A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode

Faut-il avoir peur de la grippe chez la femme enceinte ?

International audienceDuring pregnancy both mother and foetus are at increased risk of being infected with either pandemic or seasonal influenza viruses, and it is thus legitimate to implement enhanced surveillance for infection particularly with the A/H1N1v and discuss priority vaccine administration. We will review the alterations in immunologic parameters which lead to some degree of cellular immunodeficiency, but also in anatomic changes and pulmonary restrictions which contribute to this suceptibility of pregnant women to severe complications of an influenza infection. We also provide an update on the epidemiological data available for the A/H1N1v infection in this population, and discuss the benefit/risk ratio of treatment with the antiviral medications.Les femmes enceintes constituent classiquement un terrain fragile et à haut risque de complications sévères au cours de processus infectieux et notamment au cours de la grippe, expliquant la vigilance actuelle des autorités de santé envers cette population à risque de contracter le virus A/H1N1v. Se pose également le problème de l’attitude thérapeutique et de lévaluation des bénéfices et des risques pour le foetus et la mère lors de la prescription non seulement du vaccin, mais aussi des antiviraux. Dans cet article nous faisons le point des données épidémiologiques et de morbi-mortalité disponibles pour la population de femmes enceintes en ce qui concerne la pandémie actuelle A/H1N1v mais en se référant également aux pandémies antérieures et aux infections grippales saisonnières ; nous rappelons les modifications d’ordre immunologique, hémodynamique, et anatomique ventilatoire liées à la grossesse qui entraînent une susceptibilité particulière vis-à-vis d’agents infectieux dont le virus grippal

Iatrogenic Cushing's Syndrome Induced by Posaconazole

International audienceIatrogenic 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 neve

Defective functions of polymorphonuclear neutrophils in patients with common variable immunodeficiency

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Infections fongiques et granulomatose septique chronique de la physiopathologie aux nouvelles perspectives thérapeutiques

Chronic granulomatous disease is a genetic disorder responsible for a defect in the NADPH oxidase of phagocytic cells. It impairs the oxidative burst necessary to the intracellular inactivation of microorganisms and predisposes to an increased risk of infections by various microorganisms, including fungi like Aspergillus spp. and other less frequently encountered or emerging fungal species. Here we review the genetic basis, pathogenesis and clinical presentation associated with fungal infections in chronic granulomatous disease as well as the current prophylaxis and newly available therapies.SCOPUS: re.jinfo:eu-repo/semantics/publishe

No evidence for major adverse events related to suspicion of Ebola in France, 2014-2015

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