Non-lesional skin in atopic dermatitis (AD) is abnormal; however, the pathobiology of lesional and non-lesional skin and the definition of endotypes are not clearly understood.

A study was therefore conducted to define lesional and non-lesional endotypes of AD by building an early life prospective cohort of children with AD, called the Mechanisms of Progression from AD to Asthma in Children (MPAACH) cohort.

In this study, investigators evaluated lesional and non-lesional skin TEWL, filaggrin (FLG) and alarmin (S100A8,S100A9) expression, staphylococcal colonization, and patterns of aeroallergen and food sensitization in order to define the non-lesional and lesional phenotypes and endotypes.

There were pathophysiologic changes in lesional and non-lesional skin and were found to be associated with SCORAD. Non-lesional skin had characteristics of diseased skin, such as low FLG and high alarmin expression, and heightened S. aureus colonization. According to a multivariate model, non-lesional, and not lesional, FLG expression was tied to the development of co-sensitization and moderate-severe AD. Lesional skin revealed further deficits in FLG expression, but alarmin expression was the same as in non-lesional skin.

Events in the non-lesional skin were thus shown to promote the development of AD severity and co-sensitization. The evidence thus points to the presence of a subclinical eczema endotype that may predispose to the development of allergic disease in the absence of overt eczema.

Source: Biagini Myers JM, Sherenian MG, Baatyrbek Kyzy A, et al. Events in Normal Skin Promote Early-life Atopic Dermatitis - the MPAACH Cohort. J Allergy Clin Immunol Pract. 2020 Apr 14.