Topical treatment of psoriatic skin with methotrexate cream: a clinical, pharmacokinetic, and histological study.

Five patients were treated with either 0.25% methotrexate cream or placebo in a double blind trial. The evaluation showed no clinical or histological effect although the drug was absorbed from the skin. Methotrexate (MTX) accumulated in locally treated psoriasis plaques as well as in untreated plaques. The psoriatic skin concentrations were increased by a factor of 119 and 4, respectively. This observation is discussed in relation to the possible role of action of methotrexate in psoriasis. We suggest that methotrexate inhibits the chemotaxis of neutrophil leukocytes systemically and not primarily in the skin, thereby preventing development of the early stages in the psoriatic lesions.