Acute generalized exanthematous pustulosis (AGEP) is an acute febrile pustular eruption that has been reported in infants, children, and adults. In adult patients, it usually occurs as a result of a medication (accounting for about 90% of cases) and rarely follows a viral infection (enterovirus, adenovirus, cytomegalovirus [CMV], Epstein-Barr virus [EBV], hepatitis B, parvovirus B19) or mercury exposure. Pediatric cases may be more commonly associated with infectious causes compared to adults. AGEP in the setting of treatment for COVID-19 infection (including antimalarial and macrolide or cephalosporin antibiotic) has been reported. Brown recluse spider (Loxosceles reclusa) bites have led to AGEP, possibly related to the venom's promotion of interleukin (IL)-8 and granulocyte macrophage colony-stimulating factor (GM-CSF) cytokines.

The syndrome occurs within 2 weeks of starting the inciting medication, usually as soon as 48 hours after initial drug ingestion. Fever, typically up to 39°C (102.2°F), is a near constant feature and persists about 1 week. The rash of AGEP consists of tiny, superficial pustules that develop on erythematous plaques. Burning and pruritus are frequently reported. Lesions resolve within 1-2 weeks with fine, pinpoint areas of desquamation. Mucous membrane involvement occurs in atypical AGEP and its presence portends to worse outcome.

Acute localized exanthematous pustulosis, or ALEP, is a localized variant of AGEP. The clinical presentation and course resemble that of AGEP, but the eruption is often localized to the face, neck or chest, and fever is not a common feature. Localized penile and lower extremity involvement has also been reported.

A severe form of AGEP can be associated with septic shock, presenting with hemodynamic instability and multiorgan dysfunction, including renal failure. Other skin findings, including atypical targetoid lesions, vesicles, and facial edema, have been reported. According to a single tertiary care center, this atypical, severe form of AGEP was found in 22% of patients with AGEP.

The causative drugs in AGEP are primarily antibiotics, typically beta-lactam antibiotics (penicillins, aminopenicillins, cephalosporins) and macrolides (azithromycin), but many other drug culprits have been reported, including norfloxacin, calcium channel blockers (eg, diltiazem, nifedipine), antimalarials, doxycycline, vancomycin, isoniazid, carbamazepine, acetaminophen, quinidine, itraconazole, piperazine, NSAIDs (eg, ibuprofen), metronidazole, and pyrimethamine. ALEP has most frequently been reported following beta-lactam antibiotics but has also been described secondary to other antibiotics and a variety of other medication classes. Severe AGEP with septic shock has been reported with vancomycin, amoxicillin, trimethoprim-sulfamethoxazole, metronidazole, and clindamycin.