Étude rétrospective sur l efficacité et la tolérance de l ivermectine per os chez 27 nourrissons atteints de gale récalcitrante

La gale est en nette recrudescence depuis plusieurs années et atteint particulièrement les nourrissons. L ivermectine per os n est pas autorisée chez l enfant pesant moins de 15 kg car sa sécurité d emploi n a pas été établie. Nous rapportons les observations de 27 nourrissons qui ont reçu un traitement par ivermectine par os pour une gale récalcitrante ou récidivante malgré tous les topiques employés. L objectif principal de cette étude était d étudier l efficacité et les effets secondaires de la molécule dans cette série. Matériel et Méthode : Il s agissait d une étude rétrospective réalisée dans le service de Dermatologie du CHU de Rouen entre le 1er janvier 2009 et le 1er mars 2013. 27 enfants de moins de 15 kg recevaient un traitement par ivermectine à J0 et J14 à 200 g/kg, après la réalisation d au moins deux traitements topiques sans succès, après information éclairée des parents. Les enfants étaient examinés un mois plus tard en consultation et les parents étaient interrogés sur la survenue d effets indésirables avec la molécule. Les parents étaient rappelés trois mois après le traitement, pour vérifier qu aucun autre effet indésirable n était survenu. Résultats : Le taux de guérison était de 70,3% (19 sur 27) après le 1er mois. Tous les enfants avaient ingéré correctement la molécule. Les effets indésirables constatés étaient transitoires et bénins (vomissement, majoration de l eczéma, xérose cutanée, majoration du prurit, agitation). Discussion : Cette étude montre l efficacité de l ivermectine chez le nourrisson et l absence de survenue d effet indésirable neurologique grave dans cette petite série. Une revue de la littérature incite à penser que la toxicité neurologique de l ivermectine chez le nourrisson ne devrait pas être différente de celle de l adulte. Mais ces données nécessitent de réaliser davantage d études chez le nourrisson avant de conclure à une innocuité de la molécule.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Malformations veineuses chez l'enfant (étude rétrospective de 45 cas)

La prise en charge des malformations veineuses (MV) chez les enfants est peu rapportée. Objectif : Evaluer les caractéristiques et la prise en charge d'enfants porteurs de MV. Méthode : Etude rétrospective ayant inclus les enfants porteurs de MV, suivis à la consultation pluridisciplinaire angiome au CHU de Rouen entre 2000 et 2012. Résultats : 45 enfants (23 filles et 22 garçons) ont été inclus. L'âge médian était de 7 ans et le suivi médian de 4,5 ans. Les MV étaient localisées au visage (35,5%), aux MI (35,5%), aux MS (22%) et au tronc (7%) : 11 MV étaient de grande taille et 16 avaient une atteinte musculaire. La MV était découverte tardivement chez 22 enfants. La MV était symptomatique chez 41 enfants (91%). Les principaux symptômes étaient : augmentation de volume (32 cas), gêne fonctionnelle (23 cas), douleurs (31 cas),- déformation (17 cas), saignements (5 cas), thromboses (9 cas) et gêne sociale (21 cas). Les douleurs étaient plus fréquemment retrouvées en cas de taille importante (p.0,009), d'atteinte musculaire (p=0,001), de déformation (p=0,007), de phiébolithes (p.0,034) et d'épisodes de TV (p=0,04). Les traitements proposés ont été : 1/ une compression élastique chez 12 enfants, 2/ un traitement antalgique (palier I ou AINS) chez 17 enfants, 3/ des séquences d'HBPM en cas de TV, (hors AMM), chez 6 enfants, poursuivies en continu (2 cas) ou relayées par de l'aspirine (3 cas), 4/ une sclérothérapie chez 5 enfants, 5/ des actes chirurgicaux chez 6 enfants. Ces prises en charge ont permis une amélioration partielle chez 20/23 enfants traités, avec une récidive des phénomènes douloureux pour 11 d'entre eux. Conclusion : La prise en charge des MV chez l'enfant doit être adaptée au cas par cas, en fonction de la symptomatologie, de l'âge, de la localisation, de l'étendue de la MV et des thérapeutiques souvent hors AMM en pédiatrie. L'amélioration des symptômes n'est souvent que transitoire.ROUEN-BU Médecine-Pharmacie (765402102) / SudocSudocFranceF

Balloon cell nevus: Histologic and dermoscopic features

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iPSC reprogramming of fibroblasts from a patient with a Rothmund-Thomson syndrome RTS

International audienceRothmund-Thomson Syndrome (RTS) is a rare autosomal recessive disease that manifests several clinical features of accelerated aging. These findings include atrophic skin and pigment changes, alopecia, osteopenia, cataracts, and an increased incidence of cancer for patients. Mutations in RECQL4 gene are responsible for cases of RTS. RECQL4 belongs to the RECQ DNA helicase family which has been shown to participate in many aspects of DNA metabolism. To be able to study the cellular defects related to the pathology, we derived an induced pluripotent cell line from RTS patient fibroblasts, with the ability to re-differentiate into the three embryonic germ layers

Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression

International audienceBackground Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown. Objective To determine ex v ivo cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel. Methods We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology. Results Spontaneous TNFα, IL-6, IL-1β, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1β serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS ( p = 0.04). Conclusion Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1β, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra

Biologics combined with conventional systemic agents for the treatment of children with severe psoriasis. Real-life data from the BiPe cohorts and a practice survey among French and Italian pediatric dermatologists

International audienceCombined therapies involve the use of multiple drugs to increase efficacy and reduce the toxicity of individual treatments. We evaluated the use of combinations of conventional systemic therapies and biologics in children with psoriasis in daily practice. This two-part study used data from the 170 children in the Franco-Italian BiPe cohorts to evaluate the use, efficacy, and safety of combined conventional systemic–biologic therapies, and from a survey carried out among French and Italian dermatologists to better understand the reasons for using or avoiding these combinations. In total, 33 children (19.4%) from 13 dermatology centers received 48 combined conventional systemic–biologic therapies (cumulative duration: 43.6 years), including three triple combination therapies (acitretin–methotrexate, with a TNF-alpha inhibitor). A total of 14 different combinations were used, most frequently etanercept–acitretin (n = 10), adalimumab–acitretin (n = 7), adalimumab–methotrexate (n = 5), and ustekinumab–methotrexate (n = 5). The combined therapies were started at biologic initiation in 41 cases (85.4%), and after a period of biologic monotherapy in the remaining 7 cases. Mean PGA and PASI scores decreased between baseline and M3 with all the combinations used. Four serious adverse events were reported, all with favorable outcomes. The survey was completed by 61 dermatologists: 39 (63.9%) had previously used or planned to use the combined therapies, most commonly TNF-alpha inhibitors with acitretin or methotrexate. The main reason for using these treatments was to improve the outcome of biologic therapies in cases of partial efficacy or loss of efficacy. Combined therapies have been used frequently in the treatment of childhood psoriasis, in a range of clinical situations and in variable drug combinations, without significant toxicity. Although the use of these combined therapies needs to be clarified in future management guidelines, these combined therapies should be considered for the treatment of children with severe psoriasis, psoriatic arthritis, and recalcitrant disease

Search for RASA1 Variants in Capillary Malformations of the Legs in 113 Children: Results from the French National Paediatric Cohort CONAPE

Patients with an inherited autosomal-dominant disorder, capillary malformation–arteriovenous malformation (CM-AVM), frequently have mutations in Ras P21 protein activator 1 (RASA1). The aims of this study were to determine the prevalence of germline RASA1 variants in a French multicentre national cohort of children, age range 2–12 years, with sporadic occurrence of capillary malformation (CM) of the legs, whatever the associated abnormalities, and to identify genotype–phenotype correlates. DNA was extracted from leukocytes in blood samples, purified and amplified, and all exons of the RASA1 gene were analysed. Among 113 children analysed, 7 had heterozygous variants (6.1%). Four different variants were identified; 2 were new. In children with RASA1 variants, CMs were more frequently bilateral and multifocal. In conclusion, RASA1 variants are rarely found in children with sporadic CM of lower limbs without CM-AVM syndrome. CMs in this study were heterogeneous, and no disease-causing relationship could be proven

Search for RASA1 Variants in Capillary Malformations of the Legs in 113 Children: Results from the French National Paediatric Cohort CONAPE

International audiencePatients with an inherited autosomal-dominant disorder, capillary malformation-arteriovenous malformation (CM-AVM), frequently have mutations in Ras P21 protein activator 1 (RASA1). The aims of this study were to determine the prevalence of germline RASA1 variants in a French multicentre national cohort of children, age range 2-12 years, with sporadic occurrence of capillary malformation (CM) of the legs, whatever the associated abnormalities, and to identify genotype-phenotype correlates. DNA was extracted from leukocytes in blood samples, purified and amplified, and all exons of the RASA1 gene were analysed. Among 113 children analysed, 7 had heterozygous variants (6.1%). Four different variants were identified; 2 were new. In children with RASA1 variants, CMs were more frequently bilateral and multifocal. In conclusion, RASA1 variants are rarely found in children with sporadic CM of lower limbs without CM-AVM syndrome. CMs in this study were heterogeneous, and no disease-causing relationship could be proven

Biallelic pathogenic variants in the lanosterol synthase gene LSS involved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome.

International audiencePurpose Lanosterol synthase (LSS) gene was initially described in families with extensive congenital cataracts. Recently, a study has highlighted LSS associated with hypotrichosis simplex. We expanded the phenotypic spectrum of LSS to a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. It is a rare autosomal recessive condition characterized by hypotrichosis and intellectual disability (ID) or developmental delay (DD), frequently associated with early-onset epilepsy and other dermatological features. Methods Through a multicenter international collaborative study, we identified LSS pathogenic variants in APMR individuals either by exome sequencing or LSS Sanger sequencing. Splicing defects were assessed by transcript analysis and minigene assay. Results We reported ten APMR individuals from six unrelated families with biallelic variants in LSS. We additionally identified one affected individual with a single rare variant in LSS and an allelic imbalance suggesting a second event. Among the identified variants, two were truncating, seven were missense, and two were splicing variants. Quantification of cholesterol and its precursors did not reveal noticeable imbalance. Conclusion In the cholesterol biosynthesis pathway, lanosterol synthase leads to the cyclization of (S)-2,3-oxidosqualene into lanosterol. Our data suggest LSS as a major gene causing a rare recessive neuroectodermal syndrome