Management and Cause of Acute Generalized Exanthematous Pustulosis (AGEP)
Cause
AGEP is primarily a drug-induced reaction, with medications responsible for over 90% of cases, most commonly antibiotics including beta-lactams (ampicillin/amoxicillin), quinolones, pristinamycin, anti-infective sulfonamides, terbinafine, (hydroxy)chloroquine, and diltiazem. 1, 2
Pathophysiology
- The neutrophil attractant chemokine IL-8 drives the inflammatory cascade, with target cell killing occurring via both perforin and FAS-mediated pathways 3
- Less common triggers include infections, vaccinations, ingestion of various substances, and spider bites 4
Management
Immediate withdrawal of the suspected causative drug is the single most critical intervention, as AGEP is self-limited and typically resolves within 1-2 weeks after drug discontinuation. 1, 2, 5
Initial Assessment
- Quantify body surface area (BSA) involvement: mild-moderate (10-30% BSA) versus severe (>30% BSA) 6
- Obtain bacterial cultures before initiating any antimicrobial therapy if secondary infection is suspected 6
- Document fever, leukocytosis, and any systemic organ involvement 4, 5
Treatment Algorithm by Severity
Mild to Moderate AGEP (10-30% BSA):
- Apply topical low to moderate potency corticosteroids to affected areas 6, 1
- Provide gentle skin care with emollients 6
- Avoid unnecessary antibiotics to prevent further drug exposure 1
Severe AGEP (>30% BSA or systemic symptoms):
- Administer systemic corticosteroids: prednisone 0.5-1 mg/kg body weight for 7 days, then taper over 4-6 weeks 6
- Hold immune checkpoint inhibitor therapy if AGEP is immunotherapy-related until resolution to grade 1 6
- Consider inpatient management for close monitoring 7
Symptomatic Management
- Prescribe oral antihistamines for severe pruritus 6
- Consider gabapentin or pregabalin for refractory pruritus 6
- Administer appropriate antibiotics based on culture sensitivities for at least 14 days if secondary bacterial infection is confirmed 6
Follow-up
- Reassess after 2 weeks of initial therapy 6
- Escalate treatment or reconsider diagnosis if no improvement or worsening occurs 6
- Obtain dermatology consultation for persistent or severe cases 6
- Arrange allergological work-up after acute phase resolution to identify the causative agent and prevent future exposures 7
Critical Diagnostic Considerations
AGEP must be distinguished from other pustular eruptions, particularly generalized pustular psoriasis, drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and infectious causes. 8, 4
- Histopathology reveals spongiform subcorneal and/or intraepidermal pustules with neutrophilic and eosinophilic infiltration and papillary dermal edema 2, 5
- AGEP typically has rapid onset (within 48 hours of drug exposure) and prompt resolution (within 2 weeks), distinguishing it from pustular psoriasis which has a more chronic course 4, 2
Common Pitfalls
- Do not empirically start antibiotics without culture confirmation, as this introduces additional potential drug triggers 1
- Do not confuse AGEP with infectious pustulosis—AGEP pustules are sterile 4, 5
- While topical and systemic corticosteroids are widely used, strong evidence for their effectiveness is lacking; however, they remain standard practice based on expert consensus 7