A 52-year-old woman with recently diagnosed rheumatoid arthritis comes to the physician complaining of decreased appetite, sore throat, and mild nausea for the past 2 weeks. She has no fevers, vomiting, or dark or bloody stools. She has been treated with oral naproxen daily and methotrexate weekly for the last 6 weeks with improvement of joint symptoms. She also takes ranitidine for occasional heartburn and senna for chronic constipation.
Her temperature is 36.7° C (98° F), blood pressure is 120/70 mm Hg, and pulse is 78/min. Oral examination shows several shallow ulcers on the buccal mucosa and hard palate as well as mild pharyngeal erythema. No enlarged lymph nodes are palpated. There are no skin rashes. The abdomen is soft and nontender. The small hand joints are mildly swollen and tender to palpation bilaterally. A small effusion is present in the right knee.
Laboratory results are as follows:

Liver function tests are normal.
Which of the following is the best next step in management of this patient?

Question

A 52-year-old woman with recently diagnosed rheumatoid arthritis comes to the physician complaining of decreased appetite, sore throat, and mild nausea for the past 2 weeks.  She has no fevers, vomiting, or dark or bloody stools.  She has been treated with oral naproxen daily and methotrexate weekly for the last 6 weeks with improvement of joint symptoms.  She also takes ranitidine for occasional heartburn and senna for chronic constipation.
Her temperature is 36.7° C (98° F), blood pressure is 120/70 mm Hg, and pulse is 78/min.  Oral examination shows several shallow ulcers on the buccal mucosa and hard palate as well as mild pharyngeal erythema.  No enlarged lymph nodes are palpated.  There are no skin rashes.  The abdomen is soft and nontender.  The small hand joints are mildly swollen and tender to palpation bilaterally.  A small effusion is present in the right knee.
Laboratory results are as follows:

Liver function tests are normal.
Which of the following is the best next step in management of this patient?

Quizplus · Accepted Answer

This rheumatoid arthritis patient's symptoms suggest common methotrexate (MTX) toxicity. MTX depletes folic acid by interfering with its metabolism and leads to possible complications, including stomatitis and megaloblastic anemia. Stomatitis usually occurs with high-dose methotrexate but can also occur at low doses. Stomatitis can persist for days to weeks, interfere with eating, and may lead to premature discontinuation of MTX. All patients taking MTX should receive folic acid at 1 mg/day with dose increases to 5 mg/day based on symptoms. Folic acid supplementation usually improves stomatitis. Patients without symptom improvement after folic acid supplementation may need to discontinue MTX (Choice A). Other common toxicities such as fever, gastrointestinal disturbances, and rash usually occur within days of the weekly MTX dose. Fever can be caused by MTX, but infection must be excluded. Gastrointestinal complaints (eg, nausea, upset stomach) may be relieved with histamine H2 blockers or proton pump inhibitors. A punctuate, macular rash affecting the extremities but sparing the trunk may occur, but it usually fades by the next week's dose. Life-threatening complications include direct hepatocyte damage causing hepatotoxicity or worsening hepatotoxicity in viral hepatitis patients, pulmonary damage, myelosuppression, and nephrotoxicity. Chest x-ray is required prior to starting MTX. All patients should also have a viral hepatitis panel prior to MTX therapy and either be treated or receive therapy to suppress viral replication. Periodic monitoring includes serum aminotransferase, albumin, complete blood count, and creatinine. (Choice B) Naproxen toxicity usually presents with anion gap metabolic acidosis, worsening renal dysfunction, hypertension, and anemia due to bleeding gastrointestinal ulcers. (Choice C) Oral acyclovir treats herpes simplex labialis, which usually presents with painful vesicles at the vermillion border of the lips. This patient does not have a vesicular eruption. (Choice D) Prednisone can improve rheumatoid arthritis symptoms and treat allergic reactions. However, this patient's symptoms have improved on MTX and do not require prednisone. She also does not have a diffuse rash or eosinophilia to suspect an allergic reaction. Educational objective: Common toxicities of methotrexate include fever, stomatitis, macular rash, gastrointestinal disturbances, and hematologic abnormalities (megaloblastic anemia). Stomatitis and megaloblastic anemia can be prevented by folic acid supplementation. __________ References: Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. (http://www.ncbi.nlm.nih.gov/pubmed/11465701) Effect of folic or folinic acid supplementation on methotrexate-associated safety and efficacy in inflammatory disease: a systematic review. (http://www.ncbi.nlm.nih.gov/pubmed/18945303)

A 52-Year-Old Woman with Recently Diagnosed Rheumatoid Arthritis Comes to the Physician