Key Facts

Drug eruptions are among the most common adverse drug reactions and a frequent cause of dermatology consultation. Distinguishing mild from severe reactions is critical, as severe cutaneous adverse reactions (SCARs) carry significant mortality.

Epidemiology

• Cutaneous adverse drug reactions occur in ~2–3% of hospitalised patients
• Morbilliform eruption: most common (~75%)
• SJS/TEN: rare (~1–6 per million/year) but potentially fatal
• DRESS: rare (~1 per 10,000 exposures to high-risk drugs)

Aetiology

Common causative drugs:

• Antibiotics: penicillins, cephalosporins, sulfonamides (co-trimoxazole)
• Anticonvulsants: carbamazepine, phenytoin, lamotrigine
• Allopurinol
• NSAIDs
• Antiretrovirals: nevirapine, abacavir

Pathophysiology

• Type A (dose-dependent): predictable, pharmacological - e.g. steroid-induced acne
• Type B (idiosyncratic): unpredictable, immune-mediated - e.g. SJS/TEN, DRESS
• Immune mechanisms:
  • Type I (IgE-mediated): urticaria, anaphylaxis - minutes to hours
  • Type IV (T-cell mediated): morbilliform, SJS/TEN, DRESS - days to weeks
• HLA associations: HLA-B5701 → abacavir hypersensitivity; HLA-B5801 → allopurinol DRESS/SJS; HLA-A*3101 → carbamazepine

Morbilliform (Exanthematous) Eruption

• Widespread, symmetrical, erythematous macules and papules
• Often starts on trunk, spreads to limbs
• Onset 7–14 days after drug initiation (or 1–2 days on re-exposure)
• Mild pruritus; no mucosal involvement
• Resolves with desquamation after drug withdrawal

Fixed Drug Eruption

• Well-demarcated, round, violaceous/brown patch
• Recurs at SAME site on re-exposure - classic exam clue
• Common sites: lips, genitalia, hands
• Causative drugs: co-trimoxazole, NSAIDs, paracetamol, tetracyclines

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)

• Onset 2–8 weeks after drug initiation
• High fever, widespread maculopapular rash (may become oedematous/purpuric)
• Facial oedema
• Lymphadenopathy
• Eosinophilia (>1.5 × 10⁹/L) and/or atypical lymphocytes
• Organ involvement: hepatitis (most common), nephritis, pneumonitis, myocarditis
• RegiSCAR scoring system for diagnosis

AGEP

• Acute onset widespread sterile pustules on erythematous base
• Fever, neutrophilia
• Usually 1–3 days after drug (commonly antibiotics - penicillins, macrolides)
• Resolves rapidly after drug withdrawal

Red Flags - Severe Cutaneous Adverse Reactions (SCARs)

• Mucosal involvement (eyes, mouth, genitals) → SJS/TEN
• Skin pain/tenderness out of proportion → TEN
• Facial oedema + eosinophilia + organ dysfunction → DRESS
• Nikolsky sign positive → SJS/TEN
• Widespread pustules + fever → AGEP

Bedside

• Full drug history: timeline of all medications vs rash onset - crucial
• Clinical photography: document rash pattern and extent
• BSA assessment: percentage of skin involvement (SJS/TEN grading)
• Nikolsky sign: if epidermal detachment suspected

Bloods

• FBC with differential: eosinophilia (DRESS), neutrophilia (AGEP)
• LFTs: hepatitis (DRESS)
• U&Es, creatinine: renal involvement (DRESS)
• CRP: systemic inflammation
• Blood film: atypical lymphocytes (DRESS - may mimic lymphoma)

Biopsy

• Skin biopsy: helpful when diagnosis uncertain - interface dermatitis (drug eruption), subcorneal pustules (AGEP), full-thickness necrosis (TEN)

Special Tests

• Patch testing: can identify causative drug in delayed reactions (specialist centres - performed 6 weeks after resolution)
• Drug-specific lymphocyte stimulation test: research tool
• HLA typing: before starting high-risk drugs (e.g. HLA-B5701 before abacavir; HLA-B5801 before allopurinol in high-risk populations)
• MHRA Yellow Card reporting: report ALL suspected ADRs

General Principles

• Withdraw the suspected drug IMMEDIATELY - cornerstone of management
• Document allergy clearly in notes, drug chart, and electronic records
• Supportive care: emollients, antihistamines for pruritus

Morbilliform Eruption

• Withdraw drug
• Emollients, topical corticosteroids, oral antihistamines
• Resolves over 1–2 weeks

Fixed Drug Eruption

• Withdraw drug; avoid future exposure
• Potent topical corticosteroid for residual pigmentation/inflammation

DRESS

• Withdraw drug immediately
• Systemic corticosteroids: prednisolone 0.5–1 mg/kg/day - taper slowly over months (risk of flare on rapid withdrawal)
• Monitor organ function: LFTs, U&Es, echocardiogram if myocarditis suspected
• Screen for HHV-6 reactivation (common in DRESS)
• Long taper (3–6 months) often needed

AGEP

• Withdraw drug - usually self-resolves within 1–2 weeks
• Supportive: emollients, antipyretics
• Short course topical steroids if symptomatic

SJS/TEN - See dedicated topic

Referral Criteria

• Dermatology: diagnostic uncertainty, suspected SCAR, patch testing referral
• Burns unit/ICU: TEN (managed as burn patient)
• Allergy clinic: future drug avoidance counselling, cross-reactivity assessment

• Morbilliform: resolves within 1–2 weeks of drug withdrawal; excellent prognosis
• Fixed drug eruption: recurs on re-exposure; post-inflammatory hyperpigmentation may persist
• DRESS: mortality ~5–10%; organ involvement determines severity; may take months to resolve
• AGEP: excellent prognosis; self-resolves in 1–2 weeks after drug withdrawal
• SJS: mortality ~5%; TEN: mortality ~25–30%
• Drug allergy documentation prevents recurrence - lifelong avoidance necessary

Drug Eruption Classification

High-Risk Drugs for Severe Reactions