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Home > D. General pathology > Therapy, Toxics and drugs > methotrexate


Monday 28 November 2005

Methotrexate is a folate antagonist that is used for long-term treatment of rheumatoid arthritis, psoriasis and inflammatory bowel disease.

Pathology: MTX-induced diseases

- MTX-induced lymphoproliferative disorders
- MTX-induced liver injury

The canals of Hering may be the target of methotrexate-related scarring.

The risk of liver toxicity is exacerbated with heavy alcohol use, pre-existing liver disease, daily dosing and high cumulative dose.

Minor elevation in liver enzymes occurs in 20–50% of patients but does not necessarily imply significant toxicity.

The histological features of methotrexate-related toxicity range from minor fatty change, hepatocyte anisonucleosis, mild portal-based inflammation, and focal necrosis to more severe hepatocellular necrosis, fibrosis and cirrhosis.

Methotrexate may exacerbate or precipitate steatohepatitis in patients with risk factors such as obesity and diabetes.

Some patients with high cumulative dose can have steatohepatitis-like histology without other risk factors.

Patients on long-term methotrexate need close monitoring. Liver biopsy is necessary in patients who develop deranged liver function following methotrexate therapy. A grading scheme has been proposed to assess toxicity (Roenigk classification).


- van der Veen MJ, Dekker JJ, Dinant HJ, van Soesbergen RM, Bijlsma JW. Fatal pulmonary fibrosis complicating low dose methotrexate therapy for rheumatoid arthritis. J Rheumatol. 1995 Sep;22(9):1766-8. PMID: 8523359