Allopurinol DRESS CKD Risk HLA-B5801 — ESENeph MCQ

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ModerateChronic Kidney DiseaseAllopurinol DRESS CKD Risk HLA-B5801ESENeph

A 55-year-old man with CKD G3b (eGFR 38 mL/min/1.73m2) develops gout. He is started on allopurinol 100 mg daily and titrated up. At 300 mg daily, his serum urate is 340 umol/L (target <360). He then develops a widespread erythematous maculopapular rash, fever 39°C, facial oedema, hepatitis (ALT 5x ULN), and eosinophilia. What is this reaction?

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Correct answer: A — Allopurinol DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)

DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) is a severe delayed hypersensitivity reaction to allopurinol, typically occurring 2-8 weeks after initiation. It presents with widespread rash, fever, facial oedema, hepatitis, and eosinophilia. CKD is a major risk factor because reduced renal clearance of oxypurinol (the active metabolite) increases drug exposure. HLA-B*5801 is strongly associated with allopurinol hypersensitivity, particularly in Southeast Asian, Korean, and African American populations — screening is recommended in high-risk ethnic groups before starting allopurinol. Management: immediate allopurinol discontinuation (never rechallenge), systemic corticosteroids, and supportive care. Mortality is 5-10%.

Reference: Stamp et al 2016 – HLA-B5801 Allopurinol; MHRA 2024 – Allopurinol Safety