Treatment of erythematous acne scars using 595‐nm pulsed dye laser combined with 1565‐nm ResurFX nonablative fractional laser

Acne vulgaris is a common inflammatory disease associated with various sequelae after skin lesion remission. Acne erythema has been considered simple erythema or a vascular lesion; however, because the understanding of this disease has improved, acne erythema is currently considered an early scar with erythematous components.

of Groups A and B were determined using a global scarring grading system and exhibited statistically significant differences.The quantitative score of Group A was higher than that of Group B (6.67 ± 3.46 vs. 4.98 ± 2.44).The erythema areas of the groups differed significantly after treatment, with Group B exhibiting more notable score improvements (5.00 [3.10, 7.10] vs. 2.80 [1.65, 4.60]; Z = 3.072; p < 0.05).

Conclusions:
The combined use of the PDL and NAFL is safe and effective for erythematous acne scars.
[Correction added on 9 March 2024 after first online publication: Degrees for the first six authors have been updated in this version.]Acne vulgaris is a common inflammatory disease.Approximately 80.2% of patients with acne vulgaris experience various sequelae after skin lesion remission, such as facial postinflammatory erythema or postinflammatory hyperpigmentation, and approximately 43% of patients experience acne scars. 1 Acne erythema has been considered simple erythema or a vascular lesion; however, with the enhanced understanding of and histopathological insights regarding acne vulgaris, it is now considered an early scar with erythematous components. 2 Acne erythema manifests as flat or slightly depressed scars against a background of erythema with or without pigmentation 3 and is referred to as an erythematous acne scar (Figure 1).The 1565-nm nonablative fractional laser (NAFL) has been commonly used for the early treatment of acne scars. 4Vascular occlusion also plays a crucial role in preventing early scar formation.Several studies have reported the effective improvement of traumatic scars with the combination of a 595-nm pulsed dye laser (PDL) and NAFL. 5 Additionally, the efficacy of a half-face comparative experiment using a PDL and NAFL for acne erythema has been demonstrated. 2However, there are no published studies regarding specific treatment for erythematous acne scars.During this study, we used both a PDL and NAFL to treat this type of scar and investigated the effectiveness, safety, and feasibility of this treatment approach.

| Testing methods
This randomized, prospective, clinical trial included 90 participants who were randomly divided into the experimental group (Group A; n = 45) or control group (Group B; n = 45).Randomization was performed using sealed opaque envelopes.Group A received only NAFL (M22-ResurFX™; Lumenis, Salt Lake City, UT, USA) treatment.
Group B received combined treatment with the NAFL and PDL (Vbeam; Candela Medical, Marlborough, MA, USA).Treatment was performed once, and the follow-up period was 4 weeks.
Local anesthesia was not administered before treatment.For Group A, the treatment energy was set to 40-60 mJ, with a spot density of 150 spots/cm 2 , and two passes were performed.The endpoint was the presence of erythema and wheals at the treatment site (Figure 2).Participants in Group B first received treatment with the PDL and a cooling device using a spot size of 7 mm, pulse width of In areas with deeper and smaller-diameter scars, an additional 3-mm overlap was applied with a pulse width of 10 ms, energy of 21 J/ cm 2 , and cooling of 20 ms/20 ms.The primary endpoints were mild erythema and swelling.Additionally, after PDL treatment, the participants in Group B immediately received NAFL treatment with parameters similar to those used for group A, and the primary endpoints were erythema and swelling (Figure 3).Assessments were performed by a dermatologist at baseline and 4 weeks after treatment.
After laser treatment, the participants were instructed to apply sunscreen (sun protection factor, 30; protection grade of UVA, >++) and wash their face with a gentle soap-free cleanser.Additionally, they were advised to avoid sun exposure and the use of cosmetics.

| Efficacy formulation criteria
Clinical measurements were performed during each evaluation after treatment.A ThinkView skin analyzer (Taiwan) was used to count both inflammatory and noninflammatory acne lesions and measure the erythema index of the most prominent lesion.Facial photographs of the frontal, oblique, 45°, and lateral views were obtained at baseline and before treatment using a digital camera (Canon PowerShot S95; Canon, Tokyo, Japan).The objective indicators were the acne grade, erythema score, patient satisfaction, and adverse events.
Acne grading was performed by independent physicians.To determine the severity of facial scars, the Goodman and Baron grading system, which is a qualitative global grading system for scarring, 6 and the Goodman and Baron score, which is a quantitative global grading system for scarring, 7 were used.Furthermore, the D value was presented as the difference between the baseline and posttreatment Goodman and Baron scores.
The severity of erythema with the acne lesions was determined by an independent physician who performed a clinical assessment of the erythema area.Additionally, the effect of erythema treatment was classified as complete cure, significant improvement, partial improvement, or no effect.Complete cure was defined as regression of the erythema area by 90%-100% and nearly absent color (barely noticeable to the naked eye).
Significant improvement was defined as regression of the erythema area by 60%-90% and noticeably lightened color.Partial improvement was defined as regression of the erythema area by 30%-60% and lightened color.No effect was defined as regression of the erythema area by less than 30% and no noticeable color change.The effectiveness rate was calculated as follows: effectiveness rate = n (complete cure + significant improvement + partial improvement)/n (total cases) × 100%.
The participants were asked to rate their satisfaction with treatment results as follows: very satisfied, satisfied, neutral, or dissatisfied.Adverse events were evaluated according to pain severity using a numeric rating scale (NRS) ranging from 0 to 10, with 0 representing no pain and 10 representing the most intense pain imaginable.All participants were asked to rate their pain severity immediately after the procedure.Moreover, any adverse events

| Statistical analysis
Statistical analyses were performed using SPSS software (version 26.0;IBM Corp., Armonk, NY, USA).Descriptive statistics, including the mean, standard deviation, median, lower quartile, upper quartile, and percentage, were used to summarize the data.The statistical significance of differences between groups was assessed using the chi-squared test or Fisher's exact test for categorical data, Student's t-test for normally distributed numerical data, or the Mann-Whitney U-test for non-normally distributed numerical data; p < 0.05 was considered statistically significant.

| General information
Most participants had Fitzpatrick skin types II to IV, with types III to IV being the most common (96.6%).Among the study participants, 83 (92.2%) were female and 7 (7.8%) were male.The average age of all participants was 26.98 ± 4.62 years (range, 18-49 years), and the average disease duration of all participants was 23.44 ± 14.44 months (range, 2-60 months).There was no statistically significant difference in the baseline clinical data of all participants (p > 0.05) (Table 1).

| Goodman and Baron grades and scores
The Goodman and Baron grades (χ 2 = 12.415; p = 0.004) and scores (t = 2.675; p = 0.009) of the groups were statistically significantly different after a single treatment.In Group B, the grade of 91.1% of cases decreased by one to two grades; however, in Group A, the grade of 42.2% of cases decreased by one to two grades.This difference was statistically significant (χ 2 = 36.009;p = 0.001).The score of Group B (4.98 ± 2.44) was significantly lower than that of group A (6.67 ± 3.46) (Figure 4).Additionally, the D values of the groups were significantly different (Z = 4.325; p = 0.001).The score of Group B (3.00 [1.00, 4.00]) notably decreased and was better than that of Group A (1.00 [0, 2.00]).

| Observation of the Erythema Area
After treatment, the acne erythema area of group A differed significantly from that of group B (5.00 [3.10, 7.10] vs. 2.80 [1.65, 4.60]; Z = 3.072; p = 0.002) (Figure 5).The improvement in the erythema areas of both groups was also statistically significantly different As shown in Table 2, a significant difference was observed in the treatment effectiveness rates of both groups (χ 2 = 20.295;p < 0.001).Group B achieved an effectiveness rate of 88.9%, which was significantly higher than that of group A (66.7%).

| Adverse events
Using the NRS, all participants reported pain scores ranging from 3 to 6; these scores were not statistically significantly different between groups (Z = 1.619; p = 0.106).Regarding adverse events, within 7 days after treatment, 86.6% of patients experienced redness and swelling, 78.8% reported scab formation, and 36.6% developed purpura.These adverse events generally resolved within 1 week.Four (4.4%) patients reported other adverse events such as pigmentation changes.However, none of the patients experienced depigmentation or scarring.

| DISCUSS ION
Erythema is a characteristic feature of early acne scarring.Therefore, early vascular intervention may help prevent progression to more severe scarring.Notably, 95% of doctors considered PDL as the firstline treatment option for these scars. 3However, the penetration depth of the PDL is only approximately 52 μm; therefore, its efficacy for closing deeper dermal blood vessels and stimulating collagen proliferation in atrophic scars is limited. 5Conversely, the NAFL has a penetration depth of approximately 1000 μm and predominantly targets water, which is a major component of blood vessels.When applied to the skin, the NAFL may cause photothermal damage to the vascular system of the skin, thereby closing the deeper vessels. 8ditionally, fractional lasers create numerous microthermal zones in the dermis that can stimulate the regeneration of dermal collagen and improve early acne scarring. 9e use of the NAFL alone to treat acne scars has been the common approach for mild to moderate early acne scars because of its advantages such as short downtime, minimal pain, and tolerability, particularly for individuals with darker skin types. 3However, the achievement of satisfactory clinical responses often requires four to eight sessions of NAFL treatment. 10During our study, after a single treatment, the rate of erythema improvement was 66.7% using the NAFL alone, whereas combination therapy (PDL and NAFL treatment) resulted in a significantly higher rate (88.9%).This improvement may have been attributable to several factors.Previous studies of PDL described two recommended energy settings, one advocating medium pulse durations and slightly higher energy (7-10 mm; 6-10 J/cm 2 ; 6-10 ms) and one advocating shorter pulse durations and slightly lower energy (5-12 mm; 4.5-6 J/cm 2 ; 0.45-1.5 ms). 11ring our study, we chose the following higher-energy settings: spot size of 7 mm, pulse width of 6 ms, and energy of 8 to 9. with an additional spot size of 3 mm, pulse width of 10 ms, and energy of 21 J/cm 2 .This decision was made because we observed that the use of a 3-mm spot with an energy setting of 21 J/cm 2 was particularly effective for treating deeper, smaller-diameter scars.The energy range of the 7-mm spot was 10-20 J/cm 2 , whereas that of the 10-mm spot was 4 to 10 J/cm 2 .However, for the 3-mm spot, the energy range was 20 to 40 J/cm 2 .Therefore, although the 7-mm and 10-mm spots penetrated deeper, the energy was lower.Based on our experience, a 3-mm spot was considered more effective for small but deep areas of redness.
Patients with inflammatory papules often have a few associated acne scars.According to previous reports, treatment using the NAFL was as effective and satisfactory as low-dose oral isotretinoin (0.5 mg/kg/day). 12The patients responded well to treatment, as evidenced by their Goodman scores.The score of group B (4.98 ± 2.44) was significantly lower than that of group A (6.67 ± 3.46) after treatment.Additionally, the D value of group B (3.00 [1.00, 4.00]) notably decreased and was better than that of group A (1.00 [0, 2.00]).
Treatment comprising both the NAFL and PDL is effective not only for acne erythema and scars but also for inflammatory papules because of the ability of the PDL to reduce the production of porphyrins through photothermal effects, leading to vascular closure, and induce the production of transforming growth factorβ, thereby improving inflammatory acne. 13Therefore, the combination of the PDL and NAFL is especially meaningful for patients with erythematous acne scars who also have a few associated inflammatory papules.
However, there are concerns that excessive photothermal effects may trigger acne outbreaks.To address this issue, needle extractions were performed to treat closed comedones and blackheads before treatment.Additionally, the following lower-energy settings of the PDL were used to treat inflammatory papules: spot size of 7 mm, pulse width of 6 ms, and energy level of 8 to 8.5 J/cm 2 .The NAFL treatment parameters were set to 150 spots/cm 2 and 40 to 45 mJ.
Despite these low energy settings, effective treatment goals can still be achieved (Figures 6 and 7).
The most commonly observed postoperative adverse events were flushing and purpura; patients treated with a high-energy PDL experienced these events more frequently.However, these reactions typically subsided within 10 days. 13Only 4.4% of the patients experienced postinflammatory hyperpigmentation, which was likely related to natural postinflammatory changes after the resolution of inflammatory papules.Pain experienced during the procedure was generally rated as approximately 3 to 6 using the NRS; these pain levels were deemed tolerable by most patients, and there was no statistically significant difference in these scores between groups.
This study had some limitations.The treatment duration and subsequent observation period were short.Therefore, these limited timeframes may not have fully captured the long-term outcomes and effects of treatment.Future studies with extended treatment periods should be performed to enable a more comprehensive evaluation of the efficacy and durability of treatment.
TA B L E 2 Erythema treatment effectiveness.F I G U R E 6 Four weeks after treatment with the 1565-nm nonablative fractional laser.
This randomized, single-blind, experimental study was approved by the Dermatology Ethics Committee (MR-44-22-022873).All participants with facial acne were recruited through the online distribution of a leaflet regarding the study.This study included 90 patients and was conducted from January to March 2021.All participants provided informed consent.The inclusion criteria were as follows: age older than 18 years (both sexes were included); clinical diagnosis of mild or moderate facial erythematous scars; the availability of complete data; and adherence to the research protocol.All patients voluntarily participated in this experiment.The exclusion criteria were as follows: pregnancy or potential pregnancy; concurrent systemic diseases, such as cardiovascular diseases, liver or kidney diseases, epilepsy, diabetes, and lupus erythematosus; photosensitivity or a history of psychiatric disorders or psychological abnormalities; the presence of skin lesions with local ulceration; active bacterial, viral, or fungal infections or suspected skin cancer in the treatment area; history of acne treatment, including tretinoin treatment within 6 months before the study, systemic antibiotic treatment within 1 month before the study, contraceptive treatment within 3 months before the study, and local acne treatment within 1 month before the study; concurrent active vitiligo or psoriasis; and the use of hydroxy acids or glycolic acid topically or facial photon, fractional laser, dermabrasion, or radiofrequency microneedling treatments within 3 months before the study.

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E Y W O R D S acne erythema scar, nonablative fractional laser, pulsed dye laser F I G U R E 1 Erythematous acne scars.| 2017 ZHOU et al. 6 ms, energy of 8 to 9.5 J/cm 2 , cooling of 20 ms/20 ms, and one pass.

F I G U R E 2
Before and after treatment with the 1565-nm nonablative fractional laser.F I G U R E 3 Before and after treatment with the 595-nm pulsed dye laser and 1565-nm nonablative fractional laser.related to treatment were recorded and assessed 4 weeks after treatment.Participants were allowed to undergo further consultations or seek medical treatment at a nearby hospital during this period if necessary.

5 J/cm 2 ,F I G U R E 4 F I G U R E 5
Changes in the Goodman and Baron scores of the two groups.# t = 0.205 and p = 0.838 versus the baseline values of group A. *t = 6.791 and p < 0.001 versus the baseline values of Group A. **t = 8.495 and p < 0.001 versus the baseline values of Group B and t = 2.675 and p = 0.009 versus the postprocedure values of Group A. Observation of changes in the erythema area of the two groups.#Z = 0.682 and p = 0.495 versus the baseline values of Group A. *Z = 4.910 and p < 0.001 versus the baseline values of Group A. **Z = 5.844 and p < 0.001 versus the baseline values of Group B and Z = 3.072 and p = 0.002 versus the postprocedure values of Group A.