No controlled trials have tested the efficacy of methotrexate in pemphigus, but a few case series describe its use. Lever and Schaumburg-Lever10 treated 20 patients with methotrexate alone or in combination with prednisone. Two of nine patients with mild disease who received methotrexate alone achieved complete remission. Another five patients with mild disease received prednisone plus methotrexate. One patient in this group achieved remission. Yet another treatment group consisted of patients with moderate-to-severe disease, all of whom received high-dose prednisone (>180mg/day) followed by "maintenance" doses of prednisone plus methotrexate. Three of six patients were free of lesions at the time of publication and two of these three were also off medication. Overall, five of the 20 patients enrolled in the study achieved complete remission. One patient died of sepsis.

Reports of serious side-effects associated with methotrexate have largely precluded its use in pemphigus in recent years. These reports led many investigators to believe that methotrexate predisposed patients to sepsis. However, a recent report by Smith and Bystryn23 suggested that the increased incidence of infection observed in previous studies may be attributed to higher than necessary doses of methotrexate (>20 mg/week). In a series of nine patients, all of whom had had been treated unsuccessfully with another adjuvant agent, Smith and Bystryn23 reported that 17-5 mg/week or less was sufficient to induce a disease-free state in six patients, although there is no mention of the duration of methotrexate therapy required to achieve this. In all patients disease activity flared once methotrexate therapy was stopped. Corticosteroid therapy was discontinued once disease control was achieved. No side-effects were mentioned.

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