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Objectives To characterise the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically-guided multivariate model. Methods The HLH Study Group of the Spanish Group of Autoimmune Diseases (GEAS) was formed in 2013 with the aim of collecting a large series of Spanish adult patients with HLH with substantial experience in the management of patients with systemic diseases. By October 2017, the database included 151 consecutive patients who fulfilled at least 5 of the 8 criteria proposed by the Histiocytosis Society in 2004. Results The cohort consisted of 151 patients (91 male, mean age 51.4 years). After a mean follow-up of 17 months, 80 (53%) patients died. With respect to the HLH-dependent variables, adenopathies (HR 0.63, p=0.040), low platelets (HR 3.39, p=0.008), leukopenia (HR 1.81, p=0.047), severe hyponatremia (HR 1.61, p=0.042), disseminated intravascular coagulation (HR 1.87, p=0.034), bacterial infection (HR 1.99, p=0.025), mixed microbiological infections (HR 3.42, p=0.008) and >1 infectious trigger (HR 2.95, p=0.003) were associated with death. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia (p 1 (p=0.011) infections and glucocorticoid monotherapy (p=0.021). After adjusting for confounding variables, platelets 1 infectious trigger (HR 3.43) and mixed microbiological infection (HR 2.96) remained significant. Multivariate Cox proportional hazards regression analysis identified >1 infectious trigger (HR 2.60, 95% CI 1.16 to 5.84) as the only variable independently associated with death. Conclusions The mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with >1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation and therapeutic management. Disclosure of Interest None declared

Introduction La litterature rapporte de rares observations d’infection par VHE associee a une vascularite [1] , [2] . Le pronostic de ces vascularites et de l’infection par le VHE merite d’etre decrit car l’infection par le VHE peut evoluer vers la cirrhose chez certains patients immunodeprimes et cela peut etre prevenu par un traitement antiviral [3] . Nous rapportons une observation de vascularite necrosante avec chondrite et syndrome de Sweet evoquant une polychondrite contemporaine d’une infection aigue par le VHE. Observation Une patiente âgee de 64 ans, sans antecedent particulier, etait hospitalisee en raison d’une fievre d’installation recente avec asthenie intense, des myalgies et polyarthrite. Durant l’hospitalisation apparaissait une chondrite de l’oreille gauche, un purpura vasculaire et des placards cutanes tres inflammatoires et infiltres sur les membres evoquant un syndrome de Sweet. L’hemogramme retrouvait une forte elevation du taux de polynucleaires neutrophiles et de la CRP ainsi que des transaminases. Le bilan infectieux retrouvait uniquement une serologie VHE avec IgM positives. L’infection aigue a VHE etait confirmee par la PCR dans les selles. Le bilan immunologique incluant recherche d’ANCA et de cryoglobulinemie ne retrouvait pas d’anomalie specifique. Les biopsies de peau permettaient de conclure a une dermatose neutrophilique et a une vascularite avec necrose fibrinoide. Medullogramme et biopsie osteomedullaire n’apportaient pas d’argument pour une hemopathie. L’ensemble du tableau clinique et paraclinique conduisait a envisager le diagnostic de premiere poussee de polychondrite atrophiante avec vascularite necrosante. Malgre un traitement par methylprednisolone en bolus puis par prednisone a 1 mg/kg/j apparaissaient de nouvelles lesions purpuriques necrotiques. Un premier bolus de cyclophosphamide (0,7 g/m2) etait prescrit, mais se revelait insuffisant a controler la maladie avec apparition de necroses de deux phalanges des orteils et persistance du syndrome inflammatoire ainsi que d’une polynucleose marquee. La maladie se stabilisait apres un deuxieme bolus prescrit 8 jours apres le premier. La patiente etait ensuite traitee selon un schema classique de vascularite necrosante. Le bilan hepatique se normalisait rapidement et definitivement. Elle a recu successivement cyclophosphamide, azathioprine, methorexate, et reste sous 5 mg/jour de prednisone. La maladie evolue maintenant depuis 3 ans sur un mode essentiellement articulaire, avec apparition d’une arthropathie inflammatoire destructrice digitale. Une seule poussee de vascularite tres limitee a ete observee. L’hepatite ne s’est pas reactivee. Discussion L’association d’une vascularite a l’infection par le VHE est tres rarement rapportee dans la litterature. Il s’agissait d’une vascularite cryoglobulinemique et d’un purpura rhumatoide [1] , [2] . Dans notre observation, l’infection pourrait avoir ete le declencheur de la maladie inflammatoire, qui s’est ensuite autonomisee. Le VHE peut entrainer une infection chronique cirrhogene chez les patients greffes et certains ayant une infection prolongee par le VIH. En revanche, son pronostic parait bon chez des patients presentant un rhumatisme inflammatoire chronique sous immunosuppresseurs [4] . Conclusion L’infection par le VHE pourrait etre un evenement declencheur de vascularite. Un traitement par immunodepresseur majeur ne doit pas etre retarde dans ce contexte par crainte d’aggraver l’hepatite. Une surveillance de l’infection reste requise jusqu’a guerison.

Background HScore is a numeric scoring system recently proposed by Fardet et al in 2014, designed to estimate the risk of having hemophagocytic syndrome (HS) in adults. Objectives The objective of this study is to analyze the potential use of the HScore as a prognostic factor in a large cohort of Spanish patients with adult HS. Methods In June 2013, the Study Group of Autoimmune Diseases (GEAS-SEMI) created the National Registry of Adult Patients with HS. Patients were diagnosed according to the fulfillment of the Histiocytosis Society criteria proposed in 1991 and updated in 2004. The HScore includes 9 clinical, laboratory and histopathological criteria, and the score may range from 0 to a maximum of 337 points. Results By January 2015, the REGHEM registry included 111 adult patients with HS, 65 (59%) men and 46 (41%) women, with a mean age at diagnosis of 49.16 years (range 12-85 years); nineteen patients (17%) were not born in Spain (58% from Latin America, 21% from Africa and 16% from Asia). Tissular hemophagocytosis was confirmed in 97/107 (87%) cases. The main underlying diseases diagnosed before HS were autoimmune/rheumatological diseases in 36 (33%) patients, chronic infections in 24 (22%) and neoplasia in 25 (23%) patients. The great majority of patients required ICU admission and death occurred in 59 (53%). The HScore was retrospectively calculated in 61 patients in whom all the criteria required could be applied: the mean HScore was 230,03 (range, 58-306). No significant differences for the mean HScore were found with respect to gender, age at diagnosis, underlying diseases, or severe internal organ involvement (pulmonary, renal or central nervous system). However, a higher mean HScore was found in foreign patients (257 vs 222, p=0.02), in patients with concomitant infections with confirmed microbiological isolation (243 vs 214, p=0.022) and in those who required vital support (248 vs 212, p=0.004). Patients who died showed a higher mean HScore in comparison with survivors (241 vs 217, p=0.05). Conclusions Hemophagocytic syndrome is a life-threatening multisystemic disease that often requires vital support in intensive care units. Despite this and the use of a complex therapeutic approach, half of the patients died. We found higher HScores in patients presenting with a complicated HS (concomitant infections, need for vital support and death). The use of the new HScore as prognostic factor may help to identify patients with a poor outcome. Disclosure of Interest None declared