Diagnosis: Acute generalized exanthematous pustulosis (AGEP)
The acute rash with minute pustules and associated leukocytosis with neutrophilia and eosinophilia led to an early diagnosis of AGEP, which may have been triggered by azithromycin—the patient’s only recent medication. AGEP is a severe cutaneous eruption that may be associated with systemic involvement. Medications are usually implicated, and patients often seek urgent evaluation.
AGEP typically begins as an acute eruption in the intertriginous sites of the axilla, groin, and neck, but often becomes more generalized.1,2 The diagnosis is strongly suggested by the condition’s key features: fever (97% of cases) and leukocytosis (87%) with neutrophilia (91%) and eosinophilia (30%); leukocytosis peaks 4 days after pustulosis occurs and lasts for about 12 days.1 Although common, fever is not always documented in patients with AGEP. 3 (Our patient was a case in point.) While not a key characteristic of AGEP, our patient’s weight gain was likely explained by the severe edema secondary to his inflammatory skin eruption.
Medications are implicated, but pathophysiology is unknown
In approximately 90% of AGEP cases, medications such as antibiotics and calcium channel blockers are implicated; however, the lack of such an association does not preclude the diagnosis.1,4 In cases of drug reactions, the eruption typically develops 1 to 2 days after a medication is begun, and the pustules typically resolve in fewer than 15 days.5 In 17% of patients, systemic involvement can occur and can include the liver, kidneys, bone marrow, and lungs.6 A physical exam, review of systems, and a laboratory evaluation can help rule out systemic involvement and guide additional testing.
AGEP has an incidence of 1 to 5 cases per million people per year, affecting women slightly more frequently than men.7 While the pathophysiology is not well understood, AGEP and its differential diagnoses are categorized as T cell-related inflammatory responses.4,7
Distinguishing AGEP from some look-alikes
There are at least 4 severe cutaneous eruptions that might be confused with AGEP, all of which may be associated with fever. They include: drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome; Stevens-Johnson syndrome (SJS); toxic epidermal necrolysis (TEN); and pustular psoriasis.8-10 The clinical features that may help differentiate these conditions from AGEP include timeline, mucocutaneous features, organ system involvement, and histopathologic findings.4,8
DRESS occurs 2 to 6 weeks after drug exposure, rather than a few days, as is seen with AGEP. It often involves morbilliform erythema and facial edema with substantial eosinophilia and possible nephritis, pneumonitis, myocarditis, and thyroiditis.9 Unlike AGEP, DRESS does not have a predilection for intertriginous anatomic locations.
SJS and TEN occur 1 to 3 weeks after drug exposure. These conditions manifest with the development of bullae, atypical targetoid lesions, painful dusky erythema, epidermal necrosis, and mucosal involvement at multiple sites. Tubular nephritis, tracheobronchial necrosis, and multisystem organ failure can occur, with reported mortality rates of 5% to 35%.8,11