A 28-year-old woman with Crohn's disease (Montreal classification: ileal/ileocolic location, inflammatory behaviour, frequent relapses) is started on azathioprine. After 8 weeks, she develops fever, arthralgia, and a rash — she is suspected to have azathioprine-induced hypersensitivity. Her TPMT enzyme activity was found to be normal prior to starting. If restarted on a different thiopurine after recovery, what is the correct approach?
- A Azathioprine hypersensitivity is a class effect of thiopurines — do not restart any thiopurine
- B Switch to methotrexate as the first-line alternative immunomodulator
- C Switch to 6-mercaptopurine (6-MP) as the reaction is often azathioprine-specific, not a class effect ✓
- D Desensitise to azathioprine by restarting at 10 mg/day and gradually escalating
Explanation
Azathioprine hypersensitivity syndrome (fever, arthralgia, rash, GI symptoms) occurs in 2–5% of patients on AZA. Importantly, this reaction is often specific to azathioprine and does not represent a class effect of all thiopurines. 6-mercaptopurine (6-MP) is the active metabolite of azathioprine; the hypersensitivity is usually triggered by the imidazole side chain of azathioprine (not present in 6-MP). Studies have shown that approximately 50–70% of patients who cannot tolerate azathioprine due to non-pancreatic hypersensitivity can tolerate 6-MP. TPMT testing is relevant for myelosuppression prediction, not hypersensitivity. Methotrexate is an alternative if 6-MP is also not tolerated, particularly in Crohn's disease.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.