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Acute generalized exanthematous pustulosis in Adult
Other Resources UpToDate PubMed

Acute generalized exanthematous pustulosis in Adult

Contributors: Erin X. Wei MD, Vivian Wong MD, PhD, Susan Burgin MD
Other Resources UpToDate PubMed


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 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.

The causative drugs 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.


L27.0 – Generalized skin eruption due to drugs and medicaments taken internally
L53.8 – Other specified erythematous conditions

702617007 – Acute generalized exanthematous pustulosis

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Acute Pustular psoriasis (von Zumbusch type) – AGEP and pustular psoriasis both present with diffuse pustules and fever. AGEP is often distinguished by antecedent medication exposure. On biopsy, pustular psoriasis displays psoriasiform acanthosis. Personal or family history of psoriasis, pustules lasting longer than 15 days, and arthritis all favor pustular psoriasis over AGEP.
  • Bacterial Folliculitis – AGEP pustules are typically nonfollicular and will have a negative Gram stain and culture on a confluent base of erythema, as opposed to the isolated follicular papules of bacterial folliculitis.
  • Drug-induced hypersensitivity syndrome (DRESS) – Pustules have rarely been reported in this setting. Consider this diagnosis especially in a patient with facial edema, lymphadenopathy, and atypical lymphocytes on peripheral smear.
  • Stevens-Johnson syndrome / Toxic epidermal necrolysis (SJS/TEN) – Bullae and targetoid lesions have rarely been reported in AGEP in association with the more typical clinical findings outlined above. In AGEP, full-thickness necrosis of the epidermis and widespread denudation do not occur.
  • Exanthematous drug eruption
  • Viral exanthem
  • Candidiasis
  • Miliaria pustulosa

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Management Pearls

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Drug Reaction Data

Below is a list of drugs with literature evidence indicating an adverse association with this diagnosis. The list is continually updated through ongoing research and new medication approvals. Click on Citations to sort by number of citations or click on Medication to sort the medications alphabetically.

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Last Reviewed:03/28/2021
Last Updated:02/10/2022
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Acute generalized exanthematous pustulosis in Adult
A medical illustration showing key findings of Acute generalized exanthematous pustulosis (AGEP) : Fever, Widespread distribution, WBC elevated, Reaction 2 days to 2 weeks after drug
Clinical image of Acute generalized exanthematous pustulosis - imageId=888896. Click to open in gallery.  caption: 'Myriad tiny pustules and background erythema on the face, ear, and neck.'
Myriad tiny pustules and background erythema on the face, ear, and neck.
Copyright © 2024 VisualDx®. All rights reserved.