Risk-benefit assessment of methotrexate in the treatment of severe psoriasis

Methotrexate is an established and highly effective systemic treatment for severe psoriasis, including the pustular and erythrodermic forms. It has been widely used during the last 3 decades. For this reason, the long term adverse effects of methotrexate are well known, in contrast to other relatively new systemic treatments like cyclosporin and retinoids. The most frequent adverse effects occurring during methotrexate therapy are abnormal liver function tests, nausea and gastric complaints. The most feared adverse effects are myelosuppression and hepatotoxicity. Because hepatotoxicity is related to a high cumulative dose of methotrexate, rotational therapy or an intermittent instead of a continuous treatment schedule are advised. The histological assessment of liver biopsies, according to the international guidelines, remains the gold standard for detection of liver damage until equally reliable noninvasive screening methods for liver damage--tentatively dynamic hepatic scintigraphy (DHS) or measurement of levels of serum aminoterminal propeptide of type III procollagen--are well evaluated. Low dose methotrexate therapy is relatively well tolerated, provided that there is careful patient selection and regular monitoring for adverse effects and drug interactions during methotrexate therapy is carried out. The long term clinical efficacy and relative safety of methotrexate remain impressive.