Acute Generalized Exanthematous Pustulosis

Acute generalised exanthematous pustulosis (AGEP) is an acute, febrile, pustular drug eruption, usually appearing within 48 hours of starting the offending drug, and resolving within 2 weeks.

• Incidence is 1 to 5 per million per year. Drug causes in over 90%: aminopenicillins (amoxicillin), macrolides, quinolones, hydroxychloroquine, terbinafine, diltiazem, and anti-malarials.
• Other triggers: viral infection (parvovirus, CMV, EBV), mercury exposure, and spider bites.
• Neutrophil mediated process with IL-36 and IL-8; IL36RN mutations in some patients.
• Mortality is about 2 to 5%, mostly in older and comorbid patients.

• Abrupt onset of fever (above 38 degrees Celsius) with oedematous erythema and dozens to hundreds of non-follicular, sterile, pinhead pustules (under 5 mm), starting in flexures and face, spreading to trunk and limbs.
• Burning or itch, facial oedema, and mild mucosal involvement (less than SJS/TEN).
• Pustules desquamate in 1 to 2 weeks (collarette scaling). Rare organ involvement (liver, kidney, bone marrow).

• Blood: neutrophilia (over 7 x 10^9/L), sometimes mild eosinophilia, raised CRP, mild renal or hepatic derangement, and hypocalcaemia in some.
• Skin biopsy: subcorneal or intraepidermal spongiform pustules, papillary oedema, and perivascular neutrophils and eosinophils.
• EuroSCAR validation score: morphology, course, pustule duration, histology.
• Pustule cultures sterile. Patch testing 4 to 6 weeks later may identify culprit.
• Exclude pustular psoriasis (previous history, longer course), DRESS, SJS/TEN, subcorneal pustular dermatosis, and pustular viral eruptions.

• Stop the causative drug. Most cases resolve in about 15 days.
• Supportive: antipyretics, hydration, emollients, wet dressings, antiseptic baths.
• Topical corticosteroids (clobetasol 0.05% or mometasone) once daily for 3 to 7 days to reduce inflammation and itch.
• Systemic corticosteroids (prednisolone 0.5 to 1 mg/kg for 3 to 5 days) for extensive or severe cases, with limited evidence.
• Refractory: ciclosporin 3 to 5 mg/kg, infliximab 5 mg/kg, etanercept, or spesolimab for IL-36 pathway disease (generalised pustular psoriasis overlap).
• Treat secondary infection if suspected, and monitor renal and hepatic function.
• Patch testing and allergy documentation after recovery; avoid the culprit and related agents.