View
220
Download
0
Category
Preview:
Citation preview
Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2013 Article ID 673078 14 pageshttpdxdoiorg1011552013673078
Review ArticleAdd-On Effect of Chinese Herbal Medicine Bath to Phototherapyfor Psoriasis Vulgaris A Systematic Review
Jason Jingjie Yu1 Claire Shuiqing Zhang2 Anthony Lin Zhang2 Brian May2
Charlie Changli Xue23 and Chuanjian Lu13
1 Department of Dermatology The Second Clinical College Guangzhou University of Chinese Medicine Guangzhou 510120 China2 Traditional amp Complementary Medicine Research Program Health Innovations Research Institute School of Health SciencesRMIT University Bundoora Campus Melbourne VIC 3083 Australia
3 Guangdong Provincial Academy of Chinese Medical Sciences and Guangdong Provincial Hospital of Chinese MedicineGuangzhou 510120 China
Correspondence should be addressed to Chuanjian Lu luchuanjian888vipsinacom
Received 13 March 2013 Revised 14 June 2013 Accepted 20 June 2013
Academic Editor Tai-Long Pan
Copyright copy 2013 Jason Jingjie Yu et alThis is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
Psoriasis vulgaris is the most common form of psoriasis Phototherapy has been proven effective for psoriasis but side effectshave become a concern Chinese herbal medicine (CHM) bath combined with phototherapy has been used in clinical settings butthe additional benefit requires evaluation This review aims to evaluate the additional benefit and safety of adding CHM bath tophototherapy for psoriasis vulgaris Cochrane library PubMed Embase CNKI and CQVIP were searched from their inceptions to6 August 2012 Randomized controlled trials (RCTs) comparing CHM bath plus phototherapy to phototherapy alone for psoriasisvulgaris were included Data was analyzed using Review Manager 510 Thirteen RCTs were included in the review and eightwere included in the meta-analysis Meta-analysis showed higher efficacy of CHM bath plus phototherapy when compared withphototherapy alone in terms of PASI 60 (RR 125 95 CI 118ndash132) Mild adverse events were reported in ten studies but thesecould be alleviated by reducing UV dosage or applying emollient In conclusion CHM bath appears to be a beneficial and safeadjunctive therapy to phototherapy for psoriasis vulgaris However these results should be interpreted with caution due to the lowmethodological quality of the included studies
1 Introduction
Psoriasis is a chronic inflammatory and systemic disorderthat is characterized by scaling and erythematous plaqueswhich may be severely pruritic or painful The prevalence ofpsoriasis varies in different regions of the world with an aver-age prevalence of approximately 2 in western industrializedcountries [1 2] Psoriasis is associated with metabolic syn-drome and several inflammatory diseases including rheuma-toid arthritis and Crohnrsquos disease [3] For most patientspsoriasis brings varying degrees of lifelong restriction notonly from the skin lesions but also from joint pain andstiffness in some patients with arthritic type psoriasis andeven severe discrimination in some cases [4] In additionpsoriasis causes significant economic burden in health carecosts and losses in productivity [4]
Psoriasis vulgaris (or plaque psoriasis) is the most com-mon clinical manifestation of psoriasis affecting approxi-mately 80 to 90 of psoriasis patients [1 4] with its maincharacteristic being erythematosquamous plaques at certainsites [1 4] Inappropriate medication or infection may causepsoriasis vulgaris to transfer to other types of psoriasisincluding erythrodermic or pustular types [1 4]
Phototherapy involves exposure of patients to specificwavelengths of light either ultraviolet A (UVA) or ultravioletB (UVB) [1 4] It has been widely used as an effective ther-apeutic approach for psoriasis and is considered free of theside effects associated with conventional systemic therapies[1 4] However some undesirable side effects can be inducedby phototherapy including erythema and pruritus [18ndash21]Long-term use of phototherapy especially the combinationof oral methoxsalen (psoralen) and ultraviolet A radiation
2 Evidence-Based Complementary and Alternative Medicine
(PUVA) therapy [4 22] increases the risk of developingskin cancer Chinese herbal medicine (CHM) bath com-bined with phototherapy have been widely used in clinicalpractice for patients with psoriasis It has been reportedthat the combination of CHM bath with phototherapy hassuperior efficacy [5 6] and fewer side effects and can reduceultraviolet (UV) dosage in comparison with phototherapyalone [5] However a systematic review following rigorousmethodology to evaluate the evidence is lacking Thereforethis study aims to evaluate the efficacy and safety of CHMbath combined with phototherapy for psoriasis vulgaris
2 Methods
21 SearchMethods TheCochrane library PubMed EmbaseChina National Knowledge Infrastructure (CNKI) and Chi-nese Scientific Journals Full Text Database (CQVIP) weresearched from their respective inceptions to 6 August 2012Search terms were in three groups clinical condition (psori-asis etc) intervention (herbal medicine bath phototherapyetc) and study type (controlled trial etc) with adjustmentsfor different databases The reference lists of retrieved reviewarticles were searched for additional studies
22 Study Selection Criteria Randomized controlled trials(RCTs) published in English or Chinese regardless of publi-cation type that comparedCHMbath plus phototherapywithphototherapy alone for psoriasis vulgaris using symptomscoring systems to evaluate the efficacy were consideredThe phototherapy was defined as UVA andor UVB Co-interventions were allowed as long as the same interventionwas administered in both arms of the study Studies of othertypes of psoriasis using other forms of CHM were excluded
23 Data Extraction Data were extracted into a predefinedform in Excel and categorized by two authors (Jason JingjieYu and Claire Shuiqing Zhang)
24 Risk of Bias Assessment Two authors (Jason Jingjie Yuand Claire Shuiqing Zhang) assessed the studies using theCochrane collaborationrsquos tool for assessing risk of bias [23]Any disagreement was resolved through discussion with athird author (Lin Zhang)
25 Meta-Analysis Studies with consistent interventionsoutcome measures and sufficient data were pooled inthe meta-analysis using the Cochrane Review Manager 51(RevMan51) [23] Dichotomous data was assessed usingrisk ratio (RR) with a 95 confidence interval (CI) [23] Afixed-effect or random-effect model was used according toheterogeneity [23]
3 Results
The searches yielded 907 relevant articles After remov-ing duplicates 813 records remained 79 full articles wereretrieved for further evaluation after screening titles andabstracts Thirteen studies satisfied all selection criteria and
were included in this review All were published in ChineseEight studies were included in the meta-analysis (Figure 1)
31 Description of Studies The characteristics of includedstudies are summarized in Table 1
311 Participants All included RCTs were conducted inhospitals in China a total of 2168 outpatient participants wereinvolved in the 13 studies whilst there were 1226 participantsin the eight studies included in themeta-analysisThe averageages of the participants ranged from 274 to 458 years Tenstudies specified the western medicine (WM) diagnosticcriteria used for patient recruitment [5 6 8ndash10 12ndash15 17] andfour studies employed Chinese medicine (CM) syndromedifferentiation criteria [5 9 14 15] The key points of thediagnostic criteria referred to in these studies were consistentwith ldquoGuidelines on the treatment of psoriasis vulgarisrdquo [4] orldquoConsensus of Diagnosis and Treatment of Psoriasis Vulgarisin Integrative Medicine (China)rdquo [24] The disease durationranged from one to 13 years Four studies recruited patientswith psoriasis vulgaris at the stable stage [5 6 8 17] whilethe other studies did not provide such information None ofthe studies used symptom severity as their inclusion criteriaAll studies claimed balanced baseline data Psoriasis Area andSeverity Index (PASI) scores were reported in four studiesand the average PASI ranged from 109 to 402 at baseline[5 7 14 15] Dermatology Life Quality Index (DLQI) or BodySurface Area (BSA) data were not measured in any of thestudies
312 Interventions In regard to the phototherapy elevenstudies employed narrowband (NB)-UVB [5ndash8 10ndash16] onestudy used a combination of UVA and UVB [9] and onestudy used UVA [17] None used PUVA The dosages ofphototherapy varied across studies Six studies usedNB-UVB(310 to 315 nm) with 02 to 04 Jcm2 as the initial dosage andthen increased the dose by 01 Jcm2 each time [6 7 10 12 1315] Phototherapy was usually 2 to 3 sessions a week and thetotal duration was 21 to 90 days (Table 1)
The CHM formula used for the bath varied across the 13studies (Table 2)Themost frequently used herbs were Salviamiltiorrhiza root (Dan shen) [6 8ndash10 12 13 16] Dictamnusdasycarpus bark (Bai xian pi) [6 7 9 10 12 13 16] Sophoraflavescens root (Ku shen) [7 8 10 11 14 16 17] and Kochiascoparia fruit (Di fu zi) [6 7 10ndash13 17] The CHM bath wasconducted before phototherapy for 20 to 30 minutes in eachtreatment session
Co-interventions were used in both arms of five studiesthey were (1) PuLian ointmentmdashScutellaria baicalensis root(Huang qin) Phellodendron amurense bark (Huang bo) andpetroleum jelly [6] (2) Bing Huang Fu Le ointmentmdashRheumpalmatum root (Da huang) Curcuma longa rhizome (Jianghuang) Scutellaria baicalensis root (Huang qin) Glycyrrhizauralensis root (Gan cao) sulphur (Liu huang) syntheticborneol (Bing pian) and menthol (Bo he nao) [7] (3) ureaemollient (produced by the hospital) which was used asmoisturizer in three studies [7 14 24] and (4) glycyrrhizintablets [24] In addition two studies conducted one-week
Evidence-Based Complementary and Alternative Medicine 3
Iden
tifica
tion
Scre
enin
gEl
igib
ility
Inclu
ded
Records identified through database searches
(n = 907)
Records after duplicates removed (n = 813 )
Titles and abstracts screened (n = 813 )
Records excluded (n = 734)
E1 non-CHM bath (n = 484) E2 non-RCT (n = 136)E3 nonpsoriasis vulgaris (n = 93)E4 laboratory studies (n = 21)
Full-text articles assessed for eligibility
(n = 79 ) Full-text articles excluded(n = 66)
E1 non-CHM bath (n = 62) E2 duplications (n = 2)E3 not evaluate CHM bathefficacy (n = 1) E4 non RCT (n = 1)Studies included in
qualitative synthesis (n = 13 )
Studies included in quantitative synthesis
(meta-analysis) (n = 8)
Full-text articles excluded(n = 5)
E1 did not use PASI 60 as outcome measure (n = 3)E2 phototherapy using UVA + UVB (n = 1)E3 phototherapy using UVA (n = 1)
Duplicates(n = 94)
Figure 1 study selection PRISMA flow chart CHM Chinese herbal medicine RCT randomized controlled trial PASI the psoriasis areaand severity index UVAUVB ultraviolet AB
pretrial treatments as co-interventions in both arms usingacitretin capsules [11] or halometasone emollient [14]
313 Outcome Measures The primary outcome measure inall 13 studies was ldquototal effective raterdquo (TER) which wasdefined as PASI score reduction in ten studies [5ndash10 12 1415 17] lesion improvement based on other criteria in twostudies [11 16] and one study did not specify the criteria used[13] Actual PASI score was also reported in four studies [5 714 15] Based on a European consensus on treatment goalsfor moderate to severe psoriasis PASI 50 is the minimumrequirement for the efficacy of any therapy for psoriasis butthese criteria were not followed in any of the included studies[25]
In general the effectiveness of the interventions wasreported in four levels ldquoclinically curedrdquo ldquoremarkably effec-tiverdquo ldquoeffectiverdquo and ldquoineffectiverdquo according to the reductionof PASI or symptom scores in the included studies except forone study that used three levels (clinically cured remarkablyeffective and ineffective) [16] However the definition ofthese levels varied across studies For example in studiesusing PASI score as the measurement [5ndash10 12 14 15 17]the levels of effectiveness were defined as PASI (95-60-20)[14] PASI (90-60-25) [5ndash9 17] or PASI (90-60-30) [15] ForPASI (95-60-20) ldquoclinically curedrdquo was defined as a PASIscore reduction of 95 to 100 ldquoremarkably effectiverdquo wasa reduction of 60 to 94 ldquoeffectiverdquo was a reduction of 20to 59 and ldquoineffectiverdquo was a reduction of 0 to 19 [14]
4 Evidence-Based Complementary and Alternative Medicine
Table1Ch
aracteris
ticso
fthirteenstu
dies
ofCh
ineseh
erbalm
edicineb
athcombinedwith
phototherapy
forp
soria
sis
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Cuietal2008
[5]
hospita
lBe
ijing
and
Anshan
China
6257
4582plusmn
13893872
plusmn1217
years
CHM
bath20m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB
50of
MED
asinitial
dosageincreased
by01Jcm
2
each
timemaxim
umdo
sage
25Jcm
2 twicea
week
56days
noinform
ation
16sessions
TERbasedon
PASI
(90-60-25)
PASI
score
TER(T9677C
7193
1205942=27755
119875lt001)
PASI
score(T
416plusmn74
0C
1140plusmn1164)
NB-UVBaveraged
osage
T(995plusmn476)Jcm
2 C
(1277plusmn505)Jcm
2
(119875lt001)
Adversee
vents(redn
ess
pruritu
s)rateT
484
(362)C
315
8(1857)
(1205942=119119875lt001)
noSA
E
Guetal2009
[6]
hospita
lUrumqiC
hina
8996
3115
3284
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
PuLian
ointment
bid
NB-UVB(311nm
)03Jcm
2as
initialdo
sageincreased
by01Jcm
2each
timeqo
dPu
Lian
ointmentbid
28days
6mon
ths
14sessions
TERbasedon
PASI
(90-60-25)
relap
serate
durin
gfollo
wup
TER(T9438C
8438
1205942=48
119875lt005)
relap
seratedu
ring
follo
wup
(T1081C
3030
119875lt005)
Mild
redn
esspruritu
sandskin
dryn
ess(T
1089C
2396)
(1205942=510119875lt005)
skin
pigm
entatio
nin
all
(resolvedwith
out
medicalassis
tance
with
in2mon
ths)
noSA
E
Linetal2010
[7]
hospita
lHefeiC
hina
9590
2952plusmn
638
2742plusmn628
years
CHM
bath
20ndash30m
inthree
times
aweek
NB-UVB
consistent
with
control
interventio
nBing
Hua
ngFu
Leointmentafte
rNB-UVB
qd
NB-UVB(311nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
110second
sthreetim
esaw
eek
Bing
Hua
ngFu
Leointmentafte
rNB-UVB
qd
49days
noinform
ation
20sessions
TERbasedon
PASI
(90-60-25)
PASI
score
TER(T967
C70
1205942=1769119875lt001)
PASI
score(T
1115plusmn811
C1474plusmn90
5)
Redn
ess(T
995C
22901205942=444
119875lt005)pruritu
s(T
1195C
2690
1205942=494119875lt005)skin
dryn
ess(T
1595C
1790119875gt005)
noSA
E
Liuetal2005
[8]
hospita
lSh
ijiazhu
ang
China
4040
36235
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB(311ndash
313n
m)008
or01Jcm
2as
initialdo
sage
increasedby
001ndash0
03Jcm
2
each
timeqo
d
40days
noinform
ation
20sessions
TERbasedon
PASI
(90-60-25)
TER(T950
C825
119875lt001)
Noinform
ation
Liuetal2
004[9]
hospita
lDalian
China
1511
79
noinform
ation
CHM
bath20m
in
qodUVA
andUVB
consistentw
ithcontrolintervention
UVA
(540
0120583Wcm
2 )016
Jcm
2
asinitialdo
sageqod
UVB
(350ndash4
60120583Wcm
2 )200Jcm
2
asinitialqod
increased
by10ndash20
each
time
No
inform
ation
12mon
ths
No
inform
ation
TERbasedon
PASI
(90-60-25)
relap
serate
durin
gfollo
wup
TER(T9007C
8883
119875gt005)
relap
seratedu
ring
follo
wup
(T1523C
3519
119875lt005)
Redn
esspruritu
s(T
1015
1C
1017
9)
noSA
E
Evidence-Based Complementary and Alternative Medicine 5
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Shietal2011[10]
hospita
lBe
ijing
China
170168
noinform
ation
CHM
bath20m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB(310ndash315nm
)02ndash04Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
56days
noinform
ation
28sessions
TERbasedon
PASI
(90-60-20)
TER(T847
C702
119875lt001)
Mild
redn
esspruritu
s(T111
70C
29168)
skin
pigm
entatio
nin
all
(resolvedwith
out
medicalassis
tance
with
in3mon
ths)
noSA
E
Wangetal2010
[11]
hospita
lNanchon
gCh
ina
7070
noinform
ation
Acitretin
capsules
foro
ne-w
eekpretria
ltre
atment20
mgqd
CH
Mbath30m
in3
times
aweek
NB-UVB
consistent
with
control
interventio
n
Acitretin
capsulescon
sistent
with
treatmentintervention
NB-UVB
05Jcm
2as
initial
dosageincreased
by10ndash20
each
time3tim
esaw
eekor
1-2tim
esaw
eek(if
lesio
nsredu
ced)
21days
noinform
ation
9sessions
TERbasedon
lesio
nscore
(90-70-30)
TER(T7714
C
5857
1205942=5534
119875lt005)
Redn
esspruritu
s(T
670C
570)
noSA
E
Wangetal2011
[12]
hospita
lKa
ifeng
China
5050
382375
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollient
after
NB-UVB
qd
NB-UVB(310ndash315nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
10ndash20
each
timeqo
durea
emollient
after
NB-UVB
qd
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-20)
TER(T860
C720
119875lt005)
Mild
skin
dryn
ess
burningpain
after
NB-UVB(T450C
550)
noSA
E
Wangetal2012
[13]
hospita
lKa
ifeng
China
6060
383371
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollient
after
NB-UVB
qod
glycyrrhizin
tablets
2tabletstid
NB-UVB(310ndash315nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
10ndash20
each
timeqo
durea
emollient
after
NB-UVB
qodglycyrrhizin
tablets2tabletstid
28days
noinform
ation
14sessions
TER
TER(T917
C
777
1205942=8239119875lt005)
Skin
dryn
essbu
rning
pain
after
NB-UVB(T
460C
560)
noSA
E
Wuetal2011
[14]
hospita
lCh
engduCh
ina
7565
325348
years
Halom
etason
eem
ollient
for
one-weekpre-trial
treatmentqd
CHM
bath15ndash20
min
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollientqd
Halom
etason
eemollient
consistentw
ithtre
atment
interventio
nNB-UVB
(310ndash315nm
)05ndash06Jcm
2as
initialdo
sageincreased
by01Jcm
2each
timeqo
durea
emollientqd
40days
noinform
ation
20sessions
TERbasedon
PASI
(95-60-20)
PASI
score
TER(T7867C
5692
1205942=1054
119875lt001)
PASI
score(T
924plusmn217
C546plusmn18
6)
Slight
light
skin
dryn
ess
burningpain
after
NB-UVB(T275C
365)
noSA
E
6 Evidence-Based Complementary and Alternative Medicine
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Wuetal2010
[15]
hospita
lGuang
zhou
Ch
ina
4039
3645plusmn
8523667plusmn
836
years
CHM
bath
15ndash20m
inqod
NB-UVB
consistent
with
control
interventio
n
NB-UVB(311ndash
315n
m)
03ndash05Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
90days
noinform
ation
45sessions
TERbasedon
PASI
(90-60-30)
PASI
score
TER(T7500C
5128
1205942=478
119875=0029)
PASI
score(T
421plusmn12
2C
645plusmn227)
Skin
dryn
esspruritu
s(T540C
539)skin
pigm
entatio
nin
all
noSA
E
YanandZh
ang
2009
[16]
hospita
lXirsquoan
China
4238
noinform
ation
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB
03Jcm
2as
initial
dosageincreased
by02Jcm
2 qo
d
80days
noinform
ation
40sessions
TERbasedon
lesio
nelim
ination
TER(T880
C421
119875lt005)
Noinform
ation
Zhou
andHuang
2005
[17]
hospita
lNanning
China
143129
35362
years
CHM
bath30m
in
qodUVA
consistentw
ithcontrolintervention
UVA
4Jc
m2as
initialdo
sage
increasedby
1Jcm
2 qo
d
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-25)
TER(T8042C
64
0119875lt001)
Noinform
ation
Qdon
cead
aybidtwicea
daytid
three
times
adayand
qodon
cein
everytwodaysC
HMC
hinese
herbalmedicineNB-UVB
narrow
band
ultravioletB
UVA
ultravioletA
MED
minim
alerythemad
osethe
minim
umdo
seofradiationthatprod
ucesskin
erythemaTE
Rtotaleffectiver
atecalculated
asthep
ercentageo
fldquocuredandremarkablye
ffectiverdquocasesPA
SI(95-60-20)ldquoClinicallycuredrdquo-PASI
scorereductio
nof
95to
100
ldquoremarkablyeffectiv
erdquo-PASI
scorer
eductio
nof
60to
94ldquoeffectiv
erdquo-PASI
scorer
eductio
nof
20to
59and
ldquoineffectiv
erdquo-PASI
scorer
eductio
nof
0to
19PASI
(90-60-20)PASI
(90-60-25)and
PASI
(90-60-30)
refertoeffectiv
enesslevels
usingd
ifferentp
ropo
rtions
ofPA
SIscorereductio
nlesio
nscore(90-70-30)effectiv
enesslevels
basedon
thereductio
nofpsoriatic
lesio
nsarea
andseveritylesio
nelim
ination
effectiv
enesslevels
basedon
thee
liminationof
lesio
n(90ndash
100
30ndash
59or0
ndash29
refertoclinically
curedremarkablyeffectiv
eandineffectiv
eaccording
ly)SA
Eserio
usadversee
vent
Evidence-Based Complementary and Alternative Medicine 7
Table 2 Chinese herbal medicine bath ingredients used in the thirteen studies
Author year(reference) Chinese herbal medicine bath formula
Cui et al 2008 [5] Galla Chinensis (Wu bei zi) Cortex Phellodendri Chinensis (Huang bo) Radix Angelica Sinensis (Dang gui)Rhizoma Curcumae Longae (Jiang huang) Fructus Psoraleae (Bu gu zhi) (no information of dosage)
Gu et al 2009 [6]Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 30 g Radix Angelica Sinensis (Dang gui) Spica Prunellae (Xiaku cao) 30 g Fructus Kochiae (Di fu zi) 30 g Cortex Dictamni (Bai xian pi) 30 g Cortex Phellodendri Chinensis(Huang bo) 30 g Folium Isatidis (Da qing ye) 30 g Rhizoma Smilacis Glabrae (Tu fu ling) 30 g
Lin et al 2010 [7]
Rhizoma Smilacis Glabrae (Tu fu ling) 30 g Fructus Kochiae (Di fu zi) 15 g Radix Angelica Sinensis (Dang gui) 20 gCortex Dictamni (Bai xian pi) 20 g Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 20 g Radix SophoraFlavescens (Ku shen) 15 g Fructus Cnidii (She chuang zi) 20 g Fructus Xanthii (Cang er zi) 15 g Radix Stemonae(Bai bu) 15 g Cortex Pseudolaricis (Tu jing pi) 10 g Fructus Tribuli (Ji li) 15 g Radix et Rhizoma Rhei (Da huang) 10 g
Liu et al 2005 [8]
Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 30 g Fructus Cnidii (She chuang zi) 30 g Radix SophoraFlavescens (Ku shen) 30 g Pericarpium Zanthoxyli (Hua jiao) 30 gHerba cum Radice Patriniae (Bai jiang cao) 30 gRhizoma et Radix Polygoni Cuspidati (Hu zhang) 30 g Herba Portulacae (Ma chi xian) 30 g Radix et RhizomaSalviae Miltiorrhizae (Dan shen) 20 g Rhizoma Atractylodis (Cang zhu) 15 g
Liu et al 2004 [9]
Blood-heat syndrome Folium Isatidis (Da qing ye) Radix Rehmanniae (Di huang) Radix Paeoniae Rubra (Chishao) Rhizoma Smilacis Glabrae (Tu fu ling) Radix Arnebiae (Zi cao) Cortex Moutan (Mu dan pi) Blood-stasissyndrome Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) Semen Persicae (Tao ren) Flos Carthami (Honghua) Rhizoma Curcumae (E zhu) Caulis Spatholobi (Ji xue teng) Blood-dryness syndrome Radix Rehmanniae (Dihuang) Radix Angelica Sinensis (Dang gui) Cortex Dictamni (Bai xian pi) Herba Hedyotis (Bai hua she she cao)Rhizoma Smilacis Glabrae (Tu fu ling) (no information of dosage)
Shi et al 2011 [10]Caulis Impatientis (Tou gu cao) Cacumen Platycladi (Ce bai ye) Cortex Dictamni (Bai xian pi) Radix et RhizomaSalviae Miltiorrhizae (Dan shen) Radix Angelica Sinensis (Dang gui) Semen Persicae (Tao ren) Radix SophoraFlavescens (Ku shen) Fructus Kochiae (Di fu zi) Margarita (Zhen zhu) (no information of dosage)
Wang et al 2010 [11] Flos Chrysanthemi Indici (Ye ju hua) 240 g Pericarpium Zanthoxyli (Hua jiao) 120 g Rhizoma Smilacis Glabrae (Tufu ling) 150 g Radix Sophora Flavescens (Ku shen) 300 g Fructus Kochiae (Di fu zi) 300 g
Wang et al 2011 [12]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wang et al 2012 [13]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wu et al 2011 [14]Radix Sophora Flavescens (Ku shen) Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) Flos ChrysanthemiIndici (Ye ju hua) Herba Violae (Zi hua di ding) Flos Lonicerae Japonicae (Jin yin hua) Fructus Cnidii (She chuangzi) Glycyrrhiza uralensis root (no information of dosage)
Wu et al 2010 [15]Radix Rehmanniae (Di huang) 40 g Flos Lonicerae Japonicae (Jin yin hua) 30 g Herba Violae (Zi hua di ding) 30 gHerba Taraxaci (Pu gong ying) 30 g Zaocys (Wu shao she) 15 g Radix Scutellariae (Huang qin) 30 g RadixArnebiae seu Lithospermi (Zi cao) 30 g
Yan and Zhang2009 [16]
Radix Sophora Flavescens (Ku shen) 30 g Fructus Cnidii (She chuang zi) 30 g Radix Clematidis (Wei ling xian)30 g Cortex Dictamni (Bai xian pi) 30 g Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 20 g RhizomaAtractylodis (Cang zhu) 20 g Rhizoma Smilacis Glabrae (Tu fu ling) 20 g
Zhou and Huang2005 [17]
Rhizoma Coptidis (Huang lian) 10 g Cortex Phellodendri Chinensis (Huang bo) 20 g Radix Sophora Flavescens (Kushen) 20 g Radix Sanguisorbae (Di yu) 20 g Cortex Mahonia bealei (Tu Huang bo) 60 g Pericarpium Granati (Shiliu pi) 15 g Fructus Kochiae (Di fu zi) 15 g Herba Senecionis Scandens (Qian li guang) 30 g
Since PASI 60 was used in ten studies [5ndash10 12 14 15 17] asthe benchmark of ldquoremarkably effectiverdquo for TER calculationit was selected to be the outcome for pooling studies formeta-analysis in this review Three studies were excludedfrom meta-analysis because two of them used TER basedon a scoring system other than PASI for which there wasno evidence supporting it as an appropriate approach toevaluate therapeutic effect [11 16] and one was excluded dueto lack of a clear description of how ldquolesion improvementrdquowas measured [13]
314 Efficacy All thirteen studies reported that the com-bination of CHM bath and phototherapy had a superiorefficacy compared to phototherapy alone in terms of TERIn addition Cui et al 2008 reported that the administrationof CHM bath could significantly reduce NB-UVB averagedosage [5]
315 Followup Followup and relapse rate were reported intwo studies [6 9] In one the relapse rate of the treatmentgroup was 152 compared with 352 for control [9] In the
8 Evidence-Based Complementary and Alternative Medicine
other the rates were 108 for the treatment group and 303in the control In both cases a significant difference betweenthe two groups was reported (119875 lt 005) but a definition ofldquorelapserdquo was not provided in either study
316 Dropouts One study reported the number of dropoutsduring the treatment period without detailed reasons [6]All other studies reported that the number of patients whocompleted the trial was same as the number randomized
317 Adverse Events (AEs) Three studies did not reportany AEs [8 11 17] The most frequent AEs reported by theother ten studies were pruritus (7 studies) skin dryness (6studies) redness (6 studies) burning pain (3 studies) andskin pigmentation (3 studies) Three studies [5ndash7] reportedsignificantly higher rates of redness and pruritus in the UVBcontrol groups One of these three studies also reportedno significant difference between groups for skin dryness[7] The other seven studies that reported on AEs did notprovide details of between-group comparisons of AEs AllAEs reported in the ten studies could be resolved by reducingUV dosage or applying emollient No serious adverse event(SAE) was reported
32 Risks of Bias Assessment Risk of bias was assessed follow-ing the Cochrane Handbook 510 [23] and is summarized inFigure 2 Although all thirteen studies claimed ldquorandomizedrdquoonly six studies described the specific randomization meth-ods [5 6 10 12ndash14] Among them the random sequence gen-eration in four studies was appropriate [6 12ndash14] and assessedas ldquolow riskrdquo one study was assessed as ldquohigh riskrdquo due to theuse of patientsrsquo visiting order [15] one study used ldquoenvelopesrdquofor randomization which is not an adequate description tojudge bias therefore it was assessed as ldquounclearrdquo [5] Theother seven studies were considered ldquounclearrdquo due to thelack of information about randomization [7ndash11 16 17] Forallocation concealment method the study that used patientsrsquovisiting order for group allocation was judged ldquohigh riskrdquo[15] while the other twelve studies did not provide adequateinformation and therefore obtained judgments of ldquounclearrdquoFor all thirteen studies no information was provided forblinding of participants personnel or outcome assessors Infact blinding was impossible for participants and personnelin these studies due to the design One study reported thenumber of dropouts without reasons hence it was judged asldquounclearrdquo for incomplete outcome data [6] the other twelvestudies were assessed as ldquolow riskrdquo because they reported thatall participants finished the study A ldquolow riskrdquo assessmentwas given to all studies in terms of ldquoselective outcomereportingrdquo as the outcomes reported in the results sectionmatched the methods section However none had a protocolregistered
33 Meta-Analysis Two studies were not pooled in themeta-analysis since they used different forms of phototherapy com-pared to the others one combined UVA andUVB [9] and theother used UVA [17] Three studies were not included in themeta-analysis because they did not employPASI 60 [11 13 16]
Rand
om se
quen
ce g
ener
atio
n (s
elec
tion
bias
)
Cui et al 2008
Gu et al 2009 +
Lin et al 2010
Liu et al 2004
Liu et al 2005
Shi et al 2011
Wang et al 2010
Wang et al 2011 +
Wang et al 2012 +
Wu et al 2010 minus
Wu et al 2011 +
Yan and Zhang 2009
Zhou and Huang 2005 A
lloca
tion
conc
ealm
ent (
sele
ctio
n bi
as)
minus
Blin
ding
of p
artic
ipan
ts an
d pe
rson
nel (
perfo
rman
ce b
ias)
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
Blin
ding
of o
utco
me a
sses
smen
t (de
tect
ion
bias
)
Inco
mpl
ete o
utco
me d
ata (
attr
ition
bia
s)
++++++++++++
Sele
ctiv
e rep
ortin
g (r
epor
ting
bias
)
+++++++++++++
Figure 2 Risk of bias summary
As a result eight RCTs which used NB-UVB as phototherapyand PASI 60 for TER calculation were pooled in the meta-analysis These were divided into two groups based on studydesign as followsGroup 1 CHM Bath + NB-UVB versus NB-UVB Four studies[5 8 10 15] showed a higher TER (PASI 60) for CHM bathplus phototherapy compared with phototherapy alone (RR125 95 CI 115ndash136) without heterogeneity (1198682 = 0)(Figure 3) There was diversity in the herbs used in thesestudies but two studies had twomain herbs Ku shen andDanshen in common [8 10] The pooled result for these studiesfavoured the addition of the herbal bath (RR 119 95 CI108ndash132 1198682 = 0)Group 2 CHMBath +NB-UVB+Emollient versus NB-UVB+Emollient Four studies [6 7 12 14] showed a higher TER(PASI 60) for CHM bath plus phototherapy plus externallyapplied emollient cream compared with phototherapy plusthe same cream (RR 124 95 CI 115ndash135) The hetero-geneity was moderate (1198682 = 52) (Figure 3) Of the fourstudies three had main herbs in common [6 7 12] and ofthese Gu et al 2009 and Wang et al 2011 studies [6 12] were
Evidence-Based Complementary and Alternative Medicine 9
Study or subgroup CHM bath + NB-UVB NB-UVB Risk ratio Risk ratioEvents Total Events Total Weight MH fixed and 95 CI MH fixed and 95 CI
111 CHM bath + NB-UVB versus NB-UVB Cui et al 2008 60 62 41 57 99 135 [114 159]Liu et al 2005 38 40 33 40 76 115 [098 135]Shi et al 2011 144 170 118 168 274 121 [107 136]Wu et al 2010 30 40 20 39 47 146 [103 208]Subtotal (95 CI) 312 304 496 125 [115 136]Total events 272 212
112 CHM bath + NB-UVB + emollient versus NB-UVB + emollient
Gu et al 2009 84 89 81 96 180 112 [101 124] Lin et al 2010 89 95 63 90 149 134 [116 155] Wang et al 2011 43 50 36 50 83 119 [097 147] Wu et al 2011 59 75 37 65 92 138 [108 176] Subtotal (95 CI) 309 301 504 124 [115 135]
Total events 275 217
Total (95 CI) 621 605 100 125 [118 132]Total events 547 429
01 1 10NB-UVB CHM bath +
NB-UVB
Heterogeneity 1205942 = 286 df = 3 (P = 041) I2 = 0Test for overall effect Z = 517 (P lt 000001)
Heterogeneity 1205942 = 620 df = 3 (P = 010) I2 = 52Test for overall effect Z = 536 (P lt 000001)
Heterogeneity 1205942 = 914 df = 7 (P = 024) I2 = 23Test for overall effect Z = 744 (P lt 000001)Test for subgroup differences 1205942 = 001 df = 1 (P = 094) I2 = 0
Figure 3 Forest plot of clinical efficacy (PASI 60) PASI the psoriasis area and severity index PASI 60 the percentage of participants whoachieved PASI scores reduced by ge60 CHM Chinese herbal medicine NB-UVB narrowband ultraviolet
the most similar in that they shared Dan shen and Bai xianpi When the dissimilar study [12] was excluded there waslittle change in the result (RR 121 95 CI 112ndash132) andthe heterogeneity remained moderate (1198682 = 54) but whenthe pooling was limited to the two studies with the mostsimilar CHMs (Gu et al 2009 and Wang et al 2011) [6 12]the heterogeneity was removed (RR 114 95 CI 104ndash1261198682= 0)Overall the above eight studies [5ndash8 10 12 14 15] had
a higher TER (PASI 60) for CHM bath plus phototherapycompared with the phototherapy (RR 125 95CI 118ndash132)The heterogeneity was relatively low (1198682 = 23) (Figure 3)
4 Discussion
41 Efficacy of Phototherapy Combined with CHM Bath forPsoriasis All thirteen studies reported that CHM bath plusphototherapy had superior efficacy to phototherapy alone Inthe meta-analysis for group 1 (CHM bath + NB-UVB versusNB-UVB) all studies used the same primary outcome mea-sure did not use other supplementary treatment and therewas no heterogeneity so this result can be considered themost robust Nevertheless none of the studies employed anidentical herbal bath formulation although there were herbalingredients in common In contrast there was considerablevariation in study design in group 2 (CHMbath +NB-UVB+emollient versus NB-UVB + emollient) and this was reflectedin the heterogeneity found in the meta-analysis results Infact some co-intervention medications used in group 2 such
as PuLian ointment and Bing Huang Fu Le ointment havebeen reported to have therapeutic effects on psoriasis [26 27]Whether there was any interaction between the interventionsand co-interventions was unclear
42 Possible Mechanisms of Action for Phototherapy Com-bined with CHM Bath In psoriasis treatment phototherapymainly produces local immunosuppressive effects and anti-proliferative effects [1 4] The primary immunosuppressiveactions are reducing mobility of antigen-presenting Langer-hans cells and inhibiting T lymphocyte activation [1 4] Inaddition phototherapy inhibits epidermal hyperproliferationby interactions with keratinocyte DNA [1 4] It has beenreported thatmore than 50of patients treated by photother-apy achieved at least 75 improvement in PASI score (PASI75) after four to six weeks based on the recommendationsof the latest treatment guideline for psoriasis vulgaris [4]In this review for the ten studies [5ndash10 12 14 15 17] thatused PASI 60 for calculating TER more than 50 of controlgroup patients (611 out of 913) achieved PASI 60 after fourto eight weeks treatment with phototherapy Although theproportion of control group patients who achieved PASI 75was not specifically assessed this result indicates that thephototherapy was effective
The additional therapeutic effects of the CHM bath couldbe attributable to three main aspects (1) the thermotherapyeffects (2) the effects of a water bath and (3) the specifictherapeutic effects of the CHMs used in the baths Each ofthese aspects is discussed below
10 Evidence-Based Complementary and Alternative Medicine
421 Thermal Effects Hyperthermia is not a new conceptbut research interest into its application in the treatmentof psoriasis is relatively recent [28] Early utilization ofhyperthermia for psoriasis followed on from the ideas thatthe severity of psoriasis would reduce during warm summermonths and a benefit of hyperthermia had been shown forkilling cancer cells [29] Orenbergrsquos study in 1980 which usedultrasound induced heat to treat psoriasis showed a benefitfor psoriasis lesion remission [29] Later it was demonstratedthat hyperthermia induced by topical exothermic pads [30]infrared [31] ormicrowave [32]was also effective for psoriasisplaques The advantage of using a hot water bath is that itis a simple inexpensive approach that can be used to treatrelatively large body areas [33]
422 Water Baths (Balneotherapy) Since hyperthermia hasproven beneficial for psoriasis lesions the simple modalityof using warm or hot water became popular Nowadaysvarious types of water bath therapy are considered safetreatments for dermatological conditions and are practicedin many countries Well-known balneotherapy sites includethe Dead Sea in Israel the Kangal hot spring in Turkeythe Kusatsu hot spring in Japan and the Blue Lagoonin Iceland In particular the Dead Sea is known to beeffective for the treatment of psoriasis [34] The mecha-nisms by which diseases respond to balneotherapy probablyincorporate chemical thermal and mechanical effects [35]It was suggested by a clinical study that simple repetitivewater bath hyperthermia was effective in the treatment ofpsoriasis by improving psoriatic lesions reducing edema andrelieving pruritus [28] In addition the water itself couldremove psoriatic scale [36] which may be beneficial for skinabsorption of phototherapy Previous studies have shownthat water bath markedly increased photosensitivity to UVB[37 38]
423 Specific Effects of the CHMs Used in the Baths Onlyone of the herbs used in one study Psoralea corylifolia (Bugu zhi) [5] is known to increase photosensitivity thereforethe overall effectiveness reported for the CHM baths doesnot appear to be due to pharmacological enhancement of theeffects of the phototherapy
In order to investigate the plausibility of the CHMsused in the baths having antipsoriatic actions experimentalreports on the actions of the main herbal ingredients wereexamined The most frequently used herbs in the includedstudies were Salvia miltiorrhiza root (Dan shen) [6 8 9 1213 16 23] Dictamnus dasycarpus bark (Bai xian pi) [6 79 10 12 13 16] Sophora flavescens root (Ku shen) [7 8 1011 14 16 17] and Kochia scoparia fruit (Di fu zi) [6 7 10ndash13 17] which were each used in seven studies Each of theseherbs has a history of topical application in the manage-ment of dermatological disorders [39] Also experimentalstudies have been conducted on extracts andor compoundsderived from these herbs with regard to actions relevant topsoriasis
Salvia miltiorrhiza (Dan shen) root and its constituenttanshinones and salvianolic acids have received considerable
research attention for the treatment and prevention of cardio-vascular disorders [40] These compounds have been shownto have free radical scavenging and anti-inflammatory effects[40ndash42] Also a number of its constituent tanshinones havebeen reported to have antiproliferative or proapoptotic effectsin cancer cell lines [43] More specifically an in vitro studyof mouse keratinocytes indicated that tanshinone IIA timeand dose dependently inhibited cell growth by inducingapoptosis via caspase cascade [44] Another possible mech-anism of action for tanshinone IIA in keratinocytes is viainhibiting the dimerization of the activator protein 1 (AP-1)transcription factor resulting in reduced interferon sensitivitywhich in turn could lead to a reduced inflammatory response[45]
Jiang et al 2008 [46] reported that an extract of theroot bark of Dictamnus dasycarpus (Bai xian pi) inhibitedhistamine release and reduced scratching behaviour in amouse anaphylaxismodel In vitro anti-inflammatory activityhas been reported for a root-bark extract [47] and for itsconstituents fraxinellone [48] and obacunone [49] Also itsessential oil and a number of compounds including dictam-nine preskimmianine and fraxinellone have demonstratedantitumour activity [47]
In the case of Sophora flavescens (Ku shen) root anextract inhibited histamine release both in vitro and in vivo[50 51] and other experimental studies have reported anti-inflammatory effects for its constituent alkaloids matrine[52 53] and oxymatrine [54] and for its total flavonoids [55]Its flavonoids and chalcones both demonstrate antioxidantactivity [56] Antitumour activities have been reported invitro for both matrine and oxymatrine as well as for anumber of flavonoids [57] of which trifolirhizin has shownboth anti-inflammatory and antiproliferative actions [58]and kurarinone showed inhibition of immune response [59]In human keratinocytes an extract inhibited proinflamma-tory chemokines [60] A Sophora flavescens extract showedantipruritic effects in a mouse model [61] and in a contactdermatitis mouse model the topical application of a Sophoraflavescens extract reduced hyperplasia edema spongiosisand infiltration of mononuclear cells [51]
A series of studies have reported that the 70 ethanolextract and its component momordin Ic from the driedfruits of Kochia scoparia (Di fu zi) had antinociceptive andanti-inflammatory [62] antiallergic [63] and antipruriticeffects [64] An orally administered extract was found to beactive in a rheumatoid arthritis model in rats [65]
Each of the above studies provides evidence that thesefour herbs have anti-inflammatory antiproliferative andorantipruritic activity all of which are of relevance to thetreatment of psoriasis However this evidence is indirect withonly a few studies testing topical application Consequentlywhether the additional therapeutic effects of the CHM bathsin the studies included in this review were produced by thespecific effects of the CHMs and the effect of the warm waterbaths or were just nonspecific effects of an additional inter-vention remains unclear Therefore future studies shouldinclude a control group that uses a colored warm water bathplus phototherapy to investigate the specific efficacy of theCHMs
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
2 Evidence-Based Complementary and Alternative Medicine
(PUVA) therapy [4 22] increases the risk of developingskin cancer Chinese herbal medicine (CHM) bath com-bined with phototherapy have been widely used in clinicalpractice for patients with psoriasis It has been reportedthat the combination of CHM bath with phototherapy hassuperior efficacy [5 6] and fewer side effects and can reduceultraviolet (UV) dosage in comparison with phototherapyalone [5] However a systematic review following rigorousmethodology to evaluate the evidence is lacking Thereforethis study aims to evaluate the efficacy and safety of CHMbath combined with phototherapy for psoriasis vulgaris
2 Methods
21 SearchMethods TheCochrane library PubMed EmbaseChina National Knowledge Infrastructure (CNKI) and Chi-nese Scientific Journals Full Text Database (CQVIP) weresearched from their respective inceptions to 6 August 2012Search terms were in three groups clinical condition (psori-asis etc) intervention (herbal medicine bath phototherapyetc) and study type (controlled trial etc) with adjustmentsfor different databases The reference lists of retrieved reviewarticles were searched for additional studies
22 Study Selection Criteria Randomized controlled trials(RCTs) published in English or Chinese regardless of publi-cation type that comparedCHMbath plus phototherapywithphototherapy alone for psoriasis vulgaris using symptomscoring systems to evaluate the efficacy were consideredThe phototherapy was defined as UVA andor UVB Co-interventions were allowed as long as the same interventionwas administered in both arms of the study Studies of othertypes of psoriasis using other forms of CHM were excluded
23 Data Extraction Data were extracted into a predefinedform in Excel and categorized by two authors (Jason JingjieYu and Claire Shuiqing Zhang)
24 Risk of Bias Assessment Two authors (Jason Jingjie Yuand Claire Shuiqing Zhang) assessed the studies using theCochrane collaborationrsquos tool for assessing risk of bias [23]Any disagreement was resolved through discussion with athird author (Lin Zhang)
25 Meta-Analysis Studies with consistent interventionsoutcome measures and sufficient data were pooled inthe meta-analysis using the Cochrane Review Manager 51(RevMan51) [23] Dichotomous data was assessed usingrisk ratio (RR) with a 95 confidence interval (CI) [23] Afixed-effect or random-effect model was used according toheterogeneity [23]
3 Results
The searches yielded 907 relevant articles After remov-ing duplicates 813 records remained 79 full articles wereretrieved for further evaluation after screening titles andabstracts Thirteen studies satisfied all selection criteria and
were included in this review All were published in ChineseEight studies were included in the meta-analysis (Figure 1)
31 Description of Studies The characteristics of includedstudies are summarized in Table 1
311 Participants All included RCTs were conducted inhospitals in China a total of 2168 outpatient participants wereinvolved in the 13 studies whilst there were 1226 participantsin the eight studies included in themeta-analysisThe averageages of the participants ranged from 274 to 458 years Tenstudies specified the western medicine (WM) diagnosticcriteria used for patient recruitment [5 6 8ndash10 12ndash15 17] andfour studies employed Chinese medicine (CM) syndromedifferentiation criteria [5 9 14 15] The key points of thediagnostic criteria referred to in these studies were consistentwith ldquoGuidelines on the treatment of psoriasis vulgarisrdquo [4] orldquoConsensus of Diagnosis and Treatment of Psoriasis Vulgarisin Integrative Medicine (China)rdquo [24] The disease durationranged from one to 13 years Four studies recruited patientswith psoriasis vulgaris at the stable stage [5 6 8 17] whilethe other studies did not provide such information None ofthe studies used symptom severity as their inclusion criteriaAll studies claimed balanced baseline data Psoriasis Area andSeverity Index (PASI) scores were reported in four studiesand the average PASI ranged from 109 to 402 at baseline[5 7 14 15] Dermatology Life Quality Index (DLQI) or BodySurface Area (BSA) data were not measured in any of thestudies
312 Interventions In regard to the phototherapy elevenstudies employed narrowband (NB)-UVB [5ndash8 10ndash16] onestudy used a combination of UVA and UVB [9] and onestudy used UVA [17] None used PUVA The dosages ofphototherapy varied across studies Six studies usedNB-UVB(310 to 315 nm) with 02 to 04 Jcm2 as the initial dosage andthen increased the dose by 01 Jcm2 each time [6 7 10 12 1315] Phototherapy was usually 2 to 3 sessions a week and thetotal duration was 21 to 90 days (Table 1)
The CHM formula used for the bath varied across the 13studies (Table 2)Themost frequently used herbs were Salviamiltiorrhiza root (Dan shen) [6 8ndash10 12 13 16] Dictamnusdasycarpus bark (Bai xian pi) [6 7 9 10 12 13 16] Sophoraflavescens root (Ku shen) [7 8 10 11 14 16 17] and Kochiascoparia fruit (Di fu zi) [6 7 10ndash13 17] The CHM bath wasconducted before phototherapy for 20 to 30 minutes in eachtreatment session
Co-interventions were used in both arms of five studiesthey were (1) PuLian ointmentmdashScutellaria baicalensis root(Huang qin) Phellodendron amurense bark (Huang bo) andpetroleum jelly [6] (2) Bing Huang Fu Le ointmentmdashRheumpalmatum root (Da huang) Curcuma longa rhizome (Jianghuang) Scutellaria baicalensis root (Huang qin) Glycyrrhizauralensis root (Gan cao) sulphur (Liu huang) syntheticborneol (Bing pian) and menthol (Bo he nao) [7] (3) ureaemollient (produced by the hospital) which was used asmoisturizer in three studies [7 14 24] and (4) glycyrrhizintablets [24] In addition two studies conducted one-week
Evidence-Based Complementary and Alternative Medicine 3
Iden
tifica
tion
Scre
enin
gEl
igib
ility
Inclu
ded
Records identified through database searches
(n = 907)
Records after duplicates removed (n = 813 )
Titles and abstracts screened (n = 813 )
Records excluded (n = 734)
E1 non-CHM bath (n = 484) E2 non-RCT (n = 136)E3 nonpsoriasis vulgaris (n = 93)E4 laboratory studies (n = 21)
Full-text articles assessed for eligibility
(n = 79 ) Full-text articles excluded(n = 66)
E1 non-CHM bath (n = 62) E2 duplications (n = 2)E3 not evaluate CHM bathefficacy (n = 1) E4 non RCT (n = 1)Studies included in
qualitative synthesis (n = 13 )
Studies included in quantitative synthesis
(meta-analysis) (n = 8)
Full-text articles excluded(n = 5)
E1 did not use PASI 60 as outcome measure (n = 3)E2 phototherapy using UVA + UVB (n = 1)E3 phototherapy using UVA (n = 1)
Duplicates(n = 94)
Figure 1 study selection PRISMA flow chart CHM Chinese herbal medicine RCT randomized controlled trial PASI the psoriasis areaand severity index UVAUVB ultraviolet AB
pretrial treatments as co-interventions in both arms usingacitretin capsules [11] or halometasone emollient [14]
313 Outcome Measures The primary outcome measure inall 13 studies was ldquototal effective raterdquo (TER) which wasdefined as PASI score reduction in ten studies [5ndash10 12 1415 17] lesion improvement based on other criteria in twostudies [11 16] and one study did not specify the criteria used[13] Actual PASI score was also reported in four studies [5 714 15] Based on a European consensus on treatment goalsfor moderate to severe psoriasis PASI 50 is the minimumrequirement for the efficacy of any therapy for psoriasis butthese criteria were not followed in any of the included studies[25]
In general the effectiveness of the interventions wasreported in four levels ldquoclinically curedrdquo ldquoremarkably effec-tiverdquo ldquoeffectiverdquo and ldquoineffectiverdquo according to the reductionof PASI or symptom scores in the included studies except forone study that used three levels (clinically cured remarkablyeffective and ineffective) [16] However the definition ofthese levels varied across studies For example in studiesusing PASI score as the measurement [5ndash10 12 14 15 17]the levels of effectiveness were defined as PASI (95-60-20)[14] PASI (90-60-25) [5ndash9 17] or PASI (90-60-30) [15] ForPASI (95-60-20) ldquoclinically curedrdquo was defined as a PASIscore reduction of 95 to 100 ldquoremarkably effectiverdquo wasa reduction of 60 to 94 ldquoeffectiverdquo was a reduction of 20to 59 and ldquoineffectiverdquo was a reduction of 0 to 19 [14]
4 Evidence-Based Complementary and Alternative Medicine
Table1Ch
aracteris
ticso
fthirteenstu
dies
ofCh
ineseh
erbalm
edicineb
athcombinedwith
phototherapy
forp
soria
sis
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Cuietal2008
[5]
hospita
lBe
ijing
and
Anshan
China
6257
4582plusmn
13893872
plusmn1217
years
CHM
bath20m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB
50of
MED
asinitial
dosageincreased
by01Jcm
2
each
timemaxim
umdo
sage
25Jcm
2 twicea
week
56days
noinform
ation
16sessions
TERbasedon
PASI
(90-60-25)
PASI
score
TER(T9677C
7193
1205942=27755
119875lt001)
PASI
score(T
416plusmn74
0C
1140plusmn1164)
NB-UVBaveraged
osage
T(995plusmn476)Jcm
2 C
(1277plusmn505)Jcm
2
(119875lt001)
Adversee
vents(redn
ess
pruritu
s)rateT
484
(362)C
315
8(1857)
(1205942=119119875lt001)
noSA
E
Guetal2009
[6]
hospita
lUrumqiC
hina
8996
3115
3284
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
PuLian
ointment
bid
NB-UVB(311nm
)03Jcm
2as
initialdo
sageincreased
by01Jcm
2each
timeqo
dPu
Lian
ointmentbid
28days
6mon
ths
14sessions
TERbasedon
PASI
(90-60-25)
relap
serate
durin
gfollo
wup
TER(T9438C
8438
1205942=48
119875lt005)
relap
seratedu
ring
follo
wup
(T1081C
3030
119875lt005)
Mild
redn
esspruritu
sandskin
dryn
ess(T
1089C
2396)
(1205942=510119875lt005)
skin
pigm
entatio
nin
all
(resolvedwith
out
medicalassis
tance
with
in2mon
ths)
noSA
E
Linetal2010
[7]
hospita
lHefeiC
hina
9590
2952plusmn
638
2742plusmn628
years
CHM
bath
20ndash30m
inthree
times
aweek
NB-UVB
consistent
with
control
interventio
nBing
Hua
ngFu
Leointmentafte
rNB-UVB
qd
NB-UVB(311nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
110second
sthreetim
esaw
eek
Bing
Hua
ngFu
Leointmentafte
rNB-UVB
qd
49days
noinform
ation
20sessions
TERbasedon
PASI
(90-60-25)
PASI
score
TER(T967
C70
1205942=1769119875lt001)
PASI
score(T
1115plusmn811
C1474plusmn90
5)
Redn
ess(T
995C
22901205942=444
119875lt005)pruritu
s(T
1195C
2690
1205942=494119875lt005)skin
dryn
ess(T
1595C
1790119875gt005)
noSA
E
Liuetal2005
[8]
hospita
lSh
ijiazhu
ang
China
4040
36235
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB(311ndash
313n
m)008
or01Jcm
2as
initialdo
sage
increasedby
001ndash0
03Jcm
2
each
timeqo
d
40days
noinform
ation
20sessions
TERbasedon
PASI
(90-60-25)
TER(T950
C825
119875lt001)
Noinform
ation
Liuetal2
004[9]
hospita
lDalian
China
1511
79
noinform
ation
CHM
bath20m
in
qodUVA
andUVB
consistentw
ithcontrolintervention
UVA
(540
0120583Wcm
2 )016
Jcm
2
asinitialdo
sageqod
UVB
(350ndash4
60120583Wcm
2 )200Jcm
2
asinitialqod
increased
by10ndash20
each
time
No
inform
ation
12mon
ths
No
inform
ation
TERbasedon
PASI
(90-60-25)
relap
serate
durin
gfollo
wup
TER(T9007C
8883
119875gt005)
relap
seratedu
ring
follo
wup
(T1523C
3519
119875lt005)
Redn
esspruritu
s(T
1015
1C
1017
9)
noSA
E
Evidence-Based Complementary and Alternative Medicine 5
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Shietal2011[10]
hospita
lBe
ijing
China
170168
noinform
ation
CHM
bath20m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB(310ndash315nm
)02ndash04Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
56days
noinform
ation
28sessions
TERbasedon
PASI
(90-60-20)
TER(T847
C702
119875lt001)
Mild
redn
esspruritu
s(T111
70C
29168)
skin
pigm
entatio
nin
all
(resolvedwith
out
medicalassis
tance
with
in3mon
ths)
noSA
E
Wangetal2010
[11]
hospita
lNanchon
gCh
ina
7070
noinform
ation
Acitretin
capsules
foro
ne-w
eekpretria
ltre
atment20
mgqd
CH
Mbath30m
in3
times
aweek
NB-UVB
consistent
with
control
interventio
n
Acitretin
capsulescon
sistent
with
treatmentintervention
NB-UVB
05Jcm
2as
initial
dosageincreased
by10ndash20
each
time3tim
esaw
eekor
1-2tim
esaw
eek(if
lesio
nsredu
ced)
21days
noinform
ation
9sessions
TERbasedon
lesio
nscore
(90-70-30)
TER(T7714
C
5857
1205942=5534
119875lt005)
Redn
esspruritu
s(T
670C
570)
noSA
E
Wangetal2011
[12]
hospita
lKa
ifeng
China
5050
382375
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollient
after
NB-UVB
qd
NB-UVB(310ndash315nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
10ndash20
each
timeqo
durea
emollient
after
NB-UVB
qd
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-20)
TER(T860
C720
119875lt005)
Mild
skin
dryn
ess
burningpain
after
NB-UVB(T450C
550)
noSA
E
Wangetal2012
[13]
hospita
lKa
ifeng
China
6060
383371
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollient
after
NB-UVB
qod
glycyrrhizin
tablets
2tabletstid
NB-UVB(310ndash315nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
10ndash20
each
timeqo
durea
emollient
after
NB-UVB
qodglycyrrhizin
tablets2tabletstid
28days
noinform
ation
14sessions
TER
TER(T917
C
777
1205942=8239119875lt005)
Skin
dryn
essbu
rning
pain
after
NB-UVB(T
460C
560)
noSA
E
Wuetal2011
[14]
hospita
lCh
engduCh
ina
7565
325348
years
Halom
etason
eem
ollient
for
one-weekpre-trial
treatmentqd
CHM
bath15ndash20
min
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollientqd
Halom
etason
eemollient
consistentw
ithtre
atment
interventio
nNB-UVB
(310ndash315nm
)05ndash06Jcm
2as
initialdo
sageincreased
by01Jcm
2each
timeqo
durea
emollientqd
40days
noinform
ation
20sessions
TERbasedon
PASI
(95-60-20)
PASI
score
TER(T7867C
5692
1205942=1054
119875lt001)
PASI
score(T
924plusmn217
C546plusmn18
6)
Slight
light
skin
dryn
ess
burningpain
after
NB-UVB(T275C
365)
noSA
E
6 Evidence-Based Complementary and Alternative Medicine
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Wuetal2010
[15]
hospita
lGuang
zhou
Ch
ina
4039
3645plusmn
8523667plusmn
836
years
CHM
bath
15ndash20m
inqod
NB-UVB
consistent
with
control
interventio
n
NB-UVB(311ndash
315n
m)
03ndash05Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
90days
noinform
ation
45sessions
TERbasedon
PASI
(90-60-30)
PASI
score
TER(T7500C
5128
1205942=478
119875=0029)
PASI
score(T
421plusmn12
2C
645plusmn227)
Skin
dryn
esspruritu
s(T540C
539)skin
pigm
entatio
nin
all
noSA
E
YanandZh
ang
2009
[16]
hospita
lXirsquoan
China
4238
noinform
ation
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB
03Jcm
2as
initial
dosageincreased
by02Jcm
2 qo
d
80days
noinform
ation
40sessions
TERbasedon
lesio
nelim
ination
TER(T880
C421
119875lt005)
Noinform
ation
Zhou
andHuang
2005
[17]
hospita
lNanning
China
143129
35362
years
CHM
bath30m
in
qodUVA
consistentw
ithcontrolintervention
UVA
4Jc
m2as
initialdo
sage
increasedby
1Jcm
2 qo
d
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-25)
TER(T8042C
64
0119875lt001)
Noinform
ation
Qdon
cead
aybidtwicea
daytid
three
times
adayand
qodon
cein
everytwodaysC
HMC
hinese
herbalmedicineNB-UVB
narrow
band
ultravioletB
UVA
ultravioletA
MED
minim
alerythemad
osethe
minim
umdo
seofradiationthatprod
ucesskin
erythemaTE
Rtotaleffectiver
atecalculated
asthep
ercentageo
fldquocuredandremarkablye
ffectiverdquocasesPA
SI(95-60-20)ldquoClinicallycuredrdquo-PASI
scorereductio
nof
95to
100
ldquoremarkablyeffectiv
erdquo-PASI
scorer
eductio
nof
60to
94ldquoeffectiv
erdquo-PASI
scorer
eductio
nof
20to
59and
ldquoineffectiv
erdquo-PASI
scorer
eductio
nof
0to
19PASI
(90-60-20)PASI
(90-60-25)and
PASI
(90-60-30)
refertoeffectiv
enesslevels
usingd
ifferentp
ropo
rtions
ofPA
SIscorereductio
nlesio
nscore(90-70-30)effectiv
enesslevels
basedon
thereductio
nofpsoriatic
lesio
nsarea
andseveritylesio
nelim
ination
effectiv
enesslevels
basedon
thee
liminationof
lesio
n(90ndash
100
30ndash
59or0
ndash29
refertoclinically
curedremarkablyeffectiv
eandineffectiv
eaccording
ly)SA
Eserio
usadversee
vent
Evidence-Based Complementary and Alternative Medicine 7
Table 2 Chinese herbal medicine bath ingredients used in the thirteen studies
Author year(reference) Chinese herbal medicine bath formula
Cui et al 2008 [5] Galla Chinensis (Wu bei zi) Cortex Phellodendri Chinensis (Huang bo) Radix Angelica Sinensis (Dang gui)Rhizoma Curcumae Longae (Jiang huang) Fructus Psoraleae (Bu gu zhi) (no information of dosage)
Gu et al 2009 [6]Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 30 g Radix Angelica Sinensis (Dang gui) Spica Prunellae (Xiaku cao) 30 g Fructus Kochiae (Di fu zi) 30 g Cortex Dictamni (Bai xian pi) 30 g Cortex Phellodendri Chinensis(Huang bo) 30 g Folium Isatidis (Da qing ye) 30 g Rhizoma Smilacis Glabrae (Tu fu ling) 30 g
Lin et al 2010 [7]
Rhizoma Smilacis Glabrae (Tu fu ling) 30 g Fructus Kochiae (Di fu zi) 15 g Radix Angelica Sinensis (Dang gui) 20 gCortex Dictamni (Bai xian pi) 20 g Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 20 g Radix SophoraFlavescens (Ku shen) 15 g Fructus Cnidii (She chuang zi) 20 g Fructus Xanthii (Cang er zi) 15 g Radix Stemonae(Bai bu) 15 g Cortex Pseudolaricis (Tu jing pi) 10 g Fructus Tribuli (Ji li) 15 g Radix et Rhizoma Rhei (Da huang) 10 g
Liu et al 2005 [8]
Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 30 g Fructus Cnidii (She chuang zi) 30 g Radix SophoraFlavescens (Ku shen) 30 g Pericarpium Zanthoxyli (Hua jiao) 30 gHerba cum Radice Patriniae (Bai jiang cao) 30 gRhizoma et Radix Polygoni Cuspidati (Hu zhang) 30 g Herba Portulacae (Ma chi xian) 30 g Radix et RhizomaSalviae Miltiorrhizae (Dan shen) 20 g Rhizoma Atractylodis (Cang zhu) 15 g
Liu et al 2004 [9]
Blood-heat syndrome Folium Isatidis (Da qing ye) Radix Rehmanniae (Di huang) Radix Paeoniae Rubra (Chishao) Rhizoma Smilacis Glabrae (Tu fu ling) Radix Arnebiae (Zi cao) Cortex Moutan (Mu dan pi) Blood-stasissyndrome Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) Semen Persicae (Tao ren) Flos Carthami (Honghua) Rhizoma Curcumae (E zhu) Caulis Spatholobi (Ji xue teng) Blood-dryness syndrome Radix Rehmanniae (Dihuang) Radix Angelica Sinensis (Dang gui) Cortex Dictamni (Bai xian pi) Herba Hedyotis (Bai hua she she cao)Rhizoma Smilacis Glabrae (Tu fu ling) (no information of dosage)
Shi et al 2011 [10]Caulis Impatientis (Tou gu cao) Cacumen Platycladi (Ce bai ye) Cortex Dictamni (Bai xian pi) Radix et RhizomaSalviae Miltiorrhizae (Dan shen) Radix Angelica Sinensis (Dang gui) Semen Persicae (Tao ren) Radix SophoraFlavescens (Ku shen) Fructus Kochiae (Di fu zi) Margarita (Zhen zhu) (no information of dosage)
Wang et al 2010 [11] Flos Chrysanthemi Indici (Ye ju hua) 240 g Pericarpium Zanthoxyli (Hua jiao) 120 g Rhizoma Smilacis Glabrae (Tufu ling) 150 g Radix Sophora Flavescens (Ku shen) 300 g Fructus Kochiae (Di fu zi) 300 g
Wang et al 2011 [12]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wang et al 2012 [13]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wu et al 2011 [14]Radix Sophora Flavescens (Ku shen) Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) Flos ChrysanthemiIndici (Ye ju hua) Herba Violae (Zi hua di ding) Flos Lonicerae Japonicae (Jin yin hua) Fructus Cnidii (She chuangzi) Glycyrrhiza uralensis root (no information of dosage)
Wu et al 2010 [15]Radix Rehmanniae (Di huang) 40 g Flos Lonicerae Japonicae (Jin yin hua) 30 g Herba Violae (Zi hua di ding) 30 gHerba Taraxaci (Pu gong ying) 30 g Zaocys (Wu shao she) 15 g Radix Scutellariae (Huang qin) 30 g RadixArnebiae seu Lithospermi (Zi cao) 30 g
Yan and Zhang2009 [16]
Radix Sophora Flavescens (Ku shen) 30 g Fructus Cnidii (She chuang zi) 30 g Radix Clematidis (Wei ling xian)30 g Cortex Dictamni (Bai xian pi) 30 g Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 20 g RhizomaAtractylodis (Cang zhu) 20 g Rhizoma Smilacis Glabrae (Tu fu ling) 20 g
Zhou and Huang2005 [17]
Rhizoma Coptidis (Huang lian) 10 g Cortex Phellodendri Chinensis (Huang bo) 20 g Radix Sophora Flavescens (Kushen) 20 g Radix Sanguisorbae (Di yu) 20 g Cortex Mahonia bealei (Tu Huang bo) 60 g Pericarpium Granati (Shiliu pi) 15 g Fructus Kochiae (Di fu zi) 15 g Herba Senecionis Scandens (Qian li guang) 30 g
Since PASI 60 was used in ten studies [5ndash10 12 14 15 17] asthe benchmark of ldquoremarkably effectiverdquo for TER calculationit was selected to be the outcome for pooling studies formeta-analysis in this review Three studies were excludedfrom meta-analysis because two of them used TER basedon a scoring system other than PASI for which there wasno evidence supporting it as an appropriate approach toevaluate therapeutic effect [11 16] and one was excluded dueto lack of a clear description of how ldquolesion improvementrdquowas measured [13]
314 Efficacy All thirteen studies reported that the com-bination of CHM bath and phototherapy had a superiorefficacy compared to phototherapy alone in terms of TERIn addition Cui et al 2008 reported that the administrationof CHM bath could significantly reduce NB-UVB averagedosage [5]
315 Followup Followup and relapse rate were reported intwo studies [6 9] In one the relapse rate of the treatmentgroup was 152 compared with 352 for control [9] In the
8 Evidence-Based Complementary and Alternative Medicine
other the rates were 108 for the treatment group and 303in the control In both cases a significant difference betweenthe two groups was reported (119875 lt 005) but a definition ofldquorelapserdquo was not provided in either study
316 Dropouts One study reported the number of dropoutsduring the treatment period without detailed reasons [6]All other studies reported that the number of patients whocompleted the trial was same as the number randomized
317 Adverse Events (AEs) Three studies did not reportany AEs [8 11 17] The most frequent AEs reported by theother ten studies were pruritus (7 studies) skin dryness (6studies) redness (6 studies) burning pain (3 studies) andskin pigmentation (3 studies) Three studies [5ndash7] reportedsignificantly higher rates of redness and pruritus in the UVBcontrol groups One of these three studies also reportedno significant difference between groups for skin dryness[7] The other seven studies that reported on AEs did notprovide details of between-group comparisons of AEs AllAEs reported in the ten studies could be resolved by reducingUV dosage or applying emollient No serious adverse event(SAE) was reported
32 Risks of Bias Assessment Risk of bias was assessed follow-ing the Cochrane Handbook 510 [23] and is summarized inFigure 2 Although all thirteen studies claimed ldquorandomizedrdquoonly six studies described the specific randomization meth-ods [5 6 10 12ndash14] Among them the random sequence gen-eration in four studies was appropriate [6 12ndash14] and assessedas ldquolow riskrdquo one study was assessed as ldquohigh riskrdquo due to theuse of patientsrsquo visiting order [15] one study used ldquoenvelopesrdquofor randomization which is not an adequate description tojudge bias therefore it was assessed as ldquounclearrdquo [5] Theother seven studies were considered ldquounclearrdquo due to thelack of information about randomization [7ndash11 16 17] Forallocation concealment method the study that used patientsrsquovisiting order for group allocation was judged ldquohigh riskrdquo[15] while the other twelve studies did not provide adequateinformation and therefore obtained judgments of ldquounclearrdquoFor all thirteen studies no information was provided forblinding of participants personnel or outcome assessors Infact blinding was impossible for participants and personnelin these studies due to the design One study reported thenumber of dropouts without reasons hence it was judged asldquounclearrdquo for incomplete outcome data [6] the other twelvestudies were assessed as ldquolow riskrdquo because they reported thatall participants finished the study A ldquolow riskrdquo assessmentwas given to all studies in terms of ldquoselective outcomereportingrdquo as the outcomes reported in the results sectionmatched the methods section However none had a protocolregistered
33 Meta-Analysis Two studies were not pooled in themeta-analysis since they used different forms of phototherapy com-pared to the others one combined UVA andUVB [9] and theother used UVA [17] Three studies were not included in themeta-analysis because they did not employPASI 60 [11 13 16]
Rand
om se
quen
ce g
ener
atio
n (s
elec
tion
bias
)
Cui et al 2008
Gu et al 2009 +
Lin et al 2010
Liu et al 2004
Liu et al 2005
Shi et al 2011
Wang et al 2010
Wang et al 2011 +
Wang et al 2012 +
Wu et al 2010 minus
Wu et al 2011 +
Yan and Zhang 2009
Zhou and Huang 2005 A
lloca
tion
conc
ealm
ent (
sele
ctio
n bi
as)
minus
Blin
ding
of p
artic
ipan
ts an
d pe
rson
nel (
perfo
rman
ce b
ias)
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
Blin
ding
of o
utco
me a
sses
smen
t (de
tect
ion
bias
)
Inco
mpl
ete o
utco
me d
ata (
attr
ition
bia
s)
++++++++++++
Sele
ctiv
e rep
ortin
g (r
epor
ting
bias
)
+++++++++++++
Figure 2 Risk of bias summary
As a result eight RCTs which used NB-UVB as phototherapyand PASI 60 for TER calculation were pooled in the meta-analysis These were divided into two groups based on studydesign as followsGroup 1 CHM Bath + NB-UVB versus NB-UVB Four studies[5 8 10 15] showed a higher TER (PASI 60) for CHM bathplus phototherapy compared with phototherapy alone (RR125 95 CI 115ndash136) without heterogeneity (1198682 = 0)(Figure 3) There was diversity in the herbs used in thesestudies but two studies had twomain herbs Ku shen andDanshen in common [8 10] The pooled result for these studiesfavoured the addition of the herbal bath (RR 119 95 CI108ndash132 1198682 = 0)Group 2 CHMBath +NB-UVB+Emollient versus NB-UVB+Emollient Four studies [6 7 12 14] showed a higher TER(PASI 60) for CHM bath plus phototherapy plus externallyapplied emollient cream compared with phototherapy plusthe same cream (RR 124 95 CI 115ndash135) The hetero-geneity was moderate (1198682 = 52) (Figure 3) Of the fourstudies three had main herbs in common [6 7 12] and ofthese Gu et al 2009 and Wang et al 2011 studies [6 12] were
Evidence-Based Complementary and Alternative Medicine 9
Study or subgroup CHM bath + NB-UVB NB-UVB Risk ratio Risk ratioEvents Total Events Total Weight MH fixed and 95 CI MH fixed and 95 CI
111 CHM bath + NB-UVB versus NB-UVB Cui et al 2008 60 62 41 57 99 135 [114 159]Liu et al 2005 38 40 33 40 76 115 [098 135]Shi et al 2011 144 170 118 168 274 121 [107 136]Wu et al 2010 30 40 20 39 47 146 [103 208]Subtotal (95 CI) 312 304 496 125 [115 136]Total events 272 212
112 CHM bath + NB-UVB + emollient versus NB-UVB + emollient
Gu et al 2009 84 89 81 96 180 112 [101 124] Lin et al 2010 89 95 63 90 149 134 [116 155] Wang et al 2011 43 50 36 50 83 119 [097 147] Wu et al 2011 59 75 37 65 92 138 [108 176] Subtotal (95 CI) 309 301 504 124 [115 135]
Total events 275 217
Total (95 CI) 621 605 100 125 [118 132]Total events 547 429
01 1 10NB-UVB CHM bath +
NB-UVB
Heterogeneity 1205942 = 286 df = 3 (P = 041) I2 = 0Test for overall effect Z = 517 (P lt 000001)
Heterogeneity 1205942 = 620 df = 3 (P = 010) I2 = 52Test for overall effect Z = 536 (P lt 000001)
Heterogeneity 1205942 = 914 df = 7 (P = 024) I2 = 23Test for overall effect Z = 744 (P lt 000001)Test for subgroup differences 1205942 = 001 df = 1 (P = 094) I2 = 0
Figure 3 Forest plot of clinical efficacy (PASI 60) PASI the psoriasis area and severity index PASI 60 the percentage of participants whoachieved PASI scores reduced by ge60 CHM Chinese herbal medicine NB-UVB narrowband ultraviolet
the most similar in that they shared Dan shen and Bai xianpi When the dissimilar study [12] was excluded there waslittle change in the result (RR 121 95 CI 112ndash132) andthe heterogeneity remained moderate (1198682 = 54) but whenthe pooling was limited to the two studies with the mostsimilar CHMs (Gu et al 2009 and Wang et al 2011) [6 12]the heterogeneity was removed (RR 114 95 CI 104ndash1261198682= 0)Overall the above eight studies [5ndash8 10 12 14 15] had
a higher TER (PASI 60) for CHM bath plus phototherapycompared with the phototherapy (RR 125 95CI 118ndash132)The heterogeneity was relatively low (1198682 = 23) (Figure 3)
4 Discussion
41 Efficacy of Phototherapy Combined with CHM Bath forPsoriasis All thirteen studies reported that CHM bath plusphototherapy had superior efficacy to phototherapy alone Inthe meta-analysis for group 1 (CHM bath + NB-UVB versusNB-UVB) all studies used the same primary outcome mea-sure did not use other supplementary treatment and therewas no heterogeneity so this result can be considered themost robust Nevertheless none of the studies employed anidentical herbal bath formulation although there were herbalingredients in common In contrast there was considerablevariation in study design in group 2 (CHMbath +NB-UVB+emollient versus NB-UVB + emollient) and this was reflectedin the heterogeneity found in the meta-analysis results Infact some co-intervention medications used in group 2 such
as PuLian ointment and Bing Huang Fu Le ointment havebeen reported to have therapeutic effects on psoriasis [26 27]Whether there was any interaction between the interventionsand co-interventions was unclear
42 Possible Mechanisms of Action for Phototherapy Com-bined with CHM Bath In psoriasis treatment phototherapymainly produces local immunosuppressive effects and anti-proliferative effects [1 4] The primary immunosuppressiveactions are reducing mobility of antigen-presenting Langer-hans cells and inhibiting T lymphocyte activation [1 4] Inaddition phototherapy inhibits epidermal hyperproliferationby interactions with keratinocyte DNA [1 4] It has beenreported thatmore than 50of patients treated by photother-apy achieved at least 75 improvement in PASI score (PASI75) after four to six weeks based on the recommendationsof the latest treatment guideline for psoriasis vulgaris [4]In this review for the ten studies [5ndash10 12 14 15 17] thatused PASI 60 for calculating TER more than 50 of controlgroup patients (611 out of 913) achieved PASI 60 after fourto eight weeks treatment with phototherapy Although theproportion of control group patients who achieved PASI 75was not specifically assessed this result indicates that thephototherapy was effective
The additional therapeutic effects of the CHM bath couldbe attributable to three main aspects (1) the thermotherapyeffects (2) the effects of a water bath and (3) the specifictherapeutic effects of the CHMs used in the baths Each ofthese aspects is discussed below
10 Evidence-Based Complementary and Alternative Medicine
421 Thermal Effects Hyperthermia is not a new conceptbut research interest into its application in the treatmentof psoriasis is relatively recent [28] Early utilization ofhyperthermia for psoriasis followed on from the ideas thatthe severity of psoriasis would reduce during warm summermonths and a benefit of hyperthermia had been shown forkilling cancer cells [29] Orenbergrsquos study in 1980 which usedultrasound induced heat to treat psoriasis showed a benefitfor psoriasis lesion remission [29] Later it was demonstratedthat hyperthermia induced by topical exothermic pads [30]infrared [31] ormicrowave [32]was also effective for psoriasisplaques The advantage of using a hot water bath is that itis a simple inexpensive approach that can be used to treatrelatively large body areas [33]
422 Water Baths (Balneotherapy) Since hyperthermia hasproven beneficial for psoriasis lesions the simple modalityof using warm or hot water became popular Nowadaysvarious types of water bath therapy are considered safetreatments for dermatological conditions and are practicedin many countries Well-known balneotherapy sites includethe Dead Sea in Israel the Kangal hot spring in Turkeythe Kusatsu hot spring in Japan and the Blue Lagoonin Iceland In particular the Dead Sea is known to beeffective for the treatment of psoriasis [34] The mecha-nisms by which diseases respond to balneotherapy probablyincorporate chemical thermal and mechanical effects [35]It was suggested by a clinical study that simple repetitivewater bath hyperthermia was effective in the treatment ofpsoriasis by improving psoriatic lesions reducing edema andrelieving pruritus [28] In addition the water itself couldremove psoriatic scale [36] which may be beneficial for skinabsorption of phototherapy Previous studies have shownthat water bath markedly increased photosensitivity to UVB[37 38]
423 Specific Effects of the CHMs Used in the Baths Onlyone of the herbs used in one study Psoralea corylifolia (Bugu zhi) [5] is known to increase photosensitivity thereforethe overall effectiveness reported for the CHM baths doesnot appear to be due to pharmacological enhancement of theeffects of the phototherapy
In order to investigate the plausibility of the CHMsused in the baths having antipsoriatic actions experimentalreports on the actions of the main herbal ingredients wereexamined The most frequently used herbs in the includedstudies were Salvia miltiorrhiza root (Dan shen) [6 8 9 1213 16 23] Dictamnus dasycarpus bark (Bai xian pi) [6 79 10 12 13 16] Sophora flavescens root (Ku shen) [7 8 1011 14 16 17] and Kochia scoparia fruit (Di fu zi) [6 7 10ndash13 17] which were each used in seven studies Each of theseherbs has a history of topical application in the manage-ment of dermatological disorders [39] Also experimentalstudies have been conducted on extracts andor compoundsderived from these herbs with regard to actions relevant topsoriasis
Salvia miltiorrhiza (Dan shen) root and its constituenttanshinones and salvianolic acids have received considerable
research attention for the treatment and prevention of cardio-vascular disorders [40] These compounds have been shownto have free radical scavenging and anti-inflammatory effects[40ndash42] Also a number of its constituent tanshinones havebeen reported to have antiproliferative or proapoptotic effectsin cancer cell lines [43] More specifically an in vitro studyof mouse keratinocytes indicated that tanshinone IIA timeand dose dependently inhibited cell growth by inducingapoptosis via caspase cascade [44] Another possible mech-anism of action for tanshinone IIA in keratinocytes is viainhibiting the dimerization of the activator protein 1 (AP-1)transcription factor resulting in reduced interferon sensitivitywhich in turn could lead to a reduced inflammatory response[45]
Jiang et al 2008 [46] reported that an extract of theroot bark of Dictamnus dasycarpus (Bai xian pi) inhibitedhistamine release and reduced scratching behaviour in amouse anaphylaxismodel In vitro anti-inflammatory activityhas been reported for a root-bark extract [47] and for itsconstituents fraxinellone [48] and obacunone [49] Also itsessential oil and a number of compounds including dictam-nine preskimmianine and fraxinellone have demonstratedantitumour activity [47]
In the case of Sophora flavescens (Ku shen) root anextract inhibited histamine release both in vitro and in vivo[50 51] and other experimental studies have reported anti-inflammatory effects for its constituent alkaloids matrine[52 53] and oxymatrine [54] and for its total flavonoids [55]Its flavonoids and chalcones both demonstrate antioxidantactivity [56] Antitumour activities have been reported invitro for both matrine and oxymatrine as well as for anumber of flavonoids [57] of which trifolirhizin has shownboth anti-inflammatory and antiproliferative actions [58]and kurarinone showed inhibition of immune response [59]In human keratinocytes an extract inhibited proinflamma-tory chemokines [60] A Sophora flavescens extract showedantipruritic effects in a mouse model [61] and in a contactdermatitis mouse model the topical application of a Sophoraflavescens extract reduced hyperplasia edema spongiosisand infiltration of mononuclear cells [51]
A series of studies have reported that the 70 ethanolextract and its component momordin Ic from the driedfruits of Kochia scoparia (Di fu zi) had antinociceptive andanti-inflammatory [62] antiallergic [63] and antipruriticeffects [64] An orally administered extract was found to beactive in a rheumatoid arthritis model in rats [65]
Each of the above studies provides evidence that thesefour herbs have anti-inflammatory antiproliferative andorantipruritic activity all of which are of relevance to thetreatment of psoriasis However this evidence is indirect withonly a few studies testing topical application Consequentlywhether the additional therapeutic effects of the CHM bathsin the studies included in this review were produced by thespecific effects of the CHMs and the effect of the warm waterbaths or were just nonspecific effects of an additional inter-vention remains unclear Therefore future studies shouldinclude a control group that uses a colored warm water bathplus phototherapy to investigate the specific efficacy of theCHMs
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 3
Iden
tifica
tion
Scre
enin
gEl
igib
ility
Inclu
ded
Records identified through database searches
(n = 907)
Records after duplicates removed (n = 813 )
Titles and abstracts screened (n = 813 )
Records excluded (n = 734)
E1 non-CHM bath (n = 484) E2 non-RCT (n = 136)E3 nonpsoriasis vulgaris (n = 93)E4 laboratory studies (n = 21)
Full-text articles assessed for eligibility
(n = 79 ) Full-text articles excluded(n = 66)
E1 non-CHM bath (n = 62) E2 duplications (n = 2)E3 not evaluate CHM bathefficacy (n = 1) E4 non RCT (n = 1)Studies included in
qualitative synthesis (n = 13 )
Studies included in quantitative synthesis
(meta-analysis) (n = 8)
Full-text articles excluded(n = 5)
E1 did not use PASI 60 as outcome measure (n = 3)E2 phototherapy using UVA + UVB (n = 1)E3 phototherapy using UVA (n = 1)
Duplicates(n = 94)
Figure 1 study selection PRISMA flow chart CHM Chinese herbal medicine RCT randomized controlled trial PASI the psoriasis areaand severity index UVAUVB ultraviolet AB
pretrial treatments as co-interventions in both arms usingacitretin capsules [11] or halometasone emollient [14]
313 Outcome Measures The primary outcome measure inall 13 studies was ldquototal effective raterdquo (TER) which wasdefined as PASI score reduction in ten studies [5ndash10 12 1415 17] lesion improvement based on other criteria in twostudies [11 16] and one study did not specify the criteria used[13] Actual PASI score was also reported in four studies [5 714 15] Based on a European consensus on treatment goalsfor moderate to severe psoriasis PASI 50 is the minimumrequirement for the efficacy of any therapy for psoriasis butthese criteria were not followed in any of the included studies[25]
In general the effectiveness of the interventions wasreported in four levels ldquoclinically curedrdquo ldquoremarkably effec-tiverdquo ldquoeffectiverdquo and ldquoineffectiverdquo according to the reductionof PASI or symptom scores in the included studies except forone study that used three levels (clinically cured remarkablyeffective and ineffective) [16] However the definition ofthese levels varied across studies For example in studiesusing PASI score as the measurement [5ndash10 12 14 15 17]the levels of effectiveness were defined as PASI (95-60-20)[14] PASI (90-60-25) [5ndash9 17] or PASI (90-60-30) [15] ForPASI (95-60-20) ldquoclinically curedrdquo was defined as a PASIscore reduction of 95 to 100 ldquoremarkably effectiverdquo wasa reduction of 60 to 94 ldquoeffectiverdquo was a reduction of 20to 59 and ldquoineffectiverdquo was a reduction of 0 to 19 [14]
4 Evidence-Based Complementary and Alternative Medicine
Table1Ch
aracteris
ticso
fthirteenstu
dies
ofCh
ineseh
erbalm
edicineb
athcombinedwith
phototherapy
forp
soria
sis
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Cuietal2008
[5]
hospita
lBe
ijing
and
Anshan
China
6257
4582plusmn
13893872
plusmn1217
years
CHM
bath20m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB
50of
MED
asinitial
dosageincreased
by01Jcm
2
each
timemaxim
umdo
sage
25Jcm
2 twicea
week
56days
noinform
ation
16sessions
TERbasedon
PASI
(90-60-25)
PASI
score
TER(T9677C
7193
1205942=27755
119875lt001)
PASI
score(T
416plusmn74
0C
1140plusmn1164)
NB-UVBaveraged
osage
T(995plusmn476)Jcm
2 C
(1277plusmn505)Jcm
2
(119875lt001)
Adversee
vents(redn
ess
pruritu
s)rateT
484
(362)C
315
8(1857)
(1205942=119119875lt001)
noSA
E
Guetal2009
[6]
hospita
lUrumqiC
hina
8996
3115
3284
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
PuLian
ointment
bid
NB-UVB(311nm
)03Jcm
2as
initialdo
sageincreased
by01Jcm
2each
timeqo
dPu
Lian
ointmentbid
28days
6mon
ths
14sessions
TERbasedon
PASI
(90-60-25)
relap
serate
durin
gfollo
wup
TER(T9438C
8438
1205942=48
119875lt005)
relap
seratedu
ring
follo
wup
(T1081C
3030
119875lt005)
Mild
redn
esspruritu
sandskin
dryn
ess(T
1089C
2396)
(1205942=510119875lt005)
skin
pigm
entatio
nin
all
(resolvedwith
out
medicalassis
tance
with
in2mon
ths)
noSA
E
Linetal2010
[7]
hospita
lHefeiC
hina
9590
2952plusmn
638
2742plusmn628
years
CHM
bath
20ndash30m
inthree
times
aweek
NB-UVB
consistent
with
control
interventio
nBing
Hua
ngFu
Leointmentafte
rNB-UVB
qd
NB-UVB(311nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
110second
sthreetim
esaw
eek
Bing
Hua
ngFu
Leointmentafte
rNB-UVB
qd
49days
noinform
ation
20sessions
TERbasedon
PASI
(90-60-25)
PASI
score
TER(T967
C70
1205942=1769119875lt001)
PASI
score(T
1115plusmn811
C1474plusmn90
5)
Redn
ess(T
995C
22901205942=444
119875lt005)pruritu
s(T
1195C
2690
1205942=494119875lt005)skin
dryn
ess(T
1595C
1790119875gt005)
noSA
E
Liuetal2005
[8]
hospita
lSh
ijiazhu
ang
China
4040
36235
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB(311ndash
313n
m)008
or01Jcm
2as
initialdo
sage
increasedby
001ndash0
03Jcm
2
each
timeqo
d
40days
noinform
ation
20sessions
TERbasedon
PASI
(90-60-25)
TER(T950
C825
119875lt001)
Noinform
ation
Liuetal2
004[9]
hospita
lDalian
China
1511
79
noinform
ation
CHM
bath20m
in
qodUVA
andUVB
consistentw
ithcontrolintervention
UVA
(540
0120583Wcm
2 )016
Jcm
2
asinitialdo
sageqod
UVB
(350ndash4
60120583Wcm
2 )200Jcm
2
asinitialqod
increased
by10ndash20
each
time
No
inform
ation
12mon
ths
No
inform
ation
TERbasedon
PASI
(90-60-25)
relap
serate
durin
gfollo
wup
TER(T9007C
8883
119875gt005)
relap
seratedu
ring
follo
wup
(T1523C
3519
119875lt005)
Redn
esspruritu
s(T
1015
1C
1017
9)
noSA
E
Evidence-Based Complementary and Alternative Medicine 5
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Shietal2011[10]
hospita
lBe
ijing
China
170168
noinform
ation
CHM
bath20m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB(310ndash315nm
)02ndash04Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
56days
noinform
ation
28sessions
TERbasedon
PASI
(90-60-20)
TER(T847
C702
119875lt001)
Mild
redn
esspruritu
s(T111
70C
29168)
skin
pigm
entatio
nin
all
(resolvedwith
out
medicalassis
tance
with
in3mon
ths)
noSA
E
Wangetal2010
[11]
hospita
lNanchon
gCh
ina
7070
noinform
ation
Acitretin
capsules
foro
ne-w
eekpretria
ltre
atment20
mgqd
CH
Mbath30m
in3
times
aweek
NB-UVB
consistent
with
control
interventio
n
Acitretin
capsulescon
sistent
with
treatmentintervention
NB-UVB
05Jcm
2as
initial
dosageincreased
by10ndash20
each
time3tim
esaw
eekor
1-2tim
esaw
eek(if
lesio
nsredu
ced)
21days
noinform
ation
9sessions
TERbasedon
lesio
nscore
(90-70-30)
TER(T7714
C
5857
1205942=5534
119875lt005)
Redn
esspruritu
s(T
670C
570)
noSA
E
Wangetal2011
[12]
hospita
lKa
ifeng
China
5050
382375
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollient
after
NB-UVB
qd
NB-UVB(310ndash315nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
10ndash20
each
timeqo
durea
emollient
after
NB-UVB
qd
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-20)
TER(T860
C720
119875lt005)
Mild
skin
dryn
ess
burningpain
after
NB-UVB(T450C
550)
noSA
E
Wangetal2012
[13]
hospita
lKa
ifeng
China
6060
383371
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollient
after
NB-UVB
qod
glycyrrhizin
tablets
2tabletstid
NB-UVB(310ndash315nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
10ndash20
each
timeqo
durea
emollient
after
NB-UVB
qodglycyrrhizin
tablets2tabletstid
28days
noinform
ation
14sessions
TER
TER(T917
C
777
1205942=8239119875lt005)
Skin
dryn
essbu
rning
pain
after
NB-UVB(T
460C
560)
noSA
E
Wuetal2011
[14]
hospita
lCh
engduCh
ina
7565
325348
years
Halom
etason
eem
ollient
for
one-weekpre-trial
treatmentqd
CHM
bath15ndash20
min
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollientqd
Halom
etason
eemollient
consistentw
ithtre
atment
interventio
nNB-UVB
(310ndash315nm
)05ndash06Jcm
2as
initialdo
sageincreased
by01Jcm
2each
timeqo
durea
emollientqd
40days
noinform
ation
20sessions
TERbasedon
PASI
(95-60-20)
PASI
score
TER(T7867C
5692
1205942=1054
119875lt001)
PASI
score(T
924plusmn217
C546plusmn18
6)
Slight
light
skin
dryn
ess
burningpain
after
NB-UVB(T275C
365)
noSA
E
6 Evidence-Based Complementary and Alternative Medicine
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Wuetal2010
[15]
hospita
lGuang
zhou
Ch
ina
4039
3645plusmn
8523667plusmn
836
years
CHM
bath
15ndash20m
inqod
NB-UVB
consistent
with
control
interventio
n
NB-UVB(311ndash
315n
m)
03ndash05Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
90days
noinform
ation
45sessions
TERbasedon
PASI
(90-60-30)
PASI
score
TER(T7500C
5128
1205942=478
119875=0029)
PASI
score(T
421plusmn12
2C
645plusmn227)
Skin
dryn
esspruritu
s(T540C
539)skin
pigm
entatio
nin
all
noSA
E
YanandZh
ang
2009
[16]
hospita
lXirsquoan
China
4238
noinform
ation
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB
03Jcm
2as
initial
dosageincreased
by02Jcm
2 qo
d
80days
noinform
ation
40sessions
TERbasedon
lesio
nelim
ination
TER(T880
C421
119875lt005)
Noinform
ation
Zhou
andHuang
2005
[17]
hospita
lNanning
China
143129
35362
years
CHM
bath30m
in
qodUVA
consistentw
ithcontrolintervention
UVA
4Jc
m2as
initialdo
sage
increasedby
1Jcm
2 qo
d
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-25)
TER(T8042C
64
0119875lt001)
Noinform
ation
Qdon
cead
aybidtwicea
daytid
three
times
adayand
qodon
cein
everytwodaysC
HMC
hinese
herbalmedicineNB-UVB
narrow
band
ultravioletB
UVA
ultravioletA
MED
minim
alerythemad
osethe
minim
umdo
seofradiationthatprod
ucesskin
erythemaTE
Rtotaleffectiver
atecalculated
asthep
ercentageo
fldquocuredandremarkablye
ffectiverdquocasesPA
SI(95-60-20)ldquoClinicallycuredrdquo-PASI
scorereductio
nof
95to
100
ldquoremarkablyeffectiv
erdquo-PASI
scorer
eductio
nof
60to
94ldquoeffectiv
erdquo-PASI
scorer
eductio
nof
20to
59and
ldquoineffectiv
erdquo-PASI
scorer
eductio
nof
0to
19PASI
(90-60-20)PASI
(90-60-25)and
PASI
(90-60-30)
refertoeffectiv
enesslevels
usingd
ifferentp
ropo
rtions
ofPA
SIscorereductio
nlesio
nscore(90-70-30)effectiv
enesslevels
basedon
thereductio
nofpsoriatic
lesio
nsarea
andseveritylesio
nelim
ination
effectiv
enesslevels
basedon
thee
liminationof
lesio
n(90ndash
100
30ndash
59or0
ndash29
refertoclinically
curedremarkablyeffectiv
eandineffectiv
eaccording
ly)SA
Eserio
usadversee
vent
Evidence-Based Complementary and Alternative Medicine 7
Table 2 Chinese herbal medicine bath ingredients used in the thirteen studies
Author year(reference) Chinese herbal medicine bath formula
Cui et al 2008 [5] Galla Chinensis (Wu bei zi) Cortex Phellodendri Chinensis (Huang bo) Radix Angelica Sinensis (Dang gui)Rhizoma Curcumae Longae (Jiang huang) Fructus Psoraleae (Bu gu zhi) (no information of dosage)
Gu et al 2009 [6]Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 30 g Radix Angelica Sinensis (Dang gui) Spica Prunellae (Xiaku cao) 30 g Fructus Kochiae (Di fu zi) 30 g Cortex Dictamni (Bai xian pi) 30 g Cortex Phellodendri Chinensis(Huang bo) 30 g Folium Isatidis (Da qing ye) 30 g Rhizoma Smilacis Glabrae (Tu fu ling) 30 g
Lin et al 2010 [7]
Rhizoma Smilacis Glabrae (Tu fu ling) 30 g Fructus Kochiae (Di fu zi) 15 g Radix Angelica Sinensis (Dang gui) 20 gCortex Dictamni (Bai xian pi) 20 g Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 20 g Radix SophoraFlavescens (Ku shen) 15 g Fructus Cnidii (She chuang zi) 20 g Fructus Xanthii (Cang er zi) 15 g Radix Stemonae(Bai bu) 15 g Cortex Pseudolaricis (Tu jing pi) 10 g Fructus Tribuli (Ji li) 15 g Radix et Rhizoma Rhei (Da huang) 10 g
Liu et al 2005 [8]
Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 30 g Fructus Cnidii (She chuang zi) 30 g Radix SophoraFlavescens (Ku shen) 30 g Pericarpium Zanthoxyli (Hua jiao) 30 gHerba cum Radice Patriniae (Bai jiang cao) 30 gRhizoma et Radix Polygoni Cuspidati (Hu zhang) 30 g Herba Portulacae (Ma chi xian) 30 g Radix et RhizomaSalviae Miltiorrhizae (Dan shen) 20 g Rhizoma Atractylodis (Cang zhu) 15 g
Liu et al 2004 [9]
Blood-heat syndrome Folium Isatidis (Da qing ye) Radix Rehmanniae (Di huang) Radix Paeoniae Rubra (Chishao) Rhizoma Smilacis Glabrae (Tu fu ling) Radix Arnebiae (Zi cao) Cortex Moutan (Mu dan pi) Blood-stasissyndrome Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) Semen Persicae (Tao ren) Flos Carthami (Honghua) Rhizoma Curcumae (E zhu) Caulis Spatholobi (Ji xue teng) Blood-dryness syndrome Radix Rehmanniae (Dihuang) Radix Angelica Sinensis (Dang gui) Cortex Dictamni (Bai xian pi) Herba Hedyotis (Bai hua she she cao)Rhizoma Smilacis Glabrae (Tu fu ling) (no information of dosage)
Shi et al 2011 [10]Caulis Impatientis (Tou gu cao) Cacumen Platycladi (Ce bai ye) Cortex Dictamni (Bai xian pi) Radix et RhizomaSalviae Miltiorrhizae (Dan shen) Radix Angelica Sinensis (Dang gui) Semen Persicae (Tao ren) Radix SophoraFlavescens (Ku shen) Fructus Kochiae (Di fu zi) Margarita (Zhen zhu) (no information of dosage)
Wang et al 2010 [11] Flos Chrysanthemi Indici (Ye ju hua) 240 g Pericarpium Zanthoxyli (Hua jiao) 120 g Rhizoma Smilacis Glabrae (Tufu ling) 150 g Radix Sophora Flavescens (Ku shen) 300 g Fructus Kochiae (Di fu zi) 300 g
Wang et al 2011 [12]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wang et al 2012 [13]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wu et al 2011 [14]Radix Sophora Flavescens (Ku shen) Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) Flos ChrysanthemiIndici (Ye ju hua) Herba Violae (Zi hua di ding) Flos Lonicerae Japonicae (Jin yin hua) Fructus Cnidii (She chuangzi) Glycyrrhiza uralensis root (no information of dosage)
Wu et al 2010 [15]Radix Rehmanniae (Di huang) 40 g Flos Lonicerae Japonicae (Jin yin hua) 30 g Herba Violae (Zi hua di ding) 30 gHerba Taraxaci (Pu gong ying) 30 g Zaocys (Wu shao she) 15 g Radix Scutellariae (Huang qin) 30 g RadixArnebiae seu Lithospermi (Zi cao) 30 g
Yan and Zhang2009 [16]
Radix Sophora Flavescens (Ku shen) 30 g Fructus Cnidii (She chuang zi) 30 g Radix Clematidis (Wei ling xian)30 g Cortex Dictamni (Bai xian pi) 30 g Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 20 g RhizomaAtractylodis (Cang zhu) 20 g Rhizoma Smilacis Glabrae (Tu fu ling) 20 g
Zhou and Huang2005 [17]
Rhizoma Coptidis (Huang lian) 10 g Cortex Phellodendri Chinensis (Huang bo) 20 g Radix Sophora Flavescens (Kushen) 20 g Radix Sanguisorbae (Di yu) 20 g Cortex Mahonia bealei (Tu Huang bo) 60 g Pericarpium Granati (Shiliu pi) 15 g Fructus Kochiae (Di fu zi) 15 g Herba Senecionis Scandens (Qian li guang) 30 g
Since PASI 60 was used in ten studies [5ndash10 12 14 15 17] asthe benchmark of ldquoremarkably effectiverdquo for TER calculationit was selected to be the outcome for pooling studies formeta-analysis in this review Three studies were excludedfrom meta-analysis because two of them used TER basedon a scoring system other than PASI for which there wasno evidence supporting it as an appropriate approach toevaluate therapeutic effect [11 16] and one was excluded dueto lack of a clear description of how ldquolesion improvementrdquowas measured [13]
314 Efficacy All thirteen studies reported that the com-bination of CHM bath and phototherapy had a superiorefficacy compared to phototherapy alone in terms of TERIn addition Cui et al 2008 reported that the administrationof CHM bath could significantly reduce NB-UVB averagedosage [5]
315 Followup Followup and relapse rate were reported intwo studies [6 9] In one the relapse rate of the treatmentgroup was 152 compared with 352 for control [9] In the
8 Evidence-Based Complementary and Alternative Medicine
other the rates were 108 for the treatment group and 303in the control In both cases a significant difference betweenthe two groups was reported (119875 lt 005) but a definition ofldquorelapserdquo was not provided in either study
316 Dropouts One study reported the number of dropoutsduring the treatment period without detailed reasons [6]All other studies reported that the number of patients whocompleted the trial was same as the number randomized
317 Adverse Events (AEs) Three studies did not reportany AEs [8 11 17] The most frequent AEs reported by theother ten studies were pruritus (7 studies) skin dryness (6studies) redness (6 studies) burning pain (3 studies) andskin pigmentation (3 studies) Three studies [5ndash7] reportedsignificantly higher rates of redness and pruritus in the UVBcontrol groups One of these three studies also reportedno significant difference between groups for skin dryness[7] The other seven studies that reported on AEs did notprovide details of between-group comparisons of AEs AllAEs reported in the ten studies could be resolved by reducingUV dosage or applying emollient No serious adverse event(SAE) was reported
32 Risks of Bias Assessment Risk of bias was assessed follow-ing the Cochrane Handbook 510 [23] and is summarized inFigure 2 Although all thirteen studies claimed ldquorandomizedrdquoonly six studies described the specific randomization meth-ods [5 6 10 12ndash14] Among them the random sequence gen-eration in four studies was appropriate [6 12ndash14] and assessedas ldquolow riskrdquo one study was assessed as ldquohigh riskrdquo due to theuse of patientsrsquo visiting order [15] one study used ldquoenvelopesrdquofor randomization which is not an adequate description tojudge bias therefore it was assessed as ldquounclearrdquo [5] Theother seven studies were considered ldquounclearrdquo due to thelack of information about randomization [7ndash11 16 17] Forallocation concealment method the study that used patientsrsquovisiting order for group allocation was judged ldquohigh riskrdquo[15] while the other twelve studies did not provide adequateinformation and therefore obtained judgments of ldquounclearrdquoFor all thirteen studies no information was provided forblinding of participants personnel or outcome assessors Infact blinding was impossible for participants and personnelin these studies due to the design One study reported thenumber of dropouts without reasons hence it was judged asldquounclearrdquo for incomplete outcome data [6] the other twelvestudies were assessed as ldquolow riskrdquo because they reported thatall participants finished the study A ldquolow riskrdquo assessmentwas given to all studies in terms of ldquoselective outcomereportingrdquo as the outcomes reported in the results sectionmatched the methods section However none had a protocolregistered
33 Meta-Analysis Two studies were not pooled in themeta-analysis since they used different forms of phototherapy com-pared to the others one combined UVA andUVB [9] and theother used UVA [17] Three studies were not included in themeta-analysis because they did not employPASI 60 [11 13 16]
Rand
om se
quen
ce g
ener
atio
n (s
elec
tion
bias
)
Cui et al 2008
Gu et al 2009 +
Lin et al 2010
Liu et al 2004
Liu et al 2005
Shi et al 2011
Wang et al 2010
Wang et al 2011 +
Wang et al 2012 +
Wu et al 2010 minus
Wu et al 2011 +
Yan and Zhang 2009
Zhou and Huang 2005 A
lloca
tion
conc
ealm
ent (
sele
ctio
n bi
as)
minus
Blin
ding
of p
artic
ipan
ts an
d pe
rson
nel (
perfo
rman
ce b
ias)
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
Blin
ding
of o
utco
me a
sses
smen
t (de
tect
ion
bias
)
Inco
mpl
ete o
utco
me d
ata (
attr
ition
bia
s)
++++++++++++
Sele
ctiv
e rep
ortin
g (r
epor
ting
bias
)
+++++++++++++
Figure 2 Risk of bias summary
As a result eight RCTs which used NB-UVB as phototherapyand PASI 60 for TER calculation were pooled in the meta-analysis These were divided into two groups based on studydesign as followsGroup 1 CHM Bath + NB-UVB versus NB-UVB Four studies[5 8 10 15] showed a higher TER (PASI 60) for CHM bathplus phototherapy compared with phototherapy alone (RR125 95 CI 115ndash136) without heterogeneity (1198682 = 0)(Figure 3) There was diversity in the herbs used in thesestudies but two studies had twomain herbs Ku shen andDanshen in common [8 10] The pooled result for these studiesfavoured the addition of the herbal bath (RR 119 95 CI108ndash132 1198682 = 0)Group 2 CHMBath +NB-UVB+Emollient versus NB-UVB+Emollient Four studies [6 7 12 14] showed a higher TER(PASI 60) for CHM bath plus phototherapy plus externallyapplied emollient cream compared with phototherapy plusthe same cream (RR 124 95 CI 115ndash135) The hetero-geneity was moderate (1198682 = 52) (Figure 3) Of the fourstudies three had main herbs in common [6 7 12] and ofthese Gu et al 2009 and Wang et al 2011 studies [6 12] were
Evidence-Based Complementary and Alternative Medicine 9
Study or subgroup CHM bath + NB-UVB NB-UVB Risk ratio Risk ratioEvents Total Events Total Weight MH fixed and 95 CI MH fixed and 95 CI
111 CHM bath + NB-UVB versus NB-UVB Cui et al 2008 60 62 41 57 99 135 [114 159]Liu et al 2005 38 40 33 40 76 115 [098 135]Shi et al 2011 144 170 118 168 274 121 [107 136]Wu et al 2010 30 40 20 39 47 146 [103 208]Subtotal (95 CI) 312 304 496 125 [115 136]Total events 272 212
112 CHM bath + NB-UVB + emollient versus NB-UVB + emollient
Gu et al 2009 84 89 81 96 180 112 [101 124] Lin et al 2010 89 95 63 90 149 134 [116 155] Wang et al 2011 43 50 36 50 83 119 [097 147] Wu et al 2011 59 75 37 65 92 138 [108 176] Subtotal (95 CI) 309 301 504 124 [115 135]
Total events 275 217
Total (95 CI) 621 605 100 125 [118 132]Total events 547 429
01 1 10NB-UVB CHM bath +
NB-UVB
Heterogeneity 1205942 = 286 df = 3 (P = 041) I2 = 0Test for overall effect Z = 517 (P lt 000001)
Heterogeneity 1205942 = 620 df = 3 (P = 010) I2 = 52Test for overall effect Z = 536 (P lt 000001)
Heterogeneity 1205942 = 914 df = 7 (P = 024) I2 = 23Test for overall effect Z = 744 (P lt 000001)Test for subgroup differences 1205942 = 001 df = 1 (P = 094) I2 = 0
Figure 3 Forest plot of clinical efficacy (PASI 60) PASI the psoriasis area and severity index PASI 60 the percentage of participants whoachieved PASI scores reduced by ge60 CHM Chinese herbal medicine NB-UVB narrowband ultraviolet
the most similar in that they shared Dan shen and Bai xianpi When the dissimilar study [12] was excluded there waslittle change in the result (RR 121 95 CI 112ndash132) andthe heterogeneity remained moderate (1198682 = 54) but whenthe pooling was limited to the two studies with the mostsimilar CHMs (Gu et al 2009 and Wang et al 2011) [6 12]the heterogeneity was removed (RR 114 95 CI 104ndash1261198682= 0)Overall the above eight studies [5ndash8 10 12 14 15] had
a higher TER (PASI 60) for CHM bath plus phototherapycompared with the phototherapy (RR 125 95CI 118ndash132)The heterogeneity was relatively low (1198682 = 23) (Figure 3)
4 Discussion
41 Efficacy of Phototherapy Combined with CHM Bath forPsoriasis All thirteen studies reported that CHM bath plusphototherapy had superior efficacy to phototherapy alone Inthe meta-analysis for group 1 (CHM bath + NB-UVB versusNB-UVB) all studies used the same primary outcome mea-sure did not use other supplementary treatment and therewas no heterogeneity so this result can be considered themost robust Nevertheless none of the studies employed anidentical herbal bath formulation although there were herbalingredients in common In contrast there was considerablevariation in study design in group 2 (CHMbath +NB-UVB+emollient versus NB-UVB + emollient) and this was reflectedin the heterogeneity found in the meta-analysis results Infact some co-intervention medications used in group 2 such
as PuLian ointment and Bing Huang Fu Le ointment havebeen reported to have therapeutic effects on psoriasis [26 27]Whether there was any interaction between the interventionsand co-interventions was unclear
42 Possible Mechanisms of Action for Phototherapy Com-bined with CHM Bath In psoriasis treatment phototherapymainly produces local immunosuppressive effects and anti-proliferative effects [1 4] The primary immunosuppressiveactions are reducing mobility of antigen-presenting Langer-hans cells and inhibiting T lymphocyte activation [1 4] Inaddition phototherapy inhibits epidermal hyperproliferationby interactions with keratinocyte DNA [1 4] It has beenreported thatmore than 50of patients treated by photother-apy achieved at least 75 improvement in PASI score (PASI75) after four to six weeks based on the recommendationsof the latest treatment guideline for psoriasis vulgaris [4]In this review for the ten studies [5ndash10 12 14 15 17] thatused PASI 60 for calculating TER more than 50 of controlgroup patients (611 out of 913) achieved PASI 60 after fourto eight weeks treatment with phototherapy Although theproportion of control group patients who achieved PASI 75was not specifically assessed this result indicates that thephototherapy was effective
The additional therapeutic effects of the CHM bath couldbe attributable to three main aspects (1) the thermotherapyeffects (2) the effects of a water bath and (3) the specifictherapeutic effects of the CHMs used in the baths Each ofthese aspects is discussed below
10 Evidence-Based Complementary and Alternative Medicine
421 Thermal Effects Hyperthermia is not a new conceptbut research interest into its application in the treatmentof psoriasis is relatively recent [28] Early utilization ofhyperthermia for psoriasis followed on from the ideas thatthe severity of psoriasis would reduce during warm summermonths and a benefit of hyperthermia had been shown forkilling cancer cells [29] Orenbergrsquos study in 1980 which usedultrasound induced heat to treat psoriasis showed a benefitfor psoriasis lesion remission [29] Later it was demonstratedthat hyperthermia induced by topical exothermic pads [30]infrared [31] ormicrowave [32]was also effective for psoriasisplaques The advantage of using a hot water bath is that itis a simple inexpensive approach that can be used to treatrelatively large body areas [33]
422 Water Baths (Balneotherapy) Since hyperthermia hasproven beneficial for psoriasis lesions the simple modalityof using warm or hot water became popular Nowadaysvarious types of water bath therapy are considered safetreatments for dermatological conditions and are practicedin many countries Well-known balneotherapy sites includethe Dead Sea in Israel the Kangal hot spring in Turkeythe Kusatsu hot spring in Japan and the Blue Lagoonin Iceland In particular the Dead Sea is known to beeffective for the treatment of psoriasis [34] The mecha-nisms by which diseases respond to balneotherapy probablyincorporate chemical thermal and mechanical effects [35]It was suggested by a clinical study that simple repetitivewater bath hyperthermia was effective in the treatment ofpsoriasis by improving psoriatic lesions reducing edema andrelieving pruritus [28] In addition the water itself couldremove psoriatic scale [36] which may be beneficial for skinabsorption of phototherapy Previous studies have shownthat water bath markedly increased photosensitivity to UVB[37 38]
423 Specific Effects of the CHMs Used in the Baths Onlyone of the herbs used in one study Psoralea corylifolia (Bugu zhi) [5] is known to increase photosensitivity thereforethe overall effectiveness reported for the CHM baths doesnot appear to be due to pharmacological enhancement of theeffects of the phototherapy
In order to investigate the plausibility of the CHMsused in the baths having antipsoriatic actions experimentalreports on the actions of the main herbal ingredients wereexamined The most frequently used herbs in the includedstudies were Salvia miltiorrhiza root (Dan shen) [6 8 9 1213 16 23] Dictamnus dasycarpus bark (Bai xian pi) [6 79 10 12 13 16] Sophora flavescens root (Ku shen) [7 8 1011 14 16 17] and Kochia scoparia fruit (Di fu zi) [6 7 10ndash13 17] which were each used in seven studies Each of theseherbs has a history of topical application in the manage-ment of dermatological disorders [39] Also experimentalstudies have been conducted on extracts andor compoundsderived from these herbs with regard to actions relevant topsoriasis
Salvia miltiorrhiza (Dan shen) root and its constituenttanshinones and salvianolic acids have received considerable
research attention for the treatment and prevention of cardio-vascular disorders [40] These compounds have been shownto have free radical scavenging and anti-inflammatory effects[40ndash42] Also a number of its constituent tanshinones havebeen reported to have antiproliferative or proapoptotic effectsin cancer cell lines [43] More specifically an in vitro studyof mouse keratinocytes indicated that tanshinone IIA timeand dose dependently inhibited cell growth by inducingapoptosis via caspase cascade [44] Another possible mech-anism of action for tanshinone IIA in keratinocytes is viainhibiting the dimerization of the activator protein 1 (AP-1)transcription factor resulting in reduced interferon sensitivitywhich in turn could lead to a reduced inflammatory response[45]
Jiang et al 2008 [46] reported that an extract of theroot bark of Dictamnus dasycarpus (Bai xian pi) inhibitedhistamine release and reduced scratching behaviour in amouse anaphylaxismodel In vitro anti-inflammatory activityhas been reported for a root-bark extract [47] and for itsconstituents fraxinellone [48] and obacunone [49] Also itsessential oil and a number of compounds including dictam-nine preskimmianine and fraxinellone have demonstratedantitumour activity [47]
In the case of Sophora flavescens (Ku shen) root anextract inhibited histamine release both in vitro and in vivo[50 51] and other experimental studies have reported anti-inflammatory effects for its constituent alkaloids matrine[52 53] and oxymatrine [54] and for its total flavonoids [55]Its flavonoids and chalcones both demonstrate antioxidantactivity [56] Antitumour activities have been reported invitro for both matrine and oxymatrine as well as for anumber of flavonoids [57] of which trifolirhizin has shownboth anti-inflammatory and antiproliferative actions [58]and kurarinone showed inhibition of immune response [59]In human keratinocytes an extract inhibited proinflamma-tory chemokines [60] A Sophora flavescens extract showedantipruritic effects in a mouse model [61] and in a contactdermatitis mouse model the topical application of a Sophoraflavescens extract reduced hyperplasia edema spongiosisand infiltration of mononuclear cells [51]
A series of studies have reported that the 70 ethanolextract and its component momordin Ic from the driedfruits of Kochia scoparia (Di fu zi) had antinociceptive andanti-inflammatory [62] antiallergic [63] and antipruriticeffects [64] An orally administered extract was found to beactive in a rheumatoid arthritis model in rats [65]
Each of the above studies provides evidence that thesefour herbs have anti-inflammatory antiproliferative andorantipruritic activity all of which are of relevance to thetreatment of psoriasis However this evidence is indirect withonly a few studies testing topical application Consequentlywhether the additional therapeutic effects of the CHM bathsin the studies included in this review were produced by thespecific effects of the CHMs and the effect of the warm waterbaths or were just nonspecific effects of an additional inter-vention remains unclear Therefore future studies shouldinclude a control group that uses a colored warm water bathplus phototherapy to investigate the specific efficacy of theCHMs
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
4 Evidence-Based Complementary and Alternative Medicine
Table1Ch
aracteris
ticso
fthirteenstu
dies
ofCh
ineseh
erbalm
edicineb
athcombinedwith
phototherapy
forp
soria
sis
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Cuietal2008
[5]
hospita
lBe
ijing
and
Anshan
China
6257
4582plusmn
13893872
plusmn1217
years
CHM
bath20m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB
50of
MED
asinitial
dosageincreased
by01Jcm
2
each
timemaxim
umdo
sage
25Jcm
2 twicea
week
56days
noinform
ation
16sessions
TERbasedon
PASI
(90-60-25)
PASI
score
TER(T9677C
7193
1205942=27755
119875lt001)
PASI
score(T
416plusmn74
0C
1140plusmn1164)
NB-UVBaveraged
osage
T(995plusmn476)Jcm
2 C
(1277plusmn505)Jcm
2
(119875lt001)
Adversee
vents(redn
ess
pruritu
s)rateT
484
(362)C
315
8(1857)
(1205942=119119875lt001)
noSA
E
Guetal2009
[6]
hospita
lUrumqiC
hina
8996
3115
3284
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
PuLian
ointment
bid
NB-UVB(311nm
)03Jcm
2as
initialdo
sageincreased
by01Jcm
2each
timeqo
dPu
Lian
ointmentbid
28days
6mon
ths
14sessions
TERbasedon
PASI
(90-60-25)
relap
serate
durin
gfollo
wup
TER(T9438C
8438
1205942=48
119875lt005)
relap
seratedu
ring
follo
wup
(T1081C
3030
119875lt005)
Mild
redn
esspruritu
sandskin
dryn
ess(T
1089C
2396)
(1205942=510119875lt005)
skin
pigm
entatio
nin
all
(resolvedwith
out
medicalassis
tance
with
in2mon
ths)
noSA
E
Linetal2010
[7]
hospita
lHefeiC
hina
9590
2952plusmn
638
2742plusmn628
years
CHM
bath
20ndash30m
inthree
times
aweek
NB-UVB
consistent
with
control
interventio
nBing
Hua
ngFu
Leointmentafte
rNB-UVB
qd
NB-UVB(311nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
110second
sthreetim
esaw
eek
Bing
Hua
ngFu
Leointmentafte
rNB-UVB
qd
49days
noinform
ation
20sessions
TERbasedon
PASI
(90-60-25)
PASI
score
TER(T967
C70
1205942=1769119875lt001)
PASI
score(T
1115plusmn811
C1474plusmn90
5)
Redn
ess(T
995C
22901205942=444
119875lt005)pruritu
s(T
1195C
2690
1205942=494119875lt005)skin
dryn
ess(T
1595C
1790119875gt005)
noSA
E
Liuetal2005
[8]
hospita
lSh
ijiazhu
ang
China
4040
36235
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB(311ndash
313n
m)008
or01Jcm
2as
initialdo
sage
increasedby
001ndash0
03Jcm
2
each
timeqo
d
40days
noinform
ation
20sessions
TERbasedon
PASI
(90-60-25)
TER(T950
C825
119875lt001)
Noinform
ation
Liuetal2
004[9]
hospita
lDalian
China
1511
79
noinform
ation
CHM
bath20m
in
qodUVA
andUVB
consistentw
ithcontrolintervention
UVA
(540
0120583Wcm
2 )016
Jcm
2
asinitialdo
sageqod
UVB
(350ndash4
60120583Wcm
2 )200Jcm
2
asinitialqod
increased
by10ndash20
each
time
No
inform
ation
12mon
ths
No
inform
ation
TERbasedon
PASI
(90-60-25)
relap
serate
durin
gfollo
wup
TER(T9007C
8883
119875gt005)
relap
seratedu
ring
follo
wup
(T1523C
3519
119875lt005)
Redn
esspruritu
s(T
1015
1C
1017
9)
noSA
E
Evidence-Based Complementary and Alternative Medicine 5
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Shietal2011[10]
hospita
lBe
ijing
China
170168
noinform
ation
CHM
bath20m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB(310ndash315nm
)02ndash04Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
56days
noinform
ation
28sessions
TERbasedon
PASI
(90-60-20)
TER(T847
C702
119875lt001)
Mild
redn
esspruritu
s(T111
70C
29168)
skin
pigm
entatio
nin
all
(resolvedwith
out
medicalassis
tance
with
in3mon
ths)
noSA
E
Wangetal2010
[11]
hospita
lNanchon
gCh
ina
7070
noinform
ation
Acitretin
capsules
foro
ne-w
eekpretria
ltre
atment20
mgqd
CH
Mbath30m
in3
times
aweek
NB-UVB
consistent
with
control
interventio
n
Acitretin
capsulescon
sistent
with
treatmentintervention
NB-UVB
05Jcm
2as
initial
dosageincreased
by10ndash20
each
time3tim
esaw
eekor
1-2tim
esaw
eek(if
lesio
nsredu
ced)
21days
noinform
ation
9sessions
TERbasedon
lesio
nscore
(90-70-30)
TER(T7714
C
5857
1205942=5534
119875lt005)
Redn
esspruritu
s(T
670C
570)
noSA
E
Wangetal2011
[12]
hospita
lKa
ifeng
China
5050
382375
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollient
after
NB-UVB
qd
NB-UVB(310ndash315nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
10ndash20
each
timeqo
durea
emollient
after
NB-UVB
qd
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-20)
TER(T860
C720
119875lt005)
Mild
skin
dryn
ess
burningpain
after
NB-UVB(T450C
550)
noSA
E
Wangetal2012
[13]
hospita
lKa
ifeng
China
6060
383371
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollient
after
NB-UVB
qod
glycyrrhizin
tablets
2tabletstid
NB-UVB(310ndash315nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
10ndash20
each
timeqo
durea
emollient
after
NB-UVB
qodglycyrrhizin
tablets2tabletstid
28days
noinform
ation
14sessions
TER
TER(T917
C
777
1205942=8239119875lt005)
Skin
dryn
essbu
rning
pain
after
NB-UVB(T
460C
560)
noSA
E
Wuetal2011
[14]
hospita
lCh
engduCh
ina
7565
325348
years
Halom
etason
eem
ollient
for
one-weekpre-trial
treatmentqd
CHM
bath15ndash20
min
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollientqd
Halom
etason
eemollient
consistentw
ithtre
atment
interventio
nNB-UVB
(310ndash315nm
)05ndash06Jcm
2as
initialdo
sageincreased
by01Jcm
2each
timeqo
durea
emollientqd
40days
noinform
ation
20sessions
TERbasedon
PASI
(95-60-20)
PASI
score
TER(T7867C
5692
1205942=1054
119875lt001)
PASI
score(T
924plusmn217
C546plusmn18
6)
Slight
light
skin
dryn
ess
burningpain
after
NB-UVB(T275C
365)
noSA
E
6 Evidence-Based Complementary and Alternative Medicine
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Wuetal2010
[15]
hospita
lGuang
zhou
Ch
ina
4039
3645plusmn
8523667plusmn
836
years
CHM
bath
15ndash20m
inqod
NB-UVB
consistent
with
control
interventio
n
NB-UVB(311ndash
315n
m)
03ndash05Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
90days
noinform
ation
45sessions
TERbasedon
PASI
(90-60-30)
PASI
score
TER(T7500C
5128
1205942=478
119875=0029)
PASI
score(T
421plusmn12
2C
645plusmn227)
Skin
dryn
esspruritu
s(T540C
539)skin
pigm
entatio
nin
all
noSA
E
YanandZh
ang
2009
[16]
hospita
lXirsquoan
China
4238
noinform
ation
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB
03Jcm
2as
initial
dosageincreased
by02Jcm
2 qo
d
80days
noinform
ation
40sessions
TERbasedon
lesio
nelim
ination
TER(T880
C421
119875lt005)
Noinform
ation
Zhou
andHuang
2005
[17]
hospita
lNanning
China
143129
35362
years
CHM
bath30m
in
qodUVA
consistentw
ithcontrolintervention
UVA
4Jc
m2as
initialdo
sage
increasedby
1Jcm
2 qo
d
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-25)
TER(T8042C
64
0119875lt001)
Noinform
ation
Qdon
cead
aybidtwicea
daytid
three
times
adayand
qodon
cein
everytwodaysC
HMC
hinese
herbalmedicineNB-UVB
narrow
band
ultravioletB
UVA
ultravioletA
MED
minim
alerythemad
osethe
minim
umdo
seofradiationthatprod
ucesskin
erythemaTE
Rtotaleffectiver
atecalculated
asthep
ercentageo
fldquocuredandremarkablye
ffectiverdquocasesPA
SI(95-60-20)ldquoClinicallycuredrdquo-PASI
scorereductio
nof
95to
100
ldquoremarkablyeffectiv
erdquo-PASI
scorer
eductio
nof
60to
94ldquoeffectiv
erdquo-PASI
scorer
eductio
nof
20to
59and
ldquoineffectiv
erdquo-PASI
scorer
eductio
nof
0to
19PASI
(90-60-20)PASI
(90-60-25)and
PASI
(90-60-30)
refertoeffectiv
enesslevels
usingd
ifferentp
ropo
rtions
ofPA
SIscorereductio
nlesio
nscore(90-70-30)effectiv
enesslevels
basedon
thereductio
nofpsoriatic
lesio
nsarea
andseveritylesio
nelim
ination
effectiv
enesslevels
basedon
thee
liminationof
lesio
n(90ndash
100
30ndash
59or0
ndash29
refertoclinically
curedremarkablyeffectiv
eandineffectiv
eaccording
ly)SA
Eserio
usadversee
vent
Evidence-Based Complementary and Alternative Medicine 7
Table 2 Chinese herbal medicine bath ingredients used in the thirteen studies
Author year(reference) Chinese herbal medicine bath formula
Cui et al 2008 [5] Galla Chinensis (Wu bei zi) Cortex Phellodendri Chinensis (Huang bo) Radix Angelica Sinensis (Dang gui)Rhizoma Curcumae Longae (Jiang huang) Fructus Psoraleae (Bu gu zhi) (no information of dosage)
Gu et al 2009 [6]Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 30 g Radix Angelica Sinensis (Dang gui) Spica Prunellae (Xiaku cao) 30 g Fructus Kochiae (Di fu zi) 30 g Cortex Dictamni (Bai xian pi) 30 g Cortex Phellodendri Chinensis(Huang bo) 30 g Folium Isatidis (Da qing ye) 30 g Rhizoma Smilacis Glabrae (Tu fu ling) 30 g
Lin et al 2010 [7]
Rhizoma Smilacis Glabrae (Tu fu ling) 30 g Fructus Kochiae (Di fu zi) 15 g Radix Angelica Sinensis (Dang gui) 20 gCortex Dictamni (Bai xian pi) 20 g Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 20 g Radix SophoraFlavescens (Ku shen) 15 g Fructus Cnidii (She chuang zi) 20 g Fructus Xanthii (Cang er zi) 15 g Radix Stemonae(Bai bu) 15 g Cortex Pseudolaricis (Tu jing pi) 10 g Fructus Tribuli (Ji li) 15 g Radix et Rhizoma Rhei (Da huang) 10 g
Liu et al 2005 [8]
Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 30 g Fructus Cnidii (She chuang zi) 30 g Radix SophoraFlavescens (Ku shen) 30 g Pericarpium Zanthoxyli (Hua jiao) 30 gHerba cum Radice Patriniae (Bai jiang cao) 30 gRhizoma et Radix Polygoni Cuspidati (Hu zhang) 30 g Herba Portulacae (Ma chi xian) 30 g Radix et RhizomaSalviae Miltiorrhizae (Dan shen) 20 g Rhizoma Atractylodis (Cang zhu) 15 g
Liu et al 2004 [9]
Blood-heat syndrome Folium Isatidis (Da qing ye) Radix Rehmanniae (Di huang) Radix Paeoniae Rubra (Chishao) Rhizoma Smilacis Glabrae (Tu fu ling) Radix Arnebiae (Zi cao) Cortex Moutan (Mu dan pi) Blood-stasissyndrome Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) Semen Persicae (Tao ren) Flos Carthami (Honghua) Rhizoma Curcumae (E zhu) Caulis Spatholobi (Ji xue teng) Blood-dryness syndrome Radix Rehmanniae (Dihuang) Radix Angelica Sinensis (Dang gui) Cortex Dictamni (Bai xian pi) Herba Hedyotis (Bai hua she she cao)Rhizoma Smilacis Glabrae (Tu fu ling) (no information of dosage)
Shi et al 2011 [10]Caulis Impatientis (Tou gu cao) Cacumen Platycladi (Ce bai ye) Cortex Dictamni (Bai xian pi) Radix et RhizomaSalviae Miltiorrhizae (Dan shen) Radix Angelica Sinensis (Dang gui) Semen Persicae (Tao ren) Radix SophoraFlavescens (Ku shen) Fructus Kochiae (Di fu zi) Margarita (Zhen zhu) (no information of dosage)
Wang et al 2010 [11] Flos Chrysanthemi Indici (Ye ju hua) 240 g Pericarpium Zanthoxyli (Hua jiao) 120 g Rhizoma Smilacis Glabrae (Tufu ling) 150 g Radix Sophora Flavescens (Ku shen) 300 g Fructus Kochiae (Di fu zi) 300 g
Wang et al 2011 [12]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wang et al 2012 [13]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wu et al 2011 [14]Radix Sophora Flavescens (Ku shen) Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) Flos ChrysanthemiIndici (Ye ju hua) Herba Violae (Zi hua di ding) Flos Lonicerae Japonicae (Jin yin hua) Fructus Cnidii (She chuangzi) Glycyrrhiza uralensis root (no information of dosage)
Wu et al 2010 [15]Radix Rehmanniae (Di huang) 40 g Flos Lonicerae Japonicae (Jin yin hua) 30 g Herba Violae (Zi hua di ding) 30 gHerba Taraxaci (Pu gong ying) 30 g Zaocys (Wu shao she) 15 g Radix Scutellariae (Huang qin) 30 g RadixArnebiae seu Lithospermi (Zi cao) 30 g
Yan and Zhang2009 [16]
Radix Sophora Flavescens (Ku shen) 30 g Fructus Cnidii (She chuang zi) 30 g Radix Clematidis (Wei ling xian)30 g Cortex Dictamni (Bai xian pi) 30 g Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 20 g RhizomaAtractylodis (Cang zhu) 20 g Rhizoma Smilacis Glabrae (Tu fu ling) 20 g
Zhou and Huang2005 [17]
Rhizoma Coptidis (Huang lian) 10 g Cortex Phellodendri Chinensis (Huang bo) 20 g Radix Sophora Flavescens (Kushen) 20 g Radix Sanguisorbae (Di yu) 20 g Cortex Mahonia bealei (Tu Huang bo) 60 g Pericarpium Granati (Shiliu pi) 15 g Fructus Kochiae (Di fu zi) 15 g Herba Senecionis Scandens (Qian li guang) 30 g
Since PASI 60 was used in ten studies [5ndash10 12 14 15 17] asthe benchmark of ldquoremarkably effectiverdquo for TER calculationit was selected to be the outcome for pooling studies formeta-analysis in this review Three studies were excludedfrom meta-analysis because two of them used TER basedon a scoring system other than PASI for which there wasno evidence supporting it as an appropriate approach toevaluate therapeutic effect [11 16] and one was excluded dueto lack of a clear description of how ldquolesion improvementrdquowas measured [13]
314 Efficacy All thirteen studies reported that the com-bination of CHM bath and phototherapy had a superiorefficacy compared to phototherapy alone in terms of TERIn addition Cui et al 2008 reported that the administrationof CHM bath could significantly reduce NB-UVB averagedosage [5]
315 Followup Followup and relapse rate were reported intwo studies [6 9] In one the relapse rate of the treatmentgroup was 152 compared with 352 for control [9] In the
8 Evidence-Based Complementary and Alternative Medicine
other the rates were 108 for the treatment group and 303in the control In both cases a significant difference betweenthe two groups was reported (119875 lt 005) but a definition ofldquorelapserdquo was not provided in either study
316 Dropouts One study reported the number of dropoutsduring the treatment period without detailed reasons [6]All other studies reported that the number of patients whocompleted the trial was same as the number randomized
317 Adverse Events (AEs) Three studies did not reportany AEs [8 11 17] The most frequent AEs reported by theother ten studies were pruritus (7 studies) skin dryness (6studies) redness (6 studies) burning pain (3 studies) andskin pigmentation (3 studies) Three studies [5ndash7] reportedsignificantly higher rates of redness and pruritus in the UVBcontrol groups One of these three studies also reportedno significant difference between groups for skin dryness[7] The other seven studies that reported on AEs did notprovide details of between-group comparisons of AEs AllAEs reported in the ten studies could be resolved by reducingUV dosage or applying emollient No serious adverse event(SAE) was reported
32 Risks of Bias Assessment Risk of bias was assessed follow-ing the Cochrane Handbook 510 [23] and is summarized inFigure 2 Although all thirteen studies claimed ldquorandomizedrdquoonly six studies described the specific randomization meth-ods [5 6 10 12ndash14] Among them the random sequence gen-eration in four studies was appropriate [6 12ndash14] and assessedas ldquolow riskrdquo one study was assessed as ldquohigh riskrdquo due to theuse of patientsrsquo visiting order [15] one study used ldquoenvelopesrdquofor randomization which is not an adequate description tojudge bias therefore it was assessed as ldquounclearrdquo [5] Theother seven studies were considered ldquounclearrdquo due to thelack of information about randomization [7ndash11 16 17] Forallocation concealment method the study that used patientsrsquovisiting order for group allocation was judged ldquohigh riskrdquo[15] while the other twelve studies did not provide adequateinformation and therefore obtained judgments of ldquounclearrdquoFor all thirteen studies no information was provided forblinding of participants personnel or outcome assessors Infact blinding was impossible for participants and personnelin these studies due to the design One study reported thenumber of dropouts without reasons hence it was judged asldquounclearrdquo for incomplete outcome data [6] the other twelvestudies were assessed as ldquolow riskrdquo because they reported thatall participants finished the study A ldquolow riskrdquo assessmentwas given to all studies in terms of ldquoselective outcomereportingrdquo as the outcomes reported in the results sectionmatched the methods section However none had a protocolregistered
33 Meta-Analysis Two studies were not pooled in themeta-analysis since they used different forms of phototherapy com-pared to the others one combined UVA andUVB [9] and theother used UVA [17] Three studies were not included in themeta-analysis because they did not employPASI 60 [11 13 16]
Rand
om se
quen
ce g
ener
atio
n (s
elec
tion
bias
)
Cui et al 2008
Gu et al 2009 +
Lin et al 2010
Liu et al 2004
Liu et al 2005
Shi et al 2011
Wang et al 2010
Wang et al 2011 +
Wang et al 2012 +
Wu et al 2010 minus
Wu et al 2011 +
Yan and Zhang 2009
Zhou and Huang 2005 A
lloca
tion
conc
ealm
ent (
sele
ctio
n bi
as)
minus
Blin
ding
of p
artic
ipan
ts an
d pe
rson
nel (
perfo
rman
ce b
ias)
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
Blin
ding
of o
utco
me a
sses
smen
t (de
tect
ion
bias
)
Inco
mpl
ete o
utco
me d
ata (
attr
ition
bia
s)
++++++++++++
Sele
ctiv
e rep
ortin
g (r
epor
ting
bias
)
+++++++++++++
Figure 2 Risk of bias summary
As a result eight RCTs which used NB-UVB as phototherapyand PASI 60 for TER calculation were pooled in the meta-analysis These were divided into two groups based on studydesign as followsGroup 1 CHM Bath + NB-UVB versus NB-UVB Four studies[5 8 10 15] showed a higher TER (PASI 60) for CHM bathplus phototherapy compared with phototherapy alone (RR125 95 CI 115ndash136) without heterogeneity (1198682 = 0)(Figure 3) There was diversity in the herbs used in thesestudies but two studies had twomain herbs Ku shen andDanshen in common [8 10] The pooled result for these studiesfavoured the addition of the herbal bath (RR 119 95 CI108ndash132 1198682 = 0)Group 2 CHMBath +NB-UVB+Emollient versus NB-UVB+Emollient Four studies [6 7 12 14] showed a higher TER(PASI 60) for CHM bath plus phototherapy plus externallyapplied emollient cream compared with phototherapy plusthe same cream (RR 124 95 CI 115ndash135) The hetero-geneity was moderate (1198682 = 52) (Figure 3) Of the fourstudies three had main herbs in common [6 7 12] and ofthese Gu et al 2009 and Wang et al 2011 studies [6 12] were
Evidence-Based Complementary and Alternative Medicine 9
Study or subgroup CHM bath + NB-UVB NB-UVB Risk ratio Risk ratioEvents Total Events Total Weight MH fixed and 95 CI MH fixed and 95 CI
111 CHM bath + NB-UVB versus NB-UVB Cui et al 2008 60 62 41 57 99 135 [114 159]Liu et al 2005 38 40 33 40 76 115 [098 135]Shi et al 2011 144 170 118 168 274 121 [107 136]Wu et al 2010 30 40 20 39 47 146 [103 208]Subtotal (95 CI) 312 304 496 125 [115 136]Total events 272 212
112 CHM bath + NB-UVB + emollient versus NB-UVB + emollient
Gu et al 2009 84 89 81 96 180 112 [101 124] Lin et al 2010 89 95 63 90 149 134 [116 155] Wang et al 2011 43 50 36 50 83 119 [097 147] Wu et al 2011 59 75 37 65 92 138 [108 176] Subtotal (95 CI) 309 301 504 124 [115 135]
Total events 275 217
Total (95 CI) 621 605 100 125 [118 132]Total events 547 429
01 1 10NB-UVB CHM bath +
NB-UVB
Heterogeneity 1205942 = 286 df = 3 (P = 041) I2 = 0Test for overall effect Z = 517 (P lt 000001)
Heterogeneity 1205942 = 620 df = 3 (P = 010) I2 = 52Test for overall effect Z = 536 (P lt 000001)
Heterogeneity 1205942 = 914 df = 7 (P = 024) I2 = 23Test for overall effect Z = 744 (P lt 000001)Test for subgroup differences 1205942 = 001 df = 1 (P = 094) I2 = 0
Figure 3 Forest plot of clinical efficacy (PASI 60) PASI the psoriasis area and severity index PASI 60 the percentage of participants whoachieved PASI scores reduced by ge60 CHM Chinese herbal medicine NB-UVB narrowband ultraviolet
the most similar in that they shared Dan shen and Bai xianpi When the dissimilar study [12] was excluded there waslittle change in the result (RR 121 95 CI 112ndash132) andthe heterogeneity remained moderate (1198682 = 54) but whenthe pooling was limited to the two studies with the mostsimilar CHMs (Gu et al 2009 and Wang et al 2011) [6 12]the heterogeneity was removed (RR 114 95 CI 104ndash1261198682= 0)Overall the above eight studies [5ndash8 10 12 14 15] had
a higher TER (PASI 60) for CHM bath plus phototherapycompared with the phototherapy (RR 125 95CI 118ndash132)The heterogeneity was relatively low (1198682 = 23) (Figure 3)
4 Discussion
41 Efficacy of Phototherapy Combined with CHM Bath forPsoriasis All thirteen studies reported that CHM bath plusphototherapy had superior efficacy to phototherapy alone Inthe meta-analysis for group 1 (CHM bath + NB-UVB versusNB-UVB) all studies used the same primary outcome mea-sure did not use other supplementary treatment and therewas no heterogeneity so this result can be considered themost robust Nevertheless none of the studies employed anidentical herbal bath formulation although there were herbalingredients in common In contrast there was considerablevariation in study design in group 2 (CHMbath +NB-UVB+emollient versus NB-UVB + emollient) and this was reflectedin the heterogeneity found in the meta-analysis results Infact some co-intervention medications used in group 2 such
as PuLian ointment and Bing Huang Fu Le ointment havebeen reported to have therapeutic effects on psoriasis [26 27]Whether there was any interaction between the interventionsand co-interventions was unclear
42 Possible Mechanisms of Action for Phototherapy Com-bined with CHM Bath In psoriasis treatment phototherapymainly produces local immunosuppressive effects and anti-proliferative effects [1 4] The primary immunosuppressiveactions are reducing mobility of antigen-presenting Langer-hans cells and inhibiting T lymphocyte activation [1 4] Inaddition phototherapy inhibits epidermal hyperproliferationby interactions with keratinocyte DNA [1 4] It has beenreported thatmore than 50of patients treated by photother-apy achieved at least 75 improvement in PASI score (PASI75) after four to six weeks based on the recommendationsof the latest treatment guideline for psoriasis vulgaris [4]In this review for the ten studies [5ndash10 12 14 15 17] thatused PASI 60 for calculating TER more than 50 of controlgroup patients (611 out of 913) achieved PASI 60 after fourto eight weeks treatment with phototherapy Although theproportion of control group patients who achieved PASI 75was not specifically assessed this result indicates that thephototherapy was effective
The additional therapeutic effects of the CHM bath couldbe attributable to three main aspects (1) the thermotherapyeffects (2) the effects of a water bath and (3) the specifictherapeutic effects of the CHMs used in the baths Each ofthese aspects is discussed below
10 Evidence-Based Complementary and Alternative Medicine
421 Thermal Effects Hyperthermia is not a new conceptbut research interest into its application in the treatmentof psoriasis is relatively recent [28] Early utilization ofhyperthermia for psoriasis followed on from the ideas thatthe severity of psoriasis would reduce during warm summermonths and a benefit of hyperthermia had been shown forkilling cancer cells [29] Orenbergrsquos study in 1980 which usedultrasound induced heat to treat psoriasis showed a benefitfor psoriasis lesion remission [29] Later it was demonstratedthat hyperthermia induced by topical exothermic pads [30]infrared [31] ormicrowave [32]was also effective for psoriasisplaques The advantage of using a hot water bath is that itis a simple inexpensive approach that can be used to treatrelatively large body areas [33]
422 Water Baths (Balneotherapy) Since hyperthermia hasproven beneficial for psoriasis lesions the simple modalityof using warm or hot water became popular Nowadaysvarious types of water bath therapy are considered safetreatments for dermatological conditions and are practicedin many countries Well-known balneotherapy sites includethe Dead Sea in Israel the Kangal hot spring in Turkeythe Kusatsu hot spring in Japan and the Blue Lagoonin Iceland In particular the Dead Sea is known to beeffective for the treatment of psoriasis [34] The mecha-nisms by which diseases respond to balneotherapy probablyincorporate chemical thermal and mechanical effects [35]It was suggested by a clinical study that simple repetitivewater bath hyperthermia was effective in the treatment ofpsoriasis by improving psoriatic lesions reducing edema andrelieving pruritus [28] In addition the water itself couldremove psoriatic scale [36] which may be beneficial for skinabsorption of phototherapy Previous studies have shownthat water bath markedly increased photosensitivity to UVB[37 38]
423 Specific Effects of the CHMs Used in the Baths Onlyone of the herbs used in one study Psoralea corylifolia (Bugu zhi) [5] is known to increase photosensitivity thereforethe overall effectiveness reported for the CHM baths doesnot appear to be due to pharmacological enhancement of theeffects of the phototherapy
In order to investigate the plausibility of the CHMsused in the baths having antipsoriatic actions experimentalreports on the actions of the main herbal ingredients wereexamined The most frequently used herbs in the includedstudies were Salvia miltiorrhiza root (Dan shen) [6 8 9 1213 16 23] Dictamnus dasycarpus bark (Bai xian pi) [6 79 10 12 13 16] Sophora flavescens root (Ku shen) [7 8 1011 14 16 17] and Kochia scoparia fruit (Di fu zi) [6 7 10ndash13 17] which were each used in seven studies Each of theseherbs has a history of topical application in the manage-ment of dermatological disorders [39] Also experimentalstudies have been conducted on extracts andor compoundsderived from these herbs with regard to actions relevant topsoriasis
Salvia miltiorrhiza (Dan shen) root and its constituenttanshinones and salvianolic acids have received considerable
research attention for the treatment and prevention of cardio-vascular disorders [40] These compounds have been shownto have free radical scavenging and anti-inflammatory effects[40ndash42] Also a number of its constituent tanshinones havebeen reported to have antiproliferative or proapoptotic effectsin cancer cell lines [43] More specifically an in vitro studyof mouse keratinocytes indicated that tanshinone IIA timeand dose dependently inhibited cell growth by inducingapoptosis via caspase cascade [44] Another possible mech-anism of action for tanshinone IIA in keratinocytes is viainhibiting the dimerization of the activator protein 1 (AP-1)transcription factor resulting in reduced interferon sensitivitywhich in turn could lead to a reduced inflammatory response[45]
Jiang et al 2008 [46] reported that an extract of theroot bark of Dictamnus dasycarpus (Bai xian pi) inhibitedhistamine release and reduced scratching behaviour in amouse anaphylaxismodel In vitro anti-inflammatory activityhas been reported for a root-bark extract [47] and for itsconstituents fraxinellone [48] and obacunone [49] Also itsessential oil and a number of compounds including dictam-nine preskimmianine and fraxinellone have demonstratedantitumour activity [47]
In the case of Sophora flavescens (Ku shen) root anextract inhibited histamine release both in vitro and in vivo[50 51] and other experimental studies have reported anti-inflammatory effects for its constituent alkaloids matrine[52 53] and oxymatrine [54] and for its total flavonoids [55]Its flavonoids and chalcones both demonstrate antioxidantactivity [56] Antitumour activities have been reported invitro for both matrine and oxymatrine as well as for anumber of flavonoids [57] of which trifolirhizin has shownboth anti-inflammatory and antiproliferative actions [58]and kurarinone showed inhibition of immune response [59]In human keratinocytes an extract inhibited proinflamma-tory chemokines [60] A Sophora flavescens extract showedantipruritic effects in a mouse model [61] and in a contactdermatitis mouse model the topical application of a Sophoraflavescens extract reduced hyperplasia edema spongiosisand infiltration of mononuclear cells [51]
A series of studies have reported that the 70 ethanolextract and its component momordin Ic from the driedfruits of Kochia scoparia (Di fu zi) had antinociceptive andanti-inflammatory [62] antiallergic [63] and antipruriticeffects [64] An orally administered extract was found to beactive in a rheumatoid arthritis model in rats [65]
Each of the above studies provides evidence that thesefour herbs have anti-inflammatory antiproliferative andorantipruritic activity all of which are of relevance to thetreatment of psoriasis However this evidence is indirect withonly a few studies testing topical application Consequentlywhether the additional therapeutic effects of the CHM bathsin the studies included in this review were produced by thespecific effects of the CHMs and the effect of the warm waterbaths or were just nonspecific effects of an additional inter-vention remains unclear Therefore future studies shouldinclude a control group that uses a colored warm water bathplus phototherapy to investigate the specific efficacy of theCHMs
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 5
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Shietal2011[10]
hospita
lBe
ijing
China
170168
noinform
ation
CHM
bath20m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB(310ndash315nm
)02ndash04Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
56days
noinform
ation
28sessions
TERbasedon
PASI
(90-60-20)
TER(T847
C702
119875lt001)
Mild
redn
esspruritu
s(T111
70C
29168)
skin
pigm
entatio
nin
all
(resolvedwith
out
medicalassis
tance
with
in3mon
ths)
noSA
E
Wangetal2010
[11]
hospita
lNanchon
gCh
ina
7070
noinform
ation
Acitretin
capsules
foro
ne-w
eekpretria
ltre
atment20
mgqd
CH
Mbath30m
in3
times
aweek
NB-UVB
consistent
with
control
interventio
n
Acitretin
capsulescon
sistent
with
treatmentintervention
NB-UVB
05Jcm
2as
initial
dosageincreased
by10ndash20
each
time3tim
esaw
eekor
1-2tim
esaw
eek(if
lesio
nsredu
ced)
21days
noinform
ation
9sessions
TERbasedon
lesio
nscore
(90-70-30)
TER(T7714
C
5857
1205942=5534
119875lt005)
Redn
esspruritu
s(T
670C
570)
noSA
E
Wangetal2011
[12]
hospita
lKa
ifeng
China
5050
382375
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollient
after
NB-UVB
qd
NB-UVB(310ndash315nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
10ndash20
each
timeqo
durea
emollient
after
NB-UVB
qd
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-20)
TER(T860
C720
119875lt005)
Mild
skin
dryn
ess
burningpain
after
NB-UVB(T450C
550)
noSA
E
Wangetal2012
[13]
hospita
lKa
ifeng
China
6060
383371
years
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollient
after
NB-UVB
qod
glycyrrhizin
tablets
2tabletstid
NB-UVB(310ndash315nm
)03ndash05Jcm
2as
initialdo
sage
increasedby
10ndash20
each
timeqo
durea
emollient
after
NB-UVB
qodglycyrrhizin
tablets2tabletstid
28days
noinform
ation
14sessions
TER
TER(T917
C
777
1205942=8239119875lt005)
Skin
dryn
essbu
rning
pain
after
NB-UVB(T
460C
560)
noSA
E
Wuetal2011
[14]
hospita
lCh
engduCh
ina
7565
325348
years
Halom
etason
eem
ollient
for
one-weekpre-trial
treatmentqd
CHM
bath15ndash20
min
qodNB-UVB
consistentw
ithcontrolintervention
urea
emollientqd
Halom
etason
eemollient
consistentw
ithtre
atment
interventio
nNB-UVB
(310ndash315nm
)05ndash06Jcm
2as
initialdo
sageincreased
by01Jcm
2each
timeqo
durea
emollientqd
40days
noinform
ation
20sessions
TERbasedon
PASI
(95-60-20)
PASI
score
TER(T7867C
5692
1205942=1054
119875lt001)
PASI
score(T
924plusmn217
C546plusmn18
6)
Slight
light
skin
dryn
ess
burningpain
after
NB-UVB(T275C
365)
noSA
E
6 Evidence-Based Complementary and Alternative Medicine
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Wuetal2010
[15]
hospita
lGuang
zhou
Ch
ina
4039
3645plusmn
8523667plusmn
836
years
CHM
bath
15ndash20m
inqod
NB-UVB
consistent
with
control
interventio
n
NB-UVB(311ndash
315n
m)
03ndash05Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
90days
noinform
ation
45sessions
TERbasedon
PASI
(90-60-30)
PASI
score
TER(T7500C
5128
1205942=478
119875=0029)
PASI
score(T
421plusmn12
2C
645plusmn227)
Skin
dryn
esspruritu
s(T540C
539)skin
pigm
entatio
nin
all
noSA
E
YanandZh
ang
2009
[16]
hospita
lXirsquoan
China
4238
noinform
ation
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB
03Jcm
2as
initial
dosageincreased
by02Jcm
2 qo
d
80days
noinform
ation
40sessions
TERbasedon
lesio
nelim
ination
TER(T880
C421
119875lt005)
Noinform
ation
Zhou
andHuang
2005
[17]
hospita
lNanning
China
143129
35362
years
CHM
bath30m
in
qodUVA
consistentw
ithcontrolintervention
UVA
4Jc
m2as
initialdo
sage
increasedby
1Jcm
2 qo
d
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-25)
TER(T8042C
64
0119875lt001)
Noinform
ation
Qdon
cead
aybidtwicea
daytid
three
times
adayand
qodon
cein
everytwodaysC
HMC
hinese
herbalmedicineNB-UVB
narrow
band
ultravioletB
UVA
ultravioletA
MED
minim
alerythemad
osethe
minim
umdo
seofradiationthatprod
ucesskin
erythemaTE
Rtotaleffectiver
atecalculated
asthep
ercentageo
fldquocuredandremarkablye
ffectiverdquocasesPA
SI(95-60-20)ldquoClinicallycuredrdquo-PASI
scorereductio
nof
95to
100
ldquoremarkablyeffectiv
erdquo-PASI
scorer
eductio
nof
60to
94ldquoeffectiv
erdquo-PASI
scorer
eductio
nof
20to
59and
ldquoineffectiv
erdquo-PASI
scorer
eductio
nof
0to
19PASI
(90-60-20)PASI
(90-60-25)and
PASI
(90-60-30)
refertoeffectiv
enesslevels
usingd
ifferentp
ropo
rtions
ofPA
SIscorereductio
nlesio
nscore(90-70-30)effectiv
enesslevels
basedon
thereductio
nofpsoriatic
lesio
nsarea
andseveritylesio
nelim
ination
effectiv
enesslevels
basedon
thee
liminationof
lesio
n(90ndash
100
30ndash
59or0
ndash29
refertoclinically
curedremarkablyeffectiv
eandineffectiv
eaccording
ly)SA
Eserio
usadversee
vent
Evidence-Based Complementary and Alternative Medicine 7
Table 2 Chinese herbal medicine bath ingredients used in the thirteen studies
Author year(reference) Chinese herbal medicine bath formula
Cui et al 2008 [5] Galla Chinensis (Wu bei zi) Cortex Phellodendri Chinensis (Huang bo) Radix Angelica Sinensis (Dang gui)Rhizoma Curcumae Longae (Jiang huang) Fructus Psoraleae (Bu gu zhi) (no information of dosage)
Gu et al 2009 [6]Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 30 g Radix Angelica Sinensis (Dang gui) Spica Prunellae (Xiaku cao) 30 g Fructus Kochiae (Di fu zi) 30 g Cortex Dictamni (Bai xian pi) 30 g Cortex Phellodendri Chinensis(Huang bo) 30 g Folium Isatidis (Da qing ye) 30 g Rhizoma Smilacis Glabrae (Tu fu ling) 30 g
Lin et al 2010 [7]
Rhizoma Smilacis Glabrae (Tu fu ling) 30 g Fructus Kochiae (Di fu zi) 15 g Radix Angelica Sinensis (Dang gui) 20 gCortex Dictamni (Bai xian pi) 20 g Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 20 g Radix SophoraFlavescens (Ku shen) 15 g Fructus Cnidii (She chuang zi) 20 g Fructus Xanthii (Cang er zi) 15 g Radix Stemonae(Bai bu) 15 g Cortex Pseudolaricis (Tu jing pi) 10 g Fructus Tribuli (Ji li) 15 g Radix et Rhizoma Rhei (Da huang) 10 g
Liu et al 2005 [8]
Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 30 g Fructus Cnidii (She chuang zi) 30 g Radix SophoraFlavescens (Ku shen) 30 g Pericarpium Zanthoxyli (Hua jiao) 30 gHerba cum Radice Patriniae (Bai jiang cao) 30 gRhizoma et Radix Polygoni Cuspidati (Hu zhang) 30 g Herba Portulacae (Ma chi xian) 30 g Radix et RhizomaSalviae Miltiorrhizae (Dan shen) 20 g Rhizoma Atractylodis (Cang zhu) 15 g
Liu et al 2004 [9]
Blood-heat syndrome Folium Isatidis (Da qing ye) Radix Rehmanniae (Di huang) Radix Paeoniae Rubra (Chishao) Rhizoma Smilacis Glabrae (Tu fu ling) Radix Arnebiae (Zi cao) Cortex Moutan (Mu dan pi) Blood-stasissyndrome Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) Semen Persicae (Tao ren) Flos Carthami (Honghua) Rhizoma Curcumae (E zhu) Caulis Spatholobi (Ji xue teng) Blood-dryness syndrome Radix Rehmanniae (Dihuang) Radix Angelica Sinensis (Dang gui) Cortex Dictamni (Bai xian pi) Herba Hedyotis (Bai hua she she cao)Rhizoma Smilacis Glabrae (Tu fu ling) (no information of dosage)
Shi et al 2011 [10]Caulis Impatientis (Tou gu cao) Cacumen Platycladi (Ce bai ye) Cortex Dictamni (Bai xian pi) Radix et RhizomaSalviae Miltiorrhizae (Dan shen) Radix Angelica Sinensis (Dang gui) Semen Persicae (Tao ren) Radix SophoraFlavescens (Ku shen) Fructus Kochiae (Di fu zi) Margarita (Zhen zhu) (no information of dosage)
Wang et al 2010 [11] Flos Chrysanthemi Indici (Ye ju hua) 240 g Pericarpium Zanthoxyli (Hua jiao) 120 g Rhizoma Smilacis Glabrae (Tufu ling) 150 g Radix Sophora Flavescens (Ku shen) 300 g Fructus Kochiae (Di fu zi) 300 g
Wang et al 2011 [12]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wang et al 2012 [13]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wu et al 2011 [14]Radix Sophora Flavescens (Ku shen) Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) Flos ChrysanthemiIndici (Ye ju hua) Herba Violae (Zi hua di ding) Flos Lonicerae Japonicae (Jin yin hua) Fructus Cnidii (She chuangzi) Glycyrrhiza uralensis root (no information of dosage)
Wu et al 2010 [15]Radix Rehmanniae (Di huang) 40 g Flos Lonicerae Japonicae (Jin yin hua) 30 g Herba Violae (Zi hua di ding) 30 gHerba Taraxaci (Pu gong ying) 30 g Zaocys (Wu shao she) 15 g Radix Scutellariae (Huang qin) 30 g RadixArnebiae seu Lithospermi (Zi cao) 30 g
Yan and Zhang2009 [16]
Radix Sophora Flavescens (Ku shen) 30 g Fructus Cnidii (She chuang zi) 30 g Radix Clematidis (Wei ling xian)30 g Cortex Dictamni (Bai xian pi) 30 g Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 20 g RhizomaAtractylodis (Cang zhu) 20 g Rhizoma Smilacis Glabrae (Tu fu ling) 20 g
Zhou and Huang2005 [17]
Rhizoma Coptidis (Huang lian) 10 g Cortex Phellodendri Chinensis (Huang bo) 20 g Radix Sophora Flavescens (Kushen) 20 g Radix Sanguisorbae (Di yu) 20 g Cortex Mahonia bealei (Tu Huang bo) 60 g Pericarpium Granati (Shiliu pi) 15 g Fructus Kochiae (Di fu zi) 15 g Herba Senecionis Scandens (Qian li guang) 30 g
Since PASI 60 was used in ten studies [5ndash10 12 14 15 17] asthe benchmark of ldquoremarkably effectiverdquo for TER calculationit was selected to be the outcome for pooling studies formeta-analysis in this review Three studies were excludedfrom meta-analysis because two of them used TER basedon a scoring system other than PASI for which there wasno evidence supporting it as an appropriate approach toevaluate therapeutic effect [11 16] and one was excluded dueto lack of a clear description of how ldquolesion improvementrdquowas measured [13]
314 Efficacy All thirteen studies reported that the com-bination of CHM bath and phototherapy had a superiorefficacy compared to phototherapy alone in terms of TERIn addition Cui et al 2008 reported that the administrationof CHM bath could significantly reduce NB-UVB averagedosage [5]
315 Followup Followup and relapse rate were reported intwo studies [6 9] In one the relapse rate of the treatmentgroup was 152 compared with 352 for control [9] In the
8 Evidence-Based Complementary and Alternative Medicine
other the rates were 108 for the treatment group and 303in the control In both cases a significant difference betweenthe two groups was reported (119875 lt 005) but a definition ofldquorelapserdquo was not provided in either study
316 Dropouts One study reported the number of dropoutsduring the treatment period without detailed reasons [6]All other studies reported that the number of patients whocompleted the trial was same as the number randomized
317 Adverse Events (AEs) Three studies did not reportany AEs [8 11 17] The most frequent AEs reported by theother ten studies were pruritus (7 studies) skin dryness (6studies) redness (6 studies) burning pain (3 studies) andskin pigmentation (3 studies) Three studies [5ndash7] reportedsignificantly higher rates of redness and pruritus in the UVBcontrol groups One of these three studies also reportedno significant difference between groups for skin dryness[7] The other seven studies that reported on AEs did notprovide details of between-group comparisons of AEs AllAEs reported in the ten studies could be resolved by reducingUV dosage or applying emollient No serious adverse event(SAE) was reported
32 Risks of Bias Assessment Risk of bias was assessed follow-ing the Cochrane Handbook 510 [23] and is summarized inFigure 2 Although all thirteen studies claimed ldquorandomizedrdquoonly six studies described the specific randomization meth-ods [5 6 10 12ndash14] Among them the random sequence gen-eration in four studies was appropriate [6 12ndash14] and assessedas ldquolow riskrdquo one study was assessed as ldquohigh riskrdquo due to theuse of patientsrsquo visiting order [15] one study used ldquoenvelopesrdquofor randomization which is not an adequate description tojudge bias therefore it was assessed as ldquounclearrdquo [5] Theother seven studies were considered ldquounclearrdquo due to thelack of information about randomization [7ndash11 16 17] Forallocation concealment method the study that used patientsrsquovisiting order for group allocation was judged ldquohigh riskrdquo[15] while the other twelve studies did not provide adequateinformation and therefore obtained judgments of ldquounclearrdquoFor all thirteen studies no information was provided forblinding of participants personnel or outcome assessors Infact blinding was impossible for participants and personnelin these studies due to the design One study reported thenumber of dropouts without reasons hence it was judged asldquounclearrdquo for incomplete outcome data [6] the other twelvestudies were assessed as ldquolow riskrdquo because they reported thatall participants finished the study A ldquolow riskrdquo assessmentwas given to all studies in terms of ldquoselective outcomereportingrdquo as the outcomes reported in the results sectionmatched the methods section However none had a protocolregistered
33 Meta-Analysis Two studies were not pooled in themeta-analysis since they used different forms of phototherapy com-pared to the others one combined UVA andUVB [9] and theother used UVA [17] Three studies were not included in themeta-analysis because they did not employPASI 60 [11 13 16]
Rand
om se
quen
ce g
ener
atio
n (s
elec
tion
bias
)
Cui et al 2008
Gu et al 2009 +
Lin et al 2010
Liu et al 2004
Liu et al 2005
Shi et al 2011
Wang et al 2010
Wang et al 2011 +
Wang et al 2012 +
Wu et al 2010 minus
Wu et al 2011 +
Yan and Zhang 2009
Zhou and Huang 2005 A
lloca
tion
conc
ealm
ent (
sele
ctio
n bi
as)
minus
Blin
ding
of p
artic
ipan
ts an
d pe
rson
nel (
perfo
rman
ce b
ias)
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
Blin
ding
of o
utco
me a
sses
smen
t (de
tect
ion
bias
)
Inco
mpl
ete o
utco
me d
ata (
attr
ition
bia
s)
++++++++++++
Sele
ctiv
e rep
ortin
g (r
epor
ting
bias
)
+++++++++++++
Figure 2 Risk of bias summary
As a result eight RCTs which used NB-UVB as phototherapyand PASI 60 for TER calculation were pooled in the meta-analysis These were divided into two groups based on studydesign as followsGroup 1 CHM Bath + NB-UVB versus NB-UVB Four studies[5 8 10 15] showed a higher TER (PASI 60) for CHM bathplus phototherapy compared with phototherapy alone (RR125 95 CI 115ndash136) without heterogeneity (1198682 = 0)(Figure 3) There was diversity in the herbs used in thesestudies but two studies had twomain herbs Ku shen andDanshen in common [8 10] The pooled result for these studiesfavoured the addition of the herbal bath (RR 119 95 CI108ndash132 1198682 = 0)Group 2 CHMBath +NB-UVB+Emollient versus NB-UVB+Emollient Four studies [6 7 12 14] showed a higher TER(PASI 60) for CHM bath plus phototherapy plus externallyapplied emollient cream compared with phototherapy plusthe same cream (RR 124 95 CI 115ndash135) The hetero-geneity was moderate (1198682 = 52) (Figure 3) Of the fourstudies three had main herbs in common [6 7 12] and ofthese Gu et al 2009 and Wang et al 2011 studies [6 12] were
Evidence-Based Complementary and Alternative Medicine 9
Study or subgroup CHM bath + NB-UVB NB-UVB Risk ratio Risk ratioEvents Total Events Total Weight MH fixed and 95 CI MH fixed and 95 CI
111 CHM bath + NB-UVB versus NB-UVB Cui et al 2008 60 62 41 57 99 135 [114 159]Liu et al 2005 38 40 33 40 76 115 [098 135]Shi et al 2011 144 170 118 168 274 121 [107 136]Wu et al 2010 30 40 20 39 47 146 [103 208]Subtotal (95 CI) 312 304 496 125 [115 136]Total events 272 212
112 CHM bath + NB-UVB + emollient versus NB-UVB + emollient
Gu et al 2009 84 89 81 96 180 112 [101 124] Lin et al 2010 89 95 63 90 149 134 [116 155] Wang et al 2011 43 50 36 50 83 119 [097 147] Wu et al 2011 59 75 37 65 92 138 [108 176] Subtotal (95 CI) 309 301 504 124 [115 135]
Total events 275 217
Total (95 CI) 621 605 100 125 [118 132]Total events 547 429
01 1 10NB-UVB CHM bath +
NB-UVB
Heterogeneity 1205942 = 286 df = 3 (P = 041) I2 = 0Test for overall effect Z = 517 (P lt 000001)
Heterogeneity 1205942 = 620 df = 3 (P = 010) I2 = 52Test for overall effect Z = 536 (P lt 000001)
Heterogeneity 1205942 = 914 df = 7 (P = 024) I2 = 23Test for overall effect Z = 744 (P lt 000001)Test for subgroup differences 1205942 = 001 df = 1 (P = 094) I2 = 0
Figure 3 Forest plot of clinical efficacy (PASI 60) PASI the psoriasis area and severity index PASI 60 the percentage of participants whoachieved PASI scores reduced by ge60 CHM Chinese herbal medicine NB-UVB narrowband ultraviolet
the most similar in that they shared Dan shen and Bai xianpi When the dissimilar study [12] was excluded there waslittle change in the result (RR 121 95 CI 112ndash132) andthe heterogeneity remained moderate (1198682 = 54) but whenthe pooling was limited to the two studies with the mostsimilar CHMs (Gu et al 2009 and Wang et al 2011) [6 12]the heterogeneity was removed (RR 114 95 CI 104ndash1261198682= 0)Overall the above eight studies [5ndash8 10 12 14 15] had
a higher TER (PASI 60) for CHM bath plus phototherapycompared with the phototherapy (RR 125 95CI 118ndash132)The heterogeneity was relatively low (1198682 = 23) (Figure 3)
4 Discussion
41 Efficacy of Phototherapy Combined with CHM Bath forPsoriasis All thirteen studies reported that CHM bath plusphototherapy had superior efficacy to phototherapy alone Inthe meta-analysis for group 1 (CHM bath + NB-UVB versusNB-UVB) all studies used the same primary outcome mea-sure did not use other supplementary treatment and therewas no heterogeneity so this result can be considered themost robust Nevertheless none of the studies employed anidentical herbal bath formulation although there were herbalingredients in common In contrast there was considerablevariation in study design in group 2 (CHMbath +NB-UVB+emollient versus NB-UVB + emollient) and this was reflectedin the heterogeneity found in the meta-analysis results Infact some co-intervention medications used in group 2 such
as PuLian ointment and Bing Huang Fu Le ointment havebeen reported to have therapeutic effects on psoriasis [26 27]Whether there was any interaction between the interventionsand co-interventions was unclear
42 Possible Mechanisms of Action for Phototherapy Com-bined with CHM Bath In psoriasis treatment phototherapymainly produces local immunosuppressive effects and anti-proliferative effects [1 4] The primary immunosuppressiveactions are reducing mobility of antigen-presenting Langer-hans cells and inhibiting T lymphocyte activation [1 4] Inaddition phototherapy inhibits epidermal hyperproliferationby interactions with keratinocyte DNA [1 4] It has beenreported thatmore than 50of patients treated by photother-apy achieved at least 75 improvement in PASI score (PASI75) after four to six weeks based on the recommendationsof the latest treatment guideline for psoriasis vulgaris [4]In this review for the ten studies [5ndash10 12 14 15 17] thatused PASI 60 for calculating TER more than 50 of controlgroup patients (611 out of 913) achieved PASI 60 after fourto eight weeks treatment with phototherapy Although theproportion of control group patients who achieved PASI 75was not specifically assessed this result indicates that thephototherapy was effective
The additional therapeutic effects of the CHM bath couldbe attributable to three main aspects (1) the thermotherapyeffects (2) the effects of a water bath and (3) the specifictherapeutic effects of the CHMs used in the baths Each ofthese aspects is discussed below
10 Evidence-Based Complementary and Alternative Medicine
421 Thermal Effects Hyperthermia is not a new conceptbut research interest into its application in the treatmentof psoriasis is relatively recent [28] Early utilization ofhyperthermia for psoriasis followed on from the ideas thatthe severity of psoriasis would reduce during warm summermonths and a benefit of hyperthermia had been shown forkilling cancer cells [29] Orenbergrsquos study in 1980 which usedultrasound induced heat to treat psoriasis showed a benefitfor psoriasis lesion remission [29] Later it was demonstratedthat hyperthermia induced by topical exothermic pads [30]infrared [31] ormicrowave [32]was also effective for psoriasisplaques The advantage of using a hot water bath is that itis a simple inexpensive approach that can be used to treatrelatively large body areas [33]
422 Water Baths (Balneotherapy) Since hyperthermia hasproven beneficial for psoriasis lesions the simple modalityof using warm or hot water became popular Nowadaysvarious types of water bath therapy are considered safetreatments for dermatological conditions and are practicedin many countries Well-known balneotherapy sites includethe Dead Sea in Israel the Kangal hot spring in Turkeythe Kusatsu hot spring in Japan and the Blue Lagoonin Iceland In particular the Dead Sea is known to beeffective for the treatment of psoriasis [34] The mecha-nisms by which diseases respond to balneotherapy probablyincorporate chemical thermal and mechanical effects [35]It was suggested by a clinical study that simple repetitivewater bath hyperthermia was effective in the treatment ofpsoriasis by improving psoriatic lesions reducing edema andrelieving pruritus [28] In addition the water itself couldremove psoriatic scale [36] which may be beneficial for skinabsorption of phototherapy Previous studies have shownthat water bath markedly increased photosensitivity to UVB[37 38]
423 Specific Effects of the CHMs Used in the Baths Onlyone of the herbs used in one study Psoralea corylifolia (Bugu zhi) [5] is known to increase photosensitivity thereforethe overall effectiveness reported for the CHM baths doesnot appear to be due to pharmacological enhancement of theeffects of the phototherapy
In order to investigate the plausibility of the CHMsused in the baths having antipsoriatic actions experimentalreports on the actions of the main herbal ingredients wereexamined The most frequently used herbs in the includedstudies were Salvia miltiorrhiza root (Dan shen) [6 8 9 1213 16 23] Dictamnus dasycarpus bark (Bai xian pi) [6 79 10 12 13 16] Sophora flavescens root (Ku shen) [7 8 1011 14 16 17] and Kochia scoparia fruit (Di fu zi) [6 7 10ndash13 17] which were each used in seven studies Each of theseherbs has a history of topical application in the manage-ment of dermatological disorders [39] Also experimentalstudies have been conducted on extracts andor compoundsderived from these herbs with regard to actions relevant topsoriasis
Salvia miltiorrhiza (Dan shen) root and its constituenttanshinones and salvianolic acids have received considerable
research attention for the treatment and prevention of cardio-vascular disorders [40] These compounds have been shownto have free radical scavenging and anti-inflammatory effects[40ndash42] Also a number of its constituent tanshinones havebeen reported to have antiproliferative or proapoptotic effectsin cancer cell lines [43] More specifically an in vitro studyof mouse keratinocytes indicated that tanshinone IIA timeand dose dependently inhibited cell growth by inducingapoptosis via caspase cascade [44] Another possible mech-anism of action for tanshinone IIA in keratinocytes is viainhibiting the dimerization of the activator protein 1 (AP-1)transcription factor resulting in reduced interferon sensitivitywhich in turn could lead to a reduced inflammatory response[45]
Jiang et al 2008 [46] reported that an extract of theroot bark of Dictamnus dasycarpus (Bai xian pi) inhibitedhistamine release and reduced scratching behaviour in amouse anaphylaxismodel In vitro anti-inflammatory activityhas been reported for a root-bark extract [47] and for itsconstituents fraxinellone [48] and obacunone [49] Also itsessential oil and a number of compounds including dictam-nine preskimmianine and fraxinellone have demonstratedantitumour activity [47]
In the case of Sophora flavescens (Ku shen) root anextract inhibited histamine release both in vitro and in vivo[50 51] and other experimental studies have reported anti-inflammatory effects for its constituent alkaloids matrine[52 53] and oxymatrine [54] and for its total flavonoids [55]Its flavonoids and chalcones both demonstrate antioxidantactivity [56] Antitumour activities have been reported invitro for both matrine and oxymatrine as well as for anumber of flavonoids [57] of which trifolirhizin has shownboth anti-inflammatory and antiproliferative actions [58]and kurarinone showed inhibition of immune response [59]In human keratinocytes an extract inhibited proinflamma-tory chemokines [60] A Sophora flavescens extract showedantipruritic effects in a mouse model [61] and in a contactdermatitis mouse model the topical application of a Sophoraflavescens extract reduced hyperplasia edema spongiosisand infiltration of mononuclear cells [51]
A series of studies have reported that the 70 ethanolextract and its component momordin Ic from the driedfruits of Kochia scoparia (Di fu zi) had antinociceptive andanti-inflammatory [62] antiallergic [63] and antipruriticeffects [64] An orally administered extract was found to beactive in a rheumatoid arthritis model in rats [65]
Each of the above studies provides evidence that thesefour herbs have anti-inflammatory antiproliferative andorantipruritic activity all of which are of relevance to thetreatment of psoriasis However this evidence is indirect withonly a few studies testing topical application Consequentlywhether the additional therapeutic effects of the CHM bathsin the studies included in this review were produced by thespecific effects of the CHMs and the effect of the warm waterbaths or were just nonspecific effects of an additional inter-vention remains unclear Therefore future studies shouldinclude a control group that uses a colored warm water bathplus phototherapy to investigate the specific efficacy of theCHMs
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
6 Evidence-Based Complementary and Alternative Medicine
Table1Con
tinued
Authoryear
setting
locatio
n
Participant
(TC)
averagea
ge(TC)
Treatm
ent
interventio
nsCon
trolinterventions
Treatm
ent
and
follo
wup
duratio
n
Total
treatment
sessions
Outcome
measures
Results
Num
bero
fpartic
ipant
repo
rted
adversee
vents
(n=)SAE
Wuetal2010
[15]
hospita
lGuang
zhou
Ch
ina
4039
3645plusmn
8523667plusmn
836
years
CHM
bath
15ndash20m
inqod
NB-UVB
consistent
with
control
interventio
n
NB-UVB(311ndash
315n
m)
03ndash05Jcm
2as
initialdo
sage
increasedby
01Jcm
2each
time
qod
90days
noinform
ation
45sessions
TERbasedon
PASI
(90-60-30)
PASI
score
TER(T7500C
5128
1205942=478
119875=0029)
PASI
score(T
421plusmn12
2C
645plusmn227)
Skin
dryn
esspruritu
s(T540C
539)skin
pigm
entatio
nin
all
noSA
E
YanandZh
ang
2009
[16]
hospita
lXirsquoan
China
4238
noinform
ation
CHM
bath30m
in
qodNB-UVB
consistentw
ithcontrolintervention
NB-UVB
03Jcm
2as
initial
dosageincreased
by02Jcm
2 qo
d
80days
noinform
ation
40sessions
TERbasedon
lesio
nelim
ination
TER(T880
C421
119875lt005)
Noinform
ation
Zhou
andHuang
2005
[17]
hospita
lNanning
China
143129
35362
years
CHM
bath30m
in
qodUVA
consistentw
ithcontrolintervention
UVA
4Jc
m2as
initialdo
sage
increasedby
1Jcm
2 qo
d
28days
noinform
ation
14sessions
TERbasedon
PASI
(90-60-25)
TER(T8042C
64
0119875lt001)
Noinform
ation
Qdon
cead
aybidtwicea
daytid
three
times
adayand
qodon
cein
everytwodaysC
HMC
hinese
herbalmedicineNB-UVB
narrow
band
ultravioletB
UVA
ultravioletA
MED
minim
alerythemad
osethe
minim
umdo
seofradiationthatprod
ucesskin
erythemaTE
Rtotaleffectiver
atecalculated
asthep
ercentageo
fldquocuredandremarkablye
ffectiverdquocasesPA
SI(95-60-20)ldquoClinicallycuredrdquo-PASI
scorereductio
nof
95to
100
ldquoremarkablyeffectiv
erdquo-PASI
scorer
eductio
nof
60to
94ldquoeffectiv
erdquo-PASI
scorer
eductio
nof
20to
59and
ldquoineffectiv
erdquo-PASI
scorer
eductio
nof
0to
19PASI
(90-60-20)PASI
(90-60-25)and
PASI
(90-60-30)
refertoeffectiv
enesslevels
usingd
ifferentp
ropo
rtions
ofPA
SIscorereductio
nlesio
nscore(90-70-30)effectiv
enesslevels
basedon
thereductio
nofpsoriatic
lesio
nsarea
andseveritylesio
nelim
ination
effectiv
enesslevels
basedon
thee
liminationof
lesio
n(90ndash
100
30ndash
59or0
ndash29
refertoclinically
curedremarkablyeffectiv
eandineffectiv
eaccording
ly)SA
Eserio
usadversee
vent
Evidence-Based Complementary and Alternative Medicine 7
Table 2 Chinese herbal medicine bath ingredients used in the thirteen studies
Author year(reference) Chinese herbal medicine bath formula
Cui et al 2008 [5] Galla Chinensis (Wu bei zi) Cortex Phellodendri Chinensis (Huang bo) Radix Angelica Sinensis (Dang gui)Rhizoma Curcumae Longae (Jiang huang) Fructus Psoraleae (Bu gu zhi) (no information of dosage)
Gu et al 2009 [6]Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 30 g Radix Angelica Sinensis (Dang gui) Spica Prunellae (Xiaku cao) 30 g Fructus Kochiae (Di fu zi) 30 g Cortex Dictamni (Bai xian pi) 30 g Cortex Phellodendri Chinensis(Huang bo) 30 g Folium Isatidis (Da qing ye) 30 g Rhizoma Smilacis Glabrae (Tu fu ling) 30 g
Lin et al 2010 [7]
Rhizoma Smilacis Glabrae (Tu fu ling) 30 g Fructus Kochiae (Di fu zi) 15 g Radix Angelica Sinensis (Dang gui) 20 gCortex Dictamni (Bai xian pi) 20 g Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 20 g Radix SophoraFlavescens (Ku shen) 15 g Fructus Cnidii (She chuang zi) 20 g Fructus Xanthii (Cang er zi) 15 g Radix Stemonae(Bai bu) 15 g Cortex Pseudolaricis (Tu jing pi) 10 g Fructus Tribuli (Ji li) 15 g Radix et Rhizoma Rhei (Da huang) 10 g
Liu et al 2005 [8]
Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 30 g Fructus Cnidii (She chuang zi) 30 g Radix SophoraFlavescens (Ku shen) 30 g Pericarpium Zanthoxyli (Hua jiao) 30 gHerba cum Radice Patriniae (Bai jiang cao) 30 gRhizoma et Radix Polygoni Cuspidati (Hu zhang) 30 g Herba Portulacae (Ma chi xian) 30 g Radix et RhizomaSalviae Miltiorrhizae (Dan shen) 20 g Rhizoma Atractylodis (Cang zhu) 15 g
Liu et al 2004 [9]
Blood-heat syndrome Folium Isatidis (Da qing ye) Radix Rehmanniae (Di huang) Radix Paeoniae Rubra (Chishao) Rhizoma Smilacis Glabrae (Tu fu ling) Radix Arnebiae (Zi cao) Cortex Moutan (Mu dan pi) Blood-stasissyndrome Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) Semen Persicae (Tao ren) Flos Carthami (Honghua) Rhizoma Curcumae (E zhu) Caulis Spatholobi (Ji xue teng) Blood-dryness syndrome Radix Rehmanniae (Dihuang) Radix Angelica Sinensis (Dang gui) Cortex Dictamni (Bai xian pi) Herba Hedyotis (Bai hua she she cao)Rhizoma Smilacis Glabrae (Tu fu ling) (no information of dosage)
Shi et al 2011 [10]Caulis Impatientis (Tou gu cao) Cacumen Platycladi (Ce bai ye) Cortex Dictamni (Bai xian pi) Radix et RhizomaSalviae Miltiorrhizae (Dan shen) Radix Angelica Sinensis (Dang gui) Semen Persicae (Tao ren) Radix SophoraFlavescens (Ku shen) Fructus Kochiae (Di fu zi) Margarita (Zhen zhu) (no information of dosage)
Wang et al 2010 [11] Flos Chrysanthemi Indici (Ye ju hua) 240 g Pericarpium Zanthoxyli (Hua jiao) 120 g Rhizoma Smilacis Glabrae (Tufu ling) 150 g Radix Sophora Flavescens (Ku shen) 300 g Fructus Kochiae (Di fu zi) 300 g
Wang et al 2011 [12]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wang et al 2012 [13]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wu et al 2011 [14]Radix Sophora Flavescens (Ku shen) Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) Flos ChrysanthemiIndici (Ye ju hua) Herba Violae (Zi hua di ding) Flos Lonicerae Japonicae (Jin yin hua) Fructus Cnidii (She chuangzi) Glycyrrhiza uralensis root (no information of dosage)
Wu et al 2010 [15]Radix Rehmanniae (Di huang) 40 g Flos Lonicerae Japonicae (Jin yin hua) 30 g Herba Violae (Zi hua di ding) 30 gHerba Taraxaci (Pu gong ying) 30 g Zaocys (Wu shao she) 15 g Radix Scutellariae (Huang qin) 30 g RadixArnebiae seu Lithospermi (Zi cao) 30 g
Yan and Zhang2009 [16]
Radix Sophora Flavescens (Ku shen) 30 g Fructus Cnidii (She chuang zi) 30 g Radix Clematidis (Wei ling xian)30 g Cortex Dictamni (Bai xian pi) 30 g Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 20 g RhizomaAtractylodis (Cang zhu) 20 g Rhizoma Smilacis Glabrae (Tu fu ling) 20 g
Zhou and Huang2005 [17]
Rhizoma Coptidis (Huang lian) 10 g Cortex Phellodendri Chinensis (Huang bo) 20 g Radix Sophora Flavescens (Kushen) 20 g Radix Sanguisorbae (Di yu) 20 g Cortex Mahonia bealei (Tu Huang bo) 60 g Pericarpium Granati (Shiliu pi) 15 g Fructus Kochiae (Di fu zi) 15 g Herba Senecionis Scandens (Qian li guang) 30 g
Since PASI 60 was used in ten studies [5ndash10 12 14 15 17] asthe benchmark of ldquoremarkably effectiverdquo for TER calculationit was selected to be the outcome for pooling studies formeta-analysis in this review Three studies were excludedfrom meta-analysis because two of them used TER basedon a scoring system other than PASI for which there wasno evidence supporting it as an appropriate approach toevaluate therapeutic effect [11 16] and one was excluded dueto lack of a clear description of how ldquolesion improvementrdquowas measured [13]
314 Efficacy All thirteen studies reported that the com-bination of CHM bath and phototherapy had a superiorefficacy compared to phototherapy alone in terms of TERIn addition Cui et al 2008 reported that the administrationof CHM bath could significantly reduce NB-UVB averagedosage [5]
315 Followup Followup and relapse rate were reported intwo studies [6 9] In one the relapse rate of the treatmentgroup was 152 compared with 352 for control [9] In the
8 Evidence-Based Complementary and Alternative Medicine
other the rates were 108 for the treatment group and 303in the control In both cases a significant difference betweenthe two groups was reported (119875 lt 005) but a definition ofldquorelapserdquo was not provided in either study
316 Dropouts One study reported the number of dropoutsduring the treatment period without detailed reasons [6]All other studies reported that the number of patients whocompleted the trial was same as the number randomized
317 Adverse Events (AEs) Three studies did not reportany AEs [8 11 17] The most frequent AEs reported by theother ten studies were pruritus (7 studies) skin dryness (6studies) redness (6 studies) burning pain (3 studies) andskin pigmentation (3 studies) Three studies [5ndash7] reportedsignificantly higher rates of redness and pruritus in the UVBcontrol groups One of these three studies also reportedno significant difference between groups for skin dryness[7] The other seven studies that reported on AEs did notprovide details of between-group comparisons of AEs AllAEs reported in the ten studies could be resolved by reducingUV dosage or applying emollient No serious adverse event(SAE) was reported
32 Risks of Bias Assessment Risk of bias was assessed follow-ing the Cochrane Handbook 510 [23] and is summarized inFigure 2 Although all thirteen studies claimed ldquorandomizedrdquoonly six studies described the specific randomization meth-ods [5 6 10 12ndash14] Among them the random sequence gen-eration in four studies was appropriate [6 12ndash14] and assessedas ldquolow riskrdquo one study was assessed as ldquohigh riskrdquo due to theuse of patientsrsquo visiting order [15] one study used ldquoenvelopesrdquofor randomization which is not an adequate description tojudge bias therefore it was assessed as ldquounclearrdquo [5] Theother seven studies were considered ldquounclearrdquo due to thelack of information about randomization [7ndash11 16 17] Forallocation concealment method the study that used patientsrsquovisiting order for group allocation was judged ldquohigh riskrdquo[15] while the other twelve studies did not provide adequateinformation and therefore obtained judgments of ldquounclearrdquoFor all thirteen studies no information was provided forblinding of participants personnel or outcome assessors Infact blinding was impossible for participants and personnelin these studies due to the design One study reported thenumber of dropouts without reasons hence it was judged asldquounclearrdquo for incomplete outcome data [6] the other twelvestudies were assessed as ldquolow riskrdquo because they reported thatall participants finished the study A ldquolow riskrdquo assessmentwas given to all studies in terms of ldquoselective outcomereportingrdquo as the outcomes reported in the results sectionmatched the methods section However none had a protocolregistered
33 Meta-Analysis Two studies were not pooled in themeta-analysis since they used different forms of phototherapy com-pared to the others one combined UVA andUVB [9] and theother used UVA [17] Three studies were not included in themeta-analysis because they did not employPASI 60 [11 13 16]
Rand
om se
quen
ce g
ener
atio
n (s
elec
tion
bias
)
Cui et al 2008
Gu et al 2009 +
Lin et al 2010
Liu et al 2004
Liu et al 2005
Shi et al 2011
Wang et al 2010
Wang et al 2011 +
Wang et al 2012 +
Wu et al 2010 minus
Wu et al 2011 +
Yan and Zhang 2009
Zhou and Huang 2005 A
lloca
tion
conc
ealm
ent (
sele
ctio
n bi
as)
minus
Blin
ding
of p
artic
ipan
ts an
d pe
rson
nel (
perfo
rman
ce b
ias)
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
Blin
ding
of o
utco
me a
sses
smen
t (de
tect
ion
bias
)
Inco
mpl
ete o
utco
me d
ata (
attr
ition
bia
s)
++++++++++++
Sele
ctiv
e rep
ortin
g (r
epor
ting
bias
)
+++++++++++++
Figure 2 Risk of bias summary
As a result eight RCTs which used NB-UVB as phototherapyand PASI 60 for TER calculation were pooled in the meta-analysis These were divided into two groups based on studydesign as followsGroup 1 CHM Bath + NB-UVB versus NB-UVB Four studies[5 8 10 15] showed a higher TER (PASI 60) for CHM bathplus phototherapy compared with phototherapy alone (RR125 95 CI 115ndash136) without heterogeneity (1198682 = 0)(Figure 3) There was diversity in the herbs used in thesestudies but two studies had twomain herbs Ku shen andDanshen in common [8 10] The pooled result for these studiesfavoured the addition of the herbal bath (RR 119 95 CI108ndash132 1198682 = 0)Group 2 CHMBath +NB-UVB+Emollient versus NB-UVB+Emollient Four studies [6 7 12 14] showed a higher TER(PASI 60) for CHM bath plus phototherapy plus externallyapplied emollient cream compared with phototherapy plusthe same cream (RR 124 95 CI 115ndash135) The hetero-geneity was moderate (1198682 = 52) (Figure 3) Of the fourstudies three had main herbs in common [6 7 12] and ofthese Gu et al 2009 and Wang et al 2011 studies [6 12] were
Evidence-Based Complementary and Alternative Medicine 9
Study or subgroup CHM bath + NB-UVB NB-UVB Risk ratio Risk ratioEvents Total Events Total Weight MH fixed and 95 CI MH fixed and 95 CI
111 CHM bath + NB-UVB versus NB-UVB Cui et al 2008 60 62 41 57 99 135 [114 159]Liu et al 2005 38 40 33 40 76 115 [098 135]Shi et al 2011 144 170 118 168 274 121 [107 136]Wu et al 2010 30 40 20 39 47 146 [103 208]Subtotal (95 CI) 312 304 496 125 [115 136]Total events 272 212
112 CHM bath + NB-UVB + emollient versus NB-UVB + emollient
Gu et al 2009 84 89 81 96 180 112 [101 124] Lin et al 2010 89 95 63 90 149 134 [116 155] Wang et al 2011 43 50 36 50 83 119 [097 147] Wu et al 2011 59 75 37 65 92 138 [108 176] Subtotal (95 CI) 309 301 504 124 [115 135]
Total events 275 217
Total (95 CI) 621 605 100 125 [118 132]Total events 547 429
01 1 10NB-UVB CHM bath +
NB-UVB
Heterogeneity 1205942 = 286 df = 3 (P = 041) I2 = 0Test for overall effect Z = 517 (P lt 000001)
Heterogeneity 1205942 = 620 df = 3 (P = 010) I2 = 52Test for overall effect Z = 536 (P lt 000001)
Heterogeneity 1205942 = 914 df = 7 (P = 024) I2 = 23Test for overall effect Z = 744 (P lt 000001)Test for subgroup differences 1205942 = 001 df = 1 (P = 094) I2 = 0
Figure 3 Forest plot of clinical efficacy (PASI 60) PASI the psoriasis area and severity index PASI 60 the percentage of participants whoachieved PASI scores reduced by ge60 CHM Chinese herbal medicine NB-UVB narrowband ultraviolet
the most similar in that they shared Dan shen and Bai xianpi When the dissimilar study [12] was excluded there waslittle change in the result (RR 121 95 CI 112ndash132) andthe heterogeneity remained moderate (1198682 = 54) but whenthe pooling was limited to the two studies with the mostsimilar CHMs (Gu et al 2009 and Wang et al 2011) [6 12]the heterogeneity was removed (RR 114 95 CI 104ndash1261198682= 0)Overall the above eight studies [5ndash8 10 12 14 15] had
a higher TER (PASI 60) for CHM bath plus phototherapycompared with the phototherapy (RR 125 95CI 118ndash132)The heterogeneity was relatively low (1198682 = 23) (Figure 3)
4 Discussion
41 Efficacy of Phototherapy Combined with CHM Bath forPsoriasis All thirteen studies reported that CHM bath plusphototherapy had superior efficacy to phototherapy alone Inthe meta-analysis for group 1 (CHM bath + NB-UVB versusNB-UVB) all studies used the same primary outcome mea-sure did not use other supplementary treatment and therewas no heterogeneity so this result can be considered themost robust Nevertheless none of the studies employed anidentical herbal bath formulation although there were herbalingredients in common In contrast there was considerablevariation in study design in group 2 (CHMbath +NB-UVB+emollient versus NB-UVB + emollient) and this was reflectedin the heterogeneity found in the meta-analysis results Infact some co-intervention medications used in group 2 such
as PuLian ointment and Bing Huang Fu Le ointment havebeen reported to have therapeutic effects on psoriasis [26 27]Whether there was any interaction between the interventionsand co-interventions was unclear
42 Possible Mechanisms of Action for Phototherapy Com-bined with CHM Bath In psoriasis treatment phototherapymainly produces local immunosuppressive effects and anti-proliferative effects [1 4] The primary immunosuppressiveactions are reducing mobility of antigen-presenting Langer-hans cells and inhibiting T lymphocyte activation [1 4] Inaddition phototherapy inhibits epidermal hyperproliferationby interactions with keratinocyte DNA [1 4] It has beenreported thatmore than 50of patients treated by photother-apy achieved at least 75 improvement in PASI score (PASI75) after four to six weeks based on the recommendationsof the latest treatment guideline for psoriasis vulgaris [4]In this review for the ten studies [5ndash10 12 14 15 17] thatused PASI 60 for calculating TER more than 50 of controlgroup patients (611 out of 913) achieved PASI 60 after fourto eight weeks treatment with phototherapy Although theproportion of control group patients who achieved PASI 75was not specifically assessed this result indicates that thephototherapy was effective
The additional therapeutic effects of the CHM bath couldbe attributable to three main aspects (1) the thermotherapyeffects (2) the effects of a water bath and (3) the specifictherapeutic effects of the CHMs used in the baths Each ofthese aspects is discussed below
10 Evidence-Based Complementary and Alternative Medicine
421 Thermal Effects Hyperthermia is not a new conceptbut research interest into its application in the treatmentof psoriasis is relatively recent [28] Early utilization ofhyperthermia for psoriasis followed on from the ideas thatthe severity of psoriasis would reduce during warm summermonths and a benefit of hyperthermia had been shown forkilling cancer cells [29] Orenbergrsquos study in 1980 which usedultrasound induced heat to treat psoriasis showed a benefitfor psoriasis lesion remission [29] Later it was demonstratedthat hyperthermia induced by topical exothermic pads [30]infrared [31] ormicrowave [32]was also effective for psoriasisplaques The advantage of using a hot water bath is that itis a simple inexpensive approach that can be used to treatrelatively large body areas [33]
422 Water Baths (Balneotherapy) Since hyperthermia hasproven beneficial for psoriasis lesions the simple modalityof using warm or hot water became popular Nowadaysvarious types of water bath therapy are considered safetreatments for dermatological conditions and are practicedin many countries Well-known balneotherapy sites includethe Dead Sea in Israel the Kangal hot spring in Turkeythe Kusatsu hot spring in Japan and the Blue Lagoonin Iceland In particular the Dead Sea is known to beeffective for the treatment of psoriasis [34] The mecha-nisms by which diseases respond to balneotherapy probablyincorporate chemical thermal and mechanical effects [35]It was suggested by a clinical study that simple repetitivewater bath hyperthermia was effective in the treatment ofpsoriasis by improving psoriatic lesions reducing edema andrelieving pruritus [28] In addition the water itself couldremove psoriatic scale [36] which may be beneficial for skinabsorption of phototherapy Previous studies have shownthat water bath markedly increased photosensitivity to UVB[37 38]
423 Specific Effects of the CHMs Used in the Baths Onlyone of the herbs used in one study Psoralea corylifolia (Bugu zhi) [5] is known to increase photosensitivity thereforethe overall effectiveness reported for the CHM baths doesnot appear to be due to pharmacological enhancement of theeffects of the phototherapy
In order to investigate the plausibility of the CHMsused in the baths having antipsoriatic actions experimentalreports on the actions of the main herbal ingredients wereexamined The most frequently used herbs in the includedstudies were Salvia miltiorrhiza root (Dan shen) [6 8 9 1213 16 23] Dictamnus dasycarpus bark (Bai xian pi) [6 79 10 12 13 16] Sophora flavescens root (Ku shen) [7 8 1011 14 16 17] and Kochia scoparia fruit (Di fu zi) [6 7 10ndash13 17] which were each used in seven studies Each of theseherbs has a history of topical application in the manage-ment of dermatological disorders [39] Also experimentalstudies have been conducted on extracts andor compoundsderived from these herbs with regard to actions relevant topsoriasis
Salvia miltiorrhiza (Dan shen) root and its constituenttanshinones and salvianolic acids have received considerable
research attention for the treatment and prevention of cardio-vascular disorders [40] These compounds have been shownto have free radical scavenging and anti-inflammatory effects[40ndash42] Also a number of its constituent tanshinones havebeen reported to have antiproliferative or proapoptotic effectsin cancer cell lines [43] More specifically an in vitro studyof mouse keratinocytes indicated that tanshinone IIA timeand dose dependently inhibited cell growth by inducingapoptosis via caspase cascade [44] Another possible mech-anism of action for tanshinone IIA in keratinocytes is viainhibiting the dimerization of the activator protein 1 (AP-1)transcription factor resulting in reduced interferon sensitivitywhich in turn could lead to a reduced inflammatory response[45]
Jiang et al 2008 [46] reported that an extract of theroot bark of Dictamnus dasycarpus (Bai xian pi) inhibitedhistamine release and reduced scratching behaviour in amouse anaphylaxismodel In vitro anti-inflammatory activityhas been reported for a root-bark extract [47] and for itsconstituents fraxinellone [48] and obacunone [49] Also itsessential oil and a number of compounds including dictam-nine preskimmianine and fraxinellone have demonstratedantitumour activity [47]
In the case of Sophora flavescens (Ku shen) root anextract inhibited histamine release both in vitro and in vivo[50 51] and other experimental studies have reported anti-inflammatory effects for its constituent alkaloids matrine[52 53] and oxymatrine [54] and for its total flavonoids [55]Its flavonoids and chalcones both demonstrate antioxidantactivity [56] Antitumour activities have been reported invitro for both matrine and oxymatrine as well as for anumber of flavonoids [57] of which trifolirhizin has shownboth anti-inflammatory and antiproliferative actions [58]and kurarinone showed inhibition of immune response [59]In human keratinocytes an extract inhibited proinflamma-tory chemokines [60] A Sophora flavescens extract showedantipruritic effects in a mouse model [61] and in a contactdermatitis mouse model the topical application of a Sophoraflavescens extract reduced hyperplasia edema spongiosisand infiltration of mononuclear cells [51]
A series of studies have reported that the 70 ethanolextract and its component momordin Ic from the driedfruits of Kochia scoparia (Di fu zi) had antinociceptive andanti-inflammatory [62] antiallergic [63] and antipruriticeffects [64] An orally administered extract was found to beactive in a rheumatoid arthritis model in rats [65]
Each of the above studies provides evidence that thesefour herbs have anti-inflammatory antiproliferative andorantipruritic activity all of which are of relevance to thetreatment of psoriasis However this evidence is indirect withonly a few studies testing topical application Consequentlywhether the additional therapeutic effects of the CHM bathsin the studies included in this review were produced by thespecific effects of the CHMs and the effect of the warm waterbaths or were just nonspecific effects of an additional inter-vention remains unclear Therefore future studies shouldinclude a control group that uses a colored warm water bathplus phototherapy to investigate the specific efficacy of theCHMs
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 7
Table 2 Chinese herbal medicine bath ingredients used in the thirteen studies
Author year(reference) Chinese herbal medicine bath formula
Cui et al 2008 [5] Galla Chinensis (Wu bei zi) Cortex Phellodendri Chinensis (Huang bo) Radix Angelica Sinensis (Dang gui)Rhizoma Curcumae Longae (Jiang huang) Fructus Psoraleae (Bu gu zhi) (no information of dosage)
Gu et al 2009 [6]Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 30 g Radix Angelica Sinensis (Dang gui) Spica Prunellae (Xiaku cao) 30 g Fructus Kochiae (Di fu zi) 30 g Cortex Dictamni (Bai xian pi) 30 g Cortex Phellodendri Chinensis(Huang bo) 30 g Folium Isatidis (Da qing ye) 30 g Rhizoma Smilacis Glabrae (Tu fu ling) 30 g
Lin et al 2010 [7]
Rhizoma Smilacis Glabrae (Tu fu ling) 30 g Fructus Kochiae (Di fu zi) 15 g Radix Angelica Sinensis (Dang gui) 20 gCortex Dictamni (Bai xian pi) 20 g Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 20 g Radix SophoraFlavescens (Ku shen) 15 g Fructus Cnidii (She chuang zi) 20 g Fructus Xanthii (Cang er zi) 15 g Radix Stemonae(Bai bu) 15 g Cortex Pseudolaricis (Tu jing pi) 10 g Fructus Tribuli (Ji li) 15 g Radix et Rhizoma Rhei (Da huang) 10 g
Liu et al 2005 [8]
Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) 30 g Fructus Cnidii (She chuang zi) 30 g Radix SophoraFlavescens (Ku shen) 30 g Pericarpium Zanthoxyli (Hua jiao) 30 gHerba cum Radice Patriniae (Bai jiang cao) 30 gRhizoma et Radix Polygoni Cuspidati (Hu zhang) 30 g Herba Portulacae (Ma chi xian) 30 g Radix et RhizomaSalviae Miltiorrhizae (Dan shen) 20 g Rhizoma Atractylodis (Cang zhu) 15 g
Liu et al 2004 [9]
Blood-heat syndrome Folium Isatidis (Da qing ye) Radix Rehmanniae (Di huang) Radix Paeoniae Rubra (Chishao) Rhizoma Smilacis Glabrae (Tu fu ling) Radix Arnebiae (Zi cao) Cortex Moutan (Mu dan pi) Blood-stasissyndrome Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) Semen Persicae (Tao ren) Flos Carthami (Honghua) Rhizoma Curcumae (E zhu) Caulis Spatholobi (Ji xue teng) Blood-dryness syndrome Radix Rehmanniae (Dihuang) Radix Angelica Sinensis (Dang gui) Cortex Dictamni (Bai xian pi) Herba Hedyotis (Bai hua she she cao)Rhizoma Smilacis Glabrae (Tu fu ling) (no information of dosage)
Shi et al 2011 [10]Caulis Impatientis (Tou gu cao) Cacumen Platycladi (Ce bai ye) Cortex Dictamni (Bai xian pi) Radix et RhizomaSalviae Miltiorrhizae (Dan shen) Radix Angelica Sinensis (Dang gui) Semen Persicae (Tao ren) Radix SophoraFlavescens (Ku shen) Fructus Kochiae (Di fu zi) Margarita (Zhen zhu) (no information of dosage)
Wang et al 2010 [11] Flos Chrysanthemi Indici (Ye ju hua) 240 g Pericarpium Zanthoxyli (Hua jiao) 120 g Rhizoma Smilacis Glabrae (Tufu ling) 150 g Radix Sophora Flavescens (Ku shen) 300 g Fructus Kochiae (Di fu zi) 300 g
Wang et al 2011 [12]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wang et al 2012 [13]
Radix Scutellariae (Huang qin) Herba cum Radice Patriniae (Bai jiang cao) Herba Taraxaci (Pu gong ying) RadixPaeoniae Rubra (Chi shao) Cortex Moutan (Mu dan pi) Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) RadixAsparagi (Tian dong) Radix Rehmanniae (Di huang) Cortex Dictamni (Bai xian pi) Fructus Kochiae (Di fu zi)Rhizoma Atractylodis (Cang zhu) (no information of dosage)
Wu et al 2011 [14]Radix Sophora Flavescens (Ku shen) Radix et Rhizoma Cynanchi Paniculati (Xu chang qing) Flos ChrysanthemiIndici (Ye ju hua) Herba Violae (Zi hua di ding) Flos Lonicerae Japonicae (Jin yin hua) Fructus Cnidii (She chuangzi) Glycyrrhiza uralensis root (no information of dosage)
Wu et al 2010 [15]Radix Rehmanniae (Di huang) 40 g Flos Lonicerae Japonicae (Jin yin hua) 30 g Herba Violae (Zi hua di ding) 30 gHerba Taraxaci (Pu gong ying) 30 g Zaocys (Wu shao she) 15 g Radix Scutellariae (Huang qin) 30 g RadixArnebiae seu Lithospermi (Zi cao) 30 g
Yan and Zhang2009 [16]
Radix Sophora Flavescens (Ku shen) 30 g Fructus Cnidii (She chuang zi) 30 g Radix Clematidis (Wei ling xian)30 g Cortex Dictamni (Bai xian pi) 30 g Radix et Rhizoma Salviae Miltiorrhizae (Dan shen) 20 g RhizomaAtractylodis (Cang zhu) 20 g Rhizoma Smilacis Glabrae (Tu fu ling) 20 g
Zhou and Huang2005 [17]
Rhizoma Coptidis (Huang lian) 10 g Cortex Phellodendri Chinensis (Huang bo) 20 g Radix Sophora Flavescens (Kushen) 20 g Radix Sanguisorbae (Di yu) 20 g Cortex Mahonia bealei (Tu Huang bo) 60 g Pericarpium Granati (Shiliu pi) 15 g Fructus Kochiae (Di fu zi) 15 g Herba Senecionis Scandens (Qian li guang) 30 g
Since PASI 60 was used in ten studies [5ndash10 12 14 15 17] asthe benchmark of ldquoremarkably effectiverdquo for TER calculationit was selected to be the outcome for pooling studies formeta-analysis in this review Three studies were excludedfrom meta-analysis because two of them used TER basedon a scoring system other than PASI for which there wasno evidence supporting it as an appropriate approach toevaluate therapeutic effect [11 16] and one was excluded dueto lack of a clear description of how ldquolesion improvementrdquowas measured [13]
314 Efficacy All thirteen studies reported that the com-bination of CHM bath and phototherapy had a superiorefficacy compared to phototherapy alone in terms of TERIn addition Cui et al 2008 reported that the administrationof CHM bath could significantly reduce NB-UVB averagedosage [5]
315 Followup Followup and relapse rate were reported intwo studies [6 9] In one the relapse rate of the treatmentgroup was 152 compared with 352 for control [9] In the
8 Evidence-Based Complementary and Alternative Medicine
other the rates were 108 for the treatment group and 303in the control In both cases a significant difference betweenthe two groups was reported (119875 lt 005) but a definition ofldquorelapserdquo was not provided in either study
316 Dropouts One study reported the number of dropoutsduring the treatment period without detailed reasons [6]All other studies reported that the number of patients whocompleted the trial was same as the number randomized
317 Adverse Events (AEs) Three studies did not reportany AEs [8 11 17] The most frequent AEs reported by theother ten studies were pruritus (7 studies) skin dryness (6studies) redness (6 studies) burning pain (3 studies) andskin pigmentation (3 studies) Three studies [5ndash7] reportedsignificantly higher rates of redness and pruritus in the UVBcontrol groups One of these three studies also reportedno significant difference between groups for skin dryness[7] The other seven studies that reported on AEs did notprovide details of between-group comparisons of AEs AllAEs reported in the ten studies could be resolved by reducingUV dosage or applying emollient No serious adverse event(SAE) was reported
32 Risks of Bias Assessment Risk of bias was assessed follow-ing the Cochrane Handbook 510 [23] and is summarized inFigure 2 Although all thirteen studies claimed ldquorandomizedrdquoonly six studies described the specific randomization meth-ods [5 6 10 12ndash14] Among them the random sequence gen-eration in four studies was appropriate [6 12ndash14] and assessedas ldquolow riskrdquo one study was assessed as ldquohigh riskrdquo due to theuse of patientsrsquo visiting order [15] one study used ldquoenvelopesrdquofor randomization which is not an adequate description tojudge bias therefore it was assessed as ldquounclearrdquo [5] Theother seven studies were considered ldquounclearrdquo due to thelack of information about randomization [7ndash11 16 17] Forallocation concealment method the study that used patientsrsquovisiting order for group allocation was judged ldquohigh riskrdquo[15] while the other twelve studies did not provide adequateinformation and therefore obtained judgments of ldquounclearrdquoFor all thirteen studies no information was provided forblinding of participants personnel or outcome assessors Infact blinding was impossible for participants and personnelin these studies due to the design One study reported thenumber of dropouts without reasons hence it was judged asldquounclearrdquo for incomplete outcome data [6] the other twelvestudies were assessed as ldquolow riskrdquo because they reported thatall participants finished the study A ldquolow riskrdquo assessmentwas given to all studies in terms of ldquoselective outcomereportingrdquo as the outcomes reported in the results sectionmatched the methods section However none had a protocolregistered
33 Meta-Analysis Two studies were not pooled in themeta-analysis since they used different forms of phototherapy com-pared to the others one combined UVA andUVB [9] and theother used UVA [17] Three studies were not included in themeta-analysis because they did not employPASI 60 [11 13 16]
Rand
om se
quen
ce g
ener
atio
n (s
elec
tion
bias
)
Cui et al 2008
Gu et al 2009 +
Lin et al 2010
Liu et al 2004
Liu et al 2005
Shi et al 2011
Wang et al 2010
Wang et al 2011 +
Wang et al 2012 +
Wu et al 2010 minus
Wu et al 2011 +
Yan and Zhang 2009
Zhou and Huang 2005 A
lloca
tion
conc
ealm
ent (
sele
ctio
n bi
as)
minus
Blin
ding
of p
artic
ipan
ts an
d pe
rson
nel (
perfo
rman
ce b
ias)
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
Blin
ding
of o
utco
me a
sses
smen
t (de
tect
ion
bias
)
Inco
mpl
ete o
utco
me d
ata (
attr
ition
bia
s)
++++++++++++
Sele
ctiv
e rep
ortin
g (r
epor
ting
bias
)
+++++++++++++
Figure 2 Risk of bias summary
As a result eight RCTs which used NB-UVB as phototherapyand PASI 60 for TER calculation were pooled in the meta-analysis These were divided into two groups based on studydesign as followsGroup 1 CHM Bath + NB-UVB versus NB-UVB Four studies[5 8 10 15] showed a higher TER (PASI 60) for CHM bathplus phototherapy compared with phototherapy alone (RR125 95 CI 115ndash136) without heterogeneity (1198682 = 0)(Figure 3) There was diversity in the herbs used in thesestudies but two studies had twomain herbs Ku shen andDanshen in common [8 10] The pooled result for these studiesfavoured the addition of the herbal bath (RR 119 95 CI108ndash132 1198682 = 0)Group 2 CHMBath +NB-UVB+Emollient versus NB-UVB+Emollient Four studies [6 7 12 14] showed a higher TER(PASI 60) for CHM bath plus phototherapy plus externallyapplied emollient cream compared with phototherapy plusthe same cream (RR 124 95 CI 115ndash135) The hetero-geneity was moderate (1198682 = 52) (Figure 3) Of the fourstudies three had main herbs in common [6 7 12] and ofthese Gu et al 2009 and Wang et al 2011 studies [6 12] were
Evidence-Based Complementary and Alternative Medicine 9
Study or subgroup CHM bath + NB-UVB NB-UVB Risk ratio Risk ratioEvents Total Events Total Weight MH fixed and 95 CI MH fixed and 95 CI
111 CHM bath + NB-UVB versus NB-UVB Cui et al 2008 60 62 41 57 99 135 [114 159]Liu et al 2005 38 40 33 40 76 115 [098 135]Shi et al 2011 144 170 118 168 274 121 [107 136]Wu et al 2010 30 40 20 39 47 146 [103 208]Subtotal (95 CI) 312 304 496 125 [115 136]Total events 272 212
112 CHM bath + NB-UVB + emollient versus NB-UVB + emollient
Gu et al 2009 84 89 81 96 180 112 [101 124] Lin et al 2010 89 95 63 90 149 134 [116 155] Wang et al 2011 43 50 36 50 83 119 [097 147] Wu et al 2011 59 75 37 65 92 138 [108 176] Subtotal (95 CI) 309 301 504 124 [115 135]
Total events 275 217
Total (95 CI) 621 605 100 125 [118 132]Total events 547 429
01 1 10NB-UVB CHM bath +
NB-UVB
Heterogeneity 1205942 = 286 df = 3 (P = 041) I2 = 0Test for overall effect Z = 517 (P lt 000001)
Heterogeneity 1205942 = 620 df = 3 (P = 010) I2 = 52Test for overall effect Z = 536 (P lt 000001)
Heterogeneity 1205942 = 914 df = 7 (P = 024) I2 = 23Test for overall effect Z = 744 (P lt 000001)Test for subgroup differences 1205942 = 001 df = 1 (P = 094) I2 = 0
Figure 3 Forest plot of clinical efficacy (PASI 60) PASI the psoriasis area and severity index PASI 60 the percentage of participants whoachieved PASI scores reduced by ge60 CHM Chinese herbal medicine NB-UVB narrowband ultraviolet
the most similar in that they shared Dan shen and Bai xianpi When the dissimilar study [12] was excluded there waslittle change in the result (RR 121 95 CI 112ndash132) andthe heterogeneity remained moderate (1198682 = 54) but whenthe pooling was limited to the two studies with the mostsimilar CHMs (Gu et al 2009 and Wang et al 2011) [6 12]the heterogeneity was removed (RR 114 95 CI 104ndash1261198682= 0)Overall the above eight studies [5ndash8 10 12 14 15] had
a higher TER (PASI 60) for CHM bath plus phototherapycompared with the phototherapy (RR 125 95CI 118ndash132)The heterogeneity was relatively low (1198682 = 23) (Figure 3)
4 Discussion
41 Efficacy of Phototherapy Combined with CHM Bath forPsoriasis All thirteen studies reported that CHM bath plusphototherapy had superior efficacy to phototherapy alone Inthe meta-analysis for group 1 (CHM bath + NB-UVB versusNB-UVB) all studies used the same primary outcome mea-sure did not use other supplementary treatment and therewas no heterogeneity so this result can be considered themost robust Nevertheless none of the studies employed anidentical herbal bath formulation although there were herbalingredients in common In contrast there was considerablevariation in study design in group 2 (CHMbath +NB-UVB+emollient versus NB-UVB + emollient) and this was reflectedin the heterogeneity found in the meta-analysis results Infact some co-intervention medications used in group 2 such
as PuLian ointment and Bing Huang Fu Le ointment havebeen reported to have therapeutic effects on psoriasis [26 27]Whether there was any interaction between the interventionsand co-interventions was unclear
42 Possible Mechanisms of Action for Phototherapy Com-bined with CHM Bath In psoriasis treatment phototherapymainly produces local immunosuppressive effects and anti-proliferative effects [1 4] The primary immunosuppressiveactions are reducing mobility of antigen-presenting Langer-hans cells and inhibiting T lymphocyte activation [1 4] Inaddition phototherapy inhibits epidermal hyperproliferationby interactions with keratinocyte DNA [1 4] It has beenreported thatmore than 50of patients treated by photother-apy achieved at least 75 improvement in PASI score (PASI75) after four to six weeks based on the recommendationsof the latest treatment guideline for psoriasis vulgaris [4]In this review for the ten studies [5ndash10 12 14 15 17] thatused PASI 60 for calculating TER more than 50 of controlgroup patients (611 out of 913) achieved PASI 60 after fourto eight weeks treatment with phototherapy Although theproportion of control group patients who achieved PASI 75was not specifically assessed this result indicates that thephototherapy was effective
The additional therapeutic effects of the CHM bath couldbe attributable to three main aspects (1) the thermotherapyeffects (2) the effects of a water bath and (3) the specifictherapeutic effects of the CHMs used in the baths Each ofthese aspects is discussed below
10 Evidence-Based Complementary and Alternative Medicine
421 Thermal Effects Hyperthermia is not a new conceptbut research interest into its application in the treatmentof psoriasis is relatively recent [28] Early utilization ofhyperthermia for psoriasis followed on from the ideas thatthe severity of psoriasis would reduce during warm summermonths and a benefit of hyperthermia had been shown forkilling cancer cells [29] Orenbergrsquos study in 1980 which usedultrasound induced heat to treat psoriasis showed a benefitfor psoriasis lesion remission [29] Later it was demonstratedthat hyperthermia induced by topical exothermic pads [30]infrared [31] ormicrowave [32]was also effective for psoriasisplaques The advantage of using a hot water bath is that itis a simple inexpensive approach that can be used to treatrelatively large body areas [33]
422 Water Baths (Balneotherapy) Since hyperthermia hasproven beneficial for psoriasis lesions the simple modalityof using warm or hot water became popular Nowadaysvarious types of water bath therapy are considered safetreatments for dermatological conditions and are practicedin many countries Well-known balneotherapy sites includethe Dead Sea in Israel the Kangal hot spring in Turkeythe Kusatsu hot spring in Japan and the Blue Lagoonin Iceland In particular the Dead Sea is known to beeffective for the treatment of psoriasis [34] The mecha-nisms by which diseases respond to balneotherapy probablyincorporate chemical thermal and mechanical effects [35]It was suggested by a clinical study that simple repetitivewater bath hyperthermia was effective in the treatment ofpsoriasis by improving psoriatic lesions reducing edema andrelieving pruritus [28] In addition the water itself couldremove psoriatic scale [36] which may be beneficial for skinabsorption of phototherapy Previous studies have shownthat water bath markedly increased photosensitivity to UVB[37 38]
423 Specific Effects of the CHMs Used in the Baths Onlyone of the herbs used in one study Psoralea corylifolia (Bugu zhi) [5] is known to increase photosensitivity thereforethe overall effectiveness reported for the CHM baths doesnot appear to be due to pharmacological enhancement of theeffects of the phototherapy
In order to investigate the plausibility of the CHMsused in the baths having antipsoriatic actions experimentalreports on the actions of the main herbal ingredients wereexamined The most frequently used herbs in the includedstudies were Salvia miltiorrhiza root (Dan shen) [6 8 9 1213 16 23] Dictamnus dasycarpus bark (Bai xian pi) [6 79 10 12 13 16] Sophora flavescens root (Ku shen) [7 8 1011 14 16 17] and Kochia scoparia fruit (Di fu zi) [6 7 10ndash13 17] which were each used in seven studies Each of theseherbs has a history of topical application in the manage-ment of dermatological disorders [39] Also experimentalstudies have been conducted on extracts andor compoundsderived from these herbs with regard to actions relevant topsoriasis
Salvia miltiorrhiza (Dan shen) root and its constituenttanshinones and salvianolic acids have received considerable
research attention for the treatment and prevention of cardio-vascular disorders [40] These compounds have been shownto have free radical scavenging and anti-inflammatory effects[40ndash42] Also a number of its constituent tanshinones havebeen reported to have antiproliferative or proapoptotic effectsin cancer cell lines [43] More specifically an in vitro studyof mouse keratinocytes indicated that tanshinone IIA timeand dose dependently inhibited cell growth by inducingapoptosis via caspase cascade [44] Another possible mech-anism of action for tanshinone IIA in keratinocytes is viainhibiting the dimerization of the activator protein 1 (AP-1)transcription factor resulting in reduced interferon sensitivitywhich in turn could lead to a reduced inflammatory response[45]
Jiang et al 2008 [46] reported that an extract of theroot bark of Dictamnus dasycarpus (Bai xian pi) inhibitedhistamine release and reduced scratching behaviour in amouse anaphylaxismodel In vitro anti-inflammatory activityhas been reported for a root-bark extract [47] and for itsconstituents fraxinellone [48] and obacunone [49] Also itsessential oil and a number of compounds including dictam-nine preskimmianine and fraxinellone have demonstratedantitumour activity [47]
In the case of Sophora flavescens (Ku shen) root anextract inhibited histamine release both in vitro and in vivo[50 51] and other experimental studies have reported anti-inflammatory effects for its constituent alkaloids matrine[52 53] and oxymatrine [54] and for its total flavonoids [55]Its flavonoids and chalcones both demonstrate antioxidantactivity [56] Antitumour activities have been reported invitro for both matrine and oxymatrine as well as for anumber of flavonoids [57] of which trifolirhizin has shownboth anti-inflammatory and antiproliferative actions [58]and kurarinone showed inhibition of immune response [59]In human keratinocytes an extract inhibited proinflamma-tory chemokines [60] A Sophora flavescens extract showedantipruritic effects in a mouse model [61] and in a contactdermatitis mouse model the topical application of a Sophoraflavescens extract reduced hyperplasia edema spongiosisand infiltration of mononuclear cells [51]
A series of studies have reported that the 70 ethanolextract and its component momordin Ic from the driedfruits of Kochia scoparia (Di fu zi) had antinociceptive andanti-inflammatory [62] antiallergic [63] and antipruriticeffects [64] An orally administered extract was found to beactive in a rheumatoid arthritis model in rats [65]
Each of the above studies provides evidence that thesefour herbs have anti-inflammatory antiproliferative andorantipruritic activity all of which are of relevance to thetreatment of psoriasis However this evidence is indirect withonly a few studies testing topical application Consequentlywhether the additional therapeutic effects of the CHM bathsin the studies included in this review were produced by thespecific effects of the CHMs and the effect of the warm waterbaths or were just nonspecific effects of an additional inter-vention remains unclear Therefore future studies shouldinclude a control group that uses a colored warm water bathplus phototherapy to investigate the specific efficacy of theCHMs
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
8 Evidence-Based Complementary and Alternative Medicine
other the rates were 108 for the treatment group and 303in the control In both cases a significant difference betweenthe two groups was reported (119875 lt 005) but a definition ofldquorelapserdquo was not provided in either study
316 Dropouts One study reported the number of dropoutsduring the treatment period without detailed reasons [6]All other studies reported that the number of patients whocompleted the trial was same as the number randomized
317 Adverse Events (AEs) Three studies did not reportany AEs [8 11 17] The most frequent AEs reported by theother ten studies were pruritus (7 studies) skin dryness (6studies) redness (6 studies) burning pain (3 studies) andskin pigmentation (3 studies) Three studies [5ndash7] reportedsignificantly higher rates of redness and pruritus in the UVBcontrol groups One of these three studies also reportedno significant difference between groups for skin dryness[7] The other seven studies that reported on AEs did notprovide details of between-group comparisons of AEs AllAEs reported in the ten studies could be resolved by reducingUV dosage or applying emollient No serious adverse event(SAE) was reported
32 Risks of Bias Assessment Risk of bias was assessed follow-ing the Cochrane Handbook 510 [23] and is summarized inFigure 2 Although all thirteen studies claimed ldquorandomizedrdquoonly six studies described the specific randomization meth-ods [5 6 10 12ndash14] Among them the random sequence gen-eration in four studies was appropriate [6 12ndash14] and assessedas ldquolow riskrdquo one study was assessed as ldquohigh riskrdquo due to theuse of patientsrsquo visiting order [15] one study used ldquoenvelopesrdquofor randomization which is not an adequate description tojudge bias therefore it was assessed as ldquounclearrdquo [5] Theother seven studies were considered ldquounclearrdquo due to thelack of information about randomization [7ndash11 16 17] Forallocation concealment method the study that used patientsrsquovisiting order for group allocation was judged ldquohigh riskrdquo[15] while the other twelve studies did not provide adequateinformation and therefore obtained judgments of ldquounclearrdquoFor all thirteen studies no information was provided forblinding of participants personnel or outcome assessors Infact blinding was impossible for participants and personnelin these studies due to the design One study reported thenumber of dropouts without reasons hence it was judged asldquounclearrdquo for incomplete outcome data [6] the other twelvestudies were assessed as ldquolow riskrdquo because they reported thatall participants finished the study A ldquolow riskrdquo assessmentwas given to all studies in terms of ldquoselective outcomereportingrdquo as the outcomes reported in the results sectionmatched the methods section However none had a protocolregistered
33 Meta-Analysis Two studies were not pooled in themeta-analysis since they used different forms of phototherapy com-pared to the others one combined UVA andUVB [9] and theother used UVA [17] Three studies were not included in themeta-analysis because they did not employPASI 60 [11 13 16]
Rand
om se
quen
ce g
ener
atio
n (s
elec
tion
bias
)
Cui et al 2008
Gu et al 2009 +
Lin et al 2010
Liu et al 2004
Liu et al 2005
Shi et al 2011
Wang et al 2010
Wang et al 2011 +
Wang et al 2012 +
Wu et al 2010 minus
Wu et al 2011 +
Yan and Zhang 2009
Zhou and Huang 2005 A
lloca
tion
conc
ealm
ent (
sele
ctio
n bi
as)
minus
Blin
ding
of p
artic
ipan
ts an
d pe
rson
nel (
perfo
rman
ce b
ias)
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
minus
Blin
ding
of o
utco
me a
sses
smen
t (de
tect
ion
bias
)
Inco
mpl
ete o
utco
me d
ata (
attr
ition
bia
s)
++++++++++++
Sele
ctiv
e rep
ortin
g (r
epor
ting
bias
)
+++++++++++++
Figure 2 Risk of bias summary
As a result eight RCTs which used NB-UVB as phototherapyand PASI 60 for TER calculation were pooled in the meta-analysis These were divided into two groups based on studydesign as followsGroup 1 CHM Bath + NB-UVB versus NB-UVB Four studies[5 8 10 15] showed a higher TER (PASI 60) for CHM bathplus phototherapy compared with phototherapy alone (RR125 95 CI 115ndash136) without heterogeneity (1198682 = 0)(Figure 3) There was diversity in the herbs used in thesestudies but two studies had twomain herbs Ku shen andDanshen in common [8 10] The pooled result for these studiesfavoured the addition of the herbal bath (RR 119 95 CI108ndash132 1198682 = 0)Group 2 CHMBath +NB-UVB+Emollient versus NB-UVB+Emollient Four studies [6 7 12 14] showed a higher TER(PASI 60) for CHM bath plus phototherapy plus externallyapplied emollient cream compared with phototherapy plusthe same cream (RR 124 95 CI 115ndash135) The hetero-geneity was moderate (1198682 = 52) (Figure 3) Of the fourstudies three had main herbs in common [6 7 12] and ofthese Gu et al 2009 and Wang et al 2011 studies [6 12] were
Evidence-Based Complementary and Alternative Medicine 9
Study or subgroup CHM bath + NB-UVB NB-UVB Risk ratio Risk ratioEvents Total Events Total Weight MH fixed and 95 CI MH fixed and 95 CI
111 CHM bath + NB-UVB versus NB-UVB Cui et al 2008 60 62 41 57 99 135 [114 159]Liu et al 2005 38 40 33 40 76 115 [098 135]Shi et al 2011 144 170 118 168 274 121 [107 136]Wu et al 2010 30 40 20 39 47 146 [103 208]Subtotal (95 CI) 312 304 496 125 [115 136]Total events 272 212
112 CHM bath + NB-UVB + emollient versus NB-UVB + emollient
Gu et al 2009 84 89 81 96 180 112 [101 124] Lin et al 2010 89 95 63 90 149 134 [116 155] Wang et al 2011 43 50 36 50 83 119 [097 147] Wu et al 2011 59 75 37 65 92 138 [108 176] Subtotal (95 CI) 309 301 504 124 [115 135]
Total events 275 217
Total (95 CI) 621 605 100 125 [118 132]Total events 547 429
01 1 10NB-UVB CHM bath +
NB-UVB
Heterogeneity 1205942 = 286 df = 3 (P = 041) I2 = 0Test for overall effect Z = 517 (P lt 000001)
Heterogeneity 1205942 = 620 df = 3 (P = 010) I2 = 52Test for overall effect Z = 536 (P lt 000001)
Heterogeneity 1205942 = 914 df = 7 (P = 024) I2 = 23Test for overall effect Z = 744 (P lt 000001)Test for subgroup differences 1205942 = 001 df = 1 (P = 094) I2 = 0
Figure 3 Forest plot of clinical efficacy (PASI 60) PASI the psoriasis area and severity index PASI 60 the percentage of participants whoachieved PASI scores reduced by ge60 CHM Chinese herbal medicine NB-UVB narrowband ultraviolet
the most similar in that they shared Dan shen and Bai xianpi When the dissimilar study [12] was excluded there waslittle change in the result (RR 121 95 CI 112ndash132) andthe heterogeneity remained moderate (1198682 = 54) but whenthe pooling was limited to the two studies with the mostsimilar CHMs (Gu et al 2009 and Wang et al 2011) [6 12]the heterogeneity was removed (RR 114 95 CI 104ndash1261198682= 0)Overall the above eight studies [5ndash8 10 12 14 15] had
a higher TER (PASI 60) for CHM bath plus phototherapycompared with the phototherapy (RR 125 95CI 118ndash132)The heterogeneity was relatively low (1198682 = 23) (Figure 3)
4 Discussion
41 Efficacy of Phototherapy Combined with CHM Bath forPsoriasis All thirteen studies reported that CHM bath plusphototherapy had superior efficacy to phototherapy alone Inthe meta-analysis for group 1 (CHM bath + NB-UVB versusNB-UVB) all studies used the same primary outcome mea-sure did not use other supplementary treatment and therewas no heterogeneity so this result can be considered themost robust Nevertheless none of the studies employed anidentical herbal bath formulation although there were herbalingredients in common In contrast there was considerablevariation in study design in group 2 (CHMbath +NB-UVB+emollient versus NB-UVB + emollient) and this was reflectedin the heterogeneity found in the meta-analysis results Infact some co-intervention medications used in group 2 such
as PuLian ointment and Bing Huang Fu Le ointment havebeen reported to have therapeutic effects on psoriasis [26 27]Whether there was any interaction between the interventionsand co-interventions was unclear
42 Possible Mechanisms of Action for Phototherapy Com-bined with CHM Bath In psoriasis treatment phototherapymainly produces local immunosuppressive effects and anti-proliferative effects [1 4] The primary immunosuppressiveactions are reducing mobility of antigen-presenting Langer-hans cells and inhibiting T lymphocyte activation [1 4] Inaddition phototherapy inhibits epidermal hyperproliferationby interactions with keratinocyte DNA [1 4] It has beenreported thatmore than 50of patients treated by photother-apy achieved at least 75 improvement in PASI score (PASI75) after four to six weeks based on the recommendationsof the latest treatment guideline for psoriasis vulgaris [4]In this review for the ten studies [5ndash10 12 14 15 17] thatused PASI 60 for calculating TER more than 50 of controlgroup patients (611 out of 913) achieved PASI 60 after fourto eight weeks treatment with phototherapy Although theproportion of control group patients who achieved PASI 75was not specifically assessed this result indicates that thephototherapy was effective
The additional therapeutic effects of the CHM bath couldbe attributable to three main aspects (1) the thermotherapyeffects (2) the effects of a water bath and (3) the specifictherapeutic effects of the CHMs used in the baths Each ofthese aspects is discussed below
10 Evidence-Based Complementary and Alternative Medicine
421 Thermal Effects Hyperthermia is not a new conceptbut research interest into its application in the treatmentof psoriasis is relatively recent [28] Early utilization ofhyperthermia for psoriasis followed on from the ideas thatthe severity of psoriasis would reduce during warm summermonths and a benefit of hyperthermia had been shown forkilling cancer cells [29] Orenbergrsquos study in 1980 which usedultrasound induced heat to treat psoriasis showed a benefitfor psoriasis lesion remission [29] Later it was demonstratedthat hyperthermia induced by topical exothermic pads [30]infrared [31] ormicrowave [32]was also effective for psoriasisplaques The advantage of using a hot water bath is that itis a simple inexpensive approach that can be used to treatrelatively large body areas [33]
422 Water Baths (Balneotherapy) Since hyperthermia hasproven beneficial for psoriasis lesions the simple modalityof using warm or hot water became popular Nowadaysvarious types of water bath therapy are considered safetreatments for dermatological conditions and are practicedin many countries Well-known balneotherapy sites includethe Dead Sea in Israel the Kangal hot spring in Turkeythe Kusatsu hot spring in Japan and the Blue Lagoonin Iceland In particular the Dead Sea is known to beeffective for the treatment of psoriasis [34] The mecha-nisms by which diseases respond to balneotherapy probablyincorporate chemical thermal and mechanical effects [35]It was suggested by a clinical study that simple repetitivewater bath hyperthermia was effective in the treatment ofpsoriasis by improving psoriatic lesions reducing edema andrelieving pruritus [28] In addition the water itself couldremove psoriatic scale [36] which may be beneficial for skinabsorption of phototherapy Previous studies have shownthat water bath markedly increased photosensitivity to UVB[37 38]
423 Specific Effects of the CHMs Used in the Baths Onlyone of the herbs used in one study Psoralea corylifolia (Bugu zhi) [5] is known to increase photosensitivity thereforethe overall effectiveness reported for the CHM baths doesnot appear to be due to pharmacological enhancement of theeffects of the phototherapy
In order to investigate the plausibility of the CHMsused in the baths having antipsoriatic actions experimentalreports on the actions of the main herbal ingredients wereexamined The most frequently used herbs in the includedstudies were Salvia miltiorrhiza root (Dan shen) [6 8 9 1213 16 23] Dictamnus dasycarpus bark (Bai xian pi) [6 79 10 12 13 16] Sophora flavescens root (Ku shen) [7 8 1011 14 16 17] and Kochia scoparia fruit (Di fu zi) [6 7 10ndash13 17] which were each used in seven studies Each of theseherbs has a history of topical application in the manage-ment of dermatological disorders [39] Also experimentalstudies have been conducted on extracts andor compoundsderived from these herbs with regard to actions relevant topsoriasis
Salvia miltiorrhiza (Dan shen) root and its constituenttanshinones and salvianolic acids have received considerable
research attention for the treatment and prevention of cardio-vascular disorders [40] These compounds have been shownto have free radical scavenging and anti-inflammatory effects[40ndash42] Also a number of its constituent tanshinones havebeen reported to have antiproliferative or proapoptotic effectsin cancer cell lines [43] More specifically an in vitro studyof mouse keratinocytes indicated that tanshinone IIA timeand dose dependently inhibited cell growth by inducingapoptosis via caspase cascade [44] Another possible mech-anism of action for tanshinone IIA in keratinocytes is viainhibiting the dimerization of the activator protein 1 (AP-1)transcription factor resulting in reduced interferon sensitivitywhich in turn could lead to a reduced inflammatory response[45]
Jiang et al 2008 [46] reported that an extract of theroot bark of Dictamnus dasycarpus (Bai xian pi) inhibitedhistamine release and reduced scratching behaviour in amouse anaphylaxismodel In vitro anti-inflammatory activityhas been reported for a root-bark extract [47] and for itsconstituents fraxinellone [48] and obacunone [49] Also itsessential oil and a number of compounds including dictam-nine preskimmianine and fraxinellone have demonstratedantitumour activity [47]
In the case of Sophora flavescens (Ku shen) root anextract inhibited histamine release both in vitro and in vivo[50 51] and other experimental studies have reported anti-inflammatory effects for its constituent alkaloids matrine[52 53] and oxymatrine [54] and for its total flavonoids [55]Its flavonoids and chalcones both demonstrate antioxidantactivity [56] Antitumour activities have been reported invitro for both matrine and oxymatrine as well as for anumber of flavonoids [57] of which trifolirhizin has shownboth anti-inflammatory and antiproliferative actions [58]and kurarinone showed inhibition of immune response [59]In human keratinocytes an extract inhibited proinflamma-tory chemokines [60] A Sophora flavescens extract showedantipruritic effects in a mouse model [61] and in a contactdermatitis mouse model the topical application of a Sophoraflavescens extract reduced hyperplasia edema spongiosisand infiltration of mononuclear cells [51]
A series of studies have reported that the 70 ethanolextract and its component momordin Ic from the driedfruits of Kochia scoparia (Di fu zi) had antinociceptive andanti-inflammatory [62] antiallergic [63] and antipruriticeffects [64] An orally administered extract was found to beactive in a rheumatoid arthritis model in rats [65]
Each of the above studies provides evidence that thesefour herbs have anti-inflammatory antiproliferative andorantipruritic activity all of which are of relevance to thetreatment of psoriasis However this evidence is indirect withonly a few studies testing topical application Consequentlywhether the additional therapeutic effects of the CHM bathsin the studies included in this review were produced by thespecific effects of the CHMs and the effect of the warm waterbaths or were just nonspecific effects of an additional inter-vention remains unclear Therefore future studies shouldinclude a control group that uses a colored warm water bathplus phototherapy to investigate the specific efficacy of theCHMs
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 9
Study or subgroup CHM bath + NB-UVB NB-UVB Risk ratio Risk ratioEvents Total Events Total Weight MH fixed and 95 CI MH fixed and 95 CI
111 CHM bath + NB-UVB versus NB-UVB Cui et al 2008 60 62 41 57 99 135 [114 159]Liu et al 2005 38 40 33 40 76 115 [098 135]Shi et al 2011 144 170 118 168 274 121 [107 136]Wu et al 2010 30 40 20 39 47 146 [103 208]Subtotal (95 CI) 312 304 496 125 [115 136]Total events 272 212
112 CHM bath + NB-UVB + emollient versus NB-UVB + emollient
Gu et al 2009 84 89 81 96 180 112 [101 124] Lin et al 2010 89 95 63 90 149 134 [116 155] Wang et al 2011 43 50 36 50 83 119 [097 147] Wu et al 2011 59 75 37 65 92 138 [108 176] Subtotal (95 CI) 309 301 504 124 [115 135]
Total events 275 217
Total (95 CI) 621 605 100 125 [118 132]Total events 547 429
01 1 10NB-UVB CHM bath +
NB-UVB
Heterogeneity 1205942 = 286 df = 3 (P = 041) I2 = 0Test for overall effect Z = 517 (P lt 000001)
Heterogeneity 1205942 = 620 df = 3 (P = 010) I2 = 52Test for overall effect Z = 536 (P lt 000001)
Heterogeneity 1205942 = 914 df = 7 (P = 024) I2 = 23Test for overall effect Z = 744 (P lt 000001)Test for subgroup differences 1205942 = 001 df = 1 (P = 094) I2 = 0
Figure 3 Forest plot of clinical efficacy (PASI 60) PASI the psoriasis area and severity index PASI 60 the percentage of participants whoachieved PASI scores reduced by ge60 CHM Chinese herbal medicine NB-UVB narrowband ultraviolet
the most similar in that they shared Dan shen and Bai xianpi When the dissimilar study [12] was excluded there waslittle change in the result (RR 121 95 CI 112ndash132) andthe heterogeneity remained moderate (1198682 = 54) but whenthe pooling was limited to the two studies with the mostsimilar CHMs (Gu et al 2009 and Wang et al 2011) [6 12]the heterogeneity was removed (RR 114 95 CI 104ndash1261198682= 0)Overall the above eight studies [5ndash8 10 12 14 15] had
a higher TER (PASI 60) for CHM bath plus phototherapycompared with the phototherapy (RR 125 95CI 118ndash132)The heterogeneity was relatively low (1198682 = 23) (Figure 3)
4 Discussion
41 Efficacy of Phototherapy Combined with CHM Bath forPsoriasis All thirteen studies reported that CHM bath plusphototherapy had superior efficacy to phototherapy alone Inthe meta-analysis for group 1 (CHM bath + NB-UVB versusNB-UVB) all studies used the same primary outcome mea-sure did not use other supplementary treatment and therewas no heterogeneity so this result can be considered themost robust Nevertheless none of the studies employed anidentical herbal bath formulation although there were herbalingredients in common In contrast there was considerablevariation in study design in group 2 (CHMbath +NB-UVB+emollient versus NB-UVB + emollient) and this was reflectedin the heterogeneity found in the meta-analysis results Infact some co-intervention medications used in group 2 such
as PuLian ointment and Bing Huang Fu Le ointment havebeen reported to have therapeutic effects on psoriasis [26 27]Whether there was any interaction between the interventionsand co-interventions was unclear
42 Possible Mechanisms of Action for Phototherapy Com-bined with CHM Bath In psoriasis treatment phototherapymainly produces local immunosuppressive effects and anti-proliferative effects [1 4] The primary immunosuppressiveactions are reducing mobility of antigen-presenting Langer-hans cells and inhibiting T lymphocyte activation [1 4] Inaddition phototherapy inhibits epidermal hyperproliferationby interactions with keratinocyte DNA [1 4] It has beenreported thatmore than 50of patients treated by photother-apy achieved at least 75 improvement in PASI score (PASI75) after four to six weeks based on the recommendationsof the latest treatment guideline for psoriasis vulgaris [4]In this review for the ten studies [5ndash10 12 14 15 17] thatused PASI 60 for calculating TER more than 50 of controlgroup patients (611 out of 913) achieved PASI 60 after fourto eight weeks treatment with phototherapy Although theproportion of control group patients who achieved PASI 75was not specifically assessed this result indicates that thephototherapy was effective
The additional therapeutic effects of the CHM bath couldbe attributable to three main aspects (1) the thermotherapyeffects (2) the effects of a water bath and (3) the specifictherapeutic effects of the CHMs used in the baths Each ofthese aspects is discussed below
10 Evidence-Based Complementary and Alternative Medicine
421 Thermal Effects Hyperthermia is not a new conceptbut research interest into its application in the treatmentof psoriasis is relatively recent [28] Early utilization ofhyperthermia for psoriasis followed on from the ideas thatthe severity of psoriasis would reduce during warm summermonths and a benefit of hyperthermia had been shown forkilling cancer cells [29] Orenbergrsquos study in 1980 which usedultrasound induced heat to treat psoriasis showed a benefitfor psoriasis lesion remission [29] Later it was demonstratedthat hyperthermia induced by topical exothermic pads [30]infrared [31] ormicrowave [32]was also effective for psoriasisplaques The advantage of using a hot water bath is that itis a simple inexpensive approach that can be used to treatrelatively large body areas [33]
422 Water Baths (Balneotherapy) Since hyperthermia hasproven beneficial for psoriasis lesions the simple modalityof using warm or hot water became popular Nowadaysvarious types of water bath therapy are considered safetreatments for dermatological conditions and are practicedin many countries Well-known balneotherapy sites includethe Dead Sea in Israel the Kangal hot spring in Turkeythe Kusatsu hot spring in Japan and the Blue Lagoonin Iceland In particular the Dead Sea is known to beeffective for the treatment of psoriasis [34] The mecha-nisms by which diseases respond to balneotherapy probablyincorporate chemical thermal and mechanical effects [35]It was suggested by a clinical study that simple repetitivewater bath hyperthermia was effective in the treatment ofpsoriasis by improving psoriatic lesions reducing edema andrelieving pruritus [28] In addition the water itself couldremove psoriatic scale [36] which may be beneficial for skinabsorption of phototherapy Previous studies have shownthat water bath markedly increased photosensitivity to UVB[37 38]
423 Specific Effects of the CHMs Used in the Baths Onlyone of the herbs used in one study Psoralea corylifolia (Bugu zhi) [5] is known to increase photosensitivity thereforethe overall effectiveness reported for the CHM baths doesnot appear to be due to pharmacological enhancement of theeffects of the phototherapy
In order to investigate the plausibility of the CHMsused in the baths having antipsoriatic actions experimentalreports on the actions of the main herbal ingredients wereexamined The most frequently used herbs in the includedstudies were Salvia miltiorrhiza root (Dan shen) [6 8 9 1213 16 23] Dictamnus dasycarpus bark (Bai xian pi) [6 79 10 12 13 16] Sophora flavescens root (Ku shen) [7 8 1011 14 16 17] and Kochia scoparia fruit (Di fu zi) [6 7 10ndash13 17] which were each used in seven studies Each of theseherbs has a history of topical application in the manage-ment of dermatological disorders [39] Also experimentalstudies have been conducted on extracts andor compoundsderived from these herbs with regard to actions relevant topsoriasis
Salvia miltiorrhiza (Dan shen) root and its constituenttanshinones and salvianolic acids have received considerable
research attention for the treatment and prevention of cardio-vascular disorders [40] These compounds have been shownto have free radical scavenging and anti-inflammatory effects[40ndash42] Also a number of its constituent tanshinones havebeen reported to have antiproliferative or proapoptotic effectsin cancer cell lines [43] More specifically an in vitro studyof mouse keratinocytes indicated that tanshinone IIA timeand dose dependently inhibited cell growth by inducingapoptosis via caspase cascade [44] Another possible mech-anism of action for tanshinone IIA in keratinocytes is viainhibiting the dimerization of the activator protein 1 (AP-1)transcription factor resulting in reduced interferon sensitivitywhich in turn could lead to a reduced inflammatory response[45]
Jiang et al 2008 [46] reported that an extract of theroot bark of Dictamnus dasycarpus (Bai xian pi) inhibitedhistamine release and reduced scratching behaviour in amouse anaphylaxismodel In vitro anti-inflammatory activityhas been reported for a root-bark extract [47] and for itsconstituents fraxinellone [48] and obacunone [49] Also itsessential oil and a number of compounds including dictam-nine preskimmianine and fraxinellone have demonstratedantitumour activity [47]
In the case of Sophora flavescens (Ku shen) root anextract inhibited histamine release both in vitro and in vivo[50 51] and other experimental studies have reported anti-inflammatory effects for its constituent alkaloids matrine[52 53] and oxymatrine [54] and for its total flavonoids [55]Its flavonoids and chalcones both demonstrate antioxidantactivity [56] Antitumour activities have been reported invitro for both matrine and oxymatrine as well as for anumber of flavonoids [57] of which trifolirhizin has shownboth anti-inflammatory and antiproliferative actions [58]and kurarinone showed inhibition of immune response [59]In human keratinocytes an extract inhibited proinflamma-tory chemokines [60] A Sophora flavescens extract showedantipruritic effects in a mouse model [61] and in a contactdermatitis mouse model the topical application of a Sophoraflavescens extract reduced hyperplasia edema spongiosisand infiltration of mononuclear cells [51]
A series of studies have reported that the 70 ethanolextract and its component momordin Ic from the driedfruits of Kochia scoparia (Di fu zi) had antinociceptive andanti-inflammatory [62] antiallergic [63] and antipruriticeffects [64] An orally administered extract was found to beactive in a rheumatoid arthritis model in rats [65]
Each of the above studies provides evidence that thesefour herbs have anti-inflammatory antiproliferative andorantipruritic activity all of which are of relevance to thetreatment of psoriasis However this evidence is indirect withonly a few studies testing topical application Consequentlywhether the additional therapeutic effects of the CHM bathsin the studies included in this review were produced by thespecific effects of the CHMs and the effect of the warm waterbaths or were just nonspecific effects of an additional inter-vention remains unclear Therefore future studies shouldinclude a control group that uses a colored warm water bathplus phototherapy to investigate the specific efficacy of theCHMs
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
10 Evidence-Based Complementary and Alternative Medicine
421 Thermal Effects Hyperthermia is not a new conceptbut research interest into its application in the treatmentof psoriasis is relatively recent [28] Early utilization ofhyperthermia for psoriasis followed on from the ideas thatthe severity of psoriasis would reduce during warm summermonths and a benefit of hyperthermia had been shown forkilling cancer cells [29] Orenbergrsquos study in 1980 which usedultrasound induced heat to treat psoriasis showed a benefitfor psoriasis lesion remission [29] Later it was demonstratedthat hyperthermia induced by topical exothermic pads [30]infrared [31] ormicrowave [32]was also effective for psoriasisplaques The advantage of using a hot water bath is that itis a simple inexpensive approach that can be used to treatrelatively large body areas [33]
422 Water Baths (Balneotherapy) Since hyperthermia hasproven beneficial for psoriasis lesions the simple modalityof using warm or hot water became popular Nowadaysvarious types of water bath therapy are considered safetreatments for dermatological conditions and are practicedin many countries Well-known balneotherapy sites includethe Dead Sea in Israel the Kangal hot spring in Turkeythe Kusatsu hot spring in Japan and the Blue Lagoonin Iceland In particular the Dead Sea is known to beeffective for the treatment of psoriasis [34] The mecha-nisms by which diseases respond to balneotherapy probablyincorporate chemical thermal and mechanical effects [35]It was suggested by a clinical study that simple repetitivewater bath hyperthermia was effective in the treatment ofpsoriasis by improving psoriatic lesions reducing edema andrelieving pruritus [28] In addition the water itself couldremove psoriatic scale [36] which may be beneficial for skinabsorption of phototherapy Previous studies have shownthat water bath markedly increased photosensitivity to UVB[37 38]
423 Specific Effects of the CHMs Used in the Baths Onlyone of the herbs used in one study Psoralea corylifolia (Bugu zhi) [5] is known to increase photosensitivity thereforethe overall effectiveness reported for the CHM baths doesnot appear to be due to pharmacological enhancement of theeffects of the phototherapy
In order to investigate the plausibility of the CHMsused in the baths having antipsoriatic actions experimentalreports on the actions of the main herbal ingredients wereexamined The most frequently used herbs in the includedstudies were Salvia miltiorrhiza root (Dan shen) [6 8 9 1213 16 23] Dictamnus dasycarpus bark (Bai xian pi) [6 79 10 12 13 16] Sophora flavescens root (Ku shen) [7 8 1011 14 16 17] and Kochia scoparia fruit (Di fu zi) [6 7 10ndash13 17] which were each used in seven studies Each of theseherbs has a history of topical application in the manage-ment of dermatological disorders [39] Also experimentalstudies have been conducted on extracts andor compoundsderived from these herbs with regard to actions relevant topsoriasis
Salvia miltiorrhiza (Dan shen) root and its constituenttanshinones and salvianolic acids have received considerable
research attention for the treatment and prevention of cardio-vascular disorders [40] These compounds have been shownto have free radical scavenging and anti-inflammatory effects[40ndash42] Also a number of its constituent tanshinones havebeen reported to have antiproliferative or proapoptotic effectsin cancer cell lines [43] More specifically an in vitro studyof mouse keratinocytes indicated that tanshinone IIA timeand dose dependently inhibited cell growth by inducingapoptosis via caspase cascade [44] Another possible mech-anism of action for tanshinone IIA in keratinocytes is viainhibiting the dimerization of the activator protein 1 (AP-1)transcription factor resulting in reduced interferon sensitivitywhich in turn could lead to a reduced inflammatory response[45]
Jiang et al 2008 [46] reported that an extract of theroot bark of Dictamnus dasycarpus (Bai xian pi) inhibitedhistamine release and reduced scratching behaviour in amouse anaphylaxismodel In vitro anti-inflammatory activityhas been reported for a root-bark extract [47] and for itsconstituents fraxinellone [48] and obacunone [49] Also itsessential oil and a number of compounds including dictam-nine preskimmianine and fraxinellone have demonstratedantitumour activity [47]
In the case of Sophora flavescens (Ku shen) root anextract inhibited histamine release both in vitro and in vivo[50 51] and other experimental studies have reported anti-inflammatory effects for its constituent alkaloids matrine[52 53] and oxymatrine [54] and for its total flavonoids [55]Its flavonoids and chalcones both demonstrate antioxidantactivity [56] Antitumour activities have been reported invitro for both matrine and oxymatrine as well as for anumber of flavonoids [57] of which trifolirhizin has shownboth anti-inflammatory and antiproliferative actions [58]and kurarinone showed inhibition of immune response [59]In human keratinocytes an extract inhibited proinflamma-tory chemokines [60] A Sophora flavescens extract showedantipruritic effects in a mouse model [61] and in a contactdermatitis mouse model the topical application of a Sophoraflavescens extract reduced hyperplasia edema spongiosisand infiltration of mononuclear cells [51]
A series of studies have reported that the 70 ethanolextract and its component momordin Ic from the driedfruits of Kochia scoparia (Di fu zi) had antinociceptive andanti-inflammatory [62] antiallergic [63] and antipruriticeffects [64] An orally administered extract was found to beactive in a rheumatoid arthritis model in rats [65]
Each of the above studies provides evidence that thesefour herbs have anti-inflammatory antiproliferative andorantipruritic activity all of which are of relevance to thetreatment of psoriasis However this evidence is indirect withonly a few studies testing topical application Consequentlywhether the additional therapeutic effects of the CHM bathsin the studies included in this review were produced by thespecific effects of the CHMs and the effect of the warm waterbaths or were just nonspecific effects of an additional inter-vention remains unclear Therefore future studies shouldinclude a control group that uses a colored warm water bathplus phototherapy to investigate the specific efficacy of theCHMs
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 11
43 Safety of Phototherapy Combined with CHM Bath forPsoriasis Erythema and pruritus were the most commonundesirable side effects of phototherapy reported by previousstudies [18ndash21] Consistently some mild AEs related tophototherapy were reported by the ten studies included inthis review Three of them [5ndash7] concluded that the AEs inthe treatment group were fewer than in the control groupHowever none of the studies evaluated whether long-termuse of a CHM bath could decrease the phototherapy dosageor frequency and consequently reduce the AEs caused byphototherapy
With regard to the frequently used CHMs some AEshave been found for their oral use Gastrointestinal reactionsand headache have been reported following the use of Salviamiltiorrhiza root (Dan shen) [40] and liver toxicity has beenassociated withDictamnus dasycarpus bark (Bai xian pi) [66]However no reports of AEs relating to the topical use ofthe four main herbs were located Furthermore no reportsof phototoxicity associated with the oral or topical use ofthe four main herbs could be found Therefore these CHMbaths appear to be safe for the management of psoriasis inthe dosages used and over the short term
44 Outcome Measures PASI 60 was suggested by ldquoCon-sensus of Diagnosis and Treatment of Psoriasis Vulgaris inIntegrative Medicinerdquo in China [24] as a suitable thresholdfor effectiveness Consequently most of the included studiesspecified the numbers of participants who achieved PASI 60However this approach is not consistent with the treatmentgoals accepted internationally (PASI 75 or 50) this limitscomparisons with international studies [25]
Moreover three studies were excluded from meta-analysis since they used nonstandard scoring systems [11 1316] The inconsistency in effective rate calculations used inpsoriasis studies was remarked upon in a recent review whichsuggested unifying the diagnostic and efficacy evaluationstandards for psoriasis [67] In addition since PASI score onlyfocuses on lesion severity other measurements such as BSAfor assessing lesion size should be included in studies in orderto provide a more complete assessment of overall severity
45 Implications for Practice CHMbath combinedwith pho-totherapy appears to be safe and may produce an additionalbenefit as an external treatment approach for psoriasis Anadvantage of this method is it does not involve oral ingestionof medication Its main limitations in clinical practice are theavailability of bath facilities and the time required to preparethe bath Based on the results of these studies the four mainherbs should be considered as key herbs when preparing asuitable bath formula
46 Implications for Research None of the studiesmentionedblinding of participants investigators or outcome assessorstherefore it could not be confirmed that the CHM bathswere responsible for the additional effects or whether thesewere nonspecific effects due to the addition of an extra inter-vention In future studies a double-blind placebo-controlleddesign should be conducted Followup is also important in
future studies to evaluate the long-term efficacy and safety ofthis therapy Intention-to-treat analysis is necessary to reducereporting bias
Although psoriasis itself is not a life-threatening condi-tion it has a significant impact on the sufferersrsquo quality oflife (QoL) [68 69] Quality of life is widely considered to bean important treatment goal [4 25] but none of the thirteenstudies investigated the effect on patientsrsquo QoL Future studiesshould incorporate a QoL assessment such as the DLQIquestionnaire
Psoriasis causes significant economic burden to patientsand society [1 4] Phototherapy is generally provided in anoutpatient department in China This requires patients totravel to the hospital duringworking hours two or three timesa weekTherefore the cost-effectiveness of treatments shouldbe assessed in future studies [4]
5 Conclusions
Chinese herbal medicine bath combined with phototherapyappears to show superior efficacy compared to phototherapyalone However there were methodological flaws in eachof the included studies which could have led to bias Thiscombined therapy appears to be safe in the short term butthere was no long-time monitoring of efficacy and safety ofthese CHM baths combined with phototherapy A number ofthe herbs used frequently in the baths have been evaluated inexperimental studies and found to have actions of relevanceto psoriasis treatment so further investigation of these andother herbal bath ingredients is warranted
Conflict of Interests
The authors declared no conflict of interests
Acknowledgments
The authors acknowledge the funding support providedby (1) Guangdong Provincial Academy of Chinese MedicalSciences China (2) International Science amp TechnologyCooperation Program of the Ministry of Science and Tech-nology of China and (3) the Financial Industry TechnologyResearch Development Program of Guangdong Province ofChina and support to the first author provided by the Schoolof Health Sciences RMIT University
References
[1] A Menter A Gottlieb S R Feldman et al ldquoGuidelines of carefor the management of psoriasis and psoriatic arthritis Section1 Overview of psoriasis and guidelines of care for the treatmentof psoriasis with biologicsrdquo Journal of the American Academy ofDermatology vol 58 no 5 pp 826ndash850 2008
[2] D Pathirana A D Ormerod P Saiag et al ldquoEuropean S3-guidelines on the systemic treatment of psoriasis vulgarisrdquo Jour-nal of the European Academy of Dermatology and Venereologyvol 23 supplement 2 pp 1ndash70 2009
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
12 Evidence-Based Complementary and Alternative Medicine
[3] M Augustin K Reich G Glaeske I Schaefer and M RadtkeldquoCo-morbidity and age-related prevalence of psoriasis anal-ysis of health insurance data in Germanyrdquo Acta Dermato-Venereologica vol 90 no 2 pp 147ndash151 2010
[4] ANastW-H Boehncke UMrowietz et al ldquoS3mdashguidelines onthe treatment of psoriasis vulgaris (English version) UpdaterdquoJournal of the German Society of Dermatology vol 10 no 2 ppS1ndashS95 2012
[5] B-N Cui Y-X Sun andW-L Liu ldquoClinical efficacy of narrowband ultraviolet bin combined with yuyin recipe in treatingpsoriasis vulgarisrdquo Chinese Journal of Integrated Traditional andWestern Medicin vol 28 no 4 pp 355ndash357 2008
[6] Y Gu H X Liu C H Zhang et al ldquoClinical observation oftraditional chinese medical herbs bath combined with narrow-band ultraviolet B for the treatment of psoriasis vulgarisrdquoChinese Journal of Dermatology amp Venereology no 4 pp 243ndash244 2009
[7] G S Lin H Y Wang D F Luo et al ldquoChinese herbalmedicine bath combined with NB-UVB for psorasis vulgarisrdquoActa Universitatis Medicinalis Anhui no 3 pp 404ndash406 2010
[8] H Q Liu M J Lei and G H Wang ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB for40 patients with psoriasis vulgarisrdquo New Journal of TraditionalChinese Medicine no 2 pp 53ndash54 2005
[9] X G Liu S P Song and C L Tang ldquoClinical observationof Chinese herbal medicine bath combined with phototherapyfor psoriasis vulgarisrdquo Liaoning Journal of Traditional ChineseMedicine no 12 p 1019 2004
[10] X L Shi Y M Pan H Y Ma and X F Yang ldquoTreatmentof psoriasis vulgaris by NB-UVB combined with traditionalChinese materia medica bath a clinical observationrdquo ChineseJournal of Laser Medicine and Surgery no 5 pp 314ndash317 2011
[11] J Wang CM Deng and J Li ldquoTherapeutic effect of traditionalChinese medicine bath combined with narrowband UVB onpsoriasisrdquoMedical Journal ofWest China no 12 pp 2304ndash23052010
[12] Z X Wang H J Wang Z H Yu et al ldquoClinical observationof Chinese herbal medicine bath combined with NB-UVB forpsoriasis vulgarisrdquo Journal of Henan University no 3 pp 226ndash227 2011
[13] Z X Wang H J Wang Q N Geng et al ldquoA clinical studyon psoriasis vulgaris by use of triple therapyrdquo China MedicalEngineering no 4 pp 29ndash31 2012
[14] B Wu X D Chen D Xia et al ldquoClinical observation ofChinese herbal medicine combined with NB-UVB for psoriasisvulgarisrdquo Chinese Journal of Dermatovenereology in IntegrativeTraditional and Western Medicine no 5 pp 304ndash305 2011
[15] L NWu L N Huang and R Z Xue ldquoClinical observation andnursing of psoriasis vulgaris treated with narrow-band UVBcombined with Chinese herb bathrdquo Journal of Diagnosis andTherapy on Dermato-Venereology no 3 pp 242ndash244 2010
[16] L X Yan and J Y Zhang ldquoThe nursing experience of Chineseherbal medicine bath combined with NB-UVB for psoriasisvulgarisrdquo Shaanxi Journal of Traditional Chinese Medicine no10 pp 1349ndash1350 2009
[17] M Zhou and G Y Huang ldquoClinical observation of ShufuPowder combined with UVA for psoriasisrdquo Liaoning Journal ofTraditional Chinese Medicine no 10 pp 44ndash45 2005
[18] P M Gordon B L Diffey J N S Matthews and P M Farr ldquoArandomized comparison of narrow-band TL-01 phototherapyand PUVA photochemotherapy for psoriasisrdquo Journal of the
American Academy of Dermatology vol 41 no 5 pp 728ndash7321999
[19] N Amornpinyokeit and P Asawanonda ldquo8-methoxypsoralencream plus targeted narrowband ultraviolet B for psoriasisrdquoPhotodermatology Photoimmunology and Photomedicine vol22 no 6 pp 285ndash289 2006
[20] E J Cooper R M Herd G C Priestley and J A AHunter ldquoA comparison of bathwater and oral delivery of8-methoxypsoralen in PUVA therapy for plaque psoriasisrdquoClinical and Experimental Dermatology vol 25 no 2 pp 111ndash114 2000
[21] P G Calzavara-Pinton B Ortel H Honigsmann C Zaneand G De Panfilis ldquoSafety and effectiveness of an aggressiveand individualized bath-PUVA regimen in the treatment ofpsoriasisrdquo Dermatology vol 189 no 3 pp 256ndash259 1994
[22] E Holzle H Honigsmann M Rocken K Ghoreschi andP Lehmann ldquoRecommendations for phototherapy and pho-tochemotherapyrdquo Journal of the German Society of Dermatologyvol 1 no 12 pp 985ndash997 2003
[23] J P T Higgins and S GreenCochrane Handbook For SystematicReviews of Interventions Version 5 1 0 [Updated March 2011]The Cochrane Collaboration 2011 httphandbookcochraneorg
[24] ldquoConsensus on integrative medicine diagnosis and treatment ofpsoriasis vulgaris (2009)rdquo Chinese Journal of Dermatovenereol-ogy in Integrative Traditional andWesternMedicine no 5 p 3282009
[25] U Mrowietz K Kragballe K Reich et al ldquoDefinition oftreatment goals for moderate to severe psoriasis a Europeanconsensusrdquo Archives of Dermatological Research vol 303 no 1pp 1ndash10 2011
[26] P Wang J Gao Dilinuer and X M Pu ldquoThe clinical obser-vation of the binhuangfule ointment for treating psoriasisrdquoChinese Journal of Dermatology amp Venereology no 12 pp 774ndash775 2006
[27] L X Zhang D Q Yang P H Song et al ldquoPu Lian ointmentin the treatment of psoriasisrdquo Journal of External Therapy ofTraditional Chinese Medicine no 5 pp 22ndash23 2000
[28] D R Boreham H C Gasmann and R E J Mitchel ldquoWaterbath hyperthermia is a simple therapy for psoriasis and alsostimulates skin tanning in response to sunlightrdquo InternationalJournal of Hyperthermia vol 11 no 6 pp 745ndash754 1995
[29] E K Orenberg D G Deneau and E M Farber ldquoResponseof chronic psoriatic plaques to localized heating induced byultrasoundrdquo Archives of Dermatology vol 116 no 8 pp 892ndash897 1980
[30] H Urabe K Nishitani and H Kohda ldquoHyperthermia in thetreatment of psoriasisrdquo Archives of Dermatology vol 117 no 12pp 770ndash774 1981
[31] W Westerhof A H Siddiqui R H Cormane and A ScholtenldquoInfrared hyperthermia and psoriasisrdquo Archives of Dermatolog-ical Research vol 279 no 3 pp 209ndash210 1987
[32] J Keddy-Grant S Garnis-Jones J Adam et al ldquoComplicationsof microwave hyperthermia treatment of psoriasisrdquo Journal ofthe American Academy of Dermatology vol 22 no 4 pp 651ndash653 1990
[33] E K Orenberg F R Noodleman J A Koperski D Poundsand E M Farber ldquoComparison of heat delivery systems forhyperthermia treatment of psoriasisrdquo International Journal ofHyperthermia vol 2 no 3 pp 231ndash241 1986
[34] H Matz E Orion and R Wolf ldquoBalneotherapy in dermatol-ogyrdquo Dermatologic Therapy vol 16 no 2 pp 132ndash140 2003
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Evidence-Based Complementary and Alternative Medicine 13
[35] A Nasermoaddeli and S Kagamimori ldquoBalneotherapy inmedicine a reviewrdquo Environmental Health and PreventiveMedicine vol 10 no 4 pp 171ndash179 2005
[36] H B Routh K R Bhowmik L C Parish and J A WitkowskildquoBalneology mineral water and spas in historical perspectiverdquoClinics in Dermatology vol 14 no 6 pp 551ndash554 1996
[37] J Boer A A Schothorst B Boom J Hermans and DSuurmond ldquoInfluence of water and salt solutions on UVB irra-diation of normal skin and psoriasisrdquoArchives of DermatologicalResearch vol 273 no 3-4 pp 247ndash259 1982
[38] T Gambichler and F Schropl ldquoChanges of minimal erythemadose after water and salt water bathsrdquo Photodermatology Pho-toimmunology and Photomedicine vol 14 no 3-4 pp 109ndash1111998
[39] X Li Chinese Materia Medica Combinations and ApplicationsDonica 2002
[40] L Zhou Z Zuo andM S S Chow ldquoDanshen an overview of itschemistry pharmacology pharmacokinetics and clinical userdquoJournal of Clinical Pharmacology vol 45 no 12 pp 1345ndash13592005
[41] J H-C Ho and C-Y Hong ldquoSalvianolic acids small com-pounds with multiple mechanisms for cardiovascular protec-tionrdquo Journal of Biomedical Science vol 18 no 1 article 30 2011
[42] X Wang S L Morris-Natschke and K-H Lee ldquoNew develop-ments in the chemistry and biology of the bioactive constituentsof TanshenrdquoMedicinal Research Reviews vol 27 no 1 pp 133ndash148 2007
[43] Y Zhang P Jiang M Ye S H Kim C Jiang and J Lu ldquoTan-shinones sources pharmacokinetics and anti-cancer activitiesrdquoInternational Journal of Molecular Sciences vol 13 no 10 pp13621ndash13666 2012
[44] F-L Li R Xu Q-C Zeng et al ldquoTanshinone IIA inhibitsgrowth of keratinocytes through cell cycle arrest and apoptosisunderlying treatment mechanism of psoriasisrdquo Evidence-basedComplementary and Alternative Medicine vol 2012 Article ID927658 14 pages 2012
[45] E Pedersen Z Wang A Stanley et al ldquoRAC1 in keratinocytesregulates crosstalk to immune cells by Arp23-dependent con-trol of STAT1rdquo Journal of Cell Science vol 125 Part 22 pp 5379ndash5390 2012
[46] S Jiang Y NakanoM A Rahman R Yatsuzuka and C KameildquoEffects of aDictamnus dasycarpus T extract on allergicmodelsinmicerdquo Bioscience Biotechnology and Biochemistry vol 72 no3 pp 660ndash665 2008
[47] X Gao P-H Zhao and J-F Hu ldquoChemical constituents ofplants from the genus Dictamnusrdquo Chemistry and Biodiversityvol 8 no 7 pp 1234ndash1244 2011
[48] J-H Kim Y-M Park J-S Shin et al ldquoFraxinellone inhibitslipopolysaccharide-induced inducible nitric oxide synthase andcyclooxygenase-2 expression by negatively regulating nuclearfactor-kappa B in RAW2647macrophages cellsrdquo Biological andPharmaceutical Bulletin vol 32 no 6 pp 1062ndash1068 2009
[49] K N Chidambara Murthy G K Jayaprakasha and B S PatilldquoApoptosismediated cytotoxicity of citrus obacunone in humanpancreatic cancer cellsrdquo Toxicology in Vitro vol 25 no 4 pp859ndash867 2011
[50] M H Hong J Y Lee H Jung et al ldquoSophora flavescens Aitoninhibits the production of pro-inflammatory cytokines throughinhibition of the NF 120581BI120581B signal pathway in human mast cellline (HMC-1)rdquo Toxicology in Vitro vol 23 no 2 pp 251ndash2582009
[51] H Kim M R Lee G S Lee W G An and S I Cho ldquoEffectof Sophora flavescens Aiton extract on degranulation of mastcells and contact dermatitis induced by dinitrofluorobenzene inmicerdquo Journal of Ethnopharmacology vol 142 no 1 pp 253ndash258 2012
[52] J-Y Liu J-H Hu Q-G Zhu F-Q Li J Wang and H-J Sun ldquoEffect of matrine on the expression of substance Preceptor and inflammatory cytokines production in human skinkeratinocytes and fibroblastsrdquo International Immunopharma-cology vol 7 no 6 pp 816ndash823 2007
[53] B Zhang Z-Y Liu Y-Y Li et al ldquoAntiinflammatory effects ofmatrine in LPS-induced acute lung injury in micerdquo EuropeanJournal of Pharmaceutical Sciences vol 44 no 5 pp 573ndash5792011
[54] P Zheng F-L Niu W-Z Liu Y Shi and L-G Lu ldquoAnti-inflammatory mechanism of oxymatrine in dextran sulfatesodium-induced colitis of ratsrdquoWorld Journal of Gastroenterol-ogy vol 11 no 31 pp 4912ndash4915 2005
[55] J H Jin J S Kim S S Kang K H Son H W Chang andH P Kim ldquoAnti-inflammatory and anti-arthritic activity oftotal flavonoids of the roots of Sophora flavescensrdquo Journal ofEthnopharmacology vol 127 no 3 pp 589ndash595 2010
[56] H A Jung D-M Jeong H Y Chung et al ldquoRe-evaluation ofthe antioxidant prenylated flavonoids from the roots of Sophoraflavescensrdquo Biological and Pharmaceutical Bulletin vol 31 no 5pp 908ndash915 2008
[57] M Sun H Cao L Sun et al ldquoAntitumor activities of kushenliterature reviewrdquo Evidence-Based Complementary and Alterna-tive Medicine vol 2012 Article ID 373219 11 pages 2012
[58] H ZhouH Lutterodt Z Cheng and L Yu ldquoAnti-inflammatoryand antiproliterative activities of trifolirhizin a flavonoid fromSophora flavescens rootsrdquo Journal of Agricultural and FoodChemistry vol 57 no 11 pp 4580ndash4585 2009
[59] B H Kim K M Na I Oh et al ldquoKurarinone regulatesimmune responses through regulation of the JAKSTAT andTCR-mediated signaling pathwaysrdquo Biochemical Pharmacologyvol 85 no 8 pp 1134ndash1144 2013
[60] S-I Jeong Y-E Lee and S I Jang ldquo(2S)-21015840-methox-ykurarinone from Sophora flavescens suppresses cutaneousT cell-attracting chemokineCCL27 expression induced byinterleukin-tumor necrosis factor-120572 via heme oxygenase-1 inhuman keratinocytesrdquo Journal of medicinal food vol 13 no 5pp 1116ndash1124 2010
[61] T Yamaguchi-Miyamoto T Kawasuji Y Kuraishi and HSuzuki ldquoAntipruritic effects of Sophora flavescens on acuteand chronic itch-related responses in micerdquo Biological andPharmaceutical Bulletin vol 26 no 5 pp 722ndash724 2003
[62] H Matsuda Y Dai Y Ido S Ko M Yoshikawa and M KuboldquoStudies on Kochiae Fructus III Antinociceptive and antiin-flammatory effects of 70 ethanol extract and its componentmomordin Ic from dried fruits of Kochia scoparia Lrdquo Biologicaland Pharmaceutical Bulletin vol 20 no 10 pp 1086ndash1091 1997
[63] HMatsuda YDai Y IdoM Yoshikawa andMKubo ldquoStudieson Kochiae Fructus IV Anti-allergic effects of 70 ethanolextract and its component momordin Ic from dried fruits ofKochia scoparia Lrdquo Biological and Pharmaceutical Bulletin vol20 no 11 pp 1165ndash1170 1997
[64] H Matsuda Y Dai Y Ido et al ldquoStudies on Kochiae FructusV Antipruritic effects of oleanolic acid glycosides and thestructure-requirementrdquo Biological and Pharmaceutical Bulletinvol 21 no 11 pp 1231ndash1233 1998
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
14 Evidence-Based Complementary and Alternative Medicine
[65] J Choi K-T Lee H-J Jung H-S Park and H-J Park ldquoAnti-rheumatoid arthritis effect of the Kochia scoparia fruits andactivity comparison of momordin Ic its prosapogenin andsapogeninrdquo Archives of Pharmacal Research vol 25 no 3 pp336ndash342 2002
[66] J S Jang E G Seo C Han et al ldquoFour cases of toxic liver injuryassociated with Dictamnus dasycarpusrdquo The Korean Journal ofHepatology vol 14 no 2 pp 206ndash212 2008
[67] N Li Y Q Li H Y Li W Guo and Y P Bai ldquoEfficacy ofexternally applied chinese herbal drugs in treating psoriasis asystematic reviewrdquo Chinese Journal of Integrative Medicine vol18 no 3 pp 222ndash229 2012
[68] G Krueger J Koo M Lebwohl A Menter R S Stern andT Rolstad ldquoThe impact of psoriasis on quality of life resultsof a 1998 National Psoriasis Foundation patient-membershipsurveyrdquo Archives of Dermatology vol 137 no 3 pp 280ndash2842001
[69] P A J Russo R Ilchef and A Cooper ldquoPsychiatric morbidityin psoriasis a reviewrdquo Australasian Journal of Dermatology vol45 no 3 pp 155ndash160 2004
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Submit your manuscripts athttpwwwhindawicom
Stem CellsInternational
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
MEDIATORSINFLAMMATION
of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Behavioural Neurology
EndocrinologyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Disease Markers
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
BioMed Research International
OncologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Oxidative Medicine and Cellular Longevity
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
PPAR Research
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
ObesityJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Computational and Mathematical Methods in Medicine
OphthalmologyJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Diabetes ResearchJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Research and TreatmentAIDS
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Gastroenterology Research and Practice
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Parkinsonrsquos Disease
Evidence-Based Complementary and Alternative Medicine
Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom
Recommended