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Acute generalised exanthematous pustulosis (AGEP) - drug allergy

Authoring team

Signs and allergic patterns of suspected drug allergy with timing of onset

Immediate, rapidly evolving reactions

  • Anaphylaxis - a severe multi-system reaction characterised by:
    • erythema, urticaria or angioedema and
    • hypotension and/or bronchospasm
  • Urticaria or angioedema without systemic features
  • Exacerbation of asthma (for example, with non-steroidal anti-inflammatory drugs [NSAIDs])

Onset usually less than 1 hour after drug exposure (previous exposure not always confirmed)

Non-immediate reactions without systemic involvement

  • Widespread red macules or papules (exanthema-like)
  • Fixed drug eruption (localised inflamed skin)

Onset usually 6-10 days after first drug exposure or within 3 days of second exposure

Non-immediate reactions with systemic involvement

Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome (DHS) characterised by:

  • widespread red macules, papules or erythroderma
  • fever
  • lymphadenopathy
  • liver dysfunction
  • eosinophilia

Onset usually 2-6 weeks after first drug exposure or within 3 days of second exposure

Toxic epidermal necrolysis or Stevens-Johnson syndrome characterised by:

  • painful rash and fever (often early signs)
  • mucosal or cutaneous erosions vesicles, blistering or epidermal detachment
  • red purpuric macules or erythema multiforme

Onset usually 7-14 days after first drug exposure or within 3 days of second exposure

Acute generalised exanthematous pustulosis (AGEP) characterised by:

  • widespread pustules
  • fever
  • neutrophilia

Onset usually 3-5 days after first drug exposure

Common disorders caused, rarely, by drug allergy:

  • eczema
  • hepatitis
  • nephritis
  • photosensitivity vasculitis

Time of onset variable

With respect to DRESS, study evidence (2) found:

  • most common drug causes were found to be antibiotics (74%) and anticonvulsants (21%)
  • most common comorbidities were epilepsy (26%) and hypertension (26%)

A study analysed patients with DRESS reported through the US Food and Drug Administration Adverse Event Reporting System (FAERS) (3):

  • total of 26 831 patients with DRESS were identified, of which 99.67% were classified as having a serious adverse reaction
    • overall mortality was 6.9% (1846 deaths)
    • female patients were more frequently affected than male patients
    • adults aged 18–64 years represented the largest group
    • allopurinol, lamotrigine and vancomycin were the most frequently suspected drugs, accounting for over 30% of reports

Reference:

  1. NICE (September 2014). Drug allergy: diagnosis and management of drug allergy in adults, children and young people
  2. Del Pozzo-Magana, BR, Rieder, MJ, Garcia-Bournissen, F, Lazo-Langner, A. Drug reaction with eosinophilia and systemic symptoms (DRESS): A tertiary care centre retrospective study. Br J Clin Pharmacol. 2022; 1- 8. doi:10.1111/bcp.15354
  3. Castellana E, Chiappetta MR. Drug rash with eosinophilia and systemic symptoms: descriptive analysis of pharmacovigilance. European Journal of Hospital Pharmacy Published Online First: 22 January 2026.

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