Azathioprine myelotoxicity — SCE Rheumatology MCQ

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EasyRheumatological pharmacologyAzathioprine myelotoxicitySCE Rheumatology

A 46-year-old man with clinically quiescent vasculitis started azathioprine 4 weeks ago. His pretreatment thiopurine methyltransferase activity was below the laboratory reference range but not absent. He now presents with fever and painful oral ulceration. His neutrophil count is 0.4 × 10^9/L. What is the most likely explanation for the neutropenia?

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Correct answer: A — Azathioprine-induced bone marrow suppression

The diagnosis is azathioprine-induced bone marrow suppression. Severe neutropenia developing shortly after azathioprine initiation, together with reduced pretreatment TPMT activity, is characteristic of thiopurine myelotoxicity. Reduced TPMT activity increases exposure to cytotoxic thioguanine nucleotides and therefore the risk of leukopenia and rapid marrow suppression. Fever and oral ulceration are important manifestations of profound neutropenia and require urgent assessment for neutropenic sepsis as well as immediate interruption of azathioprine. Vasculitis relapse would require evidence of renewed organ inflammation and does not explain the pharmacogenetic association. Azathioprine hypersensitivity more typically causes fever with rash, gastrointestinal symptoms, myalgia or organ dysfunction rather than isolated profound neutropenia. Felty syndrome requires rheumatoid arthritis, usually with splenomegaly. A viral cause is less likely given the drug timing and reduced TPMT activity.

Reference: Tillomed Laboratories Ltd. Azathioprine 25 mg Film-Coated Tablets: Summary of Product Characteristics, sections 4.2, 4.4 and 4.8; text revised 2025. https://www.medicines.org.uk/emc/product/11142/smpc