Actinic Keratosis

Clinical Definition and Features

Actinic keratoses (AKs), also known as solar keratoses, are benign, red, scaly tumors of the epidermis caused by cumulative effects of solar radiation on the skin and are mostly manifested on body sites that receive high sun exposure (such as the face, ears, scalp, dorsal forearms, and hands) in older, pale-skinned populations.

Clinical manifestation

Actinic keratoses first appear as flesh-colored to pink, flat or slightly raised, well-defined, scaly lesions that usually occur on the scalp, neck, ears, and dorsum of the hands.

These lesions feel rough on palpation and usually arise from obviously sun-damaged skin (dry, wrinkled, atrophic, and telangiectatic).

Whereas parts of seborrheic keratoses Opens in new window can be scraped off easily with the fingernail or a tongue blade, this is not at all true of actinic lesions.

A horny, keratotic, conical protuberance, called a cutaneous horn Opens in new window, may develop from an actinic keratosis. Systemic chemotherapy may inflame AKs, resembling a drug rash in sun-exposed sites.

Prevalence by Age, Sex, and Body Site

Actinic keratosis has higher predilection among men than women of the same age. In Northern European and North American whites. AKs are uncommon before the age of 40 years.

White Australians in their 30s have similar AK prevalence to that of Northern Europeans in their 70s. The body site distribution of AKs is characteristic and reflects the sites of heaviest sun exposure.

In population based-surveys, the face, forearms and backs of the hands are the sites of the vast majority of prevalent AKs, with the relative site distribution depending on factors like local climate and culture.

In north west England, the sites most affected are (in order) the scalp, forehead, ears, cheek, chin and jaw. Similarly, in southeast Queensland, all affected persons had prevalent AKs on the upper limbs (60%) or head (40%), but prevalent AKs were also noted on the trunk and lower limbs in a material proportion of participants.

In the Netherlands, the face was most commonly affected among people with less than 10 prevalent AKs, but the scalp was the site most affected on those with more than 10 AKs (all in bald men).

In a detailed study of AK site distribution in a clinical referral setting in Korea, 95% of AKs were seen on the head and neck, specifically, the cheek (44%), forehead (15%) and nose (10%).

There is a net increase of AKs with increasing age, and the reported annual incidence rates in prospectively followed community samples range from 9% in persons over the age of 60 years in South Wales, to 19% and 60% per year in people aged 40-99 years who were previously unaffected and affected, respectively, in southern Australia, to 53% and 30% in men and women, respectively, aged 30-69 years in subtropical Australia.

Epidemiology

The epidemiology of AKs reflects their causation by cumulative sun exposure, with the highest prevalence seen in pale-skinned people whose accumulated sun exposure is high.

AKs may be very numerous (over 50), and in people with severe photodamage, contiguous AKs may coalescence into large areas of patchily inflamed and keratotic skin (Figure X-1).

These fields of abnormal skin are known as areas of field change or field cancerization Opens in new window, and in these situations, AKs cause cosmetic disfigurement and physical irritation.

AKs are of public health importance because their presence flags significantly raised risks of basal cell carcinoma Opens in new window, squamous cell carcinoma (SCC) Opens in new window and melanoma Opens in new window.

This is because AKs, along with other similar biomarkers like solar elastosis and pigmentation changes, including solar lentigines, are biomarkers of large cumulative doses of ultraviolet radiation to the skin in susceptible people. Moreover, a minute proportion of AKs undergo malignant transformation to SCC. AKs are of economic importance in affected populations because annual treatment costs are very high.

Risk Factors

Pigmentation

AKs occur more often among people of European ancestry who have light complexions, light hair and eye color, a propensity to sunburn and many freckles than among people who have darker skin, hair and eye color and sunburn rarely.

Sun Exposure

The causal role of solar radiation exposure is supported by the consistent observation of the highest prevalence in fair-skinned, sun-sensitive people living at low latitudes where solar ultraviolet radiation is most intense and high year round.

Fair-skinned migrants from high- to low-latitude countries have a lower AK prevalence than native-born residents, and people with heavy cumulative sun exposure and multiple sunburns have 2–3-fold higher risks of AKs than the others.

Immunosuppression

Because immune surveillance plays a key role in skin tumorigenesis, immunosuppression is associated with AKs. Best studies are white organ transplant recipients whose increased risk of developing benign and premalignant lesions associated with skin cancer compared with that of the general population has been documented widely.

The most common benign lesions are warty verrucous keratoses that often co-occur with AKs and can be difficult to differentiate. In contrast to organ transplant recipients of European ancestry, Asian organ transplant recipients have a low risk of developing AKs.

Therapeutics

Primary prevention of actinic keratosis is achieved by reducing cumulative sun exposure. The main sun-protective behaviors are limiting outdoor sun exposure as much as possible between the hours of 10 am and 2 pm, either by staying indoors or, if outdoors, seeking deep shade or wearing sun-protective clothing and sunscreen.

Sunscreen application is the most common means of skin protection when in the sun, and regular use of sunscreen has been shown to protect against the development of AKs in adults in 3 randomized controlled trials.

The first trial was conducted over a 7-month period in 431 white volunteer residents of Maryborough, Victoria who had prevalent AKs at baseline.

The participants were randomized to apply either broad-spectrum SPF 17 sunscreen or placebo (base-cream) to their head, neck, forearms and backs of hands every morning, and they reapplied if necessary during the day.

Regular sunscreen use in the short term reduced the mean number of new AKs by 0.6 (standard error ± 0.3) in the sunscreen intervention group, while this number was increased by 1.0 (standard error ± 0.3) in the placebo group, corresponding to a rate ratio of 0.62 (95% CI = 0.54–0.71).

Sunscreen allocation was also associated with remission of existing AK. A small randomized controlled trial including 50 volunteer patients with prevalent AKs or past keratinocyte cancers was carried out in a specialized dermatology clinic in the US over a 2-year period.

Patients randomly assigned to apply SPF 29 sunscreen daily showed a 36% reduction in new AKs compared with a placebo group using sunscreen base.

Finally, 1,621 adult residents of the Nambour community in Queensland, Australia were randomized either to apply broad-spectrum SPF 16 sunscreen to their head, neck, forearms and backs of hands every morning, with reapplication as necessary, or to use sunscreen at their usual discretionary rate.

Allocation to daily sunscreen use significantly reduced the rate of AK acquisition among participants of the Nambour Trial by 22% in the first 2 years, although the protective effect diminished during the second half of the intervention period.

As above, a range of other factors has been suggested as having possible protective effects on AKs. These include taking NSAIDS and consumption of a low-fat diet or of certain food groups, like oily fish, but such protection has not been confirmed through evaluation in randomized controlled trials.

In two small Phase II randomized controlled trials that were carried out to evaluate oral nicotinamide (vitamin B3) (500 mg twice or once daily) as a potential AK preventive in immunocompetent patients, there were relative reductions in AK counts of 35% and 29%, respectively, in those allocated to nicotinamide supplements compared with those taking placebo supplements.

These promising results await evaluation in a larger Phase III trial.

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