Acne vulgaris is the eighth most prevalent disease worldwide, affecting nearly 10% of the population.1 The prevalence is 85% in adolescents,2 and up to 12% are still affected as adults.3,4 Scarring is a common permanent consequence of acne, affecting up to 95% of patients with acne, predominantly in the face.5
Acne and scarring can have a profound psychological impact on affected individuals and are linked to anxiety, depression, and even suicide.6–8 Several other aspects of quality of life are also affected because patients may suffer from poor self-esteem, embarrassment, lowered academic performance, and unemployment.9–14
Most acne scars are atrophic, that is, characterized by loss of tissue. There is no general consensus on classification of atrophic scars, although lesions are generally categorized into ice-pick, boxcar, and rolling scars.15 As there is no standard therapy in clinical practice, the choice of treatment must be adapted to each patient. In addition, because of the heterogeneity of scarring in patients, both in terms of scar types present and scar severity, a combination of treatment modalities is usually required (discussed in Sanchez Viera 2015).16 The goal with treatment is generally to reduce, but not completely remove the scars.17 Current treatment options include dermabrasion, chemical peeling, laser resurfacing, subcision, punch techniques, and tissue-augmenting agents such as hyaluronic acid (HA).15,17–19 Given the prevalence and psychological impact of scarring, further clinical studies are needed to gather clinical evidence for optimal treatment methods with minimal downtime and maintained long-term effect.
Restylane Vital Lidocaine (also known as Restylane Skinboosters Vital Lidocaine) is manufactured by Galderma (Uppsala, Sweden) using the patented NASHA technology and contains 20-mg/mL stabilized HA gel of nonanimal origin and 0.3% lidocaine. Studies have shown that treatment with HA gel improves skin-surface roughness, texture, elasticity, and hydration.20–22
The main objective of this study was to evaluate improvement of depressed atrophic facial acne scars and the surrounding skin after injection of HA gel at 3 consecutive treatment sessions 4 weeks apart.
Materials and Methods
Twelve subjects were included in this open noncomparative 36-week pilot study performed at 1 center in Belgium (ClinicalTrials.gov Identifier: NCT01807455). All subjects provided signed informed consent, and the study was approved by an independent ethics committee. Eligible subjects had atrophic depressed facial acne scars (less than 4 mm in diameter) that covered more than half of the face (i.e., were rated as at least Score 3 on the 5-graded scale for acne scar severity [SCAR-S],23 [Table 1]). Larger scars or ice-pick scars could not cover more than 25% of the face and were not to be treated.
Exclusion criteria included permanent facial tissue augmentation, active skin disease, and hypersensitivity to HA or lidocaine. Subjects treated with isotretinoin within 12 months were excluded, as were subjects who had had temporary facial tissue augmentation within this period.
Treatment Sessions and Injection Procedure
Treatment was given at 3 treatment sessions scheduled 4 weeks apart (at Weeks 0, 4, and 8), and subjects were followed for 36 weeks after the first treatment session. An optional maintenance treatment was given at Week 36, and these subjects were followed for an additional 4-week safety evaluation period. Subjects receiving all planned treatments were to be included in both the intention-to-treat (ITT) and safety populations. Effectiveness analyses were based on the ITT population.
Before injections, the treatment area was cleaned with an antiseptic solution. The use of a local anesthetic cream containing 2.5% lidocaine and 2.5% prilocaine (EMLA; AstraZeneca, Södertälje, Sweden) was optional.
Subjects received full-face HA gel treatment to achieve general improvement in skin quality. The HA gel was administered using multiple retrograde linear injections with approximately 20-μL HA gel per injection point. Using the same HA gel, scars were treated by dermal layer injections of approximately 20-μL HA gel per injection point. Injections were administered as close together as possible based on investigator's judgment, using the copacked 30-G needle and the retrograde short linear threading technique. In more detail, to achieve optimal placement of the gel, the needle was inserted next to the scar, and several passes were made in 1 direction below the scar while placing amounts of gel during needle withdrawal adequate to achieve lifting of the scar. The needle was thereafter inserted in a 90° angle to the original direction, and several additional passes were performed while also placing gel under the scar (Figure 1). Up to 2 mL was injected into each side of the face at each treatment session, taking both the full-face skin rejuvenation treatment and the scar treatment into account. Gentle massaging and cooling of the treatment area was permitted after treatment.
Scale for Acne Scar Severity
Acne scar severity was assessed live by the investigator in a standardized setting (regarding e.g., distance, light, and facial expression) using the SCAR-S. Subjects were considered improved if their SCAR-S score had improved by at least 1 grade from the baseline assessment.
Global Aesthetic Improvement Scale
Subjects and investigators evaluated aesthetic improvement by comparing standardized post-treatment photographs with baseline photographs. Changes in appearance were rated on the global aesthetic improvement scale (GAIS [Table 2]) by responding to: “With respect to acne scarring and skin quality, how would you describe the result of treatment compared to the photos taken before treatment?”
Subject Satisfaction Questionnaire
Subjects' satisfaction with the treatment in terms of overall facial appearance and sensation and perception of the facial skin was evaluated by using a subject satisfaction questionnaire. The effect of treatment on subjects' self-esteem, self-confidence, and confidence in social situations was also assessed.
Local tolerability reactions, that is, anticipated injection-related reactions such as bruising, swelling, redness, pain, tenderness, itching, and bumps were assessed for 14 days after each treatment session using subject diaries and reported as adverse events (AEs) if ongoing at last day of diary reporting. Reports were to be based on reactions from both treatment of acne scars and treatment of the surrounding skin. Adverse events were recorded throughout the study.
Subject Disposition and Baseline Characteristics
Twelve Caucasian subjects (8 women and 4 men) with a mean age of 33 years (range 27–43 years) were included in the study. At baseline, subjects had moderate (n = 7) or severe (n = 5) acne scars according to SCAR-S. All subjects completed the 3 treatment sessions and all follow-up visits and were included in both the ITT and safety populations.
The mean volume of HA gel used per treatment session (i.e., for treatment of both acne scars and the surrounding skin) was 3.8 mL (range 2.0–4.0 mL). The mean total volume used was 11.3 mL (range 6.0–12.0 mL), including all 3 treatment sessions. The EMLA cream was used before all, except 2, treatments.
Five subjects received the optional maintenance treatment (mean volume: 2.6 mL [range 2.0–4.0 mL]). The remaining 7 subjects were either already satisfied with the treatment result or did not want another injection procedure.
Scale for Acne Scar Severity
Scale for acne scar severity ratings had improved for 25%, 50%, and 67% of subjects at Weeks 4, 12, and 36, respectively (Table 3). The percentage of subjects with a SCAR-S rating of “severe” was 42% before treatment and decreased to 0% at Week 12 through Week 36. Moreover, the percentage of subjects with a SCAR-S rating of “mild” was 25% at Week 12 and increased to 42% at Week 36 (Figure 2). At Week 36, one subject (8%) had a SCAR-S rating of “almost clear.”
Global Aesthetic Improvement Scale
Using the GAIS, most subjects assessed their acne scarring and skin quality to be improved (i.e., somewhat, much, or very much improved) at all time points. The percentage of subjects who assessed their acne scarring and skin quality to be much or very much improved increased from 8% at Week 4 to 41% at Week 12 and then further to 59% at Week 36 (Figure 3).
The investigator assessed that 100% of subjects had improved acne scarring and skin quality at Week 8 (after 2 treatment sessions; data not shown), and that 92% were still improved at Week 36 (Figure 4). The percentage of subjects who were assessed to have much or very much improved acne scarring and skin quality increased from 0% at Week 4 to 50% at Week 12 and then further to 83% at Week 36.
Neither the subjects nor the investigator assessed the subjects' acne scarring and skin quality to be worse at any time point.
The percentage of subjects who were satisfied with the overall appearance of their face increased from 33% at baseline to 83% at Week 36 (Table 4). The percentage of subjects who were satisfied with the sensation and perception of their skin had also increased at Week 36 compared with baseline; the highest increase occurred for perception of skin structure and glow.
In addition, 83% of subjects reported improved self-esteem and self-confidence at Week 36 and 42% reported improved confidence in social situations (Table 5).
Local tolerability reactions were reported from diaries by all subjects at some point within 14 days after the 3 treatment sessions. Redness, swelling, and bumps were experienced by the vast majority of subjects after all treatment sessions. A total of 92% of subjects experienced bruising and pain after the first session. After the second and third treatment sessions, bruising was experienced by 75% and 73% of subjects and pain by 92% and 64% of subjects, respectively. Most reactions were mild to moderate in intensity and resolved within 14 days after treatment.
Eight subjects had 29 AEs that were related to the injection procedure (Table 6); none was serious. Most treatment-related AEs were mild to moderate in intensity, and all had resolved at study end. The most frequently reported AEs were bumps, ongoing at Day 14 (coded as implant site nodule [9 events in 5 subjects]) and implant site erythema (8 events in 5 subjects) with a median duration of 29 and 23 days, respectively. Nine AEs in 4 subjects were of severe intensity and resolved spontaneously after a median number of 26 days.
The results from this pilot study showed that 3 treatment sessions with HA gel effectively reduced acne scar severity and improved facial aesthetic appearance.
Improvement in acne scar severity developed gradually over time, and at Week 36, the majority of subjects (67%) had improved SCAR-S ratings. When assessing global facial aesthetic appearance, both subjects and the investigator assessed improvements in most subjects already after 4 weeks; at Week 36, the percentage of improved subjects had increased to 92-100%. Moreover, the percentage of subjects with much or very much improved aesthetic appearance increased from less than 10% at 4 weeks to 59% to 83% at 36 weeks; see Figure 5 for photographs of a representative subject before treatment and after 36 weeks. Although the relative contribution of the acne scarring and skin quality factors could not be assessed separately in the GAIS evaluations because both factors were incorporated into the same GAIS question, the overall GAIS and SCAR-S results clearly show a gradual improvement of acne scars after the HA gel treatment. Furthermore, aesthetic improvement rates were high, despite the fact that the results might potentially have been influenced by the presence of scars that were not allowed to be treated (i.e., coexisting ice-pick scars or other atrophic scars larger than 4 mm in diameter covering up to 25% of the face).
The treatment also improved subjects' satisfaction with the overall facial appearance and skin quality in terms of perception and sensation of the skin. These satisfaction results are in line with the GAIS and SCAR-S improvements and with previous studies using the same HA gel.20–22 The HA gel treatment also improved self-esteem and self-confidence in more than 80% of subjects. As people affected by acne and acne scars may have a lowered quality of life,10,13 these results could be clinically important.
The fact that the improvements in scar severity, GAIS, and subject satisfaction were high at study end is encouraging. Results seen at study end may be due to still-present HA gel but may also involve an ongoing HA gel–induced collagenization process24 as improvements developed gradually over time. Furthermore, as only a small 30-G needle was used for injections of acne scars and the surrounding skin, the use of the needle itself most likely did not contribute significantly to the result, but a relative contribution to the final results cannot be excluded.
The amount of HA gel used in this study (mean 3.8 mL used per subject and treatment session) is relatively large but is explained by the fact that except from treatment of the scars, subjects received concurrent full-face skin rejuvenation treatment with the same HA gel.
Most AEs reported in the study were mild to moderate and expected after these types of injections. The investigator assessed all AEs to be related to the injection procedure and not to the product itself. Specifically, the implant site nodules were considered caused by the injection technique that was used to achieve optimal placement of the gel. No serious AEs occurred during the study.
Limitations of the study include its open-label design, few included subjects, and that the same investigator performed both treatments and assessments, thus introducing risk of investigator bias despite precautionary measures taken in terms of standardized assessments. Despite the limitations, the results of this pilot study support that HA gel treatment of both acne scars and the surrounding skin could constitute a valuable treatment option for moderate-to-severe acne scarring. Further studies are, however, needed to confirm the aesthetic and psychological effects of HA gel treatment of acne scars.
This pilot study demonstrated that treatment with HA gel was safe and effectively improved the appearance of atrophic, facial acne scars, and the overall appearance of the face. The effects of HA gel developed gradually over time with the largest improvement observed at 36 weeks. The treatment was generally well tolerated.
The authors thank Dr. Carolina Edwartz (Galderma Aesthetics) for editorial assistance.
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© 2018 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
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