This paper by Dr. Patrick Treacy Medical Director Ailesbury Clinics Ltd. sought to establish the efficacy and safety profile the dermal filler, calcium hydroxylapatite filler in the treatment of atrophic acne scars. Forty two subjects with differing degrees of atrophic acne scars were treated with this filler over an eighteen month period and the results are published below
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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
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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
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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
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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
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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
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