Anais
Brasileiros
de
Dermatologia
www.anaisdedermatologia.org.br
INVESTIGATION
A
randomized
half-body,
double
blind,
controlled
trial
on
the
effects
of
a
pH-modified
moisturizer
vs.
standard
moisturizer
in
mild
to
moderate
atopic
dermatitis
夽,夽夽
Siew
Wen
Goh
a,f,
Adawiyah
Jamil
b,f,∗,
Nazarudin
Safian
c,
Norazirah
Md
Nor
a,f,
Norliza
Muhammad
d,
Nur
Liyana
Saharudin
eaDermatologyUnit,MedicalDepartment,UniversityKebangsaanMalaysiaMedicalCentre,KualaLumpur,Malaysia bDepartmentofMedicine,UniversityKebangsaanMalaysiaMedicalCenter,KualaLumpur,Malaysia
cDepartmentofCommunityHealth,FacultyofMedicine,UniversityKebangsaanMalaysiaMedicalCentre,KualaLumpur,Malaysia dDepartmentofPharmacology,FacultyofMedicine,UniversityKebangsaanMalaysia,KualaLumpur,Malaysia
eDepartmentofPharmacy,UniversityKebangsaanMalaysiaMedicalCentre,KualaLumpur,Malaysia
fDermatologyUnit,DepartmentofMedicine,UniversityKebangsaanMalaysiaMedicalCenter,KualaLumpur,Malaysia
Received30May2019;accepted25November2019
Availableonline21March2020
KEYWORDS Dermatitis,atopic; Eczema;
Emollients
Abstract
Background: HigherskinpHinatopicdermatitiscontributestoimpairedepidermalbarrier.A
moisturizercompatiblewithphysiologicalpHcouldimproveatopicdermatitis.
Objective: TodeterminetheeffectofaphysiologicallycompatiblepHmoisturizerinatopic dermatitis.
Methods: Arandomizedhalfbody,doubleblind,controlledtrialinvolvingpatientswith
sta-bleatopicdermatitiswasperformed.pH-modifiedmoisturizerandstandardmoisturizerwere
appliedtohalfbodyfor6weeks.
Results: Atotal of6(16.7%)males and30 (83.3%)femalesparticipated.SkinpHreductions
fromweek0,week2and6weresignificantattheforearms(5.315[0.98]to4.85[0.54]to5.04
[0.78],p=0.02)andabdomen(5.25 [1.01],4.82[0.64],5.01[0.59],p=0.00) butnotatthe
shins(5.01[0.80],4.76[0.49],4.85[0.79],p=0.09)withpH-modified moisturizer.
Transepi-dermalwaterloss(TEWL)attheforearmsdecreased(4.60[2.55]to3.70[3.10]to3.00[3.55],
p=0.00),abdomen(3.90[2.90]to2.40[3.45]to2.70[2.25],p=0.046).SCORADimprovedfrom
14.1±12.75to10.5±13.25to7±12.25,p=0.00. Instandardmoisturizergroup,pH
reduc-tionsweresignificantattheforearms(5.29[0.94]to4.84[0.55]to5.02[0.70],p=0.00)and
夽 Howtocitethisarticle: WenGS,JamilA,SafianN,MdNorM,MuhammadN,SaharudinNL.Arandomizedhalf-body,double blind, controlledtrialontheeffectsofapH-modifiedmoisturizervs.standardmoisturizerinmildtomoderateatopicdermatitis.AnBrasDermatol. 2020;95:320---5.
夽夽StudyconductedattheDermatologyUnit,DepartmentofMedicine,UniversityKebangsaanMalaysiaMedicalCenter,KualaLumpur, Malaysia.
∗Correspondingauthor.
E-mail:[email protected](A.Jamil). https://doi.org/10.1016/j.abd.2019.11.007
0365-0596/©2020SociedadeBrasileiradeDermatologia.PublishedbyElsevierEspa˜na,S.L.U.ThisisanopenaccessarticleundertheCC BYlicense(http://creativecommons.org/licenses/by/4.0/).
abdomen (5.25 [1.09], 4.91[0.63],5.12 [0.66],p=0.00). TEWL atthe forearmwere (4.80
[2.95],4.10[2.15],4.60[3.40],p=0.67),shins(3.80[1.40],3.50[2.35],4.00[2.50],p=0.91)
andabdomen(3.70[2.45],4.10[3.60],3.40[2.95],p=0.80).SCORADimprovedfrom14.2±9.1
to10.9±10.65to10.5±11,p=0.00.ReductioninpHwasobservedwithbothmoisturizerswhile
TEWLsignificantlyimprovedwithpH-modifiedmoisturizer.pH-modifiedmoisturizerresultedin
greaterpH,TEWLandSCORADimprovementshoweverthedifferenceswerenotsignificantfrom
standardmoisturizer.
Studylimitation: Skinhydrationwasnotevaluated.
Conclusion: Moisturizationisbeneficialforatopicdermatitis;useofphysiologicallycompatible
pHmoisturizerispromising.
©2020SociedadeBrasileira deDermatologia.PublishedbyElsevierEspa˜na,S.L.U.Thisisan
openaccessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).
Introduction
Atopic dermatitis (AD) is a chronically relapsing inflam-matory skin disease withincreasing prevalence, affecting 0.2---24.6% of children worldwide.1 The estimated
preva-lencein ourcountrywas12.6% withan increase of0.49% yearly.1 Pathophysiology of AD involves complex
interac-tionsbetweengeneticfactors,theimmunesystemandthe environment.ElevationofskinpHisanimportant patholog-icalcomponentthatcauseincreasedproteasesactivityand inhibitionoflipidlamellaesynthesis,leadingtobreakdown of the epidermal barrier.2 Normal adults and adolescents
have skin pH of 4---5.3 Patientwith AD hashigher pH
val-ues inlesional and nonlesional skin comparedto healthy population.3
PhysiologicacidicskinpHplaysanimportantrolein pre-servingintegrityoftheepidermalbarrier;ithasyettobe adequatelyappliedasthecoreconceptinADmanagement. Skin acidification in murine models improved epidermal integrity, transepidermal water loss (TEWL), accelerated barrierrecovery4andpreventedAD.2,5,6Itprevented
emer-gence of oxazolone-induced AD, reduced Th2-dominant inflammation,normalizedexpressionofantimicrobial pep-tides and inhibited generation of cytokines.5 Skin barrier
and permeability function in normal mice improved with increased activities of -glucocerebrosidase and sphin-gomyelinase, and reductionin serine protease dependent degradationofdesmogleins.4Applicationofthemurineskin
acidification concept in restoration of physiological skin acidityinADanditseffectondiseaseseveritystillrequires furtherinvestigation.
Our study aimed to determine the effect of pH 4.5 moisturizerinrestorationofepidermalbarrierinAD.A mois-turizerwithpHthatismorecompatiblewithphysiological pH could improvethe skin pH in AD and subsequently its diseaseseverity.
Methods
A randomized half-body, double-blind, controlled study comparing a pH-modified moisturizer with a standard commercial moisturizer was performed. Inclusion criteria werepatientsaged12---65yearsdiagnosedwithADaccording totheHanifin---RadjkaCriteria,7andstablemildto
moder-ateADfor1monthpriortorecruitment.Exclusioncriteria wererecurrentinfections,>1%bodysurfaceareawithskin
erosions, known allergy or irritation reaction to aqueous cream,glycerine,methylparabenorpropylparaben,change intreatmentregime4weeksbeforerecruitment,pregnancy andbreastfeeding.
Half body randomizationwas performed using sequen-tiallynumbered,opaque sealedenvelopes(SNOSE). Inves-tigators and patients were blinded throughout the study. Patientswere instructed toapply one moisturizer onone sideof thebodyfromtheneckbelowandonemoisturizer ontheothersidetwiceadayfor6weeks.Allothertopical andoraltreatmentsthepatientswereusingpriortostudy enrollmentexceptmoisturizerswerecontinued.
MeasurementsofskinpHandtransepidermalwaterloss (TEWL)wereperformedat baseline(week0), week2and week6at6pre-determinedsites,bilateralforearms,right and left side of abdomen and bilateral anterior shins. Patientsrestedforatleast20minat22◦Cinrelative humid-ityof55---60%. Measurements wereperformed at least 5h aftermoisturizerandothertopicaltherapyapplication.Skin pHwasassessedbyHannaInstrumentsH199181. Transepi-dermalwaterlosswasassessedbyTewameterTM300.Three readings were taken per assessment and an average was obtained. A modified objective SCORing Atopic Dermati-tis(SCORAD) wasusedtodetermine diseaseseverity. The A component was doubled in the calculation of the final score. The assessment of itch and sleeplessness in com-ponentC wasexcluded asit wasdifficult todifferentiate theseverityof itchoneachsideof thebodyand impossi-bletodetermine theeffectofsymptomsfromhalf ofthe body to accounts for sleeplessness. The modified objec-tiveSCORADwascalculatedas2(A/5)+7B/2.Scoreof<15 wasconsidered mild,15---40 wasmoderate, while>40 was severe.8Itchwasevaluatedusingavisualanalogscore(VAS)
of 0---10 with0 representing noitch, and 10 representing mostsevereitch.TheDermatologyLifeQualityIndex Ques-tionnaire(DLQI)9wereusedtodeterminethediseaseeffect
onthepatients’qualityoflife.SCORAD,itchscoreandDLQI weredeterminedatbaseline(week0),week2andatweek 6.
Thestandardcommercialmoisturizerusedwasaqueous creammanufacturedbyKCKPharmaceuticalIndustriesSdn Bhd.Theingredientsinclude9%emulsifyingwax,6%liquid paraffin,15%whitesoftparaffin,0.15%methylparabenand 0.08%propylparaben.ThecreamhaspHof7.32---7.58 mea-suredbyLAQUApH meterbyHORIBAScientific.ThepHof thismoisturizerwasmodifiedtoachievethedesiredpHof 4.5by addingcitric acid 5%. Citric acid waschosen asit
waseasilyavailable.Citricacidformsasmallcomponentof thenaturalmoisturizingfactorsandtopicalapplicationhas beenshowntobebeneficialinichthyiosis,increased epider-malthicknessandincreaseddermalglycosaminoglycan.10,11
ThepH-modifiedcream remainedstableover3 monthsat roomtemperaturewithoutchangesincolor,smell,texture, consistency and pH. Boththe standard commercial mois-turizer cream and pH-modified cream have similar color, smell, texture and consistency. The study was approved byResearch Ethics Committee,the National University of MalaysiaresearchcodeFF-2018-058.Fundingwasobtained fromtheFundamentalResearchGrant,NationalUniversity ofMalaysiawiththesameresearchcode.Sample sizewas calculatedwitheffectsizeof0.2andstandarddeviationof theoutcomeof0.18basedontheresultsofDanbyetal.12
Two-tailedalphalevelwassetat0.05,betalevel0.2.Using theformula(1/q1+1/q0)(Z˛+Zˇ)2/(E/S)2,thesamplesize
was36withconsiderationof20%dropoutrate.13SPSS
sta-tistical software was used for statistical analyses. Where thereweremorethan2variablescompared,p-valueswere obtained using Friedman test. Wilcoxon test was used to determine changes between baseline, week 2 and week 6.Mann---Whitneytestwasusedtoanalyzethedifferences betweenstandardmoisturizerandpH-modifiedmoisturizer groups;p-value<0.05wasconsideredsignificant.
Results
ThirtysixpatientswithADparticipatedinthestudy.Thirty patientswerefemaleswhile6weremales.Theageranged from12to64yearswhilethemedian agewas24.5(28.7) yearsold.Therewere20(55.6%)Malays,9(25%)Chinese,5 (13.9%)Indians and 2 (5.5%)of other ethnicities. Twenty-one (58.3%) patients had allergic rhinitis or sinusitis, 12 (33.3%)hadallergicconjunctivitisandfoodallergy respec-tively,and29(80.6%)hadpositiveallergytest.Thirty(83.3%) patients were on moisturizers and 31 (86.1%) on topical steroid application, 15 (41.7%) of them required antihis-tamine.Thetypesofmoisturizersusedbythepatientswere: aqueouscream13(36.1%),aqueouscreamwithglycerin12 (33.3%), paraffin 3 (8.3%), others 2 (5.6%) i.e. 1 oatmeal based and 1 urea based moisturizer while 6 (16.7%) not usinganymoisturizer.Baselinediseaseseverityassessments revealedmodifiedobjectiveSCORADmedianvalueof14.3 (10.7),bodysurfacearea(BSA)was1.0(1.5),itchscorewas 4(3)andDLQIwas7.5(5.75).Characteristicsofthestudy populationaresummarizedintable1.
pH-modifiedmoisturizer
SkinpHdecreasedfromweek0toweek6atallsites,greater reduction was observed at week 2. The values increased slightly fromweek 2 toweek 6 but remainedlower than baseline(Table2).ThepHreductionsfromweek0toweek 6weresignificant attheforearms5.315(0.98)atweek0, 4.85(0.54)atweek2,5.04(0.78)atweek6,p=0.024and abdomen5.25(1.01)atweek0,4.82(0.64)atweek2,5.01 (0.59)atweek6,p=0.000butnotattheshins5.01(0.80) at week 0,4.76 (0.49)at week 2, 4.85 (0.79)at week 6,
p=0.088. TEWL decreased fromweek 0 to week 6 at all sites.TEWLsignificantlydecreasedfrom4.60(2.55)atweek
Table1 Characteristicsofthestudypopulation.
Characteristics n(%)ormedian(IQR)
Age,years 24.5(28.7) Gender Male 6(16.7%) Female 30(83.3%) Ethnicity Malay 20(55.6%) Chinese 9(25%) Indian 5(13.9%) Others 2(5.5%) Co-morbidities Allergicrhinitis/sinusitis 21(58.3%) Bronchialasthma 9(25%) Urticaria/angioedema 11(30.5%) Allergicconjunctivitis 12(33.3%) Foodallergy 12(33.3%) Drugallergy 5(13.9%)
Positivepick/Patchtest/serumIgE 29(80.6%)
Treatment Moisturizer 30(83.3%) Topicalsteroids 31(86.1%) Systemicimmunosuppressant 0(0%) Antihistimine 15(41.7%) Typeofmoisturizer Aqueouscream 13(36.1%)
Aqueouscreamwithglycerine 12(33.3%)
Paraffin 3(8.3%)
Others 2(5.6%)
Nomoisturizer 6(16.7%)
Diseaseseverity
ModifiedobjectiveSCORAD 14.3(10.7)
BSA 1.0(1.5)
DLQI 7.5(5.75)
Itchscore 4(3)
0to3.70(3.10)atweek 2and3.00 (3.55)at week6with
p=0.00at theforearms(Table2). Attheabdomen, TEWL decreasedfrom3.90(2.90)atweek0to2.40(3.45)atweek 2butincreasedslightlyto2.70(2.25)atweek 6,p=0.05. The changesobserved overtheshins werenotsignificant, TEWLatweek0was3.70(2.30),3.50(2.25)atweek2and 3.50(2.85)atweek6,p=0.10.ThechangesinskinpHand TEWL atthepH modified moisturizerapplication sitesare presentedintable2.SCORADimprovedsignificantly,median SCORADwas14.1(12.75)atweek0,10.5(13.25)atweek2 and7(12.65)atweek6,p=0.00(Table3).
Standardmoisturizer
SimilarpatternofreductioninskinpHfromweek0toweek 6withgreaterreductionatweek2wasobservedatstandard moisturizer application sites (Table 2). The pH reduction wassignificantattheforearm,5.29(0.94)atweek0;4.84 (0.55) at week 2 and5.02 (0.70) at week 6, p=0.00 and the abdomen 5.25 (1.09) at week 0, 4.91(0.63) at week
Table2 pHandTEWLvaluesatweeks0,2and6atpH-modifiedmoisturizerandstandardmoisturizerapplicationsites.
Parameter Site Week pH-modifiedmoisturizer Standardmoisturizer p-Value
pH Forearm 0 5.32(0.98) 5.29(0.94) 0.90 2 4.85(0.54) 4.84(0.55) 6 5.04(0.78) 5.02(0.70)b Abdomen 0 5.25(1.01) 5.25(1.09) 0.74 2 4.82(0.64) 4.91(0.63) 6 5.01(0.59)a 5.12(0.66)b Shin 0 5.01(0.80) 4.98(0.91) 0.70 2 4.76(0.49) 4.79(0.50) 6 4.85(0.79) 4.93(0.82) TEWL Forearm 0 4.60(2.55) 4.80(2.95) 0.27 2 3.70(3.10) 4.10(2.15) 6 3.00(3.55)a 4.60(3.40) Abdomen 0 3.90(2.90) 3.70(2.45) 0.25 2 2.40(3.45) 4.10(3.60) 6 2.70(2.25)a 3.40(2.95) Shin 0 3.70(2.30) 3.80(1.40) 0.23 2 3.50(2.25) 3.50(2.35) 6 3.50(2.85) 4.00(2.50)
a p-Value<0.05comparingweek0toweek6inpH-modifiedmoisturizergroup. b p-Value<0.05comparingweek0toweek6instandardmoisturizergroup.
Table3 TheeffectofstandardmoisturizerversuspH-modifiedmoisturizerondiseaseseverity(SCORAD),DLQIanditchscore.
Parameters Week0 Week2 Week6 p-Value
SCORAD
pH-modifiedmoisturizer 14.1(12.75) 10.5(13.25) 7(12.65) 0.00
Standardmoisturizer 14.2(9.1) 10.9(10.65) 10.5(11) 0.00
DLQI 8.00(5.25) 5.00(7.00) 3.00(4.25) 0.00
Itchscore 4.00(3.00) 3.00(3.00) 3.00(3.25) 0.00
2, 5.12 (0.66) at week 6, p=0.00. There pH changes at the shin were notsignificant with4.98 (0.91) at week 0, 4.79(0.50)atweek2,and4.93(0.82)atweek6,p=0.432. TEWLattheforearmsandshinsshowednon-significantslight reductionsat week2 followedbyan incrementat week 6 (Table2).TEWLattheforearmwas4.80(2.95)atweek0, 4.10(2.15)atweek2,and4.60(3.40)atweek6,p=0.67. Attheshins,TEWLwas3.80(1.40)atweek0,3.50(2.35)at week2and4.00(2.50)atweek6,p=0.913.TEWLincreased transientlyandlaterdecreasedtobelowbaselinevalueson theabdomenmeasuring3.70(2.45)atweek0,4.10(3.60) at week2 and3.40(2.95) atweek 6,p=0.80. Resultsfor pHandTEWLatstandardmoisturizerapplicationssitesare presented in table 2. SCORAD improved significantly with
p=0.00,the medianvalue atweek 0was14.2(9.1), 10.9 (10.65)atweek2and10.5(11)atweek6(Table3).
pH-modifiedmoisturizervsstandardmoisturizer
GreaterpHreductionwasobservedatpH-modified moistur-izersitesat theabdomenandshin(Table2).TEWLvalues wereloweratpH-modifiedmoisturizersitesatforearmand abdomen(Table2).SCORADwereloweratthepH-modified moisturizersitesatweek2andweek6(Table3).However, therewerenostatisticallysignificantdifferencesinthepH,
TEWLandSCORADvaluesbetweenthestandardmoisturizer andpH-modifiedmoisturizersites.ImprovementinSCORAD wasmirroredbysignificantreductioninitchscoresandDLQI (Table3).
One patient developed ipsilateral erythema requiring topicalcorticosteroid mostlikelyduetoareactiontothe pH-modifiedmoisturizer.Twopatientsdevelopedmildflares which were symmetrical and bilateral. Other side effect reportedwashypertrichosis(n=2)overbothlegsupon com-pletionofthestudy.Anotherpatientreportedmildtingling sensation withpH modified moisturizer application which disappearedaftertwoweeks.
Discussion
The clinical andbiophysical effectsof moisturizers onAD skin are under-explored despite extensive use of various typesofmoisturizersinstandard ADmanagement.14,15 The
effectsofmineraloils,acommoningredientinmoisturizers ontheskin barrierinAD patientsarepoorlydocumented. Aqueouscreamwaschosenasthemoisturizerinthisstudy asitis the preferredmoisturizer inmost of ourpatients, cost-effectiveandis moreamendable topHmodification. Aqueouscream ispreferredbyourpatientsasitfeelsless greasy,animportantfactorthatfacilitatecomplianceinour
tropicalhotandhumidweather.Theaqueouscreamdidnot containsodiumlaurethsulfate(SLS),whichisthemostlikely agentresponsibleforadverseeffectsreportedwithaqueous cream.16,17,18AqueouscreamwithSLScausedreduced
stra-tumcorneumthicknesswithincreaseinTEWLafter4weeks of regular application.15,16 We observed improvements in
bothpH and TEWLwithaqueous cream (without SLS),pH values were significantly lower from baseline at 6 weeks while therewasnosignificant changes inTEWL. This sug-geststhattheuseofSLSratherthanaqueouscreamshould beprohibitedforleave-onorwash-offpurposesbutfurther confirmatoryevidenceisrequired.
OurresultsshowedthatskinpH,TEWLandAD severity improvedwithmoisturizerapplicationirrespectiveofthepH ofthemoisturizerused.Inclusionofmoisturizersin mana-gementofADhasbeenshowntoimproveddiseaseseverity, reducedflaresanddecreasedtheamountoftopical corticos-teroidrequirementcomparedwithnomoisturizer.15 These
effectswereobservedwithvarioustypesofmoisturizers.15
TherelationshipbetweenclinicalADimprovementwith bio-physicalparameters likepH, TEWLand hydration arestill unclear as these are not evaluated in most moisturizer studies.14 Reduction in clinical severity scores seemed to
beaccompaniedbyimprovementinskinhydration withno change in TEWL.14 Dataon effectof moisturizerson skin
pHis evenmorelacking. Theeffectof amoisturizer with pH 4.92 (Diprobase® cream) was compared with aqueous
cream (containing SLS) and another moisturizer with pH 7.13 (DoublebaseTM gel) in patients with quiescent AD.12
Skin pH and hydration increased while TEWL decreased transientlyfollowingasingleapplicationofallthree mois-turizers. pH increasedsignificantly with DoublebaseTM gel
andDiprobase® creamupon28daysofrepeateduse,there
were no changes in TEWL but hydration wasbetter with DoublebaseTMgel.ThepHofthemoisturizersdidnotseem
toaffect skin pH andTEWL differently. The differencein hydration maybe attributed to humectant component of DoublebaseTM gel as the other moisturizers contain only
occlusive agents. Occlusive dressings have been demon-strated to improve skin hydration, but caused increased pHandTEWL.19,20 Longterm useofocclusivemoisturizers
containingparaffinmayresultinthesameeffect.The sur-facepHchangesthatresultsfrommoisturizerapplicationis mostlikelyinadequatetoovercometheeffectsoftheskin’s intrinsicbufferingmechanisms.Inaddition,concomitantuse ofskincleansersandtopicalsteroidswhicharemore alka-lineinformulationmayhaveoverwhelmedtheeffectofthe moisturizer.
While pH changeswithboth moisturizerswere compa-rable, we observed significant TEWL improvement at pH-modified moisturizer sites which was not observed at standardmoisturizersites.TEWLreductionistypicallynot achievedby application of most moisturizers irrespective of its ingredients.12,14 TEWL reduction is seen with
topi-calpharmacologicalinterventionssuchascorticosteroidand calcineurininhibitor.21Thebenefitofphysiologically
compa-tiblepHmoisturizermaybeduetoitseffectonTEWLrather thanskinsurfacepH.AcidificationofADskininhibits activ-ityofpH-sensitiveserineproteasesthat isresponsible for accelerateddesquamation andincrease synthesis oflipids forformationoftheextracellularlamellarmatrix,2bothare
keycomponentsofthepermeabilitybarrierrepresentedby
TEWL.Evaluationofstratumcorneumcompoundsisneeded tofurtherinvestigatethisaspect.
Bothmoisturizerswerewelltolerated,mildandtransient adverseeffectswereobserved.Allpatientshavepreviously usedaqueouscreamwithoutexperiencingadverseeffects.
Limitationsofthisstudyincludetheabsenceofawashout periodofthepatients’moisturizerpriortoinitiationofthe studymoisturizer.BaselinepHwasobtainedatleast5hafter the last application of the patients’ routine moisturizer. However,themajorityof patientswereeithermoisturizer naïve,usingaqueouscream,oraqueouscreamin combina-tionwithglycerin.Inaddition,washoutwasnotperformed toavoid triggeringdiseaseflare.We didnotmeasureskin hydration,thusisunabletoshowtherelationshipbetween hydrationandpH.Thestatusofthestudyparticipants’ filag-grin deficiency wasnot determined; thiscould affect the interpretationofourresults.
Conclusion
Standard aqueous cream and pH-modified aqueous cream bothimprovedskinpH.Therewerenosignificantdifferences in pHand TEWLvaluesbetween thetwomoisturizers. pH reductionwasobservedwithbothmoisturizers.Therewas significantTEWLimprovementwithpH-modifiedmoisturizer wasnotobservedwithstandardmoisturizer.Applicationof bothmoisturizersresulted inimprovementofAD. Moistur-izer with physiological pH is useful as an adjunct in the treatmentofAD.
Financial
support
Fundamental research grant from National University of Malaysia,Malaysia.
Authors’
contributions
GohSiewWen:Statisticanalysis;approvalofthefinal ver-sion of the manuscript; conception and planning of the study;elaborationandwritingofthemanuscript;obtaining, analysis,andinterpretation ofthe data;effective partici-pationinresearchorientation;intellectualparticipationin thepropaedeuticand/ortherapeuticconductofthestudied cases;criticalreviewoftheliterature;criticalreviewofthe manuscript.
Adawiyah Jamil: Approval of the final version of the manuscript; conception andplanning of the study; elabo-ration and writing of the manuscript; obtaining, analysis, and interpretation of the data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; criticalreview of themanuscript.
NazarudinSafian:Statisticanalysis;approvalofthefinal versionofthemanuscript;conception andplanning ofthe study; obtaining,analysis,andinterpretation of thedata; effectiveparticipationinresearchorientation;intellectual participationin thepropaedeuticand/or therapeutic con-ductofthestudiedcases.
NorazirahMdNor:Statisticanalysis;approvalofthefinal versionofthemanuscript;conceptionandplanningof the study;elaborationandwritingofthemanuscript;obtaining, analysis,andinterpretation ofthedata; effective partici-pationinresearchorientation;intellectualparticipationin thepropaedeuticand/ortherapeuticconductofthestudied cases;criticalreviewofthemanuscript.
Norliza Muhammad: Approval of the final version of the manuscript; conception and planning of the study; elaborationandwritingofthemanuscript;obtaining, anal-ysis,andinterpretationofthedata;effectiveparticipation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases;criticalreviewofthemanuscript.
NurLiyanaSaharudin:Approvalofthefinalversionofthe manuscript;conceptionandplanningofthestudy; elabora-tionandwriting ofthemanuscript;effectiveparticipation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; critical review of themanuscript.
Conflicts
of
interest
Nonedeclared.
Acknowledgments
We thank Julianah Ramli and Nur Arifah Muhd Rafiee for coordinatingthepatients’visitsschedule.
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