Clinical Profile of Acute Methotrexate Toxicity in Rheumatic Diseases: A Series of 15 Cases

Abstract

Background: Methotrexate (MTX) at a dose of ≤25 mg/week is one of the most prescribed disease-modifying anti-rheumatic drugs (DMARDs) in a variety of rheumatic diseases. It can potentially cause life-threatening neutropenic sepsis, and acute renal and hepatotoxicity when taken inadvertently at high doses. We aim to analyse the clinical profile and risk factors of patients who presented with acute MTX toxicity. Methods: All patients presenting to the Rheumatology department with a history of inadvertent consumption of higher doses of MTX (>25 mg/week), from July 2021 to May 2023 were included. Additional data was extracted from hospital electronic medical health records. The clinical profile, risk factors, and outcome of patients with MTX toxicity were analysed. Results: The median age of the patients in our cohort was 52 IQR (40–62.5) years, with 80% females. The median cumulative dose of MTX was 120 mg (IQR 95–150). The reason for overdose in our cohort was medication error in comprehending once-weekly dosing. The most common major adverse event was neutropenia (80%). All our patients had stomatitis, with half of them having oral bleeding. Gastrointestinal adverse events like vomiting and diarrhoea were seen in 60% and 13% of the patients, respectively. Our cohort had two patients who succumbed to the complications due to neutropenic sepsis. The dose of MTX did not correlate with the severity of the disease or duration of hospital stay; however, the latter was significantly influenced by lower absolute neutrophil count (ANC). Conclusion: Acute MTX toxicity is one of the severe rheumatological emergencies and the toxicity profile includes haematological, gastrointestinal, hepatic, and renal adverse events. Severe neutropenia leading to sepsis can be fatal if not intervened early.