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Methotrexate-associated myelosuppression with suspected neutropenic sepsis — MSRA MCQ

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Hardall topics relevant for this examMethotrexate-associated myelosuppression with suspected neutropenic sepsisMSRA

A 64-year-old woman with rheumatoid arthritis takes methotrexate 20 mg once weekly and folic acid 5 mg once weekly. Her renal function and routine full blood count were normal 1 month ago. Five days ago, an out-of-hours clinician prescribed trimethoprim for presumed uncomplicated urinary tract infection. She now presents with a temperature of 38.3°C, rigors, severe sore throat, painful mouth ulcers and new widespread bruising. She is alert, her blood pressure is 118/72 mmHg and pulse is 102 beats/minute. Same-day blood results, available during the consultation, show neutrophils 0.4 × 10⁹/L, platelets 68 × 10⁹/L and haemoglobin 94 g/L. What is the most appropriate management now?

Educational content. Not a substitute for clinical judgement or local policy.

Reveal the answer and explanation

Correct answer: E — Stop trimethoprim and methotrexate, and arrange immediate hospital assessment for suspected neutropenic sepsis

Explanation lettering: D = shown as A · A = shown as C · E = shown as D · C = shown as E

This patient has probable severe methotrexate toxicity precipitated by trimethoprim. Trimethoprim and methotrexate have additive antifolate effects, and concurrent use can cause severe bone marrow suppression. Her mucositis, bruising and pancytopenia support this diagnosis. More importantly, she has a neutrophil count of 0.4 × 10⁹/L and a temperature above 38°C. This fulfils the clinical picture of neutropenic sepsis and requires immediate secondary-care assessment; stable blood pressure does not justify community observation or oral treatment. Trimethoprim and methotrexate should both be stopped pending specialist assessment. A is unsafe because confirmed febrile neutropenia requires immediate hospital assessment rather than repeat testing. B is attractive because an antibiotic is needed, but oral community antibiotics must not delay emergency assessment and treatment. D addresses the antifolate mechanism but does not manage febrile neutropenia. E is unsafe because trimethoprim is the interacting drug and urgent rheumatology advice is not an appropriate substitute for emergency hospital management.

Reference: Managing interactions with methotrexate – NHS Specialist Pharmacy Service (Updated 30 June 2025) — https://sps.nhs.uk/articles/managing-interactions-with-methotrexate/ Suspected sepsis in people aged 16 or over: recognition, assessment and early management – Could this be sepsis? (2025) — https://www.nice.org.uk/guidance/NG253/chapter/could-this-be-sepsis