Pharmacotherapy of actinic keratosis

Actinic keratosis (AK) represents the initial intraepidermal manifestation of abnormal keratinocyte proliferation with the potential of progression to squamous cell carcinoma (SCC). When in limited numbers, clinically visible AKs are treated individually with ablative and/or surgical procedures (lesion-directed treatment), while multiple and sublinical AKs are treated with field-directed therapies that use ablative, nonablating and other topically applied treatment modalities. Owing to difficulties in predicting which AK will progress to SCC, the general rule is to treat all AKs. The goals of treatment are to eliminate the AKs, minimizing their risk of progression to invasive SCC, while pursuing good cosmetic outcomes. Prevention is the most important treatment modality for AKs. Avoidance of sun and artificial sources of ultraviolet light, applying sunscreen and self-examination are among the most effective preventive measures. Chemopreventive modalities such as retinoids, 2-(Difluoromethyl)-dl-ornithine (DFMO), perillyl alcohol, T4 endonuclease V, and dl-alpha-tocopherol are described. Lesion-directed treatment modalities include cryotherapy, surgery and electrodessication with or without curettage. Field-directed treatment modalities include nonablative and ablative laser resurfacing, dermabrasion, chemical peels, topical immunomodulators (imiquimod, 5-fluorouracil and diclofenac) and photodynamic therapy. And, finally, newer and investigational treatment modalities such as ingenol mebutate, resiquimod and betulinic acid are also being discussed.