Management of Acute Generalized Exanthematous Pustulosis (AGEP)
Immediately discontinue the suspected causative drug and provide supportive care with topical corticosteroids, as AGEP is a self-limited severe cutaneous adverse reaction that typically resolves within 1-2 weeks after drug withdrawal. 1, 2
Initial Recognition and Drug Withdrawal
AGEP is classified as a severe cutaneous adverse reaction characterized by exanthema with pustules, often accompanied by fever ≥38.5°C and facial edema 3. The most critical first step is identifying and stopping the offending medication—most commonly antibiotics (particularly beta-lactams) or diltiazem 2, 4, 5.
- Stop the suspected drug immediately upon recognition of pustular eruption on erythematous base 1, 2
- Document all medications taken in the preceding 2 months, including over-the-counter preparations, noting start dates and dose changes 6
- Obtain bacterial cultures before starting any antimicrobial therapy if secondary infection is suspected (indicated by failure to respond, painful lesions, yellow crusts, or discharge) 3, 1
Severity Assessment and Treatment Algorithm
Mild to Moderate AGEP (10-30% Body Surface Area)
- Apply topical low to moderate potency corticosteroids to affected areas 1, 3
- Provide gentle skin care with alcohol-free moisturizing creams or ointments containing 5-10% urea applied twice daily 3
- Avoid skin irritants including hot water, frequent washing, and over-the-counter anti-acne medications 3
- Consider oral antihistamines for pruritus management 1
Severe AGEP (>30% BSA or Systemic Symptoms)
Administer systemic corticosteroids: prednisone 0.5-1 mg/kg body weight for 7 days with tapering over 4-6 weeks 1, 3. This represents the standard approach for severe cases with extensive involvement or systemic manifestations.
- Hold immune checkpoint inhibitor therapy if AGEP is immunotherapy-related until resolution to grade 1 1
- Reassess after 2 weeks; if no improvement or worsening occurs, consider alternative diagnoses or escalate treatment 1, 3
- For refractory severe pruritus unresponsive to antihistamines, consider gabapentin or pregabalin 1
Management of Complications
When secondary bacterial infection is suspected:
- Obtain bacterial, viral, and fungal cultures prior to antimicrobial initiation 3, 1
- Administer appropriate antibiotics based on culture sensitivities for at least 14 days 3, 1
- Look for clinical signs: failure to respond to initial therapy, painful skin lesions, pustules on arms/legs/trunk, yellow crusts, or discharge 3
Critical Pitfalls to Avoid
Do not administer systemic corticosteroids of group A (hydrocortisone type) as the primary treatment, as rare cases of AGEP induced by systemic prednisolone have been reported 7. Instead, use topical corticosteroids of group D1 (betamethasone dipropionate type) or D2 (hydrocortisone-17-butyrate type) for topical management 7.
- Do not confuse AGEP with other severe cutaneous adverse reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (which shows skin detachment and hemorrhagic mucosal erosions) or drug reaction with eosinophilia and systemic symptoms (DRESS, which shows organ involvement and eosinophilia) 3, 8
- Do not delay drug withdrawal while awaiting confirmatory testing, as prompt removal of the offending agent is the cornerstone of management 2, 5
- Do not underestimate atypical presentations—AGEP can initially mimic toxic shock syndrome with fever, diffuse erythema, and hypotension before classic pustules emerge 4
Refractory or Severe Cases
For severe or recalcitrant AGEP not responding to standard systemic corticosteroids:
- Consider cyclosporine as second-line systemic therapy 8
- Consider intravenous immunoglobulin (IVIG) for cases with multisystem organ involvement 8
- Obtain dermatology consultation for persistent or atypical cases 1, 3
Expected Clinical Course
AGEP typically has rapid onset after drug exposure and prompt resolution within 1-2 weeks following drug discontinuation, with a characteristic desquamative recovery phase 2, 8. The presence of sterile non-follicular pustules on an erythematous base, accompanied by neutrophilia and fever, supports the diagnosis 2, 8.