A 15% Trichloroacetic Acid + 3% Glycolic Acid Chemical Peel Series Improves Appearance of Hand Lentigines: An Evaluator-Blinded, Split-Hand Prospective Trial

Abstract

BACKGROUND:

Improving the appearance of lentigines on the hands is a key component to hand rejuvenation. Soft tissue fillers revolumize hands, but do not address pigmentary changes. OBJECTIVE: This study investigated the effiacy of a 15% trichloroacetic acid (TCA) + 3% glycolic acid (GA) combination peel in improvement of appearance of hand lentigines.

METHODS

A prospective evaluator-blinded, split-hand study was performed using a 15% TCA + 3% GA peel to treat patients with hand lentigines. Subjects received a total of 3 treatments at 4-week intervals on 1 hand, with the other hand serving as an untreated control. Final photographs were taken 12 weeks after the last treatment. Two blinded board-certified dermatologists graded improvement in hand lentigines using a 5-point scale.

RESULTS

Eighteen of 20 patients completed the study (90%). The mean age was 64.4 years (SE 1.6, range 51–71). The mean pain scores were 3.8 (SE 0.4) on a 10-point scale (1 = no pain, 10 = extremely painful). Blinded evaluators correctly identified the after-treatment photographs in 16 patients (88%). Physician and patient-graded mean improvement of lentigines was significant for treated versus control hands (p < .01). No adverse events were noted.

CONCLUSION

A series of three 15% TCA + 3% GA peels are effective and safe in the treatment of hand lentigines.

Hand rejuvenation has received increased focus as an area for cosmetic treatments. The hands can “give away” a person's age based on the degree of photodamage and volume loss. Photoaging on the hands is multifactorial, ranging from subcutaneous changes (volume loss) to dermal/epidermal changes (solar elastosis or lentigines). Several products, such as calcium hydroxyapatite and hyaluronic acid fillers, are FDA-cleared for hand rejuvenation.^1–6 Although these fillers address the volume loss component, they do not address pigmentary changes, such as lentigines.^7–10

Lentigines can be effectively treated with chemical peels, which resurface the superficial portion of the epidermis to remove undesirable pigment, thereby addressing extrinsic signs of photoaging.^11–16 Specifically, trichloroacetic acid (TCA) <35% peels have been used for decades for superficial chemical peeling because of its efficacy, safety profile, and ability to correlate peel depth with color of surface frost.^17,18 The white frost caused by TCA peels is due to keratocoagulation or protein denaturation of membrane proteins.¹⁹

Furthermore, TCA peels have also been used on the body to effectively treat signs of photoaging, such as actinic damage, dyschromia, and skin quality.²⁰ Previous studies comparing TCA 35% with Q-switched lasers have shown efficacy of both modalities in treated lentigines in nonfacial areas.¹² To minimize side effects, using lower concentrations of TCA is advisable in nonfacial areas. Therefore, this study prospectively investigates the efficacy of a 15% trichloroacetic acid (TCA) + 3% glycolic acid (GA) chemical peel for treatment of lentigines on the hands.

Methods

This 6-month study was a split-hand, randomized, evaluator-blinded, single-center prospective clinical trial assessing the efficacy of a 15% TCA + 3% GA chemical peel for treatment of lentigines on the hands. Inclusion criteria included aged 21 or older, presence of 5 or more lentigines on both hands as assessed by a board-certified dermatologist, and ability to adhere to treatment and follow-up schedules. Exclusion criteria included pregnancy or lactation, cosmetic procedures on the hands within 6 months before enrollment in study, active infection on the hands, or active inflammatory disease on the hands. Subjects received a total of 3 treatments at 4-week intervals. At the baseline visit, before the first treatment, subjects were consented and randomized to determine which hand would serve as the treatment hand. Demographics, such as age, sex, Fitzpatrick skin type, ethnicity, and race, were collected at the baseline visit.

At the treatment visits occurring at weeks 0, 4, and 8, the subject's hands were initially cleansed with 70% alcohol. Clinical photograph of both hands was taken with a Canon SLR at each visit before treatment.

After photography, a 15% TCA + 3% glycolic peel (SkinCeuticals Smart TCA Peel) was applied to the posterior hand between the wrist and metacarpophalangeal joint. Approximately 3 layers of the chemical peel solution was applied, with a 2- to 3-minute wait time in between each layer to allow for frosting to appear. A level II TCA frost was reached for all patients.^21,22 The same dermatologist performed all procedures to avoid interphysician variability in the technique. Subjects were instructed to apply Epidermal Repair (a thick emollient) twice daily for 1 week and to wear Physical UV Defense SPF 50 (a zinc oxide sunscreen) daily. Subjects were followed up at 12 weeks after the last treatment.

At each visit after the initial visit, subjects were asked to rate both the control and treated hands on the Global Aesthetic Improvement Scale (GAIS), which is graded on a 1 to 5 scale (1 = exceptional improvement, 2 = very improved, 3 = improved, 4 = unchanged, and 5 = worsened). Subjects were also asked to rate their control and treated hands using a 5-point grading scale based on degree of improvement (1 = 0% improvement, 2 = 1–25% improvement, 3 = 26–50% improvement, 4 = 51–75% improvement, and 5 = 76%–100% improvement).

Two blinded board-certified dermatologists were asked to grade before and after photographs of the treated hands. They were asked to identify which photographs represented the after-treatment photograph and to grade the degree of improvement using the GAIS and a 5-point scale (1 = 0% improvement and 5 = 76–100% improvement).

All statistical analysis was performed using STATA v14, and significance was determined with p < .05. The paired samples t-test was used to compare the subject's control versus treated hands on the GAIS and 5-point improvement scale.

This study was approved by the Allendale IRB and registered as a clinical trial on https://www.ClinicalTrials.gov (NCT05471947).

Results

Twenty subjects were recruited, of which 18 (90%) completed the study. One subject was lost to follow-up after completion of 3 treatments, and another subject was lost to follow-up after completion of 1 treatment. Treatments were completed between September 2022 and March 2023, representing the late fall to winter season, during which subjects did not traditionally participate in high sun-exposure activities. The mean age was 64.4 years (SE 1.6, range 51–71). Demographics are presented in Table 1.

TABLE 1.

Demographics

Age (mean)	64.9 years (SE 1.6, range 51–73)
Sex (female)	18 (100%)
Fitzpatrick skin type
I	6
II	11
III	1
IV	0
V	0
VI	0

No adverse events, such as postinflammatory hyperpigmentation, postinflammatory erythema, or scarring, were noted during the course of treatment or follow-up. The mean pain scores were 3.8 (SE 0.4) on a 10-point scale (1 = no pain and 10 = extremely painful).

Blinded reviewers correctly identified the after-treatment photographs in 16 patients (88%). Representative before and after photographs are presented in Figures 1 and 2.

Figure 1.

A 68-year-old woman at baseline (A) and 3 months (B) after a series of three 15% TCA + 3% glycolic acid (GA) chemical peels. TCA, trichloroacetic acid.

Figure 2.

A 72-year-old woman at baseline (A) and 3 months (B) after a series of three 15% TCA + 3% glycolic acid (GA) chemical peels. TCA, trichloroacetic acid.

Physician-graded mean improvement of lentigines measured on a 5-point grading scale was significant for treated (4.2, SE 0.21) versus control hands (1.3, SE 0.2; p < .01). Subject-graded mean improvement of lentigines on a 5-point grading scale was significant for treated (4.3, SE 0.3) versus control (1.3, SE 0.1; p < 1; Table 2). Three patients reported <50% improvement. Their demographics (ages 63, 63, and 64; subject GAIS 3, 3, and 3) were similar to the rest of the cohort.

TABLE 2.

Patient-Reported Improvement on a 5-Point Scale

Effect of 15% TCA + 3% GA peels	Number of Patients (%)
No improvement	0 (0)
1%–25% improvement	1 (6)
26%–50% improvement	2 (11)
51%–75% improvement	6 (33)
76%–100% improvement	9 (50)

GA, glycolic acid; TCA, trichloroacetic acid.

Physician-graded mean GAIS scores were significant for treated (2, SE 0.18) versus control hands (4.2, SE 0.21; p < .01). Subject-graded mean GAIS scores were significant for treated (2.1, SE 0.16) versus control hands (4.5, SE 0.19; p < .01).

Discussion

This split-hand, prospective study evaluated the efficacy of 3 sessions of a 15% TCA + 3% glycolic peel for improvement in hand lentigines. At the 12-week follow-up, the treated hand showed a statistically significant improvement when graded by blinded board-certified dermatologists and the unblinded patient.

Lentigines of the hands are characterized by increased melanin production and pigment retention within keratinocytes. Because these pigmentary changes occur within the epidermis or at the dermal–epidermal junction, lentigines can be effectively treated with superficial resurfacing modalities such as cryotherapy or chemical peels.^14–16 Furthermore, chromophore-specific devices targeting pigment, such as laser or other energy-based devices, can also be effective.^12,23–26

Focal treatment of lentigines using TCA has previously been reported. Chun and colleagues¹⁶ treated 49 patients with solar lentigines using 50% to 65% TCA, showing a good clinical response in 42 patients (82%) . However, peels using higher concentrations of TCA (>35%) can produce severe complications including scarring and persistent postinflammatory hyperpigmentation. Risks of complications are reduced with lower concentrations of TCA because of the reepithelialization from unaffected hair follicles. Furthermore, lower concentrations of TCA have a shallower depth of penetration, thus reducing the risk of scarring.²⁷ Therefore, it is suggested to use the lowest concentration of TCA necessary to achieve the desired response when treating lentigines.

The 15% TCA + 3% GA used in this study harnesses the safety profile of a lower TCA concentration. Understanding the specific formulation of the TCA peel (weight/weight vs weight/volume) affects the strength of a peel and reliability of the formulation because a 15% weight/weight TCA formulation is different than a 15% weight/volume TCA formulation.²⁸

The 3% GA component produces a keratolytic effect on the stratum corneum. Previous electron microscopy studies of low-dose GA (2%–5%) have shown desmosomal breakdown of the stratum corneum with minimal to no change to the epidermis.^29–31 This effect allows for improved penetration of 15% TCA through the stratum corneum and epidermis, thus producing the desired clinical effect using lower strength TCA.

Chemical peels have also been compared with cryotherapy for treatment of lentigines on the hands. Lugo-Janer and colleagues¹³ conducted a split-hand study of cryotherapy versus 30% TCA (spot treatment) in a cohort of 25 patients. Although both therapies were effective, cryotherapy had a higher percentage of patients showing moderate or marked improvement. However, 86% of subjects believed that cryotherapy was more painful and 76% believed that cryotherapy took longer to heal compared with TCA. Similarly, Raziee and colleagues¹⁵ compared cryotherapy with 33% TCA (spot treatment) in a split-hand study and found that cryotherapy was slightly superior to spot treatment with TCA, but subjects found that cryotherapy was significantly more painful with longer healing time.

In addition to cryotherapy, energy-based devices, such as intense pulsed light (IPL), pulsed-dye lasers, Er:YAG, and picosecond and Q-switch Nd:YAG lasers, can also be used for treatment of hand lentigines. Horibe and colleagues compared an Er:YAG laser treatment with 1 Blue Peel (proprietary TCA peel) treatment. The Er:YAG group had more side effects (edema, erythema, and warmth) immediately afterward as compared to the Blue Peel. Both groups showed excellent clinical results, but no statistical comparisons were made between the groups.³² Iraji and colleagues compared the efficacy of a QS frequency-doubled Nd:YAG (532 nm) laser versus TCA 35%. Both groups received 3 sessions every 4 weeks, and postinflammatory hyperpigmentation was noted in 1 patient in each group. Overall, patient satisfaction and lesion lightening was significantly better in the QS Nd:YAG group compared with the TCA 35% group.¹² Other studies have suggested using a combination of IPL or QS Alexandrite lasers and chemical peels for optimal results in addressing hand pigmentation.^33–35

Limitations to this study included unblinded subject ratings, small sample size (n = 18), lack of higher Fitzpatrick skin types in the study population, and lack of sex and racial/ethnic diversity.

This study demonstrates that a series of chemical peels (15% TCA + 3% GA) offer a safe and effective treatment for improving the appearance of lentigines of the hands. It is a cost-effective option compared with energy-based devices and also offers fewer side effects and downtime compared with cryotherapy. This cosmetic treatment can be combined with other modalities, such as soft tissue fillers aimed at revolumization, to improve the overall appearance of photoaged hands.