Morbilliform Drug Eruption (Maculopapular/Exanthematous Drug Eruption)
Definition
- Most common form of drug-induced rash (~95% of drug eruptions).
- Resembles viral exanthems; symmetric, widespread red maculopapular rash.
- Delayed Type IV hypersensitivity (T-cell-mediated).
| Type | Mechanism | Time | Immune Mediators | Example Conditions |
|---|---|---|---|---|
| I | IgE-mediated degranulation of mast cells & basophils | Immediate (minutes) | IgE, histamine, leukotrienes | Anaphylaxis, allergic rhinitis, urticaria, asthma |
| II | Antibody (IgG/IgM)-mediated cell destruction via complement or ADCC | Minutes to hours | IgG/IgM, complement, NK cells | Autoimmune haemolytic anaemia, Goodpasture’s syndrome, Graves’ disease |
| III | Immune complex deposition → complement activation & inflammation | Hours to days | IgG, complement, neutrophils | SLE, post-streptococcal GN, serum sickness, Arthus reaction |
| IV | T-cell mediated cytotoxicity or cytokine-mediated inflammation | Delayed (48–72 hrs) | T cells (CD4+ or CD8+), macrophages | Contact dermatitis, tuberculin reaction, Type 1 diabetes, MS |
Who Gets It
- Occurs in ~2% of people started on a new medication.
- Common offending drugs:
- Antibiotics (penicillins, cephalosporins, sulfonamides)
- Allopurinol
- Antiepileptics (phenytoin, carbamazepine, lamotrigine)
- NSAIDs
- Herbal/natural therapies
Risk Factors
- Previous drug reaction or FHx of drug eruptions
- Viral infections (EBV, HHV-6/7)
- Immunodeficiency (HIV, autoimmune disease, CF)
- Polypharmacy
Pathophysiology
- Type IV hypersensitivity → cytotoxic T-cell activation
- Inflammatory cytokine release directed at drug/metabolite or haptenated self-proteins
Clinical Features
- Latency:
- 1–2 weeks after first drug exposure
- 1–3 days if previously sensitised
- Distribution:
- Starts on trunk → spreads to limbs/neck
- Bilateral, symmetrical
- Morphology:
- Pink/red macules or papules → coalesce into patches/plaques
- +/- blanching (purpura may appear on legs)
- May mimic urticaria, target lesions, annular or polymorphous rashes
- Sparing of axillae/groin typical, unless SDRIFE pattern
- Systemic:
- ± Low-grade fever, pruritus
- Peeling (desquamation) as rash resolves
Complications (Red Flags for SCAR)
Consider SCAR if any of the following:
- Mucosal involvement
- Blisters or skin sloughing
- Painful rash
- Systemic symptoms (fever >38.5°C, malaise)
- Facial oedema
- Pustules → consider AGEP
- Eosinophilia, organ dysfunction → consider DRESS
- Generalised purpura/palpable purpura
- Erythroderma
Diagnosis
- Clinical: Temporal association with new medication
- Drug Calendar: Start date vs. rash onset
- Tests (if needed):
- CBC, LFTs, UECs, CRP
- Serology for viral mimics
- Skin biopsy (if uncertain): Interface dermatitis ± eosinophils
- No confirmatory test available for causative drug
❗ Differential Diagnosis
- Viral exanthems (measles, rubella, roseola)
- Scarlet fever
- Kawasaki disease
- Toxic erythema of infection
- GvHD
- Autoimmune/connective tissue disease
Treatment
- Withdraw culprit drug (if safe to do so)
- Symptomatic:
- Topical corticosteroids
- Emollients
- Wet wraps (for extensive inflammation)
- Oral antihistamines (limited efficacy)
- Specialist input if:
- Drug is essential or high suspicion for SCAR
Prognosis
- If drug ceased → rash improves in 48h, resolves in 1–2 weeks
- If drug continued:
- May resolve, persist, or progress to SCAR/erythroderma
Prevention
- Document allergy in medical record
- Educate patient re: re-exposure risk
- Avoid unnecessary antibiotic or high-risk drug use
References
- DermNet NZ (Dr Delwyn Dyall-Smith, A/Prof Amanda Oakley)
- Adapted for Australian clinical practice