Cytotoxic

A variety of cytotoxic agents are used for the treatment of autoimmune diseases such as pemphigus, pemphigoid, dermatomyositis, and lupus erythematosus. The most commonly administered medications include azathioprine (Imuran), cyclophosphamide (Cytoxan), and methotrexate. For the most part, these medications are used only for patients nonresponsive to steroids or in instances where steroid side effects require a lowering of the steroid dose. An exception to this occurs in the treatment of psoriasis where methotrexate can be considered as a first-line drug for widespread, debilitating disease.

Methotrexate when used in psoriasis is usually given as a once weekly oral dose of 25 mg. Most patients will begin to improve by the end of the first month and will be rather remarkably better at the end of the second month. Once maximum improvement is reached, the dose is gradually reduced to a maintenance level, which generally averages about 15 mg/week. Patients with less responsive disease sometimes require fractionation of the dosage. The mechanisms through which methotrexate improves psoriasis certainly include an antiproliferative effect on the lesional epithelial cells, but there is almost certainly an additional anti-inflammatory effect also.

The most common acute side effects occurring with methotrexate include nausea, aphthous-like ulcers of the mouth, abnormal liver function studies, and transient bone marrow depression. All of these appear to be dose related and can be managed by appropriate reduction in the amount administered at the time of the next treatment. Hepatotoxicity is a major long-term side effect. Recognition of this problem appears to require periodic liver biopsy, since, despite the presence of major structural changes, liver function abnormalities as measured by conventional tests may not be present. Liver biopsies in patients who have taken methotrexate for several years regularly reveal some degree of inflammation and fatty infiltration. About 10% of patients who have taken methotrexate for more than 5 years will also develop mild to moderate fibrosis. So far there has been no problem with drug-induced carcinogenesis or reduction in immune response sufficient to cause opportunistic infections.

This entry was posted on Tuesday, February 5th, 2008 at 12:02 pm and is filed under Diagnostic and Therapeutic Techniques. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.