Methotrexate toxicity induced by acute renal failure

Dr Strang and Dr Pullar describe methotrexate toxicity induced by acute renal failure in two patients with rheumatoid arthritis (November 2004, JRSM¹).

We had a similar experience in a patient with skin disease. Our patient was a woman of 71 who was taking methotrexate 7.5 mg weekly for psoriasis. A flare of her psoriasis, with erythroderma, necessitated admission to hospital. She was experiencing back pain from osteoporosis, for which her general practitioner had prescribed oral morphine sulphate 20 mg four times daily. She took her methotrexate as usual on Sunday and on Monday morning was found to be in acute renal failure (urea 37 mmol/L, creatinine 384 μmol/L, potassium 6.7 mmol/L, sodium 135 mmol/L). This was felt to be secondary to dehydration since she was drowsy, possibly because of the opioid analgesics and not eating or drinking. She later said she had avoided fluids so as not to need the toilet.

In addition to intravenous fluids she received three doses of 15 mg folinic acid intravenously and then oral calcium folinate. Despite this, five days after taking methotrexate she became pancytopenic (haemoglobin 8.3 g/dL, white cell count 0.20×10⁹/L, neutrophils 0.02×10⁹/L, lymphocytes 0.13×10⁹/L, platelets 28×10⁹/L). She was transfused with blood and platelets, and was also given filgrastim (G-CSF). Mouth ulcers developed at the onset of pancytopenia but her skin disease virtually cleared and there was no skin ulceration. By discharge a month later her blood indices, liver function tests and renal function tests were normal. Methotrexate was restarted two months later without further incident.