Historic perspectives of prurigo nodularis

Prurigo nodularis (PN) manifests as a chronic inflammatory skin disease characterized by the development of highly pruritic nodules. It is often accompanied by a variety of skin, metabolic, neurologic, and psychiatric comorbidities. A wealth of observational evidence indicates that PN disproportionately impacts non-White individuals, leading to a range of lasting, detrimental effects on patient quality of life and mental health. Despite its clinical significance, the underlying pathophysiologic mechanisms of PN remain elusive, contributing to the limited efficacy of existing therapeutics such as topical corticosteroids, phototherapy, and systemic treatments. A significant milestone was achieved when the US Food and Drug Administration-approved "Dupixent" (dupilumab), a human monoclonal IgG4 antibody targeting interleukin-4 and interleukin-13, as the first and only treatment for PN in adults. Nevertheless, persistent pruritus and the appearance of lesions continue to severely disrupt daily activities, sleep quality, and psychologic well-being. Given the urgent and unmet need for more effective management and general awareness, we review key historical developments in the literature and summarize pipeline therapies for this debilitating condition.