Treatment of mild‐to‐moderate facial cutaneous aging using a combination peel containing 6% trichloroacetic acid and 12% lactic acid

Chemical peeling treats facial cutaneous aging and may avoid risks in patients with sensitive skin, darker skin types, limited finances, or concern for side effects of other resurfacing techniques. Tolerability and improvement of photoaging using a combination peel containing 6% trichloroacetic acid and 12% lactic acid for treatment of mild‐to‐moderate signs of facial photoaging were assessed. This is a prospective, single‐center, single‐arm, study of 32 female subjects with mild‐to‐moderate signs of facial aging and Fitzpatrick Skin Types I–V treated with three monthly treatments of a combination peel containing 6% trichloroacetic acid and 12% lactic acid. After 3 treatments, there were statistically significant improvements in clarity, brightness, redness, pigmentation, fine lines, tactile and visual roughness, and overall appearance scores. Subjective improvements in photoaging parameters varied from 53% (fine lines) to 91% (clarity/brightness). Three treatments with a combination peel containing 6% trichloroacetic acid and 12% lactic acid achieved improvements in signs of facial photoaging. This procedure is safe and effective at treating cutaneous aging for all skin types and a viable option for patients who wish to avoid other resurfacing techniques such as laser resurfacing, microneedling among others.

regeneration which can alleviate signs of skin aging.Chemical peels also offer the benefit of adjustable strength, with stronger peels producing deeper controlled ablation of both the epidermis and underlying dermis.Based on their depth of penetration, chemical peels are classified as superficial, medium, or deep peels. 3As such, the clinician can tailor treatment to the patient's specific concerns and skin type.
Trichloroacetic acid (TCA) is commonly used in chemical peel resurfacing with demonstrated efficacy in several clinical trials and is advantageous for a lack of systemic toxicity. 4Alpha-hydroxy acids, such as lactic acid, are well-studied, standard agents in chemical peels.Sequential peels containing both TCA and lactic acid, such as Jessner's solution with TCA, have been used for effective treatment of photoaging and hyperpigmentation.TCA works in synergy with lactic acid to inhibit tyrosinase, the enzyme responsible for the production of melanin pigment. 5This synergy could be the rationale behind higher efficacy at lower dose, which is important when developing safe and effective chemical peels.Applying Jessner's solution first (containing ethanol, resorcinol, salicylic acid, and lactic acid) begins ablation of the epidermis before TCA is applied, resulting in greater efficacy of TCA in comparison to a TCA single-acid peel. 6This combination peel enables a lower concentration of applied TCA, minimizing side effects without compromising treatment results. 6While sequential chemical peels containing TCA and lactic acid has been demonstrated as effective, combination peels containing TCA and lactic acid have not been studied.It is unclear whether a change in the application schedule of both acids alters peel efficacy in treating signs of facial aging.The purpose of this prospective, single-center, single-arm study was to evaluate the tolerability and improvement of photoaging using three monthly treatments of a combination peel containing 6% TCA and 12% lactic acid (Sensi Peel, PCA SKIN®) for the treatment of mild-to-moderate signs of facial photoaging.Changes to signs of photoaging were evaluated based on Griffith's grading scores, subjects' self-assessment questionnaire responses, subjects' global aesthetic improvement score (assigned at final visit). 7High quality clinical photographs were taken before treatments and at every visit using a Canfield VISIA 4.3 camera (Canfield Scientific.).

| Pretreatment protocol
This was a prospective, single-center, single-arm, study evaluating the tolerability, and improvement of photoaging using three monthly treatments with a combination peel containing 6% TCA and 12% lactic acid for the treatment of mild-to-moderate signs of facial photoaging (hyperpigmentation, uneven skin tone, fine lines, wrinkles, texture, and overall global appearance issues).U.S. IRB approval was obtained prior to subject recruitment and enrollment.Once enrolled, pretreatment clinical photographs were obtained.The principal investigator or sub-investigator assessed the subjects' photoaging using the modified Griffiths' 10-point grading scale.All attempts were made for each investigator to see the same subject throughout their duration in the study.Due to clinic scheduling, the same evaluator was not always available.
On most occasions, patients were followed by the same investigator and to maintain consistency in scoring, the primary investigator and sub-investigator were trained for consistency in evaluation.

| Treatment protocol
Subjects underwent a treatment with a combination 6% TCA-12% lactic acid peel applied in two layers to their entire face.This treatment was repeated two more times for a total of three treatments separated by 4-week intervals over the 12-week study period.At every treatment visit, the dermatologist repeated the Griffiths' grading scale assessment prior to treatment and assessed for any treatment-related side effects including dyspigmentation, scarring, scale, crust, or erythema, from the prior visit using the safety/tolerability assessment.In addition, 1 week after the first treatment subjects received a phone call from research staff to assess facial skin response to the peel (see Table S1, which lists subjects' selfassessment questions).Clinical photographs were obtained for each participant at every visit to assess for changes in signs of facial skin aging during the study period.

| Posttreatment protocol
Four weeks after the third treatment, subjects completed the subject self-assessment questionnaire to assess response to the peels (see Table S2 and Table S3, which lists subjects' self-assessment questions and free-response forms) and rated the overall improvement in appearance using the Global Aesthetic Improvement Scale (GAIS).
Table 1 defines the GAIS rating scale.Changes in signs of photoaging were evaluated based on the following criteria: Griffiths' grading scores as assigned by the investigator, subjects' self-assessment questionnaire responses, subjects' global aesthetic improvement score at the final visit, and comparison of pretreatment and posttreatment photography.

| Statistical analysis
Descriptive statistical analysis and change from baseline calculations (Signed-Rank-Test, mean percent improvement from baseline, percent of subjects improving) were performed to analyze Griffiths' scale visual grading scores for the following parameters: clarity/brightness, evenness of skin tone (redness), evenness of skin tone (pigmentation), fine lines, overall appearance, tactile roughness, visual roughness, wrinkles (see Figure S1, which describes parameters and location assessed).Descriptive statistical analysis and change from baseline calculations were also utilized for analysis of subject tolerability scores (erythema, scale, crust, peel-induced hyperpigmentation, peel-induced hypopigmentation, and scarring).For subjective self-perception questionnaire (SPQ) score results, statistical analysis included frequency distributions of scores and analysis within-treatments using top box analysis.All statistical tests of hypothesis employed a level of significance of ≤0.05 and no adjustments were made for the number of tests performed.

| Demographics
Thirty-three subjects with mild-to-moderate signs of photoaging were recruited, and 32 completed the study.One subject was terminated early from the study as she was not compliant with the last two study visits.All subjects were female and the mean age was 46.2 years (SD 7.1 years).The study race population was 75% White/Caucasian, 12.5% Black/African American, 9.4% Asian, and 3.1% Black-White biracial.The study ethnicity population was 3.1% Hispanic.Subjects' Fitzpatrick skin types ranged from I to V, with 40.6% of the subjects exhibiting skin type III.Table 2 provides a summary of subject demographics.

| Investigator efficacy assessment (Griffiths' Scale)
Two board-certified dermatologists scored the changes in clarity/ brightness, evenness of skin tone (redness and pigmentation), fine lines, wrinkles, tactile roughness, visual roughness, and overall appearance on a 10-point scale.After three treatments, there were statistically significant improvements in clarity, brightness, evenness of skin tone (redness and pigmentation), fine lines, tactile and visual roughness, and overall appearance scores.Score improvements Very much improved Optimal cosmetic result.
2 Much Improved Marked improvement in appearance from the initial condition, but not completely optimal.
1 Improved Obvious improvement in appearance from the initial condition.

No Change
The appearance is essentially the same as baseline.
-1 Worse The appearance is worse than the original condition.
-2 Much worse Marked worsening in appearance from the initial condition.
-3 Very much worse Obvious worsening in appearance from the initial condition.

TA B L E 1 Subject global aesthetic improvement scale (GAIS).
TA B L E 2 Summary of subject demographics.*Note: Significant change from baseline.
[1] Percent change is calculated from the mean changes from baseline.
[2] Percent change is calculated individually by subject and averaged (Note if 0 at baseline, % not calculated for that subject).
achieving tolerability endpoints after the completion of each peel treatment.

| Subject self-assessment questionnaire and global aesthetic improvement scale (GAIS)
Importantly, most subjects experienced little to no sensation during peel treatments (66%) and observed little to no peeling after their treatments (91%).After the first peel, 69% of subjects reported smoother and more luminous skin texture.The average GAIS score was 0.56 (scale −3 to 3), indicating an overall trend towards subjective improvement in signs of facial skin aging after 3 treatments.(See Table S4, which summarizes subjects' responses to the subject questionnaire.)

| Clinical photographs
Subjects' photographs were reviewed by both investigators and clinically noticeable improvements were observed in subjects' brightness, mild hyperpigmentation, very fine lines, glow, and overall aesthetic appearance.Figure 1 shows Subject 05's frontal profile at baseline (left) and 12 weeks later after three 6% TCA-12% lactic acid chemical peels (right), self-a positive improvement in facial appearance.Figure 2 shows Subject 27's frontal profile with fine lines scored 8 at baseline (left) and scored 6 at 12 weeks (right) after three 6% TCA-12% lactic acid chemical peels reporting improvement in skin texture.Figure 3 shows Subject 25's split-face portrait with hyperpigmentation scored 7 at baseline (left half) and scored 3 at 12 weeks (right half) after three 6% TCA-12% lactic acid chemical peels revealing greater evenness in skin tone.Figure 4 shows Subject 28's split-face portrait with redness scored 7 at baseline (left half) and scored 3 at 12 weeks (right half) after three 6% TCA-12% lactic acid chemical peels reporting little no peeling experienced.
Figure 5 shows Subject 32's split-face portrait at baseline (left half) and 12 weeks later (right half) with GAIS score of 3 after three 6% TCA-12% lactic acid chemical peels reporting noticeable improvement in skin texture.Figure 6 shows Subject 25's angled profile with hyperpigmentation scored 7 at baseline (left) and scored 3 at 12 weeks (right) after three 6% TCA-12% lactic acid chemical peels revealing greater evenness in skin tone.Figure 7 shows Subject 27's angled profile with fine lines scored 8 at baseline (left) and scored 6 at 12 weeks (right) after three 6% TCA-12% lactic acid chemical peels reporting improvement in skin texture.Figure 8 shows Subject 32's angled profile at baseline (left) and 12 weeks later (right) with GAIS score of 3 after three 6% TCA-12% lactic acid chemical peels reporting noticeable improvement in skin texture.

| Protocol deviations
Seven protocol deviations occurred.All were due to minor outof-window visits that did not impact the results or the core study procedures.

| Adverse events
Four adverse events occurred throughout the entirety of the study.
These included one instance of subjective mild cheek swelling after the first peel that lasted 1 day, one instance of mild peel-induced hypopigmentation after the final treatment that resolved within 6 weeks, and two instances of acne flares that occurred after the second peel and resolved with oral antibiotics.All adverse events were mild, self-limited, and did not affect the outcomes of this study or subject participation in the study.

F I G U R E 1
Subject 05 -at baseline (left) and 12 weeks later after three 6% TCA-12% lactic acid chemical peels (right) self-reported a positive improvement in facial appearance (frontal side by side view).
The purpose of this study was to assess tolerability and improvement of photoaging using 3 monthly treatments of a combination 6% TCA-12% lactic acid chemical peel for the treatment of mild-tomoderate signs of facial skin photoaging.1][12] Our results reflect similar improvements in signs of facial aging.Existing trials of combination peels containing TCA have typically used medium to deep strength peels, which may explain why significant improvements in wrinkles were not achieved in this study. 8,9However, the use of 6% TCA and 12% lactic acid in combination is advantageous.
Utilization of TCA in acid peels comes with substantial risk of negative side effects. 6,9Comparison of TCA peels against TCA-glycolic acid peels have demonstrated that a lower concentration of TCA in combination with another acid reduces side effects without sacrificing treatment efficacy. 9Increasing the number of peel treatments in this study may have resulted in significant improvement in wrinkles.
Validating treatment options for signs of aging in patients of color is increasingly important to avoid side effects of hypopigmentation Fitzpatrick IV-V scores. 8A 3% retinol superficial peel has also been utilized to treat signs of photoaging in a study population with 20.8% Fitzpatrick IV-VI scores. 10Our study population of 34.4% Fitzpatrick IV-V scores clarifies that a combination 6% TCA-12% lactic acid peel is another viable treatment option for patients of color.
Limitations of the study include a small sample size and the lack of a control arm.Additionally, our findings are limited to a single-center study lacking a longer follow up.Despite these limitations, signs of photoaging demonstrated improvement in the majority of subjects as rated by two board certified dermatologists and the subjects themselves.The adverse events noted were minor and self-limited.
The single incident of hypopigmentation was mild and noted at the end of the study.The two cases of acne flares were most likely attributable to the retinol/retinoid washout period prior to beginning peel treatments.In the investigators' opinion, if retinols/retinoids were continued throughout peel treatments, as they would have in a "real world" scenario, acne exacerbations may not have occurred.
Additionally, the relative effectiveness between combination and sequential peels containing the same acids cannot be inferred.While we report promising results for use of a TC-Alactic acid combination Thirty-three healthy female subjects with mild-to-moderate signs of facial photoaging, ages 35-60 and Fitzpatrick Skin Types I-V, were recruited and screened.Before the study, subjects signed an IRB approved (US Investigational Review Board, Inc.) informed consent conforming to the ethical guidelines of the 1975 Declaration of Helsinki.Subjects discontinued the use of any retinoids or other anti-aging products, such as glycolic acid or peptides, 2 weeks prior to the first treatment.Participants discontinued use of these products throughout the duration of the study.Subjects utilized a 5-7 day post treatment regimen consisting of gentle cleanser, 1% hydrocortisone healing cream, moisturizer, sunscreen, and a spot treatment ointment, as needed, for dryness and irritation.Afterwards, subjects utilized a daily regimen of gentle cleanser, moisturizer, and sunscreen.

F I G U R E 3 F I G U R E 4
questionnaire and the GAIS.After three peel treatments, investigators statistically significant improvements in skin clarity, brightness, evenness of skin tone (redness and pigmentation), fine lines, tactile and visual roughness, and overall appearance.Most improvements were noted after the second treatment.The parameters that exhibited the greatest improvements were clarity/brightness (average of 38% improvement in 91% of subjects) and pigmentation (average of 37% improvement in 81% of subjects).Fine lines F I G U R E 2 Subject 27 -fine lines scored 8 at baseline (left) and scored 6 at 12 weeks (right) after three 6% TCA-12% lactic acid chemical peels reporting improvement in skin texture (frontal side by side view).Subject 25 -hyperpigmentation scored 7 at baseline (left) and scored 3 at 12 weeks (right) after three 6% TCA-12% lactic acid chemical peels revealing greater evenness in skin tone (frontal split-face view).Subject 28 -redness scored 7 at baseline (left) and scored 3 at 12 weeks (right) after three 6% TCA-12% lactic acid chemical peels reporting little no peeling experienced (frontal splitface view).improvedby an average of 15% in 53% of subjects after three treatments.Deeper wrinkles did not demonstrate statistically significant improvement after treatment.This result was expected, as deeper wrinkles require more aggressive resurfacing strategies such as deep chemical peels or laser resurfacing.Pigmentation and uneven skin tone tend to improve more readily from less aggressive treatments, such as the superficial peel used in this study.Subject-reported outcomes after three treatments demonstrated that the chemical peels were well-tolerated, painless, and resulted in little to no peeling in the ensuing days after each treatment.After the first peel, 69% of subjects reported smoother and more luminous skin texture.After the three peel treatments, approximately 50% of the subjects noticed positive changes in skin, improvement in overall facial appearance, and improvement in skin brightness.Around 31% of these subjects indicated that others had noticed a positive change in their skin and 56% of the subjects would recommend the peel treatments to others.Though the use of a combination 6% TCA-12% lactic acid peel is novel, our results reflect those published in the literature regarding other superficial peels for treatment of photoaging.Clinical trials have utilized a wide range of single-acid, combination, and sequential peels containing Jessner's solution, TCA, salicylic acid,

F I G U R E 5
Subject 32 -at baseline (left) and 12 weeks later (right) with GAIS score of 3 after three 6% TCA-12% lactic acid chemical peels reporting noticeable improvement in skin texture (frontal split-face view).F I G U R E 6 Subject 25hyperpigmentation scored 7 at baseline (left) and scored 3 at 12 weeks (right) after three 6% TCA-12% lactic acid chemical peels revealing greater evenness in skin tone (angled side by side view).and hyperpigmentation.Existing peel trials vary in their inclusion of patients with skin of color (Fitzpatrick IV-VI) and many fail to report participant Fitzpatrick scores.Jessner's solution (TCA sequential peel) has been demonstrated as a safe and effective treatment for hyperpigmentation in a study population with 94.5%

F I G U R E 7
Subject 27 -fine lines scored 8 at baseline (left) and scored 6 at 12 weeks (right) after three 6% TCA-12% lactic acid chemical peels reporting improvement in skin texture (angled side by side view).F I G U R E 8Subject 32 -at baseline (left) and 12 weeks later (right) with GAIS score of 3 after three 6% TCA-12% lactic acid chemical peels reporting noticeable improvement in skin texture (angled side by side view).