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Sustained response off-treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in ITP. This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response on TPO-RAs. The primary endpoint was the proportion of patients achieving SROT (platelet count > 30x109/L and no bleeding) at W24 with no other ITP-specific medications. Secondary endpoints included the proportion of sustained complete response off-treatment (SCROT, platelet count > 100x109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with median (IQR) age 58.5 years (41-73.5); 30/48 (63%) had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27/48 (56.2%, 95% CI, 41.2-70.5) achieved SROT; 15/48 (31.3%; 95% CI, 18.9-44.5) achieved SCROT at W24, and 25/48 (52.1%; 95% CI, 37.2-66.7) achieved respectively SROT and 14/48 (29.2%; 95% CI, 17.2-42.3) SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients re-challenged with TPO-RA, 11/12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA-seq revealed enrichment of a "TNFα signaling via NF-κB" signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based of progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. Clinical trial number: NCT03119974

The risk of immune thrombocytopenia (ITP) worsening during pregnancy and neonatal ITP (NITP) have never been prospectively studied. We included 180 pregnant and 168 nonpregnant women with ITP in a prospective, multicenter, observational cohort study. A total of 131 pregnant women with ITP were matched to 131 nonpregnant women with ITP by history of splenectomy, ITP status (no response, response, complete response), and duration. Groups were followed for 15 months. The primary outcome was the first occurrence of ITP worsening defined by a composite end point including bleeding events and/or severe thrombocytopenia (

To study a muscle-to-muscle standardised uptake value (SUV) ratio with FDG-PET/CT (FDG-PET) as a marker for the detection of disease activity in dermatomyositis (DM). Patients with DM (n = 24) who met the European Neuro-Muscular Centre diagnostic criteria were retrospectively identified over a 3-year period through a national survey. Muscle biopsy was performed in all patients. Maximum SUV was measured in proximal muscles (SUVPROX) that had the highest radiotracer uptake on visual grading as well as in the musculus longissimus thoracis (SUVMLT), whereas mean SUV was measured for the liver (SUVLIV). Muscle-to-liver SUV ratios for either muscle group were compared and a SUVPROX/SUVMLT ratio was calculated. SUVPROX/SUVMLT of DM patients were compared with age- and sex-matched control subjects (n = 24) with melanoma who had received FDG-PET scans. DM patients presented with proximal and symmetrical muscle uptake. Differences in SUVPROX/SUVLIV and SUVMLT/SUVLIV ratios in DM subjects were significant (p

International audience; No abstract available

Background: Thrombopoietin receptor agonists(TPO-RAs) have been thought to play only a supporting role in ITP management. Several retrospective studies and a recent prospective study have reported unexpected cases of durable remission after TPO-RAs discontinuation in adult ITP in up to 30%. However, newly diagnosed ITP cases for which spontaneous remission may occur have been included in most of these studies. Thus, the main purpose of this study was to determine the proportion of patients with either persistent or chronic phase and no recent exposure to any potentially curative therapy (i.e., splenectomy or rituximab) achieving long-term remission off-treatment at 24 and 52 months after at least 3 months of TPO-RAs exposure with a complete response (CR). Patients/methods: We conducted a nationwide prospective multicenter interventional study (NCT03119974). Inclusion criteria were: 1) Patients aged > 18 years, with persistent or chronic primary ITP, 2) A stable CR defined by a platelet count > 100 x 10 9/L for more than 2 months on TPO-RA therapy, 3) Treatment with TPO-RA for at least 3 months. Main exclusion criteria were: 1) Anticoagulation or anti-platelet treatment, 2) Previous failure of TPO-RA discontinuation, 3) Concomitant treatment with corticosteroids ± intravenous immunoglobulin 4) Rituximab or splenectomy within the 2 months preceding or after TPO-RA initiation. After inclusion, the decrease and wean of either eltrombopag or romiplostim was initiated according to a standardized protocol (respectively tapering of 25 mg every 2 weeks or tapering of 1 ug/kg every week). In any case TPO-RAs had to be stopped at week 10. In case of relapse after TPO-RA discontinuation, the decision to start a new therapy was left at every investigator discretion. The primary endpoint was the proportion of patients achieving an overall response (CR + R) at week 24 (6 months) after TPO-RAs discontinuation. Secondary outcomes were overall response rate over the study period (W52), bleeding events, and to identify predictive factors, for overall prolonged response (W24 and W52). Results: Forty-nine patients (30 females, 61%), with persistent (n=2) or chronic (n=47, 96%) chronic ITP, with a median age of 58.5 years IQR (41 to 73) fulfilling the eligibility criteria were included over 2 year-period in 22 centers from the French reference network for adult' ITP. Forty patients received eltrombopag and 9 romiplostim at the time of inclusion. One patient was excluded since she was diagnosed pregnant one day after inclusion. In intention to treat 27/48 (56.2%; 95% CI, 29.5 to 58.8) patients achieved the primary-endpoint and maintained an overall response at week 24 after TPO-RAS discontinuation with a complete response for 15/27 (55%). During the full follow-up period of 52 weeks after TPO-RAs discontinuation, overall response was observed in 25/48 (52.1%; 95% CI, 37.2 to 66.2) patients (Figure 1). Bleeding events occurred in 13/21 (61.9%) and 15/23 (65.2%) patients relapsing respectively at 24 and 52 months with a median platelet count of 31´10 9/L(26 to 39) and 31 ´10 9/L(23 to 39). No severe bleeding episode (French bleeding score > 8) occurred. Median time of relapse after tapering initiation was 8 weeks. Among 21 patients with a relapse ( Conclusion: These results showed an unexpectedly high rate of sustained off-treatment remission after TPO-RAs discontinuation in chronic ITP among patients who initially achieve a stable CR. When they occur, relapses are mainly observed within the first weeks after discontinuation, very rarely afterwards and with no severe bleeding. While no predictive factor of lasting remission has been yet identified, our study strongly supports a progressive tapering of the dose of TPO-RAs in patients achieving a stable CR on treatment. Figure 1: Relapse at 52 weeks after TPO-RAs discontinuation Figure 1 Figure 1. Disclosures Mahevas: GSK: Research Funding; Amgen: Honoraria. Viallard: Novartis: Consultancy; Grifols: Consultancy; LFB: Consultancy; Amgen: Consultancy. Moulis: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Argenx: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees. Terriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Michel: Novartis: Consultancy; Amgen: Consultancy; UCB: Honoraria; Argenx: Honoraria; Rigel: Honoraria; Alexion: Honoraria. Godeau: Sobi: Consultancy; Novartis: Consultancy; Amgen: Consultancy; Grifols: Consultancy.

Introduction Le Purpura thrombopenique immunologique (PTI) peut affecter les femmes en âge de procreer. L’effet de la grossesse sur les femmes avec un diagnostic pre-gestationnel de PTI reste incertain et n’a jamais ete etudie prospectivement. Objectif Evaluer l’effet de la grossesse sur l’evolution du PTI. Patients et methodes Etude cas-controles prospective multicentrique observationnelle (ClinicalTrials.gov NCT02892630 ) menee par 33 centres appartenant au reseau du centre reference des cytopenies auto-immunes de l’adulte. Sur une periode de 2 ans, 131 femmes enceintes avec un diagnostic pre-gestationnel de PTI et 131 femmes controles en âge de procreer ayant un PTI mais sans grossesse evolutive ont ete incluses. Les criteres d’appariement incluaient 1) un antecedent de splenectomie, 2) le statut du PTI (defini comme non repondeur, repondeur ou repondeur complet en fonction du nombre de plaquette et de la necessite de modification therapeutique dans les 2 derniers mois) et 3) la duree du PTI (persistant Resultats Une aggravation du PTI a ete significativement plus frequente chez les femmes enceintes compares aux controles, 52,7 % versus 38,2 % (p = 0,05). L’aggravation etait observee principalement pendant le 2e et le 3e trimestre. Cependant la frequence des thrombopenies severes (28,2 % versus 25,2 % p = 0,69) et l’incidence d’evenement hemorragique (22,9 % versus 15,3 %, p = 0,15) etaient similaires dans les 2 groupes, ainsi que l’incidence de survenue de saignements severes (definis par une score hemorragique de Khellaf > 7) (16 % vs 9,2 %, p = 0,69). En revanche la necessite d’une modification ou d’une intensification therapeutique (n’incluant pas la preparation a l’accouchement) a ete significativement plus frequente chez les femmes enceintes comparees aux controles [32,1 % versus 20,6 % (p = 0,01)]. Il faut cependant souligner qu’aucune augmentation des complications associees a cette hausse d’intervention therapeutique tels qu’une HTA ou un diabete n’a ete observee chez les femmes enceintes par rapport aux temoins. Enfin, compare a la periode pre-gestationnelle, une aggravation du statut du PTI a 6 mois post-partum etait notee chez 16,8 % des femmes enceintes. Cette frequence etait comparable a celle observee dans le groupe temoin apres 15 mois de suivi (16,8 %, p = 0,57). Conclusion Cette etude prospective demontre pour la premiere fois que les femmes avec un PTI sont plus intensivement traitees durant la grossesse comparees a un groupe controle apparie. Ceci ne coincide cependant pas avec une aggravation clinique ou biologique chez les femmes enceintes. A 6 mois du post-partum, la frequence d’aggravation du PTI etait faible et similaire a celle observee chez les controles temoignant du bon pronostic du PTI au cours de la grossesse. Les recommandations internationales et francaises du PNDS pour la prise en charge therapeutique des femmes enceintes atteintes d’un PTI recommandent un traitement pour les femmes ayant un nombre de plaquette

Introduction La thrombopenie immunologique neonatale (TINN) definie par un nombre de plaquettes Patients et methodes Une etude multicentrique prospective observationnelle (ClinicalTrials.gov NCT02892630 ) a ete conduite dans 33 centres appartenant au reseau du centre de reference des cytopenies auto-immunes de l’adulte. Sur une duree de 2 ans, 180 femmes enceintes avec un diagnostic de PTI pre-gestationnel ont ete incluses et 171 ont ete suivies jusqu’a leur accouchement. Le nombre de plaquettes des NN etait disponible pour 136 femmes. Les facteurs de risque de developper une TINN ont ete evalues ainsi que les complications observees chez les NN et les traitements qui leur ont ete administres. Resultats Une TINN, a ete observee chez 37 nouveau-nes (27,2 %). Une TINN plus severe avec des chiffres de plaquettes Conclusion Notre etude confirme qu’un antecedent de TINN lors d’une precedente grossesse est un facteur de risque de TINN. Nous identifions pour la premiere fois que l’aggravation du PTI chez la mere au cours de la grossesse est un facteur de risque de TINN severe. En revanche, nous ne confirmons pas un antecedent de splenectomie comme associe avec une augmentation du risque de TINN comme suggere dans des etudes retrospectives (Loustau et al, Br J Haematol 2014 ; 166 929–35). Nos resultats confirment que la survenue d’une grossesse chez une femme avec un diagnostic pre-gestationnel de PTI est associee avec un risque acceptable de saignement severe chez les NN avec TINN. Une surveillance rapprochee de la grossesse et de l’accouchement des femmes suivies pour un PTI et de leur NN est recommandee, en particulier chez les femmes qui ont un antecedent de TINN lors d’une grossesse anterieure ou chez qui on observe une aggravation de leur PTI durant la grossesse.

Background : Neonatal immune thrombocytopenia (NITP) is a well described complication in newborns of women with ITP. It is reported to occur in about 15% to 30% of neonates. Previous pregnancies with NITP or ITP refractory to splenectomy have been described as associated with NITP mostly in retrospective studies. Methods: We conducted a nationwide prospective multicenter observational case-control study (ClinicalTrials.gov NCT02892630). Thirty-three centers including in the network of ITP experts in France participated in the study. Over a two years period, we enrolled 180 pregnant women with a history of ITP diagnosed before pregnancy and 171 of them were followed up until the delivery. Neonatal platelet counts were available for 136 newborns. Risk factor for developing NITP were evaluated as well as NITP treatment and complications. Results: NITP defined as a platelet count < 100 x 109/L was observed in 37 newborns (27.2%). More severe NITP with platelet counts < 50 x 109/L and < 30 x 109/L, were reported in 19 (14%) and 13 (9.6%) newborns respectively. Intravenous immune globulins were given to 18 newborns. Their median platelet count was 25.5 x 109/L (6; 56). Platelet transfusion was used for 8 newborns with a median platelet count of 13.5 x 109/L (6; 50). NITP was complicated by a hemorrhagic event in only 2 newborns, with a fatal bleeding in 1. Decline in disease ITP status in the mother during pregnancy and previous history of NITP were identified as predictors of NITP < 50 x 109/L by a univariate analysis while only previous history of NITP was confirmed in multivariate analysis (adjusted odds ratio (OR) 4.55; 95% confidence interval (CI) 1.48-13.92; p= 0.008). Decline in ITP disease status in the mother during pregnancy was the sole predictive factor for severe NITP defined as platelet < 30 x 109/L in multivariate analysis (adjusted OR 3.99; 95% CI 1.04-15.36; p = 0.044). Conclusion: Our study confirms that for ITP women with several pregnancies, a previous history of NITP is a risk factor for NITP. We also identify for the first time worsening of disease status during pregnancy to be a novel risk factor of severe NITP. In contrast, we did not confirm that a history of splenectomy was associated with an increased risk of NITP as suggested in retrospective studies (Loustau et al, Br J Haematol 2014; 166 929-35). Our results support that pregnancy in women with ITP is associated with an acceptable risk of severe bleeding in the newborn with NITP which is low but yet existing. Hence, close monitoring of pregnancy and delivery of mothers with ITP and their newborns is required, mainly in women who have a previous history of NITP or experienced a worsening of ITP during the pregnancy. Disclosures Haioun: Takeda: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Roche: Honoraria; Servier: Honoraria; Miltenyi: Honoraria. Mahevas:GSK: Research Funding. Michel:Rigel: Consultancy; Bioverativ: Consultancy; Alexion Pharmaceuticals: Consultancy. Godeau:Novartis: Honoraria; Amgen: Honoraria; Amgen: Research Funding; LFB: Honoraria.

Background: Adult immune thrombocytopenia (ITP) is a rare autoimmune disease that can affect women of childbearing age. The effect of pregnancy on women with a pregestational diagnosis of ITP is still unclear and has never been prospectively studied. Objective: Investigate the effect of pregnancy on the course of ITP. Methods: We conducted a nationwide prospective multicenter observational case-control study (ClinicalTrials.gov NCT02892630). Thirty-three centers from the French ITP reference center network participated in the study. Over a two years period, we enrolled 131 pregnant women with a pregestational diagnosis of ITP and 131 non pregnant women of childbearing age with ITP who served as controls. Matching criteria included: history of splenectomy, disease status (defined as non-responder, responder or complete responder depending on platelet count and the need of treatment modification in the last 2 months) and ITP duration (i.e; persistent (7) (16% vs 9.2%, p= 0.11).In contrast, initiation and intensification of therapy were significantly increased in pregnant women compared to matched controls, respectively 32.1% versus 20.6% (p = 0.01) of patients. Importantly, this increased need for therapy did not lead to an increase in maternal and obstetrical complications. In particular, we found no increase of complications that could have been exacerbated by corticosteroid and intravenous immunoglobulins use such as gestational diabetes or high blood pressure. Also compared to pre-gestational period, at 6 months post-partum, only 16.8% of pregnant women showed disease worsening. This frequency was comparable in the control group after 15 months follow-up (16.8%, p = 0.57). Conclusion: The current guidelines on therapy for pregnant women with pregestational ITP are mostly based on expert opinions and retrospective studies that mainly recommend treatment for pregnant women with a platelet count < 30 x 109/L. This prospective observational study investigating ITP progression during pregnancy shows that women with ITP were more intensively treated during pregnancy compared with matched controls. Paradoxically, this does not coincide with an increased of clinical or biological worsening in pregnant womenwhich raises questions of the relevance of this therapeutic conduct although we cannot exclude that these therapies may have prevented disease progression during pregnancy. Finally in late post-partum period, disease worsening was low and seems to be link to the natural course of the disease. Disclosures Haioun: Celgene: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Roche: Honoraria; Servier: Honoraria; Amgen: Honoraria; Miltenyi: Honoraria. Mahevas:GSK: Research Funding. Michel:Rigel: Consultancy; Alexion Pharmaceuticals: Consultancy; Bioverativ: Consultancy. Godeau:Novartis: Honoraria; LFB: Honoraria; Amgen: Honoraria; Amgen: Research Funding.

Background Safety of HPV vaccines is still in question due to reports of autoimmune diseases (ADs) following HPV immunization. Objectives To assess the risk of ADs associated with HPV vaccination of female adolescents/young adults in France. Methods Systematic prospective case-referent study conducted to assess the risks associated with real-life use of HPV vaccines. Cases were female 11–25 years old with incident ADs [central demyelination/multiple sclerosis (CD/MS), connective tissue disease (CTD), Guillain-Barre syndrome (GBS), type-1 diabetes (T1D), autoimmune thyroiditis (AT), and idiopathic thrombocytopenic purpura (ITP)]. Cases were consecutively and prospectively identified at specialized centers across France (2008–2014) and individually matched by age and place of residence to referents recruited in general practice. Risk was computed using multivariate conditional logistic regression models adjusted for family history of ADs, living in France (north/south), co-medications and co-vaccinations. Results With a total of 478 definite cases matched to 1869 referents, all ADs combined were negatively associated to HPV vaccination with an adjusted odds ratio of 0.58 (95% confidence interval: 0.41–0.83). Similar results were obtained for CD/MS, AT, CT, and T1D, the last two not reaching statistical significance. No association was found for ITP and GBS. Sensitivity analyses combining definite and possible cases with secondary time window showed similar results. Conclusion Exposure to HPV vaccines was not associated with an increased risk of ADs within the time period studied. Results were robust to case definitions and time windows of exposure. Continued active surveillance is needed to confirm this finding for individual ADs.

This phase 3 multicentre randomized double-blind and placebo-controlled trial aimed to compare the efficacy and safety of rituximab (RTX) to placebo for treating newly diagnosed warm autoimmune hemolytic anemia (wAIHA) in adults receiving prednisone. Adults with a confirmed diagnosis of wAIHA who previously received corticosteroids for less than 6 weeks could be included. At inclusion, all patients received prednisone at a daily dose of 1 mg/kg for 2 weeks, then tapered according to a pre-defined recommended reduction scheme. Besides prednisone, eligible patients received 2 infusions of RTX or placebo at a fixed dose of 1,000 mg 2 weeks apart. The primary endpoint was overall response rate (complete response [CR] + partial response [PR]) in an intent-to-treat (ITT) analysis at 1 year. A total of 32 patients (17 females [53%], mean age at inclusion 71±16 years) were enrolled and randomized. In all, 27 patients were followed for at least 1 year and their data were evaluable for response. With an ITT analysis, the overall response rate at 1 year was 75% [95%CI: 47.6-92.7] with 11 CR and 1 PR with RTX versus 31% [11.0-58.7] (5 CR) with placebo (p=0.032). At 2 years, 10/16 patients with RTX versus 3/16 with placebo still showed CR (p=0.011). Overall, 8 severe infections occurred during follow-up, 6 with placebo and 2 with RTX (p=0.39). At 2 years, 6 patients with placebo had died, but none with RTX (p=0.017). Compared to placebo, RTX combined with prednisone may be effective and safe for treating newly-diagnosed wAIHA in adults. This article is protected by copyright. All rights reserved.

Although vincristine (VCR) is sometimes prescribed for newly diagnosed immune thrombocytopenia (ITP), its efficacy in refractory ITP and sustained efficacy has yet to be demonstrated. We describe our clinical experience and recommend vincristine's correct place in ITP management. This retrospective study analysed data from 35 patients with newly diagnosed (ND), persistent (P) or chronic (C) ITP treated with VCR. The initial response rate, defined as >30 × 10(9) platelets/L, reached 86% after a median of 7 [interquartile range (IQR) 6-13] days. In ND and P ITP, even when previous therapies were inefficient, initial response was 87.5%, suggesting that this treatment could be used particularly in rescue. Median survival time, without failure or relapse, was 15 months (Kaplan-Meier curve). Predictive factors (univariate analysis) of an initial and long-term response were a small number of prior treatments received. However, at 2 yr, only seven patients had sustained response. Eight (23%) patients experienced adverse events: neuropathy for seven and bowel obstruction for one. Vincristine efficacy in ITP was confirmed, and it could be a good strategy for treating resistant ITP, especially in emergencies. In this era of new therapeutics, VCR deserves to remain on the list of ITP treatments because of its initial efficacy, safety and low cost.

Objective: To report a case of a schwannoma of nasopalpebral location, occurring in a human immunodeficiency virus (HIV)-positive patient. Clinical Presentation and Intervention: A 55-year-old man presented with a nasopalpebral painless tumefaction, pneumopathy and HIV-related immunodepression after stopping combination antiretroviral therapy. Magnetic resonance imaging showed subcutaneous masses, with contrast enhancement of the left nose pyramid, internal cantus and inferior palpebral area, suspicious of Kaposi sarcoma. The resected specimen showed schwannoma histology, with tumor cells expressing S100 protein and WT1. Conclusion: The features of a rare case of facial schwannoma of nasopalpebral location in an HIV-positive patient are reported. The diagnosis may be difficult before microscopic examination, with imaging features suggesting a Kaposi sarcoma.

La Presse Medicale - In Press.Proof corrected by the author Available online since mardi 1 septembre 2015

The cause of immune thrombocytopenia (ITP) remains unknown. Studies have suggested immunizations as possible triggering factors of ITP through molecular mimicry. This case-control study explored potential associations between adult ITP and various routinely administered vaccines. A network of internal medicine and hematology centers across France recruited 198 incident (ie, newly diagnosed) cases of ITP between April 2008 and June 2011. These cases were compared with 878 age- and sex-matched controls without ITP recruited in general practice. Information on vaccination was obtained from patients' standardized telephone interviews. Sixty-six of 198 cases (33.3%) and 303 of 878 controls (34.5%) received at least 1 vaccine within the 12 months before the index date. We found no evidence of an increase in ITP after vaccination in the previous 6 or 12 months (adjusted odds ratio [OR] for the previous 12 months = 1.0; 95% confidence interval, 0.7-1.4). When the 2-month time window was used, higher ORs were observed for all vaccines (OR = 1.3). This increase was mainly attributable to the vaccination against diphtheria-tetanus-pertussis-poliomyelitis (OR = 1.5) and was not statistically significant. The results of the present study show that in an adult population, the exposure to common vaccines is on average not associated with an observable risk of developing ITP.

This Phase 3 multicentre randomized double-blind and placebo-controlled trial aimed to compare the efficacy and safety of rituximab (RTX) to placebo for treating newly diagnosed warm autoimmune hemolytic anemia (wAIHA) in adults receiving prednisone. Adults with a confirmed diagnosis of wAIHA who previously received corticosteroids for less than 6 weeks could be included. At inclusion, all patients received prednisone at a daily dose of 1 mg/kg for 2 weeks, and then tapered according to a pre-defined recommended reduction scheme. Besides prednisone, eligible patients received 2 infusions of RTX or placebo at a fixed dose of 1,000 mg 2-week apart. The primary endpoint was overall response rate (complete response [CR] + partial response [PR]) in an intent-to-treat (ITT) analysis at 1 year. A total of 32 patients (17 females [53%], mean age at inclusion 71 ± 16 years) were enrolled and randomized. In all, 27 patients were followed for at least 1 year and their data were evaluable for response. With an ITT analysis, the overall response rate at 1 year was 75% [95%CI: 47.6-92.7] with 11 CR and 1 PR with RTX versus 31% [11.0-58.7] (5 CR) with placebo (P = 0.032). At 2 years, 10/16 patients with RTX versus 3/16 with placebo still showed CR (P = 0.011). Overall, eight severe infections occurred during follow-up, six with placebo and two with RTX (P = 0.39). At 2 years, six patients with placebo had died, but none with RTX (P = 0.017). Compared to placebo, RTX combined with prednisone may be effective and safe for treating newly-diagnosed wAIHA in adults. Am. J. Hematol. 92:23-27, 2017. © 2016 Wiley Periodicals, Inc.

for the PGRx-ITP Study Group; International audience; This prospective observational cohort study aimed to explore the clinical features of incident immune thrombocytopenia in adults and predictors of outcome, while determining if a family history of autoimmune disorder is a risk factor for immune thrombocytopenia. All adults, 18 years of age or older, recently diagnosed with immune thrombocytopenia were consecutively recruited across 21 hospital centers in France. Data were collected at diagnosis and after 12 months. Predictors of chronicity at 12 months were explored using logistic regression models. The association between family history of autoimmune disorder and the risk of developing immune thrombocytopenia was explored using a conditional logistic regression model after matching each case to 10 controls. One hundred and forty-three patients were included: 63% female, mean age 48 years old (Standard Deviation=19), and 84% presented with bleeding symptoms. Median platelet count was 10×109/L. Initial treatment was required in 82% of patients. After 12 months, only 37% of patients not subject to disease-modifying interventions achieved cure. The sole possible predictor of chronicity at 12 months was a higher platelet count at baseline [Odds Ratio 1.03; 95%CI: 1.00, 1.06]. No association was found between outcome and any of the following features: age, sex, presence of either bleeding symptoms or antinuclear antibodies at diagnosis. Likewise, family history of autoimmune disorder was not associated with incident immune thrombocytopenia. Immune thrombocytopenia in adults has been shown to progress to a chronic form in the majority of patients. A lower platelet count could be indicative of a more favorable outcome.

Summary Leiomyosarcoma is rare in ileal location. We report the case of a 61 years old female patient presenting with ileal leiomyosarcoma occurring at 14 years after a uterine carcinoma treated by radiotherapy. The ileal tumor was treated by surgical resection. This tumor was peculiar by the macroscopic polypoid appearance and by expression of PDGFRA protein together with muscle differentiation proteins: smooth muscle actin, desmin and h-caldesmon. Lymph node necrotizing granuloma diagnosis on the surgical resection specimen lead to the diagnosis of tuberculosis and the patient was treated accordingly. At 3 years after the diagnosis, the patient was well, without recurrence or metastases. In conclusion, we report the case of a patient diagnosed with ileal leiomyosarcoma occurring 14 years after adjuvant radiotherapy for uterine carcinoma. Analysis of the intestinal resection specimen lead to the diagnosis of associated tuberculosis. Moreover, the leiomyosarcoma was peculiar by PDGFRA expression, feature which might be of clinical relevance since the treatment options in radioinduced tumors associated with other conditions are limited.

Background Tuberculous cerebral vasculitis is a complication of tuberculous meningitis. This study was undertaken to determine the epidemiological characteristics, context, diagnostic means and outcomes under treatment of tuberculous cerebral vasculitides. Methods All consecutive patients diagnosed with tuberculous cerebral vasculitis were identified from the databases of three Internal Medicine, one Neurology and one Infectious Disease Departments in three suburban Parisian hospitals. Results We describe 10 cases: five men and five women (median age 33.5 [range: 27–55] years). Two were infected with the human immunodeficiency virus. Nine patients had tuberculous meningitis, eight with extraneurological involvement. The following manifestations led to the diagnosis: motor deficit, acute confusional state, headaches, involvement, coma and/or seizures. The cerebral vasculitis revealed tuberculosis in three patients, but tuberculosis was already known when vasculitis was diagnosed for the seven others. The cerebral computed-tomography scan showed cerebral infarctions in five patients, hydrocephalus and tuberculomas in four, while magnetic resonance imaging detected infarctions and leptomeningitis in nine patients, pachymeningitis in one, hydrocephalus and tuberculomas in seven. Therapy combined antituberculous agents with oral corticosteroids for all patients, preceded by a methylprednisolone pulse for five patients. Outcome was favorable for nine patients. Conclusion We described the non-negligible frequency of tuberculous cerebral vasculitides, their clinical manifestations and their potential severity, and the diagnostic and monitoring contributions of magnetic resonance imaging and magnetic resonance angiography.

Resume Introduction L’existence d’une fievre au cours d’un syndrome myelodysplasique oriente vers une complication infectieuse ou une maladie systemique. Le risque de transformation des syndromes 5q– est faible. Observation Une femme de 51 ans, neutropenique, suivie pour un syndrome 5q– presentait une fievre prolongee inexpliquee. Les recherches microbiologiques etaient negatives et les antibiotiques inefficaces. Les prelevements sanguins et medullaires ne montraient pas de blastose. La biopsie hepatique mettait en evidence des cellules blastiques traduisant l’acutisation extramedullaire et le caryotype montrait une evolution clonale avec remaniements des chromosomes 5, 12 et 19. Conclusion L’absence de blastose medullaire n’elimine pas le diagnostic de transformation en leucemie aigue d’un syndrome myelodysplasique. Une biopsie tissulaire, osseuse ou hepatique, peut etre necessaire pour confirmer l’acutisation.

We report the case of a 32-year-old Indian man with symptoms suggesting Zollinger-Ellison syndrome including abdominal pain, esaphagitis, duodenal stenosis that did not improve with antisecretory medication, elevated fasting gastrin serum levels that increased after intravenous secretin injections, elevated chromogranin A serum levels and tumoral aspect of pancreatic uncus on CT scan examination. A pancreaticoduodenectomy was performed. Histological examination of the resected specimen showed that there was no endocrine tumour of the pancreas or the duodenum, but identified marked lesions of follicular and caseous tuberculosis. The final diagnosis retained pseudo Zollinger-Ellison syndrome due to gastric outlet obstruction caused by duodenal stenosis of a tuberculosis origin.

Introduction Les objectifs etaient : – de decrire pour la premiere fois dans une etude prospective les caracteristiques cliniques de patients adultes ayant un purpura thrombopenique immunologique (PTI) nouvellement diagnostique ; – d’explorer le pourcentage de passages a la chronicite (duree d’evolution du PTI > 1 an) et les facteurs predictifs d’une evolution chronique ; – de determiner si la presence d’antecedents (ATCD) familiaux de maladie auto-immune etait associee a un risque augmente de developper un PTI. Materiels et methodes Une etude de cohorte observationnelle a ete menee en France metropolitaine. Sur une duree de 28 mois, 21 medecins participant a l’etude ont recrute de maniere consecutive tous les patients de 18 ans ou plus, ayant un PTI nouvellement diagnostique. Les donnees sociodemographiques, les ATCD personnels et familiaux, les caracteristiques cliniques et biologiques du PTI et la prise en charge initiale ont ete collectees a l’inclusion. A 12 mois, les caracteristiques cliniques et biologiques du PTI ont ete renseignees, afin d’identifier une guerison ou une evolution vers la chronicite. Les facteurs associes avec une evolution chronique ont ete identifies grâce a des modeles de regression logistique univaries, la force et la significativite de l’association etant representees par l’ odds ratio (OR) et son intervalle de confiance a 95 % (IC95 %). Afin de determiner si la presence d’ATCD familiaux de maladie auto-immune etait associee a un risque augmente de developper un PTI, 10 patients temoins, non atteints de PTI, ont ete apparies a chaque patient ayant un PTI, sur l’âge, le sexe et la date d’inclusion. Le risque de developper un PTI en lien avec les ATCD familiaux a ete explore par des modeles de regression logistique univaries conditionnels. Resultats Cent cinquante-trois patients ont ete inclus : 94 (61 %) etaient des femmes, l’âge moyen etait de 48 ans (ET = 19) et 128 (84 %) patients avaient des saignements au diagnostic. Le taux median de plaquettes etait de 10 G/L. Un traitement initial a ete mis en place chez pres de 90 % des patients. Apres 12 mois, seuls 36 % des patients etaient gueris sans avoir recu de traitement type disease-modifying (rituximab ou splenectomie). Le risque de passage a la chronicite etait d’autant plus important que le chiffre de plaquettes au diagnostic etait eleve (OR : 1,0 ; IC95 % : 1,0–1,2) et qu’il n’y avait pas de saignement cutaneomuqueux initial (OR : 0,3 ; IC95 % : 0,1–1,0). Il n’y avait pas d’association entre ATCD familiaux de maladie auto-immune et risque de developper un PTI. Conclusion Le PTI chez l’adulte atteint des patients d’âge varies et en majorite des femmes. L’evolution vers la chronicite concerne la majorite des patients. Un plus haut taux de plaquettes ou l’absence de saignement cutaneomuqueux initial sont predictifs d’une evolution chronique mais la pertinence clinique de ces facteurs pronostiques a l’echelon individuelle est discutable.

Introduction L’anemie hemolytique auto-immune a anticorps chauds (AIHAc) est une maladie auto-immune rare pouvant mettre en jeu le pronostic vital notamment chez le sujet âge. Le rituximab a montre une efficacite prometteuse au cours de l’AHAIc dans plusieurs etudes retrospectives et dans 2 etudes prospectives et est regulierement utilise hors AMM dans ce contexte comme traitement de seconde ligne en cas de corticodependance ou de corticoresistance. Patients et methodes L’essai RAHIA est un essai prospectif multicentrique randomise en double insu versus placebo visant a apprecier l’efficacite et la tolerance du rituximab administre en premiere ligne en association a la corticotherapie dans l’AHAIc de l’adulte. Les criteres d’inclusion etaient les suivants : âge ≥ 18 ans ; diagnostic d’AHAIc defini par une anemie avec un taux d’hemoglobine (Hb) ≤ 10 g/dL de mecanisme hemolytique avec un test de Coombs direct positif de type IgG ou IgG + C3d, et ce en l’absence d’autre cause d’hemolyse constitutionnelle ou acquise. Seuls les patients traites par corticoides depuis moins de 6 semaines pouvaient etre inclus. Les patients avec une AHAIc secondaire etaient exclus a l’exception des patients ayant une leucemie lymphoide chronique de stade A. A l’inclusion, tous les patients recevaient de la prednisone a la dose de 1 mg/kg/j pendant 2 semaines suivi d’une decroissance tous les 10 jours jusqu’a l’arret au bout de 3 mois en cas de reponse complete et ce selon un schema pre-defini. En association a la corticotherapie, les patients eligibles recevaient soit du rituximab (bras A) a la dose fixe de 1000 mg a j1 et j15 soit un placebo (bras B) et ce en double insu. L’objectif primaire etait de comparer le taux de reponse globale (reponse complete et partielle) a 1 an dans les 2 bras. La remission complete (RC) etait definie par un taux d’Hb ≥ 11 g/dL chez la femme et 12 g/dL chez l’homme en l’absence d’hemolyse et de tout traitement et ce confirme a 2 reprises a au moins 4 semaines d’intervalle. La remission partielle (RP) etait definie par un taux d’Hb ≥ 10 g/dL en l’absence de traitement autre que la prednisone a une dose ≤ 10 mg/j. En cas d’Hb 10 mg/j et/ou de recourir a un autre traitement actif dans l’AHAI (splenectomie, immunosuppresseur) dans les 12 mois suivant l’inclusion, le patient etait considere comme en echec en intention de traiter. Le nombre de patients a inclure ( n = 32, 16 dans chaque groupe) etait calcule en faisant l’hypothese d’une reponse globale a 1 an de 80 % dans le bras rituximab versus 20 % dans le placebo (risque a a 5 % et b a 10 %). Resultats Sur les 40 patients preselectionnes, 32 patients (dont 17 femmes soit 53 %) âges en moyenne a l’inclusion de 71 ans ± 16 ans ont ete inclus et randomises. Les principales caracteristiques des patients (âge, sex-ratio, taux d’Hb et de LDH, nombre de concentres erythrocytaires transfuses au diagnostic) etaient comparables dans les 2 bras. La reponse au traitement etait evaluable chez 28 patients suivis pendant au moins 1 an. Trois patients âges respectivement de 90, 87 et 84 ans sont decedes dans le bras placebo versus aucun dans le bras rituximab ( p = 0,073) et 1 patient du bras placebo a ete exclu a la semaine 28 pour une anemie severe. A 1 an, en intention de traiter, la reponse globale (RC + RP) etait de 75 % (11 RC et 1 RP) dans la bras rituximab versus 31 % (5 RC) dans le bras placebo ( p = 0,032). Parmi les non repondeurs dans le bras placebo, 6 patients ont recu de l’azathioprine et 2 patients ont ete splenectomises. Il n’y avait pas de difference significative dans le taux de gammaglobulines a 1 an dans les 2 bras (8,1 ± 2,2 g/L versus 7,7 ± 1,5 g/L, p = 0,499). Sept episodes d’infections severes sont survenus au total chez 7 patients dans les 12 premiers mois, 5 dans le bras placebo et 2 dans le bras rituximab ( p = 0,39), incluant 2 cas de pneumocystose (1 dans chaque bras) et une pneumonie bilaterale a pneumocoque (bras placebo). Une embolie pulmonaire severe est survenue a j15 chez une patiente de 84 ans (bras placebo). Conclusion Compare a un placebo, le rituximab administre en association a la corticotherapie est une option therapeutique efficace et globalement bien toleree chez les patients adultes ayant une AIHAc nouvellement diagnostiquee avec un taux de reponse globale de 75 % a 1 an.

Introduction In immune thrombocytopenia (ITP), isotopic assessment of the site of platelet destruction using autologous111Indium-oxinate-labelled platelet sequestration study could be an helpful parameter to determine whether or not to perform splenectomy. Two independent studies have suggested that a purely splenic sequestration could be a significant predictive factor of long-term complete response after splenectomy. An increasing number of patients receives thrombopoietic receptor-agonists (TPO-RAs) but such treatments are not curative and therefore do not necessarily prevent from considering splenectomy in the course of ITP. TPO-RAs increase platelet production by inducing proliferation and differentiation of the megakaryocyte lineage. We have only very few data evaluating the impact of TPO-RAs, on mean platelet life span (MPLS), platelet production and platelet site of destruction. The aim of this study was to assess these parameters and clinical outcome of patients treated with TPO-RAs who underwent kinetic study of autologous111Indium-oxinate-labelled platelet. Patients and Methods We carried out a retrospective study in the Ile de France region, between 2008 and 2016. Patients were retrospectively selected from a prospective clinical database at the Cellular Biology Department of Saint Louis Hospital. We selected adult patients with definite ITP according to the international criteria. The isotopic method used to study platelet lifespan was previously described. Analyses were based on the radioactivity accumulation slopes in the hepatic or splenic area. We excluded patients who had received less than 3Mbeq of 111In. Data from patients' medical charts were collected using the standardized form of the Referral Center for Adult ITP. Complete response (CR) and Response (R) were defined according to standardized international criteria: platelet count > 30x 109/L with at least a doubling of the baseline value or >100 x 109/L. Results of platelet kinetic study from patients treated with TPO-RAs were compared with those from patients receiving no treatments. Results Two hundred and fifty three adults ITP patients were included. At the time of platelet kinetic study, 24 patients (10 men/14 women) with a median age of 63 years [range: 22-83] were treated with TPO-RAs (romiplostim n= 10, eltrombopag n = 14) and 229 (81 men/148 women) had no treatment. Among the TPO-RAs treated patients, some also received low dose steroids (n=6), dapsone (n=1) or intravenous immunoglobulins (n=2) at least two weeks before the kinetic study. Three were newly diagnosed, 9 had persistent ITP and 12 chronic ITP. The median platelet count was 62 x109/L [range: 22-175], and 7 patients had a platelet count > 100 x109/L. The median Mean Platelet Life Span (MPLS) was reduced in both groups (1.44 day [range: 0.4-7.5] (normal: 7-10) in patients treated with TPO-RAs), but was significantly higher in untreated patients (2.3 day [0.4-11], p = 0.004). The median turnover platelets ratio was increased in both groups (48% per day [range: 11-173] in patients treated with TPO-RAs), but was significantly lower in untreated patients (30% per day [range: 0.8-247]). Ratio of platelet production was significantly increased in patients treated with TPO-RAs (median: 2, [range: 0.1-5.0]) compared with untreated patients (median: 0.84, [range: 0.1-85.0]). Repartition of the site of platelet sequestration was similar in the two groups, 12 (50%) patients treated with TPO-RAs had a splenic uptake, versus 112 (49.1%) in untreated patients, and 2 (20%) patients treated with TPO-RAs had an hepatic uptake versus 9 (3.9%) in untreated patients. A splenectomy was performed in 9 out of the 12 patients with a purely splenic sequestration. After a median follow-up of 26 months [range 0-53], 8 (88%) had achieved CR and 1 had relapsed 5 months after splenectomy. Conclusion Our study shows that despite an increase production and turnover of platelets due to the stimulation of the megakaryopoiesis by TPO-RAs, the MPLS was clearly reduced and the repartition of platelet sequestration was not modified in patients receiving these drugs. Moreover, it would seem that a purely splenic sequestration is also predictive of CR after splenectomy in this group of patients. More importantly platelet kinetic study can be used in patients treated with TPO-RAs to position the splenectomy in the therapeutic management. Disclosures No relevant conflicts of interest to declare.

Introduction Le 18-FDG-TEP-TDM est une technique d’imagerie de plus en plus attractive depuis quelques annees pour l’exploration de pathologies inflammatoires tres diverses. Outre son indication dans le bilan d’extension et pronostique et de suivi des neoplasies [1] , son role a particulierement etait defini dans le bilan diagnostic ou l’exploration des fievres prolongees inexpliquees et des syndromes inflammatoires nus [2] devant son aptitude a deceler des causes inflammatoires, infectieuses et neoplasiques [3] . D’utilisation de plus en plus large, nous avons souhaite evaluer la cartographie de l’utilisation du 18-FDG-TEP-TDM dans un service de medecine interne : ses indications et le service rendu. Patients et methodes Il s’agit d’une etude retrospective monocentrique et descriptive. Nous avons inclus l’ensemble des patients du service de medecine interne d’un CHU de l’AP–HP ayant eu un 18-FDG-TEP-scanner entre fevrier et aout 2016. Nous avons recueilli les donnees demographiques des patients ainsi que les antecedents significatifs pour le 18-FDG-TEP (materiel etranger, neoplasie, tuberculose evolutive, vascularite des gros troncs, granulomatose), le motif d’hospitalisation et l’indication declaree du TEP-scanner classee en 6 categories (alteration de l’etat general, fievre au long cours, syndrome inflammatoire biologique, bilan d’extension d’une tuberculose ou d’une neoplasie, suspicion de vascularite des gros troncs, suspicion de recidive d’une pathologie deja connue), les resultats de celui-ci (presence ou non de fixation, SUV maximale), et le diagnostic final. Nous avons evalue a posteriori l’impact des resultats du TEP-scanner sur le diagnostic et/ou la prise en charge du patient (indispensable, utile, inutile, contreproductif…) ainsi que sa place chronologique dans la realisation des examens complementaires : en premiere ligne ou en bilan d’extension d’un diagnostic decouvert autrement… Resultats Entre le 31/08/2016 et le 31/08/2016, 80 patients ont eu un 18-FDG-TEP-TDM realise au cours d’une hospitalisation, l’âge moyen etait de 58 ± 16 ans, avec un sexe-ratio de 1. Cinquante patients avaient des antecedents impactants : neoplasie (n = 22), tuberculose (n = 9), granulomatose (n = 3), maladie auto-immune (n = 4), vascularite des gros troncs (n = 2), materiel etranger (n = 12), 30 n’avaient aucun antecedent impactant le 18-FDG-TEP-TDM. Les motifs d’hospitalisation des patients etaient l’alteration de l’etat general (31 %), un syndrome inflammatoire biologique inexplique (11 %), l’exploration d’une adenopathie (6 %), suspicion de tuberculose (20 %), suspicion d’arterite a cellules geantes (6 %), la reevaluation d’une pathologie connue (10,4 %). L’indication du 18-FDG-TEP-TDM etait l’exploration d’une alteration de l’etat general (70 %) ; une fievre au long cours (21 %) ; le bilan d’extension d’une neoplasie (15 %) ou d’une maladie de Horton (3 %), la decouverte de granulome (10 %), d’une tuberculose (30 %). Dans 12 cas, il a ete realise pour suspicion de recidive d’une pathologie connue. Soixante-deux pour cent des patients avaient un syndrome inflammatoire biologique, avec une CRP mediane a 40 mg/l [4 ; 500]. Le diagnostic final retenu etait une neoplasie dans 24 % des cas dont 68 % metastatique, une tuberculose avec localisations extrapulmonaires (12 %), une autre granulomatose (8 %), une infection (10 %), une maladie de Horton (n = 2). Le 18-FDG-TEP-TDM a ete realise en premiere intention dans 21 cas (16,8 %). Il etait anormal dans 84 % des cas avec une SUV max. moyenne de 6,4 [33,1–2]. Lorsqu’il etait negatif, il a permis d’exclure des diagnostics (neoplasiques et vascularite des gros troncs). Au total, l’apport du 18-FDG-TEP-TDM dans le diagnostic final a ete considere comme : essentiel dans 26 % des cas, aidant dans 60 % des cas. Il a ete considere inutile dans 13 % des cas et 9,6 % des examens ont mis en evidence un incidentalome. Quarante-huit examens ont permis de faire le bilan d’extension de la pathologie, et 32 examens d’eliminer le diagnostic evoque initialement. Conclusion La realisation d’un 18-FDG-TEP-TDM dans un service a haute orientation diagnostique est un recours facile du fait de sa tres forte sensibilite. Toutefois, sa faible specificite pourrait entrainer un exces d’examens secondaires ou invasifs inutiles pour le patient. Dans notre etude, nous montrons que dans 86 % des cas, cet examen a ete contributif avec toutefois 12 « incidentalomes ». L’analyse des facteurs associes a la non-contribution permettra d’en adapter la prescription et de le positionner chronologiquement dans l’exploration des patients.

Resume Nous rapportons une observation de dengue avec plasmocytose sanguine (3980 par millimetre cube) et medullaire (30 %) chez une femme de 55 ans, hospitalisee au retour d’un sejour aux Antilles pour fievre, arthralgies et thrombopenie (66 000 par millimetre cube). Le diagnostic etait confirme par la serologie. La plasmocytose au cours de la dengue est rare, sa frequence ainsi que sa correlation entre les differentes formes de l’affection reste a determiner.

Background The Human T-cell Leukemia Virus type 1 (HTLV-1) is the causative agent of several inflammatory diseases, including HTLV-1-associated inflammatory myopathies (HAIM). Little is known about the virological and immunological characteristics of this viral disease. Objectives To characterize the histological and virological features of HAIM patients, in order to better understand the pathogenetic mechanisms and unravel new biological markers of this disease. Study design We conducted a retrospective study on 13 patients with HAIM, based on blood and muscle samples. We included blood samples from HTLV-1-infected individuals without myopathy as controls. Muscle biopsies were used for a broad immunohistological evaluation of tissue damage and inflammation, as well as identification of infected cells through in situ hybridization. DNA extracted from patients’ PBMC was used to identify the virus genotype by sequencing and to assess the proviral load by quantitative PCR. Anti-viral antibodies in plasma samples were titrated by indirect immunofluorescence. Results Patients originate from HTLV-1 endemic areas, the West Indies and West Africa. Histological alterations and inflammation in patients muscles were mostly moderate, with classical features of idiopathic myositis and rare HTLV-1-infected infiltrating cells. In all patients, HTLV-1 belonged to the A subtype, transcontinental subgroup. Anti-HTLV-1 antibodies titers were high, but the proviral load was not elevated compared to asymptomatic HTLV-1 carriers. Conclusion We show here that muscle inflammation is moderate in HAIM, and accompanied by a low HTLV-1 proviral load, suggesting that the pathogenetic events do not exactly mirror those of other HTLV-1-associated inflammatory diseases.

Introduction La duree de sejours des patients est un des principaux criteres utilises pour rendre compte de l’efficience des services hospitaliers. Dans les services de medecine interne prenant en charge des patients non programmes en aval des urgences, elle depend a la fois de la pathologie, de l’organisation de la structure hospitaliere, du plateau technique a proximite, et des lits de second aval disponibles. Un des elements de bonne pratique est de prevoir des l’arrivee la duree de sejour des patients. Pour evaluer la part relative de ces differentes causes dans l’allongement de l’hospitalisation, nous avons realise une etude observationnelle monocentrique portant sur les patients de medecine interne en aval des urgences. Materiels et methodes Entre le 01/10 et le 30/11/2015, nous avons recueilli de facon prospective la duree de sejour previsible (theorique) de tous les patients en provenance des urgences hospitalises dans le service de medecine interne. Pour chaque patient, des donnees sociales, medicales, le mode de sortie et la duree reelle de sejour ont ete recueillies. La duree theorique de sejour est definie par les medecins seniors en charge du patient le lendemain de l’admission. La prolongation de l’hospitalisation est definie par une duree de sejour reelle augmentee de 50 % par rapport a la duree theorique. La cause de la prolongation de l’hospitalisation a ete recherchee a posteriori par une analyse retrospective du dossier medicale. Resultats Au total, 134 patients ont ete hospitalises dans le service de medecine interne de 32 lits, 53 % de femmes. Le score de Charlson moyen etait a 2,1 ± 2,4. 39 % des patients n’avaient aucune comorbidite. La duree moyenne de sejour reelle etait de 8,1 jours ±6,4 jours alors que la duree moyenne theorique etait de 5,4 jours ±2,9j. L’IP-DMS de l’ensemble du service est a 1,0. Les IP-DMS des deux groupes etaient de 1,24 ±0,7 dans le groupe des hospitalisations prolongees et de 0,83 ±0,6 dans l’autre groupe (p = 0,001). Trente-sept pour cent des patients ont eu une duree de sejours prolongee. Dans ce groupe, la duree moyenne de sejour etait de 13,2 jours ±8,8 jours, alors qu’elle etait de 5,3 jours ±3,2 jours dans l’autre groupe (p Discussion La determination a l’entree du patient de la duree previsible de sejour permet de mettre en evidence un allongement de la duree d’hospitalisation pour 30 % des sejours non programmes issus des urgences, le plus souvent du fait d’une evolution medicale non previsible. L’utilisation du critere empirique de depassement de plus de 50 % de la duree de sejour reelle par rapport a la duree prevue est validee par les differences significatives d’IP-DMS. L’analyse retrospective de ces « depassements » permet de mettre en evidence des dysfonctionnements organisationnels corrigibles : delais d’inscription sur trajectoire. Toutefois, dans notre etude plus de deux tiers de ces prolongations de sejour ne semblent pas liees a des problemes organisationnels mais a des problemes purement medicaux justifiant vraisemblablement une ponderation du codage du GHM dans une population precaire. Conclusion L’evaluation a l’entree des patients de la duree previsible de sejour permet de reperer a posteriori les prolongations de duree de sejour (IP-DMS > 1) et d’en analyser les causes. Dans notre etude, dans la majorite des cas, la cause de l’allongement est d’ordre medical (aggravation secondaire, decompensation des comorbidites…) et devrait pouvoir etre prise en compte par un codage adapte. Toutefois, les causes organisationnelles et optimisables sont a l’origine de 46 % des journees hospitalisations injustifiees.

Introduction: Warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease that can be life threatening especially in elderly patients. Rituximab has shown very promising efficacy in several uncontrolled studies and in one controlled trial for treating adult' wAIHA and it is commonly used off-label as a second-line treatment and as a corticosteroid-sparing agent. Methods: This phase 3 multicentre randomized (1/1 ratio) and double-blind controlled trial aimed to assess the efficacy and safety of rituximab compared to placebo for the treatment of adults with newly diagnosed wAIHA treated with prednisone. Inclusion criteria were: age ≥ 18 years with a confirmed diagnosis of wAIHA (hemoglobin level ≤ 10g/dL with hemolysis and a positive direct antiglobulin test with an anti-IgG ± anti-C3d pattern in the absence of any other cause of hereditary or acquired hemolytic anemia). Only patients previously treated with corticosteroids for less than 6 weeks could be included. Patients with secondary wAIHA (except for stage A chronic lymphocytic leukemia) were excluded. At time of inclusion, all patients were given prednisone at a daily dose of 1 mg/kg for 2 weeks and then tapered every 10 days according to a standardized procedure and stopped within 3 months in case of response. Eligible patients received in combination with prednisone (double-blind) 2 infusions of either rituximab (arm A) or placebo (arm B) at a fixed dose of 1,000 mg 2 weeks apart (on days 1 and 15 after randomization). The primary endpoint was the overall response rate (CR + PR) at 1 year in both arms. Complete remission (CR) was defined by a hemoglobin (Hb) level ≥11 g/dL (women) or 12 g/dL (men) without hemolysis (including a normal haptoglobin level) in the absence of any ongoing treatment for wAIHA, on 2 different occasions 4 weeks apart in the absence of recent transfusion. Partial remission (PR) was defined by a Hb level ≥ 10g/dL with at least a 2g increase from baseline in the absence of any other treatment than prednisone given at a daily dose ≤ 10 mg or recent transfusion. A non-response (NR) was defined by the need of receiving prednisone at a daily dose > 10mg to maintain a PR and/or any other treatment potentially active in wAIHA (i.e., splenectomy, immunosuppressors). The hypothesis for the calculation of the sample size (n = 32 patients, 16 in each arm) was, based on previous data from the literature, an 80% overall response rate (CR + PR) at 1 year in the RTX arm versus 20% in the placebo arm with an a risk of 5% and a b risk of 10%. Results: A total of 32 patients, 17 females (53%), with a mean age at inclusion of 71 (SD: 16) years were enrolled and randomized. The patients main characteristics (mean age, sex ratio, Hb and LDH levels, number of packed red cells transfused at diagnosis) were comparable in both arms. Twenty-eight patients were followed for at least 1 year and were evaluable for response. Three patients aged of 90, 84 and 87 from the placebo arm prematurely died versus none in the rituximab arm (p=0.073) and 1 patient from the placebo arm was prematurely withdrawn at Week 28 for severe anemia. At 1 year, in intention to treat, the overall response rate (CR + PR) was 75% (11 CR and 1 PR) in the rituximab arm versus 31% (5 CR) in the placebo arm (p value=0.032). Among the non-responders in the placebo arm, 6 patients were given azathioprine and 2 patients underwent splenectomy. There was no difference in the mean gammaglobulin level at 1 year between the 2 arms (8.1 ±2.2 g/l versus 7.7 ±1.5 g/l, p value 0.499). A total of 7 severe infections occurred during the first year of follow-up, 5 in the placebo group and 2 in the RTX group (p=0.39) including 2 cases of pneumocystosis (1 in each treatment arm) and 1 bilateral pneumonia due to Streptococcus pneumonia in the placebo arm. One severe pulmonary embolism occurred on day 15 in a 84-year-old woman in the placebo arm. Conclusion: Compared to placebo, rituximab given in combination with prednisone is an effective and safe option for treating adult patients with newly-diagnosed wAIHA leading to an overall response of 75% at one year. Disclosures Michel: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AMGEN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Research Funding. Off Label Use: rituximab use in AIHA. Godeau:Roche: Research Funding; Amgen: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

The association of sarcoidosis and immune thrombocytopenia (ITP) has rarely been investigated. The aim of the current retrospective study was to investigate the clinical and biological phenotypes and outcome of this association in a large series of recent patients. Twenty patients (50% men) were included. Median age at sarcoidosis and ITP diagnosis was 36 (range, 10-83 yr) and 38 (range, 21-83 yr) years, respectively. In 11 of 20 (55%) patients, sarcoidosis onset preceded ITP (median interval, 48 mo; range, 6-216 mo). In 5 of 20 (25%) patients, the 2 conditions occurred concomitantly. In 4 of 20 (20%) patients, ITP onset preceded sarcoidosis (median interval, 68 mo; range, 15-153 mo). In 4 cases, sarcoidosis and ITP were not concomitant, since 1 condition was cured before the other was declared. In 12 of 20 (60%) patients there was a simultaneous onset or relapse of both ITP and sarcoidosis. Sarcoidosis phenotype was characterized by an acute onset in 40% of patients. The visceral involvement included thoracic sites in 19 of 20 (95%) patients and extrathoracic sites in 16 of 20 (80%) patients. At ITP onset, median platelet count was 11 × 10/L (range, 3-90); 17 (85%) patients had a platelet count30 × 10/L. Seven (35%) patients had a bleeding score8 without visceral bleeding.Nineteen of the 20 (95%) patients were treated specifically for ITP. After the first-line therapy (prednisone at 1 mg/kg per day for at least 3 consecutive weeks in all patients; with IVIg in addition for 10 patients with severe bleeding score), 12 of 19 (63%) patients achieved a complete response, 6 (31.5%) had a partial response, and only 1 patient failed to respond. At the end of ITP follow-up (median, 70 mo; range, 12-142 mo), 18 (90%) patients achieved a complete response, 1 achieved a partial response, and 1 had no response. After a median follow-up of 105 months, 13 of 20 (65%) patients had persistent sarcoidosis requiring prolonged therapy, and thus sarcoidosis represented the main long-term concern. Main conclusions were 1) ITP presentation was usually severe, but response to treatment was favorable in almost all cases, with no death and no severe bleeding, in contrast with older reports, 2) sarcoidosis was remarkable for the high proportion of cases with an acute onset, a chronic course, and the need for prolonged prednisone therapy, 3) sarcoidosis and ITP onset and evolution were not always synchronous.

Immunohistochemical and virological features of HTLV-1-associated myosites: a study of 13 patients from West Indies and Africa Marion Desdouits, Olivier Cassar, Thierry Maisonobe, Alexandra Desrames, Achille Aouba, Olivier Hermine, Jacqueline Mikol, Marc Polivka, Isabelle Penisson-Besnier, Pascale Marcorelles, Fabien Zagnoli, Thomas Papo, Arnaud Lacour, Zahir Amoura, Julien Haroche, Patrick Cherin, Antonio Texeira, Anne-Sophie Morin, Franck Mortreux, Eric Wattel, Michel Huerre, Marie-Christine Cumont, Huot Khun, Sylviane Bassot, Sandra Martin-Latil, Graham Taylor, Antoine Gessain, Simona Ozden, Pierre-Emmanuel Ceccaldi

SummaryA 56-year-old woman with ankylosing spondylitis, treated for 3 months with infliximab, developed miliary tuberculosis with mediastinal lymphadenopathies and brain and splenic lesions. After initial improvement under anti-tuberculous therapy, she suffered an unexpectedly prolonged paradoxical worsening with several episodes of lymphadenopathy, including life-threatening ones, over a period of more than 14 months of follow-up. The outcome was favorable as a result of corticosteroid and surgical treatments. This phenomenon reflects a paradoxical reaction precipitated by infliximab withdrawal.

Evans syndrome (ES) is a rare disease characterized by the simultaneous or sequential development of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) and/or immune neutropenia. To better describe the characteristics and outcome of ES in adults, a survey was initiated in 2005. The data from 68 patients (60% of them women) fulfilling strict inclusion criteria for ES are reported. The mean age at time of ITP and/or AIHA onset was 52 plus or minus 33 years, both cytopenias occurred simultaneously in 37 cases (54.5%). ES was considered as “primary” in 34 patients (50%) but was associated with an underlying disorder in half of the cases, including mainly systemic lupus, lymphoproliferative disorders, and common variable immunodeficiency. All patients were given corticosteroids, but 50 of them (73%) required at least one “second-line” treatment, including splenectomy(n = 19) and rituximab (n = 11). At time of analysis, after a mean follow-up of 4.8 years, only 22 patients (32%) were in remission off treatment; 16 (24%) had died. In elderly patients, the risk of cardiovascular manifestations related to AIHA seems to be higher than the ITP-related risk of severe bleeding. In conclusion, ES is a potentially life-threatening condition that may be associated with other underlying autoimmune or lymphoproliferative disorders.

Objectives. Muckle-Wells syndrome (MWS) and familial cold autoinflammatory syndrome (FCAS) are rare periodic fevers associated with CIAS1 mutations. A third entity, the chronic infantile neurological, cutaneous, articular (CINCA) syndrome was also recently associated with mutation in the same gene. A phenotypic and genotypic continuum seems to exist from the most benign (FCAS) to the most severe forms (CINCA). Although a CIAS1 mutation can be associated with two different phenotypes. Methods. We report a family of three patients exhibiting the MWS and FCAS phenotypes. These phenotypes were associated with a novel missense mutation in CIAS1. Results. Anakinra controlled inflammatory flares in the three patients. Conclusions. FCAS, MWS and CINCA could be different phenotype expressions of the same disease.

Objective To describe characteristics and outcomes of vasculitides associated with malignancies. Methods The requirement for inclusion in this retrospective, 10-year study was development of vasculitis in patients with a progressing malignancy. Malignancies secondary to immunosuppressants used to treat vasculitis were excluded. The main characteristics of vasculitides were analyzed and compared according to the type of malignancy. Results Sixty patients were included (male/female sex ratio 2.53, mean age 62.4 years). Mean followup duration was 45.2 months. Vasculitides were cutaneous leukocytoclastic (45%), polyarteritis nodosa (36.7%), Wegener's granulomatosis (6.7%), microscopic polyangiitis (5%), and Henoch-Schonlein purpura (5%). Malignancies were distributed as follows: hematologic in 63.1%, myelodysplastic syndrome (MDS) in 32.3%, lymphoid in 29.2%, and solid tumor in 36.9%. Vasculitides were diagnosed concurrently with malignancy in 38% of the cases. Manifestations of vasculitides were fever (41.7%), cutaneous involvement (78.3%), arthralgias (46.7%), peripheral neuropathy (31.7%), renal involvement (23.3%; 11.7% glomerulonephritis, 11.7% microaneurysms, 6.7% renal insufficiency), and antineutrophil cytoplasmic antibody (20.4%). Vasculitis treatments were corticosteroids (78.3%) and immunosuppressant(s) (41.7%). Vasculitis was cured in 65% of patients, but 58.3% died, with 1 death secondary to vasculitis. Independent of subtype, patients with vasculitides associated with MDS more frequently had renal manifestations (P = 0.02) and steroid dependence (P = 0.04) and achieved complete remission less often (P = 0.04) than patients with vasculitides associated with other malignancies. Patients with vasculitides associated with a solid tumor more frequently had peripheral neurologic involvement (P = 0.05). Patients with vasculitides associated with lymphoid malignancy had less frequent arthralgias (P = 0.01) and renal involvement (P = 0.02). Conclusion Vasculitides occurring during malignancies present distinctive features according to the vasculitis subtype and nature of the malignancy.

We report the case of a 32-year-old Indian man with symptoms suggesting Zollinger-Ellison syndrome including abdominal pain, esaphagitis, duodenal stenosis that did not improve with antisecretory medication, elevated fasting gastrin serum levels that increased after intravenous secretin injections, elevated chromogranin A serum levels and tumoral aspect of pancreatic uncus on CT scan examination. A pancreaticoduodenectomy was performed. Histological examination of the resected specimen showed that there was no endocrine tumour of the pancreas or the duodenum, but identified marked lesions of follicular and caseous tuberculosis. The final diagnosis retained pseudo Zollinger-Ellison syndrome due to gastric outlet obstruction caused by duodenal stenosis of a tuberculosis origin.

Introduction La mastite granulomateuse (MG) est une maladie inflammatoire chronique du sein qui touche essentiellement les femmes en âge de procreer. Sa pathogenie est mal connue, meme si le role des corynebacteries a ete evoque. Son traitement reste mal codifie. Nous rapportons ici le cas d’une MG associee a une infection par Corynebacterium amycolatum d’evolution favorable sous antibiotherapie prolongee. Observation Une femme de 36 ans, d’origine sri lankaise, sans antecedent pathologique, consultait pour une lesion douloureuse du sein gauche. Elle presentait une masse mammaire induree mesurant 9 cm × 8 cm. La peau en regard etait inflammatoire. Une adenopathie axillaire gauche etait palpable. Parallelement, la patiente avait une febricule a 38 °C, des arthralgies des genoux et des chevilles avec un erytheme noueux en regard. Une fistulisation spontanee d’un abces apparaissait les jours suivants. Elle avait une hyperleucocytose a polynucleaires neutrophiles (respectivement 14 800/mm 3 et 11 370/mm 3 ) et une proteine C-reactive a 130 mg/L. Les hemocultures, la serologie VIH, la serologie de la brucellose et les anticorps antinucleaires etaient negatifs. La mammographie montrait une lesion du sein gauche classee ACR5. L’echographie mammaire decrivait une masse hypoechogene heterogene entouree par un halo hyperechogene a l’union des quadrants superieurs. Le scanner thoraco-abdomino-pelvien etait normal. La biopsie mammaire gauche, realisee a deux reprises, retrouvait une reaction granulomateuse epithelioide et giganto-cellulaire importante associee a des polynucleaires neutrophiles et a un infiltrat lympho-plasmocytaire, sans foyer de necrose, sans signe de vascularite, sans corps etranger ni cellule maligne. Les examens bacteriologique standard, mycobacteriologique et mycologique du sein gauche etaient negatifs. La culture prolongee sur milieu specifique etait positive a C. amycolatum . Une antibiotherapie adaptee a l’antibiogramme a donc ete debutee, d’abord par l’amoxicilline 3 g/jour pendant un mois avec relais par la doxycycline 200 mg/jour pendant 3 mois. L’evolution etait progressivement favorable, malgre la persistance d’une cicatrice en regard de la fistule. Discussion Dans la litterature, l’origine infectieuse de la MG et le role pathogene des corynebacteries restent debattus, en raison notamment de leur caractere commensal de la peau. Cependant Taylor et al. rapportent la presence de bacilles Gram positif coryneformes dans 41 % des examens directs realises sur des coupes histologiques de mastites [1] . Dans notre cas, la biopsie mammaire a ete faite dans un site relativement profond et dans des conditions steriles. De plus, le caractere monomorphe de la flore en culture, la presence d’infiltrat a polynucleaires neutrophiles et l’efficacite du traitement antibiotique sont egalement des arguments en faveur de l’origine infectieuse de la MG. C. kroppenstedtii est le plus frequemment decrit alors que C. amycolatum a ete rarement retrouve dans la MG. La presence de bacterie dans le prelevement mammaire a naturellement oriente le choix therapeutique vers une antibiotherapie adaptee qui s’est averee efficace apres un traitement prolonge. Le traitement des MG n’est pas bien codifie. La corticotherapie est jugee efficace mais les rechutes a sa decroissance sont frequentes. Divers traitements ont ete utilises avec plus ou moins de succes : les antibiotiques, la colchicine, l’hydroxychloroquine et le methotrexate. La chirurgie mammaire en dernier recours est efficace avec cependant un risque de recidive eleve (50 %) ainsi que de sequelles inesthetiques. Conclusion Les corynebacteries paraissent impliquees dans la survenue de mastite granulomateuse. Un traitement antibiotique prolonge semble efficace. Des etudes a plus grande echelle et pendant un delai suffisant permettraient de confirmer l’efficacite de l’antibiotherapie prolongee.