Acute Generalized Exanthematous Pustulosis: Clinical Characteristics, Pathogenesis, and Management

Abstract

Background: Acute generalized exanthematous pustulosis (AGEP) is a potentially severe adverse cutaneous drug reaction, which typically occurs within 24–48 h after the intake of the culprit drug. Summary: AGEP is characterized by numerous sterile subcorneal pustules on erythematous skin and in less than a third of cases it can be associated with organ manifestations possibly leading to life-threatening symptoms (e.g., cholestasis, nephritis, and lung and bone marrow involvement). In contrast to generalized pustular psoriasis, it can involve mucosal regions and typically resolves rapidly if the culprit drug is removed, and adequate therapy with topical or systemic steroids administered. Diagnosis based on patient history, clinical signs, and characteristic cutaneous histology is rarely challenging. Identification of the culprit drug may be aided by patch testing or lymphocyte transformation tests that are of limited value. Key Messages: Recent experimental data reviewed herein are supportive of an early role of drug-induced innate immune activation and innate cytokines such as interleukin (IL)-1, IL-36, and IL-17 in the pathogenesis of AGEP. This explains the rapid onset and neutrophilic character of the cutaneous inflammation, but also provides new avenues for in vitro tests aimed at better identifying the culprit drug.