Systemic Therapy for Psoriasis

Melvin Lee, MD; Robert E. Kalb, MD


Dermatology Nursing. 2008;20(2):105-111. 

In This Article


Methotrexate is an immunosuppressive agent which blocks DNA synthesis by inhibiting dihydrofolate reductase. It is typically given either as a single weekly dose of 7.5 to 25 mg per week or divided into three doses each week at 12-hour intervals (Weinstein & Frost, 1971). Methotrexate is most commonly given via the oral route, however subcutaneous administration is also an option (Zackheim, 1992). Possible advantages of subcutaneous injections include less nausea and increased bioavailability. Patients may also be more familiar with self-injection because of the proliferation of that administration route with biologic therapy.

In addition to nausea, methotrexate can cause anemia and rarely pancytopenia. Both of these side effects can be reduced with folic acid supplementation (Duhra, 1993; Ortiz et al., 1998). It was previously thought that folic acid supplementation may reduce the efficacy of methotrexate, but a recent review refutes that claim (Salim, Tan, Ilchyshyn, & Berth-Jones, 2006; Strober & Menon, 2005).

Patients on long-term methotrexate therapy also may develop cirrhosis (Gilbert, Klintmalm, Menter, & Silverman, 1990). Risk factors for this include pre-existing liver disease, alcohol use, diabetes, and obesity (Langman, Hall, & Todd, 2001). Although there is relatively little mention of screening for cirrhosis using liver biopsies in the rheumatology literature, this issue has caused much concern and controversy among dermatologists. Current American Academy of Dermatology (AAD) guidelines suggest a liver biopsy after each cumulative methotrexate dose of 1.5 g; however, more recent studies suggest that the first liver biopsy may not be necessary in patients without risk factors until 3.5 to 4 g of methotrexate have been given (Aithal et al., 2004; Langman et al., 2001).

Other tests of liver function have been investigated in an attempt to decrease the need for liver biopsies. Some recent studies suggest that liver biopsies can be avoided if PIIINP (procollagen III) levels are consistently normal (Maurice et al., 2005). Another study showed a seven-fold decrease in biopsies using a PIIINP protocol compared to AAD guidelines (Chalmers et al., 2005). Unfortunately this test is not approved for use in the United States.


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