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International audience; Background: Inflammation of unknown origin (IUO) is a challenging situation in internal medicine.Objectives: To describe the final diagnoses in IUO and assess the helpfulness of 18F-fluorodesoxyglucose positron emission tomography with computerized tomography (18F-FDG-PET/CT) in the diagnosis strategy.Results: A total of 317 IUO patients with 18F-FDG-PET/CT were enrolled. A diagnosis was reached in 228 patients: noninfectious inflammatory diseases (NIID) (37.5%), infectious diseases (18.6%), malignancies (7.9%), and non-systemic-inflammatory miscellaneous diseases (7.9%). The two leading causes of NIID were polymyalgia rheumatica and giant cell arteritis. 18F-FDG-PET/CT results were classified as true positive in 49.8% of patients and contributory in 75.1% of overall IUO patients (after the complete investigation set and a prolonged follow-up). In multivariate analysis, only C-reactive protein minimum level (≥50 mg/L) was associated with the contributory status of 18F-FDG-PET/CT.Conclusion: Within the wide spectrum of IUO underlying diseases, 18F-FDG-PET/CT is helpful to make a diagnosis and to eliminate inflammatory diseases. Obese patients constitute a specific group needing further studies

Despite a moderate prevalence in low-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML), thrombocytopenia remains a risk of severe bleeding and therapeutic options are still limited. There are only a few studies with eltrombopag (ELT), a thrombopoietin receptor agonist, in those patients. In this retrospective multicentre study, ELT was used in 50 patients with MDS and 11 with CMML, with no excess of marrow blasts and platelet counts of

Objectives: Giant cell arteritis (GCA) is associated with severe outcomes such as infections and cardiovascular diseases. We describe here the impact of GCA patients’ characteristics and treatment exposure on the occurrence of severe outcomes. Methods: Data were collected retrospectively from real-world GCA patients with a minimum of six-months follow-up. We recorded severe outcomes and treatment exposure. In the survival analysis, we studied the predictive factors of severe outcomes occurrence, including treatment exposure (major glucocorticoids (GCs) exposure (>10 g of the cumulative dose) and tocilizumab (TCZ) exposure), as time-dependent covariates. Results: Among the 77 included patients, 26% were overweight (BMI ≥ 25 kg/m2). The mean cumulative dose of GCs was 7977 ± 4585 mg, 18 patients (23%) had a major GCs exposure, and 40 (52%) received TCZ. Over the 48-month mean follow-up period, 114 severe outcomes occurred in 77% of the patients: infections—29%, cardiovascular diseases—18%, hypertension—15%, fractural osteoporosis—8%, and deaths—6%. Baseline diabetes and overweight were predictive factors of severe outcomes onset (HR, 2.41 [1.05–5.55], p = 0.039; HR, 2.08 [1.14–3.81], p = 0.018, respectively) independently of age, sex, hypertension, and treatment exposure. Conclusion: Diabetic and overweight GCA patients constitute an at-risk group requiring tailored treatment, including vaccination. The effect of TCZ exposure on the reduction of severe outcomes was not proved here.

Inflammation of unknown origin (IUO) is a challenging situation in internal medicine.To describe the final diagnoses in IUO and assess the helpfulness ofA total of 317 IUO patients withWithin the wide spectrum of IUO underlying diseases

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

Background: Few studies of daily practice for patients with giant cell arteritis (GCA) are available. This French study aimed to describe the characteristics and management of GCA in a real-life setting.Methods: Cross-sectional, non-interventional, multicenter study of patients ≥50 years old who consulted hospital-based specialists for GCA and were under treatment. Patient characteristics and journey, diagnostic methods and treatments were collected. Descriptive analyses were performed.Results: In total, 306 patients (67% females, mean age 74 ± 8 years old) were recruited by 69 physicians (internists: 85%, rheumatologists: 15%); 13% of patients had newly diagnosed GCA (diagnosis-to-visit interval 18FDG-PET, and aortic angio-CT, respectively. All patients received glucocorticoids, which were ongoing for 89%; 29% also received adjunct medication(s) (methotrexate: 19%, tocilizumab: 15%). A total of 40% had relapse(s); the median time to the first relapse was 10 months. Also, 37% had comorbidity(ies) related to or aggravated by glucocorticoids therapy.Conclusion: This large observational study provides insight into current medical practices for GCA. More than one third of patients had comorbidities related to glucocorticoid therapy for a median disease duration of 13 months. Methotrexate and tocilizumab were the most common adjunct medications.

Resume Introduction L’hemophilie acquise est une maladie auto-immune exceptionnelle. Le traitement immunosuppresseur a pour objectif d’enrayer la production d’autoanticorps inhibiteurs des facteurs VIII (FVIII) ou IX (FIX) de la coagulation. Une association corticotherapie-cyclophosphamide est recommandee en premiere intention. A partir de notre experience au CHU de Nimes, nous discutons la place du rituximab dans l’arsenal therapeutique. Methodes Nous rapportons une etude observationnelle monocentrique retrospective. Nos donnees sont discutees a la lumiere des donnees de la litterature, en particulier des cohortes EACH2 et SACHA. Resultats Huit patients dont 7 avec un anticorps anti-FVIII ont ete consecutivement inclus a partir de 2005. L’âge moyen etait de 68,5 ans avec une predominance masculine (62,5 %). Les manifestations hemorragiques etaient habituellement spontanees et superficielles. Une pathologie, notamment auto-immune ou neoplasique, etait associee chez 5 des 8 patients. Un traitement hemostatique dit « by-passant » etait prescrit pour 3 patients. Du rituximab etait prescrit pour 5 patients, dont trois fois en premiere intention, et toujours associe a la corticotherapie. Trois patients ont recu une association cyclophosphamide/cortisone, deux ont ete traites exclusivement par une corticotherapie orale. La remission etait obtenue chez tous les patients, sans rechute ulterieure. Le delai moyen pour obtenir la remission sous rituximab (apres la premiere injection) etait de 32,5 jours (10–143). Les resultats observes dans notre serie de patients sont coherents avec les donnees de la litterature. Conclusion Le rituximab semble etre un traitement efficace et bien tolere de l’hemophilie acquise auto-immune. Sa place reste cependant a preciser.

International audience; Malignancies can be associated with positive antiphospholipid antibodies but the incidence of cancer among women with the purely obstetric form of antiphospholipid syndrome (APS) is currently unknown. Our aim was to investigate the comparative incidence of cancers in women with a history of obstetric APS within a referral university hospital-based cohort (NOH-APS cohort). We performed a 17-year observational study of 1,592 non-thrombotic women with three consecutive spontaneous abortions before the 10th week of gestation or one fetal death at or beyond the 10th week of gestation. We compared the incidence of cancer diagnosis during follow-up among the cohort of women positive for antiphospholipid antibodies (n=517), the cohort of women carrying the F5 rs6025 or F2 rs1799963 polymorphism (n=279) and a cohort of women with negative thrombophilia screening results (n=796). The annualized rate of cancer was 0.300% (0.20%-0.44%) for women with obstetric APS and their cancer risk was substantially higher than that of women with negative thrombophilia screening [adjusted hazard ratio (aHR) 2.483; 95% confidence interval (CI) 1.27-4.85]. The computed standardized incidence ratio for women with obstetric APS was 2.89; 95% CI: 1.89-4.23. Among antiphospholipid antibodies, lupus anticoagulant was associated with incident cancers (aHR 2.608; 95% CI: 1.091-6.236). Our cohort study shows that the risk of cancer is substantially higher in women with a history of obstetric APS than in the general population, and in women with a similar initial clinical history but negative for antiphospholipid antibodies.

International audience; Objectives: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) are associated with systemic inflammatory and autoimmune diseases (SIADs) in 10-30% of cases. The aims of this study were (i) to evaluate the prevalence of venous thromboembolism VTE in patients presenting with both MDS/CMML and SIADs, (ii) to describe risk factors associated with thrombosis, and (iii) to analyse the impact of VTE on overall survival and transformation to acute myeloid leukaemia in comparison to patients with MDS/CMML-associated SIADs without VTE.Methods: This retrospective multicentre case-control study was conducted among patients with MDS/CMML and dysimmune disorders and featured in the French retrospective database of the French Network of Dysimmune Disorders Associated with Hemopathies (MINHEMON), diagnosed with MDS/CMML and dysimmune disorders.Results: During a median follow-up of 16 months (5-48) VTE occurred in 35 patients (21.6 %) whereas 127 patients did not. Among those with VTE, 8 patients (22.9%) experienced two or more VTE. Common prothrombotic risk factors were not significantly different in patients with or without VTE. CMML was more frequent in patients without VTE (37 % vs. 14.3%, p=0.01), whereas myelodysplasic/myeloproliferative neoplasm (MDS/MPN) was higher in VTE patients (20 % vs. 5.5 %, p=0.01). In a multivariate analysis, only MDS/CMML progression at the time of VTE (odds ratio 28.82, 95 % CI (5.52-530.70) was significantly associated with VTE. When treated with an anticoagulation therapy, bleeding occurred in 19.4% of cases (6/31). Overall survival was not significantly different between patients with and without VTE (p=0.68). Leukaemia-free survival between groups was not significantly different (p=0.83).Conclusions: VTE is a common complication in MDS/CMML-associated SIADSs with an increased risk of bleeding when treated by anticoagulants. In the MDS/CMML subgroup, SIADS flares and MDS/CMML progression seem to be prothrombotic risk factors.

International audience; A 62-year-old man, who was a heavy drinker, presented with deep asthenia, isolated fever, inflammatory syndrome (CRP 120 mg/l) and cytopenias (Hb 6.5 g/dl, platelet count 100 G/l). A whole-body CT scan found dysmorphic hepatomegaly and splenomegaly. Endoscopy revealed bleeding gastrointestinal angiodysplasia and non-bleeding oesophageal varices. After coagulation for angiodysplasia and blood transfusions, the Hb level remained around 8.5 g/dl. To investigate blood malignancy, a bone marrow biopsy revealed small-vessel vasculitis (Fig. 1A, 2), fibrinoid necrosis affecting the small vessel walls (Fig. 1A, 3), multinucleated giant cells (Fig. 1A, 1) constituting microgranulomas (Fig. 1A, 4) and...

Introduction Our objective was to evaluate characteristics, treatment and outcome of vasculitis associated with myelodysplastic syndrome (MDS) and chronic myelomonicytic leukemia (CMML) Patients and Methods Retrospective descriptive analysis of MDS/CMML-related vasculitis and comparison with MDS/CMML patients without dysimmune features. Results Seventy patients with vasculitis and MDS/CMML were included, with median age of 71.5 [21–90] years and male/female ratio of 2.3. Vasculitis was diagnosed prior to MDS/CMML in 31 patients (44%), and after in 20 patients. In comparison with MDS/CMML without autoimmune/inflammatory features, vasculitis with MDS/MPN showed no difference in MDS/CMML subtypes distribution nor International Prognostic Scoring System and CMML-specific prognostic (IPSS/CPSS) scores. Vasculitis subtypes included Giant cell arteritis in 24 patients (34%), Behcet's-like syndrome in 11 patients (20%) and polyarteritis nodosa in 6 patients (9%). Glucocorticoids (GCs) were used as first-line therapy for MDS/CMML vasculitis in 64/70 patients (91%) and 41 (59%) received combined immunosuppressive therapies during the follow-up. After a median follow-up of 33.2 months [1–162], 31 patients (44%) achieved sustained remission. At least one relapse occurred in 43 patients (61%). Relapse rates were higher in patients treated with conventional Disease Modifying Anti-Rheumatic Drug (DMARDs) (odds ratio 4.86 [95% CI 1.38 - 17.10]), but did not differ for biologics (odds ratio 0.59 [95% CI 0.11–3.20]) and azacytidine (odds ratio 1.44 [95% CI 0.21–9.76]) than under glucocorticoids. Overall survival in MDS/CMML vasculitis was not significantly different from MDS/CMML patients without autoimmune/inflammatory features (p = 0.5), but acute leukemia progression rates were decreased (log rank Conclusion This study shows no correlation of vasculitis diagnoses with subtypes and severity of MDS/CMML, and no significant impact of vasculitis on overall survival. Whereas conventional DMARDs seem to be less effective, biologics or azacytidine therapy could be considered for even low-risk MDS/CMML vasculitis.

Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) are associated with systemic inflammatory or autoimmune diseases in 10-20% of cases. Immune thrombocytopenia (ITP) is among the reportedly associated diseases, but large studies assessing the association are lacking. It is unclear whether patients with MDS or CMML and ITP have a particular phenotype or require particular management. We, therefore, analyzed the clinical spectrum, outcome and therapeutic management of patients with ITP associated with MDS or CMML, in comparison to: (i) patients with primary ITP without MDS/CMML and (ii) patients with MDS/CMML without ITP. Forty-one patients with MDS/CMML-associated ITP were included, of whom 26 (63%) had chronic ITP, 30 (73%) had low-risk myelodysplasia and 24 (59%) had CMML. An associated autoimmune disease was noted in ten (24%) patients. In comparison to patients with primary ITP, patients with MDS/CMML-associated ITP had a higher rate of severe bleeding despite similar platelet counts at diagnosis. First-line treatment consisted of glucocorticoids (98%) and intravenous immunoglobulins (56%). Patients with primary ITP were more likely to respond to intravenous immunoglobulins than were patients with MDS/CMML-associated ITP. Response rates to second-line therapies were not statistically different between patients with primary ITP or MDS/CMML-associated ITP. Four (10%) of the patients with MDS/CMML-associated ITP had multirefractory ITP whereas none of the primary ITP controls did so. After a median follow-up of 60 months, there was no difference in overall survival between patients with MDS/CMML-associated ITP or primary ITP. Leukemia-free-survival was significantly better in patients with MDS/CMML-associated ITP than in those with MDS/CMML without ITP. In conclusion, it appears that patients with MDS/CMML-associated ITP have a particular phenotype, with more severe bleeding than patients with primary ITP, a higher likelihood of multirefractory disease, but a similar response to primary ITP therapy except for intravenous immunoglobulins. Finally, compared to MDS/CMML patients without ITP, they are less likely to progress to having acute myeloid leukemia.

International audience; The patient, a 64-year-old man, was admitted to our hospital with a 6-week history of intermittent neck pain, posterior headaches, fever (39°C), and inflammatory syndrome (persistently elevated C-reactive protein level [~200 mg/liter]). Because of a dry cough, bronchopneumonia was initially suspected; however, antibiotics were not effective. He had not experienced vision loss or jaw or limb claudication and was not experiencing any headache at the time of admission. He had been diagnosed as having polymyalgia rheumatica (PMR) 3 years prior, which was still being treated with methotrexate.

Introduction L’objectif de ce travail etait de decrire les caracteristiques cliniques et biologiques, l’evolution et la reponse au traitement des patients avec une thrombopenie immunologique (TI) associee a un syndrome myelodysplasique (SMD) ou une leucemie myelomonocytaire chronique (LMMC). Patients et methodes Il s’agit d’une etude retrospective multicentrique incluant des patients ayant eu, entre 1999 et 2019, un diagnostic de SMD ou LMMC et une thrombopenie immunologique definie selon les criteres internationaux, avec un delai de survenue maximal de 10 ans entre les 2 pathologies. Les patients etaient secondairement apparies sur l’âge, le sexe, le type d’hemopathie (SMD ou LMMC) et le score pronostique IPSS-R, a des patients controles avec « SMD/LMMC sans TI » (ratio de 4 patients pour 1 temoin) issus du registre du Groupe francophone des myelodysplasies, et des patients controles « PTI primaires » sans myelodysplasie retrouvee au myelogramme (ratio de 2 patients pour 1 temoin) issus du registre Carmen. Resultats Cinquante-deux patients ont ete inclus avec un âge median de 77 ans [35–92 ans], 37 % de femmes, dont 31 LMMC (60 %) et 21 SMD (40 %) avec une predominance de SMD avec dysplasie multilignee (52 %), dysplasie unilignee (24 %) et exces de blastes (15 %), et une grande majorite (75 %) de SMD/LMMC de faible risque evolutif (IPSS-R ≤ 3,5). Les thrombopenies immunes etaient synchrones du diagnostic de SMD chez pres de la moitie des patients (46 %). Le diagnostic de thrombopenies immunes precedait celui de SMD dans 38 % des cas [−116 a −6 mois] ou survenait a distance de celui-ci dans 15 % des cas [4 a 119 mois]. Parmi les patients avec thrombopenies immunes et SMD/LMMC, 65 % avaient une thrombopenie immune chronique, 45 % avaient un syndrome hemorragique clinique, 33 % avaient une autre manifestation dysimmunitaire associee, 33 % avaient une hypergammaglobulinemie polyclonale et 43 % des anticorps anti-plaquettes par MAIPA. Cent-sept patients avec PTI primaires et 200 patients avec SMD/LMMC sans thrombopenies immunes ont ete inclus. La numeration plaquettaire mediane au diagnostic des thrombopenies immunes avec SMD/LMMC etait de 26 G/L [1–90] versus 25 G/L [1–98] dans les PTI primaires et 137 G/L [8–1488] dans le groupe SMD/LMMC. Une dysmegacaryopoiese etait plus frequemment retrouvee en cas de SMD/LMMC avec thrombopenies immunes (60 % vs 28 %, p Conclusion L’enjeu diagnostique consiste a reperer, au sein d’une composante centrale habituelle au cours de ces hemopathies, une origine peripherique immunologique de la thrombopenie accessible a un traitement specifique qui est alors calque sur celui des PTI primaires.

Background Myositis is recognized as a manifestation of primary Sjogren’s syndrome (pSS). Grading muscle involvement using the EULAR Sjogren Syndrome Disease Activity index (ESSDAI) does not require biopsy-proven active myositis or extensive immunological investigations. However, several studies have reported that a high proportion of pSS-associated myositis is either inclusion body myositis (IBM) or an overlap with idiopathic inflammatory myopathies. Objectives The objective of our study was to investigate the nature of inflammatory muscle involvement in a large sample of patients with pSS and concurrent myositis. Methods We conducted a French nation-wide survey among reference centers known for their experience in the field of systemic auto-immune diseases. Patients with physician-based diagnosis of pSS and inflammatory muscle involvement were included. They were categorized and subsequently described and compared according to the identification of an associated condition likely to explain inflammatory muscle involvement. Results 60 cases of myositis in patients with pSS were identified. Patients were mostly female (52/60) and pSS classification criteria were met in 43/60. Muscle biopsy was performed in 50/60 patients and showed inflammatory lesions in 80% of cases. An associated condition likely to explain myositis was identified in 31 patients: typical dermatomyositis rash (n=8), MCTD-specific antibodies (n=11), myositis specific antibodies (n=10), and systemic lupus erythematosus, scleroderma or ANCA associated vasculitis specific antibodies in favor of an overlap syndrome (n=7). Among the 29 patients without associated condition likely to explain myositis, 17 had a biopsy proven inflammatory muscle disease, showing histopathologic features consistent with IBM in 5 cases. 4 of the 5 patients with IBM histological features received corticosteroids and/or other immunosuppressive agents to treat muscle disease. Worsening of muscular involvement despite treatment was reported in these 4 patients. Comparative analysis showed a lower ESSDAI (p = 0.001) among patients without identified associated condition likely to explain myositis. Conclusion In most cases of concurrent pSS and myositis, inflammatory muscle involvement is explained by a context of overlap syndrome or has a histological pattern consistent with IBM. Extensive immunological investigations and muscle biopsy appear to be necessary in pSS patients with suspected inflammatory muscle involvement, in order to avoid misclassification and/or overtreatment. Disclosure of Interests Camille Houssais: None declared, Jean-baptiste Noury: None declared, Yves Allenbach: None declared, Laure Gallay: None declared, Florence Assan: None declared, Olivier Benveniste: None declared, Jonathan Broner: None declared, Pierre Duffau: None declared, Alexandra Espitia-Thibault: None declared, Anne Grasland: None declared, Sebastien SANGES: None declared, Gilles Hayem: None declared, Veronique LE GUERN: None declared, Nihal Martis: None declared, Kuberaka Marianpillai: None declared, Denis Mulleman Speakers bureau: Pfizer, Novartis, Grifols, Gaetane Nocturne: None declared, alain meyer: None declared, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Divi Cornec: None declared, Dewi Guellec: None declared

International audience

Contexte : L’enseignement de l’anglais dans les facultes de medecine est obligatoire depuis 1992 mais cette disposition est diversement respectee. Buts : Bilan et perspectives ouvertes par le partenariat entre l’Association nationale des etudiants en medecine de France (ANEMF) et le Groupe d’etude et de recherche en anglais de Specialite (GERAS) membre de la Societe des anglicistes de l’enseignement superieur (SAES). Materiel : Exploitation de differents travaux publies (articles, DEA, manuels), enquetes, reunions GERAS-ANEMF. Resultats : Les enseignants de medecine, d’abord confrontes a la difficulte d’introduire un nouvel enseignement, avec une diminution du volume horaire des matieres medicales et la necessite de deployer des ressources materielles et humaines, participent a present a l’enseignement de l’anglais. Les difficultes initiales rencontrees par les enseignants d’anglais sont compensees par des succes visibles dans certaines facultes. L’enseignement de l’anglais, loin d’etre au mieux une remediation, au pire une perte de temps, vise une competence effective en communication ecrite, orale et interpersonnelle des professionnels de la sante du XXIe siecle. Les etudiants, longtemps hostiles a la reforme, montrent desormais leur interet et souhaitent une harmonisation nationale des contenus, conscients de la necessite pour eux de pouvoir travailler en anglais. Conclusions : La mise en œuvre et le succes de la Charte d’enseignement de l’anglais elaboree par l’ANEMF et le GERAS dependront etroitement du soutien apporte par les autorites competentes de chaque faculte a ce projet, dont la visee est une aide au deroulement de la carriere et de l’activite clinique aussi bien qu’au developpement personnel des futursprofessionnels de la sante.