Cross-spectrum efficacy of spesolimab in IL-36-mediated dermatoses: a 'case study.

The nosological distinction between acute generalized exanthematous pustulosis (AGEP) and generalized pustular psoriasis (GPP) has become increasingly unclear due to shared IL-36 pathway dysregulation. This case highlights an important clinical gap: the therapeutic response to IL-36 inhibition in AGEP with wild-type IL36RN. A 15-year-old female with ERASPEN-confirmed GPP developed hydroxychloroquine-induced AGEP (EuroSCAR score = 7) despite wild-type IL36RN and CARD14. Ten days after hydroxychloroquine exposure, she presented with widespread erythema, pustules, targetoid lesions, and fever (39 °C). Histopathology revealed subcorneal pustules with eosinophilic infiltration. Acitretin provided no benefit, and cyclosporine (150 mg/day) produced only transient improvement before relapse. A single intravenous dose of spesolimab (450 mg) led to complete pustular clearance within 18 days. Sustained remission (GPPGA = 0) was observed at 5-month follow-up. Spesolimab produced rapid and durable control of IL-36-driven AGEP independent of IL36RN mutation status. These findings support IL-36 receptor blockade as a targeted therapeutic option for refractory AGEP and further position AGEP and GPP along a shared IL-36-mediated disease spectrum.