A 44-year-old woman comes to the office due to painful oral ulcers. She was initially evaluated 2 months ago for worsening pain, stiffness, and swelling in her hands; x-rays revealed periarticular osteopenia and bony erosions, and laboratory results at that time showed mild anemia with normal liver and renal function studies. Therapy with a disease-modifying drug was begun, and the patient's joint symptoms have gradually improved. However, she has developed painful ulcerations in her mouth, which make eating difficult. She has had no fever, chills, nausea, vomiting, or abdominal pain. Vital signs are within normal limits. Physical examination shows tender ulcerations of buccal mucosa and gingiva. There is no cervical lymphadenopathy. Laboratory studies reveal the following: Which of the following is the most likely cause of this patient's current symptoms?

Question

A 44-year-old woman comes to the office due to painful oral ulcers.  She was initially evaluated 2 months ago for worsening pain, stiffness, and swelling in her hands; x-rays revealed periarticular osteopenia and bony erosions, and laboratory results at that time showed mild anemia with normal liver and renal function studies.  Therapy with a disease-modifying drug was begun, and the patient's joint symptoms have gradually improved.  However, she has developed painful ulcerations in her mouth, which make eating difficult.  She has had no fever, chills, nausea, vomiting, or abdominal pain.  Vital signs are within normal limits.  Physical examination shows tender ulcerations of buccal mucosa and gingiva.  There is no cervical lymphadenopathy.  Laboratory studies reveal the following:  Which of the following is the most likely cause of this patient's current symptoms?

Quizplus · Accepted Answer

11ec25c8_d51d_3225_bc81_553326483587_MD0003_00 This patient has bilateral hand arthritis with inflammatory changes on x-ray (eg, bony erosions, osteopenia) and mild anemia (likely due to chronic inflammation). This presentation is consistent with rheumatoid arthritis (RA). Disease-modifying antirheumatic drugs (DMARDs) can improve long-term joint function and are initiated as soon as possible after diagnosis. The patient's oral ulcers and liver function test abnormalities are likely side effects of methotrexate, the preferred first-line DMARD for most patients with RA. The anti-inflammatory properties of methotrexate are mediated largely by inhibition of dihydrofolate reductase, which causes cellular folate depletion. This leads to impaired DNA synthesis, an effect that is most pronounced in rapidly dividing cells. Therefore, side effects include oral ulcers/stomatitis and bone marrow suppression (eg, macrocytic anemia). Methotrexate is also associated with hepatotoxicity, which can range from mild elevations in hepatic transaminases to chronic liver disease and cirrhosis. Much of the toxicity, including hepatotoxicity and stomatitis, can be mitigated by concurrent administration of folic (or folinic) acid, which does not reduce the effectiveness of the drug. (Choice A) Oral ulcers are a common manifestation of systemic lupus erythematosus (SLE) and are a direct effect of the underlying autoimmune process. SLE can also cause bilateral arthritis, but this is often transient and not associated with erosive changes on x-ray. (Choice B) Disseminated cytomegalovirus infection can occur in patients on immune suppressive therapy. The infection can cause cytopenias, hepatitis, and esophagitis (with ulcerations); however, other frequent manifestations include colitis (eg, diarrhea), and oral ulcers are uncommon. (Choice C) RA is associated with an increased risk of lymphoproliferative diseases and malignancy, but squamous cell malignancy is uncommon and typically presents with a singular ulceration or mass, not with multifocal oral ulcers. Methotrexate does not carry a significant risk of malignancy. (Choice E) Riboflavin (vitamin B₂) deficiency can cause angular stomatitis and cheilosis in addition to other systemic effects, including liver injury. However, oral ulcers are not typical. Regardless, methotrexate causes a functional folate, not riboflavin, deficiency. Educational objective: Methotrexate is a disease-modifying antirheumatic drug used in treatment of rheumatoid arthritis. Its effects are mediated largely by inhibition of dihydrofolate reductase, which causes folate depletion and leads to impaired DNA synthesis. Side effects include oral ulcers, macrocytic anemia, and hepatotoxicity. Much of the toxicity of methotrexate can be mitigated by the administration of folic acid, which does not reduce the effectiveness of the drug. References: Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. (http://www.ncbi.nlm.nih.gov/pubmed/23728635)

A 44-Year-Old Woman Comes to the Office Due to Painful