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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 128-135

A study to evaluate various upcoming therapies for acne scars: Head on comparison


1 Department of Dermatology, Bharati Vidyapeeth (Deemed to be University) Medical College, Pune, Maharashtra, India
2 Department of Dermatology, B. J. Medical College, Ahmedabad, Gujarat, India

Date of Submission10-Aug-2018
Date of Decision23-Sep-2018
Date of Acceptance21-Nov-2018
Date of Web Publication18-Aug-2020

Correspondence Address:
Amita H Sutaria
A 304, Sahjanand Residency, Near Helmet Circle, Memnagar, Ahmedabad - 380 052, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CDR.CDR_34_19

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  Abstract 


Background: Scarring is a most common complication of acne vulgaris which has negative psychosocial implications. Multiple surgical modalities are available for the management of scars. Very few studies are available in literature which compares these modalities head-on and in a comprehensive way. Aims and Objectives: The objective is to analyze and compare the efficacy of subcision alone as well as combination of subcision with other therapeutic modalities. Materials and Methods: The study was carried out in 95 patients with postacne scars. Patients were divided into four groups as follows: Group I (S): Subcision; Group II (S + M): Subcision + microneedling; Group III (S + P): Subcision + platelet-rich plasma (PRP); Group IV (S + T): Subcision + trichloroacetic acid (TCA) peeling; all patients were followed up with photographs at 2, 6, and 9 months after start of treatment. Goodman-Baron's qualitative score assessment was performed at the start and end of the study. In addition, we also appointed independent blinded dermatologist for evaluating clinical improvement in terms of % improvement based on serial clinical photographs. Results: Among all modalities, subcision alone group showed the least improvement while subcision plus microneedling group showed the best response. Difference in final response of (S + P) and (S + T) groups was not statistically significant, but it was better than subcision alone group. Conclusion: Subcision plus microneedling showed the best response in our study while subcision plus PRP efficacy is comparable to that of subcision plus TCA peeling.

Keywords: Acne scars, microneedling, platelet-rich plasma, subcision, trichloroacetic acid peeling


How to cite this article:
Dhamale SS, Sutaria AH, Shah BJ. A study to evaluate various upcoming therapies for acne scars: Head on comparison. Clin Dermatol Rev 2020;4:128-35

How to cite this URL:
Dhamale SS, Sutaria AH, Shah BJ. A study to evaluate various upcoming therapies for acne scars: Head on comparison. Clin Dermatol Rev [serial online] 2020 [cited 2020 Nov 26];4:128-35. Available from: https://www.cdriadvlkn.org/text.asp?2020/4/2/128/292478




  Introduction Top


Acne vulgaris is a common condition of adolescence. Facial scarring as sequelae of acne vulgaris can occur to at least some degree in up to 95% of patients.[1]

Impairment in quality of life of patients suffering from postacne scars cannot be underestimated. They can influence psychological well-being and have a significant negative effect on the quality of life of young adults.[2]

Despite its high prevalence, there is no single treatment modality that is universally effective, posing a significant challenge for dermatologists in the treatment of acne scars.[3]

Surgical modalities available for the treatment of atrophic acne scars range from microdermabrasion, chemical peeling, subcision, microneedling, resurfacing lasers to newer modalities such as platelet-rich plasma (PRP).[4]

Atrophic acne scars are subdivided into three varieties as icepick, boxcar, and rolling types. There are a number of procedures for improving and correcting acne scars. Each procedure is best suited to a particular type of acne scar and has its own risks and benefits.[4] Often, a combination of procedures may be required to obtain the best result as individual patients commonly display more than one type of scars.[4]

While deciding the appropriate combination of procedures for patients subcision is an important technique. It is the first scar revision technique that should be performed on pitted acne scars before undertaking any other technique to improve the overall outcome.[5],[6] It does so by breaking vertical collagen scarring bands which produce pitting or depression.[5] This can be followed up by any other suitable procedure to give optimal results depending on the clinical situation. However, to the best of the author's knowledge, there is paucity of studies in literature as to what combination gives the best results.

This study is an attempt to perform head-on comparison of outcomes of various existing and newer modalities like PRP when combined with subcision, in a single study frame.

The aim of our study was to evaluate the efficacy of subcision alone as well as combination of subcision with other therapeutic modalities namely microneedling, PRP, trichloroacetic acid (TCA) peeling in the treatment of atrophic acne scars.

We also sought to compare the final results obtained in each of the above groups with each other.


  Materials and Methods Top


Subjects

The present study was conducted on 95 patients suffering from atrophic postacne scarring. Patients were recruited from the dermatology outpatient department of tertiary care center in western India after getting approval from Institutional Ethics Committee.

Patients visiting the outpatient department for a complaint of postacne scarring were evaluated. Each patient was subjected to detailed history taking regarding onset, duration and severity of lesions, any history of treatment for acne and acne scars, history of any concomitant disease or any other treatment, history of keloidal tendency. A detailed clinical examination was carried out in each patient to note the skin type, extent, type, and severity of acne scarring.

Inclusion criteria

Willing patients of age group 18–45 years who were suffering from atrophic postacne scarring were included in the study.

Exclusion criteria

Patients who had a history of keloidal tendency, prior treatment for acne scarring, treatment with systemic isotretinoin in prior 6 months, bleeding tendencies, sensitivity to peeling agents, photosensitivity, herpes labialis, and systemic diseases were excluded from the study.

Pregnant and lactating patients as well as patients with unrealistic expectations were also excluded.

Patients who were willing to participate in the study were selected after counseling them regarding the modalities of treatment available, expected outcome, and possible adverse effects.

Written informed consent was obtained from each patient for study participation.

Subjects were randomly divided into four groups in the following manner;

  • Group I (S): This group underwent only three sittings of subcision
  • Group II (S + M): This group first underwent three sittings of subcision followed by three sittings of microneedling
  • Group III (S + P): This group first underwent three sittings of subcision followed by three sittings of PRP
  • Group IV (S + T): This group first underwent three sittings of subcision followed by three sittings of chemical peeling by 30% TCA.


The interval between two consecutive sittings of any procedure was 4 weeks in all groups.

Photographs of all patients were taken once before initiating treatment and then at 2, 6, and 9 months after start of the treatment. All photographs were taken with Canon™ Ixus 510 HS camera at the exposure setting of − 1 under fixed illumination and at fixed spot.

Methods

Subcision

Before the subcision procedure, patients were counseled and were instructed to stop the intake of any drugs which could potentially prolong the bleeding.

Facial skin was disinfected. The scarred area was marked with surgical pen. Subcutaneous anesthesia (Lignocaine hydrochloride 2% and adrenaline 1:200,000) was given in marked area. Once the adequate anesthesia was achieved, injection needle of 18 G was inserted at the periphery of marked site with bevel facing upward. The needle was advanced till the tip of it was resting directly beneath the scar at the dermal-subcutaneous junction and parallel to surface of the skin. Once in position, the needle was swept to and fro from one side to the other through the scar to break the fibrous bands until no resistance is felt. A snapping sound was heard as bands were broken. The needle was removed and skin squeezed circumferentially around the exit point to evacuate excess blood and prevent large hematoma formation. Small hematoma was allowed to form to support the released scar. Hemostasis was achieved with pressure and ice application. Topical antibiotics were applied after hemostasis. The subcision was repeated every 4 weeks for a total of three sittings in all study subjects.

Microneedling

Topical eutectic mixture of local anesthetics (EMLA) cream was applied under occlusion to affected area for 60 min prior to the procedure. After achieving anesthesia skin was disinfected.

Microneedling was done by roller device with 1.5 mm long needles. Roller device had 192 needles arranged in 8 rows of 24 needles each. The skin was stretched and then the roller device was moved over the entire affected area in four directions (vertical, horizontal, diagonal right and left). The endpoint was uniform pinpoint bleeding distributed evenly along the affected area. The face was then cleaned with normal saline and topical antibiotic cream was applied to face after serous oozing was stopped. The patient was advised to continue topical antibiotic for 3 days and photoprotection. The procedure was repeated every 4 weeks for total of three sittings.

Platelet rich plasma

Vacutainer containing acid citrate dextrose (ACD) solution was used for PRP preparation. Blood was collected using aseptic precautions and was immediately transferred into two vacutainers. They were gently rotated to mix the blood with the ACD solution. The vacutainers were put in the refrigerated centrifuges and 1st spin was given at 160 g for 10 min. The supernatant plasma and buffy coat were extracted from both the vacutainers with 18 G needle and transferred to another set of empty vacutainers. These vacutainers were subjected to the hard spin at 400 g for 10 min again. The platelets were seen precipitated at the bottom. The supernatant plasma was platelet-poor. Three-fourth of the supernatant plasma was aspirated and the platelets were re-suspended in the remaining volume of plasma by gently shaking to prepare the PRP. The PRP was activated by mixing it with calcium chloride in the ratio of 1:9 (CaCl2: PRP: 1:9). The affected area was anesthetized by topical EMLA cream and disinfected as above. Activated PRP was injected under the affected area by insulin syringe immediately after activating. Topical antibiotic cream was applied after the procedure and continued for 5 days.

Trichloroacetic acid peel

The test patch with 30% TCA in postauricular area was performed for each patient before being selected for procedure and those without any resultant hyper- or hypo-pigmentation of test area were selected for the procedure. All patients were primed before the procedure with depigmenting agents to prevent hyperpigmentation due to TCA. The face was degreased by spirit before the procedure.

The affected area was stretched by an assistant and then the 30% TCA peel was applied to the affected area by cotton applicator without using the force. The scarred area was completely covered systematically and the area was kept stretched till uniform white frosting appeared over the area. After the appearance of frosting, the face was washed, and ice packs were immediately applied to the treated area.

The patient was asked to maintain the strict photoprotection after the procedure to avoid posttreatment hyperpigmentation. The patient was prescribed topical moisturizer and sunscreen for use to prevent hyperpigmentation.

Clinical assessment

Clinical assessment of therapeutic outcome was performed as follows,

  1. The Goodman-Baron qualitative score assessment [Table 1] was done by treating physician at the start of the treatment and at 9 months after start of the treatment[7]
  2. Objective assessment of the result was done by the single appointed blinded dermatologist on the basis of photographs taken. Photographs were evaluated in a randomized fashion (before, during and after treatment, without labeling) to determine whether discernible clinical improvement has occurred. Improvement in the scars was assessed by the blinded observer at 2, 6, and 9 months after the start of treatment and scored in terms of % improvement as compared to baseline photograph. The value of percentage improvement obtained at 9 months was further classified into excellent (>75% improvement), very good (51%–75%), good (25%–50%), and poor (<25%) based on the quartile grading system.


Statistical analysis

The data were collected, entered, and analyzed using Statistical Package for the Social Sciences version 17 (SPSS Inc., Chicago, IL, USA). Quantitative data expressed as mean ± standard deviation while qualitative data expressed in counts or percentage. Chi-square, Wilcoxon's test, and post hoc Tukey's test have been performed to carry out P value. For all tests, P < 0.05 was suggestive of statistical significance.
Table 1: Goodman-Baron qualitative grading system for postacne scarring[7]

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  Results Top


Ninety-five patients of atrophic postacne scars who attended the dermatology outpatient department in study duration and fulfilled the inclusion criteria were included in the study. During the study, we made the following observations.

Males (57.89%, n = 55) outnumbered females (42.11%, n = 40) in our study while majority of the patients were in the 20–29 years of age group. The mean age of the study group was 23.42 ± 2.77 years.

The mean duration of scars was 2.52 ± 1.37 years. When measured with Goodman-Baron qualitative scoring 70.52% (n = 67) of patients had Grade 4 scarring, 27.36% (n = 26) had Grade 3 scarring while 2.1% (n = 2) had Grade 2 scarring.

Out of a total of 95 patients recruited, 82 patients completed the study till the end. A total of 13 patients dropped out of the study at various stages. [Table 2] demonstrates the drop out timings of patients of various study groups. Data of all patients was included in analysis as intention to treat.
Table 2: Dropout rate of patients in various study groups over the study duration

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[Table 3] demonstrates the clinical data and distribution of variables among study groups.
Table 3: Clinical data of patients and distribution of variables across study groups

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As shown in [Table 3], variables which were likely to influence the final outcome such as types of scars and number of scars were equally distributed among study groups.

[Table 4] shows the mean percentage improvement rates in study groups at 2 months, 6 months and 9 months as assessed by independent blinded observer. [Figure 1], [Figure 2], [Figure 3], [Figure 4] demonstrate the gradual improvement witnessed in study subjects in various study groups.
Table 4: Mean improvement rates in study groups at the interval of 2, 6, and 9 months as assessed by independent blinded observer

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Figure 1: Subcision alone group patient showing serial improvement. Baseline (A, A'), 2 months (B, B'), 9 months (C, C')

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Figure 2: Subcision plus microneedling group patient showing serial improvement. Baseline (A, A'), 2 months (B, B'), 9 months (C, C')

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Figure 3: Subcision plus PRP group patient showing serial improvement. Baseline (A, A'), 2 months (B, B'), 9 months (C, C')

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Figure 4: Subcision plus TCA peel group patient showing serial improvement. Baseline (A, A'), 2 months (B, B'), 9 months (C, C')

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At the end of 9 months, (S + M) group showed maximum (64.00% ± 12.354%) and subcision alone group showed the least response (36.62% ± 9.437%).

(S + P) group showed 48.00 ± 12.524% of improvement while (S + T) showed 49.95% ± 10.443% of response at the end of 9 months.

Among all groups, the difference in response at 2 months was not statistically significant but it became statistically significant at 6 months and above.

[Table 5] demonstrates the final response at 9 months quantified as per quartile scale for each group.
Table 5: Final improvement in various study groups as per quartile grading scale

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On comparing final outcomes among study groups [Table 6], we found that difference in final response among subcision alone versus rest all groups was statistically significant indicating all groups showed better response as compared to subcision alone group. This signifies that subcision alone gave inferior response than combination treatment.
Table 6: Comparison of final outcomes of all groups with each other

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Difference in the final response of S + T and S + P groups was statistically not significant (P > 0.05) indicating equal final response.

S + M group had statistically significant better (P < 0.05) response at the end of the study period when compared to rest all three groups. As said before, the S + M group had best mean improvement at the end of treatment. This signifies that subcision plus microneedling group had the best and statistically significant better response among our study groups.

[Table 7] shows mean Goodman-Baron qualitative scores in pre- and posttreatment periods. We observed decrease in mean Goodman-Baron qualitative score in all groups in posttreatment period when compared to pre-treatment period. In addition, the difference in mean scores in pre- and posttreatment periods in each group was statistically significant.
Table 7: Comparison of mean Goodman-Baron qualitative scores in pre- and posttreatment period of all study groups

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The percentage change in mean scores is maximum in S + M group while it is lowest in subcision alone group. In S + T and S + P groups, the change in scores is around of the same magnitude.

The most common side effect after subcision was postprocedure erythema, bruising and moderate edema in all patients. In all patients, it resolved in about 7–10 days. 9.47% patients (n = 9) developed small indurations in the treatment area during postprocedure period which were palpable but not visible. It resolved spontaneously in all patients in around 6 months. We did not observe any other complications besides this during the study period.

Posttreatment transient mild edema and erythema was observed in patients who underwent microneedling. It resolved in all patients in around 1 week. 13.04% (n = 3) patients from the same group also developed posttreatment hyperpigmentation. It resolved in 6 weeks in all with topical depigmenting agents.

Transient pain and bruising at the site of injection was observed in all patients of PRP which subsided in 72 h in all patients. All patients in our study complained of burning sensation at local site after injecting plasma which subsided in 24 h.

In TCA peeling erythema and postpeel exfoliation was seen in all patients in 1st week. 16% (n = 4) patients from this group experienced postpeel hyperpigmentation which cleared within 4 weeks in all.

All our patients tolerated various procedures very well without any remarkable complication.


  Discussion Top


Many studies are available in the literature evaluating single or multiple modalities at a time. Each study differs in methodology, duration, manner of use of modalities and assessment methods used for evaluation. To the best of our knowledge, there is no single study available in literature which compares plethora of modalities using the same assessment method in single study frame.

This study will help to get an idea regarding comparative efficacy of various modalities by removing various confounding factors.

In Group I (S), we received mean response rate 36.62 ± 9.437% end of 9 months.

Aalami Harandi et al. conducted a study with two groups of patients. First group of patients underwent suction treatment with microdermabrasion machine post subcision in scheduled way while second group underwent subcision followed by irregular suction.[8] This second group showed mean improvement 43.75% as per investigators and this finding is comparable to our study as mean improvement in our study was 36.62% ± 9.437%.

In a study by Balighi et al. 70% of patients undergoing subcision showed 26%–50% final improvement and 20% showed 51%–75% improvement in scars. In our study, 85.7% of patients showed 26%–50% and 4.8% showed 51%–75% final improvement.[9] None of our studies could demonstrate patient with improvement beyond 75% by subcision alone.

In Group II (S + M), the final therapeutic response was 64.00% ± 12.354%.

El-Domyati et al. conducted a study with six sittings of microneedling alone.[10] Improvement in appearance of postacne scars in terms of percentage was recorded as 51%–60%. In our study final therapeutic response was 64.00% ± 12.35% which was more than the above study.

Dogra et al. studied the response of microneedling alone. The response was measured on quartile scale and all patients had >40% improvement while majority of patients showed 50%–75% improvement. In our study also 100% of patients demonstrated >40% improvement while majority of patients (50%) showed 51%–75% improvement. Furthermore, 25% of patients showed excellent (>75%) improvement.[11]

Compared to both the above studies, slightly better results in current study can be attributed to usage of combination of modalities by us. While in above studies authors have only used single modality for treatment.

In Group III (S + P) we observed the response of 48% ± 12.524% at the end of treatment.

Gulanikar and Vidholkar carried out a study about the efficacy of PRP in acne scars.[12] Authors only used 6 sittings PRP 1 month apart. For evaluation they used scoring system similar to the one used by Lee et al.[13]

Nofal et al. studied the effects of PRP on acne scars where authors carried out 3 sittings of PRP for acne scars. The final results were assessed by quartile scale.[14]

[Table 8] demonstrates the comparison of findings of our study with findings of both the above studies using a similar scale.
Table 8: Comparison of findings of the current study with findings of a study by Gulanikar and Vidholkar[12] and Nofal et al.[14]

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As shown in [Table 8], All patients in our study have shown at least 25% improvement and 5% of patients had shown >40% improvement. Comparatively better results in our study can be attributed to subcision carried out by us prior to PRP treatment while in other studies authors have only used PRP.

In a study by Deshmukh and Belgaumkar investigators carried out split face study where one side was subjected to only subcision and another side underwent subcision and PRP for 4 sittings. They noticed 32.08% improvement in Goodman Baron Qualitative grade on a side of combination treatment. In our study, we noticed 28.17% improvement in S + P group. However, in our study procedures of subcision and PRP were sequential while in the above study they were performed in the same sitting. How this affects the final response will need further studies.[15]

We observed that out of all scars rolling and box scars responded well, while ice pick scars responded poorly. Well noted effectiveness of PRP in facial rejuvenation in literature[16] was also observed by us. Our patients reported the improvement in the appearance postprocedure and this can be utilized while considering the therapy for acne scars in individual patients.

At present, there are few studies available in literature which analyzes the effect of PRP therapy for acne scars. In addition, there is no unanimity about how to prepare PRP, method of administration, schedule of treatment.

In Group IV (S + T) of our study 49.95 ± 10.443 was the final improvement.

Tahera et al. carried out study of phenol peeling versus microneedling plus 20% TCA peel. They found out mean clinical improvement in microneedling plus TCA peel group was 69.43% ± 13.17% as was assessed by clinical appearance of scars pre- and post-treatment. Mean improvement in our patient as assessed by blinded observer was 51.50% ± 10.40%. However, in this study, authors have used microneedling immediately followed up with TCA peeling in the same sitting.[17]


  Conclusion Top


The response obtained by combining modalities was greater than any sole modality of treatment.

Subcision alone group showed the least response at the end of the study period.

Subcision plus microneedling showed the best response among all groups. This response was statistically significant than response achieved in all other groups.

When combined with subcision, PRP is comparably effective with 30% TCA peel for the treatment of acne scars and can be additional tool in the armamentarium of a dermatologist for acne scar treatment.

Limitations of study

The study duration is only 9 months which should be longer as scar maturation and neocollagenesis due to scar revision is prolonged process and 9 months may not be sufficient to observe the final response.

While evaluating the response only global improvement was considered. The response of each individual scar type to particular procedure was observed but not documented owing to scope of the study.

The sample size is relatively smaller for individual group.

PRP therapy is not yet fully standardized, and there are many variations in the method of preparation, administration, and schedule described by various authors.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Layton AM, Henderson CA, Cunliffe WJ. A clinical evaluation of acne scarring and its incidence. Clin Exp Dermatol 1994;19:303-8.  Back to cited text no. 1
    
2.
Chuah SY, Goh CL. The impact of post-acne scars on the quality of life among young adults in Singapore. J Cutan Aesthet Surg 2015;8:153-8.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Goodman GJ, Van Den Broek A. The modified tower vertical filler technique for the treatment of post-acne scarring. Australas J Dermatol 2016;57:19-23.  Back to cited text no. 3
    
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Sánchez Viera M. Management of acne scars: Fulfilling our duty of care for patients. Br J Dermatol 2015;172 Suppl 1:47-51.  Back to cited text no. 4
    
5.
Savant S. Pitted facial scar revision. In: Savant SS, editor. Textbook of Dermatosurgery & Cosmetology. 2nd ed. Mumbai: Association of Scientific Cosmetologists and Dermatosurgeons; 2005. p. 210.  Back to cited text no. 5
    
6.
Salim T, Ghiya R. Surgical management of acne scars. In: Venkataram M, editor. ACS(I) Textbook on Cutaneous and Aesthetic Surgery. 1st ed. New Delhi: Jaypee Brothers Medical Publishers; 2012. p. 395.  Back to cited text no. 6
    
7.
Goodman GJ, Baron JA. Postacne scarring: A qualitative global scarring grading system. Dermatol Surg 2006;32:1458-66.  Back to cited text no. 7
    
8.
Aalami Harandi S, Balighi K, Lajevardi V, Akbari E. Subcision-suction method: A new successful combination therapy in treatment of atrophic acne scars and other depressed scars. J Eur Acad Dermatol Venereol 2011;25:92-9.  Back to cited text no. 8
    
9.
Balighi K, Robati RM, Moslehi H, Robati AM. Subcision in acne scar with and without subdermal implant: A clinical trial. J Eur Acad Dermatol Venereol 2008;22:707-11.  Back to cited text no. 9
    
10.
El-Domyati M, Barakat M, Awad S, Medhat W, El-Fakahany H, Farag H. Multiple microneedling sessions for minimally invasive facial rejuvenation: An objective assessment. Int J Dermatol 2015;54:1361-9.  Back to cited text no. 10
    
11.
Dogra S, Yadav S, Sarangal R. Microneedling for acne scars in Asian skin type: An effective low cost treatment modality. J Cosmet Dermatol 2014;13:180-7.  Back to cited text no. 11
    
12.
Gulanikar AD, Vidholkar R. Efficacy of platelet-rich plasma in acne scars. Clin Dermatol Rev 2019;3:109-4.  Back to cited text no. 12
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13.
Lee JW, Kim BJ, Kim MN, Mun SK. The efficacy of autologous platelet rich plasma combined with ablative carbon dioxide fractional resurfacing for acne scars: A simultaneous split-face trial. Dermatol Surg 2011;37:931-8.  Back to cited text no. 13
    
14.
Nofal E, Helmy A, Nofal A, Alakad R, Nasr M. Platelet-rich plasma versus CROSS technique with 100% trichloroacetic acid versus combined skin needling and platelet rich plasma in the treatment of atrophic acne scars: A comparative study. Dermatol Surg 2014;40:864-73.  Back to cited text no. 14
    
15.
Deshmukh NS, Belgaumkar VA. Platelet-rich plasma augments subcision in atrophic acne scars: A split-face comparative study. Dermatol Surg 2019;45:90-8.  Back to cited text no. 15
    
16.
Redaelli A, Romano D, Marcianó A. Face and neck revitalization with platelet-rich plasma (PRP): Clinical outcome in a series of 23 consecutively treated patients. J Drugs Dermatol 2010;9:466-72.  Back to cited text no. 16
    
17.
Leheta TM, Abdel Hay RM, El Garem YF. Deep peeling using phenol versus percutaneous collagen induction combined with trichloroacetic acid 20% in atrophic post-acne scars; A randomized controlled trial. J Dermatolog Treat 2014;25:130-6.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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