Comprehensive Transcriptomic Profiling of Nonatopic Prurigo Nodularis in Korean Patients Reveals Il-22-driven Epidermal Stress and Neuro-immuno-fibrotic Remodelling.

Prurigo nodularis (PN) is a chronic pruritic dermatosis with incompletely defined pathogenesis, and molecular data from East Asian populations are limited. We characterized the transcriptomic signatures of non-atopic PN in Korean patients to identify pathways linked to chronic itch and lesion persistence. RNA sequencing was performed on lesional and non-lesional skin from 17 PN patients and normal skin from 11 controls, followed by differential expression, functional enrichment, and correlation analyses. Lesional PN skin showed distinct transcriptional signatures with upregulation of Th22/IL-22-related genes and IL-22-inducible epidermal stress markers (S100A7/A8/A9, SERPINB4, HRNR), along with keratinization genes (KRT6C, KRT16, KRT17). Itch severity correlated strongly (Spearman's ρ>0.7) with IL-22-inducible stress genes, IL4R, profibrotic mediators (WNT5A), JAK-STAT regulators (JAK3, SOCS1/3), neuromodulatory/epidermal-neural genes (TRPV3), and senescence markers (CDKN1A, CXCL8, PLAUR). Non-lesional skin showed intermediate expression patterns, consistent with subclinical inflammation. Despite the modest sample size and single-ethnicity design, these findings indicate that non-atopic PN in Korean patients is characterized by IL-22-driven epidermal stress, fibroblast remodelling, neuroimmune signalling, and senescence programsprogrammes, highlighting therapeutic targets including IL-31RA, IL-4Rα/JAK1, antifibrotic and senescence-directed pathways.