International consensus on the diagnosis and management of pediatric patients with hereditary angioedema with C1-Inhibitor deficiency

BACKGROUND: The consensus documents published to date on hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) have focused on adult patients. Many of the previous recommendations have not been adapted to pediatric patients. We intended to produce consensus recommendations for the diagnosis and management of pediatric patients with C1-INH-HAE. METHODS: During an expert panel meeting that took place during the 9th C1-Inhibitor Deficiency Workshop in Budapest, 2015 [w w w.haenet. hu], pediatric data were presented and discussed and a consensus developed by voting. RESULTS: The symptoms of C1-INH-HAE often present in childhood. Differential diagnosis can be difficult as abdominal pain is common in pediatric C1-INH-HAE but also commonly occurs in the general pediatric population. The early onset of symptoms may predict a more severe subsequent course of the disease. Before the age of 1 year, C1-INH levels may be lower than in adults; therefore, it is advisable to confirm the diagnosis after the age of one year. All neonates/infants with an affected C1-INH-HAE family member should be screened for C1-INH deficiency. Pediatric patients should always carry a C1-INH-HAE information card, and medicine for emergency use. The regulatory approval status of the drugs for prophylaxis and for acute treatment is different in each country. Plasma-derived C1-INH, recombinant C1-INH, and ecallantide are the only agents licensed for the acute treatment of pediatric patients. Clinical trials are underway with additional drugs. It is recommended to follow-up patients in an HAE comprehensive care centre. CONCLUSIONS: The Pediatric-focused International Consensus for the diagnosis and management of C1-INH-HAE patients was created. This article is protected by copyright. All rights reserved

Kallikrein 5 induces atopic dermatitis–like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome

Netherton syndrome (NS) is a severe genetic skin disease with constant atopic manifestations that is caused by mutations in the serine protease inhibitor Kazal-type 5 (SPINK5) gene, which encodes the protease inhibitor lymphoepithelial Kazal-type–related inhibitor (LEKTI). Lack of LEKTI causes stratum corneum detachment secondary to epidermal proteases hyperactivity. This skin barrier defect favors allergen absorption and is generally regarded as the underlying cause for atopy in NS. We show for the first time that the pro-Th2 cytokine thymic stromal lymphopoietin (TSLP), the thymus and activation-regulated chemokine, and the macrophage-derived chemokine are overexpressed in LEKTI-deficient epidermis. This is part of an original biological cascade in which unregulated kallikrein (KLK) 5 directly activates proteinase-activated receptor 2 and induces nuclear factor κB–mediated overexpression of TSLP, intercellular adhesion molecule 1, tumor necrosis factor α, and IL8. This proinflammatory and proallergic pathway is independent of the primary epithelial failure and is activated under basal conditions in NS keratinocytes. This cell-autonomous process is already established in the epidermis of Spink5−/− embryos, and the resulting proinflammatory microenvironment leads to eosinophilic and mast cell infiltration in a skin graft model in nude mice. Collectively, these data establish that uncontrolled KLK5 activity in NS epidermis can trigger atopic dermatitis (AD)–like lesions, independently of the environment and the adaptive immune system. They illustrate the crucial role of protease signaling in skin inflammation and point to new therapeutic targets for NS as well as candidate genes for AD and atopy

Localized acne induced by radiation therapy

The appearance of localized acne or comedo reaction during or shortly after radiotherapy is an unusual adverse event, but one that is probably underestimated. It can manifest as an inflammatory (papules, pustules, nodules), comedonal (open and closed comedones, Favre-Racouchot-like syndrome), or mixed presentation. We report two new cases of radiation-induced acne with different clinical aspects and discuss the main known features of this adverse event

Profil de résistance de staphylococcus aureus dans les infections cutanées communautaires de l'enfant

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Sensibilisation aux atopènes dans la dermatite atopique du nourrisson et rôle de la voie épicutanée

La sensibilisation aux atopènes est un phénomène précoce qui chevauche chronologiquement la révélation de la dermatite atopique (DA) du nourrisson (NRS). L'altération de la barrière cutanée, que l'on peut évaluer par la téwamétrie, facilite la pénétration épicutanée des atopènes. Notre hypothèse est que la sensibilisation aux atopènes est initialement épicutanée chez le NRS atteint de DA. Notre étude porte sur 59 NRS atteints de DA, chez lesquels, nous avons mesuré le SCORAD, la téwamétrie en peau saine et pratiqué un bilan allergologique exhaustif concernant 7 aéro allergènes (AA). La concentration en acariens au domicile était mesurée. Un groupe témoin d'enfants non atopiques (n=29) a été établi pour la téwamétrie. Les enfants ayant plus d'un patch-test positif avaient une téwamétrie supérieure à celle du groupe ayant 0 ou 1 patch-test positif. Cette étude confirme la prévalence élevée (89%) de la sensibilisation retardée aux AA chez le NRS atteint de DA. La fréquence d'enfants ayant des IgE spécifiques pour les AA est plus faible (32%). Ceci montre que la sensibilisation allergénique du NRS implique clairement la voie de passage percutanée. La concentration en acariens au domicile n'était pas corrélée à une sensibilisation aux acariens, il n'existait pas d'association entre l'exposition aux AA ou l'habitat et de la sensibilisation aux AA. Les enfants du groupe DA avaient une téwamétrie plus élevée que les enfants sains. Les enfants avec une téwamétrie élevée avaient un SCORAD supérieur au groupe avec une téwamétrie plus faible. A notre connaissance, cette étude est la première mesurant la téwamétrie, le SCORAD et la sensibilisation aux AA chez le NRS. Elle confirme la prévalence élevée de la sensibilitéretardée aux AA dans cette population et met en exergue le rôle essentiel et probablement inaugural de l'altération de la barrière cutanée comme facteur favorisant la sensibilisation aux AA chez le NRS atopique. Nous avons montré qu'il existe chez le NRS atteint de DA une altération de la barrière cutanéé et une association entre celle-ci et le SCORAD.BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF