Actinic keratosis


Actinic keratosis, sometimes called solar keratosis or senile keratosis, is a pre-cancerous area of thick, scaly, or crusty skin. Actinic keratosis is a disorder of epidermal keratinocytes that is induced by ultraviolet light exposure.
These growths are more common in fair-skinned people and those who are frequently in the sun. They are believed to form when skin gets damaged by UV radiation from the sun or indoor tanning beds, usually over the course of decades. Given their pre-cancerous nature, if left untreated, they may turn into a type of skin cancer called squamous cell carcinoma. Untreated lesions have up to a 20% risk of progression to squamous cell carcinoma, so treatment by a dermatologist is recommended.
Actinic keratoses characteristically appear as thick, scaly, or crusty areas that often feel dry or rough. Size commonly ranges between 2 and 6 millimeters, but they can grow to be several centimeters in diameter. Actinic keratoses are often felt before they are seen, and the texture is sometimes compared to sandpaper. They may be dark, light, tan, pink, red, a combination of all these, or have the same color as the surrounding skin.
Given the causal relationship between sun exposure and actinic keratosis growth, they often appear on a background of sun-damaged skin and in areas that are commonly sun-exposed, such as the face, ears, neck, scalp, chest, backs of hands, forearms, or lips. Because sun exposure is rarely limited to a small area, most people who have an actinic keratosis have more than one.
If clinical examination findings are not typical of actinic keratosis and the possibility of in situ or invasive squamous cell carcinoma cannot be excluded based on clinical examination alone, a biopsy or excision can be considered for definitive diagnosis by histologic examination of the lesional tissue. Multiple treatment options for actinic keratosis are available. Photodynamic therapy is one option for the treatment of numerous actinic keratosis lesions in a region of the skin, termed field cancerization. It involves the application of a photosensitizer to the skin followed by illumination with a strong light source. Topical creams, such as 5-fluorouracil or imiquimod, may require daily application to affected skin areas over a typical time course of weeks.
Cryotherapy is frequently used for few and well-defined lesions, but undesired skin lightening, or hypopigmentation, may occur at the treatment site. By following up with a dermatologist, actinic keratoses can be treated before they progress to skin cancer. If cancer does develop from an actinic keratosis lesion, it can be caught early with close monitoring, at a time when treatment is likely to have a high cure rate.

Signs and symptoms

Actinic keratoses most commonly present as a white, scaly plaque of variable thickness with surrounding redness; they have a sandpaper-like texture when felt with a gloved hand. Skin nearby the lesion often shows evidence of solar damage characterized by pigmentary alterations, being yellow or pale in color with areas of hyperpigmentation; deep wrinkles, coarse texture, purpura and ecchymoses, dry skin, and scattered telangiectasias are also characteristic.
Photoaging leads to an accumulation of oncogenic changes, resulting in a proliferation of mutated keratinocytes that can manifest as actinic keratoses or other neoplastic growths.
The lesions are usually asymptomatic, but can be tender, itch, bleed, or produce a stinging or burning sensation. Actinic keratoses are typically graded in accordance with their clinical presentation: Grade I, Grade II, and Grade III.

Variants

Actinic keratoses can have various clinical presentations, often characterized as follows:
  • Classic : Classic actinic keratoses present as white, scaly macules, papules or plaques of various thickness, often with surrounding erythema. They are usually 2–6mm in diameter but can sometimes reach several centimeters in diameter.
  • Hypertrophic : Hypertrophic actinic keratoses appears as a thicker scale or rough papule or plaque, often adherent to an erythematous base. Classic actinic keratoses can progress to become HAKs, and HAKs themselves can be difficult to distinguish from malignant lesions.
  • Atrophic: Atrophic actinic keratoses lack an overlying scale, and therefore appear as a nonpalpable change in color. They are often smooth and red and are less than 10mm in diameter.
  • Actinic keratosis with cutaneous horn: A cutaneous horn is a keratinic projection with its height at least one-half of its diameter, often conical in shape. They can be seen in the setting of actinic keratosis as a progression of an HAK, but are also present in other skin conditions. 38–40% of cutaneous horns represent actinic keratoses.
  • Pigmented actinic keratosis: Pigmented actinic keratoses are rare variants that often present as macules or plaques that are tan to brown in color. They can be difficult to distinguish from a solar lentigo or lentigo maligna.
  • Actinic cheilitis: When an actinic keratosis forms on the lip, it is called actinic cheilitis. This usually presents as a rough, scaly patch on the lip, often accompanied by the sensation of dry mouth and symptomatic splitting of the lips.
  • Bowenoid actinic keratosis: Usually presents as a solitary, erythematous, scaly patch or plaque with well-defined borders. Bowenoid actinic keratoses are differentiated from Bowen's disease by degree of epithelial involvement as seen on histology.
The presence of ulceration, nodularity, or bleeding should raise concern for malignancy. Specifically, clinical findings suggesting an increased risk of progression to squamous cell carcinoma can be recognized as "IDRBEU": I, D, R, B, E, and U. Actinic keratoses are usually diagnosed clinically, but because they are difficult to clinically differentiate from squamous cell carcinoma, any concerning features warrant biopsy for diagnostic confirmation.

Causes

The most important cause of actinic keratosis formation is solar radiation, through a variety of mechanisms. Mutation of the p53 tumor suppressor gene, induced by UV radiation, has been identified as a crucial step in actinic keratosis formation. This tumor suppressor gene, located on chromosome 17p132, allows for cell cycle arrest when DNA or RNA is damaged. Dysregulation of the p53 pathway can thus result in unchecked replication of dysplastic keratinocytes, thereby serving as a source of neoplastic growth and the development of actinic keratosis, as well as possible progression from actinic keratosis to skin cancer. Other molecular markers that have been associated with the development of actinic keratosis include the expression of p16ink4, p14, the CD95 ligand, TNF-related apoptosis-inducing ligand and TRAIL receptors, and loss of heterozygosity.
Evidence also suggests that the human papillomavirus plays a role in the development of actinic keratoses. The HPV virus has been detected in actinic keratoses, with measurable HPV viral loads measured in 40% of actinic keratoses. Similar to UV radiation, higher levels of HPV found in actinic keratoses reflect enhanced viral DNA replication. This is suspected to be related to the abnormal keratinocyte proliferation and differentiation in actinic keratoses, which facilitate an environment for HPV replication. This in turn may further stimulate the abnormal proliferation that contributes to the development of actinic keratoses and carcinogenesis.

Ultraviolet radiation

It is thought that ultraviolet radiation induces mutations in the keratinocytes of the epidermis, promoting the survival and proliferation of these atypical cells. Both UV-A and UV-B radiation have been implicated as causes of actinic keratoses. UV-A radiation reaches more deeply into the skin and can lead to the generation of reactive oxygen species, which in turn can damage cell membranes, signaling proteins, and nucleic acids. UV-B radiation causes thymidine dimer formation in DNA and RNA, leading to significant cellular mutations. In particular, mutations in the p53 tumor suppressor gene have been found in 30–50% of actinic keratosis lesion skin samples.
UV radiation has also been shown to cause elevated inflammatory markers such as arachidonic acid, as well as other molecules associated with inflammation. Eventually, over time these changes lead to the formation of actinic keratoses. Several predictors for increased actinic keratosis risk from UV radiation have been identified:
  • Extent of sun exposure: Cumulative sun exposure leads to an increased risk for development of actinic keratoses. In one study, actinic keratoses were found in 55% of fair-skinned men with high cumulative sun exposure, and in only 19% of fair-skinned men with low cumulative sun exposure in an age-matched cohort. Furthermore, the use of sunscreen has been found to significantly reduce the development of actinic keratosis lesions, and also promotes the regression of existing lesions.
  • History of sunburn: Studies show that even a single episode of painful sunburn as a child can increase an individual's risk of developing actinic keratosis as an adult. Six or more painful sunburns over the course of a lifetime was found to be significantly associated with the likelihood of developing actinic keratosis.

    Skin pigmentation

is a pigment in the epidermis that functions to protect keratinocytes from the damage caused by UV radiation; it is found in higher concentrations in the epidermis of darker-skinned individuals, affording them protection against the development of actinic keratoses.
Fair-skinned individuals have a significantly increased risk of developing actinic keratoses when compared to olive-skinned individuals, and actinic keratoses are uncommon in dark-skinned people of African descent. Other phenotypic features seen in fair-skinned individuals that are associated with an increased propensity to develop actinic keratoses include:
  • Freckling
  • Light hair and eye color
  • Propensity to sunburn
  • Inability to tan