Clinical factors influencing the effectiveness of microplasma fractional radiofrequency treatment for atrophic acne scars: A retrospective analysis

Microplasma fractional radiofrequency (MP FRF) technology has been increasingly used for acne scars. Nevertheless, little evidence has analyzed the factors influencing its effectiveness before and during treatment.


| INTRODUC TI ON
Acne vulgaris is a prevalent cutaneous condition typically affecting adolescents and adults. 1 Moderate to severe acne, in most cases, may persist and lead to permanent scarring. 1Acne scars may occur in atrophic or hypertrophic forms depending on whether collagen is lost or gained. 2 The atrophic form is more common.It is caused not only by a loss of dermal collagen but also by the destruction of sebaceous gland structures. 3Atrophic acne scars have been categorized into icepick, boxcar, and rolling scars based on their appearance. 36][7] The therapeutic principle of MP FRF is to utilize radiofrequency energy to provoke microplasma sparks, which create mild fractional ablation and thermal effects.The combination of these two effects induces rapid reepithelialization and stimulates the regeneration of dermal collagen, resulting in skin remodeling. 5,7[7][8][9] Nevertheless, little evidence has analyzed the factors influencing its effectiveness before and during treatment.Herein, we described the clinical features of 79 acne scar patients administering MP FRF therapy and evaluated the factors affecting the effect of MP FRF in resurfacing atrophic acne scars.

| Patient
Our study enrolled 79 out of 256 patients visiting our Department of Dermatology from February 2019 to February 2023 to treat atrophic acne scars.Atrophic acne scar patients who received at least one session of MP FRF treatment and had comprehensive clinical and follow-up records were screened for inclusion.All patients signed the written informed consent prior to treatment and consented to provide photographs.Patients were excluded if they had been treated with oral isotretinoin or received surgery, lasers, chemical peeling, or other types of radiofrequency treatment on skin lesions from six months before treatment to three months after treatment.The study was approved by the Ethics Committee of Beijing Jishuitan Hospital (No. K2023-080-00).

| Fractional radiofrequency treatment
Before treatment, surface anesthesia was achieved by covering the area with a eutectic mixture containing 2.5% lidocaine and 2.5% prilocaine (Tongfang Pharmaceutical Group CO. Ltd., Beijing, China) under occlusion for 1-1.5 h.After washing, the face was disinfected with 70% alcohol before treatment.After MP FRF treatment, cooling packs were applied to relieve pain and heat.Patients were instructed to wash the treated areas with sterile saline and avoid scratching for 3-5 days following each treatment.The sterile collagen dressings (Chuangfukang, Guangzhou Trauer Biotechnology Co. Ltd., Guangzhou, China) were applied to the face once daily for 1 week.In some cases, recombinant bovine basic fibroblast growth factor (rb-bFGF) gel (Befuxin, Zhuhai Yisheng Biological Bio-Pharmaceutical Co Ltd, Zhuhai, China) was applied once daily (dosage 300 IU/cm 2 ) to the treated area before decrustation.Furthermore, sunscreen or physical photoprotection was recommended to the patients.Treatment sessions were spaced 3.5 months apart on average.All patients were followed up every 2 weeks in the first month after each session and at least 3 months later after the last one.Two blinded dermatologists independently assessed high-resolution photos taken before every treatment session and during the final visit.

| Data collection
The data in our study were collected via electronic medical documents as follows: (1) age when initially treated; (2)

| Outcome ascertainment
Clinical improvement was assessed objectively and subjectively.We collected clinical manifestations on photographs, Goodman-Baron qualitative scores, and ECCA scores recorded by two blinded dermatologists before each session and during the final visit. 2,7,11The clinical improvement rate of atrophic scars (%), as the objective assessment, was expressed as the percentage decrease in ECCA scores from baseline to posttreatment: No improvement (0), mild improvement (1%-25%), moderate improvement (26%-50%), good improvement (51%-75%), excellent improvement (>75%).The improvement rate of no more than 25% divided the patients into two groups. 7,12Patient satisfaction with improvement was a subjective assessment based on a 4-point scale (1 = dissatisfaction or low satisfaction, 2 = moderate satisfaction, 3 = satisfaction, and 4 = great satisfaction). 13e adverse events included pain, crusting, erythema, edema, hyperpigmentation, hypopigmentation, sensitivity, blisters, herpes, pruritus, and scars.Posttreatment photographs were assessed by two blinded dermatologists.Patients' postoperative symptoms and assessments were recorded during each follow-up at the clinic or by telephone.

| Statistical analysis
We used SPSS version 22.0 (IBM) to perform the statistical analysis.
Continuous variables were described as mean and standard deviation (SD) if normally distributed or median and interquartile range (IQR) if skewed distributed.Differences in means and medians between groups were analyzed individually by independent samples t-test or Mann-Whitney U-test.The categorical variables were presented as numbers and proportions (%).The chi-squared or Fisher's exact test was conducted to examine their differences.The paired variables before and after treatment were tested by Wilcoxon signed-rank test.Univariable and multivariable binary logistic regression analyses were used to examine the factors related to effectiveness after the initial MP FRF treatment.A statistically significant difference was considered if p < 0.05.

| Clinical characteristics of patients
The clinical data of 256 patients with acne scars treated in our department were retrospectively analyzed.Among those, 86 patients received at least one session of MP FRF treatment, and the other 170 patients received the treatment of ablative fractional laser, chemical peeling, fractional picosecond laser, or combined treatments.After excluding two patients with incomplete clinical data, one patient received isotretinoin before MP FRF treatment, and four patients received fractional laser or subcision within 6 months before or during the MP FRF treatment, the retrospective study enrolled 79 acne scar patients (47 males and 32 females) who met the eligibility criteria.
As shown in Table 1, we summarized the demographic characteristics.When they were initially treated, the mean age was 28.84 ± 6.76 years, and the median scar course was 6 (IQR 7) years.patients used rb-bFGF gel after MP FRF treatment (Table 1).

| Clinical outcomes
Table 2 exhibited clinical improvement characteristics after MP FRF treatment.Twenty-eight (35.4%) patients improved moderately to excellent after one session (Figure 1 and Figure 2), while 51 (64.6%) had little or no improvement; 15 (55.6%) patients achieved moderate to excellent improvement after two sessions, while 12 (44.4%)showed little or no improvement; 6 (66.7%) improved moderately to excellently after three sessions, while 3 (33.3%)demonstrated mild improvement (Table 2A).ECCA scores and Goodman-Baron scores assessed by the investigators were all statistically significantly lower following MP FRF therapy (p < 0.001) (Table 2B).Additionally, after one to three sessions of MP FRF treatment, the number of patients with acne and acne scars decreased from 38 to 15, a reduction of 60.5%.
A total of 39 patients demonstrated moderate and excellent improvement after the treatment sessions.Patient satisfaction assessment revealed that 23 (29.1%) patients were moderately satisfied, 36 (45.6%) were satisfied, and 7 (8.9%) were greatly satisfied (Table 2B).

| Factors associated with the effectiveness of MP FRF treatment
We divided the patients into two groups after the initial session based on their improvement rate: the group with no or mild improvement (0%-25%) and the group with moderate to excellent improvement (>25%).Both groups of patients were compared in terms of their characteristics.As indicated in Table 3, significant differences were observed in scar course, distribution on the forehead, icepick scar type, and pretreatment Goodman-Baron scores (p < 0.05); but no differences in age, sex, skin type, smoking, staying up late, concomitant disease, use of rb-bFGF, MP FRF mode, or MP FRF energy.In accordance with the results of the univariable analysis in Table 4, scar course, distribution on the forehead, icepick scar type, and pretreatment Goodman-Baron scores were related to effectiveness.These factors were all negatively correlated with the effectiveness.In addition to the above-related factors, pretreatment ECCA scores, MP FRF mode, and MP FRF energy were also considered in the multivariable analysis based on previous studies. 12,14The result showed that the predictor of effectiveness was icepick scar type, Goodman-Baron scores, and ECCA scores before the treatment.According to Goodman-Baron qualitative scores, the severe grade before the treatment had a negative correlation with the effectiveness compared with the mild grade (OR = 0.02, 95% [0.001, 0.37], p = 0.009).The presence of icepick scars was also a negative correlation factor for effectiveness (OR = 0.06, 95% CI [0.004, 1.00], p = 0.049).Furthermore, after excluding the effects of icepick scars and pretreatment Goodman-Baron scores, ECCA scores were also correlated with effectiveness (OR = 1.04, 95% CI [1.01, 1.06], p = 0.009).

Patient characteristics Values
Age when initially treated (years) [mean (SD)] 28.84 ( TA B L E 1 Clinical characteristics of 79 patients and the treatment parameters.

| Adverse events
The MP FRF treatments were well tolerated.The common adverse events were pain, crusting, erythema, edema, and hyperpigmentation (Table 5).The mean pain scores during the treatment were

| DISCUSS ION
Atrophic acne scars are a common, permanent, and disfiguring sequelae of moderate to severe acne. 76][7][8][9] In this study, all patients received one to three sessions of MP FRF treatment.Although there were limited sessions of MP FRF treatments due to the COVID-19 pandemic, physician assessment showed that atrophic acne scars improved in varying degrees based on both ECCA and Goodman-Baron qualitative scores.Furthermore, most patients (83.6%) were moderately to greatly satisfied with MP FRF treatment.6][7] MP FRF applies a monopolar RF handpiece to discharge RF energy very close to the skin surface and transforms the nitrogen gas nearby into the plasma state, then provokes a grid of micro sparks, resulting in fractional microexfoliation and thermal effect of the epidermis and upper dermis. 5The combination of both effects contributes to the regeneration and remodeling of dermal collagen. 7Our Moderate improvement (N) 27 14 3 Good improvement (N) 1 1 3 Excellent improvement (N) 0 0 0  According to morphological features of atrophic acne scars, there are three types: icepick, boxcar, and rolling scars. 3,15Icepick scars are fine (<2 mm), V-shaped epithelial tract in most cases. 15eir openings in the epidermis are usually wider than the deepest points of infundibulum in the dermis or subcutaneous tissue since the scars taper down toward their depths. 16Boxcar scars are Ushaped pits with circular or elliptical openings (1.5-4 mm) and flat bottoms, resembling the scars after chicken pox. 15Rolling scars are broad, M-shaped depressions (>4-5 mm) with gently sloped edges caused by dermal binding. 15Boxcar and rolling scars can be further subclassified into shallow scars (0.1-0.5 mm) or deep scars (>0.5 mm) based on their depth. 16Our result showed that the presence of icepick scar type negatively correlated with the effectiveness of MP FRF treatment. 17As previously reported, this result was consistent with the finding that the mean decrease in ECCA scores of icepick scars after MP FRF treatments was the lowest of the three types. 7Future research will require a larger sample size to verify this finding.Compared to FRF and fractional laser therapy, CROSS (chemical reconstruction of skin scars) and punch excision were reported to be more effective for icepick scars. 16Furthermore, another study demonstrated that the CO 2 laser pinpoint irradiation approach was superior to 100% trichloroacetic acid CROSS for icepick acne scars. 18The targetoid CO 2 laser resurfacing technique was recently reported safe and effective in the management of icepick and boxcar acne scars. 19reover, recent research reported that non-ablative fractional laser (NAFL) combined with isotretinoin significantly improved icepick scars more than NAFL alone. 20However, as far as we know, no evidence has shown the efficacy and safety of MP FRF therapy combined with isotretinoin.Given the increased potential risk of adverse events, we followed the traditional practice at that time and suggested that patients who completed a course of isotretinoin would wait 6 months before receiving MP FRF treatment.In and qualitative evaluation of acne scars. 5,7,8,11The ECCA grading system is based on the semiquantitative, weighted assessment of various acne scar types. 2 In addition to reflecting scar types and the number of lesions, this grading system also partly reflects scar depth and extent, but it is time-consuming.Moreover, when a particular type of scar lesion exceeds 20 in number, it is challenging to compare semiquantitative scores between pretreatment and posttreatment.Goodman and Baron Qualitative Scarring Grading System categorizes acne scars into four grades Compared with carbon dioxide fractional laser (CO 2 FL), MP FRF was proven to result in more superficial microscopic treatment zones (MTZs). 23The histological studies on porcine skin had shown that the depth of the ablative zone and total MTZs in low energy MP FRF (50 W) was 84.47 ± 7.45 μm and 182.74 ± 81.87 μm, respectively.
Even with high energy MP FRF (100 W), the depth of the ablative zone   In addition, we observed that the number of scar patients with acne was reduced after MP FRF treatment.Similar to our observation, two studies previously noted that MP FRF treatment improved some active acne lesions to some extent, possibly due to thermal effects on the sebaceous gland function. 5,9Further studies are needed to investigate the efficacy and mechanism of MP FRF treatment for acne.
MP FRF treatment transmits thermal energy directly to the tissue without absorbing or transferring it through an intermediate chromophore.Therefore, MP FRF is chromophore-independent and more suitable for patients with darker skin. 56][7] It might be related to the high level of MP FRF energy (>60 W) in some patients and the preexisting skin sensitivity of some patients before treatment.All of these adverse events were resolved within 1 month.
This study contained some limitations.First, as the data were collected retrospectively and conducted at a single center, it was challenging to infer causality from variables.Second, clinical photographs made it difficult to assess acne scars accurately due to their threedimensional properties.Finally, owing to the impact of the COVID-19 pandemic, the sample size and treatment sessions were limited.

| CON CLUS IONS
This retrospective study explored the factors affecting the effectiveness of MP FRF treatment in atrophic acne scars.For all we know, this is the first study investigating the relationship between Goodman-Baron qualitative scores and the effectiveness of MP FRF treatment on acne scars.Our results showed that the severe grade before treatment had a negative correlation with the effectiveness of MP FRF treatment compared with the mild grade.The presence of icepick scars appeared negatively correlated with the effectiveness.
Our results may give clinicians a quick hint about the appropriate treatment choice based on scar types and severity.Additional treatments other than MP FRF might be required for severe acne scars and icepick scars to achieve rapid and satisfactory results.However, further multicenter, well-designed studies with larger samples and treatment sessions are required to confirm our results.
MP FRF treatment (Pixel RF, Accent XL; Alma Lasers, Caesarea, Israel) was performed on all patients in one to three sessions.In all sessions, the MP FRF device was set to IN MOTION mode with 45-75 W energy and three passes of the roller tip in different directions.Furthermore, in some sessions, especially for severe scar patients with skin type III, no skin sensitivity, and high pain thresholds, the STATIONARY mode was additionally selected before the IN MOTION mode.Icepick or deep boxcar scars, which could not be flattened by manual skin stretching, were treated one by one with the stationary tip of 55-70 W energy for those patients.The same physician performed all treatments.The treatment parameters were adjusted during the operation according to sites and subtypes of acne scars, skin type and texture, and pain tolerance.
Among them, 58.2% patients were in Fitzpatrick type III and 41.8% in Fitzpatrick type IV.Five (6.3%) smoked, and 38 (48.1%) stayed up late frequently.The concomitant diseases were listed as follows: acne in 38 (48.1%) cases, skin sensitivity in 9 (11.4%)cases, hypertrophic acne scars in 7 (8.9%)cases, polycystic ovary syndrome in 3 (3.8%)cases, and no one with keloid.The scars were on the cheek in 71 patients, tempus in 57 patients, forehead in 47 patients, nose in 31 patients, and underjaw in 15 patients.There were one to three types of atrophic scars on each patient.Before treatment, 75 (94.9%)patients had boxcar scars, 71 (89.9%) patients had icepick scars, and 60 (75.9%) patients had rolling scars.As shown in Table 2, they received 115 sessions of MP FRF therapy, with an average of 1.5 sessions.The IN MOTION mode was used in 61 (77.2%) patients, and the combination mode was used in 18 (22.8%)patients.There were 46 (58.2%) patients treated by MP FRF in low energy and 33 (41.8%) in high energy.Forty-two (53.2%)

6 .
65 ± 1.92.After MP FRF treatment, the mean crusting duration was 8.26 ± 4.01 days.No scabs were present after two weeks in most patients, and only in three (3.8%)cases, the scabs lasted longer than 2 weeks.All the patients developed erythema, and the average duration was 9.18 ± 6.42 days.The erythema persisted for 1 month only in five (6.3%) patients.Most patients (84.8%) experienced postoperative edema, which resolved within 2 weeks in all patients.Hyperpigmentation occurred in 12 (15.2%)patients and disappeared within 1 month.Twelve (15.2%) patients complained of posttreatment skin hypersensitivity, all resolved within 1 month.Eight (10.1%) patients complained of pruritus after the treatment and remised in 2 weeks.No blisters, herpes, hypopigmentation, or worsening of scarring was observed.
evaluated the factors affecting the effect of MP FRF in resurfacing atrophic acne scars.TA B L E 2 Clinical improvement.(2A) Summary of physicianassessed clinical improvement after each MP FRF treatment session.(2B) Characteristics of clinical improvement after MP FRF treatment.

F I G U R E 1
Clinical photographs of a 27-year-old male patient with mild acne scars before and after the initial session of microplasma fractional radiofrequency treatment.(A) Pretreatment.(B) Posttreatment at 12-week follow-up.
our study, only one excluded patient requested initiation of MP FRF treatment for acne scars while on isotretinoin (0.5 mg/kg.d).Despite the use of local anesthetics and oral ibuprofen, he eventually had to switch to CO 2 FL treatment because of intolerable pain during the procedure.The combination of isotretinoin and MP FRF treatment still needs further investigation.Several modalities are available to grade acne scars.Echelle d'Evaluation Clinique des Cicatrices d'acne (ECCA) grading system and Goodman and Baron Qualitative Scarring Grading System are commonly used in clinical practice for quantitative

( 1 :
macular, 2: mild, 3: moderate, and 4: severe) based on a global assessment of scar severity.2,21Although it does not show the type of scars, it provides a convenient and efficient global assessment of the depth of atrophic scars.For example, icepick and deep boxcar scars, which are deep atrophic scars, are regarded as severe scars.2,21To our knowledge, no studies have addressed the relationship between Goodman-Baron scores and the effectiveness of MP FRF therapy.In our study, we first demonstrated a negative correlation between the severe grade of the pretreatment Goodman-Baron scores and the effectiveness of MP FRF treatment.Recent research revealed that a combination of microfat and subcision was effective in treating severe atrophic acne scars (Grade 4) with a single session.22Moreover, another study recently demonstrated that MP FRF technology combined with subcision provided relatively satisfactory results in treating severe nasal depressed scars (Grade 4).8

F I G U R E 2
Clinical photographs of a 26-year-old male patient with moderate acne scars before and after the initial session of microplasma fractional radiofrequency treatment.(A) Pretreatment.(B) Posttreatment at 14week follow-up.TA B L E 3 Clinical characteristics of two groups with different improvement assessments.

a 1 indicates
the initial session.study used the roller tip in IN MOTION mode during MP FRF treatment in all patients.This may explain our results that ECCA scores correlated positively with MP FRF effectiveness after excluding the influence of the severe grade and icepick scar type.

Mild or no improvement (n = 51) Moderate and excellent improvement (n = 28) t/χ 2 /U p
Number of patients with a particular disease as each patient may have one or more concomitant diseases.Number of patients with acne scars at a particular site, given that each has acne scars at one or multiple locations.Number of patients with a particular type of acne scar, given that each has one to three types of scars.Clinical factors affecting the efficacy of MP FRF by univariable and multivariable logistic regression analysis.
24t-Test.bChi-squaredtest.eFisher'sexacttest.cMann-WhitneyU-test.dfgfindings that severe grade of Goodman-Baron scores and icepick scars were negatively correlated with the effectiveness of MP FRF treatment.Additionally, histological studies revealed that MP FRF caused more extensive thermal damage in the surrounding and adjacent areas than CO 2 FL.24Therefore, the therapeutic effects of MP FRF are correlated with both necrotic columns and thermal coagulated areas.It has been reported that MP FRF treatments using a roller tip are more suitable for scar lesions on larger areas.24OurTA B L E 4