Acute versus chronic methotrexate poisoning; a cross-sectional study

Arman Ahmadzadeh,Parinaz Parhizgar,Nasim Zamani,Seyed Kaveh Hadeiy,Hossein Hassanian-Moghaddam

doi:10.1186/s40360-019-0316-8

Arman Ahmadzadeh, Parinaz Parhizgar + Show 3 more

Open Access

https://doi.org/10.1186/s40360-019-0316-8

Copy DOI

Abstract

BackgroundData is limited on comparison of acute and chronic methotrexate (MTX) poisoning. Methotrexate is an anti-folate drug that may be prescribed in some malignant or chronic inflammatory conditions. The aim of the current study was to compare signs and symptoms, complications, treatment and final outcome of acute and chronic MTX toxicity.MethodIn a retrospective study in a referral center between March 2010 and March 2018, all patients who had been referred with the history of MTX poisoning and hospitalized due to acute or chronic poisoning were evaluated and compared.ResultsOf the total 27 patients admitted during the study period, 13 had referred with acute (group 1; consumption of MTX for less than 7 days) and 14 had referred with chronic toxicity (group 2; consumption of MTX for more than 7 days). Mean age was significantly higher in the second group (P < 0.001). Median total dose of MTX was similar between the groups (P = 0.90). Mucosal ulcers and skin lesions (P < 0.001 and 0.02, respectively) were the only symptoms significantly different between the two groups. Leukopenia (P < 0.001), thrombocytopenia (P < 0.001), and anemia (P = 0.04) were significantly more common in the second group. Blood urea nitrogen and creatinine were also significantly higher in the second group of the patients (P < 0.001 and P = 0.048). Median leucovorin administered dose was 200 mg [14, 480] versus 150 mg [75, 187] (P = 0.69) in groups 1 and 2, respectively.ConclusionsChronic MTX poisoning is more serious than acute toxicity and accompanies higher dermatologic, hematologic, and hepatic complications necessitating more aggressive treatments including administration of higher doses of leucovorin or bone marrow stimulants such as G-CSF. This may be attributable to the underlying diseases and features (including older ages) which predispose these patients to complications.

Highlights

Data is limited on comparison of acute and chronic methotrexate (MTX) poisoning
Chronic MTX poisoning is more serious than acute toxicity and accompanies higher dermatologic, hematologic, and hepatic complications necessitating more aggressive treatments including administration of higher doses of leucovorin or bone marrow stimulants such as Granulocyte - Colony Stimulating Factor (G-CSF)
This may be attributable to the underlying diseases and features which predispose these patients to complications

Summary

Introduction

Data is limited on comparison of acute and chronic methotrexate (MTX) poisoning. Methotrexate is an anti-folate drug that may be prescribed in some malignant or chronic inflammatory conditions. Methotrexate (MTX) is a folic acid analogue and antagonist used in the treatment of autoimmune diseases, blood and solid organ malignancies, dermatologic diseases, and termination of pregnancy [1, 2]. It inhibits dihydrofolate reductase interfering with the conversion of dihydrofolate to tetrahydrofolate which is the primary carbon donor for purine and pyrimidine synthesis [2]. Lo Vecchio and colleagues evaluated 13 cases with acute MTX poisoning, all of whom survived None of their cases showed toxicity and the authors, concluded that acute poisoning either intentional or accidental was usually safe [2]. They mentioned that this type of toxicity did not typically need leucovorin

Objectives

Methods

Results

Conclusion