Acute Generalized Exanthematous Pustulosis: An Integrated Study of 503 Cases with Emphasis on Drug Culprits, Clinical Features, Diagnosis and Treatment

Background: Acute generalized exanthematous pustulosis (AGEP) is a drug-induced severe cutaneous adverse reaction (SCAR) characterized by an acute extensive erythematous pustular eruption. Integrated analyses including Asian cohorts remain scarce. Methods: A total of 503 AGEP cases were analyzed by combining two distinct, routinely-collected data cohorts: (1) a literature-derived cohort (PubMed, Embase, Web of Science, and CNKI) and (2) a hospital-based clinical cohort from a tertiary-care center in China. The hospital cohort data were collected retrospectively from January 2015 to July 2025. Demographic, etiologic, clinical, laboratory and therapeutic characteristics were summarized. Drugs were stratified by median latency (3 days) into short- versus long-latency groups to explore class-specific patterns. Results: Drugs triggered 94.6% of cases, mainly β-lactam antibiotics (20.7%), non-β-lactam antibiotics (16.3%), and hydroxychloroquine (10.4%). With a 3-day median latency threshold, antibiotic-related reactions showed short latency, whereas antimalarials, analgesics, and antifungals exhibited longer latency. Hospitalization occurred in 75.1%, and systemic involvement in 20.2% (mostly hepatic or renal). Mucosal lesions were infrequent (oral 8.7%, genital 1.8%). Among those tested, patch tests were positive in 71.6%. Systemic corticosteroids were the mainstay (63.8%) of treatment, with cyclosporine (3.7%) and intravenous immunoglobulin (2.5%) used as adjuncts. A few refractory cases received biologics, including IL-17 inhibitors (eg secukinumab, brodalumab) and IL-36 receptor blockade (spesolimab), achieving partial or complete response. Eight deaths (1.6%) were documented, mainly among older, comorbid, polymedicated patients. Conclusion: AGEP displays distinct drug class–specific latency signatures and occasional systemic morbidity. We propose a conceptual AGEP causality triage framework integrating latency and allergologic evidence to enhance culprit identification in polypharmacy settings. Given the mechanistic involvement of the IL-36-Th17/IL-17 axis, biologic agents targeting IL-17 or IL-36 pathways show promise in severe or corticosteroid-refractory AGEP, warranting confirmation in larger prospective studies. Keywords: acute generalized exanthematous pustulosis, AGEP, adverse drug reaction, retrospective cohort, literature review