Fatal methotrexate toxicity: could it have been avoided?

Abstract

Methotrexate is used judiciously, only when specifically indicated. However, in this case the patient had a fatal outcome after only three doses. A young nulliparous woman diagnosed as having high-risk persistent trophoblastic disease was considered for multidrug chemotherapy. However, because of persistent low-grade fever it was decided to give only single agent, methotrexate. She developed severe toxicity which proved fatal, even before the first course could be completed. Analysing causes of this rare, unexpected outcome of methotrexate administration, suggested that estimation of serum levels can be a useful tool in monitoring patients showing hypersensitivity but this facility is rarely available especially in low-resource countries. Pharmacogenetical analysis of blood/tissue sample may be useful to help in identifying patients likely to show hypersensitivity reaction.

Mucocutaneous Ulcerations Due to Methotrexate Toxicity Mimicking Vesiculobullous Disorder: A Diagnostic Challenge

“…It is an antifolate that binds to an enzyme, dihydrofolate reductase, which catalyzes the conversion of dihydrofolate to tetrahydrofolate, the active form of folic acid. Tetrahydrofolate is required for formation of one carbon metabolites during DNA synthesis, thus ultimately leading to the inhibition of DNA synthesis (3). Methotrexate can be safely used for the treatment of psoriasis, systemic lupus erythematosus, vasculitis, and many other connective tissue disorders, etc.…”