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Cytotoxic and antimetabolic agents may be used to treat severe or refractory skin disease. The toxicities of such agents are significant and must be balanced against therapeutic advantage. In treating skin disease, most of these agents are utilized at immunomodulatory rather than cytotoxic dosages.
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Cytotoxic and antimetabolic drugs modulate the behavior of inflammatory and other cells through inhibition of cell growth and development. The cell cycle represents a conceptual schema for the sequence of growth experienced by essentially all cells (see Chapter 46). The cycle begins with the G1 phase, which is directed toward preparing the cellular apparatus for DNA synthesis. The S phase follows G1 and is devoted to DNA synthesis. At the end of DNA synthesis, the G2 phase occurs. The G2 phase is followed by the M phase, or actual cell division. Some cells may also enter a resting state of indeterminate length, termed G0. Specific cytotoxic drugs may be effective at different stages of the cell cycle.
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The cytotoxic drugs commonly used in dermatology fall into two classes: (1) antimetabolites and (2) alkylating agents. Antimetabolites mimic natural molecules and are most active while DNA is being synthesized (S phase). Alkylating agents exert effect through physicochemical interactions with DNA, such as alkylation, cross-linking, and carbamylation. The effects of alkylating agents are generally independent of the cell cycle.
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The immunosuppressive properties of cytotoxic agents (see also Chapter 233) provide benefit in immunologically mediated disease, yet these agents may predispose to infection as well. Potentially lethal infections may arise quickly in an immunosuppressed patient. Those placed on cytotoxic agents should be queried at each visit for symptoms of infection, such as fever, chills, sweating, shortness of breath, cough, headache, dysuria, and arthritis. Prompt reporting of symptoms should be encouraged.
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Methotrexate remains one of the most frequently employed antimetabolic agents in dermatology. With appropriate monitoring, an impressive record of safety with methotrexate has accumulated. Concerns regarding use of methotrexate are best addressed through ...