Actinic keratosis (AK), sometimes called solar keratosis or senile keratosis,
is a
pre-cancerous area of thick, scaly, or crusty skin.
[Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. .] Actinic keratosis is a disorder (''
-osis
OSIS or ''variant'' may refer to:
;OSIS
* Open Source Information System
* Open Scripture Information Standard
* ''Organisasi Siswa Intra Sekolah'', Indonesian for Intra-school students organization
;-osis
The suffix ''wikt:-osis, -osis'' is used ...
'') of
epidermal
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water relea ...
keratinocyte
Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells.
Basal cells in the stratum basale, basal layer (''str ...
s that is induced by
ultraviolet (UV) light exposure (''
actin-'').
These growths are more common in
fair-skinned people and those who are frequently in the
sun
The Sun is the star at the center of the Solar System. It is a nearly perfect ball of hot plasma, heated to incandescence by nuclear fusion reactions in its core. The Sun radiates this energy mainly as light, ultraviolet, and infrared radi ...
. They are believed to form when
skin
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...
gets damaged by UV radiation from the sun or indoor
tanning bed
Indoor tanning involves using a device that emits ultraviolet radiation to produce a cosmetic tan. Typically found in tanning salons, gyms, spas, hotels, and sporting facilities, and less often in private residences, the most common device is a ho ...
s, 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
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
.
Untreated lesions have up to a 20% risk of progression to squamous cell carcinoma,
so treatment by a
dermatologist
Dermatology is the branch of medicine dealing with the skin.''Random House Webster's Unabridged Dictionary.'' Random House, Inc. 2001. Page 537. . It is a speciality with both medical and surgical aspects. A dermatologist is a specialist medical ...
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
330px, Different lengths as in respect to the electromagnetic spectrum, measured by the metre and its derived scales. The microwave is between 1 meter to 1 millimeter.
The millimetre (American and British English spelling differences#-re, -er, ...
, but they can grow to be several centimeters in diameter. Notably, AKs are often felt before they are seen, and the texture is sometimes compared to
sandpaper
upright=1.35, Sheets of sandpaper with different grit sizes (40 (coarse), 80, 150, 240, 600 (fine)).
Sandpaper and glasspaper are names used for a type of coated abrasive that consists of sheets of paper or cloth with abrasive material glued to ...
. 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 AK 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 AK have more than one.
If clinical examination findings are not typical of AK and the possibility of in situ or invasive
squamous cell carcinoma (SCC) cannot be excluded based on clinical examination alone, a
biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
or
excision can be considered for definitive diagnosis by
histologic
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
examination of the lesional tissue. Multiple treatment options for AK are available.
Photodynamic therapy
Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance, used in conjunction with molecular oxygen to elicit cell death (phototoxicity).
PDT is popularly used in treating acne. It is used cl ...
(PDT) is one option the treatment of numerous AK 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
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancrea ...
or
imiquimod
Imiquimod, sold under the brand name Aldara among others, is a medication that acts as an immune response modifier that is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis. Scientists at 3M's pharmaceuticals ...
, may require daily application to affected skin areas over a typical time course of weeks.
Cryotherapy
Cryotherapy, sometimes known as cold therapy, is the local or general use of low temperatures in medical therapy. Cryotherapy may be used to treat a variety of tissue lesions. The most prominent use of the term refers to the surgical treatment, s ...
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, AKs can be treated before they progress to skin cancer. If cancer does develop from an AK 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 keratosis of the scalp](https://upload.wikimedia.org/wikipedia/commons/e/e6/Actinic_keratosis_of_the_scalp.jpg)
Actinic keratoses (AKs) most commonly present as a white, scaly
plaque
Plaque may refer to:
Commemorations or awards
* Commemorative plaque, a plate or tablet fixed to a wall to mark an event, person, etc.
* Memorial Plaque (medallion), issued to next-of-kin of dead British military personnel after World War I
* Pla ...
of variable thickness with surrounding redness; they are most notable for having a sandpaper-like texture when felt with a gloved hand. Skin nearby the lesion often shows evidence of solar damage characterized by notable pigmentary alterations, being yellow or pale in color with areas of hyperpigmentation; deep wrinkles, coarse texture,
purpura
Purpura () is a condition of red or purple discolored spots on the skin that do not blanch on applying pressure. The spots are caused by bleeding underneath the skin secondary to platelet disorders, vascular disorders, coagulation disorders, ...
and
ecchymoses
A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises occur close e ...
,
dry skin
Xeroderma, xerosis or xerosis cutis, or simply dry skin, is a skin condition characterized by excessively dry skin.
The medical term ''xeroderma'', meaning "dry skin", derives from modern Latin, ''xero-'' 'dry' + Greek ''derma'' 'skin'.
In most ...
, and scattered
telangiectasia
Telangiectasias, also known as spider veins, are small dilated blood vessels that can occur near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. These dilated blood vessels can develop anywhere on ...
s are also characteristic.
Photoaging leads to an accumulation of
oncogenic
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abno ...
changes, resulting in a proliferation of mutated
keratinocyte
Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells.
Basal cells in the stratum basale, basal layer (''str ...
s that can manifest as AKs or other neoplastic growths.
With years of sun damage, it is possible to develop multiple AKs in a single area on the skin. This condition is termed field cancerization.
The lesions are usually asymptomatic, but can be tender, itch, bleed, or produce a stinging or burning sensation.
AKs are typically graded in accordance with their clinical presentation: Grade I (easily visible, slightly palpable), Grade II (easily visible, palpable), and Grade III (frankly visible and hyperkeratotic).
Variants
![Actinic keratosis on the lip](https://upload.wikimedia.org/wikipedia/commons/a/ad/Actinic_keratosis_on_the_lip.JPEG)
Actinic keratoses can have various clinical presentations, often characterized as follows:
*Classic (or common): Classic AKs present as white, scaly
macules
A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this s ...
,
papules
A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some h ...
or plaques of various thickness, often with surrounding
erythema
Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not assoc ...
. They are usually 2–6mm in diameter but can sometimes reach several centimeters in diameter.
*Hypertrophic (or hyperkeratotic): Hypertrophic AKs (HAKs) appears as a thicker
scale or rough papule or plaque, often adherent to an erythematous base. Classic AKs can progress to become HAKs, and HAKs themselves can be difficult to distinguish from malignant lesions.
*Atrophic: Atrophic AKs lack an overlying scale, and therefore appear as a nonpalpable change in color (or macule). They are often smooth and red and are less than 10mm in diameter.
*AK with
cutaneous horn
Cutaneous horns, also known by the Latin name ''cornu cutaneum'', are unusual keratinous skin tumors with the appearance of horns, or sometimes of wood or coral. Formally, this is a clinical diagnosis for a "conical projection above the surface o ...
: 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 AKs.
*Pigmented AK: Pigmented AKs 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
Solar may refer to:
Astronomy
* Of or relating to the Sun
** Solar telescope, a special purpose telescope used to observe the Sun
** A device that utilizes solar energy (e.g. "solar panels")
** Solar calendar, a calendar whose dates indicat ...
or
lentigo maligna
Lentigo maligna is where melanocyte cells have become malignant and grow continuously along the stratum basale of the skin, but have not Invasion (cancer), invaded below the epidermis. Lentigo maligna is not the same as lentigo maligna melanoma, as ...
.
*
Actinic cheilitis
Actinic cheilitis is cheilitis (lip inflammation) caused by long term sunlight exposure. Essentially it is a burn, and a variant of actinic keratosis which occurs on the lip. It is a premalignant condition, as it can develop into squamous cell c ...
: When an AK 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 AK: Usually presents as a solitary, erythematous, scaly patch or plaque with well-defined borders. Bowenoid AKs are differentiated from
Bowen's disease
Squamous-cell skin cancer, also known as cutaneous squamous-cell carcinoma (cSCC), is one of the main types of skin cancer along with basal cell cancer and melanoma. It usually presents as a hard lump with a scaly top but can also form an ulcer. ...
by degree of epithelial involvement as seen on
histology
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
.
The presence of
ulceration
An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
,
nodularity, or
bleeding
Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vag ...
should raise concern for malignancy. Specifically, clinical findings suggesting an increased risk of progression to
squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
can be recognized as "IDRBEU": I (induration/inflammation), D (diameter > 1 cm), R (rapid enlargement), B (bleeding), E (erythema), and U (ulceration). AKs 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 AK formation is solar radiation, through a variety of mechanisms. Mutation of the
p53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
tumor suppressor gene, induced by UV radiation, has been identified as a crucial step in AK formation.
This
tumor suppressor gene
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...
, located on
chromosome 17
Chromosome 17 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 17 spans more than 83 million base pairs (the building material of DNA) and represents between 2.5 and 3% of the total D ...
p132, allows for
cell cycle
The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA (DNA replication) and some of its organelles, and subs ...
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
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
growth and the development of AK, as well as possible progression from AK to skin cancer.
Other
molecular markers A molecular marker is a molecule, sampled from some source, that gives information about its source. For example, DNA is a molecular marker that gives information about the organism from which it was taken. For another example, some proteins can be ...
that have been associated with the development of AK include the expression of p16
ink4, p14, the
CD95
The Fas receptor, also known as Fas, FasR, apoptosis antigen 1 (APO-1 or APT), cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the ''FAS'' gene. Fas ...
ligand,
TNF
Tumor necrosis factor (TNF, cachexin, or cachectin; formerly known as tumor necrosis factor alpha or TNF-α) is an adipokine and a cytokine. TNF is a member of the TNF superfamily, which consists of various transmembrane proteins with a homolog ...
-related apoptosis-inducing ligand (
TRAIL
A trail, also known as a path or track, is an unpaved lane or small road usually passing through a natural area. In the United Kingdom and the Republic of Ireland, a path or footpath is the preferred term for a pedestrian or hiking trail. Th ...
) and TRAIL receptors, and
loss of heterozygosity
Loss of heterozygosity (LOH) is a type of genetic abnormality in diploid organisms in which one copy of an entire gene and its surrounding chromosomal region are lost. Since diploid cells have two copies of their genes, one from each parent, a sing ...
.
Evidence also suggests that the
human papillomavirus
Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...
(HPV) plays a role in the development of AKs. The HPV virus has been detected in AKs, with measurable HPV viral loads (one 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
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
and
UV-B
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
radiation have been implicated as causes of AKs. UV-A radiation (wavelength 320–400 nm) reaches more deeply into the skin and can lead to the generation of
reactive oxygen species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen.
The reduction of molecular oxygen () p ...
, which in turn can damage cell membranes, signaling proteins, and nucleic acids.
UV-B
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
radiation (wavelength 290–320 nm) causes
thymidine
Thymidine (symbol dT or dThd), also known as deoxythymidine, deoxyribosylthymine, or thymine deoxyriboside, is a pyrimidine deoxynucleoside. Deoxythymidine is the DNA nucleoside T, which pairs with deoxyadenosine (A) in double-stranded DNA. I ...
dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius 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
Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''arachi ...
, 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
Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and animals include: red or reddish skin that is ho ...
: 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.
Skin pigmentation
Melanin
Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...
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 AKs.
Fair-skinned individuals have a significantly increased risk of developing AKs when compared to olive-skinned individuals (
odds ratio
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of A in the presence of B and the odds of A in the absence of B, or equivalently (due ...
s of 14.1 and 6.5, respectively),
and AKs 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 AKs include:
*
Freckling
Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that ...
* Light hair and eye color
* Propensity to sunburn
* Inability to
tan
Tan or TAN may refer to:
Businesses and organisations
* Black and Tans, a nickname for British special constables during the Irish War of Independence. By extension "Tans" can now also colloquially refer to English or British people in general, es ...
Other risk factors
*
Immunosuppression
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...
: People with a compromised immune system from medical conditions (such as AIDS) or immunosuppressive therapy (such as chronic immunosuppression after organ transplantation, or chemotherapy for cancer) are at increased risk for developing AKs. They may develop AK at an earlier age or have an increased number of AK lesions compared to immunocompetent people.
* Human papillomavirus (HPV): The role of HPV in the development of AK remains unclear, but evidence suggests that infection with the betapapillomavirus type of HPV may be associated with an increased likelihood of AK.
*
Genodermatoses
Genodermatosis is a hereditary skin disease with three inherited modes including single gene inheritance, multiple gene inheritance and chromosome inheritance. There are many different types of genodermatosis, the prevalence of genodermatosis rang ...
: Certain
genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s interfere with DNA repair after sun exposure, thereby putting these individuals at higher risk for the development of AKs. Examples of such genetic disorders include
xeroderma pigmentosum
Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in sun- ...
and
Bloom syndrome
Bloom syndrome (often abbreviated as BS in literature) is a rare autosomal recessive genetic disorder characterized by short stature, predisposition to the development of cancer, and genomic instability. BS is caused by mutations in the ''BLM'' gen ...
.
* Balding: AKs are commonly found on the scalps of balding men. The degree of baldness seems to be a risk factor for lesion development, as men with severe baldness were found to be seven times more likely to have 10 or more AKs when compared to men with minimal or no baldness.
This observation can be explained by an absence of hair causing a larger proportion of scalp to be exposed to UV radiation if other sun protection measures are not taken.
Diagnosis
![Actinic keratosis, left upper paraspinal back](https://upload.wikimedia.org/wikipedia/commons/c/c6/Actinic_keratosis%2C_left_upper_paraspinal_back.jpg)
Physicians usually diagnose actinic keratosis by doing a thorough physical examination, through a combination of visual observation and touch. However a
biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
may be necessary when the keratosis is large in diameter, thick, or bleeding, in order to make sure that the lesion is not a
skin cancer
Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
. Actinic keratosis may progress to invasive
squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
(SCC) but both diseases can present similarly upon physical exam and can be difficult to distinguish clinically.
Histological
Histology,
also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larger structures vis ...
examination of the lesion from a
biopsy
A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...
or excision may be necessary to definitively distinguish AK from
in situ
''In situ'' (; often not italicized in English) is a Latin phrase that translates literally to "on site" or "in position." It can mean "locally", "on site", "on the premises", or "in place" to describe where an event takes place and is used in ...
or invasive
SCC.
In addition to SCCs, AKs can be mistaken for other
cutaneous
Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation.
Other animal coverings, such as the arthropod exoskeleton, have different de ...
lesions including
seborrheic keratoses,
basal cell carcinoma
Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raise ...
,
lichenoid keratosis,
porokeratosis,
viral warts,
erosive pustular dermatosis of the scalp,
pemphigus foliaceus
Pemphigus foliaceus is an autoimmune blistering disease ( bullous disorder) of the skin. Pemphigus foliaceus causes a characteristic inflammatory attack at the subcorneal layer of epidermis, which results in skin lesions that are scaly or cruste ...
, inflammatory dermatoses like
psoriasis
Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...
, or
melanoma
Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
.
Biopsy
A lesion biopsy is performed if the diagnosis remains uncertain after a clinical physical exam, or if there is suspicion that the AK might have progressed to squamous cell carcinoma. The most common tissue sampling techniques include shave or punch biopsy. When only a portion of the lesion can be removed due to its size or location, the biopsy should sample tissue from the thickest area of the lesion, as SCCs are most likely to be detected in that area.
If a
shave biopsy Shave biopsy is a biopsy procedure in which a skin abnormality and a thin layer of surrounding skin are removed with a small blade for examination under a microscope. Shave biopsies are not effective in treating melanomas, but can provide a reasona ...
is performed, it should extend through to the level of the
dermis
The dermis or corium is a layer of skin between the epidermis (with which it makes up the cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from stress and strain. It is divided i ...
in order to provide sufficient tissue for diagnosis; ideally, it would extend to the mid-reticular dermis.
Punch biopsy usually extends to the
subcutaneous fat
The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and mac ...
when the entire length of the punch blade is utilized.
Histopathology
![SkinTumors-P5280060](https://upload.wikimedia.org/wikipedia/commons/7/7d/SkinTumors-P5280060.JPG)
On histologic examination, actinic keratoses usually show a collection of atypical keratinocytes with hyperpigmented or pleomorphic nuclei, extending to the
basal layer
The ''stratum basale'' (basal layer, sometimes referred to as ''stratum germinativum'') is the deepest layer of the five layers of the epidermis, the external covering of skin in mammals.
The ''stratum basale'' is a single layer of columnar or ...
of the
epidermis
The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and hypodermis. The epidermis layer provides a barrier to infection from environmental pathogens and regulates the amount of water rele ...
. A "flag sign" is often described, referring to alternating areas of
orthokeratosis
Orthokeratosis is hyperkeratosis without parakeratosis
Parakeratosis is a mode of keratinization characterized by the retention of nuclei in the stratum corneum. In mucous membranes, parakeratosis is normal.Kumar, Vinay; Fausto, Nelson; Abbas, Abu ...
and
parakeratosis
Parakeratosis is a mode of keratinization characterized by the retention of nuclei in the stratum corneum. In mucous membranes, parakeratosis is normal.Kumar, Vinay; Fausto, Nelson; Abbas, Abul (2010) ''Robbins & Cotran Pathologic Basis of Disease' ...
.
Epidermal thickening and surrounding areas of
sun-damaged skin are often seen.
The normal ordered maturation of the
keratinocyte
Keratinocytes are the primary type of Cell (biology), cell found in the epidermis (skin), epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells.
Basal cells in the stratum basale, basal layer (''str ...
s is disordered to varying degrees: there may be widening of the intracellular spaces, cytologic atypia such as abnormally large nuclei, and a mild
chronic inflammatory
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
infiltrate.
Specific findings depend on the clinical variant and particular lesion characteristics. The seven major histopathologic variants are all characterized by atypical keratinocytic proliferation beginning in the basal layer and confined to the epidermis; they include:
*Hypertrophic: Notable for marked hyperkeratosis, often with evident
parakeratosis
Parakeratosis is a mode of keratinization characterized by the retention of nuclei in the stratum corneum. In mucous membranes, parakeratosis is normal.Kumar, Vinay; Fausto, Nelson; Abbas, Abul (2010) ''Robbins & Cotran Pathologic Basis of Disease' ...
.
Keratinocytes in the
stratum malphigii may show a loss of polarity, pleomorphism, and anaplasia.
Some irregular downward proliferation into the uppermost dermis may be observed, but does not represent frank invasion.
*Atrophic: With slight hyperkeratosis and overall atrophic changes to the epidermis; the basal layer shows cells with large, hyperchromatic nuclei in close proximity to each other. These cells have been observed to proliferate into the dermis as buds and duct-like structures.
*Lichenoid: Demonstrate a band-like lymphocytic infiltrate in the papillary dermis, directly beneath the dermal-epidermal junction.
*
Achantholytic: Intercellular clefts or lacunae in the lowermost epidermal layer that result from anaplastic changes; these produce dyskeratotic cells with disrupted intercellular bridges.
*Bowenoid: This term is controversial and usually refers to full-thickness atypia, microscopically indistinguishable from Bowen's Disease.
However most dermatologists and pathologists will use it in reference to tissue samples that are notable for small foci of atypia that involve the full thickness of the epidermis, in the background of a lesion that is otherwise consistent with an AK.
*Epidermolytic: With granular degeneration.
*Pigmented: Show pigmentation in the basal layer of the epidermis, similar to a solar lentigo.
Dermoscopy
Dermoscopy
Dermatoscopy also known as dermoscopy or epiluminescence microscopy, is the examination of skin lesions with a dermatoscope. It is a tool similar to a camera to allow for inspection of skin lesions unobstructed by skin surface reflections. The de ...
is a noninvasive technique utilizing a handheld magnifying device coupled with a transilluminating lift. It is often used in the evaluation of cutaneous lesions but lacks the definitive diagnostic ability of biopsy-based tissue diagnosis. Histopathologic exam remains the gold standard.
Polarized contact dermoscopy of AKs occasionally reveals a "rosette sign," described as four white points arranged in a clover pattern, often localized to within a follicular opening.
It is hypothesized that the "rosette sign" corresponds histologically to the changes of orthokeratosis and parakeratosis known as the "flag sign."
* Non-pigmented AKs: linear or wavy vascular patterning, or a "strawberry pattern," described as unfocused vessels between hair follicles, with white-haloed follicular openings.
* Pigmented AKs: gray to brown dots or globules surrounding follicular openings, and annular-granular rhomboidal structures; often difficult to differentiate from lentigo maligna.
Prevention
Ultraviolet radiation is believed to contribute to the development of actinic keratoses by inducing mutations in epidermal keratinocytes, leading to proliferation of atypical cells. Therefore, preventive measures for AKs are targeted at limiting exposure to solar radiation, including:
* Limiting extent of sun exposure
** Avoid sun exposure during noontime hours between 10:00 AM and 2:00 PM when UV light is most powerful
** Minimize all time in the sun, since UV exposure occurs even in the winter and on cloudy days
* Using sun protection
** Applying sunscreens with
SPF ratings 30 or greater that also block both
UVA
UVA most often refers to:
* Ultraviolet A, a type of ultraviolet radiation
* University of Virginia, a public research university in Charlottesville, Virginia, United States
Uva or UVA may also refer to:
Places
* Uva, Missouri, an unincorpora ...
and
UVB
Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30 PHz) to 400 nm (750 THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
light, at least every 2 hours and after swimming or sweating
** Applying sunscreen at least 15 minutes before going outside, as this allows time for the sunscreen to be absorbed appropriately by the skin
** Wearing
sun protective clothing
Sun protective clothing is clothing specifically designed for sun protection and is produced from a fabric rated for its level of ultraviolet (UV) protection. A novel weave structure and denier (related to thread count per inch) may produce sun p ...
such as hats, sunglasses, long-sleeved shirts, long skirts, or trousers
Recent research implicating human papillomavirus (HPV) in the development of AKs suggests that HPV prevention might in turn help prevent development of AKs, as UV-induced mutations and oncogenic transformation are likely facilitated in cases of active HPV infection.
A key component of HPV prevention includes
vaccination
Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...
, and the CDC currently recommends routine vaccination in all children at age 11 or 12.
There is some data that in individuals with a history of non-melanoma skin cancer, a low-fat diet can serve as a preventative measure against future actinic keratoses.
Management
There are a variety of treatment options for AK depending on the patient and the clinical characteristics of the lesion. AKs show a wide range of features, which guide decision-making in choosing treatment. As there are multiple effective treatments, patient preference and lifestyle are also factors that physicians consider when determining the management plan for actinic keratosis.
Regular follow-up is advisable after any treatment to make sure no new lesions have developed and that old ones are not progressing. Adding topical treatment after a procedure may improve outcomes.
Medication
Topical medications are often recommended for areas where multiple or ill-defined AKs are present, as the medication can easily be used to treat a relatively large area.
Fluorouracil cream
Topical
fluorouracil
Fluorouracil (5-FU), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stomach cancer, pancreat ...
(5-FU) destroys AKs by blocking
methylation
In the chemical sciences, methylation denotes the addition of a methyl group on a substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replacing a hydrogen atom. These t ...
of
thymidylate synthetase
Thymidylate synthase (TS) () is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleo ...
, thereby interrupting DNA and RNA synthesis. This in turn prevents the proliferation of dysplastic cells in AK. Topical 5-FU is the most utilized treatment for AK, and often results in effective removal of the lesion. Overall, there is a 50% efficacy rate resulting in 100% clearance of AKs treated with topical 5-FU. 5-FU may be up to 90% effective in treating non-hyperkeratotic lesions. While topical 5-FU is a widely used and cost-effective treatment for AKs and is generally well tolerated, its potential side-effects can include: pain, crusting, redness, and local swelling.
These adverse effects can be mitigated or minimized by reducing the frequency of application or taking breaks between uses.
The most commonly used application regimen consists of applying a layer of topical cream to the lesion twice a day after washing; duration of treatment is typically 2–4 weeks to thinner skin like the cheeks and up to 8 weeks for the arms; treatment of up to 8 weeks has demonstrated a higher cure rate.
Imiquimod cream
Imiquimod
Imiquimod, sold under the brand name Aldara among others, is a medication that acts as an immune response modifier that is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis. Scientists at 3M's pharmaceuticals ...
is a topical immune-enhancing agent licensed for the treatment of genital warts.
Imiquimod stimulates the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
through the release and up-regulation of
cytokines
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
.
Treatment with Imiquimod cream applied 2–3 times per week for 12 to 16 weeks was found to result in complete resolution of AKs in 50% of people, compared to 5% of controls.
The Imiquimod 3.75% cream has been validated in a treatment regimen consisting of daily application to entire face and scalp for two 2-week treatment cycles, with a complete clearance rate of 36%.
While the clearance rate observed with the Imiquimod 3.75% cream was lower than that observed with the 5% cream (36 and 50 percent, respectively), there are lower reported rates of adverse reactions with the 3.75% cream: 19% of individuals using Imiquimod 3.75% cream reported adverse reactions including local erythema, scabbing, and flaking at the application site, while nearly a third of individuals using the 5% cream reported the same types of reactions with Imiquimod treatment.
However, it is ultimately difficult to compare the efficacy of the different strength creams directly, as current study data varies in methodology (e.g. duration and frequency of treatment, and amount of skin surface area covered).
Ingenol mebutate gel
Ingenol mebutate is a newer treatment for AK used in Europe and the United States. It works in two ways, first by disrupting cell membranes and mitochondria resulting cell death, and then by inducing antibody-dependent cellular cytotoxicity to eliminate remaining tumor cells. A 3-day treatment course with the 0.015% gel is recommended for the scalp and face, while a 2-day treatment course with the 0.05% gel is recommended for the trunk and extremities.
Treatment with the 0.015% gel was found to completely clear 57% of AK, while the 0.05% gel had a 34% clearance rate. Advantages of ingenol mebutate treatment include the short duration of therapy and a low recurrence rate. Local skin reactions including pain, itching and redness can be expected during treatment with ingenol mebutate. This treatment was derived from the petty spurge, ''
Euphorbia peplus
''Euphorbia peplus'' (petty spurge, radium weed, cancer weed, or milkweed), 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 disturbe ...
'' which has been used as a traditional remedy for keratosis.
Diclofenac sodium gel
Topical
diclofenac sodium
Diclofenac, sold under the brand name Voltaren, among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It is taken by mouth or rectally in a suppository, used by injection, o ...
gel is a nonsteroidal anti-inflammatory drug that is thought to work in the treatment of AK through its inhibition of the arachidonic acid pathway, thereby limiting the production of prostaglandins which are thought to be involved in the development of UVB-induced skin cancers.
Recommended duration of therapy is 60 to 90 days with twice daily application. Treatment of facial AK with diclofenac gel led to complete lesion resolution in 40% of cases.
Common side effects include dryness, itching, redness, and rash at the site of application.
Retinoids
Topical
retinoids
The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth.
Retinoids have many important functions throughout ...
have been studied in the treatment of AK with modest results, and the American Academy of Dermatology does not currently recommend this as first-line therapy. Treatment with
adapalene
Adapalene is a third-generation topical retinoid primarily used in the treatment of mild-moderate acne, and is also used off-label to treat keratosis pilaris as well as other skin conditions. Studies have found adapalene is as effective as othe ...
gel daily for 4 weeks, and then twice daily thereafter for a total of nine months led to a significant but modest reduction in the number AKs compared to placebo; it demonstrated the additional advantage of improving the appearance of photodamaged skin.
Topical
tretinoin
Tretinoin, also known as all-''trans'' retinoic acid (ATRA), is a medication used for the treatment of acne and acute promyelocytic leukemia. For acne, it is applied to the skin as a cream, gel or ointment. For leukemia, it is taken by mouth f ...
is ineffective as treatment for reducing the number of AKs.
For secondary prevention of AK, systemic, low-dose
acitretin
Acitretin (trade names Soriatane and Neotigason) is a second-generation retinoid. It is taken orally, and is typically used for psoriasis.
Acitretin is an oral retinoid used in the treatment of severe resistant psoriasis. Because of the potentia ...
was found to be safe, well tolerated and moderately effective in chemoprophylaxis for skin cancers in kidney transplant patients. Acitretin is a viable treatment option for organ transplant patients according to expert opinion.
Tirbanibulin
Tirbanibulin (Klisyri) was approved for medical use in the United States in December 2020, for the treatment of actinic keratosis on the face or scalp.
Procedures
Cryotherapy
Liquid nitrogen
Liquid nitrogen—LN2—is nitrogen in a liquid state at low temperature. Liquid nitrogen has a boiling point of about . It is produced industrially by fractional distillation of liquid air. It is a colorless, low viscosity liquid that is wide ...
(−195.8 °C) is the most commonly used destructive therapy for the treatment of AK in the United States.
It is a well-tolerated office procedure that does not require anesthesia.
Cryotherapy is particularly indicated for cases where there are fewer than 15 thin, well-demarcated lesions.
Caution is encouraged for thicker, more hyperkeratotic lesions, as dysplastic cells may evade treatment.
Treatment with both cryotherapy and field treatment can be considered for these more advanced lesions.
Cryotherapy is generally performed using an open-spray technique, wherein the AK is sprayed for several seconds.
The process can be repeated multiple times in one office visit, as tolerated. Cure rates from 67 to 99 percent have been reported,
depending on freeze time and lesion characteristics. Disadvantages include discomfort during and after the procedure; blistering, scarring and redness; hypo- or hyperpigmentation; and destruction of healthy tissue.
Photodynamic therapy
![Phototherapy week](https://upload.wikimedia.org/wikipedia/commons/d/d3/Phototherapy_week.png)
AKs are one of the most common dermatologic lesions for which
photodynamic therapy
Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance, used in conjunction with molecular oxygen to elicit cell death (phototoxicity).
PDT is popularly used in treating acne. It is used cl ...
, including topical
methyl aminolevulinate
Methyl aminolevulinate (MAL) is a drug used as a sensitizer in photodynamic therapy. It is a prodrug that is metabolized to protoporphyrin IX. It is marketed as Metvix.
Metvix cream is applied topically and some time later the skin is illumin ...
(MAL) or
5-aminolevulinic acid (5-ALA), is indicated.
Treatment begins with preparation of the lesion, which includes scraping away scales and crusts using a dermal curette. A thick layer of topical MAL or 5-ALA cream is applied to the lesion and a small area surrounding the lesion, which is then covered with an occlusive dressing and left for a period of time. During this time the photosensitizer accumulates in the target cells within the AK lesion. The dressings are then removed and the lesion is treated with light at a specified wavelength.
Multiple treatment regimens using different photosensitizers, incubation times, light sources, and pretreatment regimens have been studied and suggest that longer incubation times lead to higher rates of lesion clearance. Photodynamic therapy is gaining in popularity. It has been found to have a 14% higher likelihood of achieving complete lesion clearance at 3 months compared to cryotherapy, and seems to result in superior cosmetic outcomes when compared to cryotherapy or 5-FU treatment. Photodynamic therapy can be particularly effective in treating areas with multiple AK lesions.
Surgical techniques
*
Surgical excision
Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pat ...
: Excision should be reserved for cases when the AK is a thick, horny papule, or when deeper invasion is suspected and histopathologic diagnosis is necessary.
It is a rarely utilized technique for AK treatment.
*Shave excision and
curettage
Curettage ( or ), in medical procedures, is the use of a curette (French, meaning scoopMosby's Medical, Nursing & Allied Health Dictionary, Fourth Edition, Mosby-Year Book 1994, p. 422) to remove tissue by scraping or scooping.
Curettages are ...
(sometimes followed by
electrodesiccation
Cauterization (or cauterisation, or cautery) is a medical practice or technique of burning a part of a body to remove or close off a part of it. It destroys some tissue in an attempt to mitigate bleeding and damage, remove an undesired growth, or ...
when deemed appropriate by the physician
): This technique is often used for treatment of AKs, and particularly for lesions appearing more similar to squamous cell carcinoma, or those that are unresponsive to other treatments.
The surface of the lesion can be scraped away using a scalpel, or the base can be removed with a curette. Tissue can be evaluated histopathologically under the microscope, but specimens acquired using this technique are not often adequate to determine whether a lesion is invasive or intraepidermal.
*
Dermabrasion
Dermabrasion is a type of surgical skin planing, generally with the goal of removing acne, scarring and other skin or tissue irregularities, typically performed in a professional medical setting by a dermatologist or plastic surgeon trained speci ...
: Dermabrasion is useful in the treatment of large areas with multiple AK lesions. The process involves using a hand-held instrument to "sand" the skin, removing the
stratum corneum
The stratum corneum (Latin for 'horny layer') is the outermost layer of the epidermis. The human stratum corneum comprises several levels of flattened corneocytes that are divided into two layers: the ''stratum disjunctum'' and ''stratum compact ...
layer of the epidermis. Diamond fraises or wire brushes revolving at high speeds are used.
The procedure can be quite painful and requires
procedural sedation
Procedural sedation and analgesia (PSA) is a technique in which a sedating/dissociative medication is given, usually along with an analgesic medication, in order to perform non-surgical procedures on a patient. The overall goal is to induce a decr ...
and
anesthetic
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
, necessitating a hospital stay. One-year clearance rates with dermabrasion treatment are as high as 96%, but diminish drastically to 54% at five years.
Laser therapy
Laser therapy
Laser medicine consists in the use of lasers in medical diagnosis, treatments, or therapies, such as laser photodynamic therapy, photorejuvenation, and laser surgery.
Lasers
Lasers used in medicine include in principle any type of laser, but ...
using
carbon dioxide
Carbon dioxide (chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is transpar ...
() or erbium:yttrium aluminum garnet (
Er:YAG) lasers is a treatment approach being utilized with increased frequency, and sometimes in conjunction with computer scanning technology. Laser therapy has not been extensively studied, but current evidence suggests it may be effective in cases involving multiple AKs refractive to medical therapy, or AKs located in cosmetically sensitive locations such as the face. The laser has been recommended for extensive actinic cheilitis that has not responded to 5-FU.
Chemical peels
A
chemical peel
A chemical peel is a technique used to improve and smooth the texture of the skin. Facial skin is mostly treated, and scarring can be improved. Chemical peels are intended to remove the outermost layers of the skin. To accomplish this task, the ch ...
is a topically applied agent that wounds the outermost layer of the skin, promoting organized repair, exfoliation, and eventually the development of smooth and rejuvenated skin. Multiple therapies have been studied. A medium-depth peel may effectively treat multiple non-hyperkeratotic AKs. It can be achieved with 35% to 50%
trichloroacetic acid
Trichloroacetic acid (TCA; TCAA; also known as trichloroethanoic acid) is an analogue of acetic acid in which the three hydrogen atoms of the methyl group have all been replaced by chlorine atoms. Salts and esters of trichloroacetic acid are calle ...
(TCA) alone or at 35% in combination with
Jessner's solution in a once-daily application for a minimum of 3 weeks; 70%
glycolic acid
Glycolic acid (or hydroxyacetic acid; chemical formula HOCH2CO2H) is a colorless, odorless and hygroscopic crystalline solid, highly soluble in water. It is used in various skin-care products. Glycolic acid is widespread in nature. A glycolate (so ...
(α-hydroxy acid); or solid . When compared to treatment with 5-FU, chemical peels have demonstrated similar efficacy and increased ease of use with similar morbidity. Chemical peels must be performed in a controlled clinic environment and are recommended only for individuals who are able to comply with follow-up precautions, including avoidance of sun exposure. Furthermore, they should be avoided in individuals with a history of
HSV infection or
keloids
Keloid, also known as keloid disorder and keloidal scar,
is the formation of a type of scar which, depending on its maturity, is composed mainly of either type III (early) or type I (late) collagen. It is a result of an overgrowth of granulation ...
, and in those who are
immunosuppressed
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
or who are taking
photosensitizing medications.
Prognosis
![Squamous Cell Carcinoma1](https://upload.wikimedia.org/wikipedia/commons/3/35/Squamous_Cell_Carcinoma1.jpg)
Untreated AKs follow one of three paths: they can either persist as AKs, regress, or progress to invasive skin cancer, as AK lesions are considered to be on the same continuum with
squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
(SCC).
AK lesions that regress also have the potential to recur.
* Progression: The overall risk of an AK turning into invasive cancer is low. In average-risk individuals, likelihood of an AK lesion progressing to SCC is less than 1% per year.
Despite this low rate of progression, studies suggest that a full 60% of SCCs arise from pre-existing AKs, reinforcing the idea that these lesions are closely related.
* Regression: Reported regression rates for single AK lesions have ranged between 15 and 63% after one year.
* Recurrence: Recurrence rates after 1 year for single AK lesions that have regressed range between 15 and 53%.
Clinical course
Given the aforementioned differering clinical outcomes, it is difficult to predict the clinical course of any given actinic keratosis. AK lesions may also come and go—in a cycle of appearing on the skin, remaining for months, and then disappearing. Often they will reappear in a few weeks or months, particularly after unprotected sun exposure. Left untreated, there is a chance that the lesion will advance to become invasive. Although it is difficult to predict whether an AK will advance to become squamous cell carcinoma, it has been noted that squamous cell carcinomas originate in lesions formerly diagnosed as AKs with frequencies reported between 65 and 97%.
Epidemiology
Actinic keratosis is very common, with an estimated 14% of dermatology visits related to AKs. It is seen more often in fair-skinned individuals,
and rates vary with geographical location and age. Other factors such as exposure to ultraviolet (UV) radiation,
certain
phenotypic
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
features, and immunosuppression can also contribute to the development of AKs.
Men are more likely to develop AK than women, and the risk of developing AK lesions increases with age. These findings have been observed in multiple studies, with numbers from one study suggesting that approximately 5% of women ages 20–29 develop AK compared to 68% of women ages 60–69, and 10% of men ages 20–29 develop AK compared to 79% of men ages 60–69.
Geography seems to play a role in the sense that individuals living in locations where they are exposed to more UV radiation throughout their lifetime have a significantly higher risk of developing AK. Much of the literature on AK comes from Australia, where the prevalence of AK is estimated at 40–50% in adults over 40,
as compared to the United States and Europe, where prevalence is estimated at under 11–38% in adults.
One study found that those who immigrated to Australia after age 20 had fewer AKs than native Australians in all age groups.
Research
Diagnostically, researchers are investigating the role of novel biomarkers to assist in determining which AKs are more likely to develop into cutaneous or metastatic SCC. Upregulation of
matrix metalloproteinases
Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs be ...
(MMP) is seen in many different types of cancers, and the expression and production of MMP-7 in particular has been found to be elevated in SCC specifically.
The role of
serin peptidase inhibitors (Serpins) is also being investigated. SerpinA1 was found to be elevated in the keratinocytes of SCC cell lines, and SerpinA1 upregulation was correlated with SCC tumor progression ''in vivo''.
Further investigation into specific biomarkers could help providers better assess prognosis and determine best treatment approaches for particular lesions.
In terms of treatment, a number of medications are being studied. Resiquimod is a TLR 7/8 agonist that works similarly to imiquimod, but is 10 to 100 times more potent; when used to treat AK lesions, complete response rates have range from 40 to 74%.
Afamelanotide
Afamelanotide, sold under the brand name Scenesse, is a synthetic peptide and analogue of α-melanocyte stimulating hormone. It has been used to prevent skin damage from the sun in people with erythropoietic protoporphyria in the European Un ...
is a drug that induces the production of melanin by
melanocyte
Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea),
the inner ear,
vaginal epithelium, meninges,
bones,
and heart.
...
s to act as a protective factor against UVB radiation. It is being studied to determine its efficacy in preventing AKs in organ transplant patients who are on immunosuppressive therapy.
Epidermal growth factor receptor
The epidermal growth factor receptor (EGFR; ErbB-1; HER1 in humans) is a transmembrane protein that is a receptor for members of the epidermal growth factor family (EGF family) of extracellular protein ligands.
The epidermal growth factor recept ...
(EGFR) inhibitors such as
gefitinib
Gefitinib, sold under the brand name Iressa, is a medication used for certain breast, lung and other cancers. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor (EGFR) in targ ...
, and anti-EGFR antibodies such as
cetuximab
Cetuximab, sold under the brand name Erbitux, is an epidermal growth factor receptor (EGFR) inhibitor medication used for the treatment of metastatic colorectal cancer and head and neck cancer. Cetuximab is a chimeric (mouse/human) monoclonal an ...
are used in the treatment of various types of cancers, and are currently being investigated for potential use in the treatment and prevention of AKs.
See also
*
Age spot
Age or AGE may refer to:
Time and its effects
* Age, the amount of time someone or something has been alive or has existed
** East Asian age reckoning, an Asian system of marking age starting at 1
* Ageing or aging, the process of becoming older ...
*
Freckle
Freckles are clusters of concentrated melaninized cells which are most easily visible on people with a fair complexion. Freckles do not have an increased number of the melanin-producing cells, or melanocytes, but instead have melanocytes that ...
*
Lentigo
A lentigo () (plural lentigines, ) is a small pigmented spot on the skin with a clearly defined edge, surrounded by normal-appearing skin. It is a harmless (benign) hyperplasia of melanocytes which is linear in its spread. This means the hyperplasi ...
*
Squamous cell carcinoma
Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
*
List of cutaneous conditions
Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against t ...
References
External links
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Dermatology