: Interleukin-31 in Atopic Dermatitis and Prurigo Nodularis: Pathophysiology, Neuroimmune Mechanisms, and Clinical Efficacy of Nemolizumab.

Interleukin-31 (IL-31) is a central mediator in atopic dermatitis (AD) and prurigo nodularis (PN), functioning both as the principal pruritogenic cytokine, driving itch through direct neuronal activation via the IL-31RA/OSMRβ signaling axis, and as a key immunological amplifier that sustains Th2 polarization by promoting continued IL-4 and IL-13 production. Beyond these neuroimmune effects, IL-31 disrupts epidermal barrier integrity and acts directly on dermal fibroblasts to drive collagen synthesis and extracellular matrix remodeling, contributing to the lichenification of chronic AD and the hyperkeratotic nodule formation that defines PN. This narrative review integrates the mechanistic biology of IL-31 across both conditions with the clinical evidence base for nemolizumab, a humanized monoclonal antibody targeting IL-31RA, examining phase 3 trial data, long-term extension outcomes, translational biomarker evidence, and emerging real-world experience.