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.

Acute Generalized Exanthematous Pustulosis: Clinical Features, Differential Diagnosis, and Management

“…Hydroxychloroquine is the next most frequently implicated drug reported after antibiotics as a whole, with 44 cases reported in a recent review [ 52 ]. Particularly in the era of the coronavirus disease 2019 (COVID-19) pandemic from 2020 to present, there have been increased reports of hydroxychloroquine-induced AGEP, which may be secondary to increased use of the drug [ 8 , 53 – 68 ].…”

Advances in Our Understanding of the Interaction of Drugs with T-cells: Implications for the Discovery of Biomarkers in Severe Cutaneous Drug Reactions

“…Acute generalized exanthematous pustulosis or AGEP is a rare skin disease with a incidence of five cases per million and is associated with drug intake particularly with the administration of antibiotics. , Nonetheless, the use of newer antiviral drugs, such as remdesivir, has been implicated in the development of AGEP. The estimated overall mortality rate is lower than seen with SJS/TEN or DRESS ranging from 2% to 5%.…”

A Case of Acute Generalized Exanthematous Pustulosis Induced by Ceftriaxone

“…It is based on clinical features, the course of the disease, and laboratory and histopathological findings. The scoring system ranges from 0 to 12 and classifies cases into four categories: no AGEP (<0), possible (1-4), probable (5-7), and definitive (8)(9)(10)(11)(12). Histological findings support the diagnosis, and two histopathology patterns are usually observed: 1) a toxic pustuloderma with spongiform intraepidermal pustulosis, a mixed upper dermal perivascular inflammatory infiltrate, and papillary edema; or 2) a leukocytoclastic vasculitis with neutrophil collections within the epidermis [5].…”

“…It can be explained by the previous use of penicillin, resulting in sensibilization. However, one case series of 294 cases described a mean onset time of 9 days [8].…”

“…The treatment of AGEP centers on removing the causative drug, supportive care, infection prevention, and topical or systemic steroids. Even though most cases of GEP have a favorable prognosis with spontaneous recovery, complications like organ failure and infection can lead to a mortality rate as high as 5% [8].…”