Actinic keratosis ( AK ) is a thick, scaly, or crusty pre-cancer spots. This growth is more common in white people and those who are often in the sun. They are usually formed when the skin is damaged by ultraviolet (UV) radiation from the sun or an indoor tanning bed. AKs are considered potentially pre-cancerous; If left untreated, they can turn into a type of cancer called squamous cell skin cancer. Untreated lesions have up to a 20% risk of developing into squamous cell carcinoma, so treatment by a dermatologist is recommended.
This growth of growth occurs when the skin is constantly exposed to the sun from time to time. They usually appear as thick, scaly, or crusty areas that often feel dry or rough. In fact, AK is often felt before they are seen, and the texture is often compared to the sandpaper. They may be dark, light, brown, pink, red, a combination of these, or have the same color as the surrounding skin.
Actinic lesions keratosis usually ranges between 2 and 6 millimeters but can grow to be several centimeters in diameter. They often appear in areas of sun-exposed skin, such as face, ears, neck, scalp, chest, back of hand, forearm, or lips. Since they are related to sun damage to the skin, most people who have an AK have more than one.
Often, large areas of sun-exposed skin are diagnosed with a multiple-AK continuum that looks clinical with different sizes and severity, usually accompanied by subclinical lesions that become evident only in the biopsy. The concept of a skin region that shows several AKs is referred to as the field of cancer.
Diagnosis is clinically suspected on physical examination, but can be confirmed by looking at cells from lesions under a microscope. Different therapeutic options for AK are available. Photodynamic therapy (PDT) is recommended for the treatment of several AK lesions and field carcinization. This involves the application of photosensitizer to the skin followed by illumination with a strong light source. Topical creams may require daily application for affected areas of the skin for longer periods of time. Cryotherapy is often used for single lesions, but undesirable hypopigmentation may occur at the site of care. By following a dermatologist, AK can be treated before it turns into skin cancer. If skin cancer develops from an AK lesion, it can be known early with close monitoring, when treatment can be curative.
Video Actinic keratosis
Signs and symptoms
Actinic keratoses (AKs) are most commonly present as white, scaly plaques of variable thickness with redness around them; they are most famous for having a sandpaper-like texture when feeling with a gloved hand. The skin around the lesions often shows evidence of sun damage characterized by an important, yellow or pale change of pigment with a hyperpigmentation area; deep wrinkles, coarse textures, purpura and ecchymoses, dry skin, and scattered telangiectasias are also characteristics.
Fotoaging leads to the accumulation of oncogenic changes, resulting in the proliferation of mutated keratinocytes that may manifest as AK or other neoplastic growths. With years of sun damage, it is possible to develop multiple AKs in one area of ​​the skin.
Lesions are usually asymptomatic, but may be tender, itchy, bleeding, or produce a stinging or burning sensation. AK is usually assessed according to their clinical presentation: Grade I (easily visible, slightly palpable), Grade II (easily visible, palpable), and Grade III (clearly visible and hyperkeratotic).
Clinical variant
Actinic keratosis can have a variety of clinical presentations, often characterized as follows:
- Classic (or general) : Classic AK is present as a white, scaly, papular or plaque patch with varying thickness, often with erythema around it. They are usually 2-6mm in diameter but can sometimes reach several centimeters in diameter. Hypertrophic AKs (HAKs) appear as thicker scales or crude papules or plaques, often attached to the erythematous base. Classical AK can develop into RIGHT, and RIGH alone can be difficult to distinguish from malignant lesions.
- Atrophy : Atrophic AK has no scale on it, and therefore appears as an irreversible (or macular) color change. They are often smooth and red, and less than 10mm in diameter.
- AK with leather horn : The cutaneous horn is a keratinic projection with a height of at least half its diameter, often cone-shaped. They can be seen in actinic keratosis settings as a progression of HAK, but are also present in other skin conditions. 38-40% of leather horns represent AKs.
- Pigmented AK : Pigmented AK is a rare variant that is often present as a brownish-brown macula or plaque to brown. They can be difficult to distinguish from sun lentigo or malignant lentigo.
- Actinic cheilitis : When AK is formed on the lips, this is called actinic cheilitis. It usually appears as a rough and scaly scar on the lips, often accompanied by a dry mouth sensation and symptomatic lips rupture.
- Bowenoid AK : Usually a patch or scaly plaque, erythematous, scaly with clear boundaries. The AK bowenoid is distinguished from Bowen's disease by the extent of epithelial involvement as seen in histology.
The presence of ulceration, nodularity, or bleeding should increase attention to malignancy. In particular, clinical findings suggesting an increased risk of progression to squamous cell carcinoma may be recognized as "IDRBEU": I (induration/inflammation), D (diameter & gt; 1 cm), R (rapid magnification), B (hemorrhage), E (erythema) and U (ulceration). AK is usually diagnosed clinically, but because they are difficult to differentiate clinically from squamous cell carcinomas, each associated feature requires a biopsy for diagnostic confirmation.
Maps Actinic keratosis
Cause
The most important cause of AK formation is solar radiation, especially UV-B radiation (wavelength 290-320). UV-B radiation causes the formation of thymine dimers in DNA and RNA, leading to significant cellular mutations. In addition, a recent study has focused on the role of p53 tumor suppressor genes in AK formation. This tumor suppressor gene, located on chromosome 17p132, makes it possible to capture cell cycles when DNA or RNA is damaged. Degradation of p53 pathways can result in uncontrolled proliferation of dysplastic keratinocytes, thus functioning as a source of neoplastic growth and development of AK, as well as possible carcinogenesis. Other molecular markers that have been associated with AK progression include expression of p16 ink4 , CD95 ligand, induced-induced ligand (TRAIL) and TNF-related TRAIL receptors, and loss of heterozygosity.
Recent research has shown that human papillomavirus (HPV) may also play a role in the development of AK. The HPV virus has been detected in the AK, with measurable HPV viral load (1 copy of HPV-DNA per less than 50 cells) measured in 40% AK. Similar to UV radiation, higher HPV levels found in AK reflect increased viral DNA replication; is thought to be linked to keratinocyte proliferation and abnormal differentiation in AK that provides a commensal environment for HPV replication. This in turn can further stimulate abnormal proliferation that contributes to the development of AK and carcinogenesis.
AKs are most commonly seen in individuals with bright skin and are usually found on bald individual scalp.
Ultraviolet radiation
It is thought that UV radiation induces mutations in epidermal keratinocytes, promoting the proliferation of the survival of these atypical cells. Finally, this leads to the formation of AK. Specifically, mutations in the p53 tumor suppressor gene have been found in 30-50% of skin samples of AK lesions.
- The rest of the sun exposure: cumulative sun exposure causes an increased risk for AK development. In one US study, AK was found in 55% of white men with high cumulative sun exposure, and only 19% of white men with low cumulative sun exposure in the appropriate age group (percentage of women in the study). the same study was 37% and 12% respectively). Furthermore, the use of sunscreen (SPF 17 or higher) has been found to significantly reduce the progression of AK lesions, and also improve the regression of existing lesions.
- History of sunburn: Studies show that even one painful episode of sunburn as a child can increase a person's risk of developing an adult AK. Six or more painful sunburns over a lifetime were found to be significantly associated with the possibility of developing AK.
Skin pigmentation
Melanin is a pigment in the epidermis that serves to protect keratinocytes from damage caused by UV radiation; it is found in higher concentrations in the dark-skinned individual epidermis, giving them protection against the development of AK. Light-skinned individuals have a significantly increased risk of developing AK when compared to olive-skinned individuals (odds ratio of 14.1 and 6.5), and AK is uncommon in dark-skinned African Americans. Other phenotypic features seen in white individuals associated with an increased tendency to develop AK include:
- Fantasy
- Light hair color
- Trends for sunburn
- Inability to bask
Balding
AK is usually found on bald male scalp. The level of baldness appears to be a risk factor for lesion development, as men with severe baldness are found to be seven times more likely to have 10 or more AKs when compared with men with minimal or no baldness.
Other risk factors
- Immunosuppression: People taking immunosuppressive drugs, such as organ transplant patients, are 250 times more likely to develop actinic keratoses that can cause skin cancer.
- Human papillomavirus (HPV): The role of HPV in the development of AK is still unclear, but evidence suggests that infection with the HPV-type betapapillomavirus may be associated with a possible increase in AK.
- Genodermatoses: Certain genetic disorders interfere with DNA repair after sun exposure, thus putting these people at a higher risk for the development of AK. Examples of such genetic disorders include xeroderma pigmentosum and Bloom syndrome.
Diagnosis
Doctors usually diagnose actinic keratoses by performing a thorough physical examination, through a combination of visual and touching observations. However, a biopsy may be necessary when keratosis is large, thick, or bleeding, to ensure that lesions are not skin cancer. Actinic keratosis and squamous cell carcinoma (SCC) may be present simultaneously on physical examination, and many scientists argue that they are actually just different stages of the same condition. In addition to SCC, AK may be misinterpreted for other skin lesions including seborrhoeic keratosis, basal cell carcinoma, lichenoid keratosis, porokeratosis, viral warts, skin inflammation, or melanoma.
Biopsy
A lesion biopsy is performed if the diagnosis remains uncertain after clinical physical examination. The most common tissue sampling techniques include shaving or perforating the biopsy. When only partial lesions can be removed due to size or location, the biopsy should take tissue samples from the thickest area of ​​the lesion, since SCC is most likely detected in the area.
If shaving biopsy is performed, it should extend to the dermis level to provide adequate tissue for diagnosis; ideally, it will extend to the mid-reticular dermis. The punch biopsy usually extends to subcutaneous fat when the entire length of the punch blade is used.
Histopathology
In histologic examinations, actinic keratoses usually show a collection of atypical keratinocytes with hyperpigmented or pleomorphic nuclei, extending into the basal layer of the epidermis. A "flag sign" is often described, referring to the orthokeratosis region and the alternating parakeratosis. Epidermal thickening and surrounding areas of sun-damaged skin are often seen. Regular regular irregular keratinocyte maturation to varying degrees: there may be widespread intracellular space, cytological cytology such as large abnormal nuclei, and mild chronic inflammatory infiltration.
Specific findings rely on clinical variants and certain lesion characteristics. Seven major histopathological variants are all characterized by atypical keratinositic proliferation beginning in the basal layer and confined to the epidermis; they include:
- Hypertrophic : Notable for marked hyperkeratosis, often with clear parakeratosis. Keratinocytes in the stratum malphigii may indicate loss of polarity, pleomorphism, and anaplasia. Some of the irregular downward proliferation to the uppermost dermis can be observed, but does not represent a bright invasion.
- Atrophy : With slight hyperkeratosis and overall atrophic changes in the epidermis; the basal layer shows cells with large hyperchromatic nuclei adjacent to each other. These cells have been observed proliferating into the dermis as buds and duct-like structures.
- Lichenoid : Indicates lymphocytic infiltration like a band in the papillary dermis, just below the dermal-epidermal junction.
- Achantholytic : Intercellular or lacunae defects in the bottom of the epidermal layer resulting from anaplastic changes; this results in dyskeratotic cells with interrupted intracellular bridges.
- Bowenoid : This term is controversial and usually refers to atypia with full thickness, microscopically indistinguishable from Bowen disease. However most dermatologists and pathologists will use it in reference to tissue samples that are important for a small focus of atypia involving the full thickness of the epidermis, in the background of lesions consistent with AK.
- Epidermolytic : With granular degeneration.
- Pigmented : Show pigmentation in the basal layer of the epidermis, similar to sun lentigo.
Dermoscopy
Dermoscopy is a non-invasive technique that uses a hand-held magnifier combined with a transillumination lift. It is often used in the evaluation of skin lesions, but lacks the definitive diagnostic ability of a biopsy-based tissue diagnosis. Histopathological examination remains the gold standard
dermoscopic Features
Polarized AKS contact dermatoscopy occasionally shows a "rosette mark", described as four white dots arranged in a clover pattern, often localized into the opening of the follicle. It is hypothesized that "rosette marks" are histologically related to orthokeratosis and parakeratosis changes known as "flag marks".
- A non-pigmented AK: a linear or wavy vein pattern, or "strawberry pattern", is described as an unfocused blood vessel between hair follicles, with a halo-white follicle.
- A pigmented AK: gray to the point of brown or sphere around the follicle opening, and the annular-granular rhomboidal structure; often difficult to distinguish from malignant lentigo.
Prevention
Ultraviolet radiation is believed to contribute to the development of actinic keratoses by inducing mutations in epidermal keratinocytes, leading to atypical cell proliferation. Therefore, preventive measures for AK are targeted to limit exposure to solar radiation, including:
- Limit the level of sun exposure
- Avoid exposure to sunlight during the noon hours when the strongest UV rays
- Uses sun visor
- Often apply a strong sunscreen with an SPF rating of over 30 and it also blocks UVA and UVB rays
- Wearing sun-protective clothing such as hats, long-sleeved shirts, long skirts, or trousers
A recent study involving human papillomavirus (HPV) in the development of AK suggests that prevention of HPV in turn may help prevent AK progression, because UV-induced mutations and oncogenic transformation may be facilitated in cases of active HPV infection.
Management
There are many treatment options for AC dependent on the patient and clinical characteristics of the lesion. The AK shows various features, which guide the treatment decision-making. Although the overall healing rate is high, experts agree that the best treatment for AK is prevention. Follow-up is regularly recommended after treatment to ensure no new lesions develop and the old one is undeveloped.
Drugs
Fluorouracil cream
Topical Fluoracasil (5-FU) destroys AK by blocking the methylation of thymidylate synthase, thus interfering with DNA and RNA synthesis. This in turn prevents the proliferation of dysplastic cells in AK. Topical 5-FU is the most widely used treatment for AK, and often results in effective removal of lesions. Overall, there is a 50% success rate that results in 100% cleansing of topical treated AK with 5-FU. 5-FU may be up to 90% effective in treating non-hyperkeratotic lesions. The most common application regimen is to apply a topical cream layer to the lesion twice daily after washing; the duration of treatment is usually 2-4 weeks, but treatment for up to 8 weeks has shown a higher cure rate.
imiquimod cream
Imiquimod is a topical immune enhancing agent that is licensed for the treatment of genital warts. Imiquimod stimulates the immune system through the release and up-regulation of cytokines. Treatment with Imiquimod cream applied 2-3 times per week for 12 to 16 weeks was found to produce complete resolution of AK in 50% of people, compared with 5% of controls. Imiquimod Cream 3.75% has been validated in a treatment regimen consisting of daily application for the entire face and scalp for two 2-week treatment cycles, with a complete clearance rate of 36%. While the clearance rate observed with Imiquimod cream was 3.75% lower than that observed with 5% cream (36 and 50 percent, respectively), there was a reported lower rate of adverse reactions with 3.75% cream: 19% of Individuals using Imiquimod Cream 3.75% reported adverse events including local erythema, scabbing, and exfoliation at the site of the application, while nearly one-third of individuals using 5% cream reported the same type of reaction with Imiquimod treatment. However, it is ultimately difficult to compare the effectiveness of different strength creams directly, since the current study data varies in methodology (eg duration and frequency of care, and number of skin covered areas).
Ingenol mebutate gel
Ingenol mebutate is a new treatment for AK used in Europe and the United States. It works in two ways, first by disrupting cell membranes and mitochondria resulting in cell death, and then by inducing cellular cytotoxicity-dependent antibodies to remove the remaining tumor cells. A 3-day treatment course with 0.015% gel is recommended for the scalp and face, while a 2-day treatment course with 0.05% gel is recommended for stems and extremities. Treatment with 0.015% gel was found to thoroughly clear 57% of AK, whereas 0.05% gel had a clearance rate of 34%. The advantages of ingenol mebutate treatment include short duration of therapy and low relapse rate. Local skin reactions including pain, itching and redness may be expected during treatment with ingenol mebutate. This treatment comes from a small spike, Euphorbia peplus that has been used as a traditional remedy for keratosis.
Diclofenac sodium gel
Topical diclofenac sodium gel is a nonsteroidal anti-inflammatory drug that is thought to work in the treatment of AK through inhibition of the arachidonic acid pathway, thereby limiting the production of prostaglandins thought to be involved in the development of UVB-induced cancer skin. Recommended duration of therapy is 60 to 90 days with twice-daily application. Facial AK treatment with diclofenac gel leads to completion of complete lesions in 40% of cases. Common side effects include dryness, itching, redness, and rashes at the application site.
Retinoid
Topical retinoids have been studied in AK treatment with simple results. Treatment with adapalene gel daily for 4 weeks, and then twice daily a day for a total of nine months led to a significant but modest reduction in the number of AK compared to placebo; it shows the added benefit of improving the appearance of sun-damaged skin. Topical tretinoin is not as effective as a treatment to reduce the amount of AK. For the secondary prevention of AK, systemic, low-dose acitretin is found to be safe, well tolerated and effective enough in chemoprophylaxis for skin cancer in renal transplant patients.
Procedures
Cryotherapy
Liquid nitrogen (-195.8 Â ° C) is the most commonly used destructive therapy for the treatment of AK. This is a well tolerated office procedure that does not require anesthesia. Cryotherapy is especially indicated for cases where there are multiple, thin lesions, strictly defined. This is generally done by using an open spray technique, where AK is sprayed for several seconds.
This process can be repeated several times in one office visit, as tolerated. Drug levels of 67 to 99 percent have been reported, depending on the timing of clotting and the characteristics of the lesion. Losses include discomfort during and after the procedure; blistering, scarring and redness; hypo- or hyper pigmentation; and the destruction of healthy tissue.
Photodynamic therapy
AK is one of the most common dermatological lesions in which photodynamic therapy using topical methyl aminolevulinate (MAL) or 5-aminolevulinic acid (5-ALA) is indicated.
Treatment begins with the preparation of the lesion, which includes peeling scales and crusts using a dermal curette. A thick layer of topical MAL or 5-ALA cream is applied to lesions and small areas around the lesion, which are then covered with occlusive dressings and left for a period of time. During this time the photosensitizer accumulates in the target cell in the AK lesion. The dressing is then removed and the lesion is treated with light at the specified wavelength.
Several treatment regimens using different photosensitizers, incubation times, light sources, and previous treatment regimens have been investigated and show that longer incubation times lead to higher clearance of lesions. Photodynamic therapy is becoming popular. It has been found to have a 14% higher probability of achieving complete clearance of the lesion at 3 months compared with cryotherapy, and appears to produce superior cosmetic results when compared with cryotherapy or 5-FU treatment. Photodynamic therapy seems to be very effective in treating areas with many AK lesions.
Surgical technique
- Surgical excision : Excision should be made for cases when AK is thick and horny papules, or when deeper invasion is suspected and histopathologic diagnosis is required. This is a rarely used technique for AK treatment.
- Shave excision and curettage (often followed by electrodessication): This technique is often used for the treatment of AK, and especially for hyperkeratotic lesions. The surface of the lesion can be scraped with a scalpel, or the base can be removed with a curette. The tissue can be evaluated histopathologically, but the specimens obtained using this technique are not often sufficient to determine whether the lesion is invasive or intraepidermal.
- Dermabrasion : Dermabrasion is useful in the treatment of large areas with many AK lesions. This process involves the use of a hand-held device to "sand" the skin, removing the stratum corneum layer from the epidermis. Diamond frais or a high speed spinning wire brush is used. This procedure can be very painful and requires procedural sedation and anesthesia, requiring hospitalization. The one-year permit rate with dermabrasion treatment is as high as 96%, but decreases dramatically to 54% over five years.
Laser therapy
Laser therapy using carbon dioxide (CO 2 ) or erbium: yttrium aluminum garnet (Er: YAG) laser is a maintenance approach used with increasing frequency, and sometimes in conjunction with computer scanning technology. Laser therapy has not been studied extensively, but current evidence suggests it may be effective in cases involving multiple AK biases into medical therapy, or AK located in cosmetically relevant locations such as the face.
Chemical peels
Chemical peeling is a topical topical material that injures the outermost layer of the skin, promotes organized improvement, exfoliation, and finally smooth and rejuvenated skin development. Various therapies have been studied. Medium-depth skin can effectively treat some non-hyperkeratotic AKs. This can be achieved with 35% to 50% tricloroacetic acid (TCA) alone or at 35% in combination with Jessner's solution in a once-daily application for at least 3 weeks; 70% glycolic acid (? -hydroxy acid); or CO solid 2 . When compared with 5-FU treatment, chemical peels have demonstrated similar efficacy and increased ease of use with similar morbidity. Chemical exfoliation should be performed in a controlled clinical setting and is only recommended for individuals who are able to adhere to precautions, including avoiding exposure to sunlight. Furthermore, they should be avoided in individuals with a history of HSV or keloid infection, and in those who are immunosuppressed or who use photosensitizing drugs.
Prognosis
AK follows one of three pathways: they can survive as AK, retreat, or develop into invasive skin cancer, because the AK lesion is considered to be in the same sequence as squamous cell carcinoma (SCC). Retreating AK lesions also have the potential to reoccur.
- Progression: The overall risk of AK turned into a low invasive cancer. In individuals with an average risk, the likelihood of an AK lesion progressing to SCC is less than 1% per year. Despite this low rate of development, studies show that 60% of full SCCs emerge from pre-existing AK, reinforcing the idea that these lesions are closely related.
- Regression: The regression rate reported for a single AK lesion ranges from 15-63% after one year.
- Recurrence: The 1-year recurrence rate for a single acute AK lesion that has regressed is between 15-53%.
Clinical course
Actinic keratosis has three possible clinical outcomes: they can retreat, remain stable, or develop into an invasive disease. Sometimes they come and go, appear on the skin, remaining for months, and then disappear. Often they will reappear within a few weeks or months, especially after unprotected sun exposure. If left untreated, it is possible that the lesions will develop into invasive. Although it is difficult to predict whether AK will progress to squamous cell carcinoma, it has been noted that squamous cell carcinoma originates from lesions previously diagnosed as AK with a reported frequency between 65 and 97%.
Epidemiology
Actinic keratosis is very common, with an estimated 14% of dermatological visits associated with AK. It is more commonly seen in white individuals, and rates vary by location and geographical age. Other factors such as exposure to ultraviolet (UV) radiation, certain phenotypic features, and immunosuppression may also contribute to the development of AK.
Men are more likely to develop AK than women, and the risk of developing an AK lesion increases with age. These findings have been observed in several studies, with rates from one study showing that about 5% of women ages 20-29 develop AK compared with 68% of women aged 60-69, and 10% of men aged 20-29 develop an AK compared to 79% of men age 60-69 years.
Geography seems to play a role in the sense that individuals living in locations where they are exposed to UV radiation more throughout their lives have a higher risk of developing AK. Much of the literature on AK comes from Australia, where the prevalence of AK is estimated to be 40-50% in adults over 40, compared with the United States and Europe, where the prevalence is estimated to be below 11-38% in adults. One study found that those who immigrated to Australia after the age of 20 had fewer AIDs than the native Australians of all age groups.
Research
Diagnostically, researchers are investigating the role of new biomarkers to help determine which AK is more likely to develop into cutaneous SCC or metastasis. Upregulation matrix metalloproteinase (MMP) is seen in various types of cancer, and the expression and production of MMP-7 in particular have been found to increase in SCC in particular. The role of serine peptidase inhibitor (Serpin) is also under investigation. SerpinA1 was found to increase in keratinocytes from the SCC cell line, and increased SerpinA1 regulation correlated with the development of SCC in vivo tumors . Further investigation into specific biomarkers can help providers better assess the prognosis and determine the best treatment approach for specific lesions.
In terms of treatment, a number of drugs are being studied. Resiquimod is a 7/8 TLR agonist that works with imiquimod, but 10 to 100 times stronger; when used to treat an AK lesion, the complete response rate ranges from 40 to 74%. Afamelanotide is a drug that induces melanin production by melanocytes to act as a protective factor against UVB radiation. It is being studied to determine its efficacy in preventing AK in organ transplant patients using immunosuppressive therapy. Epidermal growth factor receptor (EGFR) inhibitors such as gefitinib, and anti-EGFR antibodies such as cetuximab are used in the treatment of various cancers, and are currently being investigated for potential use in the treatment and prevention of AK.
References
External links
Source of the article : Wikipedia
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