Abstract
BACKGROUND: Low dose methotrexate toxicity rarely occurs, but may present with severe complications, such as pancytopenia, hepatotoxicity, mucositis, and pneumonitis. Known risk factors for methotrexate toxicity include dosing errors, metabolic syndrome, hypoalbuminemia, renal dysfunction, lack of folate supplementation, and the concomitant use of drugs that interfere with methotrexate metabolism. Vitamin B12 deficiency leads to megaloblastic anemia and may cause pancytopenia, but its role in methotrexate toxicity has not been described. CASE PRESENTATION: We present a case of a patient with rheumatoid arthritis who was admitted with febrile neutropenia, pancytopenia, and severe mucositis, likely secondary to low dose methotrexate toxicity. She had multiple factors that potentially contributed to the development of toxicity, including concurrent sulfasalazine use for rheumatoid arthritis. An evaluation of the patient's macrocytic anemia revealed pernicious anemia. The patient's illness resolved with cessation of methotrexate and sulfasalazine, leucovorin treatment and vitamin B12 repletion. CONCLUSIONS: This case illustrates the multiple factors that may potentially contribute to low dose methotrexate toxicity and highlights the importance of testing for vitamin B12 deficiency in rheumatoid arthritis patients with macrocytic anemia. Addressing all the modifiable factors that potentially contribute to low dose methotrexate toxicity may improve outcomes.