Pancytopenia Resulting From Low-Dose Methotrexate Use: A Diagnostic Challenge

Rheumatoid arthritis (RA) is a common autoimmune disease primarily affecting small joints which leads to crippling erosion of the articular cartilage and bone. It is associated with complications related to both its disease course and treatment. Methotrexate (MTX) is a folate antagonist responsible for modulating cell-specific signaling pathways and inhibiting the proinflammatory properties of major cell lineages involved in the pathogenesis of RA. It is considered to be the first-line agent in RA because of its disease-modifying ability and safety profile at low doses. This case report discusses how a middle-aged female presented with severe bone marrow suppression secondary to MTX toxicity, an unusual presentation at the usual low-dose regimen. Her presentation overlapped with several other conditions, especially with Felty’s syndrome, a rare complication of RA, characterized by the triad of splenomegaly, neutropenia, and RA. Other differentials included hemophagocytic lymphohistiocytosis, hematologic neoplasms, drug reaction, and infection. Therefore, it was essential to exclude all possible differentials before initiating therapy. We found the corrected reticulocyte count coupled with a good response to leucovorin to be an effective way to differentiate MTX-induced pancytopenia from other possible hematologic diagnoses without the use of a bone marrow biopsy. Additionally, our case incidentally demonstrated a potential interaction between piperacillin/tazobactam and MTX.