What is the treatment for Acute Generalized Exanthematous Pustulosis (AGEP)?

Treatment of Acute Generalized Exanthematous Pustulosis (AGEP)

The cornerstone of AGEP treatment is immediate withdrawal of the offending drug, which leads to spontaneous resolution within 15 days in most cases, with supportive care and topical corticosteroids for mild-to-moderate disease, and systemic corticosteroids reserved for severe cases with extensive body surface area involvement or systemic symptoms. 1, 2, 3

Immediate Management

Drug Withdrawal

• Identify and discontinue the causative drug immediately - this is mandatory and the single most important intervention, as AGEP is self-limiting once the trigger is removed 1, 2, 4
• Most cases resolve spontaneously within 15 days after drug cessation, with pustules disappearing within a few days followed by desquamation 2, 3

Initial Assessment

• Evaluate the extent of skin involvement using body surface area (BSA): mild-to-moderate (10-30% BSA) versus severe (>30% BSA) 1
• Check for fever, neutrophilia, and peripheral eosinophilia (present in approximately one-third of patients) 2
• Assess for systemic organ involvement, which occurs in approximately 14% of cases 4
• Obtain bacterial cultures if secondary infection is suspected (look for painful lesions, yellow crusts, discharge, or failure to respond to initial management) 1

Treatment Based on Severity

Mild-to-Moderate AGEP (10-30% BSA)

• Apply topical low-to-moderate potency corticosteroids to affected areas 1
• Provide supportive care with gentle skin care and emollients 1
• No systemic treatment is typically required, as internal organs are usually not involved 2

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 1
• A 2021 retrospective study demonstrated that systemic corticosteroid treatment significantly reduced length of hospital stay (p=0.035) compared to topical corticosteroids alone, though mortality was not affected 4
• Consider hospital admission for severe cases with multisystem involvement 3, 5

Recalcitrant or Atypical Cases

• For severe or recalcitrant AGEP requiring rapid control of unstable disease, consider cyclosporine 3-5 mg/kg/day divided into two doses (start at 5 mg/kg/day for severe cases) 6, 5
• Intravenous immunoglobulin (IVIG) may be considered for severe or recalcitrant cases that fail to respond to corticosteroids 5
• Pre-treatment monitoring for cyclosporine should include complete blood count, comprehensive metabolic panel, serum creatinine, blood pressure, fasting lipid profile, electrolytes, urinalysis, and infectious disease screening 6

Management of Complications

Secondary Infection

• Obtain bacterial cultures before initiating antimicrobial therapy 1
• Administer appropriate antibiotics based on culture sensitivities for at least 14 days 1
• Secondary infections are not infrequent complications in patients with poor general medical condition and contribute to the approximately 5% mortality rate 2

Pruritus Management

• Prescribe oral antihistamines for severe pruritus 1
• Consider gabapentin or pregabalin for refractory severe pruritus 1

Follow-up and Monitoring

• Reassess after 2 weeks of initial therapy 1
• If no improvement or worsening occurs, consider alternative diagnoses (including overlap syndromes with Stevens-Johnson syndrome/toxic epidermal necrolysis, DRESS, or generalized pustular psoriasis) or escalate treatment 1, 5
• Refer to dermatology for persistent or severe cases 1
• Arrange allergological work-up after the acute phase resolves to identify the culprit drug and prevent future episodes 7

Critical Pitfalls to Avoid

• Do not rechallenge with the suspected offending drug - the most severe cases and highest mortality are associated with drug rechallenge 2
• Do not delay drug withdrawal while awaiting diagnostic confirmation - clinical suspicion warrants immediate cessation 3, 7
• Do not overlook systemic involvement - approximately 14% of patients have organ involvement requiring more aggressive management 4
• Recognize that while AGEP is generally self-limited, mortality approaches 5%, particularly in elderly patients with comorbidities and secondary infections 2