When low-dose Isn't Low-risk: Methotrexate-Induced Pancytopenia and Mucositis in a Rheumatoid Arthritis Patient

Abstract Methotrexate (MTX) has long served as a mainstay treatment for rheumatoid arthritis. While high dose methotrexate is associated with significant side effect, low dose methotrexate toxicity rarely occurs. We present a case of an 81-year-old male patient with a recent diagnosis of rheumatoid arthritis who deliberately took daily methotrexate (cumulative dose of 40mg) instead of weekly dose of 5mg for his flare-up and presented with mucositis, pancytopenia (platelet nadir of 14000/mm3, hemoglobin level of 9g/l and white blood cell count of 2530/mm3) and normal renal and hepatic function. After ruling out hematological emergencies, malignancies and infectious causes, the patient was diagnosed with low dose methotrexate (LDMTX) toxicity. The patient’s advanced age, daily methotrexate intake, alcohol use, smoking history, and possible folate pathway polymorphisms were considered contributing factors. Methotrexate was stopped and the patient was treated with leucovorin, filgrastim, and supportive care resulting in progressive and complete hematological recovery. Follow-up at one week, one month and six months showed full resolution of the cytopenia. This case underscores that LDMTX toxicity can occur even at minimal doses when taken consecutively and may be exacerbated by folate deficiency, age-related vulnerability, and genetic susceptibility. Early recognition, prompt cessation of MTX, and appropriate rescue therapy with leucovorin and G-CSF are crucial to achieving a good outcome. This case emphasizes the necessity of clear patient education regarding weekly MTX dosing to avoid dosing errors and subsequent toxicity.