Severe Myelotoxicity Following an Initial Methotrexate Dosing-Frequency Error in a Patient Treated for Suspected Rheumatoid Arthritis: A Case Report

Abstract

Introduction
Methotrexate is widely used as a disease-modifying antirheumatic drug and is generally prescribed as a once-weekly medication in inflammatory rheumatic diseases. A dosing-frequency error in which a weekly regimen is inadvertently administered on consecutive days can result in severe mucosal and hematological toxicity. We report severe methotrexate-associated myelotoxicity following an initial dosing-frequency error in a patient treated for suspected rheumatoid arthritis.
Case presentation
A 58-year-old man was admitted with odynophagia and dysphagia. He had recently been prescribed low-dose methotrexate for suspected rheumatoid arthritis, with an intended once-weekly regimen for four weeks. The patient subsequently took methotrexate for four consecutive days instead of once weekly. The clinical course was complicated by severe oral mucosal disease, documented oral candidiasis with suspected esophageal candidiasis, profound neutropenia, thrombocytopenia, and anemia. On 21 September 2026, the hemoglobin concentration was 8.4 g/dL, total leukocyte count was 1.78 × 10⁹/L, absolute neutrophil count was 0.28 × 10⁹/L, and platelet count was 80 × 10⁹/L. On 25 September, the total leukocyte count was 2.41 × 10⁹/L, with neutrophils of 9.4% and an absolute neutrophil count of approximately 0.23 × 10⁹/L; platelet count was 62 × 10⁹/L. Methotrexate was discontinued. Treatment included folinic acid, granulocyte colony-stimulating factor, antifungal therapy, antimicrobial/supportive treatment, intravenous fluids, and close hematological monitoring. Hematological recovery subsequently occurred, with hemoglobin 10.7 g/dL, total leukocyte count 5.83 × 10⁹/L, and platelet count 314 × 10⁹/L documented during subsequent testing.
Conclusion
This case demonstrates that even low-dose methotrexate can cause clinically significant myelotoxicity when a weekly regimen is inadvertently administered on consecutive days. Early recognition of the characteristic combination of mucosal toxicity and cytopenias, immediate cessation of methotrexate, folinic acid rescue, supportive management, and meticulous patient education are critical to preventing potentially fatal complications.