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Drug reactionSterile pustularICD-10 L27.0

AGEP

Acute generalised exanthematous pustulosis · pustular drug eruption

AGEP is an acute febrile sterile pustular drug reaction characterised by rapid onset (often <48 hours after antibiotics or antifungals, but up to ~11 days for other culprits such as calcium-channel blockers) of dozens to hundreds of non-follicular small pustules on background erythema, often beginning in flexures. β-lactam and macrolide antibiotics are the most frequent culprits; calcium-channel blockers, antimalarials and terbinafine are also recognised. AGEP must be distinguished from generalised pustular psoriasis, DRESS / SJS overlap, and ICI-induced pustular dermatitis. Mortality is <5% in pure AGEP.

CurrentLast reviewed 16 May 2026
Clinical image of AGEP
AGEP. Image sourced from DermNet New Zealand. Used under CC BY-NC-ND 4.0. No endorsement implied.

Aetiology

  • Onset is rapid (cf DRESS) — within ~48 hours for antibiotics, but may be longer (up to ~11 days) for other drug classes such as calcium-channel blockers.
  • Common culprits:
    • β-lactam antibiotics — amoxicillin, cephalosporins.
    • Macrolides — clarithromycin, azithromycin.
    • Calcium-channel blockers — diltiazem.
    • Antimalarials — hydroxychloroquine, chloroquine.
    • Antifungals — terbinafine.
    • Sulfonamides.
    • Paracetamol (rare).
    • Vaccines, contrast media.
    • ICI — rare but recognised.
  • IL-36 / IL-36RN pathway dysregulation overlaps with generalised pustular psoriasis; some patients carry IL36RN variants.

Clinical features (EuroSCAR criteria)

  • Rapid onset: often within 48 hours after antibiotics or antifungals, but can be later (up to ~11 days) for other culprit classes such as calcium-channel blockers.
  • Pustules: numerous (typically dozens to hundreds) small (<5 mm) non-follicular sterile pustules on background erythema.
  • Distribution: starts in flexures, then generalises.
  • Fever: typically >38°C.
  • Neutrophilia on FBC; eosinophilia in ~30%.
  • Mucosal involvement: mild or absent (cf SJS/TEN).
  • Resolution: pustules dry over 7-10 days followed by characteristic post-pustular desquamation.
  • Systemic involvement: hepatic / renal involvement in ~17% — milder than DRESS.

Investigations

  • Skin biopsy: subcorneal / intraepidermal sterile pustules with neutrophils; spongiosis; papillary dermal oedema; perivascular mixed infiltrate.
  • Pustule swab: sterile (rules out impetigo / candidiasis).
  • Bloods: neutrophilia, eosinophilia, raised CRP, mildly raised LFT in ~17%, U&E.
  • EuroSCAR scoring: confirms diagnosis (>7 points).
  • Drug history including OTC and herbal in preceding 2 weeks.
  • HLA / IL36RN testing in atypical / recurrent cases.

Differential diagnosis

  • Generalised pustular psoriasis (von Zumbusch) — personal / family history of psoriasis; recurrent flares; IL36RN mutations.
  • Subcorneal pustular dermatosis (Sneddon-Wilkinson) — chronic; hypopyon pustules.
  • DRESS — later onset (2-8 weeks); more organ involvement; pustules less prominent.
  • SJS/TEN with pustular component — mucosal involvement; full-thickness epidermal necrosis.
  • IgA pemphigus — chronic; direct immunofluorescence.
  • Bullous impetigo — bacterial; staphylococcal.
  • Candidiasis — pustule swab positive.
  • Vasculitis (pustular).

Management

  • Discontinue culprit drug immediately.
  • Symptomatic care:
    • Bland emollients.
    • Mid- to high-potency topical corticosteroids (clobetasol propionate, mometasone) — reduces pustule duration.
    • Antipyretics, fluid replacement, electrolyte management.
  • Antibiotics only if secondary bacterial infection (uncommon).
  • Systemic corticosteroids reserved for systemic involvement (organ involvement or persistent symptoms).
  • Spesolimab (anti-IL-36R; NICE TA1070 for generalised pustular psoriasis flares) — not a NICE-approved AGEP treatment, but may be discussed in exceptional severe AGEP with IL36RN-pathway involvement through specialist dermatology / immunology routes.
  • Document drug allergy; MedicAlert; counsel re class cross-reactivity.
  • Most cases resolve within 1-2 weeks of drug withdrawal.

References

  1. Sidoroff A et al. Acute generalized exanthematous pustulosis (AGEP) — a clinical reaction pattern. J Cutan Pathol. 2001;28:113-119.
  2. Sidoroff A et al. Risk factors for acute generalized exanthematous pustulosis (AGEP) — results of a multinational case-control study (EuroSCAR). Br J Dermatol. 2007;157:989-996.
  3. Szatkowski J, Schwartz RA. Acute generalized exanthematous pustulosis: a review and update. J Am Acad Dermatol. 2015;73:843-848.
  4. Hotz C et al. AGEP and IL36RN mutations: implications for management. Am J Clin Dermatol. 2020;21:1-9.

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