RESUMO
BACKGROUND: Atopic dermatitis (AD) is a common, chronic dermatosis, with onset of disease often manifesting in early infancy. Past studies evaluating the early use of moisturisers in the prevention of AD had mixed results. OBJECTIVES: To compare the incidence of moderate or severe AD and total incidence of AD in a cohort of 'at-risk' infants treated with moisturisers from the first 2 weeks of life, to a similar group without moisturisers. METHODS: We performed a single-centre, prospective, parallel-group, randomised study in infants with at least 2 first-degree relatives with atopy. Subjects were randomised into either a treatment group with moisturisers or a control group without moisturisers. Participants were assessed at 2, 6, and 12 months for AD and if present, the severity was assessed using SCORAD index. We also compared the overall incidence of AD, trans-epidermal water loss (TEWL), stratum corneum (SC) hydration, pH, and incidence of food and environmental sensitisation and allergies between both groups. Genotyping for loss-of-functions mutations in the FLG gene was conducted. RESULTS: A total of 200 subjects were recruited, with 100 subjects in each arm. There was no significant difference in incidence of moderate or severe AD, and total incidence of AD at 12 months between the treatment and control groups. There was a lower mean SCORAD in the treatment group than in the control group, but no significant difference in TEWL, SC hydration, and skin pH. No significant side-effects were reported. CONCLUSIONS: The early use of moisturisers in 'at-risk' infants does not reduce the incidence of moderate-to-severe AD and overall incidence of AD in infancy.
Assuntos
Dermatite Atópica/epidemiologia , Dermatite Atópica/prevenção & controle , Fármacos Dermatológicos/administração & dosagem , Pomadas/administração & dosagem , Propilenoglicóis/administração & dosagem , Creme para a Pele/administração & dosagem , Dodecilsulfato de Sódio/administração & dosagem , Fatores Etários , Estudos de Coortes , Dermatite Atópica/diagnóstico , Combinação de Medicamentos , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Fatores de RiscoRESUMO
Cole disease is a genodermatosis of pigmentation following a strict dominant mode of inheritance. In this study, we investigated eight patients affected with an overlapping genodermatosis after recessive inheritance. The patients presented with hypo- and hyperpigmented macules over the body, resembling dyschromatosis universalis hereditaria in addition to punctuate palmoplantar keratosis. By homozygosity mapping and whole-exome sequencing, a biallelic p.Cys120Arg mutation in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was identified in all patients. We found that this mutation, like those causing dominant Cole disease, impairs homodimerization of the ENPP1 enzyme that is mediated by its two somatomedin-B-like domains. Histological analysis revealed structural and molecular changes in affected skin that were likely to originate from defective melanocytes because keratinocytes do not express ENPP1. Consistently, RNA-sequencing analysis of patient-derived primary melanocytes revealed alterations in melanocyte development and in pigmentation signaling pathways. We therefore conclude that germline ENPP1 cysteine-specific mutations, primarily affecting the melanocyte lineage, cause a clinical spectrum of dyschromatosis, in which the p.Cys120Arg allele represents a recessive and more severe form of Cole disease.