Methotrexate* for Psoriasis

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THE efficacy of folic acid antagonists, which ushered in a new era in the treatment of psoriasis, was discovered fortuitously in 1951 when Gubner, August, and Ginsberg1 noticed rapid clearing of psoriatic skin lesions in a patient with rheumatoid arthritis treated with Aminopterin. Rees and associates2, 3 reported on the extensive use of Aminopterin, and this became an accepted agent for treating selected cases of psoriasis. In 1958, Edmundson and Guy4 reported on the oral use of Methotrexate* in cyclic dosages. Excellent results were later reported by other authors, with much fewer severe side effects than those occurring from the use of Aminopterin.

Mechanism of Action

Folic acid antagonists inhibit the enzyme, folic acid reductase, which catalyzes a necessary link in the metabolism of folic acid to tetrahydro-folic acid. The synthesis of purines, pyrimidines, and nucleic acids is subsequently dependent on this compound. Desoxyribonucleic acid (DNA) is one of the end products of folic acid metabolism; it is a vital component of all tissues, but especially of rapidly growing tissues such as the bone marrow, the gastrointestinal tract, and the skin. Van Scott and Reinertson5 postulated that normal keratinization does not occur in persons who have psoriasis, because rapid epidermal reproduction takes place, precluding full maturation of the epidermal cells. Methotrexate stops mitosis, presumably by temporarily reducing the supply of DNA, and therefore allowing normal keratinization to occur in psoriatic skin.

Toxicity studies6 have shown Methotrexate to be more effective and less toxic when given in large single doses at . . .



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