A 48-year-old man presents with a sore mouth and inflamed oral mucosa; upon inverting the lip, an abnormality is seen. Which medication is most likely causing these symptoms?

• A. Prednisone
• B. Ibuprofen
• C. Amlodipine
• D. Methotrexate

Answer: (D)

Mucositis from a folate antagonist best explains this presentation. Methotrexate disrupts DNA synthesis in rapidly dividing cells, including the cells lining the mouth. That impairment leads to inflammation, painful ulcers, and erosions of the oral mucosa. When the lip is inverted, you’d expect to see such ulcerative or inflamed mucosa, which fits methotrexate toxicity.

The other drugs don’t typically produce this pattern. Prednisone can affect healing and infection risk but isn’t a classic cause of acute mucositis with visible ulceration. Ibuprofen may irritate mucosa, yet it doesn’t usually cause the characteristic widespread oral ulcers. Amlodipine tends to cause gingival overgrowth with long-term use rather than acute mucosal ulcers.