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We describe a patient exhibiting clinical features of PRAAS due to a homozygous mutation in PSMB10. This gene encodes the only immunoproteasome subunit in which mutations have not yet been associated with PRAAS.

International audience; A girl, born with a posterior lumbosacral giant congenital nevus, developed a central nodule that expanded over a period of 14 months into a 10-cm pedunculated mass. Histological analysis of the mass revealed melanoma of myxoid, small round-cell type with areas of rhabdomyosarcomatous transformation confirmed by immunohistochemistry. RNA sequencing identified an in-frame SASS6(e14)-RAF1(e8) fusion in both components and the nevus. A RAF1 FISH break-apart test found a balanced rearrangement pattern in the nevus and an unbalanced pattern in the malignant areas. Wild-type status of NRAS and BRAF was confirmed by NGS techniques. The array-CGH profile displayed copy number alterations commonly found in rhabdomyosarcomas. Despite intensive treatment, widespread metastatic evolution of the melanomatous component was observed.

Background There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). Objective We sought to characterize patients with hypertrophic PWS presenting during childhood. Methods Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. Results A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. Limitations As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. Conclusion PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications.

Gezdirici, Alper/0000-0002-2432-9279; Gezdirici, Alper/0000-0002-2432-9279; vasse, marc/0000-0002-8784-7209; Beyens, Aude/0000-0003-0231-6861 WOS: 000493185700008 PubMed: 29952037 In ATP6V0A2-related cutis laxa, the skin phenotype varies from a wrinkly skin to prominent cutis laxa and typically associates with skeletal and neurological manifestations. The phenotype remains incompletely characterized, especially in adult patients. Glycosylation defects and reduced acidification of secretory vesicles contribute to the pathogenesis, but the consequences at the clinical level remain to be determined. Moreover, the morphology of the elastic fibres has not been studied in ATP6V0A2-related cutis laxa, nor its relation with potential clinical risks. We report on the extreme variability in ATP6V0A2-related cutis laxa in 10 novel patients, expand the phenotype with emphysema and von Willebrand disease and hypothesize on the pathogenesis that might link both with deficiency of glycosylation and with elastic fibre anomalies. Our data will affect clinical management of patients with ATP6V0A2-related cutis laxa. Special Research Fund of Ghent UniversityGhent University [01N04516]; Scientific Research Fund - Flanders

Background: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of patients with CM-AVM. Herein we studied non-RASA1 patients to further elucidate the pathogenicity of CMs and AVMs. Methods: We conducted a genome-wide linkage study on a CM-AVM family. Whole-exome sequencing was also performed on 9 unrelated CM-AVM families. We identified a candidate gene and screened it in a large series of patients. The influence of several missense variants on protein function was also studied in vitro. Results: We found evidence for linkage in 2 loci. Whole-exome sequencing data unraveled 4 distinct damaging variants in EPHB4 in 5 families that cosegregated with CM-AVM. Overall, screening of EPHB4 detected 47 distinct mutations in 54 index patients: 27 led to a premature stop codon or splice-site alteration, suggesting loss of function. The other 20 are nonsynonymous variants that result in amino acid substitutions. In vitro expression of several mutations confirmed loss of function of EPHB4. The clinical features included multifocal CMs, telangiectasias, and AVMs. Conclusions: We found EPHB4 mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics RASA1 -related CM-AVM1 and also hereditary hemorrhagic telangiectasia. RASA1 -encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs.

Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC-autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency-was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity to Candida and Staphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface.

PurposeThe purpose of this paper is to review systematically the available literature relating to the implementation of peer education to promote health and healthy behaviour in prisons.Design/methodology/approachThe authors undertook a narrative systematic review of Medline, EMBASE, CINAHL, Psychinfo, Web of Science and Cochrane databases. Relevant journals and reference lists were hand searched for relevant articles to be included in the review. Of the abstracts found, full‐text papers were retrieved for those papers deemed as possibly fulfilling the inclusion criteria of the review.FindingsA total of 3,033 abstracts were identified leading to 46 full‐text articles being retrieved, of which ten were included in the review. Peer education in prisons can have an impact on attitudes, knowledge, and behaviour intention regarding HIV risk behaviour. The research findings were inconclusive for the impact of peer education upon illicit drug use and injecting practice. There was a paucity of research evaluating the impact of peer education upon mental ill health, obesity, diet, smoking, or self‐management of chronic physical diseases.Originality/valuePeer education is effective in reducing risk of HIV transmission. It is possible that peer education for mental health issues is stigmatising, presenting an opportunity for further research activity. The impact of peer education upon illicit drug use practice, obesity, diet, smoking, and self‐management of chronic physical diseases also presents further research opportunities. Research evaluating models of active peer educator involvement in health service delivery and organisation is also lacking.

L’une des pathologies courantes en dermatologie pédiatrique est l’hémangiome, de diagnostic évident mais pas toujours posé. L’évolution qui est d’habitude bénigne peut être émaillée de complications redoutables nécessitant parfois un traitement curatif, qui a connu de grands progrès essentiellement les bétabloquants topiques, ces derniers ont fait preuve d’efficacité et de bonne tolérance. Nous rapportons le cas d’une fille âgée de 1 an qui présentait un hémangiome vulvaire non diagnostiqué et compliqué de surinfection, entrainant des vulvites répétées et résistantes aux antibiotiques usuels. L’utilisation de béta- bloquants topiques après la stérilisation de la lésion a permis une régression importante de l’hémangiome, ainsi qu’une amélioration de la qualité de vie de la patiente et de ses parents, sans aucun effet secondaire. L’hémangiome vulvaire reste fréquent et bénin mais parfois grave, Il faut y penser pour mieux traiter.

Introduction Certains angiomes plans comportent une hypertrophie tissulaire precoce differente de l’hypertrophie cutanee des « angiomes plans vieillis ». Leur profil evolutif et la reponse therapeutique semblent specifiques. L’objectif de cette etude etait d’evaluer les caracteristiques cliniques des angiomes plans precocement hypertrophiques du visage ainsi que leur reponse au traitement laser. Materiel et methodes Etude retrospective dans 12 centres dermatologiques. Les donnees etaient recueillies a l’aide d’un questionnaire standardise. Etaient recueillis : le sexe, l’âge au debut de l’hypertrophie et au moment de la consultation, la localisation de l’angiome et de l’hypertrophie, les complications associees, les eventuels traitements realises et l’âge au debut du traitement, le type de laser, le nombre de seances, la duree totale du traitement et la reponse therapeutique. Resultats Quatre-vingt cas d’angiomes plans precocement hypertrophiques ont ete recueillis. Le sex-ratio H/F etait de 0,5. L’âge de debut de l’hypertrophie etait connu dans 57 cas. Il etait en moyenne de 6,5 ans (0–15). L’hypertrophie etait congenitale dans 11 cas sur 57(19,3 %). Les troubles odontologiques etaient frequents (38,8 %). Seize autres cas (20 %) avaient d’autres complications associees (cataracte, comitialite, asymetrie de developpement des maxillaires et troubles orthophoniques). Cinquante-sept ont ete traites par laser (laser a colorant pulse dans la majorite des cas) avec une moyenne de 14 seances (1–60) sur une periode moyenne de 8,2 ans (1–22). L’âge median de debut du traitement etait de 8 ans avec des extremes de 1 mois a 58 ans. Une amelioration 90 %). Discussion A notre connaissance, une seule etude s’est interessee aux angiomes plans hypertrophiques. Sur 335 patients âges de 0 a 81 ans, une hypertrophie etait observee chez 68 patients. Cependant, il s’agissait d’hypertrophies le plus souvent tardives survenant en moyenne apres l’âge de 31 ans. Seulement 6 patients avaient une hypertrophie avant 20 ans et aucune donnee specifique n’etait rapportee pour cette population. Notre serie confirme que les patients ayant un angiome plan du visage precocement hypertrophique ont un profil particulier avec un taux eleve de complications et des taux de reponse au traitement laser largement inferieurs a ce qui est habituellement observe dans les angiomes plans non precocement hypertrophiques. Conclusion Les enfants ayant un angiome plan precocement hypertrophique doivent faire l’objet d’une surveillance particuliere en raison de la frequence des complications associees. Le traitement par laser de ces formes parait tres decevant et les patients et leurs familles doivent en etre prevenus. Des etudes genetiques apparaissent importantes afin de determiner si ce phenotype clinique est associe a une ou plusieurs mutations particulieres.