Efficacy and safety of oral tofacitinib compared to cyclosporine in prurigo nodularis: A Randomized Controlled Study with assessment of STAT1, STAT3, and STAT6 expression

Prurigo nodularis (PN), also known as Hydes prurigo, is a chronic pruritic dermatosis characterized by symmetrically distributed hyperkeratotic papules and nodules predominantly over the extremities. The immunopathogenesis of PN involves a complex interplay between Th1, Th2, Th17, and Th22 pathways, along with neuronal and fibroblastic dysregulation. Signal transducer and activator of transcription (STAT) proteins are critical mediators of the Janus kinase (JAK)/STAT signaling cascade, regulating cytokine-induced immune responses. STAT1 and STAT4 are associated with Th1, STAT3 and STAT5 with Th17, and STAT5 and STAT6 with Th2 differentiation. Elevated cytokines such as IL4, IL13, IL17, IL22, and IL31 exert their downstream effects through the JAK/STAT pathway. Previous studies have demonstrated predominant activation of STAT3 and STAT6, suggesting Th2/Th17 predominance in PN pathogenesis.This randomized controlled study aims to compare the efficacy and safety of oral tofacitinib, a JAK1/JAK3 inhibitor, with cyclosporine, a calcineurin inhibitor, in the management of prurigo nodularis. Additionally, it aims to assess the tissue expression of STAT1, STAT3, and STAT6 before and after treatment to elucidate their role in disease modulation. The study seeks to bridge the gap between immunopathogenesis and therapeutics, contributing to optimized systemic management strategies for refractory prurigo nodularis.