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Methotrexate (MTX) is one of the most effective antipsoriatic drugs available. Although it is undeniably hepatotoxic, it can be used safely in most patients with severe psoriasis if established guidelines are followed. Current opinion on the monitoring of hepatic damage is divided, however, and the need for repeated liver biopsies during MTX therapy is being re-examined. We have used MTX in a short-term protocol in our patients with psoriasis for the past 20 years, and have recently attempted to minimize or eliminate the need for liver biopsies using this regimen.Data on 244 psoriatics who were given MTX from 1981 to 2000 have been reviewed. Our protocol entailed the use of weekly oral MTX at the full therapeutic dose during episodes of peak disease activity, with tapering off of MTX when the disease subsided in response to treatment combined with natural/seasonal remission. Intensive topical and heliotherapy were encouraged throughout to facilitate the earliest possible drug withdrawal and the longest possible drug-free interval before the next relapse. Strict inclusion criteria were applied before starting MTX.A total of 243 cycles of MTX therapy have been given to 197 evaluable patients. More than 75% improvement occurred in 88% of patients in 8.5 ± 5.1 weeks. The mean cumulative dose was 709.3 ± 369.2 mg and the mean duration of follow-up was 16.5 ± 9.1 months. Fifteen (6.1%) patients had serious adverse effects requiring the cessation of therapy. Only three patients had deranged liver function tests. Thirty-four pre-MTX and 13 post-MTX liver biopsies were taken, which revealed grade I or II changes that were nonprogressive.Our experience with short-term MTX therapy has enabled us to safely administer MTX to our patients with minimal recourse to liver biopsy. In developing countries, where advanced noninvasive methods for the assessment of liver damage are unaffordable or unavailable, this interrupted, short-term regimen may present an acceptable and safe method of using MTX in carefully selected patients with severe psoriasis.