The Use of Systemic Immune Moderators in Dermatology: An Update (original) (raw)

Abstract

When inflammatory dermatoses are severe or recalcitrant to topical therapies, dermatologists are occasionally required to prescribe immunomodulatory drugs. The first-line systemic anti-inflammatory therapy is the oral administration of corticosteroids, but frequently other immunomodulatory drugs are needed to control disease activity, while at the same time limiting or even eliminating the need for corticosteroids. These immunomodulatory therapies can be divided into two broad categories: the more traditional and well-known nonsteroidal immune-modifying drugs, also commonly referred to as the systemic therapies, and the newer immunobiologic agents. The most common nonsteroidal immune-modifying drugs include the following agents: azathioprine, cyclophosphamide, cyclosporine, methotrexate, and mycophenolate mofetil (MMF). These agents are predominantly cytotoxic, but data seem to suggest that methotrexate has significant anti-inflammatory activity as well. The other category encompasses the plethora of newer immunobiologic agents that are being developed, the most well known of which include alefacept, efalizumab, etanercept, and infliximab. The current authors and others have previously reviewed the pharmacology, mode of action, and adverse effects of some of these agents [1-6]. The current article reviews new data concerning the pharmacology, mechanism of action, adverse effects, and dermatologic applications of these two categories of therapeutic agent. Familiarity with the diseasespecific clinical efficacy of each of these medications and their dosages and side-effect profiles allows for the proper and efficacious use of these drugs to treat dermatologic disease. Azathioprine Inititially used as an immunosuppressant for renal transplantation, azathioprine has been available for more than 40 years, and because of its relatively favorable therapeutic index, it is one of the more commonly used immunomodulatory drugs in dermatology. Structurally, it is a synthetic purine analog formed by attaching an imidazole ring to 6-mercaptopurine (6-MP). This analog is a prodrug and is quickly converted to 6-MP by a nonenzymatic

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