Pharmacology, Toxicology and Addiction MedicineTier 1Approach to a presentation

Associated with adverse drug interactions - cutaneous reactions

Red flags

Mucosal involvement + skin sloughing + fever - SJS/TEN
Nikolsky sign positive
Facial oedema, eosinophilia, fever, lymphadenopathy 2-8 weeks after starting a new drug - DRESS
Rapidly progressing pustular rash with fever - AGEP
Any severe cutaneous adverse reaction (SCAR) with organ involvement (transaminitis, AKI)

Differential by mechanism

Severe cutaneous adverse reactions (SCARs)

SJS/TEN - sulfonamides, allopurinol, anticonvulsants (carbamazepine, lamotrigine, phenytoin), NSAIDs, nevirapine. *HLA-B1502 (carbamazepine) and HLA-B5801 (allopurinol)* risk alleles in relevant ethnic groups
DRESS - anticonvulsants, allopurinol, sulfonamides, minocycline; 2-8 week latency, eosinophilia, visceral involvement
AGEP - beta-lactams, diltiazem; rapid onset (<48h), pustules, fever, neutrophilia

Morbilliform/exanthematous (commonest)

Beta-lactams (esp. amoxicillin with concurrent EBV), sulfonamides, anticonvulsants

Urticaria/angioedema

Beta-lactams (IgE-mediated), NSAIDs/aspirin (non-immune COX inhibition), ACE-inhibitors (bradykinin-mediated angioedema, no urticaria)

Fixed drug eruption

NSAIDs, tetracyclines, sulfonamides - recurs at the same site on re-exposure

Photosensitivity

Tetracyclines, thiazides, amiodarone, NSAIDs

Vasculitic/purpuric

Hydralazine, propylthiouracil (ANCA-associated), penicillins

Focused history

Precise timeline from drug start to rash onset (fixed drug eruption = hours to a day; DRESS = weeks)
Mucosal symptoms - eye, mouth, genital pain/erosions
Fever, sore throat preceding rash (SJS prodrome)
Prior reaction to same/related drug class
HIV status, HLA testing where relevant to specific drugs

Focused examination

Body surface area involved, mucosal surfaces (eyes, mouth, genitals)
Nikolsky sign (lateral pressure sloughs epidermis) - SJS/TEN
Facial oedema, lymphadenopathy - DRESS
Pustules on erythematous base - AGEP
Target lesions vs confluent erythema with blistering

Investigation strategy

FBE (eosinophilia - DRESS), LFT, UEC/creatinine (organ involvement)
SCORTEN score for TEN prognostication
Skin biopsy if diagnosis uncertain
HLA typing retrospectively/prospectively for high-risk drugs in relevant populations

Management

1. Stop the culprit drug immediately - the single most important step

Identify and permanently document/allergy-list the causative agent

2. SJS/TEN

Burns-unit/ICU-level supportive care, fluid and electrolyte management, wound care
IVIG or ciclosporin considered in specialist centres; no universally agreed disease-modifying therapy
Ophthalmology review early - prevent long-term scarring

3. DRESS

Systemic corticosteroids, prolonged taper (relapse common if tapered too fast)
Monitor for delayed organ involvement (thyroiditis, myocarditis) for months after

4. AGEP

Supportive care, resolves within days to weeks after drug cessation

5. Milder reactions

Antihistamines, topical steroids for morbilliform/urticarial reactions; document allergy

Traps

Continuing the culprit drug "to see if it settles" in a SCAR is dangerous - stop first, ask questions later
Amoxicillin rash in the setting of EBV/glandular fever is not a true allergy - don't label for life
ACE-inhibitor angioedema has no urticaria and does not respond to adrenaline/antihistamines reliably - mechanism is bradykinin, not histamine
DRESS can relapse weeks after apparent resolution if steroids tapered too quickly

Talk track

1. Mucosal involvement changes everything

"Skin plus mucosal erosions and fever is SJS/TEN until proven otherwise - the drug stops now."

2. Timing tells you the syndrome

"Hours to a fixed drug eruption, days to AGEP, weeks to DRESS - the latency is diagnostic."

7 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.

Get premium access