Actinic keratoses (AKs) are the most common reason for dermatologist visits in patients aged 45 years or older, and the numbers of AKs are increasing every year.1,2 Between 2007 and 2015, the number of AKs increased from 29.7 million to 35.6 million.2 With the rising incidence of AKs, dermatologists have various options for treating this skin condition. These include cryosurgery, topical 5-fluorouracil (5-FU), imiquimod, diclofenac, ingenol mebutate, photodynamic therapy (PDT), chemical peels, lasers, curettage, electrosurgery, excision, and retinoids.3
Choice of therapy depends on many factors, including patient and physician preference, extent of involvement, location of lesions, duration of lesions, response to prior treatments, comorbidities, expected patient compliance, and immunosuppression.1 While 5-FU is the standard of care, trichloroacetic acid (TCA) peels are an ideal treatment as they limit treatment duration, side effects, and cost while ensuring patient compliance.
Treatment of AKs is important because when left untreated, AKs have the potential to evolve into squamous cell carcinoma (SCC), with reported rates from 0.025% to 16%.4 Furthermore, SCC has been reported to develop in 12% to 25% of patients with multiple preexisting AKs.5
A 65-year-old woman presented to our clinic for treatment of AKs, and after discussion of treatment options, we planned for a series of full-face TCA peels. Although the current standard treatment of AKs is 5-FU, we opted to treat her with TCA peels because it is an in-office treatment with low morbidity, thereby ensuring compliance and reducing side effects. We treated her with three consecutive TCA peels separated at 2-week intervals with increasing strengths from 10% to 25% to 35%. These initial lower concentration, superficial peels gave minimal downtime and discomfort for the patient and allowed for priming of the affected areas prior to the subsequent application of the medium-depth 35% TCA chemical peel. Our patient had an excellent response to treatment with a three-physician verified 82% reduction of lesions at a 2-month follow-up (Figure 1, Figure 2).
Figure 1. A 65-year-old woman shown before (A) and after (B) a 35% TCA peel treatment to her right upper lip and nose.
Topical Treatment Options
Topical 5-FU has long been viewed as the standard therapy for the treatment of AKs given its history of good, reproducible results and relatively low cost.3 Treatment adherence has often been difficult with 5-FU given the side effects of pain, erythema, and erosions that can last for the duration of treatment.3 Despite these side effects, 5-FU continues to be reported to have some of the best, most reproducible clearance rates in those patients who are able to tolerate these side effects, with reductions of AKs reported as high as 91.7%.4 Jansen et al4 compared treatment outcomes between 5-FU, imiquimod, ingenol mebutate, and MAL-PDT and found that 5-FU had the highest cumulative probability of treatment success at 1-year follow-up, with 74.7% compared with 53.9% for imiquimod, 28.9% for ingenol mebutate, and 37.7% for MAL-PDT. Unfortunately, success with 5-FU relies on patient adherence to the duration of treatment, which can often be difficult to achieve.
Figure 2. The same patient shown before (A) and after (B) a 35% TCA peel treatment to her left nose and cheek.
TCA peels are thought to not only treat the clinically affected skin, but also to treat and remove the actinically damaged skin nearby, thereby acting as prophylaxis for future AKs and possible SCCs.5 TCA application to the skin causes protein coagulation, resulting in the resurfacing and removal of AKs.5
In contrast to other, more expensive available procedures such as lasers, TCA is inexpensive and has the potential to lower the costs of AK treatments. TCA has been considered to be a safe and effective treatment for AKs with limited morbidity, and shows histologic evidence of the treatment of photodamage.5 Jessner solution combined with 35% TCA has been noted to have equal efficacy to 5-FU at 1-year follow-up, and results in less morbidity than topical 5-FU.6 Furthermore, patients have been shown to prefer TCA over 5-FU given the convenience of a single in-office application, minimal side effects, and minimal downtime.5,6 Hantash et al5 showed that a one-time 30% TCA application had a similar reduction of AKs compared with carbon dioxide (CO₂) laser or 3 weeks of 5-FU, with an 89% reduction with TCA, a 92% reduction with CO₂ laser, and an 83% reduction with 5-FU.
In addition to using 5-FU and TCA peels, there are several other available treatment options with various pros and cons. Imiquimod is another topical cream used to treat AKs that has similar side effects to 5-FU. Less common but reported side effects also include constitutional symptoms and flu-like symptoms, which can limit adherence and future use.7 Clearance rates in the literature range widely from 45% to 85%,1 suggesting that success with imiquimod may not be reproducible. As with 5-FU, the downsides to using imiquimod are noncompliance and inadequate treatment duration due to application side effects of erythema, irritation, and burning for the duration of treatment, whereas the morbidity of TCA peels is far less and for a much shorter duration.
Cryosurgery, PDT, and Lasers
Cryosurgery is also a commonly used therapy for AKs, given its ease of use, one-time application, limited downtime compared with most topical treatments, and lack of concern for adherence to treatment given its in-office application. In the literature, complete response rates per lesion treated range from 75% to 98%, with recurrence rates of AKs estimated from 1.2% to 12% over a one-year follow-up period.1 Downsides to cryosurgery include a lack of standardization for frequency, duration, and temperature of application, as well as the inability to treat clinically subtle lesions and background photodamage.1 Further, comparative studies have shown inferiority to both imiquimod and 5-FU,1 whereas TCA has been shown to have equivalent outcomes to both 5-FU and lasers.5 While no direct comparative studies to TCA are available, cryosurgery does not have the important benefit of field treatment allowed for with TCA.
As with TCA peels, PDT also has the benefits of treating entire anatomical regions and eliminating the difficulty with patient adherence given its in-office application. Pain associated with PDT treatment is often the main side effect reported, and, in fact, has influenced patients to decline further treatment or not recommend it as a treatment to others.4 Di Nuzzo et al8 reported that despite higher clearance rates with PDT vs TCA, patients preferred TCA over PDT because of the shorter duration of discomfort with TCA and the high amount of pain experienced with PDT.
Another in-office option is laser treatment, including Er-YAG, CO₂ and thulium lasers. As with chemical peels, lasers are effectively used to treat both active AKs and the nearby sun-damaged skin with the goal of preventing the future development of AKs or SCCs.3 The risk of long-term side effects and the high cost, however, may limit its use. Weiss et al9 reported an 86.6% reduction in AKs at 6-month follow-up after up to four treatments with the fractionated 1927-nm nonablative thulium laser. Ostertag et al3 compared Er-YAG in combination with CO₂ laser to 5-FU. After 1 year, the authors found a 94% improvement in number of lesions in the laser group vs 83% in the 5-FU group.3 The laser group experienced more side effects, including edema, infection, erythema, itching, and hypopigmentation, with erythema and hypopigmentation being seen more significantly in the laser group even at 1-year follow-up.3 Unfortunately, these potential side effects with laser treatment and their substantial costs can be prohibitory for their use. Furthermore, Hantash et al5 showed TCA to be comparable to CO₂ laser for reduction of AKs, and TCA is a much less expensive option than laser treatments.
Weighing the Pros and Cons
Topical medications such as 5-FU and imiquimod have limitations in their success owing to decreased patient adherence secondary to side effects. While cryotherapy limits downtime and is an in-office treatment, the beneficial effects are restricted only to those areas which are specifically treated in the office. Laser treatments such as CO₂ and Er-YAG are good options with comparable clearance rates to alternative treatments, however, the cost is much higher and long-term side effects such as erythema and hypopigmentation must be considered.
Providers must strive to provide not only effective, but also cost-effective treatment to patients. The cost of AK treatment has continued to rise since 2004.2 Associated medical costs for visits for actinic damage that included AKs increased from $867 million in 2004 to $1.8 billion in 2013.2 Medicare Part D spending on topical AK therapy alone increased from $101 million to $133 million from 2011 to 2015.2 As a response to the increasing number of AKs being treated, reimbursements have been cut to accommodate for the rising costs of treating these AKs.2 Dermatologists should be seeking ways to decrease these costs while continuing to deliver appropriate and successful AK treatment to the aging population. TCA peels are an excellent option for potential cost reduction of AK treatment.
TCA chemical peels have been used to treat AKs for decades. They have been shown to have similar cure rates to laser and topical treatments, but with minimal downtime, low morbidity, and potentially lower overall costs. Accordingly, a series of escalating percentages of chemical peels can be considered as an alternative to other more commonly used treatment modalities for AKs. While not considered the gold standard of treatment, TCA chemical peels should be strongly considered in the armamentarium for AKs.
Dr Carter is a board-certified dermatologist and Mohs/Procedural Dermatology fellow at Affiliated Dermatologists & Dermatologic Surgeons, PA, in Morristown, NJ.
Dr Rogachefsky is the program director of the micrographic surgery and procedural dermatology fellowship and a dermatologist at Affiliated Dermatologists & Dermatologic Surgeons, PA.
Dr Lee is the medical/surgical director of Affiliated Ambulatory Surgery, PC, and the director of procedural dermatology at Affiliated Dermatologists & Dermatologic Surgeons, PA.
Disclosure: The authors report no relevant financial relationships.
1. Krawtchenko N, Roewert-huber J, Ulrich M, Mann I, Sterry W, Stockfleth E. A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up. Br J Dermatol. 2007;157(suppl 2):34-40. doi:10.1111/j.1365-2133.2007.08271.x
2. Yeung H, Baranowski ML, Swerlick RA, et al. Use and cost of actinic keratosis destruction in the Medicare Part B fee-for-service population, 2007 to 2015. JAMA Dermatol. 2018;154(11):1281-1285. doi:10.1001/jamadermatol.2018.3086
3. Ostertag JU, Quaedvlieg PJ, Van der Geer S, et al. A clinical comparison and long-term follow-up of topical 5-fluorouracil versus laser resurfacing in the treatment of widespread actinic keratoses. Lasers Surg Med. 2006;38(8):731-739. doi:10.1002/lsm.20379
4. Jansen MHE, Kessels JPHM, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380(10):935-946. doi:10.1056/NEJMoa1811850
5. Hantash BM, Stewart DB, Cooper ZA, Rehmus WE, Koch RJ, Swetter SM. Facial resurfacing for nonmelanoma skin cancer prophylaxis. Arch Dermatol. 2006;142(8):976-982. doi:10.1001/archderm.142.8.976
6. Lawrence N, Cox SE, Cockerell CJ, Freeman RG, Cruz PD Jr. A comparison of the efficacy and safety of Jessner’s solution and 35% trichloroacetic acid vs 5% fluorouracil in the treatment of widespread facial actinic keratoses. Arch Dermatol. 1995;131(2):176-181.
7. Hanna E, Abadi R, Abbas O. Imiquimod in dermatology: an overview. Int J Dermatol. 2016;55(8):831-844. doi:10.1111/ijd.13235
8. Di Nuzzo S, Cortelazzi C, Boccaletti V, et al. Comparative study of trichloroacetic acid vs. photodynamic therapy with topical 5-aminolevulinic acid for actinic keratosis of the scalp. Photodermatol Photoimmunol Photomed. 2015;31(5):233-238. doi:10.1111/phpp.12164
9. Weiss ET, Brauer JA, Anolik R, et al. 1927-nm fractional resurfacing of facial actinic keratoses: a promising new therapeutic option. J Am Acad Dermatol. 2013;68(1):98-102. doi:10.1016/j.jaad.2012.05.033