Actinic keratosis treatment - what are the options?

This article explores a skin condition known as actinic or solar keratosis and its potential treatments. 

What is actinic or solar keratosis?

Solar or actinic keratosis is a skin condition in which pigmented lesions appear and is often more prevalent in those with paler skin. This form of keratosis is associated with damage caused by exposure to UV radiation (i.e. sunlight) and results in irregular, brownish or reddish ‘scaly' lesions on the skin, which may also be accompanied by reddened borders, indicating excessive sun damage. 

These lesions may be a precursor of squamous cell carcinoma (SCC). For this reason, solar keratosis is regarded as the most common type of (potentially) malignant skin lesion.

The prevalence of solar keratosis may depend on a number of factors:

• Geographical location – It may be more common in parts of the world commonly linked to prolonged periods of sunlight exposure.
• Age – For example, up to 50% of Australians aged 40 years or more are reported to have developed solar keratosis.

Solar keratoses typically develop in areas more likely (for most demographics) to be exposed to the sun when outdoors, such as the face, neck, scalp, back of hands, forearms and legs. 

How actinic or solar keratosis develops

Solar keratosis begins at the cellular level (in epidermal keratinocytes or skin cells in the uppermost layer of skin) when the DNA in the cells sustain damage (or mutate) as a result of the harmful actions of UV radiation. This results in aberrations in these cells that allow them to resist cell death, a natural process that ensures new cells develop, function, differentiate, and then make way for new ones, and is the basis of tissue health and healing.

This process is called transformation and may cause the formation of benign growths such as solar keratoses over time. This, in turn, may lead to the growth becoming malignant. Skin keratosis that has reached the stage of malignancy is known as Bowen's disease. This may develop into full-blown squamous-cell carcinoma. Keratosis and its progression to full malignancy is associated with a number of risk factors. 

These may include:

• Caucasian ancestry and advancing age.
• Co-infection of the skin with the human papillomavirus has become associated with malignancy in solar keratosis. A protein that makes up the HPV virus may act to reduce a protein involved in the promotion of normal cell death. 
• Inflammation: This contributes to the probability of transformation and benign growth formation.
• Immunosuppression: This may also affect the risk of mutation and transformation.
• Location of the lesion: This may influence the progression to malignant carcinoma.
• Numbers of abnormal (i.e. mutated) skin cells in the epidermis; generally, a higher number of these increases the risk of malignancy.
• Male gender.
• Size (in diameter) of the lesion: This may also determine eventual malignancy.

Once solar keratosis has developed, it tends to follow one of three main outcomes. These are:

• Remission: This is the spontaneous resolution of keratotic lesions, a relatively common outcome.
• Stability: Remaining at a consistent size and shape without further complications (e.g. metastasis).
• Progression to full squamous-cell carcinoma.

Solar keratosis treatments: surgical procedures

Treatment for solar keratosis, or lesions that have progressed to malignancy, may require surgical procedures to remove these growths. These may include techniques such as:

• Cryosurgery
• Curettage
• Dermabrasion
• Excision
• Laser resurfacing

These therapies may be associated with adverse events such as infection, pain, burning and stinging sensations in the skin, redness, scarring and other disfigurements.

Cryosurgery (the application of liquid nitrogen to lesions to freeze them and separate them from the dermis below) is accurate and safe in most cases but is also associated with some adverse events, such as pigment changes in the targeted skin due to the increased susceptibility of melanocytes (pigment-producing cells) to freezing. Reduced pigmentation due to cryotherapy may occur in approximately 29% of cases, whereas paradoxical hyperpigmentation may occur in up to 6%.

Dermabrasion and laser resurfacing are also more likely to be associated with scarring, as they can cover a wider area. Most surgical treatments are regarded as most suitable and effective in cases of singular lesions or clusters of small lesions. Larger lesions and groups of lesions are generally targeted with 'field-directed' treatments. These are typically topical formations, which can cover larger areas, containing drugs that can act to interfere with the mechanisms of transformation and mutation.

How to get rid of actinic keratosis at home: topical treatments

You should speak with your healthcare professional before trying any at-home treatments for actinic keratosis.

Topical tretinoin

In the 1960s and 1970s, topical tretinoin (vitamin A) was the standard treatment for actinic keratosis and basal cell carcinoma. However, modern studies have shown that this medication alone is less effective than other treatments for these skin conditions. In fact, on its own, topical tretinoin is not considered a standard treatment for these conditions.

Topical 5-fluorouracil and actinic keratosis

Topical 5-fluorouracil (5-FU) is a cream applied to the skin to treat various skin diseases, including warts, psoriasis, vitiligo, and sunspots.

Actinic keratosis is the most common, indicated use for topical 5-FU. Studies have found 5% 5-FU cream effectively reduces actinic keratosis and the need for spot treatments.

Topical 5-FU destroys sun-damaged and pre-cancerous/cancerous cells by inducing inflammation in the skin. During treatment with topical 5-FU, the expected inflammation means patients must endure red, painful, weeping, oozing sores that form crusts and scabs for the duration of treatment and perhaps one to two weeks afterwards. Treatment usually takes four to six weeks; two to four weeks of active drug treatment with an additional two weeks of redness, blistering, and peeling of the skin.

Not surprisingly, patients and healthcare professionals are interested in shortening the time required for 5-FU treatment without making the treatment less effective. Some healthcare professionals prescribe tretinoin for two weeks before topical 5-FU treatment. 

Diclofenac

This is a nonsteroidal anti-inflammatory drug (NSAID) typically available in a 3% gel when used to treat solar keratosis. Diclofenac reduces inflammation, but it’s not known how it works to treat actinic keratosis.

Adverse events associated with diclofenac may include itching, skin dryness and contact dermatitis.

Imiquimod

This is a drug that modulates the immune response and has anti-tumour activities. It looks promising as a potential treatment for actinic keratosis but more studies are needed. 

Imiquimod may increase inflammation, which may cause adverse events such as discomfort and redness. These adverse effects are considered necessary for an effective treatment.

Related reads:

• How to take care of the skin on your face
• SPF 101 - what does SPF stand for and why does it matter?
• What you need to know about sunscreen according to the experts

References:

1. George, C. D., Lee, T., Hollestein, L., Asgari, M. M., & Nijsten, T. (2023). The Global Epidemiology of Actinic Keratosis in the General Population: A Systematic Review and Meta-Analysis. British Journal of Dermatology. https://doi.org/10.1093/bjd/ljad371
2. Steeb, T., Petzold, A., Hornung, A., Wessely, A., Berking, C., & Heppt, M. V. (2022). Spontaneous regression rates of actinic keratosis: a systematic review and pooled analysis of randomized controlled trials. Scientific Reports, 12(1). https://doi.org/10.1038/s41598-022-09722-8
3. Piquero-Casals, J., Morgado‐Carrasco, D., Gilaberte, Y., Del Río, R., Macaya-Pascual, A., Granger, C., & López‐Estebaranz, J. L. (2020). Management Pearls on the treatment of actinic keratoses and field cancerization. Dermatology and Therapy, 10(5), 903–915. https://doi.org/10.1007/s13555-020-00425-4
4. Ianhez, M., Pinto, S. A., Miot, H. A., & Bagatin, E. (2019). A randomized, open, controlled trial of tretinoin 0.05% cream vs. low-dose oral isotretinoin for the treatment of field cancerization. International Journal of Dermatology, 58(3), 365–373. https://doi.org/10.1111/ijd.14363
5. Briatico, G., Brancaccio, G., Scharf, C., Di Brizzi, E. V., Pellerone, S., Caccavale, S., Giorgio, C. M., Procaccini, E. M., Moscarella, E., & Argenziano, G. (2023). Real-World Experience with Topical 5-Fluorouracil 4% (40 mg/g) Cream for the Treatment of Actinic Keratosis. Dermatology Practical & Conceptual, e2023151. https://doi.org/10.5826/dpc.1302a151
6. Thai KE, Fergin P, Freeman M, et al. A prospective study of the use of cryosurgery for the treatment of actinic keratoses. International journal of dermatology. 2004;43(9):687-692.
7. Pomerantz H, Hogan D, Eilers D, et al. Long-term Efficacy of Topical Fluorouracil Cream, 5%, for Treating Actinic Keratosis: A Randomized Clinical Trial. JAMA Dermatol. Sep 2015;151(9):952-960. doi:10.1001/jamadermatol.2015.0502
8. Costa C, Scalvenzi M, Ayala F, Fabbrocini G, Monfrecola G. How to treat actinic keratosis? An update. Journal of Dermatological Case Reports. 2015;9(2):29-35. doi:10.3315/jdcr.2015.1199
9. Dodds A, Chia A, Shumack S. Actinic Keratosis: Rationale and Management. Dermatology and Therapy. 2014;4(1):11-31.
10. Diclofenac Topical (actinic keratosis): MedlinePlus Drug Information. (n.d.). https://medlineplus.gov/druginfo/meds/a611041.html#:~:text=Diclofenac%20topical%20gel%20(Solaraze)%20is,actinic%20keratosis%20is%20not%20known.
11. Bubna, A. K. (2015). Imiquimod - Its role in the treatment of cutaneous malignancies. Indian Journal of Pharmacology, 47(4), 354. https://doi.org/10.4103/0253-7613.161249