Skin Tape Stripping Reveals Distinct Biomarker Profiles in Chronic Hand Eczema of Patients With and Without Comorbid Atopic Dermatitis

ABSTRACT 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