The Nonlesional Skin Surface Distinguishes Atopic Dermatitis With Food Allergy as a Unique Endotype (2019)

To determine if children with atopic dermatitis and food allergy (AD FA+) to peanut have skin features that distinguish them from children with atopic dermatitis without food allergy (AD FA−) and nonatopic (NA) controls.Sixty-two children with atopic dermatitis (AD) of any severity between the ages of 4 to 17 years were recruited to National Jewish Health. The 3 groups consisted of 21 children with food allergy (AD FA+) to at least peanut, 19 without food allergy (AD FA−), and 22 NA controls. Groups were balanced for age, sex, and race and were reported to have similar AD severity.This was a prospective, clinical mechanistic study to evaluate for differences among the AD FA+, AD FA−, and NA groups. They used skin tape stripping (STS) of lesional and nonlesional skin to examine transepidermal water loss (TEWL) and stratum corneum composition. The primary outcome was TEWL area under the curve measured before STS and after 5, 10, 15, and 20 skin tape tests. This was combined with the use of proteomics, lipidomics, electron microscopy, and transcriptomics to evaluate STS samples. In addition, the microbiome was assessed by skin swabs.TEWL area under the curve assessed on nonlesional skin demonstrated that subjects with AD FA+ had a significant increase in TEWL when compared with subjects with AD FA− and NA controls. There was noted to be significantly higher amounts of filaggrin (FLG) breakdown products at skin tape tests 15 and 16 in the NA group when compared with subjects with AD FA− and AD FA+, with the AD FA+ group demonstrating the lowest amount of FLG breakdown products. They mapped shotgun metagenomics microbial sequence reads and found an increased relative abundance of Staphylococcus and Micrococcus in subjects with AD FA+ compared with NAs on nonlesional skin. In addition KRT5, KRT14 (basal markers), and KRT16 (marker of hyperproliferation) at skin tape tests 15 and 16 were all increased in the AD FA+ group compared with subjects with AD FA− and NA, suggesting poor terminal differentiation of proliferating keratinocytes. Through transcriptome analysis of STS, they found that patients with AD FA+ had more dendritic cell and Th2 immune activation signatures in nonlesional skin. These differences were found to be independent of AD severity because there were no differences in AD severity among the 2 groups with AD, measured by Scoring Atopic Dermatitis, Eczema Area and Severity Index, and Nottingham Eczema Severity Score. In addition, network analysis demonstrated that these keratins (KRT5, KRT 14, and KRT 16) were positively correlated with AD FA+ and that FLG breakdown products were negatively correlated with AD FA+.Increased TEWL, low amounts of FLG breakdown products, and increased keratin proteins in the nonlesional skin of the AD FA+ group all suggest that in children with AD FA+, skin exhibits abnormal barrier function and lack of epidermal terminal differentiation.The authors demonstrate that both AD and food allergy affect the structure of nonlesional skin at the stratum corneum. This highlights that nonlesional skin abnormalities not visible to the eye may exist in our patients with both disorders. Further insights into these differences could help to improve treatment of AD and perhaps even prevent food allergy.