Tape strips capture immune and epidermal hyperplasia markers in the major orphan ichthyoses

Prior studies in ichthyosis have demonstrated cutaneous and/or systemic immune abnormalities with barrier defects; however, the transcriptomes of the major orphan forms of ichthyosis have yet to be characterized through tape stripping, a minimally invasive sampling method validated in other inflammatory skin diseases. Skin tape strips from 27 patients with ichthyosis (9 with Netherton syndrome, 6 with congenital ichthyosiform erythroderma, 7 with lamellar ichthyosis, and 5 with epidermolytic ichthyosis) and 18 demographically matched healthy controls were analyzed with RNA sequencing. Differential expression was defined as fold change >2 and false discovery rate <0.05. All subtypes shared significant T helper (Th)17/Th22 upregulation (eg, S100A7/8/9, PI3, CCL20), and Th2 products (eg, TNFRSF4, IL13, CCR4) were particularly increased in Netherton syndrome. Tape strips additionally captured common increases in Th1 (IL1B, OASL) and IL4R upregulation in Netherton syndrome, lamellar ichthyosis, and epidermolytic ichthyosis. Although modulation of lipid markers was variable across subtypes, several epidermal differentiation complex/cornified envelope genes were increased in all or most subtypes. Disease-severity metrics were moderately correlated with increases in ceramide synthase CERS3 and Th17/Th22 and late cornified envelope markers. Changes in immune and epidermal differentiation complex/cornified envelope tape-strip markers correlated significantly and positively with those measured in biopsies. Our findings highlight tape stripping as a minimally invasive approach to profiling ichthyosis, which could provide future pathogenic and therapeutic insights.