated with giant cell arteritis (GCA). In this nationwide study by the "French Network of dysimmune disorders associated with hemopathies" (MINHEMON) the objective was to evaluate characteristics, treatment and outcome of GCA MDS-MDS/MPN. Patients and methods: Retrospective analysis of patients that presented a MDS or MDS/MPN associated with GCA. Treatment efficiency, relapse-free and overall survival of GCA MDS-MDS/MPN were compared to GCA alone. Results: Twenty-one patients with GCA MDS-MDS/MPN were included with median age 76 [42-92], M/F ratio 2.5, 8 MDS with multilineage dysplasia (38%), 4 chronic myelomonocytic leukemia (19%), at low or intermediate risk according to IPPS and IPSS-R. The prevalence of headaches, jaw claudication and anterior ischemic optic neuropathy was significantly lower in patients with GCA MDS-MDS/MPN compared to idiopathic GCA (14.3%, 0% and 0% versus 30%, 25%, and 25%, respectively; p < .05). Other clinical and histology findings were similar. All GCA patients received steroid therapy as first-line treatment. Complete or partial response was observed in 14 GCA MDS-MDS/MPN patients (66.7%), of whom 6 (28.6%) received combined immunosuppressive therapies (versus 10% of idiopathic GCA; p = .07). Relapse incidence was similar in the two groups. Steroid dependence was more frequent among GCA MDS-MDS/MPN patients (12 (57%) versus 18 (22.5%); p < .05). Relapse-free and steroid-free survivals were significantly decreased in GCA MDS-MDS/MPN patients (log rank 0.002 and 0.049 respectively), but not overall survival. Conclusion: Characteristics of GCA MDS-MDS/MPN seem different than idiopathic GCA, with a distinct clinical phenotype and poorer outcome with a higher risk of steroid dependence and relapse.

Background: Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) can be associated with vasculitis. Objectives: In this nationwide study by the “French Network of dysimmune disorders associated with hemopathies” (MINHEMON) the objective was to evaluate characteristics, treatment and outcome of vasculitis MDS-MDS/MPN. Methods: Retrospective analysis of patients that presented a MDS/MPN associated with vasculitis and compared the overall survival and acute leukemia with MDS without vasculitis. Results: Seventy patients with vasculitis and MDS/MPN were included, with a median age of 71.5 [21-90] years and male/female ratio of 2.3. Vasculitis was diagnosed prior to MDS/MPN in 31 patients (44.3%), with a median time of 27 months [1-120] between two diagnosis, and after in 20 patients (6 months [1-59]). In comparison to 183 MDS/MPN without dysimmune features showed no difference in MDS/MPN subtypes distribution nor median IPSS/CPSS scores in patients with and without vasculitis. The vasculitis subtypes was giant-cell arteritis (GCA) in 24 patients (34%). Eleven patients (20%) had Behcet’s-like syndrome and 6 patients (9%) presented with polyarteritis nodosa. Steroids (60 mg/day [0-500] of prednisone equivalent) were used as first-line therapy for MDS/MPN vasculitis in 64/70 patients (91%) and 41 (59%) received combined immunosuppressive therapies during the follow-up. After the follow-up of 33.2 months [1-162], 31 patients (44%) finally experienced sustained remission. At least one relapse during the 33.2 months [1-162] follow-up occurred in 43 patients (61%). Relapse rates were higher in patients treated by DMARDs (odds ratio at 4.86 [95% CI 1.38 - 17.10]), but did not differ from biologics (odds ratio 0.59 [95% CI 0.11-3.20]) and azacytidine (odds ratio 1.44 [95% CI 0.21-9.76]) (steroids considered as reference). Overall survival and progression to acute myeloid leukemia in MDS/MPN vasculitis were not significantly different from MDS/MPN patients without any dysimmune features (p=0.5). Conclusion: This first largest study of MDS/MPN vasculitis show no correlation of vasculitis subtypes with various subtypes and severity of MDS/MPN, and no significant impact of vasculitis on overall survival and progression to acute myeloid leukemia. The high relapse rats and steroid dependence raise the question of combined therapies to steroids. Whereas DMARDs use seem to be avoid specific azacytidine therapy could be considered for even low-risk MDS/MPN vasculitis. Acknowledgments: minhemon gfm gfev Disclosure of Interests: None declared

Introduction: We aimed to analyze patients with acute and chronic joint involvements in sarcoidosis. Methods: This is a retrospective multicenter analysis of patients with proven sarcoidosis, as defined by clinical, radiological, and histological criteria, with at least one clinical and/or ultrasonographic synovitis. Results: Thirty-nine patients with sarcoid arthropathy were included, and among them 19 had acute sarcoidosis (Lofgren's syndrome). Joint involvement and DAS44-CRP were not significantly different in acute and chronic sarcoid arthropathies. Acute forms were more frequent than chronic sarcoid arthropathy in Caucasians, without any difference of sex or age between these 2 forms. Joint involvement was frequently more symmetrical in acute than chronic forms (100 vs. 70%; p < 0.05), with a more frequent involvement in wrists and ankles in acute forms, whereas the tender and swollen joint counts and the DAS44-CRP were similar between the 2 groups. Skin lesions were significantly more frequent in patients with acute forms [17 (89%) vs. 5 (25%); p < 0.05] and were erythema nodosum in all patients with Löfgren's syndrome and sarcoid skin lesions in those with chronic sarcoidosis. Among 20 patients with chronic sarcoidosis, treatment was used in 17 (85%) cases, and consisted in NSAIDs alone ( n = 5; 25%), steroids alone ( n = 5; 25%), hydroxychloroquine ( n = 2; 20%), methotrexate ( n = 3; 15%), and TNF inhibitors ( n = 2; 10%). A complete/partial joint response was noted in 14 (70%) cases with a DAS44-CRP reduction of 2.07 [1.85–2.44] (from 3.13 [2.76–3.42] to 1.06 [0.9–1.17]; p < 0.05). Conclusion: Sarcoid arthropathies have different clinical phenotypes in acute and chronic forms and various treatment regimens such as hydroxychloroquine and methotrexate could be used in chronic forms.

Les manifestations systémiques auto-immunes et/ou inflammatoires (MAI) sont associées avec les syndromes myélodysplasiques (SMD) dans 10 à 25 % des cas. Parmi ces manifestations les vascularites sont les plus fréquentes, majoritairement la périartérite noueuse et les vascularites leucocytoclasiques cutanées. Il manque des études ayant analysées spécifiquement les caractéristiques, le pronostic et la prise en charge de ces vascularites. Dans cette large série de cas rétrospective multicentrique nous avons analysé les caractéristiques, la prise en charge et l’évolution des vascularites associées à un SMD ou une LMMC. Étude rétrospective multicentrique française, ayant inclus 70 patients présentant une vascularite associée à un SMD/LMMC. Les SMD/LMMC étaient diagnostiqués selon les critères WHO 2016 ; les vascularites associées selon les critères de la classification Chapell Hill 2012. Soixante-dix patients avec une vascularite associée à un SMD/LMMC ont été inclus, avec un âge médian de 71 ans [21–90] et 49 hommes (70 %). L’hémopathie sous-jacente était le plus souvent un SMD avec dysplasie multilignée (MDS-MLD, n = 23, 33 %) ou une LMMC (n = 16, 23 %) majoritairement avec risque faible ou intermédiaire-1 selon l’IPSS. Vingt-quatre patients avaient un diagnostic d’artérite à cellules géantes (AGC, 34 %) parmi lesquels 17 (71 %) présentaient les critères complets ACR 1990. Quatre patients présentaient une maladie de Behçet (6 %) et 7 un pseudo-Behçet (10 %). Six patients avaient un diagnostic de périartérite noueuse (9 %), sept patients (10 %) étaient classés vascularite associée aux ANCA, dont 5 avec une polyangéite microscopique et 2 avec une granulomatose avec polyangéite, 3 patients (4 %) présentaient une vascularite cryoglobulinémique et 2 (3 %) une vascularite à IgA. Dix-sept patients (24 %) présentaient une vascularite inclassée. Le BVAS au diagnostic était à 6 [0–24], le score pronostic FFS à 1 [0–3]. Les vascularites étaient diagnostiquées avant l’hémopathie dans 43 % des cas (n = 30), avec une médiane de temps de 27 mois [1–180]. La corticothérapie était utilisée en première ligne dans 91 % des cas (n = 64) avec une réponse complète ou partielle chez 39 patients (56 %). Quarante-trois patients ont présenté une rechute (61 %) avec nécessité de recours à un traitement immunosuppresseur. 19 patients (27 %) ont reçu un traitement hypométhylant (azacytidine). Le délai médian de rémission était de 13 mois [1–70]. Une corticodépendance était observée dans 32 cas (46 %). Vingt patients (29 %) sont décédés pendant le suivi. Toutes les catégories de vascularites semblent pouvoir être associées aux SMD/LMMC. Il existe dans cette cohorte une grande proportion d’AGC et de vascularites inclassées. Un groupe contrôle de vascularites idiopathiques sera comparé afin d’identifier des spécificités propres aux vascularites associées aux SMD/LMMC.

Introduction Les manifestations systemiques auto-immunes et/ou inflammatoires (MAI) sont associees avec les syndromes myelodysplasiques (SMD) dans 10 a 25 % des cas. Parmi ces manifestations les vascularites sont les plus frequentes, avec en particulier la periarterite noueuse et les vascularites leucocytoclasiques cutanees. L’association d’arterite a cellules geantes (AGC) avec les SMD/LMMC est moins bien caracterisee. Dans cette etude cas-controles nous avons analyses les caracteristiques, la prise en charge et l’evolution de l’AGC associee avec SMD/LMMC. Patients et methodes Etude retrospective multicentrique francaise, ayant inclus 21 patients presentant une arterite gigantocellulaire associee a un SMD/LMMC. Un groupe controle de AGC idiopathique a ete apparie par Age et sexe (1 pour 4, soit 80 patients). Resultats Vingt un patients avec une AGC associes a un SMD/LMMC ont ete inclus, avec un âge median de 76 ans [42–92] et 15 hommes (71 %). Le SMD sous-jacent etait le plus souvent avec dysplasies multiples et une LMMC dans 4 cas (19 %). En comparaison avec les AGC idiopathiques, les AGC-SMD/LMMC avaient une frequence similaire de signes generaux, d’atteintes oculaires, neurovasculaire centrale et la frequence d’aortite etait de 19 % (versus 20 % ; p = 0,4). La frequence de la biopsie de l’artere temporale positive etait de 33 % dans le groupe AGC-SMD/LMMC et n’etait pas differente de celle des AGC idiopathiques (46 % ; p = 0,3). Les taux de plaquettes, d’hemoglobine et de neutrophiles etaient significativement diminues en cas de SMD/LMMC associes. Le recours a un traitement immunosuppresseur en plus de la corticotherapie etait necessaire dans 6 (29 %) des AGC-SMD/LMMC versus 21 (26 %) des formes idiopathiques, avec un nombre de rechutes similaire (1 [0–1] versus 1 [0–4]), ainsi que le delai de remission avant la premiere rechute. En revanche, les patients avec une AGC-SMD/LMMC presentaient plus souvent une corticodependance en comparaison avec les patients ayant une forme idiopathique (12 (57 %) versus 18 (23 %) ; p = 0,003). Conclusion L’AGC est une manifestation qui peut etre associee avec un SMD/LMMC et ne semble pas avoir de caracteristiques particulieres en comparaison avec les formes idiopathiques, mais presente plus frequemment une corticodependance.

In the last decades, autoimmune diseases have experienced a dramatic increase in Western countries. The involvement of environmental factors is strongly suspected to explain this rise. Particularly, over the same period, obesity has followed the same outbreak. Since the exciting discovery of the secretory properties of adipose tissue, the relationship between obesity and autoimmunity and the understanding of the underlying mechanisms have become of major interest. Indeed, the fat tissue has been found to produce a wide variety of “adipokines,” involved in the regulation of numerous physiological functions, including the immune response. By conducting a systematic literature review, we extracted 329 articles regarding clinical, experimental, and pathophysiological data on the relationship between obesity, adipokines—namely leptin, adiponectin, resistin, visfatin—and various immune-mediated conditions, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), psoriasis and psoriatic arthritis (PsA), and thyroid autoimmunity (TAI), especially Hashimoto thyroiditis. The strongest levels of evidence support an increased risk of RA (OR = 1.2–3.4), MS (OR = 2), psoriasis, and PsA (OR = 1.48–6.46) in obese subjects. A higher risk of IBD, T1D, and TAI is also suggested. Moreover, obesity worsens the course of RA, SLE, IBD, psoriasis, and PsA and impairs the treatment response of RA, IBD, psoriasis, and PsA. Extensive clinical data and experimental models demonstrate the involvement of adipokines in the pathogenesis of these autoimmune diseases. Obesity appears to be a major environmental factor contributing to the onset and progression of autoimmune diseases.

IntroductionSome studies suggest that there is an increased risk of malignancies in giant cell arteritis (GCA). We aimed to describe the clinical characteristics and outcomes of GCA patients with concomitant malignancy and compare them to a GCA control group.MethodPatients with a diagnosis of GCA and malignancy and with a maximal delay of 12months between both diagnoses were retrospectively included in this study and compared to a control group of age-matched (3:1) patients from a multicenter cohort of GCA patients.ResultsForty-nine observations were collected (median age 76years). Malignancies comprised 33 (67%) solid neoplasms and 16 (33%) clonal hematologic disorders. No over-representation of a particular type of malignancy was observed. Diagnosis of GCA and malignancy was synchronous in 7 (14%) patients, while malignancy succeeded GCA in 29 (59%) patients. Malignancy was fortuitously diagnosed based on abnormalities observed in laboratory tests in 26 patients, based on imaging in 14 patients, and based on symptoms or clinical examination in the nine remaining patients. Two patients had a concomitant relapse of both conditions. When compared to the control group, patients with concomitant GCA and malignancy were more frequently male (p<0.001), with an altered general state (p<0.001), and polymyalgia rheumatica (p<0.01).ConclusionsThis study does not indicate an over-representation of any particular type of malignancy in GCA patients. Initial follow-up dictated by vasculitis may have led to an early identification of malignancy. Nevertheless, GCA male patients with an altered general state and polymyalgia rheumatica might more frequently show concomitant malignancies.

The association between smoke habit and autoimmunity has been hypothesized a long time ago. Smoke has been found to play a pathogenic role in certain autoimmune diseases as it may trigger the development of autoantibodies and act on pathogenic mechanisms possibly related with an imbalance of the immune system. Indeed, both epidemiological studies and animal models have showed the potential deleterious effect caused by smoke. For instance, smoke, by provoking oxidative stress, may contribute to lupus disease by dysregulating DNA demethylation, upregulating immune genes, thereby leading to autoreactivity. Moreover, it can alter the lung microenvironment, facilitating infections, which, in turn, may trigger the development of an autoimmune condition. This, in turn, may result in a dysregulation of immune system leading to autoimmune phenomena. Not only cigarette smoke but also air pollution has been reported as being responsible for the development of autoimmunity. Large epidemiological studies are needed to further explore the accountability of smoking effect in the pathogenesis of autoimmune diseases.

Cette étude française rétrospective multicentrique a eu comme objectif d’analyser l’atteinte articulaire au cours de la sarcoïdose aiguë et chronique afin de mieux caractériser l’attitude thérapeutique et comparer l’efficacité de différents traitements. Tout patient (≥ 18 ans) avec un diagnostic de sarcoïdose prouvée cliniquement, radiologiquement et selon les critères histologiques et avec une atteinte articulaire avec présence d’au moins une synovite clinique et/ou échographique a été inclus. Un total de 39 patients avec arthropathie sarcoïdosique a été inclus, dont 20 patients avec une forme aiguë (syndrome de Lofgren). La présentation de l’atteinte articulaire ainsi que le DAS28-CRP, utilisé comme marqueur d’activité de l’atteinte articulaire, n’étaient pas significativement différents dans les deux formes cliniques aiguë et chronique. L’atteinte oculaire était significativement plus fréquente chez les patients avec une forme chronique à différence des atteintes cutanées plus fréquentes en cours de sarcoïdose aiguë. Il n’y avait pas de différence des taux de CRP et de ECA dans les deux groupes (médiane 27 mg/L [1–180] versus 15 mg/L [1–271] ; p-value = 0,2). Pour les 39 patients, 89 lignes thérapeutiques ont été utilisées pendant un suivi médian de 18 [3–264] mois. La première ligne thérapeutique a consisté en stéroïdes seuls (18 %) ou avec hydroxychloroquine (12 %), méthotrexate (9 %), ou autres stratégies thérapeutiques immunosuppressives (3 %). Les corticoïdes, l’hydroxychloroquine, le méthotrexate et infliximab étaient associés avec une réduction significative du nombre d’articulations gonflées et douloureuses et avec un effet significatif d’épargne cortisonique. Aucune différence n’a été retrouvée sur la réponse articulaire en utilisant un score de propension concernant les différents régimes thérapeutiques. L’atteinte articulaire dans la sarcoïdose peut avoir deux présentations phénotypiques différentes, aiguë et chronique. Dans la forme chronique ou dans les formes corticorésistantes ou corticodépendantes de sarcoïdose avec atteinte articulaire, des traitements immunosuppresseurs comme le méthotrexate ou l’hydroxycloroquine semblent avoir une efficacité similaire.

PURPOSE OF THE STUDY:Takayasu arteritis (TA) is an idiopathic large vessel vasculitis, which involves the aorta and its major branches. Our aim was to examine the association between TA and the development of ischemic heart disease (IHD) and its impact on survival. STUDY DESIGN:Using data from Clalit Health Services (CHS), the largest Health Maintenance Organization (HMO) in Israel, the proportion of IHD was compared between patients diagnosed with TA and age- and gender-matched controls. Chi-square and t-tests were used for univariate analysis, and a logistic regression model was employed for multivariate analysis. Survival analysis was performed using Kaplan-Meier plots and cox regression. RESULTS:The study included 155 TA patients and 755 age- and gender-frequency matched controls. The proportion of IHD in TA patients was increased in comparison with controls (32.3% and 8.9%, p<0.001). In multivariate analysis, IHD was associated with TA (OR=6.576, 95% CI: 4.09-10.64) and male gender (OR=2.29, 95% CI: 1.43-4.26). Survival analysis over 15 years of follow-up showed a higher proportion of all-causes mortality in the TA group. In a multivariate analysis, TA (HR=2.58, 95%CI: 1.64-4.06) and IHD (HR=1.64, 95%CI: 1.05-2.55) were found to be associated with reduced survival. CONCLUSIONS:TA patients present an increased proportion of IHD, and a reduced 15-years survival rate compared to controls.

The relapse rate in antiphospholipid syndrome (APS) remains high, i.e. around 20%-21% at 5 years in thrombotic APS and 20-28% in obstetrical APS [2, 3]. Hydroxychloroquine (HCQ) appears as an additional therapy, as it possesses immunomodulatory and anti-thrombotic various effects [4-16]. Our group recently obtained the orphan designation of HCQ in antiphospholipid syndrome by the European Medicine Agency. Furthermore, the leaders of the project made the proposal of an international project, HIBISCUS, about the use of Hydroxychloroquine in secondary prevention of obstetrical and thrombotic events in primary APS. This study has been launched in several countries and at now, 53 centers from 16 countries participate to this international trial. This trial consists in two parts: a retrospective and a prospective study. The French part of the trial in thrombosis has been granted by the French Minister of Health in December 2015 (the academic trial independent of the pharmaceutical industry PHRC N PAPIRUS) and is coordinated by one of the members of the leading consortium of HIBISCUS.

Background Patients with systemic lupus erythematosus (SLE) are at higher risk than the general population of developing lymphoma. Relatively little is known about the risk factors, the treatment and the outcome of lymphoma in SLE. Objectives We aimed to describe a cohort of patients suffering from lymphoma in the setting of SLE and to study the risk factors of developing this complication. Methods We collected clinical data of SLE patients with confirmed lymphoma in a multicentric and retrospective study. SLE patients were eligible for the study if they fulfilled at least 4 of the 1997 ACR criteria for SLE. Exclusion criteria were HIV or C hepatitis infection. Results We included 38 patients (34 women and 4 men) coming from 10 different French University Hospitals. The lymphoma occurred after the diagnosis of SLE for 35 patients, with a median (range) time of 8.8 years (0–39). In their past or present medical history, 11 (29%) had a haematological involvement (5 immune thrombocytopenias, 4 autoimmune hemolytic anemias and 2 patients with both). Nine patients (24%) had associated Sjögren syndrome. 22 patients (58%) had a polyclonal hypergammaglobulinemia. Before the occurrence of the lymphoma, 18 patients (47%) had received an immunosuppressant during a median (range) period of 67 months.6–195 17 patients had an indolent B cell lymphoma (IBCL), 14 a high-grade B cell lymphoma (11 diffuse large B cell lymphoma [DLBCL]; 2 a primary DLBCL of the central nervous system; and 1 an iatrogenic immunodeficiency-associated lymphoproliferative disorder), 5 a Hodgkin’s disease (HD), and 2 a T cell lymphoma. The EBER in situ hybridization stain was positive in 7 of the 13 patients assessed (3/3 HD, 3/7 DLBCL and 1/2 IL) and was not associated with the immunosuppressant prescription. The median (range) of the survey after the lymphoma was 28.5 month (0–235.1). The 14 DLBCL patients except 1 were treated with chemotherapy: 4 died, 9 were in complete remission and 1 was in progression. Regarding the 17 IBCL, 9 patients were treated with chemotherapy, 2 patients with surgery, 1 patient with radiotherapy and 5 patients were not treated: 3 patients had to short follow-up or were lost, 1 died, 2 developed a DLBCL, 4 were stable and 7 were in complete remission. The 5 HL were treated with chemotherapy and all were in complete remission. Conclusions IBCL and DLBCL were the most common type of lymphomas in SLE patients. Data suggest a role for EBV but not for exposition to immunosuppressant in the pathogenesis of SLE-associated lymphoma. The outcome of lymphoma in the setting of SLE seems not different from the outcome of lymphoma in the general population. A case-control study is ongoing to study the risk factors associated with the occurrence of lymphoma in SLE Disclosure of Interest None declared

Background: Sarcoidosis is a multisystem, chronic, progressive, granulomatous disease. Sarcoidosis-associated pulmonary hypertension is a well described, but not common, complication of sarcoidosis. In small scale studies, it has been previously described as manifestation of advanced disease and was found to be associated increased morbidity and mortality. This study sought to assess the long-term prognostic significance of sarcoidosis-associated pulmonary hypertension (SAPH) by using data obtained from a large population-based registry which contains longitudinal follow-up data. Methods: Utilizing the records of the largest healthcare provider in Israel, we extracted a cohort consisting of sarcoidosis patients and age-and-sex matched controls. Dates of sarcoidosis registration, pulmonary hypertension and death, as well as anthropometric information and medical comorbidities, were extracted from the database. A multivariate logistic regression model was used to find variables associated with pulmonary hypertension. Cox proportional hazards method and log-rank test were used for survival analysis. Results: The cohort included 3993 sarcoidosis patients and 19,856 controls. Pulmonary hypertension was observed among 269 sarcoidosis patients (6.74%) vs. 400 controls (2.01%). Sarcoidosis was found as independently associated with pulmonary hypertension (OR 3.17). After a mean follow-up of 7.49 years (median 7.24, maximum 17.88 years), 710 (17.8%) of the sarcoidosis patients and 2121 (10.7%) of the controls had died. Both sarcoidosis and pulmonary hypertension were found to be significantly associated with an increased risk of all-cause mortality (HR 1.82 and HR 2.31, respectively). Conclusions: SAPH is associated with a poor prognosis. Proper screening methods may assess whether early identification and treatment improve life expectancy.

During the last decades, the number of Pneumocystis jirovecii pneumonia (PJP) has grown in HIV-negative patients due to the increasing use of organ transplantation, immunosuppressive drugs and targeted therapies [ [1] Wickramasekaran R.N. Jewell M.P. Sorvillo F. Kuo T. The changing trends and profile of pneumocystosis mortality in the United States, 1999–2014. Mycoses. 2017; : 607-615 Crossref PubMed Scopus (27) Google Scholar ]. Guidelines about PJP prophylaxis in immunocompromised (IC) HIV-negative patients are scarce. CD4+ cell count is less helpful in IC patients than in HIV-positive, and B cells may help clearing Pneumocystis infection [ [2] Lund F.E. Hollifield M. Schuer K. Lines J.L. Randall T.D. Garvy B.A. B cells are required for generation of protective effector and memory CD4 cells in response to Pneumocystis lung infection. J Immunol. 2006; 176: 6147-6154 Crossref PubMed Scopus (138) Google Scholar ]. Rituximab is a chimeric monoclonal antibody that targets human cell-surface glycoprotein CD20 expressed on B cells. It has gained many indications, especially off-label, for the treatment of autoimmune diseases. Serious infection rates ranging from 2% to 22% have been reported in such uses. The largest cohort of rituximab-related PJP in HIV-negative patients included 30 patients, with 90% of them suffered from blood cancer [ [3] Martin-Garrido I. Carmona E.M. Specks U. Limper A.H. Pneumocystis pneumonia in patients treated with rituximab. Chest J. 1 juill 2013; 144: 258 Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar ].

Background: Systemic inflammatory and autoimmune diseases (SIADs) associated with myelodysplastic syndromes are often difficult to treat. Corticosteroids are efficient but only usually at high doses. The use of biologics needs to be specified.Methods: In a French multicenter retrospective study, we analyzed the efficacy and safety of biologics (tumor necrosis factor-alpha [TNF-alpha] antagonists, tocilizumab, rituximab and anakinra) for SIADs associated with myelodysplastic syndromes (MDSs). Clinical, biological and overall treatment responses were evaluated. When several lines of treatment were used, data were analyzed before and at the end of each treatment line and were pooled to compare overall response among steroids, disease-modifying anti-rheumatic drugs (DMARDs) and biologics.Results: We included 29 patients (Median age 67 years [interquartile range 62-76], 83% males) with MDS-related SIADs treated with at least one biologic. The MDSs were predominantly refractory anemia with excess blasts 1 (38%) and refractory cytopenia with multilineage dysplasia (21%). The SIADs were mainly arthritis (n = 6; 20%), relapsing polychondritis (n = 8; 30%) and vasculitis (n = 10; 34%). During a 3-year median follow-up (IQR 1.3-4.5), a total of 114 lines of treatments were used for all patients: steroids alone (22%), DMARDs (23%), TNF-alpha antagonists (14%), anakinra (10%), rituximab (10%), tocilizumab (7%) and azacytidine (9%). Considering all 114 lines, overall response (complete and partial) was shown in 54% cases. Overall response was more frequent with steroids (78%) and rituximab (66%) than DMARDs (45%) and other biologics (33%) (p < 0.05). Rituximab had better response in vasculitis and TNF-a antagonists in arthritis. During follow-up, 20 patients (71%) presented at least one severe infection.Conclusion: This nationwide study demonstrates the efficacy of steroids for SIAD-associated MDSs but a high frequency of steroid dependence. The response to biologics seems low, but rituximab and azacytidine seem promising. (C) 2017 Elsevier B.V. All rights reserved.

Antiphospholipid syndrome (APS) is an autoimmune disease that manifests as recurrent venous or arterial thrombosis and/or pregnancy-related complications in the presence of persistent antiphospholipid (aPL) antibodies measured at least 3 months apart. APS occurs either as a primary condition or as a part of an underlying disorder, usually systemic lupus erythematosus (SLE). Otherwise, APS may be frequently associated with autoimmune disorders. Little is known about the association of APS and aPL antibodies with thyroid autoimmune diseases or thyroid autoantibodies. This is even more interesting that thyroid autoantibodies and aPL are both recognized causes of repeated miscarriages. Therefore, their combination is of particular importance in women of childbearing age. Several studies have pointed out an association between APS and thyroid autoimmunity, some of them suggesting common pathophysiologic processes and genetic background. A literature review was conducted on existing data on aPL/APS and thyroid autoimmune disorders, paying particular attention to the possible role of this association in obstetrical complications.

BackgroundBoth smoking and obesity have been demonstrated as risk factors in several autoimmune diseases. Little is known about the relationship between systemic lupus erythematosus (SLE) and both smoking and obesity.ObjectivesTo investigate the association between SLE, tobacco consumption and body mass index (BMI).Materials and methodsUsing data from the largest Health Maintenance Organization (HMO) in Israel, the Clalit Health Services, we searched for an association between SLE, smoking and obesity. Chi-square and t-test were used for univariate analysis, and a logistic regression model was used for multivariate analysis. Data available from Clalit Health Services database included age, sex, BMI, smoking status, socioeconomic status (SES) and diagnoses of chronic diseases.ResultsThe study included 5018 patients with SLE and 25 090 age- and sex-matched controls. In multivariate analysis, we found a significant association between smoking and SLE (OR = 191). Conversely, there was no association between BMI and SLE.ConclusionIn this study, we have shown that smoking is independently associated with SLE, whereas BMI scores were not.

La sarcoïdose est une maladie granulomateuse systémique. De rares cas de pelade et d’atteinte ostéolytique du crâne sont décrits séparément dans la littérature. Nous rapportons un cas de pelade révélant une sarcoïdose avec atteinte ostéolytique sous-jacente du crâne. Une patiente d’origine tunisienne de 57 ans aux antécédents de diabète non insulino-dépendant, de thyroïdectomie totale sur adénocarcinome papillaire thyroïdien considéré en rémission complète, et d’asthme ancien consulte pour une pelade. L’examen clinique trouve trois plaques alopéciques du cuir chevelu, rétro-auriculaire droite, temporale gauche et du vertex, initialement inflammatoires, croûteuses et prurigineuses, ayant évolué vers un aspect cicatriciel. Le reste de l’examen clinique est normal, notamment sans autre atteinte cutanéo-muqueuse, sans adénopathie ni hépato-splénomégalie. La biopsie cutanée révèle un infiltrat granulomateux et gigantocellulaire sans nécrose caséeuse. L’étude en lumière polarisée, les colorations PAS, Ziehl, bleu alcian et Verhoeff sont négatives, l’étude en immunofluorescence ne trouve aucun dépôt. Les prélèvements bactériologiques et mycologiques sont négatifs. Des traitements topiques successifs par kétoconazole puis bétaméthasone sont inefficaces. Le bilan iconographique et biologique initial est normal en dehors d’une ECA à 56 UI/L (N < 52 UI/L). Le diagnostic de sarcoïdose cutanée est retenu. Un traitement de fond par hydroxychloroquine est débuté. Six mois plus tard, la patiente se présente avec une légère extension des lésions du scalp, une asthénie marquée avec amaigrissement, une toux sèche et une dyspnée de stade II NYHA non fébrile. Le scanner montre des adénomégalies médiastino-hilaires, mésentériques et pelviennes modérément hypermétaboliques au TEP-TDM, associées à syndrome interstitiel bilatéral. Par ailleurs, le TEP-TDM révèle des lésions ostéolytiques focales du vertex et de la pointe mastoïdienne droite intensément hypermétaboliques, en regard des zones de pelade, sans autre atteinte osseuse. L’IRM cérébrale retrouve les lésions osseuses lytiques avec prise de contraste intense en T1, sans atteinte méningée ni cérébrale associée. La ponction lombaire et la biopsie de glande salivaire accessoire sont normales. Les EFR trouvent un syndrome restrictif modéré, sans trouble de la diffusion. Le diagnostic de tuberculose est écarté. Le diagnostic posé est celui de sarcoïdose associant une atteinte pulmonaire de stade 2 et une atteinte cutanée alopéciante du scalp avec ostéolyse sous-jacente. Une corticothérapie à 1 mg/kg/jour a été initiée, permettant pour l’instant une évolution favorable sur l’état général et l’atteinte pulmonaire. Si l’atteinte cutanée est fréquente et polymorphe au cours de la sarcoïdose, la pelade reste rare, avec moins de 50 cas décrits dans la littérature, prédominant dans la population afro-américaine. L’atteinte osseuse est également classique, présente dans 3 à 39 % des cas selon les séries, bien que probablement sous-estimée car asymptomatique dans plus de la moitié des cas. Elle touche préférentiellement les petits os des mains et des pieds, ou de façon plus anecdotique le squelette axial et appendiculaire. Les lésions ostéolytiques du crâne sont extrêmement rares avec une quarantaine de cas décrits à ce jour. L’association de ces deux atteintes, rapportée ici pour la première fois, apparaît exceptionnelle. Ces deux formes sont chacune fortement associées à l’existence d’atteintes systémiques, et caractérisées par une mauvaise réponse aux traitements classiques. La pelade peut être un mode de révélation de la sarcoïdose, et peut s’associer à une atteinte ostéolytique sous-jacente qu’il convient de rechercher.