A 60-year-old man with long-standing tophaceous gout and serum urate of 9.8 mg/dL is started on allopurinol 100 mg daily. Three weeks later he develops a generalized erythematous macular rash, fever (39.1°C), eosinophilia, and lymphadenopathy. Liver enzymes are elevated 5-fold. What is the most likely diagnosis?
- A Gout flare triggered by urate-lowering therapy
- B Allopurinol hypersensitivity syndrome
- C Serum sickness-like reaction to allopurinol
- D Drug reaction with eosinophilia and systemic symptoms (DRESS) ✓
Explanation
This presentation — drug rash with fever, eosinophilia, lymphadenopathy, and multi-organ involvement (hepatitis) within 2–8 weeks of starting allopurinol — is classic for DRESS syndrome (drug reaction with eosinophilia and systemic symptoms). Allopurinol is among the most common causes of DRESS, which carries significant mortality. The HLA-B*5801 allele, prevalent in Southeast Asian and Han Chinese populations, markedly increases risk. Allopurinol hypersensitivity syndrome is an older, overlapping term but DRESS is the correct current classification per RegiSCAR criteria.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.