Results of a calcium hydroxylapatitie (Radiesse) study performed on 27 patients with moderate to severe atrophic acne scarring for a period of 12 months. The results show a favorable and possible cheap alternative to laser resurfacing. A comparative HA study (hyaluronic acid) with 13 patients showed this product was of little therapeutic benefit.
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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 degrees of atrophic acne scarring were cohort. Eleven hyaluronic acid patients (85%
Full title treated with the CaHA filler over a 12‑month of total) showed a 0–25% improvement in
Problems encountered using dermal fillers, period. Thirteen patients were treated treated atrophic scars at 12 months.
particularly calcium hydroxylapatite, as a with low molecular weight cross-linked
treatment in acne scarring . hyaluronic acid in a comparative study. Conclusions
Dermal fillers, especially CaHA, can provide
Objectives Results a safe and efficacious method of treating
This article aims to establish the efficacy Most atrophic acne scars responded well atrophic acne scars. This compound appears
and safety profile of dermal fillers, especially to CaHA dermal filler treatment. Ice-pick to provide a longer-lasting effect owing
calcium hydroxyapatite (CaHA) in the scars were not treated. At 12-month to volume replenishment and possible
treatment of atrophic acne scars. evaluation, 22% of subjects showed a 75% neocollagenesis. The efficacy of hyaluronic
improvement, while 48% showed a 50% acid in repairing atrophic acne scars is not
Methods improvement. This compared to an average demonstrable.
Twenty-seven subjects with differing 0% improvement for the hyaluronic acid
Dr Patrick Treacy is
A
Medical Director of Ailesbury
Clinics Ltd and Ailesbury Hair
Clinics Ltd; Chairman of the cne occurs in approximately unhappiness, anxiety, and even suicidal thoughts as a
Irish Association of Cosmetic
Doctors and Irish Regional
95% of 16–17-year-old boys and 84% of result of their facial appearance5.
Representative of the British 16–17-year-old girls1. Although the
Association of Cosmetic
Doctors; European Medical
condition usually resolves by the Background
Advisor to Network Lipolysis mid‑20s, 1% of men and 5% of women For many years different treatment modalities have been
and the UK’s largest cosmetic still bear the signs of moderately severe used for the revision of atrophic acne scarring, with
website Consulting Rooms. He acne scarring at 40 years of age2. Some studies show varying degrees of success. Many controlled trials have
practices cosmetic medicine
in his clinics in Dublin, Cork, scarring of some degree may affect up to 95% of patients demonstrated that moderate to severe atrophic acne
London and the Middle East with acne3. The same study found that keloidal or scars can be safely improved through ablative fractional
hypertrophic truncal scarring was more common in CO2 laser resurfacing (fractional laser skin resurfacing;
email: ptreacy@gmail.com
men. This form of scarring is usually treated by using FLSR)6. Although FLSR is still the most popular
such measures as intralesional steroids, silicone therapeutic modality for the correction of acne scars, it is
sheeting, or vascular laser treatment. Atrophic scarring not always effective in all types of atrophic lesions7 — the
Keywords will often appear many years later, and can cause great more common type of defects encountered after
calcium hydroxyapatite,
hyaluronic acid, acne scars, distress in patients during their courtship years4. inflammatory acne. The use of higher energy levels
dermal fillers Affected patients report more social inhibition, might have improved the results, and also possibly
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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
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, migrate, and does not obscure diagnostic x-rays.
efficacy, and longevity in tissue17, 18. At the present time, the use of CaHA is approved by the
By its very composition, CaHA is designed to provide Food and Drug Administration (FDA) for the correction of
immediate correction and long-term biostimulatory moderate to severe facial wrinkles and folds19, 20. CaHA
neocollagenesis. Over time, the gel is absorbed, and also gained prominence during the period in which
fibroblasts appear and the process of neocollagenesis dermal fillers were being used for antiretroviral-induced
begins, stimulating the gradual growth of the patient’s facial lipoatrophy21, 22. It is known to cause persistent
own collagen. The nodules in a small percentage of people,
carboxymethylcellulose gel carrier especially if it is injected into the vermillion
volumises the ‘lost’ space and acts as a
Soft tissue filler use for acne border of the lips23. As many studies have
replacement filler; the microspheres scarring would be an attractive option established the biocompatibility and safety
stimulate neocollagenesis so that, as the to most practitioners as they require of CaHA in facial filling techniques21, the
gel dissipates, the spheres anchor into
little invasive technique and could be product has gained popularity in the US
the soft tissue. There, they serve as a and Europe for this indication, and more
scaffold for new collagen growth as early used in combination with other recently in the treatment of acne scarring24.
as 4 weeks post-injection, and then treatment modalities. HA has been used in aesthetic medicine
continue for up to at least 12 months17, 18. CaHA is not for a long time, and has an extended safety profile. In its
permanent, however. The CaHA microspheres are natural form HA has a short duration time in the tissue,
metabolised into calcium and phosphate ions through owing to enzymatic degradation and free radical
normal metabolic processes over 24 months. CaHA will metabolisation. To avoid these effects, HA gel is modified
not promote osteogenesis in soft tissues, does not through cross‑linking to form a water-insoluble polymer
hydrogel, more resistant to degradation, but with a similar
Table 1 Four-point grading scale biocompatibility as non-modified HA. Based on the
for acne scars experience of other authors, many of the available HA
preparations are too short-lived (approximately
Grade 1: Macular 3–6 months24, 25 to appropriately treat moderate to severe
Erythematous, hyper-, or hypopigmented marks acne scars) and use of such products for this purpose
would require a significant total injection volume over
Grade 2: Mild disease time, with frequent re-treatments, contributing to a
Mild atrophy, can be covered with make-up of facial hair greater total cost and time commitment for the patient.
More viscous forms of HA, such as Perlane® (Medicis
Grade 3: Moderate disease Aesthetics, Inc., Scottsdale, AZ) or Juvederm® Voluma
Moderate scarring, not covered by make-up, but can be (Allergan, Inc., Santa Barbara, CA), may be appropriate for
flattened by manual stretching of the skin patients with atrophic scars. The ideal filler for this
purpose would be long-lasting, biocompatible, and would
Grade 4: Severe disease not elicit further inflammation or granuloma formation
Scarring not flattened with manual stretching of the skin in skin already damaged by acne26.
Soft tissue filler use for acne scarring would be an
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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
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
Figure 2 17-year-old male patient (A, B, C) before treatment with Radiesse, and (D, E) immediately after ■■ 5 = 100% improvement.
treatment. 1.3 ml CaHA was used Multiple acne scar grading classification systems of
varying complexities have been introduced. The most
attractive option to most practitioners as they require basic, practical system divides atrophic acne scars into
little invasive technique and could be used in three main types: icepick, rolling, and boxcar scars29
combination with other treatment modalities, such as (Figure 1). It is common for patients to have more than one
microneedling or laser resurfacing. Although studies type of scar.
have shown that HA injections do stimulate collagen Subscision of each atrophic scar was performed 1 week
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
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.
Methods
A series of 27 patients (17 male, 10 female; skin phototypes
I–IV), with varying degrees of atrophic acne scarring, Figure 3 23-year-old female patient (A) during treatment with Radiesse, and (B) 2 weeks after
were treated in a single-centre, prospective, controlled treatment
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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.
Results
Twenty-seven patients entered this 12-month study.
Moderate to excellent clinical improvement was
observed after 4 weeks in almost all of the patients
studied (20 patients with score 4, 75–100%; siz 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
Figure 4 23-year-old male patient (A) before treatment with Radiesse, and (B) 2 weeks after treatment
score 3 (50–75% ). At 12-month evaluation, six patients
(22%) showed 75% improvement; 14 patients (48%)
prior to injection with CaHA to give a more uniform showed between 50% improvement, and five patients
aesthetic effect. Radiesse was injected using a 27 gauge (18%) showed a 25% improvement in treated atrophic
needle into the space left after subscision of the acne scars.
scar in the region of the mid- to deep dermis, although Thirteen patients entered the 12-month HA study. At
final placement also depended on the presence of 3‑month assessment, zero patients had score 4 (75–100%
fibrous and cystic tissue in this region of the skin. The improvement) and four patients (23%) had score 3 (50–
total volume of CaHA used varied with each patient, with
an end-point 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 appeared 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. Figure 5 26-year-old old male patient (A) before treatment with CaHA and (B) 4 weeks after treatment
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75% ). 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
4, of Asian origin) with minimally active acne on a
previous trial developed cellulitis and later
desquamation.
Discussion Figure 6 Improvement rates in patient cohort treatment with CaHA
There 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.
[AQ9: any limitations to this study?]
Conclusions Figure 6 Improvement rates in patient cohort treatment with HA
CaHA 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
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
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