SHM Converge Scientific Abstract ePoster Gallery-Beyond Infection: Maintaining Methotrexate in the Neutropenia Differential

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This case describes a 76-year-old man who developed fever, abdominal pain, nausea, vomiting, confusion, and profound cytopenias shortly after methotrexate was increased to 20 mg weekly for overlap granulomatosis with polyangiitis and giant cell arteritis. He was febrile and had left lower quadrant tenderness; labs showed severe leukopenia with ANC 0.03 k/µL and thrombocytopenia. CT imaging showed mild uncomplicated diverticulitis, and his serum methotrexate level was undetectable.<br /><br />He was treated for neutropenic fever with cefepime and metronidazole, methotrexate was held, and IV leucovorin rescue was started. By hospital day 5, his white count and ANC improved significantly, and he was transitioned to azathioprine.<br /><br />The key teaching point is that low-dose methotrexate toxicity can occur early, even with standard rheumatologic dosing, and can present with pancytopenia and neutropenic fever. Dosing errors, especially accidental daily use instead of weekly dosing, are a major risk factor. Importantly, serum methotrexate levels may be undetectable and therefore falsely reassuring, because toxicity reflects intracellular accumulation rather than circulating drug concentration. Diagnosis should rely on clinical suspicion, not drug levels alone.<br /><br />Methotrexate toxicity should remain in the differential for unexplained cytopenias, and early leucovorin rescue is critical when suspected. Severe low-dose methotrexate toxicity can be life-threatening, with reported mortality exceeding 40%.

Asset Subtitle

Varun Mahadevan

Meta Tag

Author List Caley Dickinson, John Gerstenberger, Varun Mahadevan

Category Clinical Vignettes

Concept Methotrexate

Concept Methotrexate Toxicity

Concept Leucovorin Rescue

Concept Low-Dose Methotrexate

Concept Pancytopenia

Distinguished Non-Finalist

Presenter Organization University of Utah Hospital, Department of Internal Medicine

Presenting Author Varun Mahadevan

Track Adult

Keywords

methotrexate toxicity

pancytopenia

neutropenic fever

leucovorin rescue

low-dose methotrexate

granulomatosis with polyangiitis

giant cell arteritis

cytopenias

undetectable methotrexate level

diverticulitis

Methotrexate

Methotrexate Toxicity

Leucovorin Rescue

Low-Dose Methotrexate

Pancytopenia