Elderly patient with pruritic eruption and new renal impairment on a new drug
An 81-year-old man with hypertension and gout is admitted with a 10-day history of a widespread pruritic eruption. He started allopurinol 3 weeks ago for a gout flare. Examination shows confluent erythematous macules with dusky centers on the trunk and limbs, early epidermal detachment on the upper back (Nikolsky sign positive in one area), oral erosions, and 2 days of fever (38.9 C). Labs: creatinine 210 micromol/L (baseline 95), eGFR 30, ALT 110 U/L, eosinophils 1.4 x 10^9/L. He is on furosemide, amlodipine, and colchicine. He is hemodynamically stable but tachycardic at 104/min.
1. What is the leading diagnosis, and which features in the history and examination are most discriminating?
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The leading diagnosis is drug reaction with eosinophilia and systemic symptoms (DRESS) or early Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN); the discriminating features point toward DRESS with early skin detachment, but SJS/TEN must be excluded.
Key discriminating features:
- Allopurinol is a classic culprit for both DRESS and SJS/TEN, especially in older patients with renal impairment (a known risk factor for allopurinol hypersensitivity).
- Eosinophilia (1.4 x 10^9/L) and renal and hepatic involvement favor DRESS.
- Mucosal erosions and a positive Nikolsky sign with epidermal detachment favor SJS/TEN and are atypical for DRESS (though DRESS can have mucosal involvement and edema).
- Timing (3 weeks) fits both (DRESS typically 2-8 weeks; SJS/TEN 4-28 days).
- Fever and tachycardia are nonspecific but support a severe cutaneous adverse reaction.
The overlap means the patient needs urgent dermatology and, ideally, dermatopathology input. Do not rely on a single feature.
2. Outline your immediate management, including drug withdrawal, investigations, and supportive care, and explain how you would resolve the diagnostic uncertainty.
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Immediate management:
- Stop allopurinol and colchicine (colchicine can cause cytopenias and is renally cleared; hold until renal function clarified). Continue essential antihypertensives.
- Fluid and electrolyte resuscitation, monitor urine output, and involve nephrology given AKI.
- Wound care for any detachment; avoid adhesives; keep the patient warm; involve a burns unit or ICU early if body surface area detachment increases.
- Analgesia and antipyretics; avoid NSAIDs if renal function impaired.
Investigations: FBC with differential, U&E, LFTs, CRP, blood cultures, urinalysis, and skin biopsy for histopathology and direct immunofluorescence (to exclude autoimmune blistering). Consider HLA-B*58:01 status (relevant to allopurinol hypersensitivity in some populations) and viral serology (HHV-6, CMV, EBV) if DRESS is suspected.
Resolving diagnostic uncertainty: The biopsy is the key discriminator. SJS/TEN shows full-thickness epidermal necrosis with sparse dermal infiltrate; DRESS shows a perivascular lymphocytic infiltrate with eosinophils and interface change without full-thickness necrosis. If there is any doubt or significant detachment, manage as SJS/TEN until proven otherwise (higher mortality, need for early transfer).
Drug therapy: If DRESS is confirmed, systemic corticosteroids (e.g., prednisolone 0.5-1 mg/kg/day) with slow taper; if SJS/TEN, early transfer to a burns/ICU unit and consider immunomodulation per local protocol (e.g., cyclosporine or etanercept) in discussion with specialists. Do not start empiric high-dose steroids before the diagnosis is clarified if SJS/TEN is possible.