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| dermatology | peer-review



dermal filler
treatment
For atrophic
acne scarring
Patrick Treacy presents the results of a study
investigating the efficacy of dermal fillers in the
treatment of atrophic acne scarring
ABSTRACT                             acne scarring were treated with   Eleven hyaluronic acid patients
Full title                           the CaHA filler over a 12‑month   (85% of total) showed a 0–25%
Problems encountered using           period. Thirteen patients were    improvement in treated
dermal fillers, particularly         treated with low molecular        atrophic scars at 12 months.
calcium hydroxylapatite, as a        weight cross-linked hyaluronic
treatment in acne scarring.          acid in a comparative study.      Conclusions
                                                                       Dermal fillers, especially
Objectives                           Results                           CaHA, can provide a safe and
This article aims to establish       Most atrophic acne scars          efficacious method of treating
the efficacy and safety profile of   responded well to CaHA dermal     atrophic acne scars. This
dermal fillers, especially calcium   filler treatment. Icepick scars   compound appears to provide
hydroxyapatite (CaHA) in the         were not treated. At 12-month     a longer-lasting effect owing
treatment of atrophic acne           evaluation, 22% of subjects       to volume replenishment and
scars.                               showed a 75% improvement,         possible neocollagenesis. The                      Dr Patrick Treacy is
                                     while 48% showed a 50%            efficacy of hyaluronic acid in                     Medical Director of Ailesbury
Methods                              improvement. This compared        repairing atrophic acne scars is                   Clinics Ltd and Ailesbury Hair
Twenty-seven subjects with           to an average 0% improvement      not demonstrable.                                  Clinics Ltd; Chairman of the
differing degrees of atrophic        for the hyaluronic acid cohort.                                                      Irish Association of Cosmetic
                                                                                                                          Doctors and Irish Regional




A
                                                                                                                          Representative of the British
                                                                                                                          Association of Cosmetic
                 cne       occurs      in             inhibition, unhappiness, anxiety, and                               Doctors; European Medical
                 approximately 95% of                 even suicidal thoughts as a result of their                         Advisor to Network Lipolysis
                 16–17-year-old boys and              facial appearance5.                                                 and the UK’s largest cosmetic
                                                                                                                          website Consulting Rooms. He
                 84% of 16–17-year-old                                                                                    practices cosmetic medicine
                 girls1. Although the                 Background                                                          in his clinics in Dublin, Cork,
                                                                                                                          London and the Middle East
                 condition        usually             For many years different treatment
resolves by the mid‑20s, 1% of men and                modalities have been used for the revision                          email: ptreacy@gmail.com
5% of women still bear the signs of                   of atrophic acne scarring, with varying
moderately severe acne scarring at                    degrees of success. Many
40  years of age2. Some studies show                  controlled       trials       have
                                                                                                Affected
scarring of some degree may affect up to              demonstrated that moderate to
95% of patients with acne3. The same                  severe atrophic acne scars can      patients report more
study found that keloidal or hypertrophic             be safely improved through social inhibition,
truncal scarring were more common in                  ablative fractional CO2 laser unhappiness,
men. This form of scarring is usually                 resurfacing (fractional laser skin
treated by using such measures as                     resurfacing; FLSR)6. Although
                                                                                          anxiety, and even
intralesional steroids, silicone sheeting,            FLSR is still the most popular suicidal thoughts as
or vascular laser treatment. Atrophic                 therapeutic modality for the a result of their facial
scarring will often appear many years                 correction of acne scars, it is not
                                                                                          appearance.                     Keywords
later, and can cause great distress in                always effective in all types of
                                                                                                                          calcium hydroxyapatite,
patients during their courtship years4.               atrophic lesions  — the more common
                                                                         7
                                                                                                                          hyaluronic acid, acne scars,
Affected patients report more social                  type of defects encountered after                                   dermal fillers



                                                                                                          prime-journal.com | March 2013

                                                                                                                                                         ❚   41
peer-review | dermatology                            |

     Table 1 Four-point grading
     scale for acne scars
                                                             Figure 1 Acne scar subtypes
                    Grade 1 Macular                                  Icepick                         Rolling                       Boxcar
     Erythematous, hyper-, or hypopigmented marks
                                                                                Skin surface
                     Grade 2 Mild disease
         Mild atrophy, can be covered with make-up of
                           facial hair

              Grade 3 Moderate disease
   Moderate scarring, not covered by make-up, but can                                                              Scar edges
     be flattened by manual stretching of the skin

                   Grade 4 Severe disease
         Scarring not flattened with manual stretching                                                                                         Fascia
                            of the skin



   inflammatory acne. The use of higher energy levels                            found in the human body as a constituent of bone and
might have improved the results, and also possibly                               teeth. The CaHA microspheres (25–45 µ) are suspended
induced significant adverse effects7. Over the past decade,                      in an aqueous carboxymethylcellulose carrier gel,
non-ablative laser resurfacing8–10, radiofrequency (RF)11,                       composed of cellulose, glycerin, and sterile water. None
and microneedling12 have been shown to create some                               of these materials should elicit a chronic inflammatory,
improvement in the appearance of these atrophic scars. A                         infectious or immune response. Multiple clinical and
number of autologous and non-                                                                   histologic studies have tended to document
autologous        techniques   attempting                                                       its safety, efficacy, and longevity in tissue17, 18.
dermal and subcutaneous augmentation
                                                      By its very composition, CaHA is             By its very composition, CaHA is designed
have been tried to improve the facial               designed to provide immediate               to provide immediate correction and
aesthetic appearance. The autologous                    correction and long‑term                long‑term biostimulatory neocollagenesis.
methods have included dermal grafting,                                                          Over time, the gel is absorbed, fibroblasts
                                                biostimulatory neocollagenesis.
fat transfer13, 14, and implantation of                                                         appear and the process of neocollagenesis
autologous fibroblasts, such as Isolagen®15.                                                    begins, stimulating the gradual growth of the
   There has been interest in non-autologous                                     patient’s own collagen. The carboxymethylcellulose gel
augmentation by way of injections of hyaluronic acid                             carrier volumises the ‘lost’ space and acts as a replacement
(HA), polymethylmethacrylate microspheres (PMMA),                                filler; the microspheres stimulate neocollagenesis so that,
and calcium hydroxylapatite (CaHA)16, 17. CaHA, the main                         as the gel dissipates, the spheres anchor into the soft
mineral component of Radiesse® (Merz Aesthetics, San                             tissue. There, they serve as a scaffold for new collagen
Mateo, CA), is a synthetic analogue of the inorganic salt                        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 fillers
                                                                                                At 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
                                                                  Figure 2 17-year-old male     of CaHA in facial filling techniques21, the product has
                                                                     patient (A, B, C) before   gained popularity in the US and Europe for this indication,
                                                                  treatment with Radiesse,
                                                                    and (D, E) immediately
                                                                                                and more recently in the treatment of acne scarring24.
                                                                      after treatment. 1.3 ml      HA has been used in aesthetic medicine for a long
                                                                            CaHA was used       time, and has an extended safety profile. In its natural


42

     ❚   March 2013 | prime-journal.com


                                                                                                                                                               13021
| dermatology | peer-review


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




             form HA has a short duration time in the tissue, owing                                 skin surface and its sharp edges manoeuvred under the
          to enzymatic degradation and free radical metabolisation.                                 defect to make subcuticular cuts or ‘cisions’. The principle
          To avoid these effects, HA gel is modified through                                        of this procedure is to break the fibrotic strands, which
          cross‑linking to form a water-insoluble polymer hydrogel,                                 tether the scar to the underlying subcutaneous tissue.
          more resistant to degradation, but with a similar                                         The depression is lifted by the releasing action of the
          biocompatibility as non-modified HA. Based on the                                         procedure, as well as from connective tissue that forms
          experience of other authors, many of the available HA                                     during the course of normal wound healing28.
          preparations are too short-lived (approximately
          3–6 months24, 25 to appropriately treat moderate to severe                                Methods
          acne scars) and use of such products for this purpose                                     A series of 27 patients (17 male, 10 female; skin phototypes
          would require a significant total injection volume over                                   I–IV), with varying degrees of atrophic acne scarring,
          time, with frequent re-treatments, contributing to a          Figure 3 23-year-old        were treated in a single-centre, prospective, controlled
                                                                        female patient (A) during
          greater total cost and time commitment for the patient.       treatment with Radiesse,
                                                                                                    study over a 1-year period. Patients were randomly
              More viscous forms of HA, such as Perlane® (Medicis       and (B) 2 weeks after       selected on the basis that they did not want to present for
          Aesthetics, Inc., Scottsdale, AZ) or Juvéderm® Voluma         treatment                   laser resurfacing as a treatment for their problem. This
          (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




3 10:38
                                                                                                          prime-journal.com | March 2013

                                                                                                                                                         ❚   45
| dermatology | peer-review

                                                                                              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
   meant the patients were enrolled sporadically, rather                                      improve overall healing. Patients who had received
than entering the study at the same time. The subjects          Figure 4 23-year-old male     synthetic collagen, HA, PMMA, CaHA, or autologous
ranged in age from 16–63  years, and all acne scarring          patient (A) before treatment  fibroblast injections to treated areas within the previous 6
                                                                with Radiesse, and (B)
severity scores fell between 4 and 30 on the Goodman                                          months were excluded from the study. Clinical
                                                                2 weeks after treatment
system (Table  1). Patients were also evaluated using                                         assessment scores were determined at each treatment
digital photography and an improvement graduation                                             session and follow-up visit. Patient satisfaction surveys
scale at each subsequent treatment visit, at 1, 3, 6, 12 and                                  and digital photography were used where they were
24 months post-procedurally:                                                                  appropriate to both parties, although both were
■■ 0 = no improvement                                                                         considered subjective, with patients tending to focus on
■■ 1 = 0–25% improvement                                                                      the smallest detail and physicians photographically
■■ 2 = 25–50% improvement                                                                     favouring the better results. All patients were reviewed at
■■ 3 = 50–75% improvement                                                                     2 or 4 weeks post‑treatment for a top-up of Radiesse, if
■■ 4 = 75–100% improvement                                                                                     required. It was noted that 17 patients
■■ 5 = 100% improvement.                                                           Subscision of each required a top-up of at least 0.15 ml CaHA at
   Multiple acne scar grading classification systems of                              atrophic scar was one of the first two visits. Smaller amounts
varying complexities have been introduced. The most                   performed 1 week prior to (< 0.1 ml) were not recorded, as it was felt
basic, practical system divides atrophic acne scars into                                                       that the patient may have seen some
three main types: icepick, rolling, and boxcar scars29                      injection with CaHA to defects under deeper scrutiny that were
(Figure 1). It is common for patients to have more than one                     give a more uniform initially missed during the procedure.
type of scar.                                                                  aesthetic effect.                 A series of 13 patients (7 male, 6 female;
                                                                                                               skin phototypes I–IV) with varying degrees
Treatment                                                                                     of atrophic acne scarring were treated in a similar manner
Subscision of each atrophic scar was performed 1  week                                        with low molecular weight cross-linked HA, and monitored
prior to injection with CaHA to give a more uniform                                           over a 12‑month period. Patients were randomly selected
aesthetic effect. Radiesse was injected using a 27  gauge                                     on the basis that they did not want to present for laser
needle into the space left after subscision of the acne scar                                  resurfacing as a treatment for their problem.
in the region of the mid- to deep dermis, although final
                                                                Figure 5 26-year-old old
placement also depended on the presence of fibrous and          male patient (A) before
                                                                                                 Results
cystic tissue in this region of the skin. The total volume of   treatment with CaHA and          Twenty-seven patients entered this 12-month study.
CaHA used varied with each patient, with an end-point           (B) 4 weeks after treatment      Moderate to excellent clinical improvement was




                                                                                                        prime-journal.com | March 2013

                                                                                                                                                          ❚   47
peer-review | dermatology                                          |

observed after 4 weeks in almost all of the patients                                                                      4, of Asian origin) with minimally active acne on a
studied (20 patients with score 4, 75–100%; six patients                                Key points                        previous trial developed cellulitis and later
with score 3, 50–75%). One patient had score 1, 0–25%                                                                     desquamation.
improvement, while no subjects scored either 0 or 5. At                             n Although fractional
                                                                                    laser skin resurfacing is
the 6-month assessment 12 patients (44% of total) had                               still the most popular                Discussion
score 4 (75–100% improvement) and 11 patients (40%) had                             therapeutic modality                  There are many methods that can be used in the
score 3 (50–75% ). At 12-month evaluation, six patients                             for the correction of                 treatment of atrophic acne scarring. Most tend to
(22%) showed 75% improvement; 14 patients (48%) showed                              acne scars, it is not                 replace the volume lost by the atrophic effects of the
                                                                                    always effective in all
between 50% improvement, and five patients (18%)                                    types of atrophic
                                                                                                                          acne. Newer injectable fillers are biocompatible and
showed a 25% improvement in treated atrophic scars.                                 lesions                               safer, and can provide an alternative means of treating
   Thirteen patients entered the 12-month HA study.                                 n Soft tissue filler use              acne scarring in patients not opting for laser resurfacing.
Moderate-to-excellent clinical improvement was observed                             for acne scarring would               The author has used the HA-based filler Matridex®
after the initial treatments in almost all of the HA patients                       be an attractive option               (BioPolymer GmbH & Co., Germany), CaHA, and the
studied At 4-week assessment, nine patients still showed                            to most practitioners, as             polyalkylimide Bio-Alcamid® (Polymekon, Brindisi,
                                                                                    they require little
moderate-to-excellent results, but this had fallen off                              invasive technique and
                                                                                                                          Italy) for this purpose over the years. Some of these
dramatically at 3-month assessment: only two patients                               could be used in                      fillers simply provide a physical filling effect, while
had score 4 (75–100% improvement) and two patients (23%                             combination with other                others induce a delayed collagen stimulatory effect (e.g.
of total) had score 3 (50–75% improvement). At 6-month                              modalities, such as                   CaHA and poly-L-lactic acid). An ideal filling
evaluation, 12 patients (92%) showed a 0–25% improvement.                           microneedling or laser                agent should restore atrophic volume and stimulate
                                                                                    resurfacing
   The author felt both of                                                                                                the dermis to synthesise new collagen for a long‑lasting
                                                                                    n Many studies have
the fillers initially provided                    CaHA is                           established the                       effect.
a       simple         physical                                                     biocompatibility and                      Based on the experience of this study, the author feels
volumising effect. There            biosynthetically                                safety of CaHA in facial              CaHA is a suitable product for this purpose, showing a
was a longevity associated             produced and                                 filling techniques. The               clearly demonstrable benefit still present at 6–12 months.
                                                                                    product has gained
with the therapeutic effect             does not elicit                             popularity in the US and
                                                                                                                          A comparative study performed with HA preparations
of         the         calcium                                                                                            showed the compound was not of medical or commercial
hydroxylapatite         (CaHA),
                                                a chronic                           Europe for this
                                                                                                                          benefit to either the physician or patient, with most of the
                                                                                    indication, and more
probably secondary to the               inflammatory                                recently in the                       product disappearing at only 6–12  weeks. More viscous
duration of the filler and                   or immune                              treatment of acne
                                                                                    scarring
                                                                                                                          forms of HA, such as HyaCorp® (BioScience GmbH,
some            level        of        response.                                                                          Germany) showed no extra benefit.
                                                                                    n This study
neocollagenesis noted in
                                                                                    documents the efficacy
other studies. There was little evidence of delayed                                 of CaHA in the                        Conclusions
biostimulatory effect of collagen formation owing to HA                             treatment of atrophic                 CaHA is biosynthetically produced and does not elicit a
injections, although the physical act of injection and                              acne scars. The author                chronic inflammatory or immune response. In vivo and
subcision was of some benefit to the patient.                                       is aware that these                   in vitro studies have established the biocompatibility and
                                                                                    benefits may last 18
   Side-effects of treatment were mostly limited in the                             months or more                        safety of CaHA. No evidence of granuloma formation,
group to mild transient erythema, bruising or localised                                                                   ossification, or foreign body reactions have been found in
oedema. Some patients required top-up or remodelling                                                                      long-term animal studies. CaHA implants have persisted
on initial review. One 23-year-old male patient (skin type                                                                intact at the injection site in areas such as the face at up to


   References
 1.	 Burton JL, Cunliffe WJ, Stafford I, Shuster   photorejuvenation and inflammatory acne           16.	 Tzikas TL. Evaluation of the Radiance FN      undergoing treatment with antiretroviral
 S. The prevalence of acne vulgaris in             vulgaris. Br J Dermatol 2006; 155(4): 748–55      soft tissue filler for facial soft tissue          drugs. Dermatol Surg 2006; 32(6): 804–8
 adolescence. Br J Dermatol 1971; 85 (2): 119–26   9.	 Nouri K, Rivas MP, Bouzari N, Faghih S.       augmentation Arch Facial Plast Surg 2004;          23.	Product used to enlarge lips can cause
 2.	 Cunliffe WJ. The acnes. London: Dunitz,       Nonablative lasers. J Cosmet Dermatol 2006;       6(4): 234–9
                                                                                                                                                        bumps. Bioform does not recommend using
 1989                                              5(2): 107–14                                      17.	 Marmur ES, Phelps R, Goldberg DJ. Clinical,   this product on the red portion of lips.
 3.	 Layton AM, Henderson CA, Cunliffe WJ. A       10.	Bellew SG, Lee C, Weiss MA, Weiss RA.         histologic and electron microscopic findings
                                                                                                     after injection of a calcium hydroxyapatite        click2houston.com
 clinical evaluation of acne scarring and its      Improvement of atrophic acne scars with a
 incidence. Clin Exp Dermatol 1994; 19(4):         1,320 nm Nd:YAG laser: retrospective study.       filler. J Cosmet Laser Ther 2004; 6(4): 223–6      24.	Goldberg DJ, Snehal A, Hussain M. Acne
 303–8                                             Dermatol Surg 2005; 31(9 Pt 2): 1218–21           18.	 Godin MS, Majmundar MV, Chrzanowski           scar correction using calcium hydroxylapatite
 4.	 Wu SF, Kinder BN, Trunnell TN, Fulton JE.     11.	 Prieto VG, Zhang PS, Sadick NS. Evaluation   DS, Dodson KM. Use of radiesse in                  in a carrier-based gel. J Cosmet Laser Ther
 Role of anxiety and anger in acne patients: a     of pulsed light and radiofrequency combined       combination with restylane for facial              2006; 8(3): 134–6
 relationship with the severity of the disorder.   for the treatment of acne vulgaris with           augmentation Arch Facial Plast Surg 2006;          25.	Alam M, Dover JS. Treatment of acne
 J Am Acad Dermatol 1988; 18(2 Pt 1): 325–33       histologic analysis of facial skin biopsies J     8(2): 92–7                                         scarring. Skin Therapy Lett 2006; 11(10): 7–9
 5.	 Cotterill JA, Cunliffe WJ. Suicide in         Cosmet Laser Ther 2005; 7(2): 63–8                19.	 Goldberg DJ. Fillers in Cosmetic
                                                                                                     Dermatology. Abingdon, Oxon, UK: Informa,          26.	Buck DW 2nd, Alam M, Kim JY. Injectable
 dermatological patients. Br J Dermatol 1997;      12.	 Majid I. Microneedling therapy in atrophic
 137(2): 246–50                                    facial scars: an objective assessment. J Cutan    2006                                               fillers for facial rejuvenation: a review. J Plast
                                                   Aesthet Surg 2009; 2(1): 26–30                    20.	Roy D, Sadick N, Mangat D. Clinical trial of   Reconstr Aesthet Surg 2009; 62(1): 11–8
 6.	 Omi T, Kawana S, Sato S, Bonan P, Naito Z.
 Fractional CO2 laser for the treatment of acne    13.	 Coleman WP Lipocytic dermal                  a novel filler material for soft tissue            27.	 Orentreich DS, Orentreich N.
 scars. J Cosmet Dermatol 2011; 10(4): 294–300     augmentation. In: Klein AW. ed, Tissue            augmentation of the face containing                Subcutaneous incisionless (subcision)
 7.	 Hedelund L, Haak CS, Togsverd-Bo K, Bogh      augmentation in clinical practice. Procedures     synthetic calcium hydroxylapatite                  surgery for the correction of depressed scars
 MK, Bjerring P, Hædersdal M. Fractional CO2       and techniques. New York: Marcel Dekker,          microspheres. Dermatol Surg 2006; 32(9):           and wrinkles. Dermatol Surg 1995; 21(6):
 laser resurfacing for atrophic acne scars: a      1998: 49–62                                       1134–9                                             543–9
 randomized controlled trial with blinded          14.	 Coleman SR. Long-term survival of fat        21.	 Comite SL, Liu JF, Balasubramanian S,         28.	Chandrashekar BS, Nandini A. Acne scar
 response evaluation. Lasers Surg Med 2012;        transplants: controlled demonstrations.           Christian MA. Treatment of HIV-associated
 44(6): 447–52                                     Aesthetic Plast Surg 1995; 19(5): 421–5           facial lipoatrophy with Radiance FN                subcision J Cutan Aesthet Surg 2010; 3(2):
                                                                                                     (Radiesse). Dermatol Online J 2004; 10(2): 2       125–6
 8.	 Seaton ED, Mouser PE, Charakida A, Alam       15.	 Chu A, et al. A pilot study to assess the
 S, Seldon PM, Chu AC. Investigation of the        efficacy of Isolagen (autologous fibroblasts)     22.	Treacy PJ, Goldberg DJ. Use of a               29.	Goodman GJ, Baron JA. Postacne scarring
 mechanism of action of nonablative                treatment in acne scarring. Br J Dermatol         biopolymer polyalkylimide filler for facial        – a quantitative global scarring grading
 pulsed-dye laser therapy in                       2006                                              lipodystrophy in HIV-positive patients             system. J Cosmet Dermatol 2006; 5(1): 48–52




48

      ❚   March 2013 | prime-journal.com
| dermatology | peer-review

 Figure 6 Improvement rates in patient cohort treatment with CaHA                                          Figure 7 Improvement rates in patient cohort treatment with HA
                      27                                                                                                         13
                                                                                                                                 12
                      24
                                                                                                                                 11
                      21                                                                                                         10
                                                                                                                                 9
 Number of patients




                      18




                                                                                                            Number of patients
                                                                                                                                 8
                      15                                                                                                         7
                      12                                                                                                         6
                                                                                                                                 5
                      9
                                                                                                                                 4
                      6                                                                                                          3
                                                                                                                                 2
                       3
                                                                                                                                  1
                      0                                                                                                          0
                                 4 weeks        12 week             24 weeks   48 weeks                                                   4 weeks           12 weeks           24 weeks        48 weeks
                             0-25%   25-50%   50-75%      75-100%                                                                     0-25%      25-50%   50-75%   75-100%




12–18 months. No skin testing is required for the                                                                                              Declaration of interest None
compound as company information states that no
animal or animal products are used in the manufacture                                                                                          Figures 2–7 ©Patrick Treacy
of the product, thus there is no risk of transmitting disease
or causing allergic reactions in patients who are sensitive                                                                                    Patrick Treacy will present on the DUBLiN Lift at AMWC
to common foods.                                                                                                                              2013: 16.30, Friday 5 April, Room Van Dongen
   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.
 4154 1_2 page_Layout 1 21/12/2012 16:22 Page 1




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Radiesse study on atrophic acne scarring

  • 1.
  • 2. | dermatology | peer-review dermal filler treatment For atrophic acne scarring Patrick Treacy presents the results of a study investigating the efficacy of dermal fillers in the treatment of atrophic acne scarring ABSTRACT acne scarring were treated with Eleven hyaluronic acid patients Full title the CaHA filler over a 12‑month (85% of total) showed a 0–25% Problems encountered using period. Thirteen patients were improvement in treated dermal fillers, particularly treated with low molecular atrophic scars at 12 months. calcium hydroxylapatite, as a weight cross-linked hyaluronic treatment in acne scarring. acid in a comparative study. Conclusions Dermal fillers, especially Objectives Results CaHA, can provide a safe and This article aims to establish Most atrophic acne scars efficacious method of treating the efficacy and safety profile of responded well to CaHA dermal atrophic acne scars. This dermal fillers, especially calcium filler treatment. Icepick scars compound appears to provide hydroxyapatite (CaHA) in the were not treated. At 12-month a longer-lasting effect owing treatment of atrophic acne evaluation, 22% of subjects to volume replenishment and scars. showed a 75% improvement, possible neocollagenesis. The Dr Patrick Treacy is while 48% showed a 50% efficacy of hyaluronic acid in Medical Director of Ailesbury Methods improvement. This compared repairing atrophic acne scars is Clinics Ltd and Ailesbury Hair Twenty-seven subjects with to an average 0% improvement not demonstrable. Clinics Ltd; Chairman of the differing degrees of atrophic for the hyaluronic acid cohort. Irish Association of Cosmetic Doctors and Irish Regional A Representative of the British Association of Cosmetic cne occurs in inhibition, unhappiness, anxiety, and Doctors; European Medical approximately 95% of even suicidal thoughts as a result of their Advisor to Network Lipolysis 16–17-year-old boys and facial appearance5. and the UK’s largest cosmetic website Consulting Rooms. He 84% of 16–17-year-old practices cosmetic medicine girls1. Although the Background in his clinics in Dublin, Cork, London and the Middle East condition usually For many years different treatment resolves by the mid‑20s, 1% of men and modalities have been used for the revision email: ptreacy@gmail.com 5% of women still bear the signs of of atrophic acne scarring, with varying moderately severe acne scarring at degrees of success. Many 40  years of age2. Some studies show controlled trials have Affected scarring of some degree may affect up to demonstrated that moderate to 95% of patients with acne3. The same severe atrophic acne scars can patients report more study found that keloidal or hypertrophic be safely improved through social inhibition, truncal scarring were more common in ablative fractional CO2 laser unhappiness, men. This form of scarring is usually resurfacing (fractional laser skin treated by using such measures as resurfacing; FLSR)6. Although anxiety, and even intralesional steroids, silicone sheeting, FLSR is still the most popular suicidal thoughts as or vascular laser treatment. Atrophic therapeutic modality for the a result of their facial scarring will often appear many years correction of acne scars, it is not appearance. Keywords later, and can cause great distress in always effective in all types of calcium hydroxyapatite, patients during their courtship years4. atrophic lesions  — the more common 7 hyaluronic acid, acne scars, Affected patients report more social type of defects encountered after dermal fillers prime-journal.com | March 2013 ❚ 41
  • 3. peer-review | dermatology | Table 1 Four-point grading scale for acne scars Figure 1 Acne scar subtypes Grade 1 Macular Icepick Rolling Boxcar Erythematous, hyper-, or hypopigmented marks Skin surface Grade 2 Mild disease Mild atrophy, can be covered with make-up of facial hair Grade 3 Moderate disease Moderate scarring, not covered by make-up, but can Scar edges be flattened by manual stretching of the skin Grade 4 Severe disease Scarring not flattened with manual stretching Fascia of the skin inflammatory acne. The use of higher energy levels found in the human body as a constituent of bone and might have improved the results, and also possibly teeth. The CaHA microspheres (25–45 µ) are suspended induced significant adverse effects7. Over the past decade, in an aqueous carboxymethylcellulose carrier gel, non-ablative laser resurfacing8–10, radiofrequency (RF)11, composed of cellulose, glycerin, and sterile water. None and microneedling12 have been shown to create some of these materials should elicit a chronic inflammatory, improvement in the appearance of these atrophic scars. A infectious or immune response. Multiple clinical and number of autologous and non- histologic studies have tended to document autologous techniques attempting its safety, efficacy, and longevity in tissue17, 18. dermal and subcutaneous augmentation By its very composition, CaHA is By its very composition, CaHA is designed have been tried to improve the facial designed to provide immediate to provide immediate correction and aesthetic appearance. The autologous correction and long‑term long‑term biostimulatory neocollagenesis. methods have included dermal grafting, Over time, the gel is absorbed, fibroblasts biostimulatory neocollagenesis. fat transfer13, 14, and implantation of appear and the process of neocollagenesis autologous fibroblasts, such as Isolagen®15. begins, stimulating the gradual growth of the There has been interest in non-autologous patient’s own collagen. The carboxymethylcellulose gel augmentation by way of injections of hyaluronic acid carrier volumises the ‘lost’ space and acts as a replacement (HA), polymethylmethacrylate microspheres (PMMA), filler; the microspheres stimulate neocollagenesis so that, and calcium hydroxylapatite (CaHA)16, 17. CaHA, the main as the gel dissipates, the spheres anchor into the soft mineral component of Radiesse® (Merz Aesthetics, San tissue. There, they serve as a scaffold for new collagen Mateo, CA), is a synthetic analogue of the inorganic salt 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 fillers At 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 Figure 2 17-year-old male of CaHA in facial filling techniques21, the product has patient (A, B, C) before gained popularity in the US and Europe for this indication, treatment with Radiesse, and (D, E) immediately and more recently in the treatment of acne scarring24. after treatment. 1.3 ml HA has been used in aesthetic medicine for a long CaHA was used time, and has an extended safety profile. In its natural 42 ❚ March 2013 | prime-journal.com 13021
  • 4. | dermatology | peer-review Soft tissue filler use for acne scarring would be an attractive option to most practitioners as they require little invasive technique. form HA has a short duration time in the tissue, owing skin surface and its sharp edges manoeuvred under the to enzymatic degradation and free radical metabolisation. defect to make subcuticular cuts or ‘cisions’. The principle To avoid these effects, HA gel is modified through of this procedure is to break the fibrotic strands, which cross‑linking to form a water-insoluble polymer hydrogel, tether the scar to the underlying subcutaneous tissue. more resistant to degradation, but with a similar The depression is lifted by the releasing action of the biocompatibility as non-modified HA. Based on the procedure, as well as from connective tissue that forms experience of other authors, many of the available HA during the course of normal wound healing28. preparations are too short-lived (approximately 3–6 months24, 25 to appropriately treat moderate to severe Methods acne scars) and use of such products for this purpose A series of 27 patients (17 male, 10 female; skin phototypes would require a significant total injection volume over I–IV), with varying degrees of atrophic acne scarring, time, with frequent re-treatments, contributing to a Figure 3 23-year-old were treated in a single-centre, prospective, controlled female patient (A) during greater total cost and time commitment for the patient. treatment with Radiesse, study over a 1-year period. Patients were randomly More viscous forms of HA, such as Perlane® (Medicis and (B) 2 weeks after selected on the basis that they did not want to present for Aesthetics, Inc., Scottsdale, AZ) or Juvéderm® Voluma treatment laser resurfacing as a treatment for their problem. This (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 3 10:38 prime-journal.com | March 2013 ❚ 45
  • 5. | dermatology | peer-review 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 meant the patients were enrolled sporadically, rather improve overall healing. Patients who had received than entering the study at the same time. The subjects Figure 4 23-year-old male synthetic collagen, HA, PMMA, CaHA, or autologous ranged in age from 16–63  years, and all acne scarring patient (A) before treatment fibroblast injections to treated areas within the previous 6 with Radiesse, and (B) severity scores fell between 4 and 30 on the Goodman months were excluded from the study. Clinical 2 weeks after treatment system (Table  1). Patients were also evaluated using assessment scores were determined at each treatment digital photography and an improvement graduation session and follow-up visit. Patient satisfaction surveys scale at each subsequent treatment visit, at 1, 3, 6, 12 and and digital photography were used where they were 24 months post-procedurally: appropriate to both parties, although both were ■■ 0 = no improvement considered subjective, with patients tending to focus on ■■ 1 = 0–25% improvement the smallest detail and physicians photographically ■■ 2 = 25–50% improvement favouring the better results. All patients were reviewed at ■■ 3 = 50–75% improvement 2 or 4 weeks post‑treatment for a top-up of Radiesse, if ■■ 4 = 75–100% improvement required. It was noted that 17 patients ■■ 5 = 100% improvement. Subscision of each required a top-up of at least 0.15 ml CaHA at Multiple acne scar grading classification systems of atrophic scar was one of the first two visits. Smaller amounts varying complexities have been introduced. The most performed 1 week prior to (< 0.1 ml) were not recorded, as it was felt basic, practical system divides atrophic acne scars into that the patient may have seen some three main types: icepick, rolling, and boxcar scars29 injection with CaHA to defects under deeper scrutiny that were (Figure 1). It is common for patients to have more than one give a more uniform initially missed during the procedure. type of scar. aesthetic effect. A series of 13 patients (7 male, 6 female; skin phototypes I–IV) with varying degrees Treatment of atrophic acne scarring were treated in a similar manner Subscision of each atrophic scar was performed 1  week with low molecular weight cross-linked HA, and monitored prior to injection with CaHA to give a more uniform over a 12‑month period. Patients were randomly selected aesthetic effect. Radiesse was injected using a 27  gauge on the basis that they did not want to present for laser needle into the space left after subscision of the acne scar resurfacing as a treatment for their problem. in the region of the mid- to deep dermis, although final Figure 5 26-year-old old placement also depended on the presence of fibrous and male patient (A) before Results cystic tissue in this region of the skin. The total volume of treatment with CaHA and Twenty-seven patients entered this 12-month study. CaHA used varied with each patient, with an end-point (B) 4 weeks after treatment Moderate to excellent clinical improvement was prime-journal.com | March 2013 ❚ 47
  • 6. peer-review | dermatology | observed after 4 weeks in almost all of the patients 4, of Asian origin) with minimally active acne on a studied (20 patients with score 4, 75–100%; six patients Key points previous trial developed cellulitis and later with score 3, 50–75%). One patient had score 1, 0–25% desquamation. improvement, while no subjects scored either 0 or 5. At n Although fractional laser skin resurfacing is the 6-month assessment 12 patients (44% of total) had still the most popular Discussion score 4 (75–100% improvement) and 11 patients (40%) had therapeutic modality There are many methods that can be used in the score 3 (50–75% ). At 12-month evaluation, six patients for the correction of treatment of atrophic acne scarring. Most tend to (22%) showed 75% improvement; 14 patients (48%) showed acne scars, it is not replace the volume lost by the atrophic effects of the always effective in all between 50% improvement, and five patients (18%) types of atrophic acne. Newer injectable fillers are biocompatible and showed a 25% improvement in treated atrophic scars. lesions safer, and can provide an alternative means of treating Thirteen patients entered the 12-month HA study. n Soft tissue filler use acne scarring in patients not opting for laser resurfacing. Moderate-to-excellent clinical improvement was observed for acne scarring would The author has used the HA-based filler Matridex® after the initial treatments in almost all of the HA patients be an attractive option (BioPolymer GmbH & Co., Germany), CaHA, and the studied At 4-week assessment, nine patients still showed to most practitioners, as polyalkylimide Bio-Alcamid® (Polymekon, Brindisi, they require little moderate-to-excellent results, but this had fallen off invasive technique and Italy) for this purpose over the years. Some of these dramatically at 3-month assessment: only two patients could be used in fillers simply provide a physical filling effect, while had score 4 (75–100% improvement) and two patients (23% combination with other others induce a delayed collagen stimulatory effect (e.g. of total) had score 3 (50–75% improvement). At 6-month modalities, such as CaHA and poly-L-lactic acid). An ideal filling evaluation, 12 patients (92%) showed a 0–25% improvement. microneedling or laser agent should restore atrophic volume and stimulate resurfacing The author felt both of the dermis to synthesise new collagen for a long‑lasting n Many studies have the fillers initially provided CaHA is established the effect. a simple physical biocompatibility and Based on the experience of this study, the author feels volumising effect. There biosynthetically safety of CaHA in facial CaHA is a suitable product for this purpose, showing a was a longevity associated produced and filling techniques. The clearly demonstrable benefit still present at 6–12 months. product has gained with the therapeutic effect does not elicit popularity in the US and A comparative study performed with HA preparations of the calcium showed the compound was not of medical or commercial hydroxylapatite (CaHA), a chronic Europe for this benefit to either the physician or patient, with most of the indication, and more probably secondary to the inflammatory recently in the product disappearing at only 6–12  weeks. More viscous duration of the filler and or immune treatment of acne scarring forms of HA, such as HyaCorp® (BioScience GmbH, some level of response. Germany) showed no extra benefit. n This study neocollagenesis noted in documents the efficacy other studies. There was little evidence of delayed of CaHA in the Conclusions biostimulatory effect of collagen formation owing to HA treatment of atrophic CaHA is biosynthetically produced and does not elicit a injections, although the physical act of injection and acne scars. The author chronic inflammatory or immune response. In vivo and subcision was of some benefit to the patient. is aware that these in vitro studies have established the biocompatibility and benefits may last 18 Side-effects of treatment were mostly limited in the months or more safety of CaHA. No evidence of granuloma formation, group to mild transient erythema, bruising or localised ossification, or foreign body reactions have been found in oedema. Some patients required top-up or remodelling long-term animal studies. CaHA implants have persisted on initial review. One 23-year-old male patient (skin type intact at the injection site in areas such as the face at up to References 1. 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  • 7. | dermatology | peer-review Figure 6 Improvement rates in patient cohort treatment with CaHA Figure 7 Improvement rates in patient cohort treatment with HA 27 13 12 24 11 21 10 9 Number of patients 18 Number of patients 8 15 7 12 6 5 9 4 6 3 2 3 1 0 0 4 weeks 12 week 24 weeks 48 weeks 4 weeks 12 weeks 24 weeks 48 weeks 0-25% 25-50% 50-75% 75-100% 0-25% 25-50% 50-75% 75-100% 12–18 months. No skin testing is required for the  Declaration of interest None compound as company information states that no animal or animal products are used in the manufacture  Figures 2–7 ©Patrick Treacy of the product, thus there is no risk of transmitting disease or causing allergic reactions in patients who are sensitive  Patrick Treacy will present on the DUBLiN Lift at AMWC to common foods. 2013: 16.30, Friday 5 April, Room Van Dongen 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. 4154 1_2 page_Layout 1 21/12/2012 16:22 Page 1 Each cannula with screw thread polycarbonate hub, is supplied one size smaller Silkann flexible aesthetic cannulas packaged with Sterimedix sharp needles than the accompanying sharp pre-hole needle, More comfortable for your patients. giving practitioners the perfect match between More efficient for you. cannula and needle to ensure maximium accuracy whilst maintaining optimum patient comfort. Available in the UK through For more information call: +44 (0)1527 405860 or visit: www.silkann.com Tel: 0800 7830605 Silkann is a registered trade mark of Sterimedix Limited sales@medfx.co.uk