Severe MTX Toxicity in Rheumatic Diseases - Analysis of 22 Cases

Background: Severe MTX (methotrexate) toxicity due to low dose MTX used in rheumatic diseases is rare but linked with a high mortality ranging from 13 to 44%. We analyzed 22 cases with a minimum toxicity of CTC (common toxicity criteria) grade 2, that were admitted to our hospital. Methods: We retrospectively analyzed epidemiological data, the weekly MTX dosage, renal function before and at the beginning of the adverse event, co-medication with influence on MTX toxicity or on renal function and potential other co-factors like infections, as well as the outcome, respectively. Results: 22 patients were involved in the study. Three patients died due to pneumonia, all other patients recovered. The main reason for toxicity was an impaired renal function (82%), either from acute renal failure or from acute on chronic renal failure or chronic renal disease stage 4. In 5 cases a dosing error, mainly with daily instead of weekly MTX intake, was the reason. Only in one case the reason remains unclear. Discussion: An impaired renal function with an estimated glomerular filtration rate (eGFR) of 11-54 ml/min was the main cause for MTX toxicity with dosage errors being the second numerous reasons. Our data are in accordance with previous case series, but the influence of reduced renal function is still higher than in the most reports. One reason might be that most case series took only into account the serum creatinine but not a calculated GFR. Serum creatinine alone underestimates the stage of renal failure in patients with lower muscle mass.