A multi-omics evaluation of the non-lesional skin surface identifies atopic dermatitis with food allergy (AD FA+) as a unique endotype

AD FA+ is associated with skin barrier dysfunction, but only one-third of AD have FA. The purpose of this study was to use a novel skin tape strip (STS) method to determine whether children with AD FA+ have stratum corneum abnormalities which distinguish them from AD without FA (AD FA-) and non-atopic (NA) controls. Children who were either AD FA+, AD FA- or NA were balanced for age, gender, and race. The 2 AD groups had similar skin severity. The primary endpoint was the area under the curve for transepidermal water loss (TEWL AUC) assessed on non-lesional skin prior to and after 5, 10, 15, and 20 STS. Epidermal biomarkers were assessed by a multi-omics approach. TEWL AUC was significantly increased in AD FA+ compared to AD FA- and NA (p<0.001). The content of filaggrin breakdown products and the proportion of ω-esterified (EOS) ceramides in non-lesional skin in AD FA+ children were significantly lower in comparison with AD FA- and NA controls (p<0.01). Metagenomic studies revealed AD FA+ non-lesional skin had increased abundance of Staphylococcus aureus. Skin transcriptome of AD FA+ was high for dendritic cell and Type 2 immune genes. Global proteomics identified aberrant markers found in proliferating keratinocytes. Network and relative importance analyses identified aberrant keratin markers and reduced filaggrin breakdown products as the major drivers of FA and increased TEWL. The most superficial compartment of non-lesional skin in AD FA+, but not AD FA- and NA, is associated with biomarkers indicative of skin barrier dysfunction and immune activation.