Drug Triggers and Clinic of Acute Generalized Exanthematous Pustulosis (AGEP): A Literature Case Series of 297 Patients

Abstract

Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction, commonly caused by drugs. Available evidence mostly relies on small studies or case reports. We collected published AGEP case reports and, subsequently, described the patient characteristics, suspect and concomitant drugs, time to onset, disease management, and clinical prognosis. This study included 297 AGEP patients (64.3% women) obtained from 250 published case reports or case series with individual patient data. AGEP affected patients of all ages, but the majority of patients (88.2%) were ≥25 years old. The most frequently reported suspect drugs were anti-infectives for systemic use (36.5%), particularly antibacterials for systemic use (31.0%), and especially beta-lactam antibacterials (18.3%) and macrolides (4.3%). Other frequent suspect drugs were antineoplastics (12.2%), and anti-inflammatory/anti-rheumatic products (5.2%) plus hydroxychloroquine (12.8%). Mean time to onset was 9.1 days (standard deviation SD 13.94). Some patients developed fever (64.3%) and systemic involvement (18.9%), and most patients (76.4%) received pharmacological treatment for AGEP. Seven patients died, although five of them were already critically ill prior to AGEP. In conclusion, antibiotics remain the most common suspected cause of AGEP. While case mortality rate may be up to 2.5%, disentangling the role of AGEP on the fatal outcome from the role of the preexisting health conditions remains challenging.