The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype

Abstract

Skin barrier dysfunction has been reported in both atopic dermatitis (AD) and food allergy (FA). However, only one-third of patients with AD have FA. The purpose of this study was to use a minimally invasive skin tape strip sampling method and a multiomics approach to determine whether children with AD and FA (AD <i>FA</i>+) have stratum corneum (SC) abnormalities that distinguish them from AD without FA (AD <i>FA</i>-) and nonatopic (NA) controls. Transepidermal water loss was found to be increased in AD <i>FA</i>+. Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD <i>FA</i>+ were substantially lower than in AD <i>FA</i>- and NA skin. These abnormalities correlated with morphologic changes in epidermal lamellar bilayer architecture responsible for barrier homeostasis. Shotgun metagenomic studies revealed that the nonlesional skin of AD <i>FA</i>+ had increased abundance of <i>Staphylococcus aureus</i> compared to NA. Increased expression of keratins 5, 14, and 16 indicative of hyperproliferative keratinocytes was observed in the SC of AD <i>FA</i>+. The skin transcriptome of AD <i>FA</i>+ had increased gene expression for dendritic cells and type 2 immune pathways. A network analysis revealed keratins 5, 14, and 16 were positively correlated with AD <i>FA</i>+, whereas filaggrin breakdown products were negatively correlated with AD <i>FA</i>+. These data suggest that the most superficial compartment of nonlesional skin in AD <i>FA</i>+ has unique properties associated with an immature skin barrier and type 2 immune activation.