Actinic Keratosis: Current Therapies and Insights Into New Treatments

Actinic keratosis (AK) lesions are common epidermal neoplasms that present as erythematous, hyper-keratotic, scaly papules on a background of chronic sun damage. It is widely accepted that AKs represent the initial manifestations in a continuum that may eventually progress to squamous cell carcinoma (SCC).^1,2 Given the high prevalence of AKs and the potential for malignant transformation, early detection by clinical evaluation and treatment are commonly indicated. The National Ambulatory Medical Care Survey on outpatient medical care in the US found that AK was the second-leading diagnosis at dermatology visits and constituted 14.6% of visits to dermatologists between 1993 and 2010.³ In 2004 alone, the prevalence of AKs in the US was estimated to be 39.5 million.⁴ Actinic keratoses typically arise on chronically sun-exposed skin surfaces such as the face, balding scalp, and dorsal forearms and hands.^1,2 As the number of neoplastic cells in the epidermis increases, the lesion becomes clinically palpable.² Importantly, it has been shown that subclinical AKs also exist in areas of chronically sun-exposed skin, a phenomenon termed “field cancerization”. ¹ In addition to treating clinically apparent AK lesions, preventative treatment and photoprotection strategies should also be directed at these areas of subclinical actinic damage. To the dermatologist, treating what is on the way is as important as what is present today.Histologically, AKs are characterized by a disorganized neo-plastic proliferation of epidermal keratinocytes. These keratinocytes display increased number of mitoses, disorganized differentiation and orientation, and nuclear pleomorphism wherein the nuclei are enlarged, irregular, and/or hyperchromatic with pale or vacuolized eosinophilic cytoplasm.² Lesions can be categorized into the following six types based on histology: hypertrophic, atrophic, bowenoid, acantholytic, lichenoid, and pigmented.¹Actinic keratoses are graded on the extent of epidermal keratinocytic dysplasia using a three-tiered classification system. Keratinocytic intraepidermal neoplasia (KIN) I describes a flat lesion with focal cellular atypia of basal and suprabasal keratinocytes limited to the lower third of the epidermis. More advanced is KIN II, which describes a hyperkeratotic papule with atypia that extends to the lower two-thirds of the epidermis. Finally, KIN III, equivalent to SCC in situ, describes a plaque with diffuse atypical keratinocytes extending through the full thickness of the epidermis.⁵The most critical risk factor associated with the development of AKs is cumulative ultraviolet (UV) damage.6 Other risk factors include fair skin (Fitzpatrick skin types I and II), male gender, baldness in men, older age, geographic latitude (proximity to the equator), and immunosuppression.^6-9 Countries such as Australia, which have large Caucasian populations and are located close to the equator, have prevalence rates as high as 40–50% in adults 40 years and older.¹ Other risk factors include