Clinical perspectives on prurigo nodularis: diagnostic challenges and novel treatment options

Prurigo nodularis (PN) is a chronic skin inflammatory condition characterized by severe, persistent itching and excoriated nodules induced by scratching. PN is strongly related to neural and immune dysfunction and negatively impacts quality of life. Treatments for PN are often off-label, highlighting the need for specifically approved agents and consensus guidelines for patient management. An Italian expert panel (including nine dermatologists) discussed four main clinical and therapeutic topics (definition and etiopathogenesis, diagnosis and staging, clinical management and therapy) based on their clinical experience and literature review. Data gaps were identified and a modified Metaplan® method was used to determine the consensus for each topic. PN, mainly affecting middle-aged and elderly adults, is a distinct disease from atopic dermatitis (AD), despite sharing some features (e.g. itch and inflammatory pathways). Although the pathophysiology of PN remains under debate, type 2 pro- inflammatory cytokines (e.g. interleukin IL-4, IL-13 and IL-31) are key mediators of both chronic pruritus and tissue changes. According to international definition, PN is a disease characterized by chronic (at least 6 months) pruritus and signs of repeated scratching, and well-defined nodules. Dupilumab (targeting the IL-4 receptor alpha inhibitor and inhibiting both IL-4 and IL-13) and nemolizumab (an IL-31 receptor alpha inhibitor) were recently approved for the treatment of PN, showing marked efficacy and favorable safety in randomised clinical trials. PN man- agement requires a better understanding of disease pathophysiology, with comprehensive patient care strategies. Novel targeted therapies, such as dupilumab, are essential for improving patient outcomes in PN.