A Case of Pancytopenia Secondary to Low - Dose Pulse Methotrexate Therapy in a Patient with Rheumatoid Arthritis and Renal Insufficiency

Abstract

Most reports on serious MTX toxicity have focused on hepatic abnormalities, while other effects, including hematologic reactions, have not been emphasized. We experienced a case of pancytopenia secondary to MTX therapy in a patient with RA and renal insufficiency. A 67-year-old woman with a 12-year history of active seropositive RA that was a response to non-steroidal anti-inflammatory drugs, hydroxychloroquinine and intra-articular steroid injections, had been followed up and was diagnosed as early chronic renal failure in October, 1993. Recently, because of significant morning stiffness and polyarthralgia, the decision was made to institute MTX treatment. This was begun as a single oral dose of 5mg/week. After 2 doses, the patient was admitted to the hospital with general weakness. Laboratory tests showed a hemoglobin level of 7.9 g/dl, WBC count 1800/mm3 and platelet count of 64000/mm3. The serum creatinine level was 6.1 mEq/dl and the BUN level was 82 mEq/dl. Liver function test results were normal, but the serum albumin level was 2.7 g/dl. The patient subsequently developed fever and blood transfusions, granulocyte colony stimulating factor(G-CSF) and intravenous prophylactic antibiotic therapy were required. Her condition was improved.In summary, Low-dose MTX-related adverse hematologic side effects, including fatal pancytopenia, are rare but are a cause of increasing concern in patients with RA and renal insufficiency. Close monitoring of associated risk factors, particulary impaired renal function, should be mandatory for all patients who are receiving MTX therapy.

Methotrexate-induced Oral Mucositis

“…In a previous study, oral mucositis was reported in patients who were prescribed low-dose MTX but ultimately overdosed either due to prescription error or patients' confusion regarding its once-weekly regime. 11,12) In this case study, however, MTX toxicity seems to have been elevated by several factors such as deficiency of FA, 13) reduced renal function, 14) and drug interaction, 13) even if the dosage of MTX does not change. In addition, while oral mucositis has commonly been known to appear as an initial sign of MTX toxicity, it actually develops relatively late after longterm MTX administration in our cases.…”

Fatal Pancytopenia in a Hemodialysis Patient After Treatment With Low-Dose Methotrexate

“…Chronic kidney disease by itself, not necessarily confined to those with ESRD, seems to predispose patients to the development of this serious complication. 13 Other risk factors reported for pancytopenia with low-dose methotrexate therapy included hypoalbuminemia, advanced age, low serum folate level, elevated mean corpuscular volume, concurrent use of NSAIDs, and concurrent medication with more than 5 drugs. 14 -16 According to a large case series of methotrexate-related pancytopenia, hypoalbuminemia, polypharmacy, advanced age, and renal insufficiency were the most common risk factors, whereas the methotrexate dose was the most predictive of pancytopenia severity.…”