Pharmacology, Toxicology and Addiction MedicineTier 2Approach to a presentation

Unusual (idiosyncratic, Type B) adverse drug reactions, e.g. Stevens-Johnson Syndrome

Red flags

Signs of a severe, rapidly progressing idiosyncratic reaction (mucocutaneous involvement with skin sloughing, systemic organ involvement, high fever) require immediate causative drug cessation and urgent specialist (dermatology/burns unit) referral, since progression can be rapid and mortality significant with conditions like Stevens-Johnson syndrome/toxic epidermal necrolysis

Differential by mechanism

Stevens-Johnson syndrome/toxic epidermal necrolysis (severe mucocutaneous reaction with skin detachment, classically from specific high-risk drugs - anticonvulsants, allopurinol, certain antibiotics, NSAIDs)

DRESS syndrome (drug reaction with eosinophilia and systemic symptoms - delayed onset, multi-organ involvement)

Simple morbilliform drug rash (the common, generally benign mimicker requiring careful distinction from the severe reactions above)

Anaphylaxis (a distinct, immediate-type Type B reaction requiring its own recognition pattern)

Focused history

Timing relative to drug exposure (Type B reactions are often delayed, sometimes 1-3 weeks after starting a new drug, distinct from immediate hypersensitivity reactions), specific culprit drug identification (recent new medications, particularly high-risk agents), rash evolution and associated symptoms (fever, mucosal involvement, eye symptoms, lymphadenopathy)
Type B reactions are, by definition, unpredictable and not clearly dose-related, unlike Type A (augmented, dose-related) reactions - this distinction should inform the index of suspicion regardless of the dose being used

Focused examination

Full skin examination including mucosal surfaces (oral, genital, ocular) given mucosal involvement's significance for distinguishing severe reactions from simple morbilliform rash
Systemic assessment (fever, lymphadenopathy, organ-specific signs) given the multi-system nature of severe idiosyncratic reactions like DRESS and SJS/TEN

Investigation strategy

Skin biopsy can support diagnosis and severity assessment in ambiguous or severe presentations
Full blood count, liver/renal function, and eosinophil count particularly relevant to DRESS syndrome given its characteristic organ involvement and eosinophilia
Naranjo scale application (see ) supports structured causality assessment when multiple concurrent drugs are potential culprits

Management

Immediate cessation of the suspected causative drug is the essential first step regardless of reaction severity, given ongoing exposure worsens outcomes
Severe reactions (SJS/TEN, DRESS): urgent specialist referral (dermatology, sometimes burns unit for extensive TEN), supportive care, and consideration of specific treatments (varies by condition and severity)
Permanent avoidance of the causative drug and structurally related agents given the risk of recurrence, often more severe, on re-exposure

Traps

Continuing the suspected causative drug while awaiting confirmation - any delay worsens outcomes in severe idiosyncratic reactions

Missing mucosal involvement as the key distinguishing feature between a benign morbilliform rash and a severe, potentially life-threatening reaction

Underestimating DRESS syndrome given its potentially delayed, insidious onset and multi-organ (not just skin) involvement, which can be misattributed to another cause if drug exposure timing isn't specifically considered

Talk track

"This looks like it could be a serious reaction to one of your medications rather than a simple rash, so we need to stop that medication immediately and get a specialist skin assessment - this type of reaction is unpredictable and not related to the dose you were taking, and once we identify the specific cause, you'll need to avoid that medication and related ones permanently."

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