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Lasers in Surgery and Medicine 39:381–385 (2007)

The Prevalence and Risk Factors of Post-Inflammatory


Hyperpigmentation After Fractional Resurfacing in Asians
Henry H.L. Chan, MBBS, MD, FRCP,1,2* D. Manstein,3 C.S. Yu,1 S. Shek,1 T. Kono,4 and W.I. Wei5
1
Division of Dermatology, Department of Medicine, University of Hong Kong, Hong Kong SAR, China
2
Division of Dermatology, Departments of Medicine and Therapeutic and Department of Paediatrics,
Chinese University of Hong Kong, Hong Kong, China
3
Department of Dermatology, Harvard Medical School, Boston
4
Department of Plastic and Reconstructive Surgery, Tokyo Women’s Medical School, Tokyo, Japan
5
Department of Surgery, University of Hong Kong, Hong Kong SAR, China

Background: Ablative laser resurfacing is considered areas. By using adequate parameters, the risk of PIH in
to be the main therapeutic option for the treatment of dark-skinned patients can be significantly reduced. Lasers
wrinkles and acne scarring. However, in Asians, post- Surg. Med. 39:381–385, 2007. ß 2007 Wiley-Liss, Inc.
inflammatory hyperpigmentation (PIH) is a common
adverse effect of laser resurfacing. Fractional resurfacing Key words: post-inflammatory hyperpigmentation, frac-
is a new concept of skin rejuvenation whereby zones of tional resurfacing, Asians
micro thermal injury are generated in the skin with the use
of a 1,540-nm laser. The risk and prevalence of hyperpig- INTRODUCTION
mentation in dark-skinned patients using this approach Ablative laser resurfacing is considered to be the main
have not been studied. therapeutic option for the treatment of wrinkles and acne
Objective: To assess the prevalence and risk factors of PIH scarring. In Asians, photoaging is associated with more
that is associated with the use of fractional resurfacing in pigmentary problems but less wrinkling [1]. Certain
Asians. adverse effects are associated with the use of ablative
Method: A retrospective study of 37 Chinese patients who resurfacing, including a long down time and the risk of
were treated with fractional resurfacing for acne scarring, pigmentary changes, especially post-inflammatory hyper-
skin rejuvenation, and pigmentation was carried out. In all pigmentation (PIH), which have made these ablative
of the cases, pre- and post-treatment clinical photographs procedures unpopular [2]. Non-ablative skin rejuvenation
(from standardized and cross-polarized views) were taken involves the use of a laser or light source together with a
using the Canfield CR system. Two independent observers cooling device to improve the features of photoaging,
assessed the photographs. A prospective study of treat- including lentigines, telangiectasia, pore size, skin texture,
ments of nine different density and energy levels that wrinkles, and skin laxity, with minimal down time.
were applied to the forearms of 18 volunteers was also However, although these non-ablative techniques are
performed. Clinical photographs were assessed pre- and associated with a shorter down time, the degree of
post-treatment for evidence of PIH. improvement appears to be limited [3,4]. More recently,
Result: In the retrospective study, 119 treatment sessions Manstein et al. [5] proposed a new concept of cutaneous re-
were performed. Sixty-eight treatment sessions were high modeling, whereby lasers are used to induce zones of
energy, low density; 51 sessions were low energy, high microscopic thermal injury that consist of marked areas of
density. Patients who underwent a high energy but low- tissue denaturation of 50–100 mm in diameter which are
density treatment (range of energy 7–20 mJ; average surrounded by normal viable tissue. As the area of thermal
energy 16.3 mJ, 1,000 MTZ) were associated with a lower injury is very small, the lateral migration of keratinocytes
prevalence of generalized PIH (7.1% vs. 12.4%) than those occurs rapidly, which leads to the complete re-epitheliali-
who underwent a low energy but high-density (range of zation of the epidermis within 24 hours. By taking into
energy 6–12 mJ; average energy 8.2 mJ, 2,000 MTZ)
treatment. However, the difference was not statistically
significant. Localized PIH occurred in the peri-oral area
This work was included in Dr. Henry H.L. Chan’s thesis that
among patients who did not receive air cooling as an was submitted to the University of Hong Kong for the conferment
adjunctive therapy. of a Ph.D.
Conclusion: Both the density and energy of the treatment *Correspondence to: Henry H.L. Chan, MBBS, MD, FRCP,
Dermatology and Laser Center, 13th Floor Club Lusitano, 16 Ice
determines the risk of PIH in dark-skinned patients. House Street, Hong Kong SAR, China. E-mail: hhlchan@hku.hk
Density may be of more important but further studies are Accepted 21 March 2007
Published online 22 May 2007 in Wiley InterScience
necessary to determine this. Cooling to prevent bulk tissue (www.interscience.wiley.com).
heating is also important, especially in small anatomical DOI 10.1002/lsm.20512

ß 2007 Wiley-Liss, Inc.


382 CHAN ET AL.

consideration the mismatch between the epidermal and TABLE 1. Energy and Density of the Nine Treated
dermal healing processes, fractional photothermolysis Areas in the Prospective Forearm Study
allows skin rejuvenation to be achieved with a minimal
Energy Number Density Total
risk of complications and a high degree of efficacy. During
Site (mJ) of passes (MTZ) MTZ
each treatment session, a variable ratio of the skin surface
is treated, the extent of which is primarily determined by 1 6 8 250 2,000
the density settings of the device and the number of passes. 2 9 8 250 2,000
Usually, about 16–20% of the skin surface is targeted per 3 12 8 250 2,000
treatment session. 4 6 1 250 250
In laser skin resurfacing, the main complication among 5 12 1 250 250
dark-skinned patients is PIH. To assess the risk and 6 24 1 250 250
prevalence of PIH among Asians who are treated with 7 16 8 125 1,000
fractional resurfacing, we performed a retrospective study 8 6 12 250 3,000
of patients who underwent fractional resurfacing using a 9 6 16 250 4,000
laser-scanning device, and a prospective forearm study
among 18 volunteers using the same device but different
parameters.
of 1 cm2 were punched out of the triple layer and the surface
METHODS AND SUBJECTS of the mask was imprinted with a fine grid pattern to allow
Retrospective Study the optical tracking system to function correctly. Again,
Optiguide BlueTM and 30% lidocaine ointment was applied
The study was conducted among Chinese patients who
to the treatment area for 1 hour. Air cooling was used in
were treated between December 17, 2004 and May 31, 2005
all of the cases. Using a digital camera, a photograph of
in a private center by a single operator (HC) using a
each patient was taken before treatment and then weekly
fractional resurfacing 1,540-nm Erbium glass laser (Fraxel
for 4 weeks. Two independent clinicians assessed the
SR, Reliant Technologies, Palo Alto, CA). The patients can
photographs for PIH, and scored them according to the
be divided into two groups: those who underwent therapy
following scale after mutual agreement.
for acne scarring, who were given a high energy but
Degree of PIH:
low density treatment, and those who underwent skin
rejuvenation for wrinkle and pigmentation, who were given
* None
a low energy but high density treatment. All of the patients
had full facial treatment. One hour before laser surgery, * Mild
Optiguide BlueTM was applied to enhance the contrast for * Moderate
the optical mouse or internal device tracking system. * Severe
Thirty-percent lidocaine ointment was applied to the face
for 1 hour without occlusion. Air cooling (Zimmer cooler, RESULTS
Telefon, Germany) was used in the treatment that took Retrospective Study
place between March 1 and May 31, but no cooling was used
Thirty-seven patients who underwent 119 treatment
in the treatments that were carried out before March 1,
sessions were included in the study. Sixty-eight sessions
2005. That is 89 out of 119 sessions did not have cooling.
used high-energy low density, while 51 sessions used low-
Photographic imaging using a Canfield Visia CR system
energy high density. For the skin rejuvenation group, an
(Canfield, NJ) was used to assess all of the patients
average energy of 8.2 mJ (range of energy 6–12 mJ) and a
before each treatment session. The system consists of a
density of 2,000 MTZ (250 MTZ X 8 passes) were used. For
configurable head support that ensures the proper and
the acne scar group, an average energy of 16.3 mJ (range of
consistent registration of the position of the patient’s head.
energy 7–20 mJ) and a density of 1,000 MTZ (125 MTZ X
The photographic images all had a 6.1-megapixel resolu-
8 passes) were used. The total overall generalized PIH rate
tion. The photographs were taken using standard light,
was 11.1% as determined by the examination of the
cross-polarization, parallel polarization, and UV light. The
standardized photographic images, and 17.1% as deter-
imagines were stored in the Canfield mirror software and
mined by the examination of the cross-polarized photo-
assessed by two independent assessors. The Fisher exact
graphs. The patients with acne scarring who underwent a
test was used to analyze the data.
high energy but low density treatment had a lower
generalized PIH rate of 7.1%, but the difference was not
Prospective Forearm Study statistically significant. The severity of PIH ranges from
Eighteen volunteers were included in this study, in mild to moderate (Tables 2 and 3).
which test areas of 1 cm2 on the inner aspect of the forearm The observers also noticed several cases of more
were treated at nine different energy and density levels, as significant localized PIH, all in the peri-oral area. These
listed in Table 1. Masks that consisted of a triple layer of incidents occurred before we started using the cooling
paper, metal foil, and paper were used to shield the edge system and occurred in patients with generalized PIH
of the test area to ensure a well-defined exposure site. Holes (Fig. 1).
FRACTIONAL RESURFACING IN ASIANS 383

TABLE 2. Prevalence of PIH in the Skin Rejuvenation/Pigment Group Versus the


Acne Scarred Group Using Standardized Lighting

Wrinkles/pigmentation Acne scar/scar

No. of sessions PIH No. of sessions PIH P-value


After 1st treatment 23 2 12 0 0.536
After 2nd treatment 30 4 10 1 1.000
After 3rd treatment 36 5 6 1 1.000
Total 89 11 (12.4%) 28 2 (7.1%) 0.731

Prospective Forearm Study the adverse effects, such as infection or scar formation, that
The results of the prospective study are listed in Table 4. are known to be associated with laser resurfacing [5]. Initial
The incidence of PIH ranged from 0% (6 and 12 mJ, observation has suggested the risk of PIH among dark-
250 MTZ) to 50% (6–12 mJ, 1,000–4,000 MTZ). The site skinned patients to be lower with fractional resurfacing
that was treated at a low energy with the highest density than with laser resurfacing [8]. There has not been any
(site 9, 6 mJ, 16 passes, 250 MTZ, total MTZ 4,000) was prior study of the incidence of PIH as a primary focus of a
associated with the highest incidence of moderate levels of paper. Incidence of PIH has been reported as an adverse
generalized PIH. Whereas low density sites (total MTZ 250) effect was reported in 1 out of 10 subjects recruited for a
had two cases of mild PIH at 24 mJ and no PIH at 6 and pilot study for the treatment of melasma [9]. Our study
12 mJ. This indicated that both the energy and density indicates that several factors may be important in deter-
of the resurfacing treatment determine the risk of PIH. mining the causes of PIH in dark-skinned patients who are
Interesting treatments other than those at a total density of treated with fractional resurfacing. Although, both the
250 MTZ showed an incidence of 50% PIH versus those energy and density of the treatment determine the risk of
treated at 250MTZ had an incidence of around 4%. This PIH, density appears to be particularly important. A small
suggested that density may be of particular importance in anatomical treatment site and inadequate epidermal cool-
the determination of PIH. ing are two other factors that are associated with the
development of PIH in dark-skinned patients after frac-
tional resurfacing.
DISCUSSION To understand the relationship between these factors
PIH is the most common complication in dark-skinned and PIH, the etiology of PIH must be examined. A recent
patients who undergo laser surgery [2,6,7]. This adverse suntan has previously been shown to increase the risk of
effect is particularly undesirable in cosmetic procedures, PIH among patients who are undergoing laser resurfacing,
and is one of the main reasons why laser resurfacing is regardless of skin type [2]. Hence, sun avoidance and
much less popular among patients with darker skin. protection at least 2 weeks before fractional resurfacing is
Although, non-ablative skin rejuvenation is associated important in the prevention of PIH.
with a high degree of safety, its efficacy, especially in the Dermatological diseases can also lead to a greater risk of
treatment of acne scarring and wrinkle improvement, is PIH, with lichenoid dermatitis such as erythema multi-
much lower than that of laser resurfacing [3,4]. forme and lichen planus known to be associated with the
By taking into consideration the mismatch between the most significant degree of PIH in any skin type. Lichenoid
healing properties of the epidermis and the dermis, dermatitis is characterized by the inflammatory disruption
fractional resurfacing aims to achieve clinical results that of the epidermal–dermal junction (EDJ), with subsequent
approach those seen in laser resurfacing, while reducing pigmentary incontinence that leads to a greater degree of

TABLE 3. Prevalence of PIH in the Skin Rejuvenation/Pigment Group Versus the


Acne Scarred Group Using Cross-Polarized Lighting

Wrinkles/pigmentation Acne scar/scar

No. of sessions PIH No. of sessions PIH P-value


After 1st treatment 23 4 12 0 0.275
After 2nd treatment 30 8 10 1 0.404
After 3rd treatment 36 6 6 1 1.000
Total 89 18 (20.2%) 28 2 (7.1%) 0.152
384 CHAN ET AL.

elevation can occur with eight or more consecutive passes,


which leads to epidermal destruction. This phenomenon is
particularly marked in small anatomical areas, as repeat
passes over a short time can cause bulk tissue heating to be
exaggerated.
Our findings have several clinical implications. First,
cooling should be used in conjunction with fractional
resurfacing, especially in dark-skinned patients. Further-
more, the reduction of the treatment density is important.
In our current practice, rather than performing 8–
12 passes and removing 16–20% of the skin per treatment
session, we reduce the number of passes from 4 to 6 and
only remove 8–10% of the skin. Finally, instead of
repeating the treatment at 1–2 week intervals, it is
now our practice to lengthen the treatment interval to 2–
4 weeks for epidermal lesions and 4–6 weeks for dermal
lesions. Preliminary data indicate that this approach is
associated with a reduction in both the down time and the
incidence of complications such as PIH, with the prevalence
of PIH being reduced to 3 out of 101 treatment sessions
Fig. 1. Localized PIH in the peri-oral area after repeated among Japanese patients [10].
passes without cooling. It is important to point out the limitations of our study.
First, although there was a definite trend of a lower
incidence of PIH in the acne scarred group, the difference
PIH. Therefore, factors that affect the EDJ are of particular was not statistically significant, probably due to the sample
importance in the development of PIH. These factors size. The forearm study suffers from the limitation that the
include the degree of inflammation and extent of disruption inner aspect of the forearm has a lower sun exposure than
at the EDJ. the face. At the same time, it is worthwhile to point out that
Although, both the energy and density of the treatment due to lower density of sebaceous follicular unit, forearm
affect the extent of epidermal–dermal disruption, density skin is more prone to laser surgery related complications
is of particular relevance, with a higher density being than the face. As a result, the risk of PIH after fractional
associated with a greater degree of PIH, as indicated by our resurfacing may be higher in the forearm. This may explain
findings. why higher incidence of PIH was observed in the forearm
As the degree of inflammation is also important, its study despite the use of cooling. We will perform further
reduction should be sought through the lengthening of the prospective studies to confirm our findings.
treatment interval to allow any residual dermal inflamma- In conclusion, although both the density and energy of
tion to completely subside. Our study also demonstrates the the treatment can increase the risk of PIH in dark-skinned
importance of adjunctive cooling, without which localized patients, density may be of particular importance. Cooling
PIH can occur, especially in small anatomical regions such to prevent bulk tissue heating is also important, especially
as the peri-oral area. In small anatomical areas there is a in small anatomical areas. In our opinion, by reducing the
risk of bulk tissue heating with repeat passes if cooling is density by half and lengthening the treatment interval, the
not used. Our unpublished data on human cadaver skin risk of PIH in dark-skinned patients can be significantly
indicate that without cooling, a significant temperature reduced.

TABLE 4. PIH Rate After Fractional Resurfacing as Observed by Independent


Observers

No. of instances Severity (mild,


Site Energy (mJ) Total MTZ of PIH (n ¼ 18) moderate, severe)
1 6 2,000 9 Mild (6), moderate (3)
2 9 2,000 9 Mild (6), moderate (3)
3 12 2,000 9 Mild (5), moderate (4)
4 6 250 0
5 12 250 0
6 24 250 2 Mild (2)
7 16 1,000 9 Mild (5), moderate (4)
8 6 3,000 9 Mild (4), moderate (5)
9 6 4,000 9 Mild (1), moderate (8)
FRACTIONAL RESURFACING IN ASIANS 385

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