Severe Pancytopenia Induced by Low-Dose Methotrexate Therapy for Rheumatoid Arthritis.

Abstract 4224

Low-dose of methotrexate (MTX), less than 20 mg per week, is a regimen, widely used for rheumatoid arthritis (RA) treatment. Whereas the hepatotoxicity of MTX is well recognized, the bone marrow toxicity is still a concern, with pancytopenia being a rare, but potentially fatal complication. Risk factors for pancytopenia include advanced age, renal impairment, infection and hypoalbuminemia. Myelosupression is more likely if MTX is taken daily. However, RA by itself can cause hematologic abnormalities, such as Felty's and large granulocyte lymphocytes syndromes. Because the management of pancytopenia secondary to MTX toxicity is completely different from the treatment of hematologic complications, bone marrow examination is important. We reported a case of pancytopenia in a patient receiving low-dose of MTX for disabling RA. A 82-year-old woman with coronary artery disease, renal insufficiency and mild dementia was admitted with 1 months history of weakness, oral ulcers and bruising. Patient's medications list included totally 15 drugs, with aspirin, tylenol, ibuprophen and low-dose of methotrexate for rheumatoid arthritis. The patient had normal CBC 4 weeks prior to admission. Upon examination, she had bruises, petechia and multiple arthritic deformities, especially of small joints. She had severe mucositis and mild pretibial edema. Laboratory investigations revealed: hemoglobin: 9.3 g/dL; MCV: 110 fl; total leukocyte count: 2.300/mm3 with neutrophil count of 800/mm3; platelets count: 6 K/uL; BUN: 17 mg/dL; creatinin: 1.4 mg/dL; folic acid level: 2.53 ng/ml; vit-B12 level, thyroid function and liver function tests were normal, except of mild hypoalbuminema. Peripheral smear showed rare megaloblasts, leucopenia, and thrombocytopenia; no blasts or large granular lymphocyte were found. Biopsy revealed markedly hypocellular bone marrow; immunophenotyping failed to show lympho- or myeloprolipherative disorders or leukemia. A diagnosis of pancytopenia secondary to MTX toxicity was made. MTX was discontinued, the patient was placed on neutropenic precautions and was treated with blood and platelets transfusions, folic acid and G-CSF. She was discharged on day 14 with normal hematologic parameters. Although infrequent, pancytopenia is a severe complication of low-dose MTX therapy. Because the main route of MTX elimination is via renal excretion, which can be inhibited by many medications (aspirin, NSAID's, probenecid, antibiotics), throughout the therapy a number of precautions are important: periodic creatinine clearance and serum albumin determination, especially in elderly patients. Dosing schedule should be clearly printed on MTX boxes. In severe cases of pancytopenia bone marrow biopsy is warranted. Consensus does not exist, but folate supplementation may reduce MTX toxicity and does prevent discontinuation of therapy. Because folate may have a benefit of cardioprotection due to its ability to prevent MTX-induced hyperhomocysteinemia, it is especially important in the treatment of elderly patients with cardiac problems.