Acne scarring—a common consequence of acne—results from the net gain or loss of collagen
fibers and subcutaneous fat during inflammatory acne vulgaris healing. The incidence
of acne scarring has not been extensively studied, but it is estimated to affect approximately
95% of acne patients.[1] Having acne scars can be emotionally and psychologically distressing to patients,
which in turn can be a high-risk factor for suicide.[2]
Studies have also shown that suffering from acne scars is linked to poor self-esteem,
reduced daily activities and social interactions, and unemployment.[3]
[4] Acne scars are classified into three types: atrophic scar, hypertrophic scar, and
keloid. Atrophic acne scar can be further divided into three subtypes: ice-pick scar,
rolling scar, and boxcar scar according to their width, depth, and three-dimensional
(3D) architectures.[5]
[6] A quantitative global acne scarring grading system is the standard for the assessment
of disease load and severity of acne scarring, and atrophic acne scar can be classified
into mild, moderate, and severe scarring according to its severity.[6]
Many treatment options are available to improve atrophic acne scars, including chemical
peels, dermabrasion/microdermabrasion, punch grafting, tissue fillers, needling, nonablative
fractional resurfacing (NAFR) lasers, and ablative lasers. However, these treatments
are often limited in variable and operator-dependent efficacies, temporary nature
of clinical improvements, and adverse effects.[7]
[8]
Carbon dioxide (CO2) laser is a well-established and effective treatment for atrophic acne scars. The
laser at a wavelength of 10,600 nm is absorbed by the water in intracellular tissues
and can selectively heat and vaporize superficial skin.[7] Through controlled heating of dermal collagen, the traditional CO2 laser can eliminate the fragmented collagen matrix and therefore promote new collagen
production and subsequently improve scar appearance.[9] However, the procedure is associated with high risk of complications and side effects,
such as lengthy recovery time, prolonged erythema, scars, hypopigmentation, and postinflammatory
hyperpigmentation (PIH), especially for patients with a darker skin phototype.[10]
[11]
Fractional photothermolysis (FP), a new technique of skin rejuvenation, was designed
to overcome these problems. To achieve homogeneous thermal damage at a particular
depth within the skin, FP creates microscopic thermal wounds—referred to as the microscopic
thermal zone—and specifically spares tissues surrounding each wound.[12] Ablative fractional carbon dioxide laser (AF CO2) treatment combines CO2 ablation with the FP system and represents a safe and effective treatment modality
for acne scarring.
Compared with conventional ablative CO2 lasers, the AF CO2 method can provide rapid reepithelialization from surrounding undamaged tissues,
thus resulting in faster recovery, reduced downtime, and greatly improved side effects
for patients.[13]
[14]
[15] Magnani and Schweiger reviewed the efficacy and safety of AF CO2 for the treatment of atrophic scarring secondary to acne vulgaris.[16]
The goal of this review was to establish individualized treatment guidelines after
analysis of the treatment procedures.
Results
The literature search yielded 337 unique articles; 30 articles met our inclusion and
exclusion criteria, comprising 12 retrospective studies (case series and case reports)[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28] and 18 prospective randomized clinical trials.[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
Patient Characteristics
This review covered a total of 512 patients enrolled in 30 studies (including 407
Asian patients in 24 studies); the patient characteristics are shown in [Table 1]. The mean age of the enrolled subjects ranged from 22 to 40 years.[18]
[19] The severity of acne scars was mostly accessed according to the Goodman and Baron
quantitative global scarring grading system,[6] with three studies[33]
[38]
[45] based on the ECCA (échelle d'évaluation clinique des cicatrices d'acné) grading
scale.[47] Thirteen studies included patients with Fitzpatrick skin type III to IV and seven
studies included type IV patients only.
Table 1
Patient characteristics
|
Study
|
Year
|
Country
|
Number of patients
|
Sex ratio (M/F)[a]
|
Age (mean or range in y)
|
Fitzpatrick skin type
|
Atrophic scars severity[b]
|
Atrophic scars types[c]
|
|
Chapas et al[17]
|
2008
|
United States
|
15
|
NA
|
28–58
|
I–IV
|
Moderate to severe
|
Boxcar, rolling, ice pick
|
|
Walgrave et al[18]
|
2009
|
United States
|
30
|
NA
|
40
|
I–V
|
Moderate to severe
|
NA
|
|
Qian et al[19]
|
2012
|
China
|
31
|
20/11
|
22.0
|
III–IV
|
Mild to severe
|
Boxcar, rolling, ice pick
|
|
Hsiao et al[20]
|
2013
|
Taiwan
|
25
|
19/6
|
30.4
|
III–IV
|
Mild to moderate
|
Boxcar, rolling, ice pick
|
|
Cho et al[21]
|
2009
|
Korea
|
20
|
7/13
|
27
|
IV
|
Mild to severe
|
NA
|
|
Huang[22]
|
2013
|
China
|
44
|
13/31
|
26
|
IV
|
Moderate to severe
|
NA
|
|
Trelles et al[23]
|
2011
|
Spain
|
10
|
NA
|
NA
|
III–IV
|
NA
|
NA
|
|
Ahmad et al[24]
|
2012
|
Pakistan
|
20
|
3/17
|
23
|
III–IV
|
Mild to moderate
|
NA
|
|
Manuskiatti et al[29]
|
2010
|
Thailand
|
13
|
5/8
|
34
|
IV
|
Mild to moderate
|
NA
|
|
Kim et al[25]
|
2014
|
South Korea and China
|
20
|
9/11
|
23.9
|
III–IV
|
NA
|
NA
|
|
Hedelund et al[30]
|
2012
|
Denmark
|
13
|
6/7
|
33
|
I–III
|
Moderate to severe
|
NA
|
|
Schweiger and Sundick[27]
|
2013
|
United States
|
6
|
5/1
|
26.5
|
NA
|
NA
|
NA
|
|
Wang et al[26]
|
2010
|
Singapore
|
5
|
4/1
|
27
|
IV
|
Moderate to severe
|
NA
|
|
Alajlan et al[28]
|
2011
|
Saudi Arabia
|
37
|
NA
|
NA
|
III–IV
|
Mild to severe
|
NA
|
|
Cho et al[35]
|
2010
|
South Korea
|
8
|
8/0
|
21.3
|
IV
|
Mild to severe
|
Rolling, boxcars, ice pick
|
|
Manuskiatti et al[46]
|
2013
|
Thailand
|
24
|
NA
|
29.5
|
IV
|
NA
|
Shallow or deep boxcar
|
|
Reinholz et al[36]
|
2015
|
Germany
|
14
|
9/5
|
28.6
|
NA
|
Severe
|
Rolling, boxcar, ice pick
|
|
Asilian et al[37]
|
2011
|
Iran
|
32
|
NA
|
26.3
|
II–IV
|
Moderate to severe
|
Rolling, boxcar, ice pick
|
|
Zhang et al[38]
|
2013
|
China
|
14
|
11/3
|
26.4
|
III–IV
|
Mild to severe
|
NA
|
|
Azzam et al[39]
|
2013
|
Egypt
|
10
|
NA
|
18–38
|
III–IV
|
NA
|
Rolling, boxcars, ice pick
|
|
Ahmed et al[40]
|
2014
|
NA
|
14
|
NA
|
22.7
|
II–V
|
NA
|
Ice pick
|
|
Cameli et al[41]
|
2014
|
NA
|
6
|
NA
|
NA
|
NA
|
NA
|
Superficial, rolling
|
|
Faghihi et al[42]
|
2016
|
China
|
16
|
4/12
|
36.8
|
II–IV
|
Moderate to severe
|
Rolling, boxcars, ice pick
|
|
Gawdat et al[43]
|
2014
|
NA
|
5
|
2/3
|
24.8
|
III–IV
|
Mild to severe
|
NA
|
|
Lee et al[44]
|
2011
|
South Korea
|
14
|
10/4
|
28.1
|
III–IV
|
Moderate to severe
|
NA
|
|
Zhou et al[45]
|
2015
|
NA
|
13
|
NA
|
NA
|
NA
|
NA
|
NA
|
|
Kim and Cho[31]
|
2009
|
South Korea
|
20
|
11/9
|
24.5
|
IV–V
|
Mild to severe
|
NA
|
|
Jung et al[32]
|
2010
|
South Korea
|
10
|
10/0
|
22.2
|
IV
|
Mild to severe
|
NA
|
|
Yuan et al[33]
|
2014
|
China
|
10
|
10
|
22–31
|
III–IV
|
Moderate to severe
|
NA
|
|
Bjørn et al[34]
|
2014
|
NA
|
13
|
NA
|
18–60
|
I–III
|
Moderate to severe
|
NA
|
Abbreviations: F, female; M, male; NA, not answered.
a Patient in the fractional carbon dioxide laser treatment group.
b Severity of the scar was determined according to Goodman and Baron.[6]
c Type of the scar was determined according to the report by Jacob et al.[5]
Most of the exclusion items for patient selection are listed in [Table 2], while exclusion criteria were not mentioned in four studies.[22]
[23]
[27]
[28] Isotretinoin use was excluded in 26 studies, except in the Kim et al[25] study where all patients received oral isotretinoin ranging from 10 to 40 mg/d.
A history of keloid scars was also excluded in the Walgrave et al, Ahmad et al, and
Gawdat et al studies.[18]
[24]
[43]
Table 2
Exclusion of patients
|
Items of exclusion
|
References
|
|
Pregnant or lactating
|
[17]
[18]
[19]
[20]
[21]
[25]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[41]
[42]
[43]
[44]
[45]
[46]
|
|
Isotretinoin use (oral retinoids within the preceding 12 or 6 mo or topical use)
|
[17]
[18]
[19]
[20]
[21]
[24]
[25]
[26]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
|
|
History of keloid scar formation
|
[17]
[19]
[20]
[21]
[25]
[26]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[44]
[45]
[46]
|
|
Cosmetic procedures (filler injections, botulinum toxin A, ablative/nonablative laser
skin resurfacing procedures, chemical reconstruction of skin scars using trichloroacetic
acid, collagen induction therapy using a microneedle therapy system) within the previous
6 or 12 mo
|
[17]
[18]
[19]
[20]
[21]
[24]
[25]
[26]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
[37]
[38]
[40]
[42]
[44]
[46]
|
|
Undergoing immune suppression
|
[19]
[21]
[32]
[33]
[35]
[37]
[38]
[40]
[43]
|
|
Active infections (localized or systemic infections status)
|
[17]
[18]
[19]
[36]
[38]
[40]
[44]
[45]
|
|
History of photosensitivity
|
[19]
[25]
[26]
[30]
[38]
[39]
|
|
Pigmentation after recent exposure to the sun or solarium
|
[25]
[30]
[34]
|
|
Current anticoagulative medication
|
[25]
[30]
[41]
[45]
|
|
History of carcinoma or cancer lesions
|
[26]
[38]
[45]
|
|
Systemic disease (diabetes or hypertension), collagen disease, diabetes
|
[39]
[41]
[42]
[44]
[45]
|
|
Active dermatitis, warts
|
[38]
[44]
[45]
|
|
Herpes simplex infection (during the previous 6 mo)
|
[31]
[34]
[40]
[42]
[45]
|
|
Allergies to lidocaine
|
[17]
[18]
|
|
Smoking
|
[17]
[18]
[26]
|
|
Corticosteroids
|
[45]
|
|
Fitzpatrick skin type of VI
|
[18]
|
|
Deep boxcar and ice-pick acne scars, active acne
|
[31]
[41]
|
|
Younger than 18 y
|
[39]
|
Treatment Procedures
All treatment procedures are summarized below. First, treatment areas were cleaned
with a mild cleanser. Then, topical anesthesia such as local anesthesia and facial
nerve blocks or oral pain-killer were applied before treatment.[17]
[18]
[20]
[21]
[22]
[25]
[26]
[29]
[30]
[32]
[33]
[34]
[35]
[38]
[42]
[43] Patients were prepared with an intravenous catheter in case extra analgesia or sedation
was required.[23] Next, alcohol or acetone was used to degrease the skin before the treatment began.
To help mitigate the pain and reduce the burning sensation experienced during the
treatment, forced air cooling system or cold air flow[18]
[21]
[23]
[31]
[35] was constantly applied to the treatment area, and wet, cold gauzes or ice packs[20]
[22]
[29]
[33]
[42]
[43]
[44] were applied immediately after the operation. Cleaning of the treated site with
tap water after the treatment was allowed in two studies,[26]
[38] but was not permitted until 24 hours or later in four studies.[22]
[23]
[25]
[33] Postoperatively, a moisturizing cream was applied to promote wound healing and prevent
dryness.[20]
[21]
[22]
[23]
[25]
[26]
[27]
[29]
[31]
[32]
[34]
[35]
[38]
[39]
[41]
[46]
Prophylactic and postoperative antiviral agents were recommended for subjects with
a documented history of herpes labialis only[21]
[29]
[32]
[34]
[35]
[38]
[44] or for all patients.[18]
[25] In two studies,[23]
[26] no oral antiherpes medication was recommended. Prophylactic antibiotics were given
to all patients in three studies,[17]
[18]
[29] while a topical antibiotic cream was recommended after the treatment in several
other studies.[19]
[25]
[39]
[41]
[42]
[43]
To prevent an inflammatory reaction and reduce facial edema, oral steroids,[21]
[32]
[35] or topical steroid creams were prescribed for the first several days.[18]
[25]
[33]
[39] Nearly all the studies recommended daily use of a broad-spectrum sunscreen to avoid
overexposure to sunlight[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[29]
[32]
[33]
[35]
[38]
[39]
[40]
[42]
[43]
[46] immediately after the treatment, while the use of sunscreen until complete healing
of crusting was recommended in five other studies.[21]
[25]
[29]
[33]
[46] A recombinant human epidermal growth factor containing hydrogel was applied four
times daily for 1 week in two studies.[22]
[33] Postoperative care was not specified in three articles.[28]
[36]
[37]
Treatment Sessions and Intervals
A summary of the 30 reviewed studies is shown in [Table 3]. Eight case series, involving a total of 95 patients, showed the benefit of CO2 laser ablation with a single session.[20]
[21]
[23]
[27]
[32]
[33]
[35]
[41] At the 4-week follow-up, the clinical improvement based on the depth of scar assessed
by both the physicians and patients was rated at over 60%.[27] In Trelles et al's[23] study, all patients had 26 to 50% improvement at 2 months. All patients in the Cameli
et al[41] study were reported to have more than 25% clinical improvement 3 months after treatment.
Similarly, at the 3-month follow-up, the quartile grading scores in the Cho et al,[21] Hsiao et al,[20] and Cho et al[35] studies were 2.41, 2.4, and 2.5, respectively, corresponding to 26 to 50% overall
improvements.
Table 3
Summary of reviewed studies
|
Study/study type
|
CO2 facility
|
Energy/density (level)[a] or coverage/spot size
|
No. of passes/treatment area
|
No. of sessions/intervals/follow-up (mo)
|
Primary results/conclusions
|
|
Chapas et al[17]/case series
|
Reliant Fraxel re:pair laser prototype
|
20–100 mJ/200–1,200 MTZ/cm2/120 μm
|
2 or 3 passes/full face
|
2–3 /1–2 mo/1, 3
|
MQGS were 2.42/4 and 2.46/4 for subjects and investigators
Immediate erythema was graded as mean 2.92/4
|
|
Walgrave et al[18]/case series
|
Reliant Fraxel re:pair laser prototype
|
20–100 mJ/600–1,600 MTZ/cm2
|
1 pass/full face
|
1–3/4–12 wk/1, 3
|
MQGS was 1.73/4 and1.42/4 for investigator at 1 and 3 mo follow-up
Average pain score was 5.9/10
|
|
Qian et al[19]/case series
|
Lumenis ActiveFx, UltraPulse 5000
|
150–200 mJ/5–6/1.2 mm
|
1 pass/full face or cheeks or forehead
|
3/2 mo/3, 12
|
Patients with excellent, good, fair, and poor improvements were 4 (12.9%), 8 (25.8%),
13 (41.9%), and 6 (19.4%) at 12 mo follow-up
4 patients exhibited posttreatment and transient PIH
|
|
Hsiao et al[20]/case series
|
Lumenis UltraPulse Encore fractional CO2 laser
|
Deep FX 12.5–15 mJ/2–3/0.12 mm
|
Cheeks or nose
|
1 session/1, 3
|
MQGS was 2.41/4 for physicians at 3 mo follow-up
Side effects were minimal and had mostly resolved by 3 mo
|
|
Cho et al[21]/case series
|
Lumenis UltraPulse Encore fractional CO2 laser
|
Deep FX 10–20 mJ/2 + Active FX 50–100 mJ/2
|
1 pass/Deep FX for acne scars + Active FX/full face
|
1 session/3
|
MQGS was 2.4/4 for physicians
Patients' satisfaction revealed that 60.0% were very satisfied or satisfied
Mean duration of posttherapy crusting or scaling was 6.3 d
Posttherapy erythema lasted 2.8 d
|
|
Huang[22]/retrospective review
|
Lumenis UltraPulse Encore fractional CO2 laser
|
Active FX 100–150 mJ/5–7; Deep FX10–15 mJ/10–15%; Active FX 100–125 mJ/1–2/120 μm
for Deep FX and 1.3 mm for Active FX
|
4–5 passes/Deep FX for acne scars + Active FX for full face
|
2–7/2–6 mo/3
|
64% had an improvement between 51 and 75%
Average overall improvement was 52.50%
Edema usually resolved within 3 d
|
|
Trelles et al[23]/retrospective study
|
Alma Pixel CO2 laser system
|
120 mJ
|
4–6 passes (scar tissue) + 2 passes (full face)
|
1 session/2
|
All patients had fair or good improvements;
Erythema free 2 mo after treatment
|
|
Ahmad et al[24]/case series
|
Max 7000, Korea
|
10–20 mJ/2–3
|
1 pass/full face
|
6/1 mo/6
|
Average improvement of 71% was observed
|
|
Manuskiatti et al[29]/single-blinded RCT
|
Hørsholm Ellipse Juvia, Ellipse A/S
|
75–105 mJ/MTZ/9.6%/500 μm
|
1 pass/full face
|
3/Average 7 wk/1, 3, 6
|
Physicians graded 85% of subjects as having 25–50% improvement
Over 50% of patients (8 of 13) rated themselves as having >50% improvement
Average pain 8.1/10; PIH was 92.3%
|
|
Kim et al[25]/retrospective study
|
Lutronic Mosaic eCO2 laser
|
30–50 mJ/100–200 MTZ/cm2
|
1–2 passes
|
1–6/> 1 mo/6
|
All patients achieved moderate-to-much improved scores
The results after 6 mo were satisfactory in all patients
Complete reepithelialization after 7 d in all patients
|
|
Hedelund et al[30]/intraindividual[b] single-blinded RCT
|
Hvidovre MedArt 610
|
48–56 mJ/13%/0.5 mm
|
1pass/cheeks, temporal and chins
|
3/4–5 wk/1, 3, 6
|
Scar texture and atrophy by physicians at 6 mo follow-up were 3.89/10 and 3.56/10
Patients' satisfaction scores was 4.5/10
Mild-to-moderate pain
|
|
Wang et al[26]/case series
|
MiXto SX, CA
|
28 J/cm2/20%/300 μm
|
1 pass/full face
|
1 session/2
|
4 patients had mild improvement; 1 patient had moderate improvement
Erythema lasted for a mean of 6 d
|
|
Schweiger and Sundick[27]/case series
|
MiXto SX, Italy
|
13–14 J/S/15–40%
|
1or 2 pass/acne scars
|
1 session/4 wk
|
3 patients had 60% improvement; 2 patients had 70% improvement; 1 patient had 75%
improvement
|
|
Kim and Cho[31]/single-blinded RCT
|
Stratek CoScan-5000
|
High energy: 50–70 mJ
Low energy: 15–35 mJ/20%/0.2 mm
|
1 pass/full face
|
3/4 wk/3
|
Observers' grading averaged 5.8/10 and 4.0/10 separately for the treatment with h-AFR
alone and l- AFR
Subjects' self-grading averaged 6.2/10 and 4.2/10 separately for the treatment with
h-AFR alone and l- AFR
Laser treatments with h-AFR alone were associated with more erythema, crusts, and
hyperpigmentation
|
|
Jung et al[32]/single-blinded split RCT
|
Lutronic Mosaic eCO2 laser
|
Low-fluence, high-density: 30 mJ/12.8%
High-fluence, low-density 70 mJ/12.3% coverage
|
1 pass/full face
|
1 session/3
|
MQGS was 2.47/4 for physicians for low-fluence, high-density CO2 FS and 3.37/4 for high-fluence, low-density
Overall satisfaction levels of the two group were not significantly different
|
|
Yuan et al[33]/single-blinded split RCT
|
Lumenis UltraPulse Encore fractional CO2 laser
|
Deep FX, group A 20 mJ/10% VS 20 mJ/20%
Group B 20 mJ/10% VS 10 mJ/10%
|
1 pass/full face
|
1 session/1, 3
|
Group A: 8/10 patients showed >50% improvement in both the lower and higher fluence
groups; patient satisfaction 5.90/10 vs. 5.95/10, average edema duration 3.10 vs.
4.50, mean pain 4.36 vs. 6.12
Group B: 8/10 patients showed >50% improvement in the lower fluence group, 9/10 patients
showed >50% improvement in the higher fluence group; patient satisfaction 5.42/10
vs. 5.30/10, average edema duration 3.50 vs. 2.50, mean pain 4.98 vs. 4.39
|
|
Bjørn et al[34]/intraindividual single-blinded split RCT
|
Lumenis UltraPulse Encore fractional CO2 laser
|
Deep FX 17.5–22.5 mJ/15%
+Active FX 105 mJ/82%
|
1 pass/full face
|
2/1 mo vs. 3 mo/1, 6
|
No differences between the different treating interval nor the occurrence of postoperative
adverse effects
Pain 7.23/10 on the first treatment
|
|
Alajlan et al[28]/retrospective study
|
FX–Lumines, CA
|
Avg.125 mJ/cm2/30%
|
1 pass/full face
|
Average 2.5/2 mo/3
|
37% of patients attained > 50% improvement with AF CO2 lasers
Patient satisfaction 65% for AF CO2 laser;
PIH was 41%
|
|
Cho et al[35]/single-blinded split RCT
|
Lumenis UltraPulse Encore fractional CO2 laser
|
Deep FX 10–20 mJ/2
Active FX 50–100 mJ/2
|
1 pass/Deep FX for acne scars + Active FX for full face
|
1 session/3
|
MQGS was 2.5/4 for physicians
50.0% of patient were slightly satisfied
Mean duration of posttherapy crusting and scaling was 7.4 d, erythema lasted 11.5
d
|
|
Manuskiatti et al[46]/single-blinded split RCT
|
Lumenis AcuPulse
|
Average 13.75 mJ/5% coverage/10 mm
|
1 pass
|
2/2 mo/1, 3, 6
|
65% of CO2 sites were rated as > 50% improvement by physicians
60% of CO2 sites were rated as > 50% improvement in patients Average pain 5.8/10, lasting for
an average of 3 h
Crusting completely sloughed off in an average of 3.3 d
|
|
Reinholz et al[36]/single-blinded split RCT
|
MultiPulse by Asclepion Laser Technologies
|
5–25 J/S/500 µm
|
1 pass
|
4/4 wk/1
|
Severity of the evaluated atrophic acne scars changed from an average of 5.8/10 points
to 3.9/10
Reduction of scar depth was 32.7% after treatment
Mean pain 5.0/10
|
|
Asilian et al[37]/single-blinded RCT
|
Alma Pixel CO2 laser system
|
350 μm
|
3 passes /full face
|
4/4 wk/6
|
Mean percent of scar improvement was 46.6% of patients
37.5% of patients had >50% improvement by physicians
PIH resolved spontaneously after 2–3 wk
|
|
Zhang et al[38]/single-blinded split RCT
|
Alma Lasers Accent
|
Deep FX mode, 20–25 mJ//2–4
|
1 pass/full face
|
3/Average 8 wk/6
|
59.2% improvement (ECCA scores)
60.6% of patients were very satisfied or satisfied
Mean duration of posttherapy erythema and scaling was 5.7 d
Average duration of PIH was 45.8 d
|
|
Azzam et al[39]/single-blinded RCT
|
DEKA SmartXide
|
15 J/S/800 μm
|
1 pass
|
3/4 wk/3
|
Almost 70% as having moderate scar improvement
Mean pain 9
PIH was seen in two patients
|
|
Ahmed et al[40]/randomized, parallel group study
|
DEKA Ultra-30 Plus: TCA VS AF CO2
|
0.9 J/S/0.12 mm
|
1 pass/acne scar
|
4/3 wk/6
|
78.0% of patients had >50% improvement by physicians
86.0% of patients rated their satisfaction as “well”
2 patients developed pustules, and another two patients developed transient PIH
|
|
Cameli et al[41]/single-blinded split RCT
|
DEKA SmartXide2
|
30 mJ/500μm
|
1 pass
|
1 session/1 wk, 3
|
30% excellent, 40% good, 30% sufficient by physician evaluation
Patient evaluation 25% excellent, 40% good, 34% sufficient, 1% insufficient
|
|
Faghihi et al[42]/single-blinded split RCT
|
Diosis, Q-ray CO2
|
30 mJ/500 μm
|
1 pass
|
2/1 mo/4
|
A fair or good response was seen in 68.8% of patients
43.8% patients reported being satisfied or very satisfied
Mean duration of edema was ∼6.3 d, erythema lasted 4.1 d
|
|
Gawdat et al[43]/single-blinded split RCT
|
DEKA SmartDOT
|
15 J/S/2/700 μm
|
1 pass/full face
|
3/1 mo/3
|
All patients achieved >50% improvement by physicians and patients assessment
Mean duration of edema was ∼3.80 d, erythema lasted 3.87 d
PIH 13.3%
|
|
Lee et al[44]/single-blinded split RCT
|
Diosis, Q-ray CO2
|
25 mJ/400 MTZ/cm2/150 μm
|
1 pass
|
2/4 wk/4
|
MQGS was 2.3/4
Duration of erythema was an average of 10.4 d
Duration of edema was an average of 7.1 d
|
|
Zhou et al[45]/split-face RCT
|
Crius, Han's Laser
|
8 W/25%
|
2 passes/acne scars
|
3/1 mo/1
|
MQGS was 2.08/4 for patients
MQGS was 2.00/4 for physicians
|
Abbreviations: AF CO2, ablative fractional carbon dioxide laser; AFR, ablative fractional resurfacing;
ECCA, échelle d'évaluation clinique des cicatrices d'acné; MTZ, microscopic thermal
zone; MQGS, mean quartile grading scores; PIH, postinflammatory hyperpigmentation;
RCT, randomized clinical trial.
a Density (level): Density (level) of the AF CO2 facility.
b Intraindividual: Two facial areas were outlined, marked, and randomized to CO2 laser treatment versus no treatment.
A total of 18 published articles reported treatments of two to seven sessions at the
intervals of 4 to 12 weeks.[17]
[18]
[19]
[24]
[26]
[28]
[29]
[30]
[31]
[36]
[37]
[38]
[39]
[40]
[42]
[43]
[44]
[45]
[46] A total of 30 patients (16 women, 14 men) received two split-face treatments at
4-week intervals in two studies.[42]
[44] Wang et al[26] and Manuskiatti et al[46] treated 25 patients with two sessions at 8-week intervals.
In five studies, 72 patients were treated with three sessions of AF CO2 at 4-week intervals.[30]
[31]
[39]
[43]
[45] At the 1-month follow-up after the last treatment, objective clinical assessment
scores were 1.89 and 2.0 based on a quartile grading in the Kim and Cho[31] and Zhou et al[45] studies, respectively. The final assessment was performed 3 months after the last
treatment, when all patients reached over 50% improvement according to the physicians'
assessment,[43] whereas a 70% improvement was achieved in the Azzam et al[39] study.
The mean clinical score of texture and atrophy on a 0 to 10 numerical scale improved
from 6.15 and 5.72 (before treatment) to 4.26 and 3.97 (p < 0.0001) at 3 months and 3.89 and 3.56 (p < 0.0001) at 6 months following the last treatment.[30] In six studies,[17]
[18]
[19]
[28]
[29]
[38] patients were treated with three sessions of AF CO2 at 8-week intervals. At 3-month follow-up after the last treatment, the mean quartile
grading scores were 1.42 and 2.46, respectively, in the Chapas et al[17] and Walgrave et al[18] studies. The percentages of patients achieving 25% improvement were 70, 85, and
84.6%, respectively, in the Qian et al,[19] Manuskiatti et al,[29] and Alajlan et al[28] studies at 3 months following the last treatment.
According to the ECCA scores,[47] the scars improved from 48.8 ± 15.1 to 19.9 ± 7.9 (59.2% improvement) in the Zhang
et al[38] study at 6 months after the last treatment. The longest follow-up time frame was
12 months after the last treatment (in Qian et al's study[19]), where 80.6% of the patients had more than fair improvements, which was a figure
higher than that recorded at the 3-month follow-up.
Three articles reported AF CO2 treatment in 60 patients with four or more sessions at 4-week intervals[36]
[37]
[40]: one prospective clinical trial[24] (conducted for six sessions at 4-week intervals, where an average of 71% improvement
was observed at the 6-month follow-up) and two retrospective reviews.[22]
[25]
The Bjørn et al[34] study conducted a split-face trial to compare the influence of treatment intervals
between 1-month and 3-month after two treatments. The results indicated that the different
intervals did not affect the improvement of scar atrophy or the occurrence of postoperative
adverse effects. It was suggested that 3-month could be a more appropriate treatment
interval.[34]
Treatment Parameters
In terms of the treatment area, full face laser treatment was conducted in 12 studies.[17]
[18]
[21]
[22]
[23]
[29]
[32]
[33]
[35]
[37]
[38]
[43] A so-called “focal acne scars treatment (FAST)” method was conducted in the Schweiger[27] study where only the acne scars were treated, and the normal skin was left untouched.
All patients in the Reinholz et al[36] study were treated only on their cheeks. A total of 24 patients' cheeks and 1 patient's
nose were treated in the Hsiao et al[20] study. In the Qian et al[19] study, 8 patients had their whole face treated; 9 patients had their cheeks and
forehead treated, and 14 patients had only their cheeks treated.
According to the Magnani and Schweiger[16] review, an average energy level of 50 mJ was selected as a cutoff point. Among the
30 studies of this review, 9 studies[19]
[21]
[22]
[23]
[28]
[29]
[34]
[35]
[37] with a total of 208 subjects utilized high energy. Ten studies[20]
[24]
[25]
[26]
[30]
[33]
[38]
[42]
[44]
[46] with 161 subjects utilized low energy. Unfortunately, we were unable to compare
the effects of different energy densities among these studies due to the lack of such
information or consistency in reporting energy density levels. However, the effects
of high and low energy with the same density of fractional lasers were compared in
Kim and Cho's split-face study.[31] At 3 months postoperatively, the mean observers' scores were 5.8 and 4.0, respectively,
for the treatment with higher energy and lower energy on a 10-point scale.
Two other articles compared the effects of different fluence and density on the acne
scars. In Jung et al's[32] study, the mean grade of clinical improvement was 2.47/4 in the low-fluence, high-density
AF CO2 group—hence lower than the mean grade of 3.37/4 in the high-fluence, low-density
AF CO2 group (p = 0.02).[32] Similar results were also found in the Yuan et al study.[33]
The application of AF CO2 was combined with other treatments in five studies.[31]
[41]
[42]
[43]
[44] The combination of AF CO2 and NAFR yielded better results than both the high and low energy AF CO2 groups.[31] Combining AF CO2 laser and radiofrequency produced better results compared with AF CO2 monotherapy without increasing the risks or side effects.[41] Applying platelet-rich plasma (PRP) in the AF CO2-treated areas had a significantly better response than AF CO2 alone in the Gawdat et al[43] and the Lee et al studies,[44] which was consistent with the results of the Faghihi study.[42] Topical application of adipose-derived stem cells in the Zhou et al study also resulted
in increased efficacy of AF CO2 treatment of atrophic acne scars.[45]
Noninvasive Assessments
Noninvasive and quantitative methods for assessing surface topography have been developed,
such as the 3D optical profiling system (Primos 3D),[17]
[36] Visioscan (VC 98)[29]
[46] with analysis software, or optical coherence tomography.[43] These techniques generate a high-resolution topographic representation of the acneiform
scars pre- and posttreatment, which can then be used to assess the degree of improvement.
Digital photographs were also taken and analyzed using the VISIA Complexion Analysis
System to establish the number of pores and follicular openings, as well as atrophic
scars and skin texture scores.[20] Reflectance confocal microscopy in Cameli et al's[41] study provided semiquantitative information on the coagulative effects of laser
beam treatment.
Compared with the physicians' and patients' evaluation, the imaging technique provides
a relatively objective and digitized measurement that is also safer than histology.
Moreover, noninvasive quantification of the status of scar and treatment outcomes
facilitated in-depth preoperative discussion with patients to set realistic expectations
for their treatments.[29]
Adverse Events
In total, 26 out of the 30 studies commented on the adverse effects associated with
the fractional CO2 laser treatment. The most common side effects noted were pain, PIH, erythema and
edema, and crusting or scaling. Relative pain scores during the laser treatment were
evaluated using 10-cm visual analog scales (VAS).[18]
[29]
[30]
[33]
[34]
[35]
[36]
[38]
[43]
[45]
[46]
Mean VAS pain scores described by the subjects ranged from 2 to 8.16.[29]
[30] The pain was found to be more evident or persisted for longer periods of time in
patients treated with a higher density or higher fluence lasers.[32]
[33] Walgrave et al[18] found that increased pain scores are correlated with increased density, but not
with increased energy of the laser.[18] Average pain scores were found to decline with successive treatment sessions.[29]
[34]
Postinflammatory hyperpigmentation (PIH) was reported in 19 articles,[17]
[18]
[19]
[20]
[21]
[22]
[24]
[28]
[29]
[31]
[32]
[33]
[34]
[35]
[37]
[38]
[39]
[40]
[46] and tend to resolve spontaneously,[18]
[19]
[21]
[32]
[33]
[35] or can be successfully treated with antipigmentation cream.[18]
[24]
[28]
[29]
[38]
[46] Most of the PIH cases resolved within 3 months (by the follow-up appointment).
Compared with the multiple-pass approach, the single-pass technique for the delivery
of the same total density was more likely to develop PIH,[19] which is consistent with the fact that PIH were found to be more evident or persisted
for longer periods of time in patients treated with higher densities or higher fluences.[33] PIH appears to be more related to the density rather than the energy of the laser
treatment. Based on the low incidence of PIH, Hsiao et al[20] considered a density of 10 to 15% to be safe.
Erythema was graded after each treatment session using several different scales, including
a 5-point scale,[44]
[45] a 0 to 10 VAS system,[42] or a numerical scale from 0 to 3.[17]
[18]
[30]
[33]
[34] Mild-to-moderate erythema (lasting an average of 2.87 days) was reported immediately
after all three treatment sessions in the Cho et al study.[21] According to patients' self-evaluations in the Kim et al study,[25] it can be present for up to approximately 1 month. Erythema was found to be more
evident or persisted for longer periods of time in patients treated with higher densities
or higher fluences of the laser.[33] In general, mild to moderate edema was noted in the treatment area in all subjects
and resolved within 1 week in most studies.
Mean duration of posttherapy crusting or scaling was approximately 7 days according
to patients' account. Mean duration of limited daily activities, such as going outdoors
or working was 4.9 ± 2.1 days. This was found to correlate significantly with the
appearance of posttherapy crusting or scaling but not with posttherapy erythema.[21]
Other adverse effects included herpes reactivation, oozing, bleeding, petechiae, stinging
sensation, cutaneous pruritus, and allergic contact dermatitis.[20]
[21]
[22]
[28]
[29]
[33]
[39]
[40] No permanent side effects were reported.
Discussion
Acne scarring results after deviation from the usual repair of the skin during the
acne healing process. The high ratio of Asian participants in the reviewed articles
was partly due to the high prevalence of acne in Asian populations. According to Lynn's
review,[48] Taiwan (East Asia) and South Asian countries have the highest worldwide prevalence
of acne among their late adolescence (range: 15–19 years) age groups. This finding
was consistent with Ghodsi et al's[49] review of several large worldwide studies on the prevalence of acne vulgaris among
adolescent age groups. It can be assumed that this subpopulation of acne patients
has serious concerns about their appearance.
The direct association between inflammatory acne lesions and the severity of scarring
indicates that the most effective means of addressing acne scarring is to prevent
its formation through good acne control.[50] In fact, patients enrolled in the reviewed studies often had active acne or were
under concurrent acne therapy. However, treatment of the scars was often delayed because
of the current recommendation that acne scar revision is performed no sooner than
6 to 12 months[51] or even 12 to 24 months[49] after completion of oral isotretinoin treatment.
It is assumed that retinoids can delay or alter reepithelialization,[52] although the role of retinoids in wound healing is debatable and controversial.
Evidence shows that topical application of tretinoin to the wound of adult model animals
increases collagen synthesis in aged skin and promotes the normal skin healing process.[53]
In Yoon et al's[54] study, isotretinoin (10 mg/d) was also confirmed to be a safe and effective treatment
for acne and acne scars when combined with fractional laser therapy. Likewise, 10
to 40 mg/d isotretinoin was used simultaneously with AF CO2 in Kim and Cho's[25] study, and the findings suggest that ablative fractional laser treatment for acne
scars is safe regardless of isotretinoin use at accumulated dose of 39 to 248 mg/kg.
Considering that acne scar treatment is a lengthy process and requires a combination
of procedures, early initiation of treatment could greatly improve the quality of
life of patients.
We recommend that isotretinoin should be used for patients with moderate-to-severe
acne during both the pre- and postoperative period except for patients undergoing
immune suppression or those with contraindications such as diabetes.
Ablative laser therapy has been linked to damaged skin barriers (dryness), accelerated
inflammatory reaction in the form of acneiform eruption or herpes simplex infections,
as well as high risk of PIH. Traditionally, application of pharmaceuticals, such as
steroids, antivirals, antibiotics, and antipigments, such as hydroquinone is a standard
protocol to address these issues. Recently, the use of dermocosmetics has been demonstrated
to improve acne, dry skin, and hyperpigmentation effectively.[55]
[56]
[57] Therefore, dermocosmetics have the potential to be used as a monotherapy or in combination
with medical treatments for postoperative skin care.
In theory, a single treatment for atrophic acne scars is always beneficial as it can
ensure high patient compliance, avoid repetition of scabbing, and minimize postoperative
sick leave from work that is often taken after every treatment session. However, acne
scar treatments are often a continuous process rather than a one-time intervention.
When multiple treatments are required to achieve preferred long-term results, an approximate
3-month interval between treatment sessions appears to be optimal.
A shorter interval may reduce the maximum wound-healing response achievable from the
previous session,[58] cause excessive transepidermal water loss, and compromise the recovery of the melanin–erythematic
index.[58] On the other hand, longer intervals could be less effective as the next treatment
has a greater tendency of injuring the tissues that are being replaced. Indeed, it
has been shown that the more collagen is rebuilt from the previous treatment, the
more damage is likely to be caused by the subsequent treatment.[34]
The treatment options for acne scars should be tailored for each patient. First, the
treatment protocol should take into account the clinical features of the scar characteristics
(depth, width, and type). Certain types of acne scarring may respond more favorably
to AF CO2 laser treatment. According to several studies, boxcar and superficial atrophic scars
respond better than deeper scars.[18]
[19] The ice-pick scar, which is usually deep and sharp, may not be a good candidate
for this approach.[22]
[28]
The current recommendation for ice-pick scars calls for skin punch excision or chemical
reconstruction techniques.[8] However, additional options are available to resolve this condition, such as filler
injections, PRP (intradermal or topical), and radiofrequency combination therapy.
Second, when AF CO2 laser is applied to the entire face, parameters (energies and passes) should be modulated
to different regions of the face. Maximum energies can be used for the primary acne
scar target areas, and most passes can be delivered to the neck, chin, lips, cheeks,
and forehead. Aggressive treatment (with high fluences and multiple passes) should
be avoided in sensitive areas, such as the neck and the eyelids to reduce the risk
of complications.[26] Skin thickness should also be considered. According to a recent study, the treatment
appeared to be more effective in younger patients with thinner skin.[59] Sebaceous skin is usually thicker,[39] and thus may necessitate increased number of passes, as well as a higher power of
fluence and treatment density. It is therefore advisable that physicians use variable
parameters for the same patient according to the assessment of the conditions.[39]
Third, treatment parameters can vary between the sessions—for example, treatment coverage
can increase throughout the treatment series. It has been observed that treatments
became more tolerable and the recovery became increasingly faster and better throughout
the treatment series.[17] It is also important that when the safety and effectiveness of the device are established
for a specific patient throughout the course of treatment, the investigator can often
become more confident with the device and outcome.[18]
