A 67-year-old woman with a history of rheumatoid arthritis treated with sulfasalazine and methotrexate for two and a half years presented with a one-month history of neck swelling. Her cumulative methotrexate dose was about 800 mg. Computed tomography (CT) showed a large mass involving the left lobe of her thyroid, along with lymphadenopathy (Figure 1A and B) and esophageal compression (Figure 1B). An incisional thyroid biopsy suggested diffuse large B-cell lymphoma. Although serology results were consistent with prior infection with Epstein–Barr virus, results from in situ hybridization of thyroid tissue were negative for the virus. We diagnosed methotrexate-related lymphoma. After withdrawal of methotrexate, the swelling of the patient’s neck gradually abated. No other treatments were used. Follow-up CT at one and a half months showed a dramatic resolution of lesions (Figure 1C and D). Complete remission was reconfirmed at a two-year follow-up visit, at which time our patient was taking only sulfasalazine for her rheumatoid arthritis.
The overall standardized incidence ratio for lymphoma in patients with rheumatoid arthritis has been estimated at 1.9 (95% confidence interval 1.3–2.7), which is similar to the incidence ratio for patients receiving methotrexate monotherapy.1 Cases of methotrexate-associated lymphoma resolving with discontinuation of the drug have been described, both in the presence and absence of latent infection with Epstein–Barr virus.2–4 Our case represents a possible adverse reaction to methotrexate based on the Naranjo scale for probability of an adverse drug reaction.5 Physicians prescribing methotrexate for rheumatoid arthritis may wish to keep in mind its associations with lymphoproliferative disorder.
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Footnotes
Competing interests: None declared.
This article has been peer reviewed.
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