A 45-year-old woman comes to the office for follow-up of arthritis. For the last year, she has had fatigue, weight loss, and progressive joint pain in the hands associated with prolonged morning stiffness. Past medical history includes hypothyroidism, for which she takes levothyroxine. The patient does not use tobacco or alcohol. Examination shows doughy swelling involving multiple metacarpophalangeal joints in both hands. Following initial diagnostic testing, a multidrug treatment regimen is started. Soon after treatment begins, she develops painful mouth ulcers and nausea. Liver function tests show new aspartate transaminase and alanine transaminase elevations. Which of the following medications is most likely responsible for the adverse effects seen in this patient?

Question

A 45-year-old woman comes to the office for follow-up of arthritis.  For the last year, she has had fatigue, weight loss, and progressive joint pain in the hands associated with prolonged morning stiffness.  Past medical history includes hypothyroidism, for which she takes levothyroxine.  The patient does not use tobacco or alcohol.  Examination shows doughy swelling involving multiple metacarpophalangeal joints in both hands.  Following initial diagnostic testing, a multidrug treatment regimen is started.  Soon after treatment begins, she develops painful mouth ulcers and nausea.  Liver function tests show new aspartate transaminase and alanine transaminase elevations.  Which of the following medications is most likely responsible for the adverse effects seen in this patient?

Quizplus · Accepted Answer

This patient, a middle-aged woman with polyarthritis, morning stiffness, and systemic symptoms, has typical features of rheumatoid arthritis (RA). Methotrexate is the preferred first-line disease-modifying treatment for most patients with moderate to severe RA. Methotrexate is a folate antimetabolite that halts purine and pyrimidine synthesis through competitive inhibition of dihydrofolate reductase. Methotrexate preferentially inhibits growth of rapidly dividing cells, such as inflammatory and neoplastic cells. However, this inhibitory effect also causes toxicity to tissues with rapid cellular turnover, such as oral and gastrointestinal mucosa (ulcerations), hair follicles (alopecia), and bone marrow (pancytopenia). Methotrexate can also cause hepatotoxicity (hepatitis, fibrosis, cirrhosis) and pulmonary fibrosis. (Choice A) Hydroxychloroquine is a well-tolerated antirheumatic drug used in mild RA and systemic lupus erythematosus. Its most significant toxicity is irreversible retinopathy, and patients should have regular ophthalmologic examinations. (Choice C) Minocycline is a tetracycline antibiotic with weak antirheumatic activity. Common side effects include photosensitivity dermatitis. (Choice D) Nonsteroidal anti-inflammatory drugs (NSAIDs [eg, naproxen]) are used for initial symptom relief in RA, although they do not prevent the long-term joint damage caused by the disease. Significant side effects include gastritis/gastric ulcers and acute kidney injury. (Choice E) Glucocorticoids are used for initial treatment and acute flares of RA. Short-term side effects include insomnia and hyperglycemia. Long-term side effects are significant and include weight gain, osteoporosis, and muscle weakness; these drugs also potentiate the risk of gastric ulcers in patients taking NSAIDs. Educational objective: Methotrexate is the preferred disease-modifying treatment for patients with moderate to severe rheumatoid arthritis. Significant adverse effects include stomatitis, bone marrow suppression, and liver function abnormalities. __________ References: Methotrexate for treating rheumatoid arthritis. (http://www.ncbi.nlm.nih.gov/pubmed/24916606)

A 45-Year-Old Woman Comes to the Office for Follow-Up of Arthritis