Fatal low-dose methotrexate toxicity: A case report and literature review

Methotrexate (MTX) is a chemotherapeutic agent that acts primarily by inhibiting the folic acid cycle. In addition to its application for treating malignancies, MTX is also used to treat chronic inflammatory diseases including psoriasis. Adverse effects have been reported even at low doses (up to 25 mg/week), and there is risk of toxicity in the form of myelosuppression, hepatotoxicity, or pulmonary fibrosis. Here, we report a case of a 67-year-old male with a past medical history of end stage renal disease on peritoneal dialysis and moderate-to-severe psoriasis with psoriatic arthritis presented with abdominal pain, diarrhea, rash, mucositis, and mucocutaneous ulcers and erosions. The patient was taking methotrexate 10 mg weekly without folic acid supplementation and was found to be pancytopenic. Despite treatment, the patient developed multiorgan failure and passed away after 16 days of hospitalization. Myelosuppression is considered the most serious side effect with the highest risk of mortality. Risk factors for toxicity include renal insufficiency, advanced age, lack of folate supplementation, drug interactions, and medication errors. Importantly, serum levels of MTX do not correlate with toxicity; therefore, folinic acid rescue therapy should be started as soon as MTX toxicity is suspected. MTX toxicity is rare with low dose, proper dose scheduling, and adherence to the recommended guidelines. It is imperative that physicians considering therapy with low dose MTX for dermatologic indications take into consideration a patient's risk factors for toxicity and monitor appropriately.