What is the treatment for generalized exanthematous pustulosis?

Treatment of Acute Generalized Exanthematous Pustulosis (AGEP)

The cornerstone of AGEP treatment is immediate discontinuation of the offending drug, which leads to spontaneous resolution in all cases, with systemic corticosteroids recommended for severe disease (>30% body surface area involvement) to reduce hospital length of stay. 1, 2

Immediate Management Steps

Drug Withdrawal

• Identify and stop all potential causative medications immediately - this is the single most critical intervention, as AGEP is self-limiting once the trigger is removed 1, 3, 4
• Antibiotics (particularly penicillins, cephalosporins, and vancomycin) are the most common culprits, accounting for >90% of cases 2, 4
• Document the causative agent in the medical record and educate the patient about future avoidance 3

Severity Assessment

• Evaluate body surface area (BSA) involvement: mild-moderate (10-30% BSA) versus severe (>30% BSA) 1
• Check for systemic involvement including fever, malaise, and organ dysfunction (occurs in approximately 14% of cases) 1, 2
• Obtain vital signs including temperature and oxygen saturation 3

Treatment Algorithm Based on Severity

Mild to Moderate AGEP (10-30% BSA)

• Apply topical low to moderate potency corticosteroids to affected areas 1, 4
• Provide supportive care with gentle skin care and emollients 1
• Maintain adequate hydration and electrolyte balance 3
• Consider oral antihistamines for severe pruritus 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 1
• Hospitalize for close monitoring and supportive care 3, 2
• Systemic corticosteroid treatment significantly reduces hospital length of stay (p=0.035) compared to topical treatment alone 2

Important caveat: While systemic corticosteroids are widely used and reduce hospitalization time, strong evidence for their effectiveness is limited - however, expert consensus and clinical experience support their use in severe cases 5

Management of Complications

Secondary Infection

• Obtain bacterial cultures before starting antimicrobial therapy if infection is suspected (look for failure to respond to initial treatment, painful lesions, yellow crusts, or discharge) 1, 3
• Administer appropriate antibiotics based on culture sensitivities for at least 14 days 1

Refractory Pruritus

• Trial gabapentin or pregabalin for severe pruritus not controlled by antihistamines 1

Diagnostic Confirmation

• Perform skin biopsy from lesional skin adjacent to a pustule showing characteristic intraepidermal pustules with neutrophilic and eosinophilic infiltration 3, 4
• Consider second biopsy for direct immunofluorescence to exclude immunobullous disorders (IgA pemphigus, bullous pemphigoid) 3

Follow-up Protocol

• Reassess after 2 weeks of initial therapy 1
• Expect resolution with desquamation typically within days to 2 weeks after drug withdrawal 6, 4
• If no improvement or worsening occurs, reconsider the diagnosis or escalate treatment 1
• Consult dermatology for persistent or severe cases 1

Special Considerations for Immunotherapy-Related AGEP

• Hold immune checkpoint inhibitor therapy until resolution to grade 1 if AGEP is immunotherapy-related 7, 1
• This is a rare but potentially lethal adverse event requiring immediate recognition 7

Prognosis

• Mortality attributed to AGEP is extremely rare to absent in modern case series 2
• All cases resolve with cessation of the offending drug 2, 4
• Skin lesions typically resolve by desquamation within 3 days to 2 weeks 6, 4