INTRODUCTION
Actinic keratoses (AKs) are hyperkeratotic, erythematous papules or plaques with overlying scale and rough texture found in sun-damaged areas of skin.1 They represent a chronic and recurring manifestation of field cancerization. AKs are most commonly diagnosed in fair-skinned individuals,2 and incidence increases with age and exposure to UV radiation.1 An analysis of the National Ambulatory Medical Care Survey (NAMCS) data from 1993–2010 found that 14.6% of dermatologist visits included a diagnosis of AK.3 Data pooled from several nation-wide surveys estimated the prevalence of AK in the United States to be 39.5 million in 2004.4
Areas of clinically sun-damaged skin are predisposed to tumorigenesis; this phenomenon is referred to as field-cancerization.5 In areas of skin with extensive sun-damage and/or multiple AKs, topical agents may be prescribed to treat overt lesions and prevent subclinical dysplasia from progressing to AK.5,6 AKs themselves may progress to squamous cell carcinoma (SCC); however, there are no clinical features unique to AK lesions which predict this transformation, and data regarding the rate of progression from AK to SCC are inconclusive.7 Therefore, the common consensus is to treat all AK lesions to prevent transformation to SCC.8 Multiple treatment modalities exist for the treatment of AK. Cryotherapy or excision may be used for individual AK lesions (lesion-directed therapy), and topicals or photodynamic therapy may be used in diffusely sun-damaged skin containing both overt and subclinical lesions (field-directed therapy).8
Topical agents have been used for the treatment of multiple AKs from the 1960s, beginning with the use of topical fluorouracil (5-FU). Dillaha et al in 1963 reported successful clearance of multiple AKs using a 20% 5-FU solution; however, patients also experienced severe inflammation, erosions, corneal and conjunctival irritation, and photosenstivity.9 Milder preparations of 5-FU and new topical agents for AK, such as the antimitotic agent tirbanibulin, have maintained treatment efficacy while substantially improving tolerability.10 The purpose of this review is to document the safety and tolerability of topical agents used for the treatment of AK.
Areas of clinically sun-damaged skin are predisposed to tumorigenesis; this phenomenon is referred to as field-cancerization.5 In areas of skin with extensive sun-damage and/or multiple AKs, topical agents may be prescribed to treat overt lesions and prevent subclinical dysplasia from progressing to AK.5,6 AKs themselves may progress to squamous cell carcinoma (SCC); however, there are no clinical features unique to AK lesions which predict this transformation, and data regarding the rate of progression from AK to SCC are inconclusive.7 Therefore, the common consensus is to treat all AK lesions to prevent transformation to SCC.8 Multiple treatment modalities exist for the treatment of AK. Cryotherapy or excision may be used for individual AK lesions (lesion-directed therapy), and topicals or photodynamic therapy may be used in diffusely sun-damaged skin containing both overt and subclinical lesions (field-directed therapy).8
Topical agents have been used for the treatment of multiple AKs from the 1960s, beginning with the use of topical fluorouracil (5-FU). Dillaha et al in 1963 reported successful clearance of multiple AKs using a 20% 5-FU solution; however, patients also experienced severe inflammation, erosions, corneal and conjunctival irritation, and photosenstivity.9 Milder preparations of 5-FU and new topical agents for AK, such as the antimitotic agent tirbanibulin, have maintained treatment efficacy while substantially improving tolerability.10 The purpose of this review is to document the safety and tolerability of topical agents used for the treatment of AK.
