Actinic keratosis

At a glance

Key points of this condition

• Actinic keratosis is a precancerous squamous lesion caused by ultraviolet exposure, and the ICD-10 code is L57.0.
• It appears on sun-exposed areas such as the face, ears, and backs of the hands as a red, scaly patch or bump.
• The risk of progression to squamous cell carcinoma is low at 0.5–3.0%, but it can become malignant if left untreated.
• Diagnosis is based mainly on the medical history and clinical findings, and lesions with bleeding, enlargement, or changes should be biopsied.
• Treatment options include drug therapy (such as 5-FU and imiquimod), cryotherapy, photodynamic therapy, and surgical excision.
• The best specialist to treat lesions around the eyes is an oculoplastic surgeon.
• Using sunscreen and avoiding sunlight are effective preventive measures.

1. What is actinic keratosis?

Actinic keratosis (Actinic Keratosis; AK) is a premalignant squamous lesion classified under ICD-10 code L57.0 and ICD-9 code 702.0. It develops on skin chronically exposed to ultraviolet light and commonly appears on sun-exposed areas such as the face, lips, ears, backs of the hands, forearms, scalp, and neck.

It is common in middle-aged to older adults, and people with fair skin types (Fitzpatrick types I and II) are at especially high risk. Squamous cell carcinoma (squamous cell carcinoma, SCC) can develop from existing actinic keratosis, but the risk of metastatic spread is low at 0.5–3.0%.

Chronic sun exposure is considered the most important environmental predisposing factor for all ocular surface tumors.

Q Is actinic keratosis cancer?

A

Actinic keratosis is not cancer; it is a premalignant lesion. The risk of progression to squamous cell carcinoma is low, at 0.5–3.0%. However, it can become malignant if left untreated, so proper diagnosis and treatment are needed.

2. Main symptoms and clinical findings

Subjective symptoms

• Scaling and redness: Erythematous lesions gradually develop on the skin.
• Rough, gritty feel: A sandpaper-like texture is characteristic.
• Itching and irritation: It may cause itching or mild irritation.
• Bleeding and change: Biopsy is indicated if there is bleeding, persistent itching, enlargement, or any change.

Clinical findings

• Lesion appearance: It appears as an erythematous (red), scaly macule (macule: a flat pigmented lesion) or papule (papule: a solid, raised lesion). It has a round, scaly appearance.
• Distribution of lesions: There may be multiple lesions. They commonly occur on the face, lips, ears, backs of the hands, forearms, scalp, and neck.
• Examination methods: It can be examined with a slit-lamp microscope, dermoscope, or the naked eye.

3. Causes and risk factors

The main cause of actinic keratosis is sun exposure, especially UVA and UVB rays. Exposure to UV radiation triggers a series of complex genetic events, leading to proliferation of squamous epithelial cells and dysplastic changes in the skin.

• UV-A (320–380 nm): The main oxidative component; it induces production of reactive oxygen species (ROS), causing oxidative damage and DNA damage.
• UV-B (280–320 nm): The main DNA-damaging component; it is directly absorbed by DNA and causes DNA damage.

The main risk factors are as follows.

• History of chronic sun exposure: This includes occupations and lifestyles with a lot of outdoor activity.
• Fair skin type: People with Fitzpatrick skin types I and II are especially susceptible.
• Not using sunscreen: The habit of going outdoors without sunscreen increases the risk.
• Indoor tanning (tanning bed): Increases the risk of squamous cell carcinoma by 58% and basal cell carcinoma by 24%.

Prevention and daily care

• Use sunscreen (SPF 30 or higher) when going outdoors.
• Try to avoid outdoor activities during the hours of strongest sunlight (10:00 to 14:00) as much as possible.
• It is important to protect your skin from sunlight with a hat, long sleeves, sunglasses, and similar measures.
• Avoid using tanning beds.

Q Who is more likely to develop it?

A

People with fair skin types (Fitzpatrick types I and II), a history of chronic sun exposure, and those who do not use sunscreen outdoors are at higher risk. Use of indoor tanning (tanning bed) also greatly increases the risk.

4. Diagnosis and testing methods

Diagnosis begins with a provisional diagnosis based on the patient’s medical history and clinical findings. Evaluate the lesion with slit-lamp microscopy, dermoscopy, and visual inspection. New or suspicious lesions require biopsy and evaluation by a pathologist.

Indications for biopsy: lesions with bleeding, persistent itching, enlargement, or change.

The main differential diagnoses are listed below.

Disease	Differential points
Squamous cell carcinoma	With invasive growth and ulceration
Bowen’s disease	An intraepidermal squamous cell carcinoma with a well-demarcated erythematous lesion
Basal cell carcinoma	With a pearly sheen and telangiectasia
Lentigo maligna	Appears as an irregular pigmented lesion

5. Standard treatments

Drug therapy

The following topical medications are effective for actinic keratosis on the face, forehead, and scalp.

• Topical 5-fluorouracil (5-FU): FDA-approved topical anticancer medication. 0.5% 5-FU with 10% salicylic acid (5-FU/SA) is considered effective for lesions on the face, forehead, and scalp.
• Imiquimod cream (Imiquimod): A topical medication with immunomodulatory effects. 2.5% and 3.75% formulations are used.
• Ingenol mebutate gel (Ingenol mebutate gel): FDA-approved topical medication.
• Topical diclofenac gel (Topical diclofenac gel): FDA-approved topical medication.

According to systematic reviews, 5-FU/SA, ingenol mebutate, and imiquimod are all effective.

Other treatments

Cryotherapy

Indications: Lesions of actinic keratosis on the face.

Performed by: Performed in a dermatology clinic. Periocular lesions are best treated by an oculoplastic surgeon.

Photodynamic therapy

Photodynamic therapy (Blue light therapy): An FDA-approved in-office treatment. It combines aminolevulinic acid (ALA) and fluorescent blue light.

TCA chemical peel: A useful option for widespread lesions.

Surgical treatment

Complete excision: Performed when there is concern for a malignant tumor.

Laser therapy: An option when there is no concern for a malignant tumor.

Observation: In many cases, progression can be monitored clinically.

Points to note during treatment

• Actinic keratosis around the eye is best treated by an oculoplastic surgeon rather than a general dermatologist.
• Cryotherapy carries a risk of burns around the eye.
• When treating eyelid lesions with a CO2 laser, caution is needed for side effects such as corneal ulcer, delayed wound healing, abnormal pigmentation, and scarring caused by overheating of the metal shield.

Q How are actinic keratoses around the eye treated?

A

Periocular actinic keratosis is best treated by an oculoplastic surgeon. Options include cryotherapy, surgical excision, and laser treatment. Cryotherapy performed in a general dermatology clinic must be done carefully because of its possible effect on the eye.

6. Pathophysiology and detailed mechanism of development

The basic mechanism of actinic keratosis is that exposure to UV radiation triggers complex genetic events, leading to proliferation of squamous cells and dysplastic changes in the skin.

UV-A induces the production of reactive oxygen species (ROS), causing oxidative damage and DNA damage. UV-B is absorbed directly by DNA and causes DNA damage. The genetic changes that accumulate through this process ultimately lead to actinic keratosis and squamous cell carcinoma.

Histologically, it is characterized by the following findings:

• Hyperkeratosis (hyperkeratosis): Excessive thickening of the stratum corneum.
• Parakeratosis (parakeratosis): A state in which nuclei remain in keratinocytes.
• Dyskeratosis (dyskeratosis): Abnormal keratinization at the individual cell level.
• Solar elastosis (solar elastosis): Degeneration of elastin in the superficial dermis.
• Increased nuclear-to-cytoplasmic ratio (N/C ratio): A finding that indicates neoplastic change.
• Pleomorphism (pleomorphism), nuclear hyperchromatism (nuclear hyperchromatism), and cellular atypia (cellular atypia): Histologic indicators of dysplasia.

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7. Latest research and future prospects (reports at the research stage)

For patients: Please read this carefully

The following content is still in the research stage or under clinical trial and is not standard treatment available at ordinary hospitals. It is reference information for professionals about future medical developments.

Application of CO2 laser resurfacing to eyelid lesions

CO2 laser (resurfacing) has begun to be used to treat actinic keratosis of the eyelid. Reports suggest that it is effective and safe for non-melanoma skin cancer when used alone or in combination with other treatments, but further research is needed to evaluate long-term effectiveness.

Reported main side effects include burns around the eye, corneal ulcers caused by overheating of the metal shield, delayed wound healing, abnormal pigmentation, and scar formation.

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8. References

• AAO BCSC Section 4: Ophthalmic Pathology and Intraocular Tumors (2011–12)
• Ortonne JP. A global survey of the recognition, perception, and management of actinic keratosis. Br J Dermatol. 2002.
• Stockfleth E, et al. New treatment recommendations for actinic keratosis from the European Dermatology Forum. Acta Derm Venereol. 2016.
• Jeffes EW, McCullough JL, Weinstein GD, Kaplan R, Glazer SD, Taylor JR. Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light. Journal of the American Academy of Dermatology. 2001;45(1):96-104. doi:10.1067/mjd.2001.114288. PMID:11423841.