Clinical presentation and management of atypical and recalcitrant acute generalized exanthematous pustulosis

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction (SCAR) characterized by sterile nonfollicular pustules on an erythematous base that form rapidly after drug exposure. AGEP is mediated by numerous cytokines produced by drug-specific T cells that mediate neutrophilic intracorneal, subcorneal, or intraepidermal pustule development. Though genetic susceptibility is not fully understood, individuals with mutations in IL-36RN may be at increased risk of AGEP development. AGEP commonly presents with leukocytosis and fever in the acute pustular phase and follows a self-limited desquamative recovery phase upon removal of offending drug. Severe cases of AGEP may have multisystem organ involvement. Atypical presentations of AGEP include localized eruptions and cases with overlapping clinical and histopathologic features associated with Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and generalized pustular psoriasis. Most cases of AGEP clear rapidly with systemic corticosteroids, but severe or recalcitrant cases may require other systemic therapies, such as cyclosporine, and intravenous immunoglobulin.