Published online: April 14, 2020
Atopic dermatitis (AD; also known as atopic eczema) is a chronic, pruritic inflammatory skin disorder with complex etiology that affects up to 20% of children worldwide and is an increasing public health problem. Aside from its significant socioeconomic effect and increased risk of serious skin infections, AD can predispose infants and children to other atopic diseases, including food allergy (FA), allergic rhinitis (AR), and asthma through a process termed the atopic march. Recently, the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases stated that a new prospective cohort study that uses multiparameter approaches to define phenotypic/endotypic subgroups of AD and to predict AD outcomes is needed. They highlighted a major gap in knowledge, i.e. what are the mechanistic underpinnings of allergic disease progression.
In a manuscript recently published in The Journal of Allergy and Clinical Immunology: In Practice, Biagini Myers et al describe the Mechanisms of Progression of Atopic Dermatitis to Asthma in CHildren (MPAACH) cohort, the first US-based early life prospective cohort of children with eczema, which was designed to fill this gap. The goals of this NIH funded cohort are to define eczema phenotypes and endotypes, dissect the mechanisms that contribute to the development of allergic co-morbidities (food allergy, allergic rhinitis, and asthma) in children with eczema, and to identify novel biomarkers (immunologic, skin, biome, physiologic, genetic, genomic, epigenetic, and environmental) that identify children at high risk for the development of asthma and wheezing phenotypes, as well as other allergic conditions. MPAACH includes nearly 600 infants and toddlers with eczema, and each child is followed prospectively with annual visits, questionnaires and biospecimen collection. At the annual visits, all children undergo a physical examination including determination of eczema severity, skin prick testing to 11 aeroallergens and 13 foods, skin barrier assessments, and biospecimens (skin tape strips, blood, contact agar plates, stool, nasal swabs) are collected. In this study, they focused on data from visit 1 from the first 400 MPAACH children. They assessed lesional and non-lesional skin by transepidermal water loss (TEWL) measurement, host keratinocyte filaggrin (FLG) expression, skin staphylococcal colonization, and host keratinocyte S100A8 and S100A9 (alarmin) expression, as well as patterns of aeroallergen and food sensitization.
In this study they report on distinct endotypes of eczema in lesional and non-lesional skin that provide novel insights into disease pathophysiology. Non-lesional skin had features characteristic of diseased skin including low FLG and high alarmin expression, and increased colonization with S. aureus. In a multivariate model, non-lesional, but not lesional, FLG expression was associated with the development of co-sensitization to both food(s) and aeroallergen(s) and the development of moderate-severe eczema. This supports that in children with eczema, barrier dysfunction is global beyond actively inflamed areas and that events in the non-lesional skin are integral to the development of atopic disorders. Collectively, the data provide novel insights into disease pathophysiology, suggesting that the events taking place in the non-lesional skin may contribute to the development of active lesions by promoting inflammation, a feed-forward subsequent decrease in FLG expression, and increased skin permeability. These findings are of high importance because very few children follow the traditional atopic march, emphasizing the need to better define eczema disease phenotypes and endotypes that allow prediction of the natural history of eczema. Their study findings suggest that management of pediatric eczema should include treatment of both lesional and non-lesional skin, because subclinical inflammation in normal-appearing areas may predispose to allergic co-morbidities and more severe disease. Further, collectively, these data suggest the presence of a subclinical eczema endotype that may predispose to the development of allergic disease in the absence of overt eczema. This may represent a new definition of the atopic march that starts with skin barrier dysfunction rather than eczema.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.