Cytotoxic and antimetabolic agents are used in dermatology to treat serious, life-threatening, and recalcitrant disease.
Methotrexate and azathioprine are commonly used in dermatology whereas thioguanine, hydroxyurea, cyclophosphamide, chlorambucil, and liposomal doxorubicin are occasionally used.
Methotrexate is U.S. Food and Drug Administration (FDA) approved for treatment of psoriasis and advanced mycosis fungoides, whereas cyclophosphamide is FDA approved for advanced mycosis fungoides only, and liposomal doxorubicin is approved for AIDS-related Kaposi sarcoma; other uses of the agent in this chapter occur on an “off-label” basis.
Cytotoxic and antimetabolic agents act through inhibition and/or interruption of the cell cycle.
Side effects and complications with these potentially dangerous medications are numerous, and close clinical followup and laboratory evaluation is necessary.
Cytotoxic agents used in dermatology, as well as those initiated for other purposes, may yield distinctive cutaneous eruptions and cutaneous sequelae.
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 their therapeutic advantages. In treating skin disease, most of these agents are utilized at the lower immunomodulatory doses rather than at the higher cytotoxic doses.
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 (Chap. 5). Specific cytotoxic drugs may be effective at different stages of the cell cycle.
The cytotoxic drugs commonly used in dermatology fall into 2 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, crosslinking, and carbamylation. The effects of alkylating agents are generally independent of the cell cycle.
The immunosuppressive properties of cytotoxic agents (see also Chap. 192) 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.
We have organized these medications into 3 groups, Antiproliferative, Cytotoxic, and Immunosuppressive/antiinflammatory.
Methotrexate (MTX) is one of the most frequently employed antimetabolic agents in dermatology. An impressive record of safety with MTX has accumulated, though patient selection and monitoring is crucial for its safe use.
Discovered in 1948, MTX was initially used as a chemotherapeutic agent to treat hematologic malignancies. In dermatology, low doses of MTX are given for the treatment of nonneoplastic diseases including psoriasis, psoriatic arthritis, and dermatomyositis. It also has been used ...