Background

Actinic keratoses, commonly known as senile keratoses or sun keratoses, are benign intraepithelial neoplasms and one of the most prevalent skin conditions examined by dermatologists.

AKs are frequently connected with prolonged sun exposure and may manifest as irregular, red, scaly papules or plaques on sun-exposed areas of the body.

AKs have the potential to develop into invasive SCC if left untreated, highlighting the significance of early identification and the establishment of a treatment plan. Several management strategies are available for AKs.

Epidemiology

Actinic keratoses are most prevalent on persistently sun-exposed regions on the body. Older individuals have a higher risk of developing these due to the longer accumulated exposure to the sun.

Regions which are more susceptible to developing actinic keratoses include the scalp, face, dorsal surface of the hands, and the back of the arms.

Risk factors which are linked to actinic keratoses are:

• Male Sex
• Older age
• Caucasians or fair individuals
• Immunosuppression
• Geographic location- areas closer to the equator
• History of skin cancer or actinic keratosis
• Chronic sun exposure
• Individuals exposed to artificial sources of UV rays
• Individuals with conditions such as xeroderma pigmentosum and albinism

Anatomy

Pathophysiology

The pathophysiology underlying the development of actinic keratoses is complicated. Through the breakdown of regulatory mechanisms involved in cell development and differentiation, excessive and accumulative UV radiation exposure can produce a multitude of pathologic alterations in epidermal keratinocytes. Inflammation and immunosuppression leads to the growth of dysplastic keratinocytes within the epidermis, which gives birth to actinic keratosis.

Etiology

Most cases of actinic keratoses develop due to the damage caused to skin because of UV radiation through chronic sun exposure.

Genetics

Prognostic Factors

Most cases of actinic keratoses regress spontaneously, due to some mechanism not completely understood. Other cases have a risk of evolving into squamous cell carcinoma.

Actinic keratoses is the most comma risk factor for squamous cell carcinoma, as most cases develop from former AKs or between a region affected by actinic keratoses. For a favorable outcome, patients are advised regular skin exams to spot new AKs and diagnose SCC in the early stages.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

• Diagnosis: A dermatologist evaluates the skin for suspicious lesions and confirms the diagnosis of actinic keratosis. Lesions may be palpated and examined under magnification, and some may require a biopsy for confirmation. 
• Preventive Measures: Patients are educated on sun protection strategies to prevent new AK lesions from forming. This includes avoiding excessive sun exposure, wearing protective clothing, and applying broad-spectrum sunscreen. 
• Topical Therapies: Topical treatments are often the first-line approach for multiple, visible AK lesions. Imiquimod (Aldara), Fluorouracil (5-FU), or Ingenol Mebutate: These creams stimulate the immune system to attack and remove abnormal cells. Treatment typically involves daily application for a defined period. Diclofenac Gel (Solaraze): This topical non-steroidal anti-inflammatory gel can be applied to the affected areas for several weeks. Tretinoin (Retin-A): A topical retinoid, it is applied to the skin to enhance cell turnover and reduce the appearance of AK lesions. 
• Cryotherapy (Cryosurgery): Liquid nitrogen is used to freeze & destroy individual AK lesions. This is a common treatment for isolated, thick AKs. 
• Photodynamic Therapy (PDT): A photosensitizing agent (typically a topical solution) is applied to the AK lesions, followed by exposure to a specific light source. The light activates the agent, which selectively destroys the abnormal cells. PDT is effective for widespread, thin AKs. 
• Chemical Peels: Chemical peels use strong acids to remove the top layer of skin, which can be beneficial for some AK lesions. Medium-depth or deep peels are typically administered by a healthcare provider. 
• Laser Therapy: Lasers can be used to target and remove AK lesions. They are especially useful for patients with multiple, visible AKs in a small area. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

non-pharmacological-treatment-of-actinic-keratosis

Lifestyle modifications: 

• Sun Protection: Apply broad-spectrum sunscreen with a sun protection factor 30 or higher to exposed skin, even on cloudy days. Reapply every two hours and after swimming or sweating. Wear wide-brimmed hats, long-sleeved shirts, long pants, and sunglasses to shield your skin and eyes from the sun’s harmful ultraviolet (UV) radiation. 
• Regular Skin Self-Examinations: Familiarize yourself with the appearance of your AK lesions and other skin spots. Perform regular self-examinations to monitor changes or new lesions. Report any concerning changes to your dermatologist. 
• Diet and Nutrition: A balanced diet including vegetables, fruits, and foods with antioxidants, as these may help protect your skin from UV damage. Consider increasing your intake of foods with skin-protecting compounds, such as lycopene (found in tomatoes), beta-carotene (found in carrots), and green tea. 
• Avoid Tanning Beds and Lamps: Refrain from using tanning beds or lamps, as they emit harmful UV radiation that can exacerbate skin damage and increase the risk of AK and skin cancer. 

• Smoking Cessation: If you smoke, consider quitting. Smoking can damage your skin and increase the risk of skin cancer. 
• Limit Alcohol Consumption: Excessive alcohol consumption can affect skin health. Moderate or limit your alcohol intake and consult with a healthcare provider if you need support to reduce your alcohol consumption. 
• Stress Management: High stress levels can impact overall health, including skin health. Practicing stress-reduction techniques like meditation, mindfulness, or yoga may help. 

Use of Topical Antineoplastic Agents in the treatment of Actinic Keratosis

Fluorouracil Topical (Fluoroplex, Efudex, Carac, Tolak): 

• Fluorouracil is a topical chemotherapy agent that interferes with the DNA synthesis of rapidly dividing cells, including precancerous and cancerous skin cells. The treatment typically involves applying the cream once or twice a day for several weeks. The duration may vary based on the extent and severity of AK lesions. 

Ingenol Mebutate Topical (Picato): 

• Ingenol mebutate is derived from the Euphorbia peplus plant and has a dual mechanism of action. It rapidly destroys AK cells by disrupting cell membranes and inducing cell death. Ingenol mebutate gel is applied directly to the AK lesions on the face, scalp, or body for a short duration. The gel is typically applied once daily for two or three consecutive days, depending on the location of the AK lesions. The shorter treatment duration is an advantage for some patients. 

Use of Topical Immunomodulator in the treatment of Actinic Keratosis

Imiquimod Topical (Aldara and Zyclara): 

• It is an immune response modifier that activates the body’s immune system to recognize and eliminate abnormal or precancerous skin cells. Patients apply Imiquimod cream (Aldara or Zyclara) directly to the affected areas of the skin. The typical treatment regimen involves applying the cream several times a week, typically three times a week for Aldara and once daily for Zyclara. The duration may vary based on the extent and severity of AK lesions. Imiquimod works by inducing an inflammatory response in the treated area. This leads to redness, swelling, and the formation of open sores or blisters. It is important to understand that this inflammatory reaction is a sign that the medication is active and stimulating the immune system to clear the AK lesions. As the inflammation subsides, the treated areas may heal with healthier skin. 

Use of Topical Photosensitizing Agents in the treatment of Actinic Keratosis

Aminolevulinic acid (Levulan Kerastick, Ameluz) 

• Aminolevulinic acid (ALA) is a photosensitizing agent that is applied topically to the skin. It is absorbed by abnormal or precancerous skin cells more than by healthy skin cells. When exposed to a specific wavelength of light, ALA is activated, leading to the production of singlet oxygen and the destruction of the targeted cells. ALA is applied as a solution or gel directly to the AK lesions. After application, there is an incubation period, during which ALA is absorbed by the targeted cells. The length of this period may vary but is typically 1 to 3 hours. 
• After the incubation period, the treated areas are exposed to a specific light source with the appropriate wavelength, typically blue or red light. The light activates ALA and selectively destroys the AK cells. The treated areas may become inflamed, and the AK lesions will eventually peel, heal, and be replaced by healthier skin. 

Use of Topical Nonsteroidal Anti-inflammatory agents in the treatment of Actinic Keratosis

Diclofenac Transdermal Gel (3%): 

• Diclofenac is an NSAID that exerts its anti-inflammatory and anti-proliferative effects by inhibiting the production of prostaglandins, which is involved in skin damage and cell growth. Diclofenac gel is applied topically to the affected areas of the skin where AK lesions are present. The duration of treatment with Diclofenac gel may vary but typically involves applying the gel to AK lesions twice daily for a defined period, which may range from several weeks to several months. Diclofenac reduces inflammation and may lead to the regression of AK lesions. It does not typically cause an inflammatory response like some other treatments, making it a more comfortable option for some patients. 

Use of Microtubule inhibitor in the treatment of Actinic Keratosis

Tirbanibulin Topical (Klisyri): 

• Tirbanibulin is a microtubule inhibitor that works by disrupting microtubules, which are structural components of cells. By affecting microtubules, Tirbanibulin impairs the ability of precancerous and cancerous cells to divide and proliferate. Patients apply Tirbanibulin cream (Klisyri) directly to the affected AK lesions on the face or scalp. The typical treatment regimen involves applying cream once daily for five consecutive days. Tirbanibulin induces a localized inflammatory response in the treated areas, leading to redness, crusting, and the elimination of AK lesions. 

cryosurgery-in-the-treatment-of-actinic-keratosis

Cryosurgery, also known as cryotherapy, is a common and effective treatment for actinic keratosis (AK), a precancerous skin condition caused by sun exposure. Here’s how cryosurgery is used in the treatment of AK: 

• Procedure: Cryosurgery involves the use of extreme cold to freeze and destroy AK lesions and the abnormal cells within them.  
• Preparation: The healthcare provider first cleans the treatment area and may use a cotton swab or spray device to apply a freezing agent, typically liquid nitrogen, directly to the AK lesions. 
• Application: Liquid nitrogen has an extremely low temperature and is applied to the AK lesions. The freezing agent freezes the affected cells, causing ice crystals to form within them. 

• Duration: The freezing process usually takes only a few seconds. The provider ensures that the freezing agent reaches the depth necessary to destroy the AK lesions. 

cosmetic-resurfacing-procedures-involved-in-actinic-keratosis

Cosmetic resurfacing procedures can be considered for the treatment of actinic keratosis (AK) when AK lesions are limited, and the patient has a desire to improve appearance and texture of skin. These procedures aim to remove the affected skin layers, promote healthy skin growth, and provide a more youthful and rejuvenated appearance. 

• Chemical Peels: These peels involve the application of a chemical solution to the skin, causing the top layer to peel off. The types of chemical peels, including superficial, medium, and deep peels. Superficial peels are commonly used for mild AK. They can improve skin texture and even out pigmentation. 
• Microdermabrasion: It uses a machine to exfoliate the outermost layer of skin, which can help improve skin texture and reduce the appearance of AK and sun damage. 
• Laser Resurfacing: Laser treatments, such as fractional laser therapy, can remove the top layers of skin and stimulate collagen production. This can help in reducing AK lesions and improving overall skin quality. 
• IPL (Intense Pulsed Light) Therapy: IPL therapy uses intense pulsed light to target pigmentation issues and reduce the appearance of sun-damaged skin. It can be used to treat AK as well. 

management-of-actinic-keratosis

Acute Phase: 

• Assessment and Diagnosis: A dermatologist evaluates the skin for AK lesions, which may appear as dry, scaly patches, and confirms the diagnosis through examination or, in some cases, a biopsy. 
• Treatment Initiation: After diagnosis, the healthcare provider determines the appropriate treatment plan based on the number, type, and location of AK lesions. 

Treatment Phase: 

• Application of Therapies: The chosen treatment modalities are applied, which might include topical medications (like 5-fluorouracil, imiquimod, diclofenac), procedures (like cryotherapy, photodynamic therapy), or other options based on the individual’s case. 

Chronic Phase: 

• Monitoring and Surveillance: After the initial treatment, regular follow-up appointments with a dermatologist are recommended. These appointments serve to monitor the skin’s response to treatment, assess for recurrence or development of new lesions, and evaluate for any signs of skin cancer. 

• Ongoing Sun Protection: Long-term sun protection measures are crucial to prevent new AK lesions and reduce the risk of skin cancer. Patients are advised to limit sun exposure, wear protective clothing, and use sunscreen regularly. 

Medication

Future Trends

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References

https://www.cedars-sinai.org/health-library/diseases-and-conditions/a/actinic-keratosis.html

https://www.ncbi.nlm.nih.gov/books/NBK557401/

Actinic Keratosis – StatPearls 

Actinic keratosis: Diagnosis and treatment