A 57-year-old man comes to the emergency department due to fevers and painful mouth ulcers. He recently began methotrexate therapy for psoriasis. However, the patient has mistakenly taken the medication daily instead of 3 times a week. His past medical history is also significant for hypertension and chronic kidney disease. Temperature is 38.1 C (100.6 F). Examination reveals multiple aphthous ulcers in the oral pharynx. A complete blood cell count is as follows: Which of the following is the best next step in management?

Question

A 57-year-old man comes to the emergency department due to fevers and painful mouth ulcers.  He recently began methotrexate therapy for psoriasis.  However, the patient has mistakenly taken the medication daily instead of 3 times a week.  His past medical history is also significant for hypertension and chronic kidney disease.  Temperature is 38.1 C (100.6 F).  Examination reveals multiple aphthous ulcers in the oral pharynx.  A complete blood cell count is as follows:  Which of the following is the best next step in management?

Quizplus · Accepted Answer

11ec160b_3c30_43f3_9249_9f07003cb08e_MD0001_00 Methotrexate (MTX) is a folic acid analog that inhibits dihydrofolate reductase (DHFR), the enzyme that converts dietary folic acid to tetrahydrofolate (THF), through direct competition. THF is a single-carbon group donor in the synthesis of purines and thymidylic acid (which contributes to pyrimidine formation). MTX functions as a chemotherapeutic agent through inhibition of DNA synthesis and as an anti-psoriasis agent through immunomodulatory effects on activated T cells. However, MTX causes death of all rapidly dividing cells, particularly those of the gastrointestinal tract (GI) mucosa (explaining this patient's aphthous ulcers) and bone marrow (explaining this patient's pancytopenia). Folinic acid (leucovorin) can reverse MTX toxicity if given early. It serves as a reduced form of folic acid thought not to require DHFR to be converted to THF and is therefore unaffected by MTX. Leucovorin is administered following high-dose MTX as part of a chemotherapeutic plan in which it serves to rescue bone marrow, and GI and other mucosal cells from MTX toxicity. In addition, when used in combination with 5-fluorouracil (5-FU), leucovorin potentiates the cytotoxic action of 5-FU (by binding thymidylate synthetase) and is frequently included in colorectal cancer chemotherapy regimens. (Choice A) Allopurinol and its metabolite, oxipurinol, are predominantly noncompetitive inhibitors of xanthine oxidase. Allopurinol is used in the treatment of gout and for prevention of tumor lysis syndrome. (Choice B) Amifostine is a cytoprotective free-radical scavenger used to decrease nephrotoxicity associated with platinum-containing and alkylating chemotherapeutic agents and to decrease xerostomia (dry mouth). (Choice C) Dexrazoxane is an iron-chelating agent that can prevent anthracycline-induced cardiotoxicity. (Choice D) Filgrastim is a granulocyte colony-stimulating factor analog used to stimulate the proliferation and differentiation of granulocytes in patients with neutropenia. (Choice F) Mesna prevents hemorrhagic cystitis due to cyclophosphamide or ifosfamide. Mesna binds acrolein, the toxic metabolite formed by these agents. (Choice G) Ondansetron (a serotonin 5-HT₃ receptor inhibitor) is used to treat nausea and vomiting following chemotherapy. Educational objective: Folinic acid (leucovorin) can reverse the toxicity of methotrexate in non-cancerous cells in the gastrointestinal mucosa and bone marrow if administered at the appropriate time. Leucovorin serves as a reduced form of folic acid that does not require the action of dihydrofolate reductase.

A 57-Year-Old Man Comes to the Emergency Department Due to Fevers