Introduction: Chronic hand eczema (CHE) is a highly prevalent inflammatory skin condition which is often resistant to conventional treatments. Molecular insights of CHE remain limited. Tape stripping combined with high-throughput RNA sequencing can now provide a better insight into CHE pathogenesis in a minimally invasive fashion.
Methods: We collected tape strip samples from lesional and non-lesional skin of 66 patients with moderate-to-severe CHE, comprising 33 with and 33 without comorbid atopic dermatitis (AD), and performed bulk RNA sequencing. Results were compared to tape strips from palmar skin of age/race/sex-matched healthy controls (HC). Differentially expressed genes (DEGs) (fold change/FCH > 1.5 and false discovery rate/FDR < 0.05) were calculated and correlated with clinical severity scores including hand eczema severity index (HECSI) and modified total lesion symptoms score (mTLSS).
Results: Tape strip isolates detected a common phenotype in CHE lesions regardless of AD status, including upregulated type-1 (IL12RB2, IFNGR1, IFNGR2, MX1) and type-2-associated inflammatory mediators (CCL22, CCL24, OX40/TNFRSF4, TSLPR/CRLF2, GATA3), paralleled by downregulated epidermal barrier markers (i.e., FLG or LORICRIN). Non-lesional skin demonstrated a similar, albeit milder, dysregulation pattern, with additional reduction in type-17 pathways. Lesional skin of CHE patients without AD showed greater skewing towards type-1 immunity (IL15RA, CXCL9), while CHE from AD patients showed a more pronounced type-2 inflammatory pattern (IL13, CCL17) and their gene expression biomarkers had greater and more significant correlations with clinical severity markers.
Conclusion: Tape stripping can capture detailed immune and skin barrier abnormalities in CHE and identify potential novel subtype-specific treatment targets. Stronger correlations in patients with AD suggest a more homogenous disease phenotype than in CHE non-AD patients.
Trial Registration: NCT03728504.
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