Literature Review: Recent Therapeutic Advances in The Management of Prurigo Nodularis: From Conventional Therapy to Biologics and Targeted Small-Molecule Agents.

Prurigo nodularis (PN) is a chronic inflammatory disease characterized by hyperkeratotic nodules on extensor surfaces, perpetuating a vicious itch-scratch cycle. Its epidemiologic burden is substantial, and diagnosis remains primarily clinical, supported by a structured diagnostic algorithm and evaluation for associated comorbidities. PN pathogenesis involves interactions among keratinocytes, immune cells, sensory nerve fibers and neuropeptides (substance P and calcitonin gene-related peptide) that elicit intense pruritus. Therapy aims to break the itch-scratch cycle and accelerate lesion resolution by reducing pruritus. Standard management with topical agents (corticosteroids, calcineurin inhibitors), systemic therapies (antihistamines, methotrexate, cyclosporine) and phototherapy often yields incomplete responses and requires prolonged treatment. Consequently, targeted therapies are critical to optimizing clinical efficacy. Dupilumab is currently the first Food and Drug Administration (FDA)-approved biologic for PN, followed by nemolizumab whereas other emerging agents-including additional monoclonal antibodies, Janus kinase (JAK) inhibitors, neurokinin-1 (NK1) receptor antagonists, opioid antagonists, and neuromodulators-remain at varying stages of clinical investigation (Phase II-III), acting on cytokine-neuroinflammatory pathways to relieve pruritus and improve patients' quality of life.