Which symptom is least likely to be a direct side effect of methotrexate?

• A. Hearing loss
• B. Mouth ulcers
• C. Elevated liver enzymes
• D. Blood cell abnormalities

Answer: (A)

Methotrexate toxicity in rheumatology most commonly hits tissues with rapid cell turnover and the liver, and it can depress the bone marrow. Mouth ulcers reflect mucosal toxicity from inhibited mucosal cell replication. Elevated liver enzymes signal hepatocellular injury from the drug’s metabolism in the liver. Blood cell abnormalities arise from bone marrow suppression, leading to anemia, leukopenia, or thrombocytopenia. Hearing loss, on the other hand, is not a typical direct adverse effect of standard methotrexate therapy and is not commonly seen in routine dosing. It may occur only rarely in certain high-dose or specialized regimens, or in conjunction with other risk factors, making it far less likely than the other listed effects.