drug rashes

quick recognition

Feature	Morbilliform	DRESS	SJS/TEN	AGEP
morphology	pruritic macules/papules, trunk + proximal extremities	morbilliform ± exfoliative/pustules, facial oedema	bullae, skin detachment, mucosal ulceration, conjunctivitis	non-follicular pustules on erythematous base
systemic features	none	fever, eosinophilia, lymphadenopathy, organ involvement (hepatitis most common)	prodromal URTI symptoms, mucous membrane involvement	fever, neutrophilia
Nikolsky sign	negative	negative	positive	negative
onset after drug	4–14 days	2–8 weeks	1–4 weeks	hours to <5 days
duration	fades 1–2 weeks	>15 days	weeks – months	1–2 weeks
mortality	negligible	≤10%	5–40%	~5%

red flags for SCAR

• skin pain or tenderness out of proportion to appearance
• mucosal involvement (oral erosions, conjunctivitis, genital ulcers)
• blistering, skin sloughing, or positive Nikolsky sign
• facial oedema
• high fever (>38.5°C)
• lymphadenopathy
• eosinophilia or atypical lymphocytes
• elevated transaminases or creatinine
• confluent erythema (>50% BSA)

→ any of these should prompt urgent dermatology consultation

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morbilliform drug eruption

• most common drug rash (>80% of CADRs) — mimics viral exanthem
• symmetrical pruritic macules and papules on trunk and proximal extremities; mucous membranes usually spared
• onset 4–14 days after culprit drug (sooner on re-exposure)
• common culprits: aminopenicillins, cephalosporins, sulfonamides, allopurinol, AEDs
• fades over 1–2 weeks after drug withdrawal

• management: antihistamines (second-generation preferred), topical corticosteroids; consider stopping drug

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DRESS (drug reaction with eosinophilia and systemic symptoms)

• longest latency of all SCARs — onset 2–8 weeks after drug; lasts >15 days
• triad: fever + rash + internal organ involvement
• morbilliform rash ± exfoliative or pustular features; may progress to erythroderma
• facial oedema (characteristic), fever, eosinophilia, atypical lymphocytes, lymphadenopathy
• organ involvement — hepatitis most common; also nephritis, pneumonitis, myocarditis
• associated with HHV-6 reactivation
• RegiSCAR score for diagnosis (fever, lymphadenopathy, eosinophilia, atypical lymphocytes, skin involvement, organ involvement, resolution >15 days)
• mortality ≤10%

management

• stop the drug
• systemic corticosteroids (prednisone 0.5–1 mg/kg/day) with slow taper over weeks to months ± IVIG
• steroid-sparing agents (cyclosporine, mycophenolate) for refractory cases
• monitor for organ involvement (LFTs, creatinine, CBC, cardiac enzymes)

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SJS/TEN (Stevens-Johnson syndrome / toxic epidermal necrolysis)

• prodromal URTI symptoms → targetoid lesions with dusky centre → bullae → mucosal ulceration, conjunctivitis, skin detachment
• Nikolsky sign positive (lateral pressure causes epidermal separation)
• differentiated by epidermal detachment %BSA:
  • SJS — <10%
  • SJS/TEN overlap — 10–30%
  • TEN — ≥30%
• onset typically 1–4 weeks after drug; lasts weeks – months
• mortality 5–40% (higher with greater BSA involvement)

SCORTEN prognostic score

Assess within 24 hours — each parameter = 1 point:

Parameter
age ≥40 years
heart rate ≥120 bpm
active cancer or haematological malignancy
BSA detached >10%
serum urea >10 mmol/L
serum bicarbonate <20 mmol/L
serum glucose >14 mmol/L

SCORTEN	predicted mortality
0–1	3.2%
2	12.1%
3	35.3%
4	58.3%
≥5	90%

management

• stop the drug immediately — early withdrawal reduces mortality
• supportive care in ICU or burn unit (wound care, fluids, nutrition, pain)
• ophthalmology consultation — ocular involvement can cause permanent sequelae
• immunomodulatory therapy — cyclosporine, corticosteroids, infliximab (Remicade), etanercept (Enbrel) — multidisciplinary decision; no consensus on best agent

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AGEP (acute generalised exanthematous pustulosis)

• shortest latency of all SCARs — hours to <5 days after drug
• dozens to hundreds of small, non-follicular sterile pustules on an erythematous base
• fever, neutrophilia (not eosinophilia)
• ~25% have oral mucosal involvement
• common culprits: aminopenicillins, macrolides, hydroxychloroquine, diltiazem
• usually self-resolves within 1–2 weeks of drug withdrawal
• management: stop drug, topical corticosteroids; systemic corticosteroids for severe/widespread cases
• mortality ~5%

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risk factors

• HIV/AIDS — markedly increased risk, especially with TMP/SMX
• EBV/infectious mononucleosis (aminopenicillin rash)
• prior drug allergy
• autoimmune disease (SLE, psoriasis)
• malignancy, bone marrow transplant recipients

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HLA screening

HLA allele	Drug	Reaction	At-risk population	Screening
HLA-B*57:01	abacavir	hypersensitivity syndrome	all	mandatory
HLA-B*15:02	carbamazepine	SJS/TEN	Southeast Asian	recommended
HLA-B*58:01	allopurinol	SJS/TEN/DRESS	Southeast Asian, African American	recommended
HLA-A*31:01	carbamazepine	DRESS/morbilliform	European, Japanese	consider

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what NOT to do

• rechallenge with culprit drug after DRESS or SJS/TEN
• dismiss a drug rash as “just a rash” without checking for systemic features (fever, eosinophilia, organ involvement, mucosal disease)
• anchor on drug rash without considering non-drug causes (viral exanthem, primary dermatologic conditions)
• continue a culprit drug through SJS/TEN or DRESS — delay in stopping increases mortality