Cardiotoxicity: An Unusual Case of Methotrexate Overdose

Abstract

The methotrexate (MTX) is an antimetabolite, whose dosages vary according to indication. It is used in the treatment of tumoral pathologies, as acute lymphoblastic leukaemias and, in rheumatology, in the rheumatoid polyarthritis (RP) and other chronic inflammatory rheumatisms The methotrexate belongs to the group of antifolates: it inhibits purine and pyrimidine synthesis, which accounts for its efficacy in the therapy of cancer as well as for some of its toxicities. Relative or absolute overdoses in low-dose methotrexate treatments for non-oncological diseases are regularly reported, either in isolated cases or in small series. The bone marrow toxicity with thrombocytopenia and leuconeutropenia is most often the first sign of general involvement. The cardiotoxicity of methotrexate is very rare, in this article we report the observation of pancytopenia associated with cardiotoxicity in a woman treated for RA, for whom the etiological investigation revealed inadvertent methotrexate intoxication by mistake of dosage.

Methotrexate-induced acute cardiotoxicity requiring veno-arterial extracorporeal membrane oxygenation support: a case report

“…Organs most often affected by MTX toxicity are the bone marrow (leukoneutropenia and thrombocytopenia), lung (pneumonitis), kidney (precipitation of MTX metabolites), brain (encephalopathy), and liver (hepatitis to fulminant liver failure). Cardiotoxicity due to MTX is extremely rare, with only one previous case report attributing MTX toxicity to cardiomyopathy [ 1 ]. Additionally, oral mucosal lesions are one of the first signs of MTX toxicity, which our patient did not have.…”

“…Thus, undernutrition will increase free MTX. Other risk factors for MTX toxicity include high doses of MTX, renal impairment, nonsteroidal antiinflammatory drugs, age over 55 years, folate deficiency, low serum albumin, and any drug that displaces MTX from its protein [ 1 ]. NSAIDs influence the pharmacokinetics of MTX by lowering renal excretion of MTX, decreasing renal perfusion, and inhibiting renal transport proteins.…”

“…There are a few case reports of MTX-induced cardiac conduction disturbances, but only one previously published case report exists of MTX-induced cardiomyopathy. This report describes a patient found to have a decrease in LV ejection fraction to 25% after mistaking her MTX dose of 5 mg/week to 5 mg/day [ 1 ]. However, this case did not describe fulminant cardiac failure as in our patient, as this patient actually presented due to pancytopenia.…”

“…Methotrexate (MTX) is an antifolate antimetabolite, commonly prescribed for tumoral pathologies, such as acute lymphoblastic leukemias, and in rheumatology for rheumatoid polyarthritis and other chronic inflammatory diseases [ 1 ]. Methotrexate inhibits the activity of dihydrofolate reductase by acting as a false substrate, which leads to defects of DNA synthesis, specifically purine and pyrimidine synthesis inhibition [ 1 ]. These attributes make MTX a powerful agent targeting autoimmune diseases and cancer.…”

“…However, MTX is also associated with numerous toxicities, including nausea, vomiting, diarrhea, myelosuppression, pancytopenia, liver dysfunction, acute renal failure, pulmonary symptoms, mucositis, stomatitis, ulceration/erosion of the gastrointestinal system, and cutaneous ulcerations [ 2 ]. In general, MTX is thought to be cardioprotective [ 3 ], and reports of MTX-induced cardiomyopathy are very rare and typically involve high doses or dosing errors [ 1 ]. After obtaining patient consent, we present a case report of MTX-induced severe, acute cardiomyopathy requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with low-to-normal drug levels.…”