Dermal Fillers in the Treatment of Acne Scars: A Review

Abstract

Acne vulgaris (AV) is the eighth most common disease in the world. This condition can impair the affected patients’ social and psychological functioning and lower their quality of life. In general, scar reduction, rather than complete scar removal, is the aim of AV treatment. Dermal abrasion, chemical peeling, laser resurfacing, subcision, punch methods, tissue-improving substances, and dermal fillers are the currently available therapeutic options. In this study, we focused on the rapidly developing field of dermal fillers used alone or in combination with other therapies to reconstruct skin affected by acne scars and to evaluate the improvement of facial appearance after using different types of dermal fillers.

INTRODUCTION

Acne vulgaris (AV) is the eighth most common disease in the world. Over 10% of the population are affected by AV, with the highest prevalence in adolescents¹. Among adolescents, the prevalence is up to 85%², while up to 12% of adults are affected³,⁴. In all ethnic groups, AV affects more than 90% of men and 80% of women⁵,⁶. Despite this, acne is neither physically dangerous nor life-threatening, but it can impair patients’ social and psychological functioning and lower their quality of life (QOL). Moderate to severe acne lesions may leave atrophic scars or post-inflammatory hyperpigmentation that can impair a patient’s QOL, lower self-esteem, and reduce social interactions⁷. Up to 95% of acne patients experience scarring as a typical long-term side effect, most frequently on the face⁸. The majority of acne scars are atrophic or marked by tissue loss. Although these lesions are typically divided into icepick, boxcar, rolling, keloidal, and hypertrophic scars, there is no universal agreement on the classification of atrophic scars⁹. Since there is no established standard of care in clinical practice, the treatment option must be customized for each patient.

Additionally, a combination of treatment approaches is typically necessary due to the variable nature of scarring among the patients in terms of both the scar types and the severity of the scars (as discussed in Sanchez Viera 2015)¹⁰. In general, scar reduction, rather than complete scar removal, is the aim of AV treatment¹¹. Dermal abrasion, chemical peeling, laser resurfacing, subcision, punch methods, tissue-improving substances, and dermal fillers are the currently available therapeutic options⁹,¹⁰,¹¹. In this study, we focused on the rapidly developing field of dermal fillers used alone or in combination with other therapies to reconstruct skin affected by acne scars and to evaluate the improvement of facial appearance after using different types of dermal fillers.

FILLER TYPES

Fillers can be categorized as either temporary (effects that endure for up to 18 months, with hyaluronic acid [HA] being one example), semi-permanent (results lasting for up to two years, with examples including calcium hydroxyapatite [CH] and poly-L-lactic acid [PLLA]), or long-lasting (effects lasting for more than three years, with examples including silicone, polymethylmethacrylate [PMMA], polyacrylamide, and polyalkylimide). Several techniques are used to inject the fillers, such as droplet injection, linear threading, fanning, or three-dimensional volumization. The augmentation of dermal and subcutaneous tissue scaffolding, as well as the acceleration and enhancement of collagen and tissue synthesis, are the postulated mechanisms of action of these fillers¹²,¹³. Despite their use in the past, human-, bovine-, and porcine-collagen-based fillers have been replaced by longer-lasting alternatives due to their limited duration of action.

TEMPORARY FILLERS

Hyaluronic acid

HA is a temporary filler that was approved by the United States Food and Drug Administration (FDA) in 2003. It is a polysaccharide composed of repeating disaccharide units of N-acetylglucosamine and D-glucuronic acid¹⁴. Intradermal injections of HA fillers stimulate collagen synthesis by activating the dermal fibroblasts. They are commonly used to restore skin volume and improve the appearance of wrinkles and nasolabial folds¹⁵. There are multiple products containing HA fillers, and each has its own characteristics¹⁶. Seven studies have been performed to assess the effectiveness of different products containing HA fillers in the treatment acne scars, and all of them showed improvements in the appearance of acne scars, with no or minimal adverse events (AEs) (Table 1)¹⁷,¹⁸,¹⁹,²⁰,²¹,²²,²³. In the most recent publication by Mahamoud et al. (2020)²³, the study incorporated a considerably larger patient population in comparison to earlier studies investigating the employment of HA for the treatment of acne scars. This study involved 30 participants who underwent three sessions of full-face fractional CO₂ laser, accompanied by intradermal HA injections or platelet-rich plasma injections on each facial side. Subsequently, the patients were monitored for a period of four weeks following each session. A significant reduction in acne scar severity was observed on both sides of the face, utilizing qualitative and quantitative assessment tools. Minimal AEs were reported in a few patients such as postprocedural pain, erythema, and edema.

Table 1. Summary of studies conducted on the use of dermal fillers in the treatment of atrophic acne scars.

Study		Indication	Aim	No. of patients	Finding
HA (temporary)
	Mahamoud et al. (2020)23	Patients with acne scars received HA injections, or PRP injections, on each face's side for comparison. Brand name: Viscoderm.	Patients underwent three sessions of full-face fractional CO2 laser, immediately followed by intradermal HA injections or PRP injections on each side of the face with four weeks between sessions.	30	Using qualitative and quantitative Goodman and Baron, both sides had a significant reduction in the severity of acne scars. Collagen and elastic fiber content increased in both, but more in the PRP-treated side.
	Kim et al. (2019)22	HA pneumatic injections were given to Fitzpatrick skin types IV~V patients with acne scars. Brand name: Unial.	Patients underwent a single treatment session. Follow-ups were given 1 and 2 months after treatment.	10	The mean scar volume values were 0.964, 0.741, and 0.566 mm3, respectively, at baseline, one month, and two months after the injection. No adverse events were reported.
	Dierickx et al. (2018)21	HA fillers were used to treat patients with moderate to severe acne scars. Brand name: Restylane.	Patients received three sessions of HA filler four weeks apart. Results were assessed up to 36 weeks after treatment.	12	Scar severity has improved in most patients (67%). Patient satisfaction with the overall facial appearance and with the sensation and perception of the skin improved in most patients. Patients' self-esteem and self-confidence also improved. AEs were redness, swelling, bumps, pain, and bruising (all resolved in 2 weeks).
	Goodman and Van Den Broek (2016)20	HA fillers were used with the vertical modified tower technique. Brand name: Juvederm Voluma (Allergan).	Patients were treated twice with three months follow up after the second treatment.	5	The mean scar count reduced from 48.8 to 15.4 after the second session. The static objective grading scale demonstrated improvement from 3.2 prior to first treatment to 2.6 at the final review.
	Patel and Tevet (2015)19	HA pneumatic injections were given to patients who had Fitzpatrick skin types IV~V with acne scars. Brand name: Belotero Balance.	Patients received two sessions at 4-week intervals of pneumatic, needleless injections of crosslinked HA. Follow up were given three months later.	2	Patient 1: acne scar grade improved from 2 to 1. Patient 2: acne scar grade improved from 3 to 2. No AEs were reported.
	Halachmi et al. (2013)18	HA pneumatic injections were given to patients who had Fitzpatrick skin types IV~V with acne scars. Brand name: Unial.	20 mg/ml microinjections of HA were used, and follow-ups were given 1~2 months later, with one follow-up visit.	12	Immediate visual improvement was noticed in all scars. Pinpoint bleeding at the injection site was the only reported AE.
	Hasson and Romero (2010)17	HA fillers were used to treat facial atrophic scars caused by acne vulgaris, dog bites, piercing, basal cell carcinoma, and leishmaniasis. Brand name: Esthelis.	The injection technique was linear threading, serial puncture, or both. Follow-ups for assessment of the injection were given immediately, one week, and one month after the injection.	12	The authors assessed the results immediately, one week, and one month after the injection. 27% had moderate improvement, 57% had good improvement, and 17% had excellent improvement. Mild erythema was the only reported AE.
PLLA (semi-permanent)
	Sapra et al. (2015)25	PLLA injections were given for the treatment of atrophic acne rolling scar. Brand name: Sculptra.	Single-arm, unblinded, open-label phase 2 study. Patients received 3 to 4 sessions if needed at four weeks intervals—follow-ups are given after six months from the first session.	22	45.5% to 68.2% of patients reported excellent improvement using photographs. Subject treatment satisfaction scores increased by 44%. AEs included one patient with a non-visible, palpable nodule.
	Rkein et al. (2014)26	Ablative fractionated CO2 laser and topical PLLA immediately after to improve atrophic scars. Brand name: Sculptra.	An uncontrolled, prospective study. Most of the patients had only one treatment session with laser and PLLA. The follow-up duration was three months after the laser and PLLA.	19	Patients had 95% scar improvement with minimalAEs, such as mild pain, erythema, and edema. One patient developed an epidermal inclusion cyst.
	Sadick and Palmisano (2009)27	PLLA injections were given to a 60-year-old white woman who had previously been treated with CO2 laser resurfacing without improvement on acne scars. Brand name: Sculptra.	Seven sessions of PLLA were given to individual acne scars. The patient was followed up twice; the first was six months after the last session, and the second 14 months after the previous session.	1	The patient reported a good improvement with minimal swelling and bruising at injection sites lasting 5~7 days.
	Sadove (2009)28	PLLA to correct dermal fat loss in macular atrophic acne scarring Brand name: Newfill.	Both patients received three sessions over 12 weeks. The first follow-up was one year after the last session, and the second was four years after the previous session.	2	Both patients reported marked improvement with only minimal swelling and redness.
	Beer (2007)12	PLLA fillers were used to treat patients with moderate to severe acne scars. Brand name: Sculptra.	Single-center, open-label, prospective study with seven sessions of PLLA. Injections were given at 1-month intervals. Patients were followed up after each treatment session.	20	A noticeable reduction in acne scar size.
CH (semi-permanent)
	Goldberg et al. (2006)31	Use of CH in acne scars. Brand name: Radiesse	Open study. Subjects underwent 1~2 injection sessions. Follow up duration was 12 months.	10	Depressed acne scars responded to treatment, but no response from icepick scars. No significant AEs.
	Koren et al. (2019)32	Combination of CH and EBD in acne scars. Brand name: Radiesse	A single center retrospective study reviewed medical records of acne scar patients between 2013~2016 who were treated with one of four treatments: ablative fractional CO2 laser, a radiofrequency bipolar device, a 1,540 nm non-ablative fractional laser, and injection of CH.	352	Injection of CH-based fillers 2~4 weeks prior to the treatment with ablative fractional CO2 laser yields a better outcome and should be recommended for suitable patients.
PMMA (permanent)
	Joseph et al (2019)34	PMMA to treat acne scars over the entire face. Brand name: Bellafil	Open-label, multicenter, single-arm non-randomized study. Patients received two treatment sessions with one month in between. Patients were followed up for seven months.	42	Using the acne scar assessment scale (ASAS), lower face responders were 92% and 97% at the 4- and 7-month marks, respectively. Upper-face responders were 64% and 67% at the 4- and 7-month marks, respectively. Only two reported skin testing-related AEs, and no AEs were attributed to PMMA dermal filler.
	Karnik et al. (2014)39	Treatment of atrophic acne scars over the cheeks using PMMA dermal fillers. Brand name: Artefill.	A double-blind, multicenter, randomized controlled trial. Patients received two treatment sessions with six months of follow-up.	147	Using Acne Scar Rating Scale, PMMA treatment improved 91% of the treated scars. In contrast, the investigators reported improvement in only 76% of the scars treated with saline. AEs were minimal.
	Epstein and Spencer (2010)40	PMMA fillers were used for the treatment of atrophic acne scars. Brand name: Artefill.	Pilot study. Patients had only one injection session, with eight months of follow-up.	14	At the eight months mark, investigators reported that 96% of treated scars showed some improvement. No AEs were reported.
	Carvalho Costa et al. (2009)13	PMMA fillers were used to determine their efficacy and safety as a facial filler. Brand name: Artefill.	Patients had 1~4 sessions with a 2-month interval. They were followed up for up to 9 years, with follow-up visits at each session, at one month and six months, then yearly thereafter.	25*	Using physical examination and before-and-after photos at 1 and 6 months, then yearly to assess the improvement, more than 85% of subjects were satisfied with their results. Most patients experienced no AEs (80%), and mild, transient AEs were reported by 20% of patients.
Silicone (permanent)
	Barnett and Barnett (2005)42	Silicone liquid injections were used to assess the improvement of acne scars.	Monthly liquid silicone injections using a technique known as the microdroplet, multiple-injection approach. Patients were followed up for 30 years, with follow-up immediately and then at 10-, 15- and 30-years posttreatment.	5	Investigators noticed an improvement in acne scars with liquid silicone injection immediately after treatment, at 10, 15, and 30 years, although the improvement was not quantified. Only minor AEs were reported.

HA: hyaluronic acid, PLLA: poly-L-lactic acid, CH: calcium hydroxyapatite, EBD: energy-based device, PMMA: polymethylmethacrylate, AE: adverse event. ^*Total patient number with different diagnoses. Of those, 25 patients received PMMA dermal filler for atrophic acne scars.

SEMI-PERMANENT FILLERS (BIO-STIMULANTS)

Poly-L-lactic acid

PLLA is a semi-permanent filler that was approved for soft tissue augmentation in 1999. Currently, PLLA dermal filler is marketed under the brand name Sculptra. It is a synthetic biodegradable polymer that corrects volume loss by stimulating the fibroblasts and, therefore, collagen synthesis. The gradual effect of PLLA on dermal volume can last for up to 2~3 years from the time of treatment²⁴. Five studies have been conducted from 2007 to 2015 to assess the efficacy and safety of PLLA for acne scars, with sample sizes varying from 1 to 80 patient. All studies demonstrated positive outcomes in enhancing the appearance of atrophic acne scars, despite the considerable variability in the number of sessions each patient received, which ranged from one to seven sessions. Additionally, the follow-up intervals in these investigations varied, extending from three months to four years after the final treatment sessions. With regard to AEs, the majority of patients in these studies exhibited minimal or no AEs. Examples of the AEs reported in these articles include mild pain, erythema, edema, swelling, and bruising. In one case, a non-visible palpable nodule and an epidermal inclusion cyst were observed (Table 1)¹²,²⁵,²⁶,²⁷,²⁸.

Calcium hydroxylapatite

CH is a naturally occurring substance in the human body, especially in human bones and teeth. The injectable form is developed using uniform CH microspheres dissolved in an aqueous carboxymethylcellulose gel carrier. Since 2006, Radiesse has been the only FDA-approved CH filler²⁹. It provides long-lasting deep dermal and subdermal soft tissue augmentation, as it can instantly create significant changes in volume and replenish lost volume³⁰. In addition to their volumizing effects, CH fillers tend to stimulate neocollagenesis and, subsequently, tissue formation, and their effects can last for up to 18 months²⁹.

Although CH fillers are commonly used, only two studies have investigated their role in the treatment of atrophic acne scars, one of which was a clinical trial that showed a beneficial effect and improvement in all treated individuals after 12 months, with the exception of deep icepick scars³¹. A recent study was conducted in 2019 by Koren et al.³² supported the use of CH fillers followed by fractional ablative CO₂ laser treatment in separate treatment sessions, as these products yielded better cosmetic outcomes compared with the other evaluated modalities (Table 1).

PERMANENT FILLERS

Polymethylmethacrylate

PMMA is a synthetic, permanent filler that was approved for soft tissue augmentation in 2006³³. In December 2014, the FDA also approved its use for moderate to severe atrophic acne scars³⁴. Currently, collagen-PMMA dermal filler is marketed under the brand name Bellafil (Suneva Medical). This is the most recent formulation of collagen-PMMA, with its particles modified to obtain a diameter of 30 to 50 µm³⁵,³⁶. This diameter was shown to have a better tolerability and resulted in fewer cases of foreign body reactions³⁷. In contrast to other biological filler materials, PMMA contains a bovine collagen carrier as well as microsphere particles that cannot be metabolized. These residual particles stimulate the replacement of the bovine collagen carrier by autologous collagen, and the induction of autologous collagen production is a unique advantage of PMMA fillers³⁸.

Four studies have been conducted to determine the efficacy of PMMA dermal filler in the treatment of atrophic acne scars, and all showed positive outcomes (Table 1)¹³,³⁴,³⁹,⁴⁰. The most recent study was conducted in 2019 by Joseph et al.³⁴ where they used Bellafil^® for full-face acne scar treatment. Participants underwent two treatment sessions with a one-month interval, followed by a seven-month follow-up period. The researchers employed the Acne Scar Assessment Scale to objectively evaluate the treatment outcomes. Scars on the lower face demonstrated a more substantial improvement compared to those on the upper face. The authors reported no filler-related AEs in their study.

Silicone

In 1983, the use of liquid silicone injection as a treatment for atrophic acne scars was first attempted⁴¹, and since then, it has been used as an off-label filler substance⁴². Given its permanent nature, side effect profile, and the scarcity of data proving its safety, the FDA has not approved liquid silicone injections for tissue augmentation, regardless of the body site⁴³. To date, a single study has been conducted to assess the efficacy and safety of liquid silicone injections in the treatment of atrophic acne scars, studied over 30 years. The investigators concluded that the treatment was effective and safe. However, only five patients were included, and the improvement was based solely on a photographic evaluation, with no objective scale employed to quantify the improvement (Table 1)⁴².

Polyacrylamide and polyalkylimide

To this day, no research has substantiated the use of polyacrylamide and polyalkylimide in the treatment of atrophic acne scars (Table 1).

CONCLUSION

Today, an increasing number of patients are seeking medical solutions for their acne scars. Acne scarring is a prevalent and challenging pathology that leads to stress and anxiety. Dermatologists have used abrasion, chemical peeling, laser resurfacing, and subcision as therapeutic options, with varying degrees of efficacy. Although the use of fillers for facial tissue augmentation is widespread, their role in the management of acne scars is yet to be capitalized. Multiple studies have been conducted to assess the efficacy and safety of dermal fillers in the treatment of acne scars. While most of them were limited by a low number of participants, they all showed promising results, with no or minimal AEs. The continuation of such studies is critical in order to further ensure the efficacy and safety of dermal fillers in the management of acne scars and the development of appropriate therapeutic protocols.