Clinical Trial

Randomized, controlled trial split-faced study of 595-nm

pulsed dye laser in the treatment of acne vulgaris and acne
erythema in adolescents and early adulthood
Ramrada Lekwuttikarn, MD, Therdpong Tempark, MD, Susheera Chatproedprai,
MD, Msc, and Siriwan Wananukul, MD

Department of Pediatrics, Chulalongkorn Abstract

University, Bangkok, Thailand
Correspondence
Siriwan Wananukul, MD
Department of Pediatrics
11th Floor, Sor Kor Building
Rama IV Rd., Pathumwan
Bangkok 10330
Thailand
E-mail: siriwanwananukul@yahoo.com
Funding: Ratchadapiseksompotch Fund,
Faculty of Medicine, Chulalongkorn
University.
Conflicts of interest: None.
The high prevalence of acne vulgaris in teenagers has increased comorbidities. Lasers
offer alternative options for acne treatment because they have rapid action, low systemic
adverse effects, and do not require everyday treatment. To study the efficacy and patients
satisfaction of 595-nm pulse dye laser (PDL) treatment of acne vulgaris and acne
erythema in adolescents and early adulthood, we designed a blocked-randomized, split-
faced 595-nm PDL (fluence 8 J/cm3 pulse duration 10 ms, spot size 7 mm, 2 session
every 2 weeks) study in patients with mild to moderate acne by comparing the laser-
treated and non-treated side. The acne lesion counts, acne erythema grading, and acne
severity grading were evaluated at baseline and 2, 4, and 8 weeks. Thirty patients were
recruited. The results showed no statistically significant difference except the papule count
at week 4 which was 1.828 on the treated side and 0.103 on the non-treated side of the
face, P-value 0.0018. There was no statistically significant difference of acne severity
grading and acne erythema grading between both sides of the face. The mean scores of
patients satisfaction on the laser-treated side were 75, 81, and 81%, respectively. The
PDL treatment in this study reveals no significant improvement in acne therapy; however,
the patients were satisfied with this laser treatment.

The adolescent period is an important time of physical, emo-

Introduction
Acne vulgaris is one of the most common adolescent problems.
The prevalence had been reported to range from 70 to 87%,
and half of adolescents continue to experience acne vulgaris as
an adult.1,2 Recently, we found an earlier onset of acne
because of the advancing onset trend of puberty.3 The face with
active acne lesions and their sequelae, such as scarring, can
negatively impact the patients psychosocial aspects: low self-
esteem, anxiety in social interaction and stigmatization causing
distress, and depression which may lead to suicidal ideation.4
Left untreated, acne lesions may persist into adulthood, which
is associated with higher unemployment rates for patients with
5
severe acne compared to adults without acne.
Acne is a multifactorial, inflammatory disorder of the pilose-
baceous follicle. At least four major factors contribute to the
formation of cutaneous acne lesions: follicular hyperkeratiniza-
tion, increased sebum production, Propionibacterium acne col-
onization, and an inflammatory response.3 Acne lesions are
classified as noninflammatory (closed and open comedones)
or inflammatory (papules, pustules, and nodulocystic acne)
884 lesions.6
tional, and social development; it is necessary to identify and
treat the affected teenagers at the proper time in order to allevi-
ate the personalized impairment of quality of life and reduce
future socioeconomic burdens from their acne treatment cost.
The procedure should require less frequency of treatment.
The traditional management in acne vulgaris includes topical
and systemic medications with various adverse effects such as
skin irritation, bacterial resistance, and potentially serious terato-
genic effects. Laser treatment of acne may have the benefit of
a faster response and lower systemic toxicities than systemic
medication. Previous studies have revealed the efficacy of laser
treatment for acne.7
Pulsed dye laser (PDL) is the laser specifically used for the
treatment of vascular lesions. The targeted chromophore is
hemoglobin. Nowadays many studies show the efficacy of PDL
in other inflammatory diseases such as psoriasis, acne vulgaris,
rosacea, and lupus erythematosus.8
Most recently, 595-nm PDLs were studied for the efficacy in
acne treatment. The mechanism of action of PDL therapy is
believed to be secondary to damage to P. acne via laser-
absorbed porphyrins.7 It is less painful, has fewer complications

International Journal of Dermatology 2017, 56, 884888 2017 The International Society of Dermatology
Lekwuttikarn et al.
and a lower downtime period when compared with other lasers,
thus it may be suitable for adolescent treatment. However, PDL
laser therapy is more expensive, and thus there are various out-
comes we need to study further for efficacy before recommend-
ing this treatment to our patients.
To our knowledge, this study will be the first English literature
to evaluate the benefits of PDL therapy for acne in adolescents.
Materials and methods
This study was approved by the Institutional Review Board,
Faculty of Medicine, Chulalongkorn University (IRB 555/56),
and written informed consent was obtained from all study
participants. Recruitment occurred from March to June 2014.
Inclusion criteria included the patients between 12 and
22 years old who had mild to moderate facial acne (an acne
severity score of 03 according to the comprehensive acne
severity scale,9 were in general good health, had no clinical
features of androgen excess, no current medication intake, and
were willing and able to comply with the protocol. Exclusion
criteria were (i) a history of prior facial laser treatment within
3 months and, (ii) the use of isotretinoin within 6 months.
To measure the real efficacy of the PDL therapy in our
patients, the previous treatments were not allowed. The
washout periods were 2 weeks for topical acne treatments,
4 weeks for oral antibiotics, and 12 weeks for contraceptive
pills.
The study design was a randomized, split-face clinical trial.
The faces of all participants were blocked-randomized for the
treated side and the opposite side left untreated and serving as
a control. The treated side of the face underwent 2 PDL
treatment times at baseline and at 2 weeks later. PDL
treatment was performed by a single physician using the
following parameters: wavelength of 595 nm, pulse duration of
10 ms, spot size 7 mm, and fluence 8 J/cm2. The overlapping
pulses (10% overlapping) were delivered in a painting motion to
cover the entire side of the face to be treated from the hairline
to the jaw line for one pass, excluding the eyelid. Two identical
lasers were used during the course of the study. At the end,
patients were offered the option of having the previously
non-treated side of the face treated.
Participants were evaluated four times, the baseline visit
(week 0), week 2, week 4, and week 8. The evaluations were
the acne lesion counts of comedones, papules, pustules, and
nodules, and the acne erythema grading (Table 1), which were
done by the physician who performed the laser treatment. The
grading of acne severity was evaluated per the comprehensive
acne severity scale (Table 2) by three pediatric dermatologists,
who were blinded to the subject treatment and assessed
standardized photographs. Participants were photographed at a
fixed distance and a defined spot position in the Division of
Pediatric Dermatology room, using a Nikon1 J1 digital camera
(Nikon Corp, Tokyo, Japan).
2017 The International Society of Dermatology
Benefits of PDL therapy for acne in adolescents Clinical Trial 885
12
Table 1 The 4-point grading of acne erythema
Grade Level of disease Characteristics
0 None Clear
1 Mild Faintly detectable erythema, light pink
2 Moderate Dull red, clearly distinguishable
3 Severe Deep/dark red
Table 2 The Comprehensive Acne Severity Scale (CASS)
Grade Description
Clear 0 No lesions to barely noticeable ones. Very few scattered
comedones and papules
Almost 1 Hardly visible from 2.5 m away. A few scattered
clear comedones, few small papules, and very few pustules
Mild 2 Easily recognizable; less than of the affected area is
involved. Many comedones, papules, and pustules
Moderate 3 More than half of the affected area is involved.
Numerous comedones, papules, and pustules
Severe 4 Entire area is involved. Covered with comedones,
numerous pustules, and papules, a few nodules and
cyst
Very 5 Highly inflammatory acne covering the affected area,
severe with nodules and cyst present
The primary objective was to compare the difference of acne
severity scale, acne lesion counts, and acne erythema grading
between the treated and untreated side of the face. We
compared the mean difference of these variable parameters by
using the paired t test analysis. The complications from the
laser treatment were accessed every visit. Participants
satisfaction was scored, using a 10-point scale (010 means
dissatisfied to very satisfied) by the participants at weeks 2, 4,
and 8.
A sample size of 30 patients, calculated by using Power and
Sample size program, provides a power of 0.85 for detecting a
difference of 2 in the reduction of mean acne severity score
from baseline between the treated and untreated sides of the
face, with a type I error rate of 0.05 for 2-tailed hypothesis and
assuming an SD of the difference of 2.
Results
We enrolled 30 participants (17 males, 56.7%) with a mean age
of 18 years (range, 13.021.6 years). Half of the participants
were blocked-randomized to receive treatment to the left side of
the face and the other half to the right side. The mean number
of pulses was 240.83 shots for the treated side of the face.
Baseline mean acne severity grading of two groups was simi-
lar: 2.25 for the treated side and 2.27 for the untreated side of
the face (P = 0.83). The baseline acne lesion counts and acne
erythema grading showed no statistically significant differences
between treated and untreated sides of the face.
International Journal of Dermatology 2017, 56, 884888
886 Clinical Trial Benefits of PDL therapy for acne in adolescents Lekwuttikarn et al.

Table 3 The results of acne severity grading and acne lesion counts before and after pulse dye laser (PDL) therapy

Baseline 02 weeks (1st PDL) 04 weeks (2nd PDL) 08 weeks

Variable Control PDL p-value Control PDL p-value Control PDL p-value Control PDL p-value

Acne severity score

Mean diff 0.09 0.07 0.95 0.30 0.23 0.22 0.47 0.46 0.89
SD (0.37) (0.40) (0.50) (0.55) (0.51) (0.57)
Mean 2.26 2.25 0.83 2.17 2.18 1.96 2.02 0.41 1.79 1.79 1.00
Comedones
Mean diff 1.37 1.83 0.25 3.21 6.48 0.42 4.00 9.39 0.10
SD (17.42) (19.48) (25.54) (24.88) (19.02) (24.04)
Mean 46.07 49.43 0.22 47.43 47.60 0.96 44.27 47.50 0.53 38.67 37.43 0.58
Papules
Mean diff 0.27 0.83 0.38 0.103 1.83 0.002 0.10 0.53 0.39
SD (2.56) (2.83) (3.03) (2.99) (3.94) (3.40)
Mean 3.53 4.33 0.07 3.27 3.59 0.66 3.73 3.10 0.25 3.43 3.80 0.48
Pustules
Mean diff 1.17 0.13 0.29 0.90 0.03 0.08 0.97 0.57 0.09
SD (3.95) (3.04) (2.72) (3.46) (2.66) (4.15)
Mean 2.67 1.63 0.10 1.50 1.50 1.00 1.77 1.67 0.79 1.70 2.20 0.33
Nodules
Mean diff 0.20 0.10 0.53 0.30 0.07 0.05 0.17 0.33 0.29
SD (0.85) (0.92) (0.79) (0.45) (0.83) (1.10)
Mean 0.17 0.30 0.26 0.37 0.40 0.85 0.47 0.37 0.48 0.33 0.27 0.42

Table 4 The results of acne erythema grading before and after pulse dye laser (PDL) therapy

Baseline 2 weeks (1st PDL) 4 weeks (2nd PDL) 8 weeks

Variables Control PDL p-value Control PDL p-value Control PDL p-value Control PDL p-value

Acne erythema grading 1.90 1.90 0.83 1.57 1.57 0.86 1.50 1.47 0.41 1.33 1.33 1.00

2 We found a statistically significant difference in reduction of

P = 0.83
papule counts at week 4 on the PDL-treated side of the face. The
1.8
P = 0.86 P = 0.41
rest of the acne lesion counts and acne severity grading for trea-
1.6 ted compared to untreated sides showed no statistically signifi-
P = 1.0 cant differences from baseline as compared to week 12 (Table 3).
1.4
There was a trend for bilateral erythema grading to decrease on
1.2 both sides of the face, but no statistically significant differences
No PDL between treated and non-treated sides (Table 4 and Fig. 1).
1
PDL
The participants were provided a high level of satisfaction with
0.8 the PDL treatment. The satisfaction scores were 7.53, 8.13, and
8.10 (of 10) at the 2nd, 4th, and 8th weeks, respectively.
0.6
The first adverse event was transient postinflammatory
0.4 hyperpigmentation which was noted in four participants (7.5%),
but all resolved spontaneously within 8 weeks. The other
0.2
adverse event was tolerable pain. All of the participants could
0 tolerate and complete the protocol laser treatment.
Baseline 2 weeks (1st PDL) 4 weeks (2nd PDL) 8 weeks

Figure 1 The results of acne erythema grading before and after Discussion
pulse dye laser (PDL) therapy
P = P-value of the difference of acne erythema grading between Nowadays, it is very challenging to discover the best therapy for
PDL treated and untreated side of face acne vulgaris especially in adolescents because the disease is

International Journal of Dermatology 2017, 56, 884888 2017 The International Society of Dermatology
Lekwuttikarn et al.
a clinically dynamic condition which shows spontaneous
improvement and flares. The therapy requires consistent com-
pliance, which is quite difficult for adolescents. Recently, the
laser treatments have become very popular because they are
faster, more convenient, and have fewer adverse events than
conventional therapy.
Our study showed a statistically significant improvement only
in papule lesion count on the PDL-treated side: 1.8 (P-value
0.0018) lesions from the baseline at week 4 and might not be
clinically significant in real dermatologic practice because of the
high cost when compared with conventional therapy. The possi-
ble causes include: our patients had more prominent comedonal
lesions than inflammatory papules and nodules; the number of
treatment sessions in our study were too few; and the duration
of follow-up may not have been long enough to see a positive
clinically significant result.
The result from our study was similar to the result of the
Orringer et al.10 study, which used a non-purpuric PDL setting
(585 nm, fluence 3 J/cm2, pulse duration 0.35 ms, spot size
7 mm). Conversely, the Seaton et al.11 study showed an
improvement of inflammatory facial acne by using only a single
treatment of PDL laser. The positive result may be attributed to
the study design, which differed from our study. They recruited
different persons for the control group and experimental group
while we used the same person. We believe that our split-faced
clinical trial reduced the confounding factors impacting the
results such as the hormonal change in adolescents, stress,
and the cosmetic usage in each person. There are many previ-
ous studies10,12 that, using the same setting with Seaton et al,11
could not show a positive effect of PDL in acne therapy. There-
fore, we increased the energy of the PDL setting (595 nm, flu-
ence 8 J/cm2, pulse duration 10 ms, spot size 7 mm), a higher
setting than Seaton et al,11 which used a non-purpuric PDL set-
ting (585 nm, fluence 1.5 and 3 J/cm2, pulse duration 0.35 ms,
spot size 5 mm): we could not demonstrate a clinically signifi-
cant improvement of acne by PDL therapy compared with no
treatment. Even though Choi et al.13 used higher energy similar
to our study and showed a positive efficacy of PDL in acne
treatment, they compared PDL and IPL therapy on a split-face
trial. However, we could not conclude the positive results came
from PDL therapy alone.
The result of acne erythema did not demonstrate a significant
difference between the treated side and nontreated side of the
face, contrasted to the Yoon et al.14 study in which the result of
acne erythema improved significantly in the treated side of the
face. This might be from the higher energy usage or difference
of Fitzpatrick skin type. The lower fluent usage in our study
may not have penetrated deeply enough to destroy these
inflammatory microvessels.15 We designed our study to use this
fluency because the participants Fitzpatrick skin types in our
study were 45, which differed from the Yoon study.
Furthermore, we found the downward trend in acne erythema
grading on both sides of the face might possibly be a placebo
2017 The International Society of Dermatology
Benefits of PDL therapy for acne in adolescents Clinical Trial 887
effect as patients perhaps pay more attention to their skin care
and/or the PDL laser increases the level of transforming growth
factor b1 (TGF-b1)16 that promotes the termination of inflamma-
tory processes17 and may cause decline in acne erythema. We
did not study the level of TGF-b1 which is our limitation. From
our study, the efficacy of PDL laser in acne erythema therapy
was inconclusive.
In summary, PDL therapy in acne vulgaris has both excellent
and ineffective results and because of the popularity of laser
therapy in acne vulgaris, we need further study to find the
appropriate setting, frequency, and duration for PDL treatment.
We need a well-controlled study for adjuvant PDL therapy from
conventional treatment before the recommendation to use the
PDL therapy in adolescent acne vulgaris is proposed.
References
1 Eichenfield LF, Krakowski AC, Piggott C, et al. Evidence-based
recommendations for the diagnosis and treatment of pediatric
acne. Pediatrics 2013; 131(Suppl 3): S163S186.
2 Dawson AL, Dellavalle RP. Acne vulgaris. BMJ 2013; 346:
f2634.
3 Mancini AJ, Baldwin HE, Eichenfield LF, et al. Acne life cycle:
the spectrum of pediatric disease. Semin Cutan Med Surg 2011;
30: S2S5.
4 Dunn LK, ONeill JL, Feldman SR. Acne in adolescents: quality
of life, self-esteem, mood, and psychological disorders.
Dermatol Online J 2011; 17: 1.
5 Gieler U, Gieler T, Kupfer JP. Acne and quality of life impact
and management. J Eur Acad Dermatol Venereol 2015; 29
(Suppl 4): 1214.
6 Clinical practice guideline for acne 2011 [Internet]. 2011.
Available from: http://www.dst.or.th/files_news/001-Guideline_Ac
ne_2011.pdf (accessed 1 Jun 2015).
7 Nouri K, Ballard CJ. Laser therapy for acne. Clin Dermatol 2006;
24: 2632.
8 Erceg A, de Jong EM, van de Kerkhof PC, et al. The
efficacy of pulsed dye laser treatment for inflammatory skin
diseases: a systemic review. J Am Acad Dermatol 2013; 69:
609615.
9 Tan JK, Tang J, Fung K, et al. Development and validation of a
comprehensive acne severity scale. J Cutan Med Surg 2007;
11: 211216.
10 Orringer JS, Kang S, Hamilton T, et al. Treatment of acne
vulgaris with a pulsed dye laser: a randomized controlled trial.
JAMA 2004; 291: 28342839.
11 Seaton ED, Charakida A, Mouser PE, et al. Pulsed-dye laser
treatment for inflammatory acne vulgaris: randomised controlled
trial. Lancet 2003; 362: 13471352.
12 Karsai S, Schmitt L, Raulin C. The pulsed-dye laser as an
adjuvant treatment modality in acne vulgaris: a randomized
controlled single-blinded trial. Br J Dermatol 2010; 163:
395401.
13 Choi YS, Suh HS, Yoon MY, et al. Intense pulsed light vs.
pulsed-dye laser in the treatment of facial acne: a randomized
split-face trial. J Eur Acad Dermatol Venereol 2010; 24:
773780.
14 Yoon HJ, Lee DH, Kim SO, et al. Acne erythema improvement
by long-pulsed 595-nm pulsed-dye laser treatment: a pilot study.
J Dermatolog Treat 2008; 19: 3844.
International Journal of Dermatology 2017, 56, 884888
888 Clinical Trial Benefits of PDL therapy for acne in adolescents
15 Panchaprateep R, Munavalli G. Low-fluence 585 nm Q-switched
Nd:YAG laser: a novel laser treatment for post-acne erythema.
Lasers Surg Med 2015; 47: 148155.
16 Seaton ED, Mouser PE, Charakida A, et al. Investigation of the
mechanism of action of nonablative pulsed-dye laser therapy in
International Journal of Dermatology 2017, 56, 884888
Lekwuttikarn et al.
photorejuvenation and inflammatory acne vulgaris. Br J
Dermatol 2006; 155: 748755.
17 Harto A, Garcia-Morales I, Belmar P, et al. Pulsed dye laser
treatment of acne. Study of clinical efficacy and mechanism of
action. Actas Dermosifiliogr 2007; 98: 415419.
2017 The International Society of Dermatology