Introduction

Atrophic acne scars usually develop as a result of aberrant collagen production and degradation during wound healing after inflammatory acne and causes significant physical and psychological distress [1]. Atrophic acne scars are classified as icepick, boxcar, and rolling scars based on depth and size of the destruction area [2].

Common atrophic acne scar treatments include lasers, dermabrasion, chemical peeling, fillers, subcision, radiofrequency, microneedling, and fat injections [3]. Relative to classical ablative CO2 lasers, ablative fractional CO2 lasers that create discrete columns of thermal damage known as the microthermal treatment zone (MTZ) spare the tissue surrounding each column, thereby minimizing side effects with similar efficacy. Although energy, treatment sessions, disease duration, and follow-up duration may influence efficacy, few studies have examined their relationship with efficacy, and it is unclear if efficacy is associated with side effects, including pigmentation. Here, we evaluated factors that can influence fractional CO2 laser efficacy in patients that present with atrophic acne scars and analyzed the relationship between adverse effects and efficacy.

Materials and methods

Patients

This retrospective study included 82 of 1034 patients who came to our laser surgery department between August 2013 and August 2019 for atrophic acne scar treatment. Inclusion criteria were acne scar patients who accepted uniform therapy utilizing CO2 laser with the same parameters across treatment sessions. Participants gave written informed consents prior to treatment. Exclusion criteria were history of pregnancy, lactation, immunosuppression, keloid scars, skin cancer, photosensitivity, allergy to lidocaine or prilocaine, laser resurfacing procedures within the preceding 6 months, and other treatments on affected skin areas.

Laser treatment

All patients received 1–3 sessions of single-pass ablative fractional CO2 laser (AcuPulse 40AES, Lumenis Laser Corp., Santa Clara, CA) with the parameter settings of 4050–11,830 mJ/cm2 maintained across treatment sessions. Topical anesthetic cream comprised of 2.5% lidocaine hydrochloric acid and 2.5% prilocaine (Tongfang Pharmaceutical Group CO. Ltd., Beijing, China) was applied to the treatment area for an hour before laser therapy. After treatment, ice packs were provided to alleviate heat and pain. Patients were prescribed 0.2% nitrofural ointment for 7-day use after the procedure and advised to avoid regular sun exposure.

Assessment of responses and complications

The information associated with acne scars, including age at onset, disease duration, Fitzpatrick skin type, treatment sessions, outcomes, and follow-up, was recorded. High-resolution photos taken at baseline and at the last visit were independently evaluated by 3 blinded investigators using ECCA scoring system. Consistency between the 3 dermatologists was assessed using intraclass correlation coefficient (ICC: poor ≤ 0.50, 0.50 < moderate ≤ 0.75, 0.75 < good ≤ 0.90, and 0.90 < excellent). Patients were asked to score their satisfaction with improvement on a 5-point scale (− 1 = worse, 0 = no change, 1 = satisfied, 2 = very satisfied, 3 = extremely satisfied). Subjective pain scores from 0 (no pain) to 10 (unbearable pain) were also obtained. Adverse events secondary to laser resurfacing, including erythema, hyperpigmentation, hypopigmentation, acne flare-up, and post-laser scar, were recorded.

Statistical Analysis

Statistical analysis was performed on SPSS version 18.0 (IBM). Data were shown as mean ± SD, median (interquartile range; IQR), and proportion (%), as appropriate. Hypothesis tests were performed by paired t test, with p ≤ 0.05 indicating statistical significance. Spearman correlation analysis was adopted, for the dependent variables of the study did not meet the normal distribution. Multiple variable linear regression analysis was used to analyze the relationship between independent and dependent variables.

Results

The demographics of the 82 patients (36 females and 46 males, mean age 23.52 ± 3.36 years) involved in this study are summarized on Table 1. Of this, 6 were classified as having Fitzpatrick skin type III, while 76 were classified as having Fitzpatrick skin type IV. ECCA scoring by the investigators revealed a statistically significant reduction in acne scars after laser therapy (Table 1, Figs. 1 and 2). Patient satisfaction assessment revealed that 32 (39.02%) were “satisfied,” 44 (53.66%) were “very satisfied,” and 6 were “extremely satisfied” (7.32%) (Table 1).

Table 1 Patient and treatment characteristics
Full size table
Fig. 1
figure 1

Pre-treatment (A) and post-treatment (B) photographs of a 19-y-old male patient. Pre-treatment ECCA score was 113.33, and post-treatment ECCA score was 66.67

Full size image
Fig. 2
figure 2

Pre-treatment (A) and post-treatment (B) photographs of a 23-y-old male patient. Pre-treatment ECCA score was 116.67, and post-treatment ECCA score was 73.33

Full size image

Analysis was done for association between treatment response and the patient gender, age, duration of course, Fitzpatrick skin type, energy density, number of treatment sessions, satisfaction, pain, erythema within or beyond 3 months, PIH within or beyond 3 months, hypopigmentation, acne flare-up, and post-laser scar. Erythema and PIH are demarcated by 3 months at which the curative effect began. This analysis showed that the number of treatment sessions and PIH within 3 months positively correlated with treatment effects (p ≤ 0.05), with those undergoing more treatment sessions or experiencing PIH within 3 months having better results (Table 2). No significant correlation was observed between other factors and the treatment efficacy.

Table 2 Regression analysis of CO2 laser efficacy on atrophic acne scar
Full size table

The most common adverse effects were pain, erythema, and pigmentation (Table 3). All patients had a pain level of 6.61 ± 1.92. Post-treatment erythema occurred in all subjects studied (100%), appearing in 80.49% of the patients lasting < 3 months and in 19.51% lasting > 3 months. PIH occurred in 60 patients (73.17%), appearing in 41.46% of the patients lasting < 3 months and in 31.71% lasting > 3 months. One patient experienced hypopigmentation (1.22%). Acne flare-up affected 8 patients (9.76%). Post-laser scars occurred in 2 patients (2.44%, Fig. 3). No other side effects, including contact dermatitis, HSV outbreak, or bacterial infection, were observed.

Table 3 Adverse effects following laser resurfacing
Full size table
Fig. 3
figure 3

Pre-treatment (A) and post-treatment (B) photographs of a 22-y-old male patient. About 1 month after treatment, cord scars appeared on the face

Full size image

Discussion

Ablative fractional laser resurfacing is crucial for atrophic acne scar treatment and is associated with up to 80% improvement and minimal adverse events [4]. Here, 1–3 treatments with the single-pass fractional CO2 laser (energy density range, 4050–11,830 mJ/cm2) significantly improved acne scars. However, treatment efficacy is also influenced by scar type [5] and severity [6], Fitzpatrick skin type [7], onset age [8], disease duration [9], follow-up [10], and timing [11] and methodology [12] of assessment. Few studies have assessed the relationship between these factors.

Energy is thought to impact acne scar laser resurfacing the most as it influences MTZ, subsequent neocollagenesis, and final treatment outcome [13]. It is reported that ablation depth in fractional resurfacing was correlated to the used energy [14]. An evaluation of response to high (50–70 mJ) and low (15–35 mJ) energy in fractional CO2 laser revealed that the average scar improvement score was better with high energy (5.8) relative to low energy (4.0) [15]. However, our analysis of correlation between efficacy and demographic characteristics and parameter settings revealed that the number of treatments was statistically significant to resurfacing outcome whatever energy, age, gender, Fitzpatrick skin type, disease duration, and follow-up are. Similarly, Tatliparmak et al. revealed the number of treatment sessions was positively correlated to the change in ECCA scores no matter what the energy was [7]. This may be attributable to penetration defects of fractional laser as ice pick acne type, which accounts for 70% of acne scars, lies deep in the dermis [16]. Therefore, differences in energy are often not enough to make statistically significant difference in a single treatment. Indeed, Mahmoud et al. reported the same degree of acne improvement using 10 mJ and 40 mJ energy settings on Er:YAG laser [17]. Besides, all the patients in this study only received 1 to 3 treatment sessions, and there is no relevant study on whether there is a plateau of efficacy when the treatment is more than 3 times. The author suggests that patients with acne scar can be given 3 laser treatment sessions to observe whether there is efficacy, otherwise other methods need to be selected.

To our knowledge, this is the first study reporting that pigmentation duration within 3 months positively correlates with treatment efficacy. Although previous studies have shown that energy heavily affects pigmentation after laser procedure [18], given that our data indicate that energy has no effect on efficacy, pigmentation may be used as a single-factor predictor of efficacy. Once the repair has started, fibroblasts migrate to the local area and secrete various cytokines, including hepatocyte growth factor (HGF), stem cell factor (SCF), and Sema7a, to promote melanocyte proliferation, leading to pigmentation [19]. Furthermore, melanocytes secrete alpha-melanocyte-stimulating hormone (a-MSH), which not only causes pigmentation but also exerts a strong anti-inflammatory effect. It can promote collagen rearrangement and increase collagen III by mediating the inflammatory phase of wound healing, thereby reducing scar formation. [20].

Here, hyperpigmentation was significant, probably due to the sensitivity of Asian Fitzpatrick skin types to injury. One case of hypopigmentation and 8 cases of acne flare-up were observed, and 2 patients reported post-laser net-like scars on the margin of the cheek near the eyelids. Hence, clinicians should be prudent when resurfacing thin skin, such as the periorbital area.

This study has some limitations. Firstly, being a retrospective study, it is difficult to determine the cause and effect between variables. Secondly, clinical photographs used for analysis were taken prior to treatment, rather than at fixed timepoints after each treatment. Thirdly, the majority of the participants in this study are Asian. Nevertheless, our findings make valuable contribution given the paucity of studies investigating this field.

Conclusion

This study indicates that the efficacy of ablative fractional CO2 laser on atrophic acne scars in Asians with Fitzpatrick skin types III–IV positively correlates with treatment sessions, other than energy, gender, age, and follow-up time. Additionally, the duration of hyperpigmentation within 3 months may predict efficacy. Evidence-based prospective studies are needed to explore the relationship between efficacy and age, gender, Fitzpatrick skin type, energy, treatment sessions, follow-up duration, and pigmentation.