Search

Resume Introduction Le syndrome de fuite capillaire idiopathique (SFCI), ou syndrome de Clarkson, est rare et met brutalement en jeu le prognostic vital. Trois phases evolutives sont decrites. La phase prodromique est aspecifique, souvent sous la forme d’un syndrome pseudo-grippal. La phase d’etat, marquee par une fuite capillaire majeure et un etat de choc hypovolemique, fait la gravite de la maladie par la survenue rapide d’une defaillance multiviscerale (DMV). L’hypovolemie contraste avec les oedemes, et l’hemoconcentration contraste avec l’hypoalbuminemie. La phase de resolution spontanee est marquee par la restauration des defaillances d’organes. Observations Nous rapportons deux cas de SFCI pris en charge en reanimation dont l’errance diagnostique initiale a probablement greve le pronostic. La premiere patiente, âgee de 28 ans a d’abord ete prise en charge pour une « polyglobulie ». Il s’agissait pourtant d’une hemoconcentration secondaire a une hypovolemie. Elle a presente un arret cardiocirculatoire lors de la deuxieme saignee avant de developper une DMV. Des immunoglobulines polyvalentes intraveineuses ont ete prescrites. L’evolution a ete favorable en reanimation. Le second patient, âge de 57 ans, a d’abord ete pris en charge pour une « myosite » (douleurs musculaires et rhabdomyolyse). Il s’agissait pourtant d’un syndrome de loges (œdeme musculaire lie a la fuite capillaire). Un etat de choc brutal evoluant vers une DMV conduisait au deces du patient en reanimation. Conclusion La physiopathologie du SFCI est inconnue et impliquerait une dysfonction endotheliale transitoire. Devant l’impossibilite de realiser des essais controles randomises pour le traitement de cette pathologie exceptionnelle, les therapeutiques symptomatiques (expansion volemique prudente, amines vasopressives) et specifiques (aminophylline intraveineuse) restent empiriques et peu efficaces. Presentant des effets controverses voire deleteres en phase de fuite, les immunoglobulines polyvalentes sont neanmoins benefiques en prophylaxie secondaire. Le diagnostic syndromique est difficile mais sa precocite est probablement l’element clef permettant une prise en charge immediate en reanimation, avant le stade des defaillances d’organe.

Introduction La necrose hemorragique des surrenales est la manifestation endocrinologique la plus frequente au cours du syndrome des antiphospholipides (SAPL). Il s’agit d’une complication classique mais rare puisqu’elle est retrouvee chez 0,4 % des patients ayant un SAPL. Il s’agit d’une thrombose veineuse des veines surrenaliennes dans un contexte de reseau vasculaire propice a l’ischemie hemorragique puisqu’il existe une veine de drainage unique, contrastant avec un reseau arteriel riche. Le traitement de reference reste les anti-vitamines K (AVK) mais le developpement des nouveaux anticoagulants oraux (NACO) dans d’autres pathologies, interroge sur leur place dans la prise en charge des patients ayant un SAPL. Nous rapportons un cas de necrose hemorragique bilaterale des surrenales chez un patient traite depuis 1 mois et demi par APIXABAN pour une thrombose veineuse profonde avec embolie pulmonaire, revelant un syndrome des antiphospholipides. Observation Un patient de 47 ans, sans antecedent notable, est diagnostique d’une phlebite de la jambe gauche devant une douleur persistante du mollet. Une anticoagulation efficace par APIXABAN 5 mg matin et soir est debutee. Devant la presence d’une dyspnee persistante rapportee par le patient, un angioscanner thoracique est realise a 1 mois, avec diagnostic d’embolie pulmonaire. A un mois et demi du diagnostic initial, il est hospitalise pour douleurs abdominales brutales intenses avec mise en evidence d’hematomes bilateraux des surrenales au scanner. En reprenant l’interrogatoire, on retrouve une observance stricte du traitement par APIXABAN. Cliniquement, l’abdomen est douloureux a la palpation mais depressible et on retrouve un livedo reticularis au niveau du dos. Le bilan biologique sous APIXABAN retrouve un TP a 42 %, un TCA allonge a 1,42 et l’absence de cytopenie. Le bilan immunologique retrouve une triple positivite pour les anticorps anti-phospholipides a des taux eleves : IgG anti-cardiolipine avec titre > 160GPL-U/mL (resultat negatif si 160 U/mL (titre negatif si Discussion La necrose hemorragique bilaterale des surrenales est une urgence diagnostique et therapeutique. Elle doit faire rechercher un SAPL car il s’agit d’une manifestation inaugurale dans un tiers des cas. Avec l’elargissement des indications des NACO se pose la question de leur utilisation dans le SAPL. Dans une cohorte prospective de 56 patients avec un SAPL traite par NACO, 6 recurrences d’evenements thrombotiques etaient rapportes : 4 chez des patients triple positifs et 2 en contexte de non adherence au traitement, pendant un suivi de 22 mois en moyenne (2–43 mois) [1] . L’etude controlee randomisee RASP ne retrouvait aucun evenement thrombotique chez les patients avec un SAPL traite par RIVAROXABAN (suivi 42 jours) [2] . Cependant en 2018, un essai controle randomise comparant l’efficacite du RIVAROXABAN par rapport a la WARFARINE chez des patients avec un SAPL a haut risque thrombotique, retrouvait des recidives de thromboses uniquement dans le groupe RIVAROXABAN (12 % versus 0 %) ayant justifie un arret precoce de l’essai apres l’inclusion de 120 patients [3] . Notre cas rapporte une inefficacite de l’APIXABAN en cas de SAPL a haut risque de thrombose. Un autre cas d’hemorragie bilaterale des surrenales associee a des anticorps anti-phospholipides sous RIVAROXABAN est rapporte dans la litterature, nous n’avons pas retrouve de cas rapporte sous APIXABAN. Conclusion Ce cas clinique illustre les limites d’un traitement par NACO pour la prevention des recidives thrombotiques chez les patients SAPL triple positifs. Il s’agit a ce jour, a notre connaissance, du seul cas rapporte de necrose bilaterale des surrenales sous APIXABAN en contexte de SAPL. Un essai randomise est en cours pour evaluer l’efficacite de l’APIXABAN dans le SAPL. Nous verrons si les resultats sont identiques aux resultats retrouves pour le RIVAROXABAN, comme peut le suggerer notre cas clinique.

Resume Introduction La pseudo-retinopathie de Purtscher regroupe l’ensemble des atteintes retiniennes semiologiquement similaires au syndrome initialement decrit en 1910 par Purtscher, mais survenant dans un contexte non traumatique. Observation Nous rapportons le cas d’une pseudo-retinopathie de Purtscher bilaterale survenue dans le cadre d’une poussee de maladie de Still de l’adulte chez une femme de 48 ans. Le diagnostic reposait sur l’examen du fond d’œil et l’angiographie a la fluoresceine. Sur la base d’une revue de la litterature, nous discutons les donnees actuelles disponibles sur la physiopathogenie de ce syndrome ainsi que sa signification pronostique. Le traitement en reste controverse. Conclusion Devant l’apparition de signes fonctionnels visuels au cours d’une maladie de Still de l’adulte, il faut evoquer une manifestation ophtalmique grave de cette pathologie, la pseudo-retinopathie de Purtscher et demander une expertise ophtalmologique.

Resume Introduction La syphilis est une maladie sexuellement transmissible. Tous les organes peuvent etre atteints, mais seul 0,6 % des patients atteints de syphilis ont une atteinte oculaire. Nous avons recueilli l’ensemble des cas de syphilis oculaire necessitant une hospitalisation au centre hospitalier universitaire (CHU) de Marseille en 2017. Patients et methodes Il s’agit d’une etude retrospective monocentrique. Le diagnostic de syphilis oculaire reposait sur l’association d’une inflammation oculaire et d’une serologie syphilitique positive. Pour chaque patient etaient notes le sexe, l’âge, le statut serologique VIH, les symptomes oculaires et extra oculaires, l’acuite visuelle initiale, la serologie syphilis, l’analyse du liquide cephalo-rachidien (LCR), le traitement, sa duree et la reponse clinique. Resultats Dix hommes et deux femmes, âges de 28 a 86 ans ont ete hospitalises. Deux patients etaient seropositifs. Les atteintes ophtalmologiques etaient heterogenes, mais les structures posterieures etaient majoritairement atteintes. Une patiente a presente un tableau d’uveite anterieure pure. Cinq patients avaient des signes extra oculaires cutanes et/ou muqueux. Aucun n’a presente de signe neurologique. L’analyse du LCR realisee pour 7 patients a permis le diagnostic de neurosyphilis certain pour un patient et probable pour 5 patients. Le LCR etait normal chez deux patients. Six patients ont beneficie d’un traitement par penicilline G et six par ceftriaxone. L’acuite visuelle s’est amelioree dans tous les cas. Discussion Nous assistons depuis plusieurs annees en France a une reemergence des cas de syphilis ophtalmologique. Son diagnostic doit etre evoque a tout âge et devant toute pathologie inflammatoire de l’œil meme en dehors d’une anamnese ou d’une clinique evocatrice. La recherche d’une co-infection par le VIH doit etre systematique. Enfin, notre etude montre que la ceftriaxone reste une alternative efficace a la penicilline G.

Neonatal immune neutropenia is observed in rare cases in newborns from mothers with idiopathic or autoimmune neutropenia, secondary to passive transfer of maternal granulocyte auto-antibodies. We performed a literature review and report four supplementary cases from the French registry of neutropenia. Only 14 cases (11 mothers, 14 newborns) have been reported. Granulocyte aggregation (GAT) and granulocyte indirect immunofluorescence test (GIFT) are the recommended laboratory procedures for antibody detection. Monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA)-confirmed antibody specificity. Antibody detection in newborns is not generally possible owing to extreme neutropenia. In half of the cases autoantibodies against neutrophils (AAN) were positive in maternal sera (7 out of 11). In some newborns tested, IgG+ AAN were also positive, with disappearance in parallel of spontaneous neutrophil count improvement. No correlation between maternal type of AAN and titer and neonatal neutropenia can be established. Neutropenia resolved spontaneously between 2 weeks and 4 months. Infections in newborns were observed in 43% of cases, with no deaths reported. Granulocyte colony-stimulating factor (G-CSF) was administered to some newborns (5 out of 14) in the case of infections. Low-dose G-CSF administered to childbearing women during pregnancy could be proposed to prevent neutropenia in newborns. From the few cases reported so far it is impossible to draw any conclusions regarding frequency, risk factors, and outcome, but the overall prognosis for newborns seems good. Because it can be associated with potentially severe neonatal infections, autoimmune neutropenia in childbearing mothers should be closely monitored in collaboration with gynecologists and pediatricians.

Objective To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. Methods We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer’s solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety. Results Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months’ follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of −9.2 [12.2] in the AD-SVF group vs −7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups. Conclusion This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Objective Patients with inflammatory myopathies (IM) are known to have an increased risk of developing malignancies. Autoimmune and inflammatory diseases occur in up to 25% of patients with myelodysplastic syndrome (MDS). This study aimed to describe the rare association between IM and MDS. Methods We report here the main characteristics, treatment, and outcome of 21 patients (11 national cases and 10 additional cases from a literature review) with IM associated to MDS. Results Median age of patients at IM diagnosis was 66 years (range 26 – 78). Diagnosis of the two conditions were concomitant in most patients (n=14/21) whereas MDS diagnosis preceded IM diagnosis in 5 patients. Different types of IM were observed but dermatomyositis was the most frequent (59%). Compared to IM without MDS (IM/MDS−), patients with MDS (IM/MDS+) were older (median 66 vs 55, p=0.3), more frequently male (sex ratio M/F 1.125 vs 0.41, p=0.14) and positive for anti-TIF1γ (24% vs 4%, p=0.0039). Antisynthetase syndrome was never observed among IM/MDS+ patients (0% vs 28%, p=0.01). MDS WHO type was not univocal, but the prognostic score was of low risk in almost all cases. IM was usually steroid sensitive (82% of patients) but often steroid dependent (56% of patients). Overall survival of IM patients with MDS was worse compared to patients with IM without MDS (p=0.0002). Conclusion IM associated with MDS are mainly represented by dermatomyositis and/or anti-TIF1γ autoantibodies. Antisynthetase syndrome has not been described in association with MDS. Despite low-risk MDS, overall survival of IM patients with MDS is worse than IM patients without MDS.

International audience; Background: The detection of additional autoantibodies is of great concern in systemic sclerosis (SSc) when those included in the ACR/EULAR classification are negative. In this context, the interest of antifibrillarin (anti-U3RNP) autoantibodies (AFAs) in the routine evaluation of SSc remains unclear. We aimed to assess the relevance of AFAs and their clinical association in SSc patients. Methods: In a multicenter observational retrospective study, we collected immunological and clinical data associated with AFA positivity in SSc (n = 42) and non-SSc patients (n = 13). Patients with SSc negative for AFAs (n = 83) were considered as a control group. AFAs were detected by indirect immunofluorescence (IIF) using HEp-2 cells, EliA or immunoblot techniques. Results: We confirmed a typical nuclear IIF pattern and showed that AFAs are mostly exclusive towards SSc conventional autoantibodies. Although also observed in non-SSc patients, high levels of AFAs with the ELiA technique allowed the diagnosis of SSc. Compared to AFA-negative SSc patients, AFA-positive SSc patients more frequently exhibited visceral involvements. They more frequently suffered from the diffuse cutaneous form and had a higher global severity of the disease. Conclusions: We demonstrate the usefulness of quantifying AFAs in the immunological exploration of SSc, especially when patients are seronegative for SSc conventional autoantibodies and display a typical IIF pattern. AFAs might constitute an interesting marker of SSc severity.

Background Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival. Methods From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes. Results A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1–6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2–5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5. Conclusions Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.

Acute severe hepatitis is a rare complication of adult-onset Still's disease (AOSD). This condition is poorly characterized. We performed a review of the medical literature to describe clinical, biological, pathological, and treatment characteristics from AOSD patients with acute severe hepatitis. Their characteristics were compared with AOSD patients without severe hepatitis. Twenty-one cases were collected including a new case reported here. Patients with severe hepatitis were mostly young adults with a median age of 28 years (range: 20 to 55 years). Overall, patients with severe hepatitis had less arthritis, macular rash, sore throat, lymphadenopathy, or splenomegaly than patients without severe hepatitis. Cytopenia was more frequent in case of severe hepatitis. Most patients were treated with steroids, and the use of biotherapies has increased over the last decade. Despite treatment, 49% of patients required liver transplantation and 24% died. Key Points • Acute severe hepatitis in adult-onset Still's disease (AOSD) is associated with liver transplantation and/or death in, respectively, 43% and 24% of cases. • Severe hepatitis is the inaugural manifestation of AOSD in half of cases. Diagnosis is difficult when extra-hepatic clinical manifestations are lacking. • The mechanism of hepatic necrosis in AOSD with severe hepatitis is unknown. Liver biopsy is not specific and should not delay treatment initiation.

Among the antibodies described in Systemic Sclerosis (SSc), anti-Th/To antibodies (anti-Th/To) are rare and have been poorly studied. Thus, little is known about the profile of anti-Th/To positive patients. From our local Biobank (Marseille, France), we retrospectively selected data for 6 patients positive for anti-Th/To with an Immunodot assay. All of them suffered from SSc, sharing clinical and biological common features such as a limited cutaneous form of SSc, a decreased lung diffusing capacity and a speckled nuclear nucleolar immunofluorescence pattern of antinuclear antibodies screening on HEp-2 cells. In order to further characterize patients positive for anti-Th/To, we performed a thorough literature review. From 402 studied patients positive for anti-Th/To, we confirmed that these antibodies are associated with the limited cutaneous form of the disease (88% of the patients), and with an SSc related-pulmonary involvement (50%). The review analysis pointed out the rarity of the anti-Th/To with an estimated mean frequency of 3.4% of all SSc patients worldwide, their usual exclusivity with respect to the specific antibodies of scleroderma, and their high specificity (around 98%) for the diagnosis of SSc., Parmi les anticorps décrits associés à la Sclérodermie Systémique (ScS), les anticorps anti-Th/To (anti-Th/To) sont rares et ont été peu étudiés. Ainsi, nous n’avons que peu de connaissance sur le profil des patients positifs pour les anti-Th/To. À partir d’une Biobanque locale (Marseille, France), nous avons sélectionné de façon rétrospective 6 patients positifs pour les anti-Th/To, en test Immunodot. Tous souffraient de ScS et partageaient des caractéristiques cliniques et biologiques communes, comme la forme cutanée limitée de la ScS, une baisse de la diffusion alvéolocapillaire pulmonaire et un aspect moucheté nucléolaire en immunofluorescence indirecte au test de dépistage des anticorps anti-nucléaires sur cellules Hep-2. Afin de caractériser davantage les patients positifs pour les anti-Th/To, nous avons réalisé une revue de la littérature sur le sujet. À partir de l’étude de 402 patients positifs pour les anti-Th/To, nous confirmons que ces anticorps sont principalement associés à la forme cutanée limitée de la maladie (88 % de l’ensemble des patients), et à une atteinte pulmonaire de la ScS (50 % de l’ensemble des patients). Cette analyse de la littérature illustre la rareté des anti-Th/To avec une fréquence moyenne estimée de 3,4 % chez tous les patients souffrant de ScS dans le monde entier, leur caractère habituellement exclusif vis-à-vis des autres autoanticorps spécifiques de la Sclérodermie, ainsi que leur grande spécificité (environ 98 %) pour le diagnostic de la ScS.

International audience; We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc). Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography. Pulmonary function tests, main manifestations and severity of the lung disease (Medsger's severity scale) were collected. KL-6 serum concentrations were significantly higher in SSc-ILD patients than in those without ILD (p < 10(-4)) and were inversely correlated with forced vital capacity, total lung capacity and diffuse lung capacity of carbon monoxide. Serum KL-6 level superior to 872 U/ml appeared as the optimal cut-off value associated with ILD. Patients with a restrictive pulmonary syndrome and dyspnoea had significant higher KL-6 serum concentrations. SSc patients with anti-topoisomerase 1 antibodies had higher KL-6 serum levels than patients with anti-centromere antibodies (p < 10(- 4)). ILD and anti-topoisomerase 1 antibodies were independent factors associated with KL-6 in multivariate analysis. Interestingly, KL-6 serum concentrations positively increased with the patient lung severity. Our study confirms that KL-6 is an accurate biomarker for the diagnosis of SSc-ILD in a French cohort of patients. High KL-6 levels should prompt physicians to assess ILD with pulmonary imaging and pulmonary functions tests. Prospective clinical studies are still required to determine whether levels of KL-6 might predict progression of ILD as well as its usefulness in the timing of therapeutic intervention.

Patients with sickle cell disease have an increased risk of venous thromboembolism (VTE) and with a mortality 2-fold higher. The anticoagulation of VTE in a young population is an important question. Indeed, hemorrhagic complications of anticoagulation may occur more frequently than in the general population. The use of a direct oral anticoagulant (DOAC) is not recommended for VTE in patients with sickle cell disease because those patients were not included in the clinical studies. We aimed to study the safety of using DOACs in a prospective cohort of patients with sickle cell disease and VTE. We prospectively followed the cohort of all sickle cell disease patients undergoing recent DOAC treatment for VTE at a sickle cell disease reference center. Twelve patients received rivaroxaban for VTE (eight women and four men). The median age was 27 years (20-45). The sickle cell disease variants included homozygous Hb SS (

Background: IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder that can affect virtually every organ. Although arterial involvements have been reported, no studies have examined the occurrence of arterial or venous thrombotic events in these patients. Objectives: To explore the frequency, the characteristics, and risk factors of arterial and venous thrombotic events in IgG4-related disease patients. Methods: An observational, descriptive, retrospective study was conducted from a multicentric national case registry for IgG4-RD. Patients fulfilled the Comprehensive Diagnostic Criteria (CDC) for IgG4-RD, and all patients with arterial or venous thrombotic events confirmed by imaging during follow-up were analyzed. Clinical, radiological, biological, histological and therapeutic characteristics were retrospectively collected using a standardized online data sheet. Results obtained in patients with thrombosis were compared to those without thrombosis. Results: One hundred eighty-nine patients with IgG4-RD (135 men/54 women, median age 61 years) were included. During a 12-months median follow-up, one or more arterial thrombotic events occurred in 10 patients and venous thrombotic events in 16 (5.3 and 8.5 events/100 patient-years, respectively). Arterial complications (coronary artery disease n=5, lower limb peripheral arterial disease n=2, mesenteric ischemia, transient ischemic attack, and carotid thrombosis: n=1) occurred on average 30 months [0-140] after the first symptoms of IgG4-RD. They were inaugural in 2 patients without any cardiovascular risk factor, and associated with IgG4-RD arterial involvement in 3 (coronary aneurysms n=2, leg arteritis n=1). Among patients with arterial thrombosis, 60% had systemic involvement (≥3 organs involved), 89% elevated serum IgG4 (> 3N in 56%), and 57% CRP >10 mg/l. Only 5/10 were treated with steroids at the time of arterial complication, and 4 had never been exposed to steroid therapy. Renal involvement was associated with the occurrence of an arterial thrombotic event (p = 0.03). Venous thromboembolic complications (deep venous thrombosis (DVT) n=12, pulmonary embolism n=4) occurred on average 24 months [0-164] after the first symptoms of IgG4-RD, but were inaugural in 6 patients. Usual venous thrombosis risk factors were found in only 3/16. Seven patients had retroperitoneal fibrosis (RPF), 2 had mediastinal fibrosis, 60% had localized IgG4-RD (≤2 organs involved), serum IgG4 level was normal in 67% and CRP Conclusion: Arterial and venous thrombotic complications are common in IgG4-RD patients. While arterial events are associated with mulitorgan involvement and elevated serum IgG4, venous thrombotic complications appear to affect more likely patients with compressive localized forms of the disease, such as RPF. Mechanisms responsible for this over-risk and clinical benefit of a preventive platelet antiaggregant or anticoagulant treatment in high risk of thrombosis subgroups remain to be evaluated. Disclosure of Interests: None declared

The aim of our study was to investigate possible differences in nailfold videocapillaroscopy (NVC) features between patients with dermatomyositis (DM), overlap myositis (OM), antisynthetase syndrome (ASS), and immune-mediated necrotizing myopathy (IMNM).We performed a cross-sectional monocentric study. All patients with inflammatory myopathies (IMs) over a 6-month period were analyzed by NVC for giant and ramified capillaries, tortuosities, capillary density, disorganization, and scleroderma pattern. Clinical, biological, and pathological characteristics were retrospectively recorded. Patients were classified as having DM, OM, ASS, or IMNM for comparison. Patients were also compared with a group of patients with systemic sclerosis (SSc).NVC was analyzed in DM (n = 17), OM (n = 8), ASS (n = 12), and IMNM (n = 6). Vascular disorganization and avascular zones were observed only in DM (11.8%) and OM (62.5%). The percentage of patients with giant capillaries was higher in OM (n = 4/8) than in DM (n = 3/17) and absent in ASS and IMNM. Frequency of ramified capillaries, tortuosities, hemorrhages, or thrombosis was not different between subgroups. A scleroderma pattern was only observed in OM patients.In this limited series of patients, we observed that DM and OM NVC abnormalities are different from ASS and IMNM. We could not determine NVC specific patterns associated with myositis-specific antibody subtypes of DM because of the small number of patients.Key Points• Nailfold videocapillaroscopy abnormalities are different in subgroups of inflammatory myopathies.• Giant capillaries, disorganization, and major capillary loss are observed in overlap myositis and dermatomyositis but not in antisynthetase syndrome (ASS) or immune-mediated necrotizing myopathy.• Nailfold videocapillaroscopy abnormalities in overlap myositis (with the exclusion of ASS) are close to systemic sclerosis.

Objective.Cardiac involvement during systemic lupus erythematosus (SLE) may include the pericardium, myocardium, valvular tissue, and coronary arteries. The aim of this study was to describe the clinical, biological, and radiological presentation of lupus myocarditis (LM) as well as the treatment response and longterm outcomes.Methods.We conducted a multicentric retrospective study of LM from January 2000 to May 2014.Results.Twenty-nine patients (3 men and 26 women) fulfilled the inclusion criteria (median age at the diagnosis of SLE: 30 yrs, range 16–57). Myocarditis was the first sign of SLE in 17/29 cases (58.6%). Troponin was elevated in 20/25 cases. Electrocardiogram results were abnormal in 25/28 cases. Echocardiography revealed low (≤ 45%) left ventricular ejection fraction (LVEF; 19/29, 66%) and pericardium effusion (20/29, 69%). Cardiac magnetic resonance imaging revealed delayed gadolinium enhancement in 9/13 patients (69%). Patients were treated with corticosteroids (n = 28), cyclophosphamide (CYC; n = 16), intravenous immunoglobulins (n = 8), and/or mycophenolate mofetil (n = 2). The median followup was 37 months. One month after the beginning of the treatment, 10/23 patients (43%) who had undergone echocardiography had an LVEF ≥ 55%. At the end of followup, 21/26 patients (81%) exhibited an LVEF ≥ 55%. Three patients died during followup, and 2 died from LM.Conclusion.LM is a severe manifestation of SLE. It can be the first manifestation of the disease or it can occur during followup, in particular in untreated patients. However, the longterm prognosis is typically positive. Patients with less severe disease exhibited good LVEF recovery without CYC.

Introduction: Southeast Asian Ovalocytosis is a dominantly inherited pathology due to a red blood cell membrane abnormal band 3 protein which is prevalent in Southeast Asia. It is associated with no clinical manifestations or induced hemolytic anemia. Case Report: We report herein a case of a 30 years old patient with both Southeast Asian Ovalocytosis and sickle cell trait who had three splenic infarctions without hypoxic situation. Since the last episode, there was no anemia and reticulocyte count and bilirubin reached normal levels. Conclusion: This abnormal band 3 protein lead to a red blood cell deshydratation which could explain polymerization of HbS and clinical manifestations. Only one case of a retinal stroke in a patient from the Comoros Islands with both Southeast Asian Ovalocytosis and a sickle cell trait has been previously reported in 2009. Splenic infarctions could be therefore another clinical manifestation of this association.

International audience; Women with scleroderma (SSc) maintain significantly higher quantities of persisting fetal microchimerism (FMc) from complete or incomplete pregnancies in their peripheral blood compared to healthy women. The non-classical class-I human leukocyte antigen (HLA) molecule HLA-G plays a pivotal role for the implantation and maintenance of pregnancy and has often been investigated in offspring from women with pregnancy complications. However data show that maternal HLA-G polymorphisms as well as maternal soluble HLA-G (sHLA-G) expression could influence pregnancy outcome. Here, we aimed to investigate the underlying role of maternal sHLA-G expression and HLA-G polymorphisms on the persistence of FMc. We measured sHLA-G levels by enzyme linked immunosorbent assay in plasma samples from 88 healthy women and 74 women with SSc. Male Mc was quantified by DYS14 real-time PCR in blood samples from 58 women who had previously given birth to at least one male child. Furthermore, eight HLA-G 5'URR/3'UTR polymorphisms, previously described as influencing HLA-G expression, were performed on DNA samples from 96 healthy women and 106 women with SSc. Peripheral sHLA-G was at lower concentration in plasma from SSc (76.2 ± 48.3 IU/mL) compared to healthy women (117.5 ± 60.1 IU/mL, p

Pachymeningitis is rare, either idiopathic or secondary to inflammatory disorders, after tumoral, surgical or infectious causes have been excluded. The fibroinflammatory IgG4-related disease is one of the etiologies of pachymeningitis with only few cases reported yet. From a single referral regional center, we evaluated the frequency of IgG4-related disease as the cause of inflammatory pachymeningitis in 10% of cases. From a National case registry of IgG4-related disease the pachymeningitis frequency was 4.1%. We report eight new cases with cranial, spinal or both involvements and a literature review of 46 pathological proven cases. We observed that IgG4-related pachymeningitis is in most cases not associated to extra-neurological manifestations of the disease. Only 27% of spinal and 40% of cranial IgG4-related pachymeningitis are associated with other disease localizations. First line treatment strategies included surgery and steroids. The use of immunosuppressants or rituximab was necessary in 18% of spinal and 54% of cranial localizations. Some patients remained with sequellae and clinical and/or radiological improvement can be difficult to obtain.

Background We conducted a monocentric retrospective study of patients with myelodysplastic syndromes (MDS) and autoimmune or inflammatory disorders (AIMs) and a literature review. We analyzed the association with subgroups of the WHO 2016 MDS classification and patient's survival in a case control study. Risk factors associated with survival were analyzed by uni- and multivariate analysis. Results From all MDS patients 11% presented with AIMs. These were heterogeneous and the most frequent where polyarthritis (25%) and autoimmune cytopenias (17%). No difference for frequency and type of AIMs was observed for the WHO 2016 MDS subgroups (p = .3). In the case control study WHO classification, karyotype abnormalities, IPSS-R and IPSS were similar in both groups. The overall survival from MDS diagnosis was better in the group with AIMs [10.3 ± 0.6 (IC95% 6.2–12.9) versus 4.8 ± 1.1 years (IC95% 4.2–8.7), p = .04]. The better survival was restricted to MDS with low or intermediate-1 IPSS [11.1 ± 1.5 (IC95% 9.9-NR) versus 8.7 ± 1.3 years (IC95% 4.8–10.3), p = .006]. The better survival was only observed when AIMs diagnosis was timely associated or appeared after MDS diagnosis (p = .04). Factors associated with a better overall survival and survival without AML were steroid dependence [respectively HR = 0.042, p = .003, (IC95% 0.005–0.33) and HR = 0.07, p = .002, (IC95% 0.013–0.39)], a diagnosis of AIMs and MDS timely associated [respectively HR = 0.05, p = .009, (IC95% 0.006–0.478) and HR = 0.1, p = .008, (IC95% 0.018–0.54)] or a diagnosis of AIMs after MDS [respectively HR = 0.024, p = .009, (IC95% 0.001–0.39) and HR = 0.04, p = .008, (IC95% 0.003–0.43)]. Conclusion Autoimmune and inflammatory diseases associated to MDS are heterogeneous. AIMs diagnosed after or concomitantly to MDS seems associated with a better survival. Prospective studies are necessary to demonstrate that autoimmunity is associated to a better control of the MDS clone.

International audience

Resume Introduction Les thymomes sont des tumeurs tres frequemment associees a des syndromes paraneoplasiques de type auto-immun. Les atteintes renales a type de glomerulonephrite ont ete rapportees dans ce cadre mais sont cependant rares et donc peu connues. Nous en rapportons une nouvelle observation, dont l’evolution favorable apres thymectomie a confirme le caractere paraneoplasique. Observation Nous rapportons l’observation d’une femme de 77 ans presentant un syndrome nephrotique d’apparition recente lie a une glomerulonephrite extra-membraneuse a l’histologie renale. Le bilan complementaire retrouve un thymome, de type B2 a l’analyse histologique. Le traitement du thymome va permettre une disparition du syndrome nephrotique. Conclusion Les glomerulonephrites extra-membraneuses peuvent etre des manifestations secondaires aux thymomes de meme que d’autres types d’atteintes renales glomerulaires. Un thymome doit donc etre recherche dans ces situations de meme qu’une atteinte renale glomerulaire doit l’etre devant la decouverte d’un thymome. L’evolution peut etre favorable apres thymectomie.

Background Different pulmonary hypertension (PH) mechanisms are associated with hereditary haemorrhagic telangiectasia (HHT). Methods and results We conducted a retrospective study of all suspected cases of PH (echocardiographically estimated systolic pulmonary artery pressure [sPAP] ≥ 40 mmHg) in patients with definite HHT recorded in the French National Reference Centre for HHT database. When right heart catheterization (RHC) was performed, PH cases were confirmed and classified among the PH groups according to the European guidelines. Among 2,598 patients in the database, 110 (4.2%) had suspected PH. Forty-seven of these 110 patients had RHC: 38/47 (81%) had a confirmed diagnosis of PH. The majority of these had isolated post-capillary PH (n = 20). We identified for the first time other haemodynamic profiles: pre-capillary pulmonary arterial hypertension (PAH) cases (n = 3) with slightly raised pulmonary vascular resistances (PVR), and combined post- and pre-capillary PH cases (n = 4). Compared to controls, survival probability was lower in patients with PAH. Conclusion This study revealed the diversity of PH mechanisms in HHT. The description of combined post- and pre-capillary PH with/or without high cardiac output (CO) suggests either a continuum between the pre- and post-capillary haemodynamic profiles or a different course in response to high CO.

Objective To assess the mortality profile of systemic lupus erythematosus (SLE) patients in France using multiple-cause-of-death analysis. Methods Data were collected between 2000 and 2009 in the French Epidemiological Center for the Medical Causes of Death database, and death certificates issued upon the death of an adult for whom SLE was an underlying cause of death (UCD) or a non–underlying cause of death (NUCD) were evaluated using multiple-cause-of-death analysis. Sex, age, sex ratio, standardized mortality rates, as well as frequency of the various causes of death were assessed, at both a national and a regional level. For the main causes of death, the observed number of deaths in relation to the expected number of deaths (O:E ratio) (standardized for age and sex) was calculated. Results During the study period, 1,593 deaths related to SLE were identified. The mean ± SD age at death was 63.5 ± 18.4 years and the sex ratio (female:male) was 3.5. The mean standardized mortality rate was 3.2 per 1 million people (range 2.7–4.1). When SLE was the UCD (n = 637), the main NUCDs were cardiovascular diseases (49.5%), infectious diseases (24.5%), and renal failure (23.2%). When SLE was an NUCD (n = 956), the most common UCDs were cardiovascular diseases (35.7%), neoplasms (13.9%), and infectious diseases (10.3%). The overall O:E ratio was >1 for infectious and cardiovascular diseases and renal failure (especially among people

BackgroundIn patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability.MethodsWe did an open-label, single arm, at one study site with 6-month follow-up among 12 female SSc patients with Cochin Hand Function Scale score >20/90. Autologous SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles. Primary outcome was the number and the severity of adverse events related to SVF-based therapy. Secondary endpoints were changes in hand disability and fibrosis, vascular manifestations, pain and quality of life from baseline to 2 and 6 months after cell therapy.FindingsAll enrolled patients had surgery, and there were no dropouts or patients lost to follow-up. No severe adverse events occurred during the procedure and follow-up. Four minor adverse events were reported and resolved spontaneously. A significant improvement in hand disability and pain, Raynaud's phenomenon, finger oedema and quality of life was observed.InterpretationThis study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months suggest potential efficacy needing confirmation in a randomised placebo-controlled trial on a larger population.FundingGFRS (Groupe Francophone de Recherche sur la Sclérodermie).Clinical Trials numberNCT01813279.

European and American recommendations have recently been published for the treatment of proliferative lupus nephritis (LN). This study aimed to describe current practice in France. An electronic survey was sent to French nephrologists and internists via their scientific society between March and December 2012. One hundred and nine specialists (60 internists, 48 nephrologists and 1 rheumatologist), mostly from hospitals, completed the survey. Low-dose cyclophosphamide (Euro-Lupus) was the first induction immunosuppressive therapy used (67%), followed by mycophenolate mofetil (MMF) (20%) and high dose CYC (NIH, 9%). Maintenance immunosuppressive therapy after an induction with CYC was preferentially MMF (58%), versus 14% for azathioprine (AZA) and 25% using either MMF or AZA without preference. After an induction with MMF, maintenance treatment was mainly MMF (77%). Antimalarial drugs were prescribed systematically by 86% of specialists. In patients in stable remission, maintenance treatment was withdrawn after 2 years (40%), 3 years (25%) or more (34%). Low-dose corticosteroids were continued in the long-term by 54% of specialists. No difference was observed between nephrologists and internists, even in the prescription of antimalarials. Treatment of proliferative LN in France is homogenous enough and is consistent with recent international recommendations.

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) can lead to end-stage renal disease in patients with renal involvement. Objective: This study evaluated the survival of AAV patients on chronic dialysis in France. Methods: Between 2002 and 2011, a total of 425 AAV patients started chronic dialysis and were registered in the Renal Epidemiology and Information Network. We analysed survival censored for renal transplantation, recovery of renal function and loss to follow-up. AAV patients were compared with 794 matched non-AAV patients on chronic dialysis. Results: A total of 166 (39%) patients with microscopic polyangiitis and 259 (61%) patients with granulomatosis with polyangiitis were registered. Within a median follow-up of 23 months, 58 (14%) patients received a renal allograft and 19 (4%) recovered renal function. Median survival on dialysis was 5.35 years (95% CI, 4.4–6.3) and survival rates at 3 months, 1, 3 and 5 years were 96%, 85%, 68% and 53%, respectively. A total of 143 (41%) patients died after a median of 16 months. Causes of death were cardiovascular (29%), infections (20%), malnutrition (13%), malignancies (4%), AAV relapse (2%), miscellaneous (14%) and unknown (18%). Multivariate logistic regression identified three independent risk factors associated with AAV patients’ mortality: age (HR = 1.05/year, P < 0.001), peripheral artery disease (HR = 2.62, P = 0.003) and frailty (HR = 2.43, P < 0.001). Survival of AAV patients did not differ from non-AAV controls, but infectious mortality was higher in AAV patients (20% vs. 8%, P < 0.001). Conclusion: Survival of AAV patients in chronic dialysis, although poor, was comparable to survival of non-AAV controls on dialysis. There was a similar burden of cardiovascular mortality, but higher infectious mortality.

Objective To evaluate the usefulness of 2-[18F]-fluoro-2-deoxy-d-glucose–positron emission tomography/computed tomography (FDG-PET/CT) in IgG4-related disease (IgG4-RD) for the staging of the disease and the followup under treatment. Methods All patients included in the French IgG4-RD registry who underwent ≥1 FDG-PET/CT scan were included in the study. Clinical, biologic, pathologic, radiologic, and FDG-PET/CT qualitative and quantitative findings were retrospectively collected and analyzed. Results Twenty-one patients were included in the study and 46 FDG-PET/CT examinations were evaluated. At either diagnosis or relapse, all evaluated patients presented abnormal 18F-FDG uptake in typical IgG4-RD localizations. In most cases, FDG-PET/CT was more sensitive than conventional imaging to detect organ involvement, especially in arteries, salivary glands, and lymph nodes. In few cases (small-sized lesions and brain or kidney contiguous lesions), false-negative results were noted. Evaluation before and after treatment showed in most cases a good correlation of FDG-PET/CT results with treatment response and disease activity. Conclusion This large retrospective study shows that FDG-PET/CT imaging is useful for the staging of IgG4-RD. Moreover, FDG-PET/CT is useful to assess the response to treatment during followup.

Resume Propos L’avenement des anticorps anti-transglutaminase tissulaire (AATG) a permis la distinction de formes frustres, latentes et silencieuses de la maladie cœliaque (MC). Le diagnostic et le suivi immunologique de la maladie doivent desormais reposer en premiere intention, en France, sur la recherche d’AATG d’isotype IgA. Au sein de l’Assistance publique–Hopitaux de Marseille, le depistage serologique de cette pathologie s’est effectue pendant plusieurs annees par le dosage concomitant des anticorps anti-endomysium (AAE) et des AATG. Dans la litterature, peu de donnees existent sur le degre de concordance des deux tests entre eux et peu de donnees epidemiologiques sur la MC en France ont ete publiees jusque-la. Methodes Nous presentons ici l’etude retrospective de 5981 patients preleves pour recherche d’anticorps associes a la MC. Apres avoir detaille les caracteristiques epidemiologiques de la cohorte, nous avons comptabilise et analyse les dossiers clinicobiologiques des patients presentant un resultat discordant pour le dosage des AAE et des AATG. Resultats Avec les 5981 patients testes, tous les âges et toutes les specialites medicales sont representes. Quatre-vingt-cinq nouveaux cas de MC ont ete depistes. Sur l’ensemble des 6516 dosages realises, seuls 31 etaient discordants. Conclusions Les donnees obtenues precisent l’epidemiologie de la MC en France. Elles soutiennent la demarche de ne garder que le dosage des AATG en premiere intention pour le diagnostic immunologique de MC.

Increasing rituximab prescription for ANCA-associated necrotizing vasculitides justifies the publication of recommendations for clinicians. Rituximab is approved in the United States to induce and maintain remission. In Europe, rituximab was recently approved for remission induction. However, governmental agencies' approvals cannot replace clinical practice guidelines. Herein, the French Vasculitis Study Group Recommendations Committee, comprised of physicians with extensive experience in the treatment of vasculitides, presents its consensus guidelines based on literature analysis, the results of prospective therapeutic trials and personal experience.

International audience; Evidence before this study We searched PubMed on June 30, 2016, for English-language cohort studies published since Jan 1, 1980, of patients with invasive listeriosis worldwide with the keywords " listeria " , " listeriosis " , " maternal " , and " neurolisteriosis ". Studies had to include epidemiological or clinical data on listeriosis. All clinical forms of infection were included (bacteraemia, neurolisteriosis, and maternal–neonatal infection). Host risk factors for listeriosis have been well identified, but the clinical features and prognostic factors of the disease are based on retrospective studies compiling heterogeneous data or random collected cases. Furthermore, no clinical trial has ever been done and medical management is not evidence based. Added value of the study Our study is the first prospective clinical study focusing on all forms of invasive listeriosis. The study is based on a national mandatory system that allowed the nearly complete capture of microbiologically proven cases. The study shows a higher burden of listeriosis than reported before: more than 80% of infected mothers experienced major fetal or neonatal complications (fetal loss, very high prematurity, early or late onset disease); only 39% of patients with neurolisteriosis survived and fully recovered. The study provides important new data to improve management and predict outcome in listeriosis, such as determination of the time window for fetal losses (

Statement of Purpose. IgG4-related disease (IgG4-RD) is usually associated to an increase of serum IgG4 levels. However other conditions have also been associated to high serum IgG4 levels.Methods. All IgG subclasses analyses performed in our hospital over a one-year period were analyzed. When IgG4 level were over 1.35 g/L, the patient’s clinical observation was analyzed and both final diagnosis and reason leading to IgG subclasses analysis were recorded. Only polyclonal increases of IgG4 were considered.Summary of the Results. On 646 IgG subclass analysis performed, 59 patients had serum IgG4 over 1.35 g/L. The final diagnosis associated to serum IgG4 increase was very variable. Most patients (25%) presented with repeated infections, 13.5% with autoimmune diseases, and 10% with IgG4-RD. Other patients presented with cancer, primary immune deficiencies, idiopathic interstitial lung disease, cystic fibrosis, histiocytosis, or systemic vasculitis and 13.5% presented with various pathologies or no diagnosis. Mean IgG4 levels and IgG4/IgG ratio were higher in IgG4-RD than in other pathologies associated to elevated IgG4 levels.Conclusions. Our study confirms that elevation of serum IgG4 is not specific to IgG4-RD. Before retaining IgG4-RD diagnosis in cases of serum IgG4 above 1.35 g/L, several other pathological conditions should be excluded.

Resume Le syndrome d’hyper-IgG4, ou maladie systemique associee aux IgG4, est une entite de description recente caracterisee par la presence d’une ou plusieurs atteintes fibro-inflammatoires d’organe, associees le plus souvent a une elevation des IgG4 seriques. Les lesions tissulaires sont caracterisees par une fibrose et un infiltrat inflammatoire lymphocytaire et plasmocytaire, avec predominance de plasmocytes IgG4+. Outre les tableaux de pancreatite sclerosante (dite « auto-immune ») les premiers decrits, les atteintes d’organe rapportees sont nombreuses et peuvent etre associees chez un meme patient. Parmi ces atteintes, on rapporte des tableaux de sialadenite, de dacryoadenite, de polyadenopathies, d’aortite, de cholangite sclerosante, de nephrite interstitielle, de fibrose retroperitoneale ou encore de pseudotumeurs inflammatoires. L’ensemble de ces atteintes d’organes, survenant le plus souvent apres 50 ans, partagent des lesions histologiques communes. L’evolution est habituellement marquee par une grande corticosensibilite. Cette revue de la litterature souligne les difficultes diagnostiques, en particulier biologiques et histologiques, essentiellement en rapport avec l’absence de criteres valides pour le diagnostic de maladie systemique associee aux IgG4. Il reste aussi a caracteriser a l’avenir l’epidemiologie et la physiopathologie de ce nouveau syndrome, mais aussi a en preciser la prise en charge therapeutique.

We conducted a retrospective survey to assess prescription practice, response rates to rituximab, and the predictive indicators for a response to rituximab therapy in patients with primary or secondary immune thrombocytopenic purpura (ITP). Data were collected retrospectively from 40 consecutive patients with ITP attending our hospital: 29 (72.5%) had primary ITP and 11 (27.5%) had secondary ITP. Rituximab was given either as four weekly injections (375 mg/m(2)) or two injections of 1,000 mg given 2 weeks apart in 30 and 10 patients, respectively. The primary objective was to evaluate overall (OR) and complete response (CR) to rituximab therapy for ITP. OR was excellent and rapid and similar when secondary ITP was excluded from the analysis: OR was achieved in 28 (71.8%) patients and CR in 22 (56.4%). But, at6 months, of the 28 responders, only 10 of 22 of the evaluable responses (45.5%) were sustained. In addition, except for the nonsignificant occurrence of antinuclear antibodies, no clinical or biological factors were predictive for OR or CR after the rituximab therapy. Twelve patients received a second course of rituximab. Overall, rituximab therapy achieved a response in two thirds of the patients, but the responders exhibited a high rate of early relapses, with no obvious difference according to the regimen of administration or rituximab dose.

Since several years, the use of intravenous immunoglobulins (IVIg) has increased. This growth has encouraged some countries to publish guidelines. In parallel, some countries have conducted audits to know how IVIg are used in clinical practice in the light of the available guidelines. The objective of this study was to assess IVIg use in three French university hospitals in 2006. All IVIg administrations were evaluated during 6 months (12 September 2005-12 March 2006) in French university hospitals of Marseille. Different data were recorded for each administration: patient characteristics, indication, formulation and quantity. During the study period, 2802 administrations of IVIg (corresponding to a total quantity of 76 780 g) have been recorded. Four hundred and thirty-five patients received at least one of these administrations. The five most reported indications were multifocal motor neuropathy (11.0% of total quantity), chronic inflammatory demyelinating polyradiculoneuropathy (10.2%), corticoresistant dermatomyositis (10.2%), immune thrombocytopaenia (9.9%) and primary immune deficiency (9.1%). According to available French recommendations, 70% of the IVIg use was for 'acknowledged indications', 9% for 'indications to be assessed' and 18% for 'unwarranted indications'. The

Increased free light chain (FLC) levels have been reported as useful in various autoimmune conditions. We investigated how FLC concentrations change upon B cell targeted therapy in systemic lupus erythematosus (SLE) patients and if they correlate with disease activity. We retrospectively studied 11 SLE patients without renal failure, whom were treated with rituximab. Quantitative determination of IgG, IgA, IgM, and serum FLC was performed before and after rituximab. At baseline, 70% had abnormal serum FLC levels, including increased kappa and lambda levels, while the kappa/lambda ratio was normal for all. A strong correlation was observed between complement C3 fraction and kappa levels (r = −0.929, P < 0.001) or lambda levels (r = −0.854, P = 0.003), but not with IgG, IgA, or IgM levels. After rituximab treatment, kappa and lambda FLC concentrations decreased significantly whilst total concentrations of IgG, IgA, and IgM also decreased but remained within the normal range. There was a strong correlation only between kappa FLC levels and complement C3 fraction consumption (r = −0.543, P = 0.003). In SLE patients without renal failure, increased FLC levels (mainly kappa) with normal kappa/lambda ratios are a common feature, and in contrast to total IgG levels, FLC concentrations correlate with biological disease activity.

Resume Introduction Le syndrome d’encephalopathie posterieure reversible est une entite clinicoradiologique caracterisee par l’association de signes cliniques neurologiques et d’un œdeme cerebral posterieur bilateral habituellement reversible en neuro-imagerie. Differentes situations pathologiques et certains traitements peuvent etre impliques dans la survenue de ce syndrome. Observation Nous rapportons l’observation d’une patiente de 19 ans, suivie pour une vascularite urticarienne hypocomplementemique, qui presentait un tableau d’encephalopathie posterieure reversible au decours de la prise d’un decongestionnant nasal contenant de la pseudo-ephedrine. L’evolution etait favorable apres arret du traitement sympathomimetique et controle tensionnel. Conclusion Le diagnostic d’encephalopathie posterieure reversible doit etre evoque chez un patient presentant un tableau clinicoradiologique compatible, en raison de son caractere reversible sous traitement adapte. La recherche d’une pathologie associee notamment auto-immune ou d’un facteur declenchant medicamenteux, en particulier la prise d’un decongestionnant nasal, doit etre systematique dans ce contexte.

Objective A number of open-label studies have suggested the potential benefit of rituximab (RTX) in systemic lupus erythematosus (SLE). However, in 2 recent randomized controlled trials (RCTs) of RTX, the primary end points were not met. We undertook this study to evaluate the safety and efficacy of RTX in off-trial patients with SLE seen in regular clinical practice. Methods We analyzed prospective data from the French AutoImmunity and Rituximab (AIR) registry, which includes data on patients with autoimmune disorders treated with RTX. Results One hundred thirty-six patients received treatment for SLE. The mean ± SD score on the Safety of Estrogens in Lupus Erythematosus: National Assessment (SELENA) version of the SLE Disease Activity Index (SLEDAI) was 11.3 ± 8.9 at baseline. Severe infections were noted in 12 patients (9%), corresponding to a rate of 6.6/100 patient-years. Most severe infections occurred within the first 3 months after the last RTX infusion. Five patients died, due to severe infection (n = 3) or refractory autoimmune disease (n = 2). Overall response was observed in 80 of 113 patients (71%) by the SELENA–SLEDAI assessment. Efficacy did not differ significantly between patients receiving RTX monotherapy and those receiving concomitant immunosuppressive agents (who had higher baseline disease activity). Articular, cutaneous, renal, and hematologic improvements were noted in 72%, 70%, 74%, and 88% of patients, respectively. Among responders, 41% experienced a relapse of disease, with a response in 91% after retreatment with RTX. Conclusion Data from the AIR registry show a satisfactory tolerance profile and clinical efficacy of RTX in patients with SLE. The contrasting results with those from recent RCTs leave open the question of the therapeutic use of RTX in SLE. Additional controlled studies with new designs are needed to define the place of RTX in the therapeutic arsenal for SLE.

Objectives. Male microchimerism (Mc) persisting from pregnancy has been found at greater frequencies and/or higher quantities in women with scleroderma (SSc) compared with controls, suggesting a possible role in disease development. Moreover, women with an HLA-compatible child have a higher risk to develop SSc. We tested the hypothesis, on our French SSc cohort, that women with lcSSc and dcSSc, two distinct clinical subsets, have a different profile in terms of Mc and HLA compatibility in families. Methods. We studied 98 women (52 lcSSc and 46 dcSSc) for male Mc, by real-time PCR, in their whole blood and/or peripheral blood mononuclear cells (PBMC). Similarly, 91 matched healthy women were analysed. Complete HLA-DRB1 typing was obtained for 58 SSc and 68 control families (proband/children). Results. Women with lcSSc (N ¼ 50) had male Mc more often in their whole blood than women with dcSSc (N ¼ 40, 20 vs 5%, P ¼ 0.038), but not significantly more than controls. By contrast, women with dcSSc (N ¼ 36) hold Mc more often in PBMC (25 vs 9%), but not significantly and have greater quantities than controls (N ¼ 82, P ¼ 0.048). This contrast is also visible in feto-maternal HLA-DRB1 compatibility, which was increased only among women with lcSSc (N ¼ 33) compared with controls (N ¼ 68, P ¼ 0.003). Conclusion. For the first time, we showed that women with lcSSc and dcSSc hold male Mc in different blood compartments. Furthermore, a distinct pattern between the two SSc subtypes is observed for feto-maternal HLA-DRB1 compatibility. These results suggest a different mechanism behind each type of disease.

Mastocytosis is an acquired orphan disease characterized by the abnormal accumulation of mast cells responsible for organ failure and systemic symptoms. Cytoreductive drugs have been shown to be effective, but have rarely resulted in complete or long-term remission. We report two patients with advanced systemic mastocytosis (SM) who were treated successfully with thalidomide, given at the maximal tolerated dosage. B and C-findings as well as clinical symptoms rapidly improved. After a follow-up of more than 1 year, the patients remained in partial remission. Thalidomide seems to be an active drug in advanced SM. However, clinical trials are warranted to define its efficacy and safety profiles.

Resume Propos La frequence de la carence en vitamine B12 a, pour consequence, une prescription courante du dosage de la vitaminemie B12 dans un service de medecine interne, qui peut paradoxalement reveler une hypervitaminemie B12. L’objectif de ce travail est d’evaluer les pathologies sous-jacentes et l’eventuel interet diagnostique des hypervitaminemies B12 dans un service de medecine interne. Methodes Il s’agit d’une etude epidemiologique retrospective, concernant les patients hospitalises dans un service de medecine interne de decembre 2005 a juillet 2006 qui presentent une hypervitaminemie B12, selon les normes du laboratoire (200–950 pg/mL). Resultats La decouverte d’une hypervitaminemie B12 n’est pas rare (18,5 % des dosages realises) et dans la plupart des cas, elle est associee a une ou plusieurs pathologies, parmi lesquelles on retrouve des hepatopathies aigues ou chroniques (notamment d’origine alcoolique), des neoplasies solides variees, des hemopathies malignes (syndrome myelodysplasiques, myeloproliferatifs, myelomes), des insuffisances renales et des anomalies hematologiques transitoires (hyperleucocytoses neutrophiliques, hypereosinophilies), les apports exogenes en B12 et la leucemie myeloide chronique (LMC) representant moins de 5 % de notre effectif. Il n’existe pas de correlation entre le taux de vitamine B12 et le nombre de pathologies associees responsables, mais des taux eleves de B12 (>1275 pg/mL) sont associes de facon significative a la presence d’hemopathies malignes (p Conclusion Les taux les plus eleves de vitaminemie B12 sont associes de maniere significative aux hemopathies malignes dans une population de medecine interne. Le laboratoire referent devrait sensibiliser les cliniciens aux nombreuses orientations diagnostiques qui peuvent decouler de la decouverte d’un taux eleve de vitaminemie B12.

Resume Propos La presence d'anticorps antiphospholipides dans les hepatites auto-immunes a ete peu etudiee. Nous avons etabli la prevalence de ces auto-anticorps dans une serie d'hepatites auto-immunes et recherche une correlation avec des manifestations cliniques, biologiques et histologiques. Methode Les anticorps antiphospholipides ont ete recherches chez 24 malades avec hepatites auto-immunes definies. Une etude cas temoin et l'analyse des cas de la litterature ont ete realisees. Resultats La prevalence des antiphospholipides est de 70,8 % (17/24). Quatre syndromes des antiphospholipides sont identifies (28,6 %). Les anticorps retrouves par ordre de frequence sont : l'IgG ACL (52,9 %), l'IgM APE (52,9 %), l'ACC (43,7 %), l'IgG Aβ2GP1 (41,2 %). L'hypergammaglobulinemie n'est pas correlee a la presence ou a l'isotype de l'antiphospholipide. L'âge moyen des patients est de 39,9 ans (± 14,1) et le sex-ratio H/F de 4/13. Sept patients sur 17 ont un diagnostic de lupus erythemateux dissemine dans le groupe antiphospholipide positif. Les caracteristiques clinicobiologiques et l'evolution de la maladie hepatique ne semblent pas liees a la presence de l'anticorps. Conclusion Nous confirmons la prevalence elevee des antiphospholipides dans les hepatites auto-immunes. Notre etude ne permet pas de retrouver des caracteristiques cliniques, biologiques ou histologiques particulieres aux hepatites auto-immunes avec APL. L'analyse longitudinale de plus grandes cohortes devrait permettre d'eclaircir cette association et les eventuelles implications therapeutiques.

Resume Introduction Le groupe des thrombopenies constitutionnelles avec macroplaquettes associees a des inclusions leucocytaires comprend plusieurs syndromes dont le syndrome de May-Hegglin. Leur mode de transmission est autosomique dominant et ces syndromes ont ete recemment regroupes dans une meme entite clinique en raison de la mise en evidence de mutations localisees au niveau d'un meme gene : le gene MYH9 . Exegese Nous rapportons la decouverte d'une nouvelle mutation du gene MYH9 lors du diagnostic d'un nouveau cas de maladie de May-Hegglin chez une jeune adulte d'origine africaine et nous presentons une revue actualisee des connaissances de son nouveau cadre nosologique : le syndrome MYH9. Conclusion Le syndrome MYH9 regroupe plusieurs entites clinicobiologiques associant de facon constante une macrothrombocytopenie et de facon variable des pseudocorps de Dohle, une atteinte renale, une cataracte, une surdite. Nous en rapportons un nouveau cas original associee a une mutation ponctuelle inconnue a ce jour.

Hemophagocytic syndrome (HPS) is characterized by an uncontrolled and poorly understood activation of T-helper 1 (Th-1) lymphocytes and macrophages. We studied 20 patients with HPS secondary to infections, autoimmune disease, lymphoma, or cancer and observed that the concentrations of serum interleukin 18 (IL-18), a strong inducer of Th-1 responses, interferon gamma (IFN-gamma) production, and stimulation of macrophages and natural killer (NK) cells were highly increased in HPS but not in control patients. In contrast, concentrations of its natural inhibitor, the IL-18 binding protein (IL-18BP), were only moderately elevated, resulting in a high level of biologically active free IL-18 in HPS (4.6-fold increase compared with controls; P < .001). Free IL-18 but not IL-12 concentrations significantly correlated with clinical status and the biologic markers of HPS such as anemia (P < .001), hypertriglyceridemia, and hyperferritinemia (P < .01) and also with markers of Th-1 lymphocyte or macrophage activation, such as elevated concentrations of IFN-gamma and soluble IL-2 and tumor necrosis factor alpha (TNF-alpha) receptor concentrations. Despite high IL-18 elevation, in vitro NK-cell cytotoxicity was severely impaired in HPS patients, in part due to NK-cell lymphopenia that was observed in a majority of patients but also secondary to an intrinsic NK-cell functional deficiency. We concluded that a severe IL-18/IL-18BP imbalance results in Th-1 lymphocyte and macrophage activation, which escapes control by NK-cell cytotoxicity and may allow for secondary HPS in patients with underlying diseases.