What systemic drugs are used to treat psoriasis?

Methotrexate, cyclosporine, and retinoids (i.e., acitretin). Because of the potential side effects of these agents, their use should be carefully considered by the physician and patient. Methotrexate suppresses DNA synthesis by inhibiting the enzyme dihydrofolate reductase. In addition to its antimitotic effects, methotrexate inhibits neutrophil function. Side effects include bone marrow suppression, stomach upset, and hepatotoxicity. Although the incidence of hepatic fibrosis and cirrhosis is low with cumulative doses ,1.5 gm, liver function tests are not a reliable indicator of methotrexate-induced hepatotoxicity, and a liver biopsy is recommended after 1.5 gm and every 1.0 to 1.5 gm thereafter. Methotrexate should be avoided in psoriatic patients who have underlying liver disease, renal disease, or are heavy drinkers. Patients who take methotrexate should be aware of its interactions with many other medications.


The antilymphocytic drug cyclosporine can be used for severe psoriasis. It has a relatively rapid onset of action, but side effects such as hypertension and nephrotoxicity limit its use as a long-term agent. The doses used, 3 to 5 mg/kg/day, are usually lower than the dosages used to inhibit organ transplant rejection.

Systemic retinoids such as acitretin are first-line agents in pustular psoriasis and also may be used to treat chronic plaque psoriasis. Unlike methotrexate and cyclosporine, retinoids do not suppress the immune system. Rather, retinoids likely mitigate the epidermal hyperproliferation seen in psoriasis. Acitretin is a potent teratogen and must be avoided in women of child-bearing age. Other systemic treatments include the “biologicals,” which will be covered in the next question.