Toxic Hepatitis due to Combination Therapy with Methotrexate and Etretinate in Psoriasis

Abstract

A case of toxic hepatitis caused by combination therapy with methotrexate and etretinate in the treatment of severe psoriasis is presented in a 47-year-old woman. The patient had received methotrexate alone for more than 10 years without any signs of severe liver damage. The liver status had been controlled by consecutive liver biopsies. The treatment was discontinued and after 2 months the liver parameters became normal.

British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology

“…41 Although this combination can be very effective, sporadic severe hepatotoxic responses have been reported. [42][43][44] The efficacy of concomitant use of acitretin with ciclosporin is not convincing 45 and, in addition, this combination carries the risk of accumulation of ciclosporin as both drugs are inactivated by the same cytochrome P-450 system.…”

Antineoplastic Agents Drug Interactions of Clinical Significance

“…Beck and Foged [12] reported a severe case of toxic hepatitis after coadministration of methotrexate and etretinate. No pharmacokinetic explanation could be found for the interaction) 13] Calcium folinate can be administered intravenously or orally, starting 4 to 24 hours after high dose methotrexate to prevent severe and sustained myelosuppression.…”

Is concomitant use of methotrexate and oral retinoids dangerous? A review of the data regarding this combination

“…Etretinate alone carries an increased risk of hypersensitivity hepatitis, prompting close monitoring of liver enzymes. [14][15][16] However, there is no mention of increased risk of hepatitis associated with concurrent use of specifically methotrexate and acitretin. Only a theoretical association exists between acitretin and methotrexate because of the ability of acitretin to be reversibly metabolized to etretinate.…”