Table of Contents
This Chapter	All Chapters

Gary M. White & Neil H. Cox

Diseases of the Skin

3	Topical Therapy

ANTINEOPLASTIC AGENTS

5-Fluorouracil

5-Fluorouracil is a topical agent that selectively kills photodamaged keratinocytes. It is effective at reducing actinic keratoses and in treatment of Bowen disease. It is applied once daily or b.i.d. for 2–4 weeks, and usually causes significant inflammation, crusting, and even erosion. It is particularly effective for actinic cheilitis of the lips. Some practitioners recommend a low-strength topical steroid for several days at the end of therapy to help return the skin to normal. Sun protection is of paramount importance both during therapy and after. Alternative regimens (e.g. b.i.d. for 2 consecutive days a week for 10–12 weeks) are recommended by many as they reduce the side effects, but such regimens involve a longer course. The most commonly used preparation is 5%, but several lower concentrations are available in the USA for a more prophylactic (secondary prevention) type of approach to actinic keratoses.

Diclofenac–hyaluronic acid

A preparation of these agents (3% and 2.5%, respectively, in a gel base) has been shown to be useful in treatment of actinic keratoses. It causes less inflammation than 5-fluorouracil does in most patients, but the benefit is less apparent.

Mustine (nitrogen mustard)

This is sometimes used topically for mycosis fungoides (Ch.33), but it is difficult to use due to irritancy of some formulations and potential toxicity to others who may come into contact with the drug.

Imiquimod

Imiquimod is an immune modifier with antiviral and antineoplastic activities. Although initially used for treatment of genital warts, it is discussed here as it seems likely to have a role for treatment of several neoplastic lesions.

Imiquimod acts at least in part by stimulating the production of proinflammatory cytokines through Toll-like receptor 7 on the surface of dendritic cells of monocyte-macrophage lineage. This activation stimulates the patient's own immune system to attack both virally infected and tumor cells. Imiquimod is proved effective against genital warts as well as in treatment of superficial malignancies and their precursors, for example actinic keratoses, Bowen disease, superficial basal cell carcinoma, and lentigo maligna (although, at the time of writing, many of these are not yet licensed indications). It may have some benefit in the treatment of common warts and molluscum contagiosum. Application is three times a week for warts and up five to seven times a week for neoplasms. Severe inflammation of the skin should be expected. Some patients develop flu-like symptoms during therapy.

Figure. 3.8 Keratoderma. Thick hyperkeratosis requires a strong keratolytic, for example urea or salicylic acid.