Therapeutic strategies for untreated capillary malformations of the head and neck region: a systematic review and meta-analyses
Journal name: American Journal of Clinical Dermatology
Gonca Cinkara 1 *, Ginger Beau Langbroek 2 *, Chantal M.A.M. van der Horst 3 , Albert Wolkerstorfer 4 , Sophie E.R. Horbach 3 , Dirk T. Ubbink 2
1. Faculty of Medicine, University of Amsterdam, Amsterdam, The Netherlands
2. Department of Surgery, Amsterdam University Medical Centers - location AMC, Amsterdam, The Netherlands
3. Department of Plastic-, Reconstructive- and Hand Surgery, Amsterdam University Medical Centers - location AMC, Amsterdam, The Netherlands
4. Department of Dermatology, Amsterdam University Medical Centers - location AMC, Amsterdam, The Netherlands
*Both authors contributed equally to this review
Corresponding author:
Ginger Beau Langbroek, Department of Surgery, Amsterdam University Medical Center (UMC) location AMC, Amsterdam, P.O. Box 22660, 1100 DD Amsterdam, The Netherlands. Telephone: 0031(0)20562974.
E-mail: g.b.langbroek@amsterdamumc.nl Funding sources: none.
Conflict of interest: all authors declare that they have no conflict of interest.
Electronic supplementary information
Supplementary Table 1. Search strategy PubMed, EMBASE and Cochrane, last searched 16 December 2020
PubMed (MEDLINE) EMBASE Classic + Embase Cochrane
("Port-Wine Stain"[Mesh] OR port-wine[tiab] OR
portwine[tiab] OR capillary malformation*[tiab] OR nevus flameus[tiab] OR naevus flammeus[tiab] OR flame nevus[tiab] OR flame naevus[tiab] OR nevus vinosus[tiab] OR naevus vinosus[tiab]) AND
("Lasers"[Mesh] OR "Laser Therapy"[Mesh] OR "Surgical Procedures,
Operative"[Mesh] OR
"surgery" [Subheading] OR
"Photochemotherapy"[Mesh]
OR "therapy" [Subheading]
OR "Tattooing"[Mesh] OR laser*[tiab] OR surger*[tiab]
OR surgical*[tiab] OR operati*[tiab] OR reconstruct*[tiab] OR tattoo*[tiab] OR camouflage*[tiab] OR photodynamic therap*[tiab])
nevus flammeus/ or (port-wine or portwine or capillary malformation* or nevus flameus or naevus flammeus or flame nevus or flame naevus or nevus vinosus or naevus vinosus).ti,ab,kw AND
exp laser/ or low level laser therapy/ or exp surgery/ or photochemotherapy/ or tattooing/ or (surgery or therapy).fs.
OR
(laser* or surger* or surgical* or operati* or reconstruct* or tattoo* or camouflage* or photodynamic therap*).ti,ab,kw.
“Port wine stain” or
“Capillary
Malformation”
Supplementary Table 2. Study characteristics of the included studies per treatment modality
Pulsed Dye Laser (PDL)
Treatment characteristics
Author (year) Country Translated Type studof
y
Total no of patients
Age (mean or
range in years)
Fitzpatrick
Skin-type Reported CM Characteristics
Pre- treatm
ent Wave- length
(nm) Spot
size (mm)
Pulse duration
(ms)
Fluence
(J/cm2) Cooling Mean No. of treatm ent session
s
Treatment interval (weeks)
Follow- up
Primary Outcome (quantitative improvement)
Secondary Outcomes (adverse
events)
Ackermann (2002) [27] German
y No RS (674 CM
lesions)A 23.0 II-III Colour: pale pink
to red and purple - 585 7 0.45 6.8 - 6.3 ⁃ 6-8
weeks Degree of
blanching ⁃
Anolik (2012)
[31] USA No RS 24 0.08 I-III ⁃ - 595 10 1.5 8.5-9.5 Yes 5 2-4 ⁃ Improvement
in %
Hyperpigmentation Hypopigmentation
Scarring Asahina
(2006) [26] Japan No PC 35A 39.0 II-IV
Colour: mixed Hypertrophic:
mixed Size: <20 -
>200 cm2
- 595 7 10 12 Yes 4 8 4 weeks Mean
clearance score Hyperpigmentation Hypopigmentation Baghad (2016)
[32] Morocc
o Yes RS 68A (18)C II-IV ⁃ - 595 10 1.5-3 8-12 - 6-10 8 ⁃ Improvement
in % ⁃
Chang (2002)
[33] Taiwan No RS 64 24.4-26.3 ⁃ Hypertrophic:
mixed - 585-
595 7 1.5 7-10 Yes 3.3 - 12
months Blanching in quartiles of %
Hyperpigmentation Hypopigmentation
Scarring Chapas (2007)
[34] USA No RS 49 < 0.6 ⁃ Surface area 5-
100 cm2 No 595 10 1.5 7.75-9.5 Yes 9.3 4-6 12
months Clearance in % Scarring Fallahi (2020)
[38] Iran No RCT 15 21.76 I-IV Structure: patchy
or nodules No 595 7 1.5 12 Yes 4 8 8
months Mean
improvement Pain
Geronemus
(2000) [39] USA No PC 16 0.3 ⁃ ⁃ - 595 7 1.5 11-12 Yes 3.2 3-6 ⁃ Clearance in %
ranges
Hyperpigmentation Hypopigmentation
Scarring Greve (2001)
[41] German
y No PC 7A 31.7D I-III Size: 10 cm2-
>100cm2 No 585 7 0.45 6 Yes 1 ⁃ ⁃ Mean
clearance in % ⁃
Huerta-Rivera
(2019) [42] Mexico Yes RS 8 39.5 III-IV ⁃ No 595 7 0.45 9-12 - 7.75 5 ⁃ Clearance in % ⁃
Huikeshoven (2007) [43]
The Netherl
ands No PC 51 23.0 ⁃ ⁃ No 585 5-7 45 6-8 Yes 6-39 ⁃ 9.5 years
Clearance in L*a*b* colour
coordinate system
⁃
Jeon (2019)
[44] USA No RS 149A 0.3 I-VI Size: 0.49-600
cm2 - 595 10 1.5 8-9 - 9.8 2-3 ⁃ Clearance in
VAS grade
Hyperpigmentation Hypopigmentation
Scarring Kelly (2002)
[45] USA No PC 14A 28.0 I-IV ⁃ No 585-
595 7 1.5 7-15 Yes 3.3 8-12 18
months Blanching in
quartiles of % Scarring Koster (2001)
[46]
The Netherl
ands No PC 70 13.3 ⁃
Colour: pale pink to dark red Hypertrophic:
mixed
No 585 5 0.45 ⁃ - 6 ⁃ ⁃
Clearance in L*a*b* colour
coordinate system
⁃
Leaute- Labreze (2002)
[49] France No RS 8 9.4 ⁃
Neurological involvement (all)
(Sturge Weber Syndrome)
- 585 3-7 0.45 5-7 - 4.1 16-24 ⁃ Decrease of
colour in % ⁃
Li (2020) [50] China No RS 261 0-60 II-III
Colour: red to purple Hypertrophic:
mixed
No 595 7 0.45-10 8-14 Yes 2-13 4-6 ⁃ Blanching score
in % ranges
Hyperpigmentation Scarring
Pain Passeron
(2014)[55] France No RCT 10A 0.9 ⁃ Size: max 100
cm2 No 595 7 1.5 8 Yes 3 4 1 month Clearance in
IGA score ⁃
Pham Cao
(2019) [58] Italy No RS 42 ⁃ ⁃
Colour: pink, red, or purple.
Hypertrophic:
mixed Size: <20 cm2 or >20 cm2.
- 595 7 1.5 11-12.5 - ⁃ ⁃ ⁃ Clearance in %
ranges ⁃
Ren (2013)
[60] China No PC 11 24.8 III-IV Colour: pink,
purple or red No 595 7 1.5 9-12 Yes 3-5 8 2
months Clearance in %
ranges ⁃
Sadeghinia
(2019) [61] Iran No PC 27 5.7 III-IV
Colour: pink to deep red Size: <20 - >40
cm2 Hypertrophy: no
No 595 7 1.5-3 9-13 Yes 6.2 4-6 ⁃ Clearance in %
ranges Hyperpigmentation Scarring
Sharma (2007)
[62] India No PC 27 21.6 IV-V
Colour: Pink, red, violet Size: <50 cm2 or
>50 cm2
- 585 7 0.45 5-7.5 Yes 6.29 4-6 ⁃ Clearance in %
ranges
Hyperpigmentation Hypopigmentation
Scarring Sommer
(2000) [63] UK No RS 10A 18.8 V ⁃ No 585 5-10 0.45 4.5-7.25 - 7.7 16 49
months Clearance in % ranges
Hyperpigmentation Hypopigmentation
Scarring Wang (2018)
[67] China No CCT 61B 19.9 III-IV Flat lesions. Size:
>9 cm2 No 595 10 0.5 8-8.5 Yes 2 4-6 2
months
Mean improvement
score
Hyperpigmentation Hypopigmentation
Scarring Wimmershoff
(2001) [69] German
y Yes RS 217A ⁃ ⁃
Colour: red to dark red
Size: <100 cm2 - 585 5-7 0.45 4-10 - ⁃ 5 ⁃ Improvement
in % ranges ⁃
Yang (2005)
[71] USA No CCT 11 (PDL)
A,B 33.7 I-IV (mixed)
Colour: pink, red and purple Hypertrophic:
mixed Size: >5 cm2
- 595 7 1.5 8 Yes 3 4 ⁃ Lightening in %
ranges -
Yu (2016) [73] China No PC 13 18.5 ⁃ ⁃ No 595 7 1.5 12 Yes 3 8 2
months
Blanching in l*a*b* colour
coordinate system
⁃
Yu (2019) [74] China No PC 26 ⁃ ⁃ ⁃ No - 7 1.5 12 Yes 2-3 ⁃ 2
months
Blanching in l*a*b* colour
coordinate system
⁃
Yuan (2008)
[72] China No RAC 275
(PDL)B 3-30 ⁃
Colour: pink and purple
Size: 5-78 cm2 No 585 5 0.30-0.45 4.8-6.5 - 3.5 -
4.1 8 5 - 30
months
Cosmetic improvement
grades
Hyperpigmentation Hypopigmentation
Scarring
Zhang (2014)
[75] China No RS 128
(PDL)B 6.9 ⁃
Colour: red and purple Hyertrophy: no Size: 4-127 cm2
No 585 5-7 - 4.8-6.5 Yes (after
treatmen
t) 1 ⁃ 2
months Blanching in % ranges
Hyperpigmentation Hypopigmentation
Scarring Neodymium-doped yttrium aluminium garnet (Nd:YAG laser)
Treatment characteristics
Author (year) Country Translated Type studof
y
Total no.
of patients
Age (mean or
range in years)
Fitzpatrick
Skin-type Reported CM Characteristics
Pre- treatm
ent Wave- length
(nm) Spot
size (mm)
Pulse duration
(ms)
Fluence
(J/cm2) Cooling Mean No. of treatm ent session
s
Treatment intervals
(weeks)
Follow- up
Primary Outcome (quantitative improvement)
Secondary Outcomes (adverse
events)
Al-Dhalimi
(2016) [29] Irak No RCT 14 22.1 III-IV
Colour: pink-red, dark-red, dark-
purple Hypertrophy: no
No 532 or
1,064 3 20-25 30-300 Yes 6 4 3
months
Improvement in quartiles of
%
Hyperpigmentation Scarring
Al-Janabi
(2017) [30] Irak No PC 16 20.8 III-IV
Colour: pink-red, dark-red, dark-
purple Hypertrophy: no
- 532 3 25 30 Yes 12 4 3
months
Improvement in quartiles of
%
⁃
Farid-ur- Rehman (2007) [37]
Pakista
n No PC 20 23.5 ⁃
Colour: pink, pink-red, red,
red-purple, purple.
Structure: patch or plaques.
No 532 2 0.0016 7.25-9.67 - 7.55 4-6 ⁃
Improvement in quartiles of
% Hyperpigmentation
Kono (2009)
[47] Japan No PC 10 14-16 III-IV Hypertrophy: all - 1,064 3 10 - 20 80-100 Yes 4 4-8 ⁃ Clearance in
quartiles of %
Hyperpigmentation Hypopigmentation
Scarring Kwiek (2017)
[48] Poland No RS 44 31.0 I-III ⁃ No 532 5 - 10 5 - 9 8-11.5 Yes 7.8 4 ⁃
Global clearance
effect (GCE) Scarring Pence (2006)
[56] Turkey No PC 88A 21.2 II-IV
Colour: pink-red, red-purple,
purple- cavernous
- 532 2 - 6 2 - 50 Max 38 Yes 5.03 8 2
months Improvement in % ranges
Hyperpigmentation Hypopigmentation
Scarring
Yang (2005)
[71] USA No CCT 11 (Nd:
YAG)A,B 33.7 I-IV
Colour: pink, red, purple, dark
purple Size: > 5 cm2 Hypertrophic:
mixed
- 1,064 7 3 - 15 40-250 Yes 3 4 ⁃ Lightening in %
ranges Scarring
Zhong (2014)
[76] China No RS 101A 16.0D III-IV Colour: pink, red,
purple, dark
purple No 1,064 3 - 10 0.1 - 300 3 - 300 Yes ⁃ 8 3
months Lightening in %
ranges ⁃
Intense pulsed light (IPL)
Treatment characteristics
Author (year) Country Translated Type
of study
Total no.
of patients
Age (mean or
range in years)
Fitzpatrick
Skin-type Reported CM Characteristics
Pre- treatm
ent Wave- length
(nm) Spot
size (mm)
Pulse duration
(ms)
Fluence
(J/cm2) Cooling Mean No. of treatm sessionent s
Treatment intervals
(weeks)
Follow- up
Primary Outcome (quantitative improvement)
Secondary Outcome (adverse events)
Dong (2010)
[36] China No PC 30 22.2 IV
Colour: purple, red, pink Hypertrophy:
mixed
No 560-
590 ⁃ 6-10.5 17-25 Yes 5 4-5 6 - 12
months Clearance in % ranges
Hyperpigmentation Hypopigmentation
Scarring Ozdemir
(2008) [54] Turkey No PC 12 26.3 II-IV Colour: pink-dark
reddish purple
Size: 5 - 15 cm2 No 585 ⁃ 2-10 18-28 Yes (after
treatmen
t) 4.75 4-6 6 - 13
months Clearance in % ranges
Hyperpigmentation Hypopigmentation
Scarring Wang (2013)
[66] China No PC 29 19.4 III-IV Colour: pink, red,
purple No 550 ⁃ 4.5-5 18-25 Yes 5 4-5 3
months Clearance in % ranges
Hyperpigmentation Hypopigmentation
Scarring Pain Photodynamic therapy (PDT)
Treatment characteristics
Author
(year) Country Translated Type study of
Total no.
patients of (mean Age
or range
in years)
Fitzpatrick Skin-type
Reported CM Characteri
stics Pre- treatm
ent
Type of drug
Drug dose (mg/kg)
Light source
Wave- length (nm)
Energy density (mJ/cm2)
Drug to light interval
(min)
Mean No.
of treatmen t sessions
Treatment intervals
(weeks) Follow-
up
Primary Outcome (quantitative improvement)
Secondary Outcomes (adverse
events)
Li-Qiang
(2018) [51] China No PC 77A 1-14 ⁃
Colour:
pink, purple Hypertrop
hy: no
No HMME 5 LED
green
light 532 96-115 20 2 8 ⁃ Improvement
in % Pain
Ma (2019)
[52] China No RS
Group 1 (PsD-007):
n=21 Group 2 (HMME):
n=17 24.33
24.06 III or IV
Colour:
pink- bright red Hyertroph y: mixed
No PsD-007
HMME 5 KTP laser 532 80-90 20-30 1 ⁃ 2
months Blanching in % ranges
Hyperpigment ation Hypopigmenta
tion Scarring
Pain
Ren (2014)
[59] China No PC 8A 24.0 - Colour:
purple No PsD-007 4-5 Nd:YAG
laser 532 96-180 20-30 ⁃ ⁃ 3 - 6
months Lightening in
% ⁃
Wen (2019)
[68] China No PC 22 3-39 -
Colour:
pink, purple Hypertrop hy: mixed
- HMME 5 LED light 532 80-100 20-30 1 ⁃ 8 weeks Blanching in % ranges ⁃
Xiao (2011)
[70] China No RS 282A 11.5 –
26.3D III-IV
Nodules papules: and some
No HMME 3.5-5 Copper
vapour laser
510.6 or
578.2 80-100 20-40 2.6-8.2 8 1 - 5
years Improvement
in % ranges ⁃
Yuan (2008)
[72] China No RAC 306
(PDT)B 3-30 ⁃
Colour:
pink and purple Hypertrop
hy: no Size: 5 - 78 cm2
No HMME 3.5-5 Copper
vapour laser
510.6
578.2 or 140-240 20-40 1.2-3.7 8 5 - 30 months
Cosmetic improvement
grades
Hyperpigment ation Hypopigmenta
tion Scarring
Zhang
(2014) [75] China No RS 132
(PDT)B 6.9 ⁃
Colour:
red, purple Size: 12 - 150 cm2 Hypertrop hy: no
No HMME 3.5 Copper
vapour
laser - 80-100 20-25 1 ⁃ 2
months Blanching in % ranges
Hyperpigment ation Hypopigmenta
tion Scarring
Other laser and light modalities
Treatment characteristics
Author
(year) Country Translated Type of study
Total no.
of patients
Age (mean
or range
in years)
Fitzpatrick
Skin-type Reported CM Characteristics
Pre- treatm
ent
Type of treatmen
t
Wave- length
(nm)
Spot size (mm)
Pulse duration
(ms)
Fluence (J/cm2) Cooli
ng
Mean No.
of treatmen t sessions
Treatment intervals
(weeks) Follow-
up
Primary Outcome (quantitative improvement)
Secondary Outcomes (adverse
events)
Ahcan
(2004) [28] Slovenia No CS 10 16.2 II- III
Colour: pale pink to red and
purple.
Homogenous texture.
No KTP+/KTP
laser 532-1,064 3 25 6- 14 Yes 1 ⁃ 8 weeks (Mean)
blanching score
Hyperpigment ation Scarring
Del Pozo
(2001) [35] Spain No PC 19A 51.5 ⁃
Hypertrophy:
yes Nodules: yes Size: 0- > 40
cm2
No CO2-laser - 10 90 10 - 2.8 ⁃ 6 weeks Improvement
in quartiles of
%
Hyperpigment ation Scarring
Mohamed
(2019) [53] Egypt No PC 37A 19.3 II-IV ⁃ No Pro-
yellow
laser 577 ⁃ 20 - 32 17 - 22
(afteYes r treat men t)
7.76 4 1
month
Improvement in quartiles of
%
⁃
Periyasamy
(2019) [57] India No RS 11 27.5 ⁃
Colour: red Hypertrophy:
mixed Nodular: mixed
- DSWL 595-1,064 7 - 10 0.5 - 40 4 - 50 Yes 5 4 ⁃ Improvement
in % ⁃
Wang (2018)
[67] China No CCT 61
(DSWL)B 19.9 III-IV Flat lesions.
Size: >9 cm2 No DSWL 595/
1,064 10 2/
15 7.5-11/
25-35 Yes 2 4-6 2
months
Mean improvement
score
Hyperpigment ation Hypopigmenta
tion Scarring Medical tattooing
Treatment characteristics
Author
(year) Country Translated Type of study
Total no.
of patients
Age (mean or range in years)
Fitzpatrick
Skin-type Reported CM Characteristics
treatmPre- ent
Device measuring
colour Tattoo instrument Needle depth (mm)
Mean No. of treatment
sessions
Treatment intervals
(weeks) Follow-up
Primary Outcome (quantitative improvement)
Secondary Outcomes (adverse
events) Grabb
(1977)
[40] USA No RS 19 (4-20) ⁃
colour: mildly red, moderately
red, very purplish-red.
- Densichron densitometer
Air-driven Styker dermatattoo
handpiece
⁃ 3.05 12-24 3.1 years Improvement
in % ⁃
Thomson (1971)
[64] Canada No RS 41 ⁃ ⁃ ⁃ - Densichron
densitometer High-speed
turbine 1.5 7.5 ⁃ 12 months
Loss of colour in qualitative
grading system
⁃
van der Velden (1993) [65]
The
Netherlands No CS 5 34.4 ⁃
Colour: light pink to purple Size: <20 cm to 1
> 100 cm2.
No ⁃ Derma injector 1.1-1.3 10.2 4-8 19.8
months Degree of
coverage ⁃
CCT, Controlled clinical trial; CM, Capillary malformation; cm2, square centimeter; CO2, carbon dioxide; CR, Case report; CS, Case series; DSWL, Dual sequential wave length; HMME, Hematoporphyrin monomethyl ether; IGA, Investigator Global Assessment;
IPL, Intense pulsed light; J/cm2, joule per square centimeter; KTP, potassium titanyl phosphate; LED light, Light emitting diode; mJ/cm2, millijoule per square centimeter; Mg/kg, milligrams per kilogram; min, minute; mm, millimeter; ms, millisecond; Nm, nanometer; Nd:YAG, neodymium-doped yttrium aluminum garnet; PC, Prospective cohort; PDL, Pulsed dye laser; PDT, Photodynamic Therapy; PsD-007, second-generation photosensitizer developed in China; PWS, Port wine stain; RAC, Retrospective analytic cohort; RCT, Randomized controlled trial; RS, Retrospective study; USA, United States of America; VAS, Visual Analogue Scale; A only patients extracted who met the inclusion criteria; B this article is described twice due to the evaluation of two therapies; C, median age; D, mean age or age range all patients; -, not reported.
Supplementary Table 3. Predefined outcomes per treatment modality
Pulsed Dye Laser (PDL) Author (year) Type of
study Total no of
patients Any quantitative improvement No of patients with
≥75% improvement Patient satisfaction Hyperpigmentation Hypopigmentation Scarring Pain Other adverse events
Ackermann
(2002)[27] RS (674 CM lesions)
674 CM lesions >50%. Mean grade of fading of CM on the neck was 2.32+/-0.87 (50%-75%), whereas on the face it ranged from 2.47+/-0.83 (50%-75%) (periorbital) and 2.69+/-1.10 (50%-75%) (perioral) to 2.73+/-0.96 (50%-75%)
(forehead/
temple).
- - - -
Anolik (2012) [31] RS 24 All patients showed 50-100% improvement. 16 - 3 0 0 - Purpura: n=24
Erythema: n=24 Edema: n=24 Asahina (2006)
[26] PC 35A 35 patients had 50% clearance. Mean clearance score: 2.80 - - 5 3 - - -
Baghad (2016)
[32] RS 68A >50% n=47 - - - -
Chang (2002) [33] RS 64
<25%: n= 12 26%-50%: n= 18 51%-75%: n= 18
>76%: n= 16
16 - 26 0 0 - -
Chapas (2007) [34] RS 49 Mean clearance: 88.6% after 12 months of treatment 44 - - - 0 - Atrophy: n=0
Fallahi (2020) [38] RCT 15
Outcomes extracted only for PDL Mean colorimetric improvement:
Medial side of the face: 3.80±2.96 Lateral side of the face: 3.80±2.96 Mean IGA score: 64.33±23.67%.
Mean PGA score: 65±20.44%.
(correlation coefficient: 0.85, P-value < 0.001)
- - - 15 Purpura: n=15
Erythema: n=15 Edema: n=15
Geronemus (2000)
[39] PC 16 n=10 (63%) had >75% clearing after approximately 4
treatment sessions. 2 infants <25% clearance 10 - 0 0 0 - Dermatitis: n=3
Greve (2001) [41] PC 7A Mean clearance with cooling = 38.6% - - - -
Huerta-Rivera
(2019) [42] RS 8 8 patients had >90% clearance after 7.75 sessions average. 8 - - - No long-term
adverse events
Huikeshoven
(2007) [43] PC 51 The median ΔE was significantly lower at follow-up (12.4;
interquartile range, 8.7 to 14.8) than before laser treatment
(15.2; interquartile range, 12.3 to 19.5; P<0.001). -
30/51 patients (59%) was satisfied with treatment outcome:
3/51 patients (6%) reported that the CM became lighter, 30/51 patients (59%) reported no change in color since
last treatment.
- - - - -
Jeon (2019) [44] RS 149A Mean VAS grade: 3.93 (median score, 4) - - 1 0 0 - -
Kelly (2002) [45] PC 14A
Blanching score:
<25%: n= 3 25-49%: n=3 50-74%: n=5
>75%: n= 3
3 - - - 0 - -
Koster (2001) [46] PC 70 ΔE reduced by 12% with each treatment, on average. - - - -
Leaute-Labreze
(2002) [49] RS 8
Results per segment of the face:
V1 50%-70% clearance: n=5 and 30%-50%: n=3 V2 30%-50% clearance: n=8
V3 <30% clearance: n=8
0 - - - -
Li (2020) [50] RS 261
Blanching score:
Complete (>90%): n=21 Significant (60-90%): n=113 Moderate (30-60%): n=100
Poor (<30%): n=27
- - 24 - 6 - Pain most patients
Topical edema (<
few hours) Passeron (2014)
[55] RCT 10A Marked improvement or complete clearance: 1/10 patients - Median VAS score was
7.0 (range 4.1–7.6) - - - - -
Pham Cao (2019)
[58] PC 42
76%-100% lightening: n=18 51%-75% lightening: n=8 26%-50% lightening: n=8 0%-25% lightening: n=8
18 - - - -
Ren (2013) [60] PC 11
Poor (< 25%), n=1 Fair (26–50%), n=3 Good (51–75%), n=2 Excellent (76–100%), n=5
5 - - - -
Sadeghinia (2019)
[61] PC 27
Mean improvement 70.74 ± 18.5%
Improvement score:
<50%: n=4 50-74%: n=9
>75%: n= 14
14 - 1 - 1 -
All patients:
purpura, erythema and edema Post-laser skin erosion, blister, or
crust: n=6 Sharma (2007)
[62] PC 27
Up to 25% lightening; n=6 26% to 50%; n=8 51% to 75%; n=8 76% to 99%; n=5 100% lightening; n=0
5 - 7 1 0 - -
Sommer (2000)
[63] RS 10A
<25%; n=2 25%-50%; n=0 51%-74%; n=4 75%-90%; n=2 >90%; n=2
4 - 4 1 2 - Blistering: n=4
Crusting: n=3
Wang (2018) [67] CCT 61 (PDL)B Mean colour improvement score: 2.5 - - 11 (<3 months) 2 0 -
Purpura and edema: n=61 Blistering and crusting: n=2 No infection, atrophy, keloid
formation.
Wimmershoff
(2001) [69] RS 217A
> 95% brightening (excellent), n=2 75–95%Brightening (very good), n=3
50–75% brightening (good), n=26 25–50% brightening (moderate), n=85
<25% brightening (poor), n=87 0% no brightening (no effect). N=14
5 - - - -
Yang (2005) [71] CCT 11 (PDL)A, B
0%; n=0 1% to25%; n=0 26%to50%; n=5 51%to75%; n=3 76% to 100%. n=3
3 - - - Pyogenic
granuloma: n=1
Yu (2016) [73] PC 13
The average ΔE for the central and lateral facial PWS sites was 3.33 (SD 1.24) and 7.40 (SD 3.54), respectively (P = .002). The
blanching rate of the PWS skin for the central and lateral facial sites was 8.68% (SD 5.19) and 34.01% (SD 16.75),
respectively (P = .003)
- - - -
Yu (2019) [74] PC 26 Mean ΔE= 10.97 (face), 7,45(neck)
Mean blanching rate: 59,9% (face) and 37,5% (neck) - - - -
Yuan (2008) [72] RAC 275 (PDL)B
(I) excellent-colour was close to nor- mal skin colour; n=23 (II) good-marked blanching, thicker lesion become flat, no
scar formation; n=113
(III) fair-partial blanching, thicker lesion become flat moderately; n=115
(IV) poor-slight blanching, thicker lesion become flat slightly;
n=21 (V) no change; n=3
23 - 16 11 6 - Skin phototoxity:
n=0 Mild fibrosis n=35
Zhang (2014) [75] RS 128 (PDL)B
>75%; n=14 51—75%; n=58 25—50%; n=42 <25%; n=11
0%; n=3
14 - 14 7 6 - Skin phototoxity:
n=0
Total 1,697C N.a. 188 N.a. 112 25 21 15 N.a.
Neodymium-doped yttrium aluminum garnet (Nd:YAG laser) Author (year) Type of
study Total no of
patients Any quantitative
improvement No of patients with
≥75% improvement Patient satisfaction Hyperpigmentation Hypopigmentation Scarring Pain Other adverse events
Al-Dhalimi (2016)
[29] RCT 14
532 nm vs 1,064 nm 0%; n=0 vs n=1 1–25%; n=2 vs n=12 26–50%; n=4 vs n=1 51–75%; n=4 vs n=0
>75%; n=4 vs n=0
4 vs 0 Mean VAS score: 7.6 +/-
2.3 vs 3.3 +/- 0.8 1 (532nm) - 0 - All patients: transient erythema,
scaliness, and burning sensation (lasting not more than 4 days)
Al-Janabi (2017)
[30] PC 16
0%; n=0 1–25%; n=1 26–50%; n=2 51–75%; n=5
>75%; n=8
8 Mean VAS score: 8.9 ±
1.1. - - - - All patients: transient erythema,
scaliness, and burning sensation (lasting not more than 5 days)
Farid-ur-Rehman
(2007) [37] PC 20
0%; n=0 1–25%; n=0 26–50%; n=2 51–75%; n=3
>75%; n=15
15 - 13 - - -
Textural changes; n=6 Eczematization; n=4 intraoperative hemorrhage ; n=2
pyogenic granuloma; n=2
Kono (2009) [47] PC 10
0%; n=0 1–25%; n=0 26–50%; n=2 51–75%; n=5
>75%; n=3
3 - 0 0 0 - No adverse events
Kwiek (2017) [48] RS 44
GCE 25; n= 44 GCE 50; n=34 GCE 75; n=17 GCE 90; n=6
17 - - - 1 - Edema: n=44 (<7 days) Bruising: n=44 (7-
14 days)
Minority of patients: Crusting/blistering
Pence (2006) [56] PC 88A
< 25%; n=0 25–49%; n=4 50–74%; n=39 75–94%; n=34 > 95%; n=11
45 - 2 (transient) 1 1 - -
Yang (2005) [71] CCT 11 (Nd:YAG)A,B 0 - 50%; n= 5 51 -75%; n=5
>75%; n=1 1 - - - 1 - -
Zhong (2014) [76] RS 101A
<25%; n=2 25–49%; n=9 50–75%; n=68
>75%; n=22
22 - - - -
Total 304C N.a. 115 N.a. 16 1 3 - N.a.
Intense Pulsed Light (IPL) Author (year) Type of
study Total no of
patients Any quantitative improvement No of patients with
≥75% improvement Patient satisfaction Hyperpigmentation Hypopigmentation Scarrin
g Pain Other adverse events
Dong (2010)
[36] PC 30
No change (0%); n=0 Mild (>0 to ≤ 25%); n=0 Some (> 25%, ≤ 50%); n= 5 Moderate (> 50%, ≤ 75%); n=16 Significant (>75% to <100%); n=9
Complete (100%); n=0
9 - 0 1 0 -
Edema (<5 days) Blisters; n=2 Swelling; n=9 (resolved within a week)
Ozdemir
(2008) [54] PC 12
No change (0%); n=0 Mild (>0 to ≤ 25%); n=1 Some (> 25%, ≤ 50%); n= 3 Moderate (> 50%, ≤ 75%); n=6 Significant (>75% to <100%); n=1
Complete (100%); n=1
2 - 2 (<9 months) 1 2 - Blisters; n=4
Swelling; n=5 (<10 days)
Wang (2013)
[66] PC 29
0–25%; n=2 26–50%; n=8 51–75%; n=15 76–100%; n=4
4
5/29 patients (17.24%) moderately to extremely satisfied after
1 session. 17/29 patients (55.17%)
moderately to extremely satisfied at
follow up.
3 (<3 months) 0 0 29 Edema: n=29 (< 2-6 h)
Purpura: n=25 (< 10 days)
Total 71 N.a. 15 N.a. 5 2 2 29 N.a.
Photodynamic therapy (PDT) Author
(year) Type of study Total no of
patients Any quantitative
improvement No of patients with ≥75%
improvement Patient satisfaction Hyperpigmentation Hypopigmentation Scarring Pain Other adverse events Li-Qiang
(2018)
[51] PC 77A
≥ 90%; n= 24
≥ 60%, < 90%; n=34 ≥ 20%, < 60%; n=14
< 20%; n=5
- - - 77 Varying degrees of burning
sensation: n=70
Ma (2019)
[52] RS
Group 1 (PsD- 007): n=21
0%; n=2
<25%; n=3 25–49%; n=7 50–75%; n=6
>75%; n=3
3 All patients: burning
sensation, edema, crusting, temporary hyperpigmentation (<2
months). Drug extravasation: n=1 in each
group. No systemic side effects in either group.
- 0 0 0 38
Group 2 (HMME):
n=17
0%; n=1
<25%; n=1 25–49%; n=10
50–75%; n=4
>75%; n=1
1
Ren (2014)
[59] PC 8A
Mean clearance rate = 56.25% in 8 patients with 20
CM lesions
>75% clearance: n=6 (7 lesions)
7 - - - No blistering, erythema, or
scabbing
Wen (2019)
[68] PC 22 patients (with
31 lesions of PWS)
≥ 90%; n= 2/31
≥ 60%, < 90%; n=6/31 ≥ 20%, < 60%; n=19/31
< 20%; n=4/31
- - - -
Xiao (2011)
[70] RS 282A >50%; n=85
<25%; n=33 - - - -
Yuan (2008)
[72] RAC 306 (PDT)B
(I) excellent-colour was close to normal skin colour; n=100 (II) good-marked blanching, thicker lesion become flat, no
scar formation; n=126 (III) fair-partial blanching, thicker lesion become flat
moderately; n=57 (IV) poor-slight blanching, thicker lesion become flat
slightly; n=23 (V) no change; n=0
100 - 22 3 13 - Skin phototoxicity; n=0
Mild fibrosis; n=0
Zhang (2014)
[75] RS 132 (PDT)B
>75%; n=33 51—75%; n=60 25—50%; n=26
<25%; n=10 no blanching; n=3
33 - 5 2 4 - Skin phototoxicity; n=0
Total 865 N.a. 144 N.a. 27 5 17 115 N.a.
Other laser and light modalities Author (year) Type of
study Total no of
patients Any quantitative
improvement No of patients with ≥75%
improvement Patient satisfaction Hyperpigmentation Hypopigmentation Scarring Pain Other adverse events Ahcan (2004)
[28] CS 10 Mean blanching score
KTP+/KTP: 2.6 +/- 0.7 (26- 75%).
1 - 10 (KTP+) - 2 (KTP) - -
Del Pozo (2001)
[35] PC 19A Mean improvement = 58.4%
for all patients. 5 - 1 - 2 - -
Mohamed (2019)
[53] PC 37A
75%-100%; n=10, 50%-74%; n=14,
25%-49%; n=7,
<25%; n=6
10 - - - Transient erythema and
irritation (<2 days): n=37
Periyasamy
(2019) [57] RS 11
< 20%; n=0 21 to 40%; n=2 41 to 60%; n=4 61 to 80%; n=4 > 80%; n=1
- - - No adverse events
Wang (2018) [67] CCT 61 (DSWL)B Mean colour improvement
score: 2.7 - - 11 (<3 months) 2 3 -
Purpura and edema: n=61 Blistering and crusting:
n=19 No infection, atrophy,
keloid formation.
Total 138C N.a. 16 N.a. 21 2 7 - N.a.
Medical tattooing Author (year) Type of study Total no of
patients Any quantitative improvement No of patients with ≥75%
improvement Patient
satisfaction Hyperpigmentation Hypopigmentation Scarring Pain Other adverse events
Grabb (1977)
[40] RS 19
Expert panel vs Patient panel Worse; n=2 vs Worse; n=0 The same; n=7 vs The same; n=2 25% better; n=8 vs 25% better; n=12
50% better; n=2 vs 50% better; n=3 75% better; n=0 vs 75% better; n=2 100% better; n=0 vs 100% better; n=0
2 - - - -
van der Velden
(1993) [65] CS 5
Patient 1: good result, no loss of color Patient 2: good result, no loss of color Patient 3: good coloration, no loss of color
Patient 4: good result, no loss of color Patient 5: good result, 95% coverage. No loss
of color
- - - -
Thomson (1971)
[64] RS 41
Mild lesion: 18.8% a bit better,81.3% quite a bit better
Medium lesions: 2.2% worse, 10.3% no better, 23.5% a bit better, 64% quite a bit
better
Severe lesions: 3.1% worse, 10.6% no better, 33.8% a bit better, 52.5% quite a bit better.
- - - -
Total score 65 N.a. 2 N.a. - - - - N.a.
CCT, Controlled clinical trial; CM, Capillary malformation; cm2, square centimeter; CS, Case series; ΔE, color difference according to L*a*b coordinate system values; GCE, Global clearance effect; HMME, Hematoporphyrin monomethyl ether; IGA, Investigator Global Assessment; IPL, Intense pulsed light; LED light, Light emitting diode; N.a., Not applicable; nm, nanometer; Nd:YAG, neodymium-doped yttrium aluminum garnet; PC, Prospective cohort; PDL, Pulsed dye laser; PDT, Photodynamic Therapy; PGA, Patient global assessment;
PsD-007, second-generation photosensitizer developed in China; PWS, Port wine stain; RAC, Retrospective analytic cohort; RCT, Randomized controlled trial; RS, Retrospective study; SD, Standard deviation; USA, United States of America; V1, ophthalmic division of the trigeminal nerve; V2, maxillary division of the trigeminal nerve; V3, mandibular division of the trigeminal nerve; VAS, Visual Analogue Scale; A, only patients extracted from the study who met the inclusion criteria; B, this article is used twice due to the evaluation of two therapies; C, total number includes double counted patients due to the inclusion of studies testing two therapies within the same patient; -, not reported.