Actinic keratosis
Encyclopedia
Actinic keratosis is a premalignant condition
of thick, scaly, or crusty patches of skin. It is more common in fair-skinned people. It is associated with those who are frequently exposed to the sun, as it is usually accompanied by solar
damage. Since some of these pre-cancers progress to squamous cell carcinoma
, they should be treated. Untreated lesions have up to twenty percent risk of progression to squamous cell carcinoma.
When skin is exposed to the sun constantly, thick, scaly, or crusty bumps appear. The scaly or crusty part of the bump is dry and rough. The growths start out as flat scaly areas, and later grow into a tough, wart-like area.
An actinic keratosis
site commonly ranges between 2 and 6 millimeters in size, and can be dark or light, tan, pink, red, a combination of all these, or have the same pigment as the surrounding skin. It may appear on any sun
-exposed area, such as the face, ears, neck, scalp, chest, backs of hands, forearms, or lips.
See also:
According to an article in the Journal of Investigative Dermatology (2005) 125, 93–97; doi:10.1111/j.0022-202X.2005.23733.x, entitled "Human Papillomavirus-DNA Loads in Actinic Keratoses Exceed those in Non-Melanoma Skin Cancers", actinic keratosis can contain a significant amount of infectious human papillomavirus. Verbatim: "HPV presents in significantly higher viral loads in actinic keratosis (AK), which are the precursor lesions of squamous cell carcinoma (SCC), than in SCC. Viral loads of 1 HPV-DNA copy per less than 50 cells were measured in 40% of AK. The higher viral loads in AK are likely to reflect enhanced HPV-DNA replication. This may be because of intense keratinocyte proliferation and differentiation in AK favoring amplification of commensalic HPV. Active HPV replication and presumably enhanced gene expression may in turn stimulate keratinocyte proliferation and contribute to carcinogenesis in these early stages of NMSC development. HPV-E6 proteins were recently shown to inhibit UV-induced apoptosis by abrogation of Bak in response to UV damage (Jackson and Storey, 2000) and to bind a protein required for repair of single strand DNA breaks (Iftner et al, 2002). Thereby, accumulation of UV-induced mutations and oncogenic transformation might be facilitated in cases of active HPV infection."
may be necessary when the keratosis is large and/or thick, to make sure that the bump is a keratosis and not a skin cancer
. Seborrheic keratoses
are other bumps that appear in groups like the actinic keratosis but are not caused by sun exposure, and are not related to skin cancers. Seborrheic keratoses may be mistaken for an actinic keratosis.
with associated loss of the granular layer, and thickening of the epidermis. The normal ordered maturation of the keratinocyte
s is disordered to varying degrees, there may be widening of the intracellular spaces, and they may also have some cytologic atypia, such as abnormally large nuclei. The underlying dermis
often shows severe actinic elastosis
and a mild chronic inflammatory infiltrate.
Regular follow-up after the treatment is advised by many doctors. The regular checks are to make sure no new bumps have developed and that old ones haven't become thicker.
s with a melanocyte-stimulating hormone
called afamelanotide
(SCENESSE®) (formerly CUV1647) for mitigation of photodynamic therapy side effects in organ transplant patients.
Another Australian biopharmaceutical company, Peplin, is also developing a topical treatment for actinic keratosis. Formed in 1998 they are currently developing Ingenol Mebutate, which is the first in a new class of compounds and which is derived from Euphorbia peplus
, or E. peplus, a rapidly growing, readily-available plant, commonly referred to as petty spurge or radium weed. The sap of E. peplus has a long history of traditional use for a variety of conditions, including the topical self-treatment of various skin disorders, such as skin cancer and pre-cancerous skin lesions. The company has recently redomiciled to the USA and is about to enter phase III trials with Ingenol Mebutate.
Premalignant condition
A precancerous condition is a disease, syndrome, or finding that, if left untreated, may lead to cancer. It is a generalized state associated with a significantly increased risk of cancer....
of thick, scaly, or crusty patches of skin. It is more common in fair-skinned people. It is associated with those who are frequently exposed to the sun, as it is usually accompanied by solar
Sun
The Sun is the star at the center of the Solar System. It is almost perfectly spherical and consists of hot plasma interwoven with magnetic fields...
damage. Since some of these pre-cancers progress to squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
, they should be treated. Untreated lesions have up to twenty percent risk of progression to squamous cell carcinoma.
When skin is exposed to the sun constantly, thick, scaly, or crusty bumps appear. The scaly or crusty part of the bump is dry and rough. The growths start out as flat scaly areas, and later grow into a tough, wart-like area.
An actinic keratosis
Keratosis
Keratosis is a growth of keratin on the skin. More specifically, it can refer to:* actinic keratosis * hydrocarbon keratosis* keratosis pilaris , also known as * seborrheic keratosis-See also:...
site commonly ranges between 2 and 6 millimeters in size, and can be dark or light, tan, pink, red, a combination of all these, or have the same pigment as the surrounding skin. It may appear on any sun
Sun
The Sun is the star at the center of the Solar System. It is almost perfectly spherical and consists of hot plasma interwoven with magnetic fields...
-exposed area, such as the face, ears, neck, scalp, chest, backs of hands, forearms, or lips.
Classification
Actinic keratoses may be divided into the following types:- Hyperkeratotic actinic keratosis
- Pigmented actinic keratosis
- Lichenoid actinic keratosis
- Atrophic actinic keratosis
See also:
- Actinic cheilitisActinic cheilitisActinic cheilitis is a form of cheilitis which is the counterpart of actinic keratosis of the skin and can develop into squamous cell carcinoma. In actinic cheilitis, there is thickening whitish discoloration of the lip at the border of the lip and skin...
- Squamous cell carcinoma in situ
Incidence
Actinic keratosis is very common, affecting half of the global population. It is seen more often in fair-skinned individuals, and prevalence can vary with geographical location and age. People who take immunosuppressive drugs, such as organ transplant patients, are 250 times more likely to develop actinic keratoses which may lead to skin cancer.Prevention
Preventive measures recommended for AK are similar to those for skin cancer:- Not staying in the sun for long periods of time without protection (e.g., sunscreenSunscreenSunblock is a lotion, spray, gel or other topical product that absorbs or reflects some of the sun's ultraviolet radiation on the skin exposed to sunlight and thus helps protect against sunburn...
, clothing, hats). - Frequently applying powerful sunscreens with SPF ratings greater than 30 and that also block both UVAUltravioletUltraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
and UVB light. - Wearing sun protective clothingSun protective clothingSun protective clothing is clothing specifically designed for sun protection and is produced from a fabric rated for its level of ultraviolet protection. A novel weave structure and denier may produce sun protective properties...
such as hats, long-sleeved shirts, long skirts, or trousers. - Avoiding sun exposure during noon hours is very helpful because ultravioletUltravioletUltraviolet light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than X-rays, in the range 10 nm to 400 nm, and energies from 3 eV to 124 eV...
light is the most powerful at that time.
According to an article in the Journal of Investigative Dermatology (2005) 125, 93–97; doi:10.1111/j.0022-202X.2005.23733.x, entitled "Human Papillomavirus-DNA Loads in Actinic Keratoses Exceed those in Non-Melanoma Skin Cancers", actinic keratosis can contain a significant amount of infectious human papillomavirus. Verbatim: "HPV presents in significantly higher viral loads in actinic keratosis (AK), which are the precursor lesions of squamous cell carcinoma (SCC), than in SCC. Viral loads of 1 HPV-DNA copy per less than 50 cells were measured in 40% of AK. The higher viral loads in AK are likely to reflect enhanced HPV-DNA replication. This may be because of intense keratinocyte proliferation and differentiation in AK favoring amplification of commensalic HPV. Active HPV replication and presumably enhanced gene expression may in turn stimulate keratinocyte proliferation and contribute to carcinogenesis in these early stages of NMSC development. HPV-E6 proteins were recently shown to inhibit UV-induced apoptosis by abrogation of Bak in response to UV damage (Jackson and Storey, 2000) and to bind a protein required for repair of single strand DNA breaks (Iftner et al, 2002). Thereby, accumulation of UV-induced mutations and oncogenic transformation might be facilitated in cases of active HPV infection."
Diagnosis
Doctors can usually identify AK by doing a thorough examination. A biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
may be necessary when the keratosis is large and/or thick, to make sure that the bump is a keratosis and not a skin cancer
Skin cancer
Skin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...
. Seborrheic keratoses
Seborrheic keratosis
A seborrheic keratosis is a noncancerous benign skin growth that originates in keratinocytes. Like liver spots, seborrheic keratoses are seen more often as people age. In fact they are sometimes humorously referred to as the "barnacles of old age". They appear in various colors, from light tan to...
are other bumps that appear in groups like the actinic keratosis but are not caused by sun exposure, and are not related to skin cancers. Seborrheic keratoses may be mistaken for an actinic keratosis.
Histopathology
Actinic keratosis usually shows focal parakeratosisParakeratosis
Parakeratosis is a mode of keratinization characterized by the retention of nuclei in the stratum corneum. Parakeratosis: The orderly but abnormal keratinisation of cells so that the keratin layer consists of plump nucleated keratinised cells instead of annular squames...
with associated loss of the granular layer, and thickening of the epidermis. The normal ordered maturation of the keratinocyte
Keratinocyte
Keratinocytes are the predominant cell type in the epidermis, the outermost layer of the human skin, constituting 95% of the cells found there. Those keratinocytes found in the basal layer of the skin are sometimes referred to as "basal cells" or "basal keratinocytes"...
s is disordered to varying degrees, there may be widening of the intracellular spaces, and they may also have some cytologic atypia, such as abnormally large nuclei. The underlying dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...
often shows severe actinic elastosis
Actinic elastosis
Actinic, or solar, elastosis is an accumulation of abnormal elastin in the dermis of the skin, and in the conjunctiva of the eye, which occurs as a result of the cumulative effects of prolonged and excessive sun exposure, a process known as photoaging.-Clinical features:Actinic elastosis usually...
and a mild chronic inflammatory infiltrate.
Treatment
Various modalities are employed in the treatment of actinic keratosis:- Diclofenac sodium 3% gel, a nonsteroidal anti-inflammatory drug. Recommended duration of therapy is 60 to 90 days.
- CryosurgeryCryosurgeryCryosurgery is the application of extreme cold to destroy abnormal or diseased tissue. The term comes from the Greek words cryo and surgery meaning "hand work" or "handiwork"....
, e.g. with liquid nitrogenLiquid nitrogenLiquid nitrogen is nitrogen in a liquid state at a very low temperature. It is produced industrially by fractional distillation of liquid air. Liquid nitrogen is a colourless clear liquid with density of 0.807 g/mL at its boiling point and a dielectric constant of 1.4...
, by "freezing off" the AKs - 5-fluorouracil (a chemotherapyChemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
agent): a cream that contains this medication causes AKs to become red and inflamed before they fall off - Photodynamic therapyPhotodynamic therapyPhotodynamic therapy is used clinically to treat a wide range of medical conditions, including malignant cancers, and is recognised as a treatment strategy which is both minimally invasive and minimally toxic...
: this new therapy involves injecting a chemical into the bloodstream, which makes AKs more sensitive to any form of light. - LaserLaserA laser is a device that emits light through a process of optical amplification based on the stimulated emission of photons. The term "laser" originated as an acronym for Light Amplification by Stimulated Emission of Radiation...
, notably CO2 and Er:YAG lasers. A Laser resurfacing technique is often used with diffuse AKs. - Electrocautery: burning off AKs with electricity
- Immune Response Modifier: topical treatment with imiquimodImiquimodImiquimod is a prescription medication that acts as an immune response modifier. It is marketed by Meda AB, Graceway Pharmaceuticals and iNova Pharmaceuticals under the trade names Aldara and Zyclara, and by Mochida as Beselna. It is also referred to as R-837.- History :The original FDA approval...
(Aldara), an immune enhancing agent - Different forms of surgerySurgerySurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
Regular follow-up after the treatment is advised by many doctors. The regular checks are to make sure no new bumps have developed and that old ones haven't become thicker.
Research
In 2007, Australia biopharmaceutical company Clinuvel Pharmaceuticals Limited began clinical trialClinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s with a melanocyte-stimulating hormone
Melanocyte-stimulating hormone
The melanocyte-stimulating hormones are a class of peptide hormones that are produced by cells in the intermediate lobe of the pituitary gland...
called afamelanotide
Afamelanotide
Afamelanotide developed at the University of Arizona is a synthetic analog of the naturally-occurring melanocortin peptide hormone alpha-melanocyte stimulating hormone that has been shown to induce skin pigmentation through melanogenesis and thereby subsequently reduce sun damage to UV exposed...
(SCENESSE®) (formerly CUV1647) for mitigation of photodynamic therapy side effects in organ transplant patients.
Another Australian biopharmaceutical company, Peplin, is also developing a topical treatment for actinic keratosis. Formed in 1998 they are currently developing Ingenol Mebutate, which is the first in a new class of compounds and which is derived from Euphorbia peplus
Euphorbia peplus
Euphorbia peplus is a species of Euphorbia, native to most of Europe, northern Africa, and western Asia, where it typically grows in cultivated arable land, gardens, and other disturbed land.Outside of its native range it is very widely naturalised and often invasive, including in Australia, New...
, or E. peplus, a rapidly growing, readily-available plant, commonly referred to as petty spurge or radium weed. The sap of E. peplus has a long history of traditional use for a variety of conditions, including the topical self-treatment of various skin disorders, such as skin cancer and pre-cancerous skin lesions. The company has recently redomiciled to the USA and is about to enter phase III trials with Ingenol Mebutate.
External links
- American Academy of Dermatology
- American Osteopathic College of Dermatology
- National Library of Medicine and the National Institute of Health
- Actinic Keratosis photo library at Dermnet
- Actinic Keratosis information
- Medicinenet's article on Actinic Keratosis
- Information on Actinic Keratosis from The Skin Cancer Foundation