Actinic Keratoses and Other Precursors of Keratinocytic Cutaneous Malignancies

Definition

Actinic keratoses (AKs) are circumscribed, rough scaly lesions that develop on exposed skin surfaces and are primarily due to chronic ultraviolet irradiation that may result from sun exposure or exposure to artificial light sources such as tanning beds, ultraviolet light phototherapy, or photochemotherapy. Similar lesions may develop following radiation from radioactive sources such as X-ray therapy. AKs were long considered in the past as premalignancies, but current thinking by most authors views these lesions as evolving squamous cell carcinoma (SCC) in situ in its earliest form.

The term actinic keratosis (AK) was coined relatively recently. It was first used by Hermann Pinkus, and, in 1959, Becker included it in his publication on dermatological nomenclature. Historically, these lesions were recognized as a complication caused by longstanding sun exposure in seamen or farmers and were termed senile keratosis or keratosis senilis. The name was given neither because of the biology of the lesions nor because of the histopathology, but because of the rough texture that could be easily appreciated clinically. In fact, in many early textbooks, they were included in chapters with other scaly conditions often referred to as ‘keratoses’ such as keratodermas and keratoderma blenorrhagicum. The term solar keratosis was applied to these lesions later by Brownstein in an attempt to reflect that they are most commonly induced by sun exposure (although they can be induced by chronic exposure from artificial sources). In that the lesion is truly neoplastic, suggestions have been offered to change the name to one that more accurately reflects the acutal nature of the process rather than its clinical appearance.

Risk factors

The propensity to develop AKs is genetically influenced and those with fair skin (Fitzpatrick types I and II), blue eyes, and red or blonde hair have a markedly increased susceptibility. Those with darker pigmentation are relatively protected, although when they become less pigmented, such as with vitiligo or albinism, AKs commonly develop. The predominant risk factor for the development of AKs is cumulative exposure to ultraviolet (UV) irradiation. Short-term, intense UV exposure also provides additional risk, although repeated long-term exposure is more important. Repeated consistent application of sunscreen has been shown to suppress the formation of AKs.

Behaviors that increase cumulative UV exposure increase the risk of developing AKs, some of which include outdoor labor, leisure activities associated with sun exposure, and the use of artificial tanning beds. The intensity of UV is greatest at latitudes closer to the equator and in areas of higher elevation, and therefore those who live in these areas are also at increased risk, especially if they have fair complexions. An important example of this can be seen in Australia and New Zealand, where the Caucasian population has the highest incidence of skin cancer and melanoma in the world. More recently, ozone depletion, which permits a higher penetrance of UV irradiation to the Earth's surface, compounds this risk, even in temperate areas. Finally, the increased longevity of the population also contributes to the increasing prevalence of AKs.

As noted above, cumulative lifetime UV irradiation is most important in the development of AKs and cutaneous SCC, with repeated sunburn playing a lesser role. This is thought to be the opposite of what is responsible for the development of basal cell carcinoma and melanoma, as intense intermittent exposures and severe sunburns in childhood are the most important risk factors.

Immunosuppression is another independent risk factor for the development of cutaneous keratinocytic malignancies. The widespread use of immunosuppressive drugs for organ transplantation, in cancer therapy, and in the treatment of rheumatologic and other inflammatory diseases has led to a significant increase in the number of immuno-suppressed patients, many of whom develop AKs and cutaneous malignancies. Often such patients have literally hundreds of lesions and cutaneous SCC is often the cause of death in these individuals. Furthermore, in immunosuppressed patients, human papillomavirus infection may be a synergistic factor in the development of AKs and SCC. This relationship does not seem to hold true for immunocompetent patients, however.

Incidence and prevalence

The incidence of AK increases with age, with less than 10% of people affected in the third decade of life but 80% affected in the sixth decade. Men tend to develop AKs at a younger age but the gender prevalence equalizes in the elderly population. As mentioned above, there is an inverse relationship between latitude and prevalence. For example, in Australia the prevalence of AKs in adults over 40 may be as high as 60%.