Exanthematous Drug Eruption

Morbiliform / Maculopapular DE — Most common form of drug-induced skin reaction, characterized by symmetric, generalized erythematous macules and papules, resembling a measles-like rash, typically appearing 1–2 weeks after initial drug exposure

Epidemiology

  • Accounts for ~90% of drug eruptions
  • More common in adults
  • Higher risk among patients receiving multiple medications or with viral infections (e.g., EBV in ampicillin reaction)

Aetiology

Drug Category
Examples
Beta-lactam antibiotics
Penicillins, Ampicillin, Amoxicillin, Cephalosporins
Sulfonamides
Cotrimoxazole
Anticonvulsants
Phenytoin, Carbamazepine, Lamotrigine
Allopurinol
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NSAIDs
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Antiretrovirals
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Pathogenesis

  • Type IV (delayed) hypersensitivity reaction
  • Mediated primarily by T lymphocytes
  • Antigen-presenting cells process the drug → T-cell activation → cytokine release (IL-2, IFN-γ) → inflammation → diffuse rash

Timeline

Exposure
Onset
First exposure
7–14 days
Re-exposure
1–3 days

Clinical presentation

Skin Manifestation

  • Maculopapular erythematous rash
  • Starts on trunk → spreads to limbs, often sparing the face initially
  • Symmetrical distribution
  • Lesions may coalesce in severe cases
  • Pruritus common
  • May have mild fever and malaise
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Associated Mucosal/Systemic findings

  • Mucosal involvement typically absent or mild
  • Systemic symptoms rare (unlike SJS/TEN or DRESS)

Investigations

Primarily clinical, based on temporal relationship with medication and rash pattern.

Helpful clues

  • New drug introduced within past 1–2 weeks
  • Rash improves when the drug is stopped
  • No mucosal erosions or systemic organ involvement

Investigations (if needed)

Test
Use
CBC
Eosinophilia may be present
LFT, RFT
To exclude severe drug reactions like DRESS
Skin biopsy
Spongiotic dermatitis, lymphocytic infiltrate around vessels

Management

Identify and discontinue the causative drug

Most important for resolution.

Symptomatic therapy

Treatment
Purpose
Oral antihistamines
Reduce pruritus
Topical corticosteroids
Control inflammation
Emollients
Repair skin barrier
Systemic steroids
Consider only in severe extensive cases

Monitoring

  • Observe for progression to severe drug reactions
  • Educate patient to avoid re-exposure to the drug

Resolution

  • Rash resolves in 1–2 weeks after drug cessation
  • May leave temporary post-inflammatory hyperpigmentation or desquamation