Methotrexate for psoriasis.

Methotrexate is an effective antipsoriatic agent and has been widely used to treat severe psoriasis since the 1960s. It is especially useful in acute generalized pustular psoriasis, psoriatic erythroderma, psoriatic arthritis and for extensive chronic plaque psoriasis in patients who are inadequately controlled by topical therapy alone. It has not, however, been formally compared with other systemic treatments for severe psoriasis such as cyclosporin, retinoids or photochemotherapy with psoralen and UVA (PUVA), but in comparison with these other therapies it is inexpensive, with correct use, its safety profile is favourable. In summary, therefore, it can be used as a short-term option to gain control of unstable psoriasis such as pustular psoriasis or erythroderma before returning to other modes of treatment, or more often, as long-term maintenance treatment. The most important potential side-effect is acute myelosuppression, which is the cause of most of the rare deaths attributable to this therapy for psoriasis. Myelosuppression is more likely in the elderly, in patients with renal impairment and/or folate depletion, and with overdose or drug interactions. Long-term therapy carries with it a risk of liver fibrosis which is related to the dosage regimen employed, and is increased by exposure to other hepatic toxins, particularly alcohol. The correlation between the risk of development of liver fibrosis, cumulative lifetime dose and duration of treatment with methotrexate is not clear-cut, but may have been overstated in some studies.