Risk Factors for Drug-Induced Acute Generalized Exanthematous Pustulosis(AGEP) from 2004 to 2024: A Real-World Study Based on the FAERS

Huafa Que,1,2 Xianglong Zheng,1,3 Xiaojian Li,1 Wanchun Wang1,3 1Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China; 2Department of Traditional Chinese Surgery, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 200030, People’s Republic of China; 3Department of Traditional Chinese Surgery, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, 330006, People’s Republic of ChinaCorrespondence: Wanchun Wang, Department of Traditional Chinese Surgery, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, 330006, People’s Republic of China, Email [email protected] Xiaojian Li, Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, 330004, People’s Republic of China, Email [email protected]: Acute Generalized Exanthematous Pustulosis (AGEP) is a rare but potentially life-threatening cutaneous adverse drug reaction. Due to its poor clinical outcomes and unclear pathogenesis, this study aimed to systematically evaluate the drug-related risk factors for AGEP using data from the FDA Adverse Event Reporting System (FAERS).Methods: This real-world, retrospective pharmacovigilance study analyzed all AGEP-related reports submitted to the FAERS database between Q1 2004 and Q4 2024. Disproportionality analysis was performed using reporting odds ratios (RORs), with Bonferroni-adjusted p-values to identify high-risk drugs. Drugs identified by univariate analysis were further evaluated through LASSO regression and multivariable logistic regression to determine risk factors associated with AGEP.Results: A total of 6,880 AGEP cases were identified, with a predominance of female patients (54.5%) and a median age of 59 years. Disproportionality analysis revealed 148 drugs with a significant signal for AGEP, mainly including antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), and antivirals. LASSO and multivariate logistic regression identified 17 drugs as risk factors for AGEP, including ceftriaxone (OR = 49.87), pantoprazole (OR = 31.39), and hydroxychloroquine (OR = 28.38). The model showed moderate predictive accuracy with an AUC of 0.69.Conclusion: This study identified multiple drug classes significantly associated with AGEP using FAERS-based adverse event data. The findings highlight a higher susceptibility in middle-aged and younger populations and underscore the importance of enhanced monitoring for high-risk medications. Given the inherent limitations of spontaneous reporting systems, further prospective studies are needed to confirm these associations and explore underlying mechanisms.Keywords: AGEP, FAERS, pharmacovigilance, disproportionality analysis