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Thiopurine Skin Cancer Risk — RACP Adult Medicine MCQ

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ModerateDermatologyThiopurine Skin Cancer RiskRACP Adult Medicine

A 40-year-old man with ulcerative colitis in remission on azathioprine presents with an unusual rash: multiple non-melanoma skin cancers (squamous cell carcinomas) in sun-exposed areas. He has been on azathioprine for 8 years. What is the most likely contributing factor?

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Correct answer: D — Underlying immunodeficiency

Long-term thiopurine use (azathioprine, mercaptopurine) increases the risk of non-melanoma skin cancers (especially SCC) by 3–5 fold. The mechanism involves azathioprine's photosensitising properties (its metabolites accumulate in skin and generate reactive oxygen species on UV exposure) and impaired DNA repair. All patients on long-term thiopurines should have regular dermatological surveillance and rigorous sun protection. The risk may warrant switching to an alternative immunosuppressant in patients with multiple skin cancers.

Reference: eTG – 2025 – Gastrointestinal; Cancer Council Australia – 2023 – Keratinocyte Cancer Guidelines