Pharmacotherapy of actinic keratosis

Abstract

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.

Ingenol Mebutate Field-Directed Treatment of UVB-Damaged Skin Reduces Lesion Formation and Removes Mutant p53 Patches

“…Here we show, using the hairless SKH-1/hr mouse model, that field-directed treatment (Berman et al, 2009;Jorizzo et al, 2010;Feldman and Fleischer, 2011) of precancerous chronically UVBirradiated skin with ingenol mebutate significantly reduced the number of skin lesions that subsequently developed. Ingenol mebutate treatment also significantly reduced the number of mutant p53 patches present in the skin.…”

“…This study thus illustrates that ingenol mebutate may find utility for the field-directed treatment of UV-damaged skin to reduce the emergence of AKs and NMSC. Such treatment may be particularly suitable for patients with multiple or recurring AKs (Berman et al, 2009;Jorizzo et al, 2010;Feldman and Fleischer, 2011) and/or patients who are at high risk of developing NMSC (Marcil and Stern, 2000).…”

A consensus approach to improving patient adherence and persistence with topical treatment for actinic keratosis

“…Our expert panel concurred that AK is being increasingly perceived as a disease but thought that awareness of the risk of AK progressing into SCC is still lacking. Physicians' awareness of this therefore needs to increase, supporting the finding of another consensus study 28 that concluded the main treatment goal is to promote a good overall outlook by minimizing the risk of progression of AK to SCC. Developing physicians' knowledge of the potential for SCC to develop would provide them with the necessary background to promote and manage a successful treatment strategy that maximizes adherence and persistence.…”

Visualization and Treatment of Subclinical Actinic Keratoses with Topical Imiquimod 5% Cream: An Observational Study

“…AK evolves slowly in the basal layer until they become thicker and clinically evident as coarse erythematous patches in early stages; later they are hyperkeratotic [3–5]. Topical imiquimod 5% cream has been shown to be useful in clearing AK lesions [6–10]. Imiquimod as a toll-like-receptor-7- (TLR-7)-agonist induces cytokines, starting an inflammatory skin reaction directed primarily against malignant or virus-infected cells, but has virtually no effect on normal skin.…”