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Background Mitral annular calcification (MAC) is a chronic inflammatory process, which is common in elderly patients and those with renal dysfunction. MAC is associated with cardiovascular morbidity, and can also be the seat of infective endocarditis (IE). Purpose The aim of this study was to test the hypothesis that IE on MAC would be prevalent in patients with renal dysfunction and more comorbidities, and thus would have more complications. Methods We retrospectively reviewed in our center, all patients diagnosed with IE according to modified Dukes criteria from December 2007 to December 2016. MAC was defined as focal echo-brightness in a nodular or band-like pattern. Results We find 119 patients with IE, whose 55 IE (46.2%) were on mitral valve, including 39 (32.7%) on native valve and 13 (10.9%) on MAC. Staphylococcus aureus was the infecting organism of 9/13 (69.2%) MAC vs. 24/106 (22.6%) of all other IE (P = 0.02); 11/42 (26.1%) of IE on mitral valve (prosthetic and native) (P = 0.01); and 6/26 (23.0%) of IE on only native mitral (P = 0.01). More abscess were find in MAC group: 10/13 (76.9%) vs. 27/106 (25.5%) of all other IE (P Conclusion MAC appears to be more often infected by Staphylococcus aureus. As it's also a predisposing factor for abscess, we think that repeated echography could allow a better track of IE on elderly patient with septicemia with Staphylococcus aureus, especially when hemocultures negativate later.

Introduction Lors de bacteriemies, la determination du profil de resistance apparait comme une etape cruciale. Bien qu’un traitement antibiotique probabiliste soit instaure, les resistances demeurent imprevisibles et peuvent etre a l’origine d’echecs therapeutiques. La rapidite de l’obtention de l’antibiogramme conditionne une bonne adaptation du traitement antibiotique et une optimisation de la prise en charge des patients bacteriemiques. Materiels et methodes Cette etude pilote prospective a ete realisee en routine entre aout 2016 et janvier 2017. Les antibiogrammes ont ete realises directement a partir des flacons d’hemocultures positives sur milieu Mueller Hinton (MH). 86 echantillons, contenant des enterobacteries (79 %) ou des Staphylococcus aureus (21 %) ont ete testes en parallele par deux methodes : le milieu MH standard (Biorad), incube 16 h et le milieu MHR (MH rapide, i2a), incube 6 a 8 h. Deux panels differents d’antibiotiques ont ete testes : 32 disques sur les bacilles a Gram negatif et 16 disques sur les S. aureus. Les diametres d’inhibition ont tous ete lus par le systeme automatique SIRscan 2000 (i2a) et ont ete interpretes en tenant compte des recommandations EUCAST 2016. Pour chaque bacterie et chaque antibiotique testes, nous avons compare la concordance des interpretations entre les deux methodes : sensible (S), intermediaire (I) ou resistant (R). Resultats Les 63 souches d’enterobacteries etaient distribuees entre 37 (58,7 %) E. coli, 12 (19,0 %) K. pneumoniae , 7 (11,1 %) E. cloacae, 3 (4,8 %) E. aerogenes, 2 (3,2 %) C. freundii, 1 (1,6 %) P. mirabilis et 1 (1,6 %) S. marcescens. Sur les 1732 tests realises, les resultats montraient 1648 (96,8 %) concordances, 33 (2,0 %) differences mineures (dm), 5 (0,3 %) differences majeures (DM) et 16 (0,9 %) differences tres majeures (DTM). Les dm etaient majoritairement constatees autour de la piperacilline. Les DTM observees concernaient principalement les Enterobacter, Citrobacter et Serratia pour la cefalexine. Dans le groupe des 18 S. aureus, nous avons trouve 259 (89,9 %) concordances, 8 (2,8 %) dm, 21 (7,3 %) DM et aucune DTM. Les differences majeures etaient principalement observees pour la cefoxitine. Conclusion Nos resultats montrent une bonne correlation entre les antibiogrammes realises en milieux MH et MHR. Bien que des differences aient ete constatees, l’utilisation du MHR est une methode rapide permettant de predire la sensibilite aux antibiotiques des enterobacteries et des S. aureus. Il apparait cependant que la cefalexine n’etait pas fiable sur les enterobacteries du groupe 3 en methode MHR, ce qui n’avait pas d’impact en clinique. De plus, la resistance a la meticilline des S. aureus n’etait pas systematiquement predictible en MHR. Notre etude, qui s’inscrit dans une etude plus globale, montre des resultats tres encourageants. L’antibiotherapie peut etre adaptee des le premier jour de positivite de l’hemoculture.

Introduction Les ulceres cutanes surviennent principalement chez les patients vasculaires, diabetiques. Parmi les complications, la surinfection de ces ulceres est un enjeu therapeutique et les diagnostics clinique et microbiologique sont souvent complexes. La PCR multiplex (ITI cartridge, Unyvero, Curetis ®) peut a partir des biopsies cutanees, detecter rapidement les pathogenes impliques : staphylocoques, enterobacteries, P. aeruginosa, bacteries anaerobies ainsi que les genes de resistance mecA/C, ermA/C, vanA/B, KPC, VIM, NDM, ctx-M, IMP, aac6’, aacA4. Un diagnostic bacteriologique precoce permettrait une prise en charge rapide et adaptee. Objectif De comparer les resultats obtenus par PCR a la bacteriologie standard. Materiels et methodes Les patients presentant un ulcere colonise/surinfecte, hospitalises au GHPSJ, de mars a juin 2017 ont ete inclus apres consentement. Une biopsie cutanee a ete prelevee sur laquelle etaient effectuees culture standard et PCR multiplex. Un antibiogramme en diffusion etait realise en cas de culture positive. Resultats Quarante-huit patients ont ete inclus dans l’etude. La biopsie etait positive en culture pour 43 patients et 29 par PCR. Les principales bacteries retrouvees en culture etaient : S. aureus (58,3 %), P. aeruginosa (37,5 %), et les enterobacteries (25 %). Pour 7 biopsies (16,3 %) les resultats etaient identiques entre PCR et culture. La PCR identifiait des bacteries non retrouvees en culture : staphylocoques a coagulase negative, anaerobies, corynebacteries, P. acnes pour 15 biopsies (34,9 %), sachant que 24 % des patients avaient recu une antibiotherapie prealable. Les genes de resistance trouves par PCR dans 4 biopsies etaient : erm, mecA, aac6’ concordants dans 100 % des cas avec l’analyse phenotypique des mecanismes de resistance. Conclusion La PCR multiplex permet de detecter rapidement les bacteries pathogenes chez les patients ayant un ulcere colonise/surinfecte. Notre etude a montre que la PCR mettait en evidence des bacteries de culture difficile non trouvees avec la bacteriologie standard. Cette premiere etude sur l’utilisation de la PCR multiplex dans ce contexte montre des resultats interessants a confronter aux donnees cliniques afin de placer ce test dans une demarche diagnostique optimale.

Herein we report two cases of infections caused by Tissierella praeacuta and a review of the literature. The first case was a septic pseudarthrosis of the left femur after multiple fractures. Two per-operative samples were positive with T. praeacuta. The patient was successfully treated by piperacillin – tazobactam and metronidazole. The second case was a bacteremia in a patient suffering from pyonephrosis and a hepatic abscess. The treatment was meropenem. No relapses were observed in both cases. Identification of the strains using MALDI-TOF coupled to mass spectrometry (MS) (Beckman coulter, France) was inconclusive in the two cases. Identification by 16S rRNA sequencing was then performed. This bacterium was susceptible to beta-lactams, chloramphenicol, rifampicine and metronidazole.

The rapid and accurate detection of influenza virus in respiratory specimens is required for optimal management of patients with acute respiratory infections. Because of the variability of the symptoms and the numerous other causes of influenza-like illness, the diagnosis of influenza cannot be made on the basis of clinical criteria alone. Thus, rapid influenza diagnostic tests have been developed such as the Alere i Influenza A&B isothermal nucleic acid assay. We prospectively evaluated the performance of the Alere i Influenza A&B assay in comparison with our routine Xpert Flu/RSV assay. Positive samples were subtyped according to the protocol from the National Influenza Center (Paris, France). A total of 96 respiratory nasal swab samples were analyzed: with both methods, 38 were positive and 56 were negative. Samples were prospectively collected from January 20 to April 8, 2015, from patient (86 adult and 10 pediatric patients) presenting with an influenza-like illness through the French influenza season. In comparison with the Xpert Flu/RSV assay, the overall sensitivity and specificity of the Alere i Influenza A&B assay were 95% and 100%, respectively. Our results indicate that the Alere i Influenza A&B assay has a good overall analytical performance and a high degree of concordance with the PCR-based Xpert Flu/RSV assay. The Alere i Influenza A&B isothermal nucleic acid amplification test is a powerful tool for influenza detection due to its high sensitivity and specificity as well as its ability to generate results within 15min.

International audience; Objective: Infections are the major cause of morbidity and mortality in immunocompromised patients. Improving microbiological diagnosis in these patients is of paramount clinical importance. Methods: We performed this multicentre, blinded, prospective, proof-of-concept study, to compare untargeted next-generation sequencing with conventional microbiological methods for first-line diagnosis of infection in 101 immunocompromised adults. Patients were followed for 30 days and their blood samples, and in some cases nasopharyngeal swabs and/or biological fluids, were analysed. At the end of the study, expert clinicians evaluated the results of both methods. The primary outcome measure was the detection rate of clinically relevant viruses and bacteria at inclusion. Results: Clinically relevant viruses and bacteria identified by untargeted next-generation sequencing and conventional methods were concordant for 72 of 101 patients in samples taken at inclusion (k test ¼ 0.2, 95% CI 0.03-0.48). However, clinically relevant viruses and bacteria were detected in a significantly higher proportion of patients with untargeted next-generation sequencing than conventional methods at inclusion (36/101 (36%) vs. 11/101 (11%), respectively, p

Introduction Lors de la realisation d’un examen cytobacteriologique des urines (ECBU), un delai de 48 h est requis avant d’obtenir l’identification, la numeration de la culture ainsi que l’antibiogramme de la bacterie mise en cause lors de l’infection urinaire. Dans le contexte actuel de l’augmentation des bacteries multi-resistantes, le profil de resistance des enterobacteries devient imprevisible, aussi bien en communautaire qu’en milieu hospitalier. Il apparait donc interessant de reduire ce delai de 48 h a 8 h afin d’adapter plus rapidement l’antibiotherapie probabiliste et d’eviter les echecs therapeutiques. Materiels et methodes Cette etude prospective a ete realisee entre aout 2016 et janvier 2017. 158 echantillons d’urines ont ete selectionnes sur les criteres suivants : franche leucocyturie > 50 leucocytes/mm 3 et presence de seuls bacilles a Gram negatif a l’examen direct. Les echantillons ont ete traites selon deux methodes : la methode de reference (48 h) consistait a ensemencer une gelose chromogene et realisation d’un antibiogramme en milieu Mueller Hinton (MH incube 20 h, Biorad). La methode rapide (8 h) consistait a ensemencer directement un antibiogramme en milieu MHR (MH rapide, i2a, incube 6 a 8 h). Un panel de 22 antibiotiques a ete teste, les diametres d’inhibition ont ete lus par le systeme SIRscan 2000 Automatic (i2a) et ont ete interpretes selon les recommandations EUCAST 2016. Pour chaque bacterie et chaque antibiotique testes, nous avons compare la concordance des interpretations entre les deux methodes : sensible (S), intermediaire (I) ou resistant (R). Resultats Les 158 souches d’enterobacteries etaient distribuees entre 119 (75 %) Escherichia Coli et 39 (25 %) autres enterobacteries. Sur les 3246 tests realises, les resultats montraient 3167 (97,6 %) concordances, 47 (1,4 %) differences mineures (dm), 13 (0,4 %) differences majeures (DM) et 19 (0,6 %) differences tres majeures (DTM). Les DTM constatees ont ete principalement observees autour de la cefalexine et de la temocilline. Les DM concernaient principalement l’amoxicilline-acide clavulanique en considerant comme diametres critiques 19–19 mm, sans differenciation d’une infection urinaire haute ou basse. Conclusion Les resultats de notre etude montrent une bonne correlation entre les resultats des antibiogrammes obtenus directement a partir de l’urine en milieu MHR et ceux obtenus a partir d’une subculture en milieu MH. Cette technique rapide entraine un gain de temps important : le delai d’obtention d’un antibiogramme est alors de 8 h, contre 48 h par rapport a la methode standard de realisation d’un ECBU, ce qui permet une adaptation therapeutique precoce. Cette technique est cependant dependante d’un inoculum bacterien minimum ainsi que du caractere monomicrobien de l’urine.

International audience; Antifungal prescription remains a challenge in pregnant women because of uncertainties regarding fetal toxicity and altered maternal pharmacokinetic parameters that may affect efficacy or increase maternal and fetal toxicity. We present updated data reviewing the available knowledge and current recommendations regarding antifungal prescription in pregnancy. Amphotericin B remains the first-choice parenteral drug in spite of its well-established toxicity. Topical drugs are used throughout pregnancy because of limited absorption. Recent data have clarified the teratogenic effect of high-dose fluconazole during the first trimester and provided reassuring cumulative data regarding its use at a single low dose in this key period. Recent data have also provided additional safety data on itraconazole and lipidic derivatives of amphotericin B. Regarding newer antifungal drugs, including posaconazole and echinocandins, clinical data are critically needed before considering prescription in pregnancy.

Parvimonas micra is a rare isolate in clinical specimens. We report a case of spondylodiscitis caused by P. micra, a rarely reported Gram positive cocci. The case was an elderly patient with joint surgery and ischaemic heart disease history. Infection resolved after adequate antibiotic therapy.

International audience; Iatrogenic Cushing's syndrome is an undesirable outcome of glucocorticoids treatment. It can be increased by pharmacologic interactions. Glucocorticoid therapy, given in association with ritonavir, and some azole treatments are causes of iatrogenic Cushing's syndrome. We present a patient with common-variable immunodeficiency who received 7 years of itraconazole therapy for bronchial colonization with Aspergillus in combination with inhaled fluticasone without any Cushingoid symptoms. After a switch to posaconazole, the patient developed Cushingoid symptoms. I atrogenic Cushing's syndrome is caused by exposure to gluco-corticoids and may be promoted by interaction with additional drugs that result in hypothalamic-pituitary-adrenal axis suppression. It is well documented in asthmatic, human immunodefi-ciency virus (HIV)-infected patients receiving inhaled steroids in combination with a ritonavir-containing antiretroviral regimen (1, 2). Steroids, whether inhaled or injected by intranasal or epi-dural routes, have usually minimal systemic effects at recommended dosages. They are metabolized mainly by CYP3A4. The combination of long-term inhaled steroids with azole derivatives, such as itraconazole, fluconazole, or voriconazole, has been reported to exacerbate hypothalamic-pituitary-adrenal axis suppression (3, 4, 5). Posaconazole is an orally active broad-spectrum antifungal triazole that inhibits cytochrome P450-dependent CYP3A4 and therefore decreases synthetic glucocorticoid hepatic metabolism (6). We report a case of a patient who presented with Cushing's syndrome following a treatment switch to posacona-zole after 7 years of itraconazole therapy without any Cushingoid symptoms. A 51-year-old woman with common-variable immunodefi-ciency associated with autoimmunity, bronchiectasis, asthma diagnosed in 1996, and a lymphoid follicular hyperplasia diagnosed in 2010 was treated by montelukast sodium (10 mg once daily), triamcinolone acetonide (55 g once daily), a long-acting ␤2-adrenergic agonist associated with inhaled glucocorticoid (salme-terol and fluticasone), risedronate (35 mg weekly), levothyroxine (75 g daily), desloratadine (5 mg daily), sertraline (25 mg daily), and intravenous immunoglobulins (IVIG). Since 2000, she was treated with itraconazole as prophylaxis for bronchial coloniza-tion with Aspergillus fumigatus without any radiologic signs of invasive aspergillosis or elevated fungal biomarkers (galactoman-nan or beta-D-glucan). In 2007, following the persistent bronchial colonization with Aspergillus fumigatus and the concomitant isolation of Aspergillus nidulans, a switch to posaconazole as prophy-laxis (200 mg three times daily) was done. She did not present any side effects during the first year of treatment. After 12 months of posaconazole treatment, she progressively presented at first a skin fragility and then a venous stasis dermatitis with weight gain (6 kg) and a moon face. Her blood pressure was 130/80 mm Hg with no postural drop, and she had a fasting blood glucose level of 5.1 mmol/liter. Initial investigations detected a low serum cortisol level (35.6 ng/ml) at 8 a.m. (normal range, Ͼ210 ng/ml). A standard short Synacthen test was abnormal, with a baseline serum cortisol concentration of 46 nmol/liter (normal, 170 to 740 nmol/liter), rising only to 206.9 nmol/liter (normal, Ͼ600 nmol/liter) at 60 min, leading to the diagnosis of corticotroph insufficiency. There was no evidence of impaired glucose tolerance. Search for antiadrenal autoantibodies was negative, with limits of interpretation in this patient in IVIG substitution, and pituitary MRI was normal. An adrenocorticotropin (ACTH; at 8 a.m.) concentration of Ͻ10 pg/ml reflects the corticotrop insuffi-ciency. Other hormonal investigations of the hypothalamic-pituitary axis were normal (at 8 a.m.): prolactin ϭ 11.1 g/liter (normal, 3 to 29 g/liter), T4 ϭ 4.7 pmol/liter (normal, 11 to 39 pmol/liter), IGF1 ϭ 91.9 g/ml (normal, ϭ 70 to 300 g/ ml). Corticosteroids supplementation was introduced by hy-drocortisone (40 mg per day), and inhaled steroids were stopped. Oral glucocorticoid therapy is a common cause of iatrogenic Cushing's syndrome. Other routes of steroid administration, such as inhalation, topical, ocular, nasal drops, or epidural injections, may also result in hypercorticism (7). This can be promoted by interaction between glucocorticoids and other drugs interfering with glucocorticoid metabolism, such as ritonavir, itraconazole, or fluconazole (8). We hypothesize that our patient probably developed clinical Cushing's syndrome as a result of elevated sys-temic concentrations of inhaled steroids, which led to cortico-troph insufficiency resulting from adrenocorticotrophic hormone suppression. Inhibition of the cytochrome P450 CYP3A4-type enzyme system by posaconazole leads to a reduction in fluticasone hepatic metabolism. With prolonged use, inhaled steroids have previously been associated with adrenal suppression. The combination of itraconazole, fluconazole, or voriconazole with inhaled steroids has occasionally been reported to cause Cushing's syndrome after a few months of combination therapy, often reversible after treatment interruption (9). Our patient was on 7 years of itraconazole therapy in combination with fluticasone and never

Mucormycosis is a life-threatening invasive fungal infection that arises among immunocompromised patients (haematological malignancies, solid organ transplantation, diabetes mellitus). The most frequent sites of infection are pulmonary, rhinocerebral, cutaneous and disseminated. Reversal of the underlying conditions is mandatory for controlling mucormycosis. Another cornerstone of mucormycosis treatment is prompt and aggressive surgery. It is achieved by extensive surgical debridement of necrotic tissues. Finally an antifungal therapy is needed. The first-line chemotherapy of mucormycosis includes high-dose liposomal amphotericin B (≥ 5 mg/kg/day). The duration of antifungal chemotherapy is not defined but guided by the resolution of all associated symptoms and findings (usually 6-8 weeks). Maintenance therapy/secondary prophylaxis by posaconazole has to be considered in persistently immuno compromised patients.

But Etablir les caracteristiques cliniques et microbiologiques, et les facteurs de risque de surmortalite dans une serie retrospective et monocentrique de 121 patients atteints d’endocardite infectieuse. Methode A partir des donnees PMSI de janvier 2009 a decembre 2013, tous les patients qui repondaient aux criteres de Dukes modifies ont ete inclus. Resultats La population comprend 121 patients dont 87 ont une endocardite certaine, de moyenne d’âge 71,1 ans. La plupart des patients (57 %) presentent une endocardite sur valve native. Les cocci Gram positifs sont les germes les plus representes (dont 24,8 % de S. aureus). Chez 15 patients (12,4 %), les hemocultures sont negatives, 70 patients ont une indication chirurgicale (57,9 %) effectuee chez 55 d’entre eux (44,7 %). Les patients operes sont plus jeunes (p = 0,002) et plus souvent porteurs d’une endocardite sur materiel prothetique (p = 0,001) que les non operes. La mortalite globale intra-hospitaliere est de 16,5 %. Deux parametres sont associes a la mortalite hospitaliere : le diabete (OR = 3,17 ; IC 95 = 1,02–9,8) et l’insuffisance renale chronique (OR = 6,62 ; IC 95 = 2,06–21,27). Les patients qui n’etaient pas operes malgre l’existence d’une indication chirurgicale avaient une mortalite tres elevee (86,7 %) par rapport aux operes (14,5 % p Conclusion L’endocardite infectieuse reste donc une maladie severe et hautement letale malgre les recentes avancees en termes diagnostique et therapeutique. La chirurgie reste un des elements clefs du traitement curatif.

Mastocytosis is characterized by a clonal mast cell proliferation with organ infiltration and uncontrolled degranulation. Although not characteristic and poorly explained, some patients develop clotting abnormalities. We retrospectively identified patients with established diagnosis of mastocytosis and related clotting abnormalities (clinical and/or biological) using the national French Reference Centre for Mastocytosis database. From our cohort of 14 adult patients with clotting abnormalities (median age 46 years [range 26–75]), 4 had a presentation suggestive of a primary hemostasis disorder alone (by their symptoms and/or abnormal clotting tests [PFA, von Willebrand's disease [vWD] screening]) and 10 had a laboratory impairment of secondary hemostasis. Among these, 7 had bleeds characteristic of a coagulation cascade disorder (severe/life-threatening in 5 and mild in 2 patients). Clotting abnormalities were of variable severity, typically related to intense crisis of degranulation, such as anaphylactic reactions, and/or to severe organ infiltration by mast cells. Importantly, classical hemostatic management with platelet transfusion, fresh frozen plasma, or vitamin K infusions was unsuccessful, as opposed to the use of agents inhibiting mast cell activity, particularly steroids. This illustrates the crucial role of mast cell mediators such as tryptase and heparin, which interfere both with primary (mainly via inhibition of von Willebrand factor) and secondary hemostasis. There was interestingly an unusually high number of aggressive mastocytosis (particularly mast cell leukemia) and increased mortality in the group with secondary hemostasis disorders (n = 5, 36% of the whole cohort). Mast cell degranulation and/or high tumoral burden induce both specific biologic antiaggregant and anticoagulant states with a wide clinical spectrum ranging from asymptomatic to life-threatening bleeds. Hemostatic control is achieved by mast cell inhibitors such as steroids.

[Graphic][1] INTRODUCTION Mast cell disease is a clonal haematological disorder resulting in organ infiltration by mast cells and uncontrolled degranulation (mast cell activation syndrome, MCAS). Although not characteristic and poorly explained, both primary (platelet’s adhesion and aggregation) and secondary (coagulation cascade leading to thrombin formation) clotting abnormalities are observed among some patients. METHODS We retrospectively identified patients with established diagnosis of mastocytosis and related clotting abnormalities (clinical and/or biological) using the French National Reference Centre for Mastocytosis database. RESULTS AND DISCUSSION Our cohort included 14 adult patients (median age of 42 [range 26-78] years, sex ratio 3.7, CKIT D816V in 13/14 cases, median tryptase of 200 [4-1240] ng/mL). Four patients had typical symptoms and/or clotting tests (PFA, von Willebrand’s disease [vWD] screening) indicating abnormalities of primary haemostasis [Table, patient 1], with n=1 confirmed and n=2 highly suspicious of vWD. They presented with either nil (n=1) or mild (n=3) mucocutaneous bleeding. This could be due to heparin binding to von Willebrand’s factor, therefore preventing platelet aggregation. Ten patients had abnormalities of coagulation cascade (prolonged PT, aPTT, reduced clotting factors II, V, VII, X), usually transient but with bleeding in 7 cases (severe/life-threatening in 5 of them ) [Table, patient 3]. Clotting abnormalities were typically accompanied by anaphylactoid symptoms of MCAS and increased by the presence of hematopoietic organ infiltration [Table, patients 2-4]. Haemostatic management (red blood cells and platelets transfusion, fresh frozen plasma, vitamin K, antifibrinolytic) was unsuccessful, while control of mast cell activity (e.g. with and steroids) would achieve haemostasis, indicating the crucial role of mast cell mediators. These mainly include tryptase and heparin, which inhibit the intrinsic pathway, inducing an anticoagulant state. The exact prevalence of clotting abnormalities in mastocytosis remains unclear and probably underestimated. However, we found a predominance of aggressive types of mastocytosis in the population with coagulation cascade abnormalities: 50% had aggressive systemic mastocytosis associated or not with a clonal haematological non mast cell lineage disease (ASM/AHNMD), 30% had mast cell leukaemia (MCL). All deceased patients (n=5, 36% of the overall population) belonged to this group. In contrast, mastocytosis was indolent in 75% of cases in the group with primary haemostasis abnormalities. | Patient number / gender; Diagnosis | Acute phase of MCAS | H/SMG | Bleeding | Biology | Clotting after episode | | | ------------------------------------------ | --------------------------- | -------------------- | ---------------- | --------------- | ---------------------- | ------------------ | ------------------------------------------------------------------------------------------------------------ | | PLT 150-300 | PTr ≥ 70% | aPTTr ≤ 1.20 | | | #1 / M; CM | no | no | Cutaneous | N | 89% | 1.23 | Spontaneously resolved | | | #2 / M; SSM-AHNMD† | yes | no | GI bleed | N | 37% | 1.75 | Resolved after steroids | | | yes | no | GI bleed | 20 | 62% | 1.41 | Resolved after symptomatic control of MCAS. | | #3 / M; aMCL | yes | yes | Acute SDH | 87 | 61% | 1.46 | Resolved after steroids | | #4 / M; ASM-AHNMD† | no | yes | None | 138 *14 | 62% *43% | 1.39 *1.97 | Worsening clotting alongside ASM progression and unrelated to the AHNMD. Response to steroids not assessable | | | | | | | | | | | Abstract 2856. Table: Description of 4 selected patients AHNMD: associated clonal haematological non mast cell lineage disease; aMCL: acute mast cell leukemia; aPTTr: activated partial thromboplastin time ratio; CM: cutaneous mastocytosis; H/SMG: hepato or splenomegaly; GI: gastrointestinal; ISM: indolent systemic mastocytosis; N: normal; SSM: smouldering systemic mastocytosis; PLT: platelet, in x103/µL; PTr: prothrombin time ratio; SDH: subdural haematoma. Reference values are indicated below PLT, PTr, aPTTr. †: patient deceased from the disease or complications of the latter. *6 months later. CONCLUSIONS AND PERSPECTIVES Blood coagulation abnormalities in mastocytosis appear secondary to a hyperactivity of the clonal mast cell, resulting in an anticoagulant state and typically presenting in the context of MCAS and/or significant mast cell proliferation. They are particularly prevalent in aggressive types of mastocytosis, and are only successfully controlled by mast cell inhibitors, notably steroids. More data are required to better correlate clinical and biological pictures, and to assess whether standard or specific clotting tests could be used as a marker of mast cell activity and potentially of poor prognosis in patients with systemic mastocytosis. Disclosures No relevant conflicts of interest to declare. [1]: /embed/inline-graphic-2.gif

Introduction Chronic granulomatous disease (CGD) is a rare inherited disorder due to a defect in NADPH oxidase, resulting in recurrent, life-threatening invasive infections and granulomatous inflammatory disorders. Although CGD is diagnosed mostly in early childhood, its prognosis has now much improved, allowing a majority of patients to reach adulthood. Very few studies have focused on the long-term outcome of adult CGD patients. Objective To study the clinical course and sequelae at various time points (age 16, 20, 30 and beyond) of CGD patients, diagnosed before 16 years of age. Method A one-year (May 2012 to May 2013) French national retrospective study of CGD patients, diagnosed before the age of 16 years, and who had reached adulthood (defined as above 16 years of age) by the time of data collection. CGD patients were screened through the registry of the French national reference center of primary immune deficiencies (CEREDIH), and data were retrieved by reviewing medical charts and collected in a pre-defined case-report form. Results Eighty CGD patients (71 male (88.7%), 59 X-linked (73.7%), with a median NBT level of 0 [range:0; 15]) were included in the study. Median ages at diagnosis and last follow-up were 2.52 years [range: 0; 15.87] and 23.9 years [range: 16.61; 59.89], respectively. Seventeen patients (21%) were older than 30 years at time of last follow-up. Seven patients (8.8%) had undergone a hematopoietic stem-cell transplantation (HSCT). A total of 553 infections requiring hospital care (382 before age 16, and 171 thereafter), occurred among all patients during follow-up. The most common sites of infection were: pulmonary (31% of total infections, involving 77.5% patients), suppurative adenitis (24% of infections, 75% of patients), and cutaneous (16.2% of infections, 60% of patients). Aspergillus spp. (17%) and Staphylococcus aureus (10.7%) were the most common pathogens. These characteristics (sites and pathogens involved), as well as the annual frequency of infections, did not vary, when compared before and after age 16. When considering granulomatous events, a total of 224 inflammatory flares, mainly digestive (50%), pulmonary (16.7%) and urologic (10.3%), occurred among 71/80 (88.8%) patients. Thirty autoimmune events (mainly discoid lupus erythematosus) also occurred among 14/80 patients (17.2%). The median age of the first inflammatory event (12.5 years [range: 0.25; 44.2]) was much higher than that of the first serious infectious event (0.97 years [range: 0; 23.9]) (figure 1). The annual frequency of inflammatory events did not however significantly increase after age 16. Concerning the long-term consequences of such repeated infectious and steroid-treated inflammatory events, the main sequelae in CGD adults were a small adult median height and weight (167.5cm [range: 138; 185] and 56 kg [range: 35; 90] at age 20), as well as mild chronic restrictive respiratory failure (26.7% of chronic dyspnoea at the age of 30 years). At the age of 16 years, only 58% of patients were in high school. After 30 years, 9/13 (69%) patients were working, and 2 had had children. Ten patients died during adulthood at a median age of 23.6 years [range: 18.2; 45.4], most of them of infectious causes. Discussion & Conclusion Adult CGD patients display similar characteristics and rates of severe infections as during their childhood. As CGD patients grow older, inflammatory flares also become a major concern, because of an older age of appearance. The high rate of handicap that these repeated infectious and inflammatory events entail in adult CGD patients, now becomes a matter of medical and social considerations. A careful follow-up is thus recommended in specialized centers. Finally, HSCT and gene therapy should be more systematically considered in order to try to avoid long-term complications, which are responsible for major disabilities. Disclosures: No relevant conflicts of interest to declare.