Best office procedures for Actinic Keratosis

What is actinic keratosis?

Actinic keratosis, also known as solar keratosis, is a precancerous skin lesion that develops due to prolonged exposure to ultraviolet (UV) radiation from the sun or indoor tanning. The condition is characterized by the proliferation of several atypical keratinocytes, leading to the formation of rough, scaly patches on the skin [1].

The prevalence of AK varies globally, ranging from 40-60% in fair-skinned populations living in sunny regions to 20% in the United States. Risk factors for developing AK include fair skin, light hair and eye color, chronic sun exposure, older age, immunosuppression, and residing in regions closer to the equator [1, 3, 4]. Individuals with outdoor occupations or hobbies and bald males are at an increased risk of developing extensive actinic damage [3, 5].

While not all AK lesions progress to skin cancer, the condition is considered a precursor to SCC, with a 5-10% risk of progression if left untreated [1]. Factors indicating a higher risk of malignant transformation include a tender, thickened, ulcerated, or enlarging appearance of the lesion [1]. Patients with multiple AK lesions (more than 10) have an estimated 10-15% chance of developing SCC at some stage [1].

The pathogenesis of AK involves a complex interplay of UV-induced DNA damage, immunosuppression, and alterations in cellular signaling pathways [6]. Chronic UV exposure leads to the accumulation of mutations in key genes responsible for regulating cell growth and differentiation, such as p53 and p16 [6]. These genetic changes, along with the suppression of the skin's immune response, contribute to the development of atypical keratinocytes and the formation of AK lesions [6].

Common symptoms of actinic keratosis

Actinic keratosis typically presents as rough, dry, or scaly patches on sun-exposed areas of the skin. These lesions can be flat or slightly raised, with a diameter usually less than 1 inch (2.5 cm). The color of AK lesions can vary, appearing red, tan, pink, white, brown, or a combination of these colors [7].

Other common symptoms of AK include:

• A gritty or sandpaper-like texture when touched
• Gradual development over time, with most lesions first appearing in people over the age of 40
• Actinic cheilitis, a variant of AK that appears on the lower lip, causing a dry, cracked, or scaly appearance
• A "strawberry pattern" on dermoscopy for non-pigmented facial AK, characterized by fine wavy vessels, scale, microerosions, and a "strawberry" appearance [20]
• A "rhomboidal pattern" on dermoscopy for pigmented AK lesions, along with scale, white globules, and a "jelly sign" [20]

It is important to note that the appearance of AK can vary, and the lesions may be difficult to distinguish from other skin conditions or early skin cancers. Regular skin examinations by a dermatologist are recommended to detect and properly diagnose AK [1].

In some cases, AK lesions may be asymptomatic, making it crucial for individuals with a history of sun exposure to undergo periodic skin checks. Early detection and treatment of AK can help prevent progression to SCC and minimize the risk of complications [1].

Patients should be educated on the importance of self-examination and reporting any new or changing skin lesions to their healthcare provider. They should also be advised to protect their skin from further sun damage by using broad-spectrum sunscreen, wearing protective clothing, and seeking shade during peak UV hours [1].

Recommended treatment for actinic keratosis

Several effective office procedures are available for treating actinic keratosis, some directed at specific lesions, others designed to treat an area of sun-damaged skin with numerous AKs, also called field-directed therapy. Treatment depends not only on the number, but also the location of the lesions, their severity, and the state of your health.[ 1] As in any treatment, reviewing the potential risks and benefits of each therapy with a healthcare provider will help you determine the most appropriate course of treatment for your condition. [2]

Topical medicine

Before or after an in-office procedure, your dermatologist may prescribe a topical cream or gel that you use at home. Topical treatments are often the first line of field-directed treatment for skin areas with multiple AK lesions, such as a bald head, or arms and legs.

There most common and effective topical treatments for AKs are fluorouracil (Carac, Efudex), miquimod (Aldara, Zyclara), and diclofenac. These medicines can cause significant skin irritation for a few weeks, including redness, inflammation, and burning. If symptoms become severe or persist beyond the expected duration, contact your doctor immediately. [1, 5, 7, 8, 9].

Pros:

• Non-invasive
• Effective for a large field of AKs that are not very thick or advanced

Cons: [1, 5, 7]

• Side effects include skin redness, itching, burning, and inflammation for a few weeks
• May interact with other medications
• May increase the risk of photosensitivity reactions, so use sun protection measures during treatment
• May not be effective on thicker, more advanced AKs

Recommended in-office procedures for actinic keratosis

Cryotherapy (freezing)

Cryotherapy is the process of freezing AK lesions with liquid nitrogen. Also known as cryosurgery or liquid nitrogen therapy, cryotherapy is a highly effective, quick, and well-tolerated treatment for actinic keratosis, particularly for patients with a limited number of lesions.

Treatment involves applying liquid nitrogen to individual AK lesions, causing them to freeze and then blister, and peel off. The procedure is quick and effective. [1, 2, 3, 4]

Petroleum jelly or a similar ointment is applied to the area to promote healing, and you will need to keep it clean and dry. [18]

These are the advantages and disadvantages of cryotherapy:

Pros:

• High efficacy rates, with clearance rates of 75-99% reported in clinical studies [18, 19]
• Quick and convenient. Treatment typically takes less than a minute per lesion [18]
• Minimal discomfort. Most patients experience only mild pain or stinging during the procedure. [18]
• Low scar risk, Cryotherapy selectively targets the AK lesions while preserving the surrounding healthy tissue [18]
• Relatively inexpensive. Cryotherapy is the most cost-effective treatment option for AKs, making it an accessible choice for many patients.
• Suitable for multiple lesions. Cryotherapy can be used to treat multiple actinic keratosis lesions in a single session.

Cons:

• Potential side effects. While it’s generally well-tolerated, cryotherapy can cause temporary side effects such as pain, swelling, blistering, and crusting of the treated area [18]. These side effects usually resolve within a few days to weeks after treatment [18]. Rarely, cryotherapy may cause hypo- or hyperpigmentation of the treated skin, particularly in individuals with darker skin types [18].
• Risk of recurrence. Actinic keratosis lesions may recur at any point after treatment, which would necessitate additional treatment.
• Limited penetration. Cryotherapy may not be effective on deeper or more invasive lesions, as cryotherapy only freezes the skin’s surface layers.
• Skill-dependent.The success of cryotherapy is somewhat dependent on the skill and experience of the provider performing the procedure.[18, 19] The provider's ability to determine the optimal freeze times can make all the difference: A systematic review found that longer freeze times (>5 seconds) and double freeze-thaw cycles were associated with higher clearance rates then shorter freeze times or single freeze-thaw cycles [19].

Overall, cryotherapy is a well-established and widely used treatment option for isolated actinic keratosis lesions, offering an effective and relatively inexpensive solution for many patients.

Surgical excision (scraping, curettage, electrosurgery)

For larger or more advanced AK lesions, surgical removal may be necessary. In this procedure, your healthcare provider first numbs the skin around the lesion, and then uses a curet to scrape off damaged cells. Scraping may be followed by electrosurgery, in which a pencil-shaped instrument is used to cut and destroy the affected tissue with an electric current. Your provider then scrapes away or cuts out the lesions and stitches the wound back together. [1, 2, 3] The wound will heal in two to three weeks.

Side effects may include infection, scarring, and changes in skin color of the affected area.

Laser ablation

This technique is increasingly used to treat actinic keratosis. Your health care provider uses High-energy laser beams from an ablative laser device to destroy AK lesions, and new skin grows back. Side effects may include scarring and discoloration of the affected skin. This procedure is precise and can be used for hard-to-reach areas [1, 2, 3].[a]

Photodynamic therapy (PDT)

Photodynamic therapy (PDT) is a well-tolerated, effective treatment for multiple AK lesions. PDT offers excellent clearance rates and cosmetic outcomes, as it selectively targets the precancerous cells while preserving the surrounding healthy tissue. PDT is particularly effective for people with multiple lesions due to its ability to treat large areas and for those looking for optimal cosmetic results.

The procedure involves the application of a photosensitizing agent, such as aminolevulinic acid (ALA) or methyl aminolevulinate (MAL), to the affected skin areas. After a period of incubation, the treated areas are exposed to a specific wavelength of light, typically from a laser or LED light source. PDT selectively targets and destroys the precancerous cells while preserving healthy tissue [1, 2, 3].

After undergoing photodynamic therapy, be advised to avoid sun exposure for 48 hours and use cold compresses to alleviate any discomfort or swelling and to minimize the risk of complications [12, 13].

Pros: [12, 13]

• Highly effective in treating AK lesions, with reported clearance rates of up to 90%
• Ability to treat large areas of field cancerization in a single session
• Targets and treats the entire field of sun-damaged skin, not just individual lesions
• Minimally invasive procedure with minimal downtime
• Excellent cosmetic outcomes with reduced risk of scarring compared to surgical excision [12, 13]
• Can be repeated as needed for new or recurrent lesions
• Potential for long-term remission, with lower recurrence rates compared to cryotherapy

Cons:

• May cause temporary side effects, including pain, stinging, burning, or redness, or swelling and crusting of the treated area. These side effects are typically mild to moderate, and resolve within a few days to weeks after treatment.
• Multiple treatment sessions may be required for optimal results
• Photosensitivity and sun avoidance are necessary for a period after treatment
• Not suitable for patients with certain photosensitivity disorders or porphyria

How does PDT compare to other treatments for AK?

Several studies have compared the efficacy of PDT to other AK treatments. A randomized controlled trial comparing MAL-PDT to cryotherapy found that PDT resulted in significantly higher complete response rates at 3 months (91% vs. 68%) and better cosmetic outcomes [14]. Another study comparing ALA-PDT to topical fluorouracil treatment demonstrated similar efficacy rates but far superior cosmetic results and patient satisfaction with PDT [15].

Combination and sequential therapies for actinic keratosis

In some cases, a combination of lesion-directed and field-directed therapies or the sequential use of field therapy followed by lesion-targeted therapy can be effective for managing AK [1, 2, 3, 9, 10, 11].

For example, cryotherapy may be used to treat individual lesions, followed by a course of topical medication to address an entire sun-damaged field or skin area [1, 2, 3, 4].

Combining PDT with topical medications or laser resurfacing has been shown to enhance outcomes. For example, pretreating the skin with a fractional laser before PDT can increase the penetration of the photosensitizer and improve the efficacy of the procedure. [16, 17]

It is also important to note that AK is a chronic condition, and patients may require ongoing monitoring and periodic retreatment to manage new or recurrent lesions. Protecting your skin from the sun and doing regular skin examinations are key to preventing the development of new AK lesions and detecting any potential progression to skin cancer. [1]

Post-procedure safety and follow-up

To ensure the best possible outcome of an in-office procedure and minimize potential complications, take these safety considerations and be sure to follow your doctor’s instructions for follow-up care.

In addition to proper follow-up care, ongoing monitoring is essential for managing actinic keratosis and reducing the risk of progression to skin cancer. Regular skin examinations and preventive strategies play crucial roles in the long-term management of AK patients.

• Sun protection: Patients with AK should be advised to limit sun exposure and use sun protection measures such as sunscreen, protective clothing, and staying in the shade when outdoors [1].
• Topical medication use: Patients using topical AK treatments should be cautioned against applying hydrocortisone or other corticosteroid medications, as these can interfere with the effectiveness of the AK treatment [1, 5].
• Post-treatment care: Patients may experience redness, swelling, blistering, or peeling after certain AK treatments. Healthcare providers should advise patients on proper skin care and sun protection during the healing process [1].
• Skin monitoring: Patients with AK have an increased risk of developing additional AK lesions or progressing to skin cancer. Regular skin examinations by a healthcare provider are recommended to monitor for new or changing lesions [1].
• Immunosuppression: Patients who are immunosuppressed, such as those with organ transplants or certain medical conditions, may be at higher risk for developing AK and should be closely monitored [1, 6, 8, 9].
• Occupational exposure: Individuals with high occupational UV exposure, such as outdoor workers, should be educated on the importance of sun protection and regular skin examinations [1-4, 7].
• Patient education: Healthcare providers should ensure patients understand the nature of AK, the importance of treatment, and the need for ongoing skin monitoring and sun protection to prevent progression to skin cancer [1].

Citations:

1. Berman, B., Bienstock, L., Kuritzky, L., Nouri, K., & Oestreicher, J. H. (2006). Actinic keratoses: sequelae and treatments. The Journal of the American Academy of Dermatology, 54(1), S79-S87.
2. Schlager, J. G., Babar, A., Khosravi, H., Zaremba, A., Eichenfield, L. F., & Anderson, R. R. (2021). Cryotherapy for actinic keratosis: A systematic literature review. Journal of the American Academy of Dermatology, 84(6), 1639-1647. https://doi.org/10.1016/j.jaad.2020.09.074
3. Lebwohl, M. (2003). Actinic keratosis: epidemiology and progression to squamous cell carcinoma. British Journal of Dermatology, 149(Suppl 66), 31-33.
4. Neale, R. E., Damian, D. L., Veierod, M. B., & Green, A. C. (2018). Prevalence of actinic keratosis and its risk factors in a representative sample of the Dutch, French and Australian populations. British Journal of Dermatology, 178(5), 1191-1198.
5. Mayo Clinic. (n.d.). Actinic Keratosis. Retrieved from https://www.mayoclinic.org/diseases-conditions/actinic-keratosis/diagnosis-treatment/drc-20354975
6. Zalaudek, I., Giacomel, J., Argenziano, G., Hofmann-Wellenhof, R., Micantonio, T., Di Stefani, A., Oliviero, M., Rabinovitz, H., & Soyer, H. P. (2006). Dermatoscopy of facial nonpigmented actinic keratosis. British Journal of Dermatology, 155(5), 951-956.
7. Medscape. (n.d.). What is the prevalence of actinic keratosis (AK)? Retrieved from https://www.medscape.com/answers/1294801-87559/what-is-the-prevalence-of-actinic-keratosis-ak
8. The Skin Cancer Foundation. (n.d.). Actinic Keratosis. Retrieved from https://www.skincancer.org/skin-cancer-information/actinic-keratosis/
9. Casari, A., Chester, J., & Pellacani, G. (2018). Actinic Keratosis and Non-Invasive Diagnostic Techniques: An Update. Biomedicines, 6(1), 8.
10. StatPearls. (2022). Actinic Keratosis. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK557401/
11. Casari, A., Chester, J., & Pellacani, G. (2018). Actinic Keratosis and Non-Invasive Diagnostic Techniques: An Update. Biomedicines, 6(1), 8. https://doi.org/10.3390/biomedicines6010008
12. Ulrich, M., Maltusch, A., Röwert-Huber, J., Gonzalez, S., Sterry, W., Stockfleth, E., & Astner, S. (2007). Actinic keratoses: non-invasive diagnosis for field cancerisation. British Journal of Dermatology, 156(s3), 13-17. https://doi.org/10.1111/j.1365-2133.2007.07860.x
13. Guitera, P., Pellacani, G., Crotty, K. A., Scolyer, R. A., Li, L. X., Bassoli, S., Vinceti, M., Rabinovitz, H., Longo, C., & Menzies, S. W. (2010). The impact of in vivo reflectance confocal microscopy on the diagnostic accuracy of lentigo maligna and equivocal pigmented and nonpigmented macules of the face. Journal of Investigative Dermatology, 130(8), 2080-2091. https://doi.org/10.1038/jid.2010.84
14. Lacour, J. P., Ulrich, C., Gilaberte, Y., von Kiedrowski, R., Sidoroff, A., Synnerstad, I., ... & Szeimies, R. M. (2015). Daylight photodynamic therapy with methyl aminolevulinate cream is effective and nearly painless in treating actinic keratoses: a randomised, controlled, double-blind study. British Journal of Dermatology, 172(4), 1021-1027.
15. Rubel, D. M., Spelman, L., Murrell, D. F., See, J. A., Hewitt, D., Foley, P., & Bosc, C. (2014). Daylight photodynamic therapy with methyl aminolevulinate cream as a convenient, similarly effective, nearly painless alternative to conventional photodynamic therapy in actinic keratosis treatment: a randomized controlled trial. British Journal of Dermatology, 171(5), 1164-1171.
16. Hillen, U., Gholam, P., Berthold, M., & Gerber, P. A. (2020). Microwave treatment for actinic keratosis: a prospective, multicenter, open-label, single-arm study. Journal of the European Academy of Dermatology and Venereology, 34(1), 115-121.
17. Blauvelt, A., Kempers, S., Lain, E., Schlesinger, T., Jarratt, M., Meng, X., ... & Bourcier, M. (2021). Phase 3 trials of tirbanibulin ointment for actinic keratosis. New England Journal of Medicine, 384(6), 512-520.
18. Stockfleth, E., Peris, K., Guillen, C., Cerio, R., Basset-Seguin, N., & Garbe, C. (2021). Efficacy and safety of tirbanibulin ointment versus vehicle for the treatment of actinic keratosis: results from two phase 3 trials. Journal of the American Academy of Dermatology, 84(5), 1165-1172.
19. Salah, M., Shalaby, S., Hegazy, R. A., & Abdel Halim, D. M. (2019). Dermoscopic Monitoring for Treatment and Follow-Up of Actinic Keratosis With 5-Aminolaevulinic Acid Photodynamic Therapy. Dermatologic Surgery, 45(1), 102-107.
20. Oster, S. E., Oster, A. J., Schöning, V., Ebert, A. D., Thoms, K. M., & Reichrath, J. (2021). Treatment Motivations and Expectations in Patients with Actinic Keratosis: A German-Wide Multicenter, Cross-Sectional Trial. Cancers, 13(12), 2944.
21. Dirschka, T., Gupta, G., Micali, G., Stockfleth, E., Basset-Seguin, N., Del Marmol, V., ... & Weiss, C. (2017). Real-world approach to actinic keratosis management: practical treatment algorithm for office-based dermatology. Journal of Dermatological Treatment, 28(5), 431-442.

[a]@andrew.dumit@gmail.com ,

Hi there, can you possibly regenerate these two to get a proc-con list? They were essentially left out of this article, and I'd like to get the citations and a more thorough understanding up them as AK in-office treatments.

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