User:Doxy cycling/sandbox

Causes
The most important cause of AK 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 AK 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 AK, as well as possible progression from AK to skin cancer. Other molecular markers that have been associated with the development of AK include the expression of p16ink4, p14, the CD95 ligand, TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptors, and loss of heterozygosity.

Evidence also suggests that the human papillomavirus (HPV) plays a role in the development of AKs. The HPV virus has been detected in AKs, with measurable HPV viral loads (1 HPV-DNA copy per less than 50 cells) measured in 40% of AKs. Similar to UV radiation, higher levels of HPV found in AKs reflect enhanced viral DNA replication. This is suspected to be related to the abnormal keratinocyte proliferation and differentiation in AKs, which facilitate an environment for HPV replication. This in turn may further stimulate the abnormal proliferation that contributes to the development of AKs and carcinogenesis.

Ultraviolet radiation
It is thought that ultraviolet (UV) 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 AKs. UV-A radiation (wavelength 320-400nm) 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 (wavelength 290–320nm) 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 AK 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 AKs. Several predictors for increased AK risk from UV radiation have been identified:


 * Extent of sun exposure: Cumulative sun exposure leads to an increased risk for development of AKs. In one U.S. study, AKs 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 (the percents for women in this same study were 37% and 12% respectively). Furthermore, the use of sunscreen (SPF 17 or higher) has been found to significantly reduce the development of AK 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 AK 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 AK.

 SOURCES 

Dinehart 2000 JAAD: Treatment of Actinic Keratoses. ****Cited on AAD website

- cryo MC used tx in US

- more than 90% effective, no anesthesia

- recommended for <= 15

- curettage +/- electrodesiccation particularly useful for biopsy-proven, suspicion for SCC, hasn't been responsive to other treatments

Feldman SR, Fleischer AB, Jr., Williford PM et al. “Destructive procedures are the standard of care for treatment of actinic keratoses.” J Am Acad Dermatol 1999 Jan; 40: 43-7. ***Cited on AAD website

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Moreover, large areas of sun-exposed skin are diagnosed with a continuum of multiple clinically visible AKs of different sizes and severities, typically accompanied by subclinical lesions that become apparent only in biopsies.

This concept of a skin area showing multiple AKs is termed field cancerization.

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AKs are most often seen in individuals with fair skin and are commonly found on the scalp of balding individuals.