Actinic keratoses (AKs or solar keratoses) are keratotic macules, papules, or plaques resulting from the intraepidermal proliferation of atypical keratinocytes in response to prolonged exposure to ultraviolet radiation. Although most AKs do not progress to squamous cell carcinoma (SCC), AKs are a concern because the majority of cutaneous SCCs arise from pre-existing AKs, and AKs that will progress to SCC cannot be distinguished from AKs that will spontaneously resolve or persist [1,2]. Because of these factors, most clinicians routinely treat AKs . Improvement in associated symptoms and cosmetic appearance can be additional benefits of treatment.
The treatment of AKs will be reviewed here. The epidemiology, clinical manifestations, and diagnosis of AKs are discussed separately. (See "Epidemiology, natural history, and diagnosis of actinic keratosis".)
Overview — Treatment options for actinic keratosis (AK) include destructive therapies (eg, surgery, cryotherapy, dermabrasion), topical medications (eg, 5-fluorouracil [5-FU], imiquimod, ingenol mebutate, diclofenac), chemical peels (eg, trichloroacetic acid), and photodynamic therapy (PDT). In general, lesion-directed treatments, such as cryotherapy and surgical procedures, are the primary approach for isolated lesions . Field-directed therapies, such as topical 5-FU, imiquimod, ingenol mebutate, and diclofenac, are particularly useful for treating areas with multiple AKs. Evidence for efficacy of these therapies is derived from multiple randomized trials and systematic reviews [4-8].
One systematic review and meta-analysis of 83 randomized trials evaluating 24 treatments in over 10,000 patients found sufficient evidence to conclude that 3% diclofenac in 2.5% hyaluronic acid, 0.5% 5-FU, 5% imiquimod, and 0.025% to 0.05% ingenol mebutate are superior to placebo for complete clearance of lesions in the treated field in patients with AKs . In addition, this systematic review and meta-analysis found that PDT performed with aminolevulinic acid (ALA-PDT) with red light or blue light or with methyl aminolevulinate (MAL-PDT) with red light was superior to placebo for the treatment of individual AK lesions . The meta-analysis also found that treatment with imiquimod or PDT generally resulted in better cosmetic outcomes than 5-FU and cryotherapy .
A subsequent network meta-analysis of 26 individual or pooled randomized trials evaluated the relative efficacy in inducing complete lesion clearance for eight main interventions for AK . This analysis suggests that topical 5-FU is the most effective treatment followed by: 5-aminolevulinic acid (ALA) PDT; topical imiquimod; ingenol mebutate; 5-methylaminolaevulinate (MAL) PDT; cryotherapy; topical diclofenac with hyaluronic acid; and placebo. However, the ranking of relative efficacies should be interpreted with caution because of the variability in the parameters used to describe the AK severity in the included studies.