Resolution of acne lesions may result in postinflammatory erythema, hyperpigmentation, or scarring. These sequelae are often the main reasons for consulting a dermatologist and take precedence over the acne itself 1. In acne, superficial peels are beneficial due to their exfoliative and anti-inflammatory effects. They also induce improvement of skin texture, pore size, and reduction of sebum. α-Hydroxy acids (AHAs) and β-Hydroxy acids (BHAs) are the most commonly used superficial chemical peeling agents. Glycolic acid (GA) is one of the AHAs that has been used widely in the treatment of acne. It leads to the reduction of corneocyte adhesion, improves abnormal keratinization in the infundibulum, decreases keratinocyte plugging, and ultimately decreases follicular occlusion 2. Salicylic acid (SA) is a BHA that has a phenolic ring in its chemical structure. It is an excellent keratolytic agent due to its ability to dissolve intercellular cement, thereby reducing corneocyte adhesion. Because of its lipophilicity, it has better penetration into the pilosebaceous unit. This property of SA accounts for its strong comedolytic effect, and its utility in the treatment of acne. The anti-inflammatory activity of SA makes it useful in rapidly decreasing facial erythema 3.
Salicylic–mandelic acid peel (SMP) is a newer combination peel that combines the properties of BHA and AHA. The advantage of this combination is that SA is lipophilic, and thus penetrates active acne lesions quickly and has anti-inflammatory properties, whereas mandelic acid has antibacterial properties 4. Mandelic acid is one of the largest AHAs, and thus penetrates the epidermis more slowly and uniformly, making it an ideal peel for acne and pigmentation 5. The aim of this study was to evaluate the efficacy and the tolerability of the combination of 20% salicylic–10% mandelic acid peel against 35% glycolic acid peel (GAP) in the treatment of active facial acne vulgaris, postacne scarring, and associated hyperpigmentation in Egyptian acne patients.
Patients and methods
This randomized clinical trial was carried out in the Dermatology and Andrology Department of Benha University Hospital in the period from March 2012 to March 2013. The study included 40 Egyptian patients with facial acne vulgaris, postacne scarring, and associated hyperpigmentation, with Fitzpatrick skin types I to IV not responding to conventional treatment for 3 or more months. Their ages ranged from 14 to 29 years. Exclusion criteria included the following: patients with nodulocystic lesions and severe acne types, for example, acne conglobata and acne fulminans; patients with a history of hypertrophic or keloid scarring, or patients with hypersensitivity to SA; patients having conditions associated with poor wound healing such as oral isotretinoin therapy within the previous 6 months, chemotherapy, or systemic steroid; patients who had recent face-lifts or uncooperative patients were also excluded. Patients signed an informed consent (parent or guardian if the patient was younger than 18 years old) after approval of the study by the research ethics committee of the Faculty of Medicine in Benha University. Oral and topical medications being taken for acne were discontinued 4 weeks before peeling.
A thorough dermatological examination was performed to determine the skin type according to Fitzpatrick’s classification (from I to IV), the acne severity according to Hayashi et al. 6 (mild, moderate, severe, or very severe), the number of each active acne vulgaris lesion according to Michaëlsson et al. 7 (comedones, papules, and pustules), the extent of postacne hyperpigmentation by calculating the approximate surface area involved (the right and the left cheeks and the forehead were taken to constitute 30% each, and the chin accounted for 10%) according to Garg et al. 5, and the classification of postacne scars according to Jacob et al. 8 (icepick, boxcar, or rolling); calculation of the total number of each type was performed.
This randomized clinical trial was carried out on 40 patients who were divided randomly, by the sealed envelope method, into two groups: group A (GA) comprised 20 patients (treated with 20% salicylic–10% mandelic acid peels) and group B (GB) comprised 20 patients (treated with 35% GAPs). The SMP was prepared by mixing SA (20 g), mandelic acid (10 g), and 70% ethyl alcohol (up to 100 ml). The GAP 35% was available as GA 70%, which was prepared by mixing GA 70% (50 ml) with distilled water (up to 100 ml). The chemicals were obtained from El-Goumhouria Co. for trading medicines, chemicals, and medical appliances (Cairo, Egypt). As a prepeel care, patients of both groups were instructed to use topical tretinoin cream 0.05% at bed time for 2 weeks before peeling 9 to assist in producing uniform penetration of the peeling agent, reducing the re-epithelialization time after peel, accelerating wound healing, and reducing the risk of complications 10. Seven peeling sessions were conducted for each group every 2 weeks [weeks 0 (base line), 2, 4, 6, 8, 10, and 12], and the patients were followed up for 2 months after the last session (week 20). At every session, cleansing was performed by cotton pads soaked with alcohol, followed by degreasing by one or two pads soaked with acetone. Sensitive areas of the face such as the lips and the nasolabial folds were protected with a thin layer of vaseline. The peeling agent was then applied over the face using cotton pads in a rubbing manner starting with the forehead, the cheeks, and the chin, taking 30–35 s using ∼0.8–1.0 ml per session. The peeled areas were observed for the development of erythema for GAP, which was considered as the end point of peeling. The patients were also asked to report when they felt a stinging or burning sensation with GAP, which was considered as the alternative end point in which erythema could not be discerned. With SMP, the patients experienced a stinging sensation that lasted for 3–5 min. After the cessation of this stinging sensation, most patients developed a uniform white crystalline precipitate (pseudo-frost) in the peeled areas (indicating the deposition of SA after its hydroethanolic vehicle had volatilized). This was considered as the end point of peeling. In patients who did not develop the pseudo-frost, the cessation of the stinging sensation was considered as the end point. Care was taken to not allow blanching to appear, which was indicative of a deeper peel causing epidermolysis. The duration of each peeling session with GA was serially increased by 1 min at each visit until a maximum of 5 min. The total duration of the peeling sessions varied from 3 to 5 min with SMP. As soon as the end point was reached, the peel was neutralized with 15% sodium bicarbonate solution (in case of GAP) or cold water (in case of SMP), and then the patients were asked to wash their faces with copious amounts of cool tap water. They were asked to pat, and not rub, the face. The patients were asked to apply a sunscreen with a sun protection factor of greater than 15 on their faces before leaving the hospital and copious moisturizing cream at home (panthenol cream).
Evaluation of active acne lesions
Evaluation was performed using a method devised by Michaëlsson et al. 7 by multiplying the number of each type by its severity index (0.05 for comedones, 1 for papules, and 2 for pustules), and by adding each sum, a total acne score was obtained. The assessment of acne lesions was performed at baseline (week 0), at each visit, and at the follow-up visit.
Evaluation of postacne hyperpigmentation
The extent of postacne hyperpigmentation was assessed by calculating the approximate surface area involved. The right and the left cheeks and the forehead were taken to constitute 30% each, and the chin accounted for 10% 5. The assessment of the severity of postacne hyperpigmentation was performed using the grade severity of hyperpigmentation according to Gold et al. 11. It was also performed at baseline (week 0) and at weeks 4, 8, 12, and 20.
Assessment of postacne scars
It was performed using the scar severity score in which the number of each type of acne scar was counted (rolling, least severe; boxcar, more severe; and icepick, most severe), and then multiplied by its weighting factor (1 for rolling, 2 for boxcar, and 3 for icepick), yielding the overall score according to Lipper and Perez 12. It was performed at baseline and at weeks 4, 8, 12, and 20.
Two uninvolved dermatologists made a subjective assessment of the improvement in the overall appearance by comparing the photographs at the baseline and those at the subsequent peeling sessions using a five-point visual analogue scale (VAS): (1) worse, (2) no change, (3) poor (<30% improvement), (4) fair (31–60% improvement), and (5) good (>60% improvement) 5. These assessments were made at weeks 4, 8, 12, and 20. Clinical photographs using a Sony Cyber-shot digital camera 8 mega pixels (Sony Corp., Tokyo, Japan) with standardized positioning were taken at baseline (week 0) and at weeks 4, 8, 12, and 20. Patient satisfaction was assessed as poor, fair, and good, with <30, 30–60, and >60% improvement, respectively. Side effects seen in each group were recorded at every session.
Collected data were tabulated and analyzed using SPSS 16 software (Statistical Package for Social Science; SPSS Inc., Chicago, Illinois, USA). Categorical data were presented as the number and percentages, whereas quantitative data were expressed as the mean and SD. The percent of improvement was calculated by Fisher’s exact test, the paired t-test, and the χ2-test. Patient satisfaction was calculated by Mc Nemar’s test and the κ test. P values less than 0.05 were considered significant and values less than 0.001 were considered highly significant.
Forty patients were included in the study. All of them (32 females and eight males) completed the study. The means±SD for age in GA and GB were 19.8±4.02 and 19.55±4.19 years, respectively. Seventeen patients were females and three patients were males in GA compared with 15 females and five males patients in GB, respectively. The mean±SD for the age of onset of acne in GA and GB was 14.40±2.30 and 14.20±1.673 years, respectively, whereas the mean±SD for the disease duration was 5.40±2.521 and 5.70±3.5703 years for GA and GB, respectively. Eighteen patients had skin type III and two patients had skin type IV in GA compared with 17 and three patients in GB, respectively. The 20 patients in GA had moderate acne compared with 19 patients with moderate acne and one with severe acne in GB. Comparison between both groups regarding age, sex, the age of onset, the duration of acne, the skin type, and the acne severity was nonsignificant (P=0.848, 0.695, 0.755, 0.761, 0.52, and 1.0, respectively).
An objective evaluation of the treatment outcomes performed by the treating physicians revealed the following:
Both agents produced improvement in comedones during the study. The difference between the two peeling agents was statistically significant from week 2 (GA 13.05±8.532, GB 21.1±11.2, P=0.025), week 4 (GA 9.10±7.376, GB 19.1±10.396, P=0.008), and week 6 (GA 5.95±4.936, GB 17.6±10.338, P=0.001) and highly significant from week 8 (GA 4.40±4.122, GB 16.30±9.979) to week 20 (GA 1.80±1.852, GB 14.3±10.032). Percentages of improvement in comedones from week 0 to week 20 were 90.2 and 35.87% in GA and GB, respectively, with a statistically significant difference (P<0.05).
Both agents led to an improvement in papules during the study. The difference between the two agents was significant from week 12 (GA 2.0±1.45, GB 3.25±1.41, P=0.006) and week 20 (GA 2.45±1.28, GB 3.4±1.57, P=0.020). Percentages of improvement in papules were 81.72 and 77.78% in GA and GB, respectively, with a statistically significant difference (P=0.006).
The difference between both groups appeared to be significant from week 10 (GA 2.65±1.725, GB 4.2±2.353, P=0.045), week 12 (GA 1.75±0.910, GB 2.95±1.468, P=0.012), and week 20 (GA 2.2±1.473, GB 3.75±1.997, P=0.026). Percentages of improvement in pustules were 85.38 and 75.65% in GA and GB, respectively, with a statistically significant difference (P=0.000).
The total acne score
Although both agents led to an improvement in the total acne score, SMP was seen to be more effective, with a significant difference from week 6 onward (Table 1). The percentage reduction in the total acne score from week 0 to week 20 was 85.29 and 68.50% in GA and GB, respectively, with a statistically significant difference (P<0.001).
The two agents caused improvement in postacne hyperpigmentation throughout the study, with a statistically significant difference between both groups from week 12 (P=0.034) to week 20 (P=0.045) (Table 2). Percentages of improvement in postacne hyperpigmentation were 66.13 and 46.88% in GA and GB, respectively, with a statistically significant difference (P=0.011).
Both agents produced an improvement in icepick scars (Table 3) with no statistically significant difference between both groups at week 20 (P=0.570). Percentages of change in icepick scars from week 0 to week 20 were 17.85 and 11.9% in GA and GB, respectively, with a statistically nonsignificant difference (P=0.259).
Both agents produced an improvement in boxcar scars (Table 4) with no statistically significant difference between the two agents at week 20 (P=0.84). Percentages of change in boxcar scars from week 0 to week 20 were 29.3 and 25.8 % in GA and GB, respectively, with a statistically nonsignificant difference (P=0.130).
According to the VAS score assessed by the two uninvolved dermatologists (Table 5), it was found that SMP had a higher overall improvement than GAP (Figs 1 and 2).
Four (20%) patients in GA developed a burning or stinging sensation against two (10%) patients in GB. Sixteen (80%) patients in GA had visible desquamation against eight (40%) patients in GB (P=0.025). Dryness was seen in three (15%) patients in GA and in two (10%) patients in GB. Acne flare was seen in two (10%) patients in each group.
The patient satisfaction score
At week 12, two patients graded their total improvement as poor, five patients as fair, and 13 patients as good in GA compared with one, 13, and 6 patients in GB, respectively (χ2=6.47, P=0.039). These results were matched with those obtained by the VAS in GA (Mc Nemar’s test=3.0, P=0.22), and the degree of agreement with the VAS was 85% (κ test=0.67, P<0.001). In GB, patient satisfaction score results were matched with those obtained by the VAS (Mc Nemar’s test=1.0, P=0.61), and the degree of agreement with the VAS was 75% (κ test=0.52, P=0.005).
The present study reported that SMP were safe and effective in the treatment of both noninflammatory and inflammatory lesions of facial acne vulgaris. After undergoing peels, the percentage of improvement from week 0 to week 20 was 90.2% in comedones, 81.72% in papules, 85.38% in pustules, 85.29 % in total acne scores, 66.13% in postacne hyperpigmentation, 17.85% in icepick scars, and 29.3% in boxcar scars. These results were comparable with those of Garg et al. 5, who evaluated the efficacy of the combination of 20% salicylic–10% mandelic acid peels in the treatment of facial acne, postacne scars, and hyperpigmentation in Indian patients. They found that the percentage of improvement from week 0 to week 24 was 45.7% in comedones, 47.7% in papules, 58.4% in pustules, 52.3% in total acne scores, 59.8% in postacne hyperpigmentation, 13.2% in icepick scars, and 23.3% in boxcar scars. The deviation between these results and the results obtained in the present study could be explained by differences in the skin type and the environmental conditions.
To the best of our knowledge, there are no published data on SMP being used for the treatment of acne, except the study of Garg et al. 5. However, many studies had evaluated the efficacy of the SA peels in the treatment of acne 13–16. Hashimoto et al. 13 evaluated the efficacy of 30% SA peels in the treatment of acne. They found that there was a 75% reduction in comedones and an improvement of the acne grade in all patients (grades II and III of acne were decreased to grade I). Dainichi et al. 14 reported a greater than 75% reduction in both inflammatory and noninflammatory acne with 30% SA peel. Joshi et al. 15 and Ahn and Kim 16 found that SA peels had a whitening effect on the skin and improved postacne hyperpigmentation.
Throughout the present study, GAP showed an improvement in both inflammatory and noninflammatory acne lesions. The percentage of improvement from week 0 to week 20 was 35.87% in comedones, 77.78% in papules, 75.65% in pustules, 68.50% in total acne scores, 46.88% in postacne hyperpigmenation, 11.9% in icepick scars, and 25.8% in boxcar scars. These results were comparable to those of Garg et al. 5, who found that the percentages of improvement from week 0 to week 24 were 20.9% in comedones, 27.3% in papules, 34.7% pustules, 27.3% in total acne scores, 46.3% in postacne hyperpigmentation, 10.4% in icepick scars, and 20.1% in boxcar scars. The results of the present study concur with those reported by Perić et al. 17. They evaluated the efficacy of 35% GAP in mild to moderate inflammatory acne. They found 76.7% reduction in papules and 80.0% reduction in pustules.
Throughout the present study, SMP was more effective than GAP in the treatment of both noninflammatory and inflammatory acne lesions. This is because of the unique lipophilic and anti-inflammatory properties of SA, which seems to be the dominant agent in the combination (SMP) 3. Moreover, mandelic acid is one of the largest AHAs and penetrates the epidermis more slowly and uniformly, making it an ideal peel for acne and pigmentation 5. GA, in contrast, is hydrophilic, which makes it a weaker comedolytic agent. Furthermore, it does not have the anti-inflammatory properties of SA. El Akhras et al. 18 compared the effect of 70% GAP and 30% SA peels in the treatment of postacne hyperpigmentation, and they reported that both agents were effective in the treatment of postacne hyperpigmentation. These results support the synergetic effect of adding mandelic acid to SA (SMP) in the treatment of postacne hyperpigmentation.
In the present study, both agents led to a subtle decrease in the number of icepick and boxcar scars with no statistically significant difference. This might be explained by the fact that both the peeling agents are superficial peels and they serve only to resurface the upper layers of the epidermis. Through an indirect mechanism, both stimulate the dermal fibroblasts to deposit more collagen, elastin, and glycosaminoglycans in the papillary dermis. A more orderly and parallel arrangement of the fibers is also seen with both agents 19. Thus, a gradual and slight decrease in the number of icepick and boxcar scars was observed. Regarding the side effects throughout the present study, it was found that both agents were tolerable to all patients: a burning or stinging sensation was found in 20% of the patients with SMP against 10% of the patients with GAP. These results concur with those obtained by Garg et al. 5. They found that 17.3% of the patients developed a burning or stinging sensation with SMP against 8.7% of patients with GAP.
In the present study, dryness was seen in 15% of the patients with SMP against 10% of the patients with GAP. In contrast, 80% of the patients with SMP had visible desquamation against 40% of the patients with GAP. These results are not in agreement with that reported by Garg et al. 5. They reported dryness only with SMP (14.28%). Also, they reported that 8.7% of the GAP patients and no patients with SMP had visible desquamation. This might be explained by the different methods of formulation of the peeling agents (vehicle) in this study.
The SMP proved to have a higher efficacy than the more commonly used GAP in the treatment of both inflammatory and noninflammatory acne and postacne hyperpigmentation, whereas both peeling agents had nonsatisfactory results in all types of acne scars. Both peeling agents were safe, with tolerable side effects.
Conflicts of interest
There are no conflicts of interest.