What Causes Acute Generalized Exanthematous Pustulosis (AGEP)?
AGEP is primarily a drug-induced severe cutaneous adverse reaction, with antibiotics (especially beta-lactams) being the most common culprits, though infections, vaccinations, and other substances can also trigger this condition. 1, 2, 3
Primary Causative Agents
Medications (Most Common Cause)
Antibiotics are the leading cause of AGEP, particularly:
- Beta-lactam antibiotics (penicillins, cephalosporins) are the most frequently implicated drugs 2, 3
- Other antibiotics also commonly trigger AGEP 1, 3
Additional medication classes that cause AGEP include:
- Antifungal agents 2
- Non-steroidal anti-inflammatory drugs (NSAIDs) 2
- Analgesics 2
- Antiarrhythmic drugs 2
- Anticonvulsant medications 2
- Antidepressant drugs 2
Non-Drug Triggers
Less common causes of AGEP include:
Pathophysiological Mechanism
AGEP is mediated by drug-specific T cells that produce numerous cytokines, leading to neutrophilic infiltration and pustule formation 4. Specifically:
- The neutrophil attractant chemokine IL-8 is involved in AGEP pathogenesis, killing target cells via both perforin and FAS-mediated pathways 5
- Drug-specific T cells produce cytokines that mediate the development of intracorneal, subcorneal, or intraepidermal pustules 4
Genetic susceptibility may play a role:
- Individuals with mutations in IL-36RN may be at increased risk of developing AGEP 4
- However, genetic predisposition is not fully understood 4
Clinical Timing
AGEP typically develops rapidly after drug exposure:
- Onset occurs within 48 hours of ingesting the causative medication in most cases 3
- The reaction is characterized by acute onset of fever, pustulosis, and leukocytosis 3
Key Clinical Pitfall
Cross-reactivity within the same drug class can occur, meaning patients who develop AGEP from one beta-lactam antibiotic may react to other beta-lactams 2. This is critical for preventing recurrence when selecting alternative medications.