BackgroundPrurigo nodularis (PN) is a chronic neuroimmune skin disorder characterized by intensely pruritic nodules, severe impairment of quality of life and significant psychosocial burden. Prior to the approval of targeted therapies, management relied on conventional agents with limited efficacy. Recent evidence of its neuroimmune pathogenesis have led to the approvement of targeted biologics. Dupilumab, a human monoclonal antibody targeting IL-4/IL-13-axis, has been the first targeted therapy approved for PN.Case presentationWe report a 75-year-old woman presenting with severe, treatment-naïve generalized pruritus (IGA PN-S 4; NRS 9/10; DLQI 21) with extensive nodular involvement of the trunk and extremities, complete sleep deprivation and important anxiety and depression (HADS.A 12; HADS-D 11). Following diagnosis of PN, treatment with dupilumab (600 mg loading dose, then 300 mg every 2 weeks) was initiated in October 2025. At approximately 6 weeks, marked pruritus reduction (NRS 3) and sleep restoration were observed. Progressive improvement continued over time. At 4 months follow-up, complete remission was nearly achieved (NRS 1, IGA PN-S 1, DLQI 2, HADS-A 4, HADS-D 3), with no adverse events reported.ConclusionThis case corroborates and extends the existing evidence on dupilumab efficacy in the treatment of moderate-to-severe PN, with particularly rapid and comprehensive responses across pruritus, skin lesions, sleep and psychosocial outcomes in an elderly patient, through IL-4/IL-13 inhibition. Our findings support dupilumab as a safe and effective targeted option for severe PN, also in older patients where conventional systemic therapies, such as corticosteroids or immunosuppressants, carry a high risk of adverse effects.