dermal filler treatment for atrophic acne scarringPatrick Treacy presents the results of a study investigating the efficacy of dermal fillers in the treatment of atrophic acne scarring

Keywords calcium hydroxyapatite, hyaluronic acid, acne scars, dermal fillers

ABsTrACT Full titleProblems encountered using dermal fillers, particularly calcium hydroxylapatite, as a treatment in acne scarring.

ObjectivesThis article aims to establish the efficacy and safety profile of dermal fillers, especially calcium hydroxyapatite (CaHA) in the treatment of atrophic acne scars.

MethodsTwenty-seven subjects with differing degrees of atrophic

acne scarring were treated with the CaHA filler over a 12-month period. Thirteen patients were treated with low molecular weight cross-linked hyaluronic acid in a comparative study.

ResultsMost atrophic acne scars responded well to CaHA dermal filler treatment. Icepick scars were not treated. At 12-month evaluation, 22% of subjects showed a 75% improvement, while 48% showed a 50% improvement. This compared to an average 0% improvement for the hyaluronic acid cohort.

Eleven hyaluronic acid patients (85% of total) showed a 0–25% improvement in treated atrophic scars at 12 months.

ConclusionsDermal fillers, especially CaHA, can provide a safe and efficacious method of treating atrophic acne scars. This compound appears to provide a longer-lasting effect owing to volume replenishment and possible neocollagenesis. The efficacy of hyaluronic acid in repairing atrophic acne scars is not demonstrable.

dr PATriCK TreACy is Medical Director of Ailesbury Clinics Ltd and Ailesbury Hair Clinics Ltd; Chairman of the Irish Association of Cosmetic Doctors and Irish Regional Representative of the British Association of Cosmetic Doctors; European Medical Advisor to Network Lipolysis and the UK’s largest cosmetic website Consulting Rooms. He practices cosmetic medicine in his clinics in Dublin, Cork, London and the Middle East

email: ptreacy@gmail.com

Acne occurs in approximately 95% of 16–17-year-old boys and 84% of 16–17-year-old girls1. Although the condition usually

resolves by the mid-20s, 1% of men and 5% of women still bear the signs of moderately severe acne scarring at 40 years of age2. some studies show scarring of some degree may affect up to 95% of patients with acne3. The same study found that keloidal or hypertrophic truncal scarring were more common in men. This form of scarring is usually treated by using such measures as intralesional steroids, silicone sheeting, or vascular laser treatment. Atrophic scarring will often appear many years later, and can cause great distress in patients during their courtship years4. Affected patients report more social

inhibition, unhappiness, anxiety, and even suicidal thoughts as a result of their facial appearance5.

BackgroundFor many years different treatment modalities have been used for the revision of atrophic acne scarring, with varying degrees of success. Many controlled trials have demonstrated that moderate to severe atrophic acne scars can be safely improved through ablative fractional CO

2 laser

resurfacing (fractional laser skin resurfacing; FLSR)6. Although FLSR is still the most popular therapeutic modality for the correction of acne scars, it is not always effective in all types of atrophic lesions7 — the more common type of defects encountered after

Affected patients report more social inhibition, unhappiness, anxiety, and even suicidal thoughts as a result of their facial appearance.

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found in the human body as a constituent of bone and teeth. the CaHA microspheres (25–45 µ) are suspended in an aqueous carboxymethylcellulose carrier gel, composed of cellulose, glycerin, and sterile water. None of these materials should elicit a chronic inflammatory, infectious or immune response. Multiple clinical and

histologic studies have tended to document its safety, efficacy, and longevity in tissue17, 18.

By its very composition, CaHA is designed to provide immediate correction and long‑term biostimulatory neocollagenesis. Over time, the gel is absorbed, fibroblasts appear and the process of neocollagenesis begins, stimulating the gradual growth of the

patient’s own collagen. the carboxymethylcellulose gel carrier volumises the ‘lost’ space and acts as a replacement filler; the microspheres stimulate neocollagenesis so that, as the gel dissipates, the spheres anchor into the soft tissue. there, they serve as a scaffold for new collagen growth as early as 4 weeks post‑injection, and then continue for up to at least 12 months17, 18. CaHA is not permanent, however. the CaHA microspheres are metabolised into calcium and phosphate ions through normal metabolic processes over 24 months. CaHA will not promote osteogenesis in soft tissues, does not migrate, and does not obscure diagnostic x‑rays.

The use of dermal fillersAt the present time, the use of CaHA is approved by the Food and drug Administration (FdA) for the correction of moderate to severe facial wrinkles and folds19, 20. CaHA also gained prominence during the period in which dermal fillers were being used for antiretroviral‑induced facial lipoatrophy21, 22. It is known to cause persistent nodules in a small percentage of people, especially if it is injected into the vermillion border of the lips23. As many studies have established the biocompatibility and safety of CaHA in facial filling techniques21, the product has gained popularity in the US and europe for this indication, and more recently in the treatment of acne scarring24.

HA has been used in aesthetic medicine for a long time, and has an extended safety profile. In its natural

By its very composition, caHA is designed to provide immediate

correction and long-term biostimulatory neocollagenesis.

inflammatory acne. the use of higher energy levels might have improved the results, and also possibly induced significant adverse effects7. Over the past decade, non‑ablative laser resurfacing8–10, radiofrequency (RF)11, and microneedling12 have been shown to create some improvement in the appearance of these atrophic scars. A number of autologous and non‑autologous techniques attempting dermal and subcutaneous augmentation have been tried to improve the facial aesthetic appearance. the autologous methods have included dermal grafting, fat transfer13, 14, and implantation of autologous fibroblasts, such as Isolagen®15.

there has been interest in non‑autologous augmentation by way of injections of hyaluronic acid (HA), polymethylmethacrylate microspheres (PMMA), and calcium hydroxylapatite (CaHA)16, 17. CaHA, the main mineral component of Radiesse® (Merz Aesthetics, San Mateo, CA), is a synthetic analogue of the inorganic salt

Table 1 Four-point grading scale for acne scars

Grade 1 MacularErythematous, hyper-, or hypopigmented marks

Grade 2 Mild diseaseMild atrophy, can be covered with make-up of

facial hair

Grade 3 Moderate diseaseModerate scarring, not covered by make-up, but can

be flattened by manual stretching of the skin

Grade 4 Severe diseaseScarring not flattened with manual stretching

of the skin

Figure 2 17-year-old male patient (A, B, C) before

treatment with Radiesse, and (D, E) immediately

after treatment. 1.3 ml CaHA was used

Icepick

Skin surface

Scar edges

Fascia

Rolling Boxcar

Figure 1 Acne scar subtypes

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Bocouture® 4 units/0.1 ml powder for solution for injection. Active substance: Botulinum toxin type A (150 kD), free from complexing proteins. Prescription-only medicine! Qualitative and quantitative composition: One vial contains: 50 LD50 units of Botulinum toxin type A (150 kD), free from complexing proteins, Human albumin, Sucrose. Therapeutic indications: For temporary improvement in the appearance of moderate to severe vertical lines between the eyebrows seen at frown (glabellar frown lines) in adults below 65 years when the severity of these lines has an important psychological impact for the patient. Contraindications: Hypersensitivity to Botulinum neurotoxin type A or to any of the excipients, generalised disorders of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syndrome). Presence of infection or inflammation at the proposed injection site. Bocouture® should not be used during pregnancy unless clearly necessary. The use of Bocouture® during lactation cannot be recommended. Undesirable effects: Usually, undesirable effects are observed within the first week after treatment and are temporary in nature. Localised pain, tenderness, itching, swelling and/or haematoma can occur in conjunction with the injection. Temporary vasovagal reactions associated with pre-injection anxiety, such as syncope, circulatory problems, nausea or tinnitus, may occur. Common ( ≥ 1/100, < 1/10): headache, muscle disorders (elevation of eyebrow)sensation of heaviness. Uncommon (≥ 1/1,000, < 1/100): bronchitis, nasopharyngitis, influenza, depression, insomnia, facial paresis (brow ptosis), vasovagal syncope, eyelid oedema,

eyelid ptosis, blurred vision, tinnitus, nausea, pruritus, skin nodule, muscle twitching, muscle cramps, injection site reactions (bruising, pruritus), tenderness, influenza like illness, fatigue (tiredness). For adverse reactions reported with the comparator product containing conventional Botulinum toxin type A complex of equal potency see Summary of Product Characteristics. General: In rare cases, localised allergic reactions, such as swelling, oedema, erythema, pruritus or rash, have been r eported after treating vertical lines between the eyebrows (glabellar frown lines) and other indications. For undesirable effects when treating other indications with Botulinum toxins see Summary of Product Characteristics. Merz Pharmaceuticals GmbH, 60048 Frankfurt/Main, Germany, Phone: ++49-69/1503-1. Date of revision of the text: July 2010 (in Germany). Further information is provided in the Summary of Product Characteristics and in the Package Leaflet.

The little bottle that’s big on results

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skin surface and its sharp edges manoeuvred under the defect to make subcuticular cuts or ‘cisions’. the principle of this procedure is to break the fibrotic strands, which tether the scar to the underlying subcutaneous tissue. the depression is lifted by the releasing action of the procedure, as well as from connective tissue that forms during the course of normal wound healing28.

MethodsA series of 27 patients (17 male, 10 female; skin phototypes I–IV), with varying degrees of atrophic acne scarring, were treated in a single‑centre, prospective, controlled study over a 1‑year period. Patients were randomly selected on the basis that they did not want to present for laser resurfacing as a treatment for their problem. this

form HA has a short duration time in the tissue, owing to enzymatic degradation and free radical metabolisation. to avoid these effects, HA gel is modified through cross‑linking to form a water‑insoluble polymer hydrogel, more resistant to degradation, but with a similar biocompatibility as non‑modified HA. Based on the experience of other authors, many of the available HA preparations are too short‑lived (approximately 3–6 months24, 25 to appropriately treat moderate to severe acne scars) and use of such products for this purpose would require a significant total injection volume over time, with frequent re‑treatments, contributing to a greater total cost and time commitment for the patient.

More viscous forms of HA, such as Perlane® (Medicis Aesthetics, Inc., Scottsdale, AZ) or Juvéderm® VOLUMA (Allergan, Inc., Santa Barbara, CA), may be appropriate for patients with atrophic scars. the ideal filler for this purpose would be long‑lasting, biocompatible, and would not elicit further inflammation or granuloma formation in skin already damaged by acne26.

Soft tissue filler use for acne scarring would be an attractive option to most practitioners as they require little invasive technique and could be used in combination with other treatment modalities, such as microneedling or laser resurfacing. Although studies have shown that HA injections do stimulate collagen formation in the short term, this effect is probably more related to the physical act of injection, rather than to the HA itself.

Subcision is a term introduced by Orentreich and Orentreich27 to describe the minor surgical procedure for treating depressed acne scars and wrinkles, using a hypodermic needle inserted through a puncture in the

Figure 3 23-year-old female patient (A) during treatment with Radiesse, and (B) 2 weeks after treatment

soft tissue filler use for acne scarring would be an attractive option to most practitioners as they require little invasive technique.

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ad-Prime-1_1 Letter-1302v3 pva RZ.indd 1 19.02.13 10:38

meant the patients were enrolled sporadically, rather than entering the study at the same time. the subjects ranged in age from 16–63 years, and all acne scarring severity scores fell between 4 and 30 on the goodman system (Table 1). Patients were also evaluated using digital photography and an improvement graduation scale at each subsequent treatment visit, at 1, 3, 6, 12 and 24 months post‑procedurally:

■ 0 = no improvement ■ 1 = 0–25% improvement ■ 2 = 25–50% improvement ■ 3 = 50–75% improvement ■ 4 = 75–100% improvement ■ 5 = 100% improvement. Multiple acne scar grading classification systems of

varying complexities have been introduced. the most basic, practical system divides atrophic acne scars into three main types: icepick, rolling, and boxcar scars29 (Figure 1). It is common for patients to have more than one type of scar.

TreatmentSubscision of each atrophic scar was performed 1 week prior to injection with CaHA to give a more uniform aesthetic effect. Radiesse was injected using a 27 gauge needle into the space left after subscision of the acne scar in the region of the mid‑ to deep dermis, although final placement also depended on the presence of fibrous and cystic tissue in this region of the skin. the total volume of CaHA used varied with each patient, with an end‑point

Figure 5 26-year-old old male patient (A) before treatment with CaHA and (B) 4 weeks after treatment

Figure 4 23-year-old male patient (A) before treatment with Radiesse, and (B) 2 weeks after treatment

being agreed between patient and physician. It was decided not to record the amount of product used as this was not felt to be contributory to the final result. Histologic evaluation of cutaneous biopsies were not obtained before or during treatment, although it was offered to at least one of the patients who had a resultant adverse reaction. Betadine® cleansing was used in most patients and doxycycline 100 mg for 2 days was given as prophylaxis in 11 patients, who were felt to be at risk of infection as they still seemed to have active acne. One patient, who had a previous photoallergic reaction to doxycycline, was prescribed Augmentin‑duo twice daily for 2 days.

Subjects were not excluded from the study on the basis of bleeding disorders or whether they were taking anticoagulants/anti‑inflammatory agents, as it was felt that while the bruising may be unsightly, it would likely improve overall healing. Patients who had received synthetic collagen, HA, PMMA, CaHA, or autologous fibroblast injections to treated areas within the previous 6 months were excluded from the study. Clinical assessment scores were determined at each treatment session and follow‑up visit. Patient satisfaction surveys and digital photography were used where they were appropriate to both parties, although both were considered subjective, with patients tending to focus on the smallest detail and physicians photographically favouring the better results. All patients were reviewed at 2 or 4 weeks post‑treatment for a top‑up of Radiesse, if

required. It was noted that 17 patients required a top‑up of at least 0.15 ml CaHA at one of the first two visits. Smaller amounts (< 0.1 ml) were not recorded, as it was felt that the patient may have seen some defects under deeper scrutiny that were initially missed during the procedure.

A series of 13 patients (7 male, 6 female; skin phototypes I–IV) with varying degrees

of atrophic acne scarring were treated in a similar manner with low molecular weight cross‑linked HA, and monitored over a 12‑month period. Patients were randomly selected on the basis that they did not want to present for laser resurfacing as a treatment for their problem.

Resultstwenty‑seven patients entered this 12‑month study. Moderate to excellent clinical improvement was

subscision of each atrophic scar was

performed 1 week prior to injection with caHA to

give a more uniform aesthetic effect.

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observed after 4 weeks in almost all of the patients studied (20 patients with score 4, 75–100%; six patients with score 3, 50–75%). One patient had score 1, 0–25% improvement, while no subjects scored either 0 or 5. At the 6‑month assessment 12 patients (44% of total) had score 4 (75–100% improvement) and 11 patients (40%) had score 3 (50–75% ). At 12‑month evaluation, six patients (22%) showed 75% improvement; 14 patients (48%) showed between 50% improvement, and five patients (18%) showed a 25% improvement in treated atrophic scars.

thirteen patients entered the 12‑month HA study. Moderate‑to‑excellent clinical improvement was observed after the initial treatments in almost all of the HA patients studied At 4‑week assessment, nine patients still showed moderate‑to‑excellent results, but this had fallen off dramatically at 3‑month assessment: only two patients had score 4 (75–100% improvement) and two patients (23% of total) had score 3 (50–75% improvement). At 6‑month evaluation, 12 patients (92%) showed a 0–25% improvement.

the author felt both of the fillers initially provided a simple physical volumising effect. there was a longevity associated with the therapeutic effect of the calcium hydroxylapatite (CaHA), probably secondary to the duration of the filler and some level of neocollagenesis noted in other studies. there was little evidence of delayed biostimulatory effect of collagen formation owing to HA injections, although the physical act of injection and subcision was of some benefit to the patient.

Side‑effects of treatment were mostly limited in the group to mild transient erythema, bruising or localised oedema. Some patients required top‑up or remodelling on initial review. One 23‑year‑old male patient (skin type

References1. Burton JL, Cunliffe WJ, Stafford I, Shuster S. The prevalence of acne vulgaris in adolescence. Br J Dermatol 1971; 85 (2): 119–262. Cunliffe WJ. The acnes. London: Dunitz, 19893. Layton AM, Henderson CA, Cunliffe WJ. A clinical evaluation of acne scarring and its incidence. Clin Exp Dermatol 1994; 19(4): 303–8 4. Wu SF, Kinder BN, Trunnell TN, Fulton JE. Role of anxiety and anger in acne patients: a relationship with the severity of the disorder. J Am Acad Dermatol 1988; 18(2 Pt 1): 325–33 5. Cotterill JA, Cunliffe WJ. Suicide in dermatological patients. Br J Dermatol 1997; 137(2): 246–50 6. Omi T, Kawana S, Sato S, Bonan P, Naito Z. Fractional CO2 laser for the treatment of acne scars. J Cosmet Dermatol 2011; 10(4): 294–3007. Hedelund L, Haak CS, Togsverd-Bo K, Bogh MK, Bjerring P, Hædersdal M. Fractional CO2 laser resurfacing for atrophic acne scars: a randomized controlled trial with blinded response evaluation. Lasers Surg Med 2012; 44(6): 447–528. Seaton ED, Mouser PE, Charakida A, Alam S, Seldon PM, Chu AC. Investigation of the mechanism of action of nonablative pulsed-dye laser therapy in

photorejuvenation and inflammatory acne vulgaris. Br J Dermatol 2006; 155(4): 748–559. Nouri K, Rivas MP, Bouzari N, Faghih S. Nonablative lasers. J Cosmet Dermatol 2006; 5(2): 107–1410. Bellew SG, Lee C, Weiss MA, Weiss RA. Improvement of atrophic acne scars with a 1,320 nm Nd:YAG laser: retrospective study. Dermatol Surg 2005; 31(9 Pt 2): 1218–2111. Prieto VG, Zhang PS, Sadick NS. Evaluation of pulsed light and radiofrequency combined for the treatment of acne vulgaris with histologic analysis of facial skin biopsies J Cosmet Laser Ther 2005; 7(2): 63–812. Majid I. Microneedling therapy in atrophic facial scars: an objective assessment. J Cutan Aesthet Surg 2009; 2(1): 26–3013. Coleman WP Lipocytic dermal augmentation. In: Klein AW. ed, Tissue augmentation in clinical practice. Procedures and techniques. New York: Marcel Dekker, 1998: 49–62 14. Coleman SR. Long-term survival of fat transplants: controlled demonstrations. Aesthetic Plast Surg 1995; 19(5): 421–5 15. Chu A, et al. A pilot study to assess the efficacy of Isolagen (autologous fibroblasts) treatment in acne scarring. Br J Dermatol 2006

16. Tzikas TL. Evaluation of the Radiance FN soft tissue filler for facial soft tissue augmentation Arch Facial Plast Surg 2004; 6(4): 234–917. Marmur ES, Phelps R, Goldberg DJ. Clinical, histologic and electron microscopic findings after injection of a calcium hydroxyapatite filler. J Cosmet Laser Ther 2004; 6(4): 223–618. Godin MS, Majmundar MV, Chrzanowski DS, Dodson KM. Use of radiesse in combination with restylane for facial augmentation Arch Facial Plast Surg 2006; 8(2): 92–719. Goldberg DJ. Fillers in Cosmetic Dermatology. Abingdon, Oxon, UK: Informa, 200620. Roy D, Sadick N, Mangat D. Clinical trial of a novel filler material for soft tissue augmentation of the face containing synthetic calcium hydroxylapatite microspheres. Dermatol Surg 2006; 32(9): 1134–921. Comite SL, Liu JF, Balasubramanian S, Christian MA. Treatment of HIV-associated facial lipoatrophy with Radiance FN (Radiesse). Dermatol Online J 2004; 10(2): 2 22. Treacy PJ, Goldberg DJ. Use of a biopolymer polyalkylimide filler for facial lipodystrophy in HIV-positive patients

undergoing treatment with antiretroviral drugs. Dermatol Surg 2006; 32(6): 804–823. Product used to enlarge lips can cause bumps. Bioform does not recommend using this product on the red portion of lips. click2houston.com24. Goldberg DJ, Snehal A, Hussain M. Acne scar correction using calcium hydroxylapatite in a carrier-based gel. J Cosmet Laser Ther 2006; 8(3): 134–625. Alam M, Dover JS. Treatment of acne scarring. Skin Therapy Lett 2006; 11(10): 7–9 26. Buck DW 2nd, Alam M, Kim JY. Injectable fillers for facial rejuvenation: a review. J Plast Reconstr Aesthet Surg 2009; 62(1): 11–827. Orentreich DS, Orentreich N. Subcutaneous incisionless (subcision) surgery for the correction of depressed scars and wrinkles. Dermatol Surg 1995; 21(6): 543–928. Chandrashekar BS, Nandini A. Acne scar subcision J Cutan Aesthet Surg 2010; 3(2): 125–629. Goodman GJ, Baron JA. Postacne scarring – a quantitative global scarring grading system. J Cosmet Dermatol 2006; 5(1): 48–52

4, of Asian origin) with minimally active acne on a previous trial developed cellulitis and later desquamation.

Discussionthere are many methods that can be used in the treatment of atrophic acne scarring. Most tend to replace the volume lost by the atrophic effects of the acne. Newer injectable fillers are biocompatible and safer, and can provide an alternative means of treating acne scarring in patients not opting for laser resurfacing. the author has used the HA‑based filler Matridex® (BioPolymer gmbH & Co., germany), CaHA, and the polyalkylimide Bio‑Alcamid® (Polymekon, Brindisi, Italy) for this purpose over the years. Some of these fillers simply provide a physical filling effect, while others induce a delayed collagen stimulatory effect (e.g. CaHA and poly‑L‑lactic acid). An ideal filling agent should restore atrophic volume and stimulate the dermis to synthesise new collagen for a long‑lasting effect.

Based on the experience of this study, the author feels CaHA is a suitable product for this purpose, showing a clearly demonstrable benefit still present at 6–12 months. A comparative study performed with HA preparations showed the compound was not of medical or commercial benefit to either the physician or patient, with most of the product disappearing at only 6–12 weeks. More viscous forms of HA, such as HyaCorp® (BioScience gmbH, germany) showed no extra benefit.

ConclusionsCaHA is biosynthetically produced and does not elicit a chronic inflammatory or immune response. In vivo and in vitro studies have established the biocompatibility and safety of CaHA. No evidence of granuloma formation, ossification, or foreign body reactions have been found in long‑term animal studies. CaHA implants have persisted intact at the injection site in areas such as the face at up to

Key points

■ Although fractional laser skin resurfacing is still the most popular therapeutic modality for the correction of acne scars, it is not always effective in all types of atrophic lesions

■ Soft tissue filler use for acne scarring would be an attractive option to most practitioners, as they require little invasive technique and could be used in combination with other modalities, such as microneedling or laser resurfacing

■ Many studies have established the biocompatibility and safety of CaHA in facial filling techniques. The product has gained popularity in the US and Europe for this indication, and more recently in the treatment of acne scarring

■ This study documents the efficacy of CaHA in the treatment of atrophic acne scars. The author is aware that these benefits may last 18 months or more

caHA is biosynthetically

produced and does not elicit

a chronic inflammatory

or immune response.

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Figure 7 Improvement rates in patient cohort treatment with HAFigure 6 Improvement rates in patient cohort treatment with CaHA

12–18 months. No skin testing is required for the compound as company information states that no animal or animal products are used in the manufacture of the product, thus there is no risk of transmitting disease or causing allergic reactions in patients who are sensitive to common foods.

this study documents the efficacy of CaHA in the treatment of atrophic acne scars. the author is aware that these benefits may last 18 months or more.

Declaration of interest None Figures 2–7 ©Patrick Treacy Patrick Treacy will present on the DUBLiN Lift at AMWC 2013: 16.30, Friday 5 April, Room Van Dongen

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