Persistent Oral Ulceration in a Patient on Methotrexate
A 58-year-old woman attends with a 5-week history of a painful ulcer on the left lateral tongue. She has rheumatoid arthritis managed with methotrexate 20 mg weekly and folic acid 5 mg on non-methotrexate days. She also takes ramipril and occasional ibuprofen. She reports unintentional weight loss of 4 kg and a 30 pack-year smoking history, having quit 2 years ago. Examination shows a 2.2 cm ulcer with rolled, indurated margins and a fixed, non-tender ipsilateral submandibular node measuring 1.5 cm. Full blood count shows macrocytosis with mean corpuscular volume 108 fL. She asks whether the ulcer is a methotrexate side effect and whether she can simply stop the drug and wait.
1. How should you interpret the ulcer and the macrocytosis, and what is the immediate management priority?
Read the worked answer
The ulcer is not adequately explained as a simple methotrexate mucositis. Drug-induced ulceration is usually widespread, symmetrical, and resolves on withdrawal; a single 2.2 cm ulcer with rolled, indurated margins persisting 5 weeks, plus a fixed ipsilateral node and weight loss, meets urgent referral criteria for suspected oral squamous cell carcinoma. The macrocytosis is a separate clue: methotrexate blocks dihydrofolate reductase, and despite folic acid supplementation a raised MCV suggests folate depletion or drug effect and should prompt checking full blood count, folate, B12, liver and renal function. Immediate priority is an urgent two-week suspected-cancer referral for biopsy and staging, not a therapeutic trial of stopping methotrexate. Stopping methotrexate without rheumatology input risks a disease flare and is not diagnostic. You should explain that a trial of withdrawal would delay cancer diagnosis, arrange the referral the same day, and communicate with the rheumatologist about the abnormal blood indices.
2. The patient asks whether she should stop ibuprofen and methotrexate before biopsy. How do you counsel her, and what drug interactions matter here?
Read the worked answer
Methotrexate is renally cleared and is retained when renal perfusion falls. NSAIDs such as ibuprofen reduce renal prostaglandin synthesis and can raise methotrexate levels, increasing myelosuppression and mucositis risk; this is more relevant at higher doses but should be flagged, and paracetamol is a safer analgesic. Methotrexate should not be stopped abruptly without rheumatology agreement, but the prescriber should be informed of the abnormal MCV and any renal impairment. For a tongue biopsy, NSAIDs are not usually a reason to cancel, but you should check platelet count and renal function because thrombocytopenia affects bleeding risk. Counsel her that the biopsy is a minor procedure, that she should continue folic acid as prescribed, avoid alcohol, and report fever, sore throat, or new mouth ulcers urgently because these may signal methotrexate toxicity. Document the discussion and share it with the rheumatology team.