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The impact of vitamin D supplementation as an adjuvant therapy on clinical outcomes in patients with severe atopic dermatitis: A randomized controlled trial



Vitamin D supplementation with standard treatment yielded positive clinical outcomes in mild and moderate atopic dermatitis; however, the potential benefit of vitamin D in severe cases remains unclear. This study aimed to evaluate the impact of vitamin D supplementation on response to standard treatment in pediatrics with severe atopic dermatitis. The patients were randomized to receive either vitamin D 3 1600 IU/day or placebo, plus baseline therapy of topical 1% hydrocortisone cream twice daily for 12 weeks. The primary endpoints were the change in mean Eczema Area and Severity Index (EASI) score at the end of the study and the mean percent change in EASI score from baseline to week 12. Eighty-six subjects completed the study. The treated group achieved a significant higher level of 25 hydroxy vitamin D (P < .001) compared to control group at week 12. The mean EASI score was significantly lower in the treatment group compared to placebo group (P = .035). The percent change in EASI score from baseline differed significantly between the supplementation (56.44 ± 29.33) and placebo (42.09 ± 19.22) groups after intervention (P = .039). Vitamin D supplementation could be an effective adjuvant treatment that improves the clinical outcomes in severe atopic dermatitis.
Pharmacol Res Perspect. 2020;e00679.    
 1 of 8
  Revised:1S eptember2020 
DOI: 10.1002/prp2.679
The impact of vitamin D supplementation as an adjuvant
therapy on clinical outcomes in patients with severe atopic
dermatitis: A randomized controlled trial
Noha O. Mansour1| Amal Ahmed Mohamed2| Maha Hussein3| Eman Eldemiry4|
Aliaa Daifalla5| Soha Hassanin6| Nourelhuda Nassar7| Doaa Ghaith8|
Eman Mohamed Salah9
This is an op en access arti cle under the ter ms of the Creative C ommons Attribution L icense, which pe rmits use, dis tribu tion and reprod uction in any med ium,
provide d the original wor k is properly cited.
© 2020 The Authors. Pharm acolog y Research & Perspe ctivespublishe dbyBritishPharmacologicalSocietyandAme ricanSociet yforPharmacol ogyand
Exper iment alTher apeut icsandJohnWil ey&SonsLtd.
Abbreviations:AD,Atopicde rmati tis;EA SI,Ec zemaAre aandSev erit yIndex;N HTMRI ,Natio nalHep atolog yandTropi calMed icineRe searc hInsti tute;V itD,vita minD.
1Pharmacy Practice Department, Faculty of
Pharma cy,Mansou raUnive rsit y,Mansour a,
2Biochemistr yDepa rtme nt,National
Hepatol ogyandTropicalMe dicineResearc h
Instit ute, Cairo, Eg ypt
3Depar tment of Dermatology a nd
Androl ogy,NationalResearchCe ntre,C airo,
4Faculty of Pharma cy, Fellow of Clinica l
Pharma colog y,CairoUni versit yHospitals,
5Depar tmentofDermatology,Vener ology,
6Biochemistry Department, Faculty
ofPharma cy,Moder nUniver sityfor
Technology and Information, Cairo, Egypt
7Clinical Pathology Department, Elsahel
8Clinical and Chemical Pathology
Depar tment ,Facult yofMedicine,Cairo
University,Giza ,Egypt
9Depar tment of Dermatology, An drolog y,
SexualM edicin eandSTDs,Facultyof
Medicine,Helw anUniversity,Cairo,Eg ypt
NohaO.Mansour,Pharm acyPractice
Depar tment ,Facult yofPharmacy,Mansoura
Vitamin D supplementation withs tandardt reatment yielded positive clinicalout-
comes in mild and moderate atopic dermatitis; however, the potential benefit of vi-
tamin D in severe cases remains unclear. This study aimed to evaluate the impact
of vitamin D supplementation on response to standard treatment in pediatrics with
severeatopicdermatitis.Thepatientswererandomizedto receiveeithervitaminD
twice daily for 12 weeks.Theprimaryendpointswerethechange in mean Eczema
AreaandSeverity Index(EASI)scoreattheend ofthestudyandthemeanpercent
change in EASI score frombaselinetoweek 12. Eighty-six subjectscompleted the
study. The treated group achieved a significant higher level of 25 hydroxy vitamin
D(P < .001)comparedtocontrolgroupatweek12.ThemeanEASIscorewassig-
nificantlylowerinthetreatmentgroup comparedtoplacebo group (P = .035). The
percentchangeinEASI score from baselinedifferedsignificantlybetween the sup-
(P =.039).VitaminDsupplementationcouldbeaneffectiveadjuvanttreatmentthat
improves the clinical outcomes in severe atopic dermatitis.
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disease with intermittent flares and debilitating effects on the
patient's qualit y of life. It is the most common skin disorder
inchildren,affecting approximately 15%to20% worldwide.1
atous plaques, and a defective epidermal barrier.2 The pathol-
ogy of AD is not entirely understood. It involves a complex
interplay of dysfunctions of immune response, genetic and
environmental factors.3 Currently, the conventional AD treat-
ments include immune modulatory agents, such as topical and/
or oral steroids and topical calcineurin inhibitors.4 The control
of patients with AD may be difficult to be achieved in some
patients; this suggests the presence of some other associated
factors. The findings obtained in both clinical and observa-
tional st udies reveal ed that the def iciency of vit amin D (Vi t
D) may be a fac tor to be conside red in the patho physiolog y
of AD.5
VitaminD3correlatewell withsynthesis of proteinsthat
are necessary for skin barrier function, these mechanisms
suggest a role of 1,25-dihydrox yvitamin D in modulating
AD severity.8M any researche s have investigate d differen ce
betwee n 25-dihydroxy vitamin D 25(O H) D levels in AD pe-
diatric patients and matched healthy control. A meta-analy-
sis of these s tudies found a m ean deference of −16 nmol/L
in pediatric AD patients compared to healthy control.6 There
is growing interest in the possible role of vit D deficiency in
the development of AD. The aggravation of AD in winter, es-
pecially in higher-latitude countries, where serum 25(OH)D
levels tend to be predominantly low in this season, has been
documented.7Inaddition ,ge neticpolym orphi smsoftheV itD
receptor have been identified as contributor to the develop-
ment of AD.8
A recent meta-analysis of interventional studies documented
that Vit Dsupplementation was linked to clinically relevant re-
duction in AD disease severit y both in adult and pediatric pa-
tients.6 The result s of this analysis must be interpreted with
caution particularly for children due to presence of multiple se-
rious limitations. First, the analysis included only one random-
izedcontrolled trial with very limitedsamplesize(n=20)inthe
age group from 1 to 18 years old.9 Another notable limitation is
that the AD patient population involved in this analysis consisted
mostly of mild and moderate AD with very few severe cases.9-
patients with severe AD who is limited yet important subset of
patient population.
To the best of our knowledge, this is the first study to inves-
tigatepotential benefits of Vit D supplementationin children
and adolescents with severe AD. Therefore, the primary aim of
in conjunction with standard treatment in severe AD.
2.1 | Study design
This study was a double blind, randomized, parallel, placebo con-
trolled clinical trialperformedattheNational HepatologyandTropical
MedicineResearchInstitute(NHTMRI),C airo,Egypt.Thestudywasap-
provedbyNHTMRIresearch ethicalcommittee.Theprotocolwasreg-
istered undertheidentifierNCT04468711.Thetrial was conducted in
accordance with Good Clinical Practice guidelines and the Declaration
ofH e ls ink i.Infor med co nse ntwasob t ai ned fr omt hepar ent sofa llc ase s.
2.2 | Subjects
Subjec ts enrolled in th e period from 6th Ju ne to 1th September,
2018. Inclusion criteria included: patients aged from 5 to 16 years
old, wit h a diagnosis of seve re AD accordi ng to Hanifin a nd Rajka
criteria, and the Eczema Area and Severity Index (EASI) score.12
Reasons for exclusion were serious skin disorder other than AD, tak-
ing systemic corticosteroids or anti-inflammatory medications, prior
vitamin D supplementation, receiving oral or topical antibiotics or
topical calcineurin inhibitors for at least 1 week prior to enrolment,
known gut absorption problem, presence of active skin infection at
baseline, and any known hepatic and/or renal disease.
Participants were allocated in 1:1 ratio to receive either vit amin
hydrocortisone cream twice daily for 3 months. We used a computer
random number generator to form the allocation list for the two com-
parison groups. Treatment allocation was concealed in sequentially
numbered, sealed, opaque envelopes from the patient s, and the out-
come assessors. The upper tolerable limit, defined as the highest level
of daily vitamin D3 intake that is safe in the general population, for
vitamin D3is3000IU/dinchildrenages4-8years,and4000IU/din
adolescents and adults.13 Data from clinical trials indicated that daily
supplem entation wi th this dose (1600/d) resul t in a clinicall y mean-
ingful AD severit y reduc tion.6 We assumed that this dose would be
safe and ef fective as well. Treatment assignment was masked from the
participants and the investigators. A diet ary history was obtained at
study entry with attention to potential sources of vitamin D, no signif-
icant group differences were prominent, and diets were stable during
the study. A single pediatric dermatologist performed all clinical eval-
uations at baseline and at the end of the study. At baseline patient
demographic data, laboratory analysis and clinical charac teristics were
2.3 | Serum 25(OH)D analysis
Two milliliters of blood were withdrawn from patients, allowed to
clot, and t hen centri fuged for 10 minute s and then kept f rozen at
−80°C at t he Centra l Labs of NHTM RI, Cairo , Egypt . Quantita tive
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determination of serum 25(OH) D, using commercial automated
ELISA, DRG International Inc, USA, according to manufacture in-
structions, was per formed.14 For the primar y analysis in this study,
we categori zed the serum 2 5(OH)D levels in to three clini cally rel-
Guidelines15whicharedeficient(<20ng/m L),in su fficie nt(21-29ng/
2.4 | Clinical assessment
Dermatological examination was performed to all the patients to as-
sessthe dermatitisseverityusing EASI score.16 It is a tool used to
evaluate the severityofeczemainfourdefinedbody regions(head
andneck,torso, arms,and legs), evaluating severity of fourclinical
tion)ona4-pointscaleandweight sthesefactorsbasedonthesize
involveme nt) to 6 (90%-100% involvement), a nd severity is m eas-
uredfrom0(clear)to3(severe)foreachsign.This providesarange
ofEASIscores from0 toa maximumscore of72.Thepotential se-
verity stratafor EASIis0almostclear,0.1-1clear,1.1-7mild,7.1-21
moderate, 21.1-50 severe, 50-72 very severe.12 Patients were clini-
cally evaluated every 4 weeks.
2.5 | Outcomes
2.5.1 | Primary endpoints
percentchangeinEA SIscorefrombaselinetoweek12.
2.5.2 | Secondary end points
Included propor tion of patients with a reduction from baseline to
week 12 of:
• ≥75%onEASIscore(E ASI75).
• ≥50%to<75%onEASIscore(EASI50).
<50%onEA SIscore(EASI<50).
2.6 | Statistical analysis
2.6.1 | Sample size
Consideringthe reduction in disease severity after VitD supple-
mentation reported by Sanchez-Armendariz et al,4 a sample size
of 84 patie nts was neede d to provide at leas t 80% power and a
two-sided type I errorless than 0.05. The sample size was calcu-
lated using the G*Power© software (Institutfür Experimentelle
Psychologie, Heinrich Heine Universität, Düsseldorf, Germany)
ve r sion 3 .1 .9.2.
StatisticalanalysiswasdoneusingIBMSPSS®St atisticsversion
as mean and standard deviation or median and range as appropri-
ate.Qualitativedata were expressed asfrequencyandpercentage.
Numeric data were tested for normalit y using Shapiro-Wilk test.
Data were found not normally distributed, so the nonparametric
tests were used. Comparison between two groups was done using
then post-Hoc test was used for pair-wise comparison based on
Kruskal-Wallisdistribution.Spearman-rho methodwasused totest
correlation between numerical variables. Wilcoxon-signed ranks
test(non-parametricpairedt-test)wasusedtocomparet woconsec-
utive measures of numerical variables.
3.1 | Participant characteristics
pleted the study and was included in the final analysis. At baseline,
both groups were comparable in demographic and clinical character-
istics. Patients’ demographics and clinical characteristics at baseline
3.2 | Serum 25 (OH) D concentrations
At base line , no statistic ally significan t difference was fo und between
both study arms regardingthe 25(OH)Dserum levels (P = .18). In
addition,distribution of 25(OH)Ddeficiency categories was similar
betwee n the two groups ( Table 1). Asso ciation betwee n baseline
25(OH) D levels andpotential deficiency risk factors wasexplored
in the whole study subjects. Inverse weak relationship was estab-
lishedbetweenbase line25(OH)Dserum levelsandthebodymass
index (BMI) (Spearman's rhor = −.4 4, P < .0 01). Weak association
was registered between baseline 25(OH)D serum levelsand initial
EASIscore(Spearman'srhor = .34, P =.001).
IntheV itDgroup,significant improvement in 25(OH) Dserum
levels was achieved postsupplementation compared to baseline
(P = <.001).Ninety-threepercent(n=4)oft hevit aminDg roupp op -
which toxicity has not been observed.17
Intheplaceb ogroup,levelof25(OH)Dwascomp arabletobase-
linelevel (P = .47) atthe end of the study.Atweek12,about 74%
of the placebo group subject s remained under levels of sufficiency
(<30ng/mL). Significantlyhigher levelwasrecordedbetweensup-
plementedgroup(36.11± 5.84) and placebo group (25.86±8.27)
attheendofthestudyregardingserum25(OH)Dlevels(P <.001).
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Table 2 showed that children supplemented with vit D fared bet-
ter than those allocated to pla cebo. At the end of the study, the mean
percentage change from baseline in EASI score was significantly
greater with vitamin D group (56.44%) than with placebo group
(42.09%) (P =.0 39) .Figure2depic tsth ed if fe re ntresponsec at egor y
attained at the end of the study. Figure 3 showed that comparable
propor tion in the vitamin D group and placebo group (52.2% vs
59.5%)experiencedmodestresponse totreatment(E ASI <50).On
contrast, different patterns were notable between supplemented
patients and those allocated to placebo group regarding percentage
FIGURE 1 CONSORTflowdiagram
showing the flow of patients throughout
the study
Assessed for eligibility (n=162)
Excluded (n=70)
Not meeting inclusion criteria (n=55)
Declined to participate (n= 15 )
Analysed (n= 44)
Drop out (n=3)
Lost to follow-up (n=2)
Non-compliance (n=1)
Allocated to Vit. D (n= 47)
Drop out (n=3)
Commencement of oral therapy
Consentwithdrawal (n
Allocated to placebo (n= 45)
Analysed (n=42)
Randomized (n= 92)
Treatment group Placebo group P value
Age(years)a 12(4.75) 11(5.5) .06
Gender;n(%) .13
Male 26(59.1) 18(42.8)
Female 18(40.9) 24(57.1)
BMI(kg /m2) 27.1(5.3) 26. 6(4.7)
BMIcategories .20
Normalweightn(%) 15(34.1) 12(28.6)
Overweightn(%) 13(29.5) 20(47.6)
Obesen(%) 16(36.4) 10(23.8)
Serum25(OH)Dlevels 22.8(6.2) 25.4(8.1) .18
Categories;n(%) .34
<20ng/mL(deficient) 15(3 4.1) 11(26.1)
20-29ng/mL(insufficient) 22(50) 19(45.2)
≥30ng/mL(suf ficient) 7(15.9) 12(28.6)
EASIscore 44.4(6.28) 46.4(5.4) .10
Calcium(mg/mL) 8.81(0.87) 8.7(1.03) .49
Parathyroidhormone(pg/mL) 32.4(5.7) 32.1(6.7) .88
TABLE 1 Baseline demographics and
clinical characteristics for both groups
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ofsupplementedpatientsachievedE ASI75vsonly7.1%ofpatients
in the placebo group.
Potential predictors that might cause superior clinical outcomes
among pat ients who achi eved EASI 75 were fu rther invest igated.
PercentchangeinEA SIscoresignificantlycorrelatedwiththemag-
nitude of change frombaselinein 25(OH)D (Spearman's rho r = .6,
P =.005). However,fair correlation was establishedbetween BMI
and % change i n EASI score (Sp earman's rho r = .54, P = .01) in
this subset of patients, which might indicate causality. To test the
hypothesis that different magnitude of change from baseline in
serum 25 (OH)D exist s among patie nts with bet ter respon se cate-
gory, the non-parametric Kruskal-Wallis test in combination with
pairwise post-hoc test was per formed to compare the respective
significant group; results presented in Figure 4. Pairwise compari-
sonsrevealedasignificantrelationshipbetweenbothEASI< 50 and
EASI 75(P < .001) and betweenEASI50 and E ASI 75 responders
(P <.001)groups.RegardingBMI,theresultsdidnotreachstatistical
significance when the different response categories were compared
regardingdistribution ofBMI among different respondents’ranks.
(P =.057).
centered around the use of topical steroid preparations and moistur-
with this initial conventional therapy might benefit from second-line
therapies, such as systemic and topical immunosuppressive medica-
tions.18Most ofthese therapieshavepotential adverseef fectsand
nearly all are off label for AD in children. The present study was de-
signed to test the hypothesis that vitamin D supplementation as an
adjuvant therapy might benefit the severe AD children, and since
recent evidence has demonstrated that it improved the clinical out-
come in mild and moderate AD pediatric patients.
According to our knowledge our study is the first to assess the
efficacy of vit D in conjunction with standard treatment in patients
of 25(OH)D deficiency was notable among all study population.
Similar finding has been previously reported in Egyptian children
with AD and in healthy control as well.3Tounde rstandthe25(OH) D
status associated with AD, the factorsthat might influence25(OH)
D deficiency were investigated. In the present study, lower base-
line 25(OH)D levels were observed inobese patients. Sometrials
reported similar inverse relationship,19 while others not.20 This neg-
ative influence of obesity has been suggested to be due to the lipo-
At the end of the study, a statistically significant difference was
themea n%chan gefromth ei rb as eline.Theimpa ctof VitDor alsup-
plementationasan adjuvanttherapyoneczemaseverity modifica-
tion has been previously investigated. In line with the results of the
present study,Oralvit Dsupplementreduced theskincolonization
TABLE 2 Changeinseverit yofADandserum25(OD)Dlevels
for both groups at the end of the study
MeanEASIscore 20.42(14.6) 27.47(10.11) .035
%changeinE ASI
from baseline
56.44(29.33) 42.09(19.22) .039
36.11(5.84) 25.86(8.27) <.0 01
Categoriesn(%) <.001
<20 ng/mL
0(0) 8(19.04)
20-29 ng/mL
3(6.81) 23(54.76)
4(93.18) 11(26.19)
FIGURE 2 SeverityofADattheendof
CI,(P <.05)
6 of 8 
     MANSOU R et Al.
of S aureus and demonstrated clinical improvement in children with
moderateeczema.9 Similarly, oralVit D supplementation has been
shown to improve winter-related AD symptoms.21 The observed im-
provement in disease severity from vitamin D supplementation has
strong biologicalplausibility as1,25 (OH)Dcontributestohallmark
features of AD: altered barrier function, immune dysregulation, and
inadequate bacterial defense. This might explain the positive impact
of supplementation recorded in the present study. Opposing our
finding, Galli et al22reportedthatdailyoralVitD3 supplementation
children. Lack of correlation with our results might be attributed to
the difference inthe patient population asthe majority (53.9%)of
presentedwithmildeczema.Likewise,Sidburyetal23 demonstrated
ina pilotstudy that VitD supplementation did not significantly in-
fluence t he severity of dis ease in children . The small sampl e size
(n=12)andshortdurationofvitDsupplementation1 might explain
this lack of connection with our result s.
The EA SI score was chose n by the internatio nal Harmonizing
OutcomesMeasures in Eczemagroup (HOME) tobe included asa
core clinical outcome measure in AD clinical trials.24Val idati ons tu d-
iesconfirmthattheE ASIscorehasadequatereliability,validity,and
responsiveness which represent the key performance properties
ne ede df oranyou tcome in str u me nt. However, da t ar ega rd ing ho wa
formation are not available.25 It can be seen from checking the band-
ing of diff erent EAS I strata th at the distri bution of sever ity scale
across strata is not equal. This skewness makes changes in the lower
end of the score more clinically important than changes in the upper
end. There are no previous reports that clearly define a responder
thresholdfor%changefromb as el in einE ASIs co reforpatientswith
severeAD ;h ow ev er, str at ifyingpa ti ent sa ccord in gt o%re duc tionin
EA SIscore stoEAS I50an dE ASI75wa sco nsideredb ymanypivot al
trials to illustrate clinically important differences.26-2 8 At the end of
the study, significant difference between the two groups was ob-
tainedregarding proportionofpatientsachieving EASI<50,EASI
50 ,a n dE A S I75( P <.0 01) .I ntr eat men tgr oup ,3 8 .6%vs 7.1% in con -
trol group achieved EASI 75. However,the percentage of non-re-
sponders deemed comparable between the supplemented patients
andthoseallocatedtoplacebo (59.5%vs52.2% ,respectively).This
indicates that some supplemented patients might achieve excessive
benefit from treatment. Indeed, diverse factors could be linked to
FIGURE 3 Percentage of patients who
achieved <50%improvementinEA SI
CI,(P <.05)
FIGURE 4 Clusteredboxplotshowing(A)thedistribution
of change in vitamin D levels [P value <.001(treatmentgroup),
=.294(placebogroup)](B)thedistributionofBMI[P value = .057
achievedEASI<50,EASI50andEA SI75
 7 of 8
this preferential response. On one hand, fair correlation between
BMIand%changeinscorewasestablishedamongEA SI75respon-
dents. Moreover, 25(OH)D deficie ncy was high prevale nt among
response to supplementation in adults29 and adolescents.30So,it
is conceivable to suggest that the high %reduction in EASIscore
postsupplementation in some obese patients might be influenced
bythebaseline 25(OH)D concentration;however,thedistribution
egories. Further studies are needed to elucidate whether response
tosupplement ationwouldva ryaccord ingtotheBMIinpatientwith
On the other hand, statistically significant difference existed be-
tween the different response categories and magnitude of change
ways. Firstly, variation in the factors that negotiate absorption ef-
ficienc y of oral supp lementat ion in the gas trointest inal trac t (GIT)
might have existed among some supplemented patients. These fac-
tors include variations in the amount and type of fatty acids,31,32
dietar y fibers, and the interaction with other fat soluble micronutri-
ents.33Se cond,thehost-associatedfactorssu chasgeneticvariation
might provide another explanation.34 Thus, it is plausible to hypoth-
patients due to variation within these previously mentioned fac tors,
however, a clear cut is yet lacking.
One limitation of our study is that the study population was com-
prised of patients with limited ethnic diversit y, potentially restrict-
ingits generalizability.Futurestudieson more diverse populations
are needed. Another limitation, lack of data from other important
domains,such as patient reported outcomes. Moreover,given the
needed to determine if the benefits of supplementation would sus-
Inconclusion, our study sug geststhat oraldaily VitDsupple-
ment might provide clinical improvement in children with severe
AD. More inves tigations are ne eded to reveal fac tors associate d
with superior clinical outcomes in some supplemented patients. We
advocatefurthermulticenters tudieswithlar gersamplesizeofeth-
nic diverse population to validate the potential benefit of vit D on
clinica l outcomes of seve re pediatri c eczema. Fur ther stu dies are
also needed to examine whether the positive impact of supplemen-
tation would be maintained in pediatrics with winter-related severe
Parti cipated in resea rch design: Eman A ., Amal, Noha , and Maha.
Conduc ted the clinic al part: Ema n A, Aliaa, M aha, Eman E., So ha,
Nourelhuda, and Doaa.Performed data analysis: Noha, Eman, and
Soha, Ema n E. Drafted t he manuscript : Maha, Nourelh uda, Doaa,
The data that support the findings of this study are available from
the corresponding author upon reasonable request.
Noha O. Mansour
Soha Hassanin
1. Avena-Woods C. Overview of atopic dermatitis. Am J Manag Care.
 2. Mesquita KDC, Igreja ACDSM, Costa IMC. Atopic dermati-
tis and vitamin D: f acts and controversies. An Bras Dermatol.
2013;8 8(6):945-953 .
 3. AhmedMohamedA,SalahAhmedEM,FaragYMK,BedairNI,Nassar
NA, G hanem AIM. Do se-respons e association b etween vit amin D
deficiency and atopic dermatitis in children, and effect modification
by gender: a case-control s tudy. J DermatologTreat. 2019;1-6.
4. Sá nchez-Armendá riz K, García- Gil A, Romero C A, et al. Oral v i-
tamin D3 5 000 IU/day as an adj uvant in the t reatment of at opic
dermatitis: a randomized control trial.Int J Dermatol.20 18;57(12):
 5. DębińskaA,Sikorska-SzaflikH,UrbanikM,BoznańskiA.Theroleof
vitamin D in atopic dermatitis. Dermatitis.2015;26(4):155-161.
6. Hat tangdi-Haridas SR, Lanham-New SA, Wong WHS, Ho MHK,
Darling A L. Vitamin D d eficiency and e ffects of vit amin D sup-
plementation on disease severity in patients with atopic dermati-
tis: a systematic review and meta-analysis in adults and children.
 7. WeilandSK, sing A , Strachan DP, Rzehak P,Pearce N. Climate
and the prevalence of symptoms of asthma, allergic rhinitis, and
atopiceczemainchildren.Occu p Environ Med.2 004 ;61(7 ): 60 9- 615 .
 8. LiangY,ChangC,LuQ.Thegeneticsandepigeneticsofatopicder-
matitis-filaggrin and other polymorphisms. Clin Rev Allergy Immunol.
9. Udompataikul M, Huajai S, Chalermchai T, Taweechotipatr M,
dermatitis: a clinical trial with staphylococcusaureus colonization
determination. J Med Assoc Thai.2015;98 (Suppl9):S23-S30.
10. Ameste jani M, Sale hi BS, Vasigh M, et a l. Vitami n D suppleme n-
tation in the treatment of atopic dermatitis: a clinical trial study. J
Drugs Dermatol.2012;11(3):327-330.
11. Javanbak ht MH, Keshav arz SA , Djalali M , et al. Rand omized con-
trolled trial using vitamins E and D supplementation in atopic der-
matitis. J Dermatol Treat.2011;22(3):144-150.
12. Zhao CY, Murrell DF. Atopic dermatitis outcome measures . In:
Maibach H , Osman N, ed s. Cutaneous Biometrics. Cham: Spr inger
International Publishing; 2019:1-28.
13. Tebben PJ, Singh R J, Kumar R. Vitamin D-mediated hyper-
calcemia: mechanisms, diagnosis , and treatment . Endocr Rev.
14. Ahmed Mohamed A, SalahA hmed EM, Abdel-AzizRTA, et al. The
impact of active vitamin D administration on the clinical outcome s
of acne vulgaris. J D ermatolog Treat. 2020;1-6.
15. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation,
treatment, and prevention of vitamin D deficiency: an Endocrine
Society Clinical Practice Guideline. J Clin Endocrinol Metab.
2011;96(7):1911-193 0.
16. HanifinJM ,ThurstonM,Om otoM,CherillR,TofteSJ,GraeberM.The
dermatitis.EASIEvaluatorGroup.Exp Dermatol.2001;10(1):11-18.
17. ViethR.VitaminDsupplement ation,25-hydroxy vitaminDconcen-
trations, and safety. Am J Clin Nutr.199 9;69(5):8 42- 856 .
8 of 8 
     MANSOU R et Al.
18. Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for
treatment of atopic dermatitis with topical therapies. J Am Acad
19. Hata TR , Audish D, Kotol P, et al. A rand omized contro lled dou-
ble-blind investigation of the effects of vitamin D dietary supple-
mentation in subjects with atopic dermatitis. J Eur Acad Dermatol
20. LimSK,HaJM,Le eYH,etal.ComparisonofvitaminDlevelsinpa-
tients with and without acne: a case-control study combined with a
randomizedcontrolledtrial.PLoS O ne.2016;11(8):e0161162.
21. CamargoCAJr,GanmaaD,SidburyR,ErdenedelgerK,Radnaakhand
N, Khandsuren B. Randomized trial of vitamin D supplement a-
tion for winter-related atopic dermatitis in children. J Aller gy Clin
22. GalliE,RocchiL,CarelloR,GiampietroPG,PaneiP,MeglioP.Serum
VitaminDlevels and Vitamin D supplementation do not correlate
withtheseverit yofchroniceczemainchildren.Eur Ann All ergy Clin
Immunol.201 5;47( 2): 41-47.
23. Sidbur y R, Sull ivan AF, Thadha ni RI, Cam argo CA Jr. Ran domized
controlled trial of vitamin D supplementation for winter-re-
lated atopic dermatitis in Boston: a pilot study. Br J Dermatol.
2008;159(1) :245 -247.
24. Schmit t J, Spuls PI , Thomas KS , et al. The H armonisi ng Outcom e
Measuresfor Eczema (HOME )st atementtoassessclinicalsignsof
atopiceczemaintrials.J Allergy Clin Immunol.2014;134(4):800-807.
25. LeshemYA,HajarT,HanifinJM,SimpsonEL.WhattheEczemaArea
an dS everi t yI nde xs cor et el lsusa bo u tt hesev er ityof at opi cd erm a-
titis: an i nterpretab ility stud y. Br J Dermatol.2015;172(5):1353-1357.
26. SilverbergJI,PinterA,PulkaG,etal.Phase2Brandomizedstudyof
nemolizumabinadultswith moderate-to-severeatopicdermatitis
and severe pruritus. J Allergy Clin Immunol.2020;145(1):173-182.
27. SilverbergJI, SimpsonEL ,ArdeleanuM,et al. Dupilumabprovide s
impor tant clinical b enefits to pat ients with atopic d ermatitis who d o
not achieve clear or almost clear skin according to the Inves tigator's
Global A ssessment: a pooled analysis of data from two phase III
trials. Br J Dermatol.2019;181(1):80-87.
28. Thaçi D, Sim pson EL, Be ck LA , et al. Effi cacy and s afety of dup -
ilumab monotherapy in adults wit h moderate-to-severe atopic
dermatitis: a pooled analysis of two phase 3 randomized trials
(LIBERT Y AD SOLO 1 and LI BERTY AD S OLO 2). J Dermatol Sci.
29. Holick MF, Chen TC . Vitam in D deficie ncy: a wor ldwide pr oblem
with hea lth consequenc es. Am J Clin Nutr.2008;87(4):S1080-S1086.
30. PutmanMS,PittsSA ,MillirenCE,FeldmanHA,Reinold K,Gordon
CM. A ran domized clinic al trial of vitam in D supplement ation in
healthy adolescents. J Adolesc Health.2013;52(5):592-598.
31. Niramitmahapanya S, Harris SS, Dawson-Hughes B. Type of di-
etary fat is associated with the 25-hydroxy vitamin D3 increment
in response to vitamin D supplementation . J Clin Endocrinol Metab.
2011;96(10 ):317 0-3174.
32. MauryaVK,Aggar walM.Factorsinfluencingtheabsor ptionofvita-
min D in GIT: an over view. J Food Sci Techno l.2017;54(12):3753-3765.
33. JohanssonS,MelhusH.VitaminAantagonizescalciumresponseto
vitamin D in man. J Bone Miner Res.2001;16(10):1899-1905.
34. FuL,YunF,OczakM,WongBY,ViethR,ColeDE.Commongenetic
supplementation. Clin Biochem.20 09;42(10-11):1174-1177.
How to cite this article:MansourNO,MohamedAA ,Hussein
adjuvant therapy on clinical outcomes in patients with severe
Res Perspect. 2020; e0 0679.
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Background: The relationship between vitamin D and atopic dermatitis (AD) is controversial. This meta-analysis is aimed at exploring vitamin D level and its deficiency in pediatric AD and at evaluating the efficacy of vitamin D supplementation. Methods: PubMed, Medline, Embase, Ovid, Cochrane Library, ISI Web of Science, and ClinicalTrials were searched. Binary variables and continuous variables were measured by odds ratio (OR) and mean difference (MD) with 95% confidence intervals, respectively. The modified Jadad scale, Newcastle-Ottawa Scale (NOS), and Cochrane's bias risk tools were used to evaluate study quality and the risk of bias of eligible studies, respectively. Results: A total of 22 literature were included in the analysis. Serum 25 (OH) D level in pediatric AD patients was significantly lower than that of the control group with a combined MD value of -8.18 (95% CI: -13.15, -3.22). Patients with AD were more prone to develop vitamin D deficiency with a combined OR value of 2.17 (95% CI: 1.15, 4.11). According to the score of SCORAD, the level of serum 25 (OH) D level in patients with severe AD was significantly lower than that in patients with mild AD (combined MD = 9.23, 95% CI: 6.92, 11.55). Both self-control studies and randomized controlled trials showed improved SCORAD score and EASI score after vitamin D supplementation. Conclusion: This meta-analysis showed lower serum 25 (OH) D level and increased risk of vitamin D deficiency in pediatric AD patients as compared with healthy controls. The serum 25 (OH) D level in severe AD patients was significantly lower than that in the mild AD patients. The SCORAD and EASI score improved after vitamin D supplementation, suggesting its beneficial effect to AD patients. At the same time, more homogeneous studies are needed to reduce confounding factors and further evaluate the impact of vitamin D treatment on the outcome of AD patients.
Background: Atopic Dermatitis (AD) is a common dermatosis in children, that includes skin architecture defects, immune dysregulation, and changes of skin flora. Several new drugs have been found to reduce the severity of AD. Vitamin D is one of the new therapies that is still controversial. The purpose of this research is to conclude the efficacy of vitamin D on atopic dermatitis severity in children aged 0-18 years old. Methods: A systematic search was conducted on the PubMed, Cochrane, ProQuest, Google Scholar, Clinical Trial website, and university repositories including studies published from January 2010 through October 2020. We compared populations, intervention, study design, and outcomes. Statistical analysis was done with Review Manager 5.4.1. Results: Eight articles met eligibility and inclusion criteria, four articles provided complete data and were analysed. Not all studies demonstrated the efficacy of vitamin D but a meta-analysis of four studies of vitamin D supplementation vs placebo found a mean difference of -0.93 (95%CI -1.76, to -0.11, p <0.001) of patient outcome, but statistically, there was no difference in cure rate (risk ratio 1.46 (95%CI 0.72, to 2.97, p =0.008) in vitamin D supplementation groups compared to placebo groups. Conclusions: Vitamin D supplementation in paediatric atopic dermatitis patients could offer improvement of disease severity but the recommended dose and duration of administration cannot be concluded yet.
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Background: Atopic dermatitis (AD), also known as eczema, is one of the most common skin disorders among children and adults, with a steep rise in diagnoses among children. Many studies have investigated the relationship between Vitamin D3 (Vit D3) and AD. Methods: A randomized controlled trial was conducted among 60 children at SCB Medical College, Cuttack from August 2014 to November 2016. Children were randomly assigned to an intervention group that received 60,000 IU of Vit. D3 every week for 6 weeks in addition to regular treatment for AD and a control group that received same treatment of AD except for Vit. D3. Both the groups were followed up at 4 weeks and 8 weeks. Results: In 60 cases of moderate to severe AD, 70% of the patients were male. About 81.7% of patients were from urban areas and 56.7% belonged to a middle socioeconomic class. In 76.6% of cases, family history of atopy was present. At baseline, mean SCORAD was 47.8±7.5 in the intervention group, and 49.2±10.3 in the control group. At baseline, serum Vitamin. D3 level (ng/ml) was 17.6±1.8 in intervention and 17.3±3.5 in control group. After Vitamin. D3 supplementation, the SCORAD improved to 12.8±5.1 (75% reduction) at 4 weeks, and 3.6±2.1 (92% reduction) at 8 weeks in the intervention group. In the control group, the mean SCORAD was 18.8±9.1 (61% reduction) at 4 weeks, and 7.3±4 (85% reduction) at 8 weeks. Discussion: The improvement of serum 25-hydroxy Vit. D3 was 134% and 366% in the intervention group compared to 78% and 121% in the observation group after 4 weeks and 8 weeks respectively. The p-values at both the time points were significant (<0.05) for the intervention group as compared to the control group. Conclusion: Short-term therapeutic supplementation of Vitamin. D3 in children with moderate to severe AD improves the clinical score. There is an inverse relationship between serum Vitamin. D3 level and severity of AD.
Relevance of topic . Atopic dermatitis is a wide-spread skin disease that can significantly reduce patient’s quality of life. Many authors around the globe conduct research to find correlation between atopic detmatitis in children, their growth, development of allergic comorbidities (food allergy in particular) and elimination diet prescription. Aim of the study . To estimate growth indices and nutritional status in children with severe atopic dermatitis and allergic comorbidities on the elimination diet. Methods . This study included children of age 0-17 years 11 months, hospitalized in Dermatology with the Laser Surgery department in the National Medical Research Centre of Children’s Health from September 2020 to May 2021. Anthropometric indices, levels of serum vitamin D, albumin, hemoglobin and total IgE were estimated in all children. Results . This study included 80 children. There was a moderate negative correlation between the number of excluded food groups, the disease longitude (p = 0.003; r = -0.333) and HAZ (p = 0.010; r = -0.351). There was a moderate negative correlation between the age of children and serum vitamin D (p = 0.040; r = -0.317) and a moderate positive - between BAZ and serum vitamin D (p = 0.030; r = 0.332). There was a weak negative correlation between serum vitamin D and total serum IgE (p = 0.033; r = -0.239) and between BAZ and serum hemoglobin (p = 0.028; r = 0.246). Conclusions . The results of this study demonstrate a low intake of vitamin D in children with severe atopic dermatitis, worsening with age. Vitamin D level correlated with BAZ, also the results showed lower vitamin D intake in children with high levels of total Ig E.
Mark Greener summarises the latest studies relevant to primary care nurses
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Background: Nemolizumab targets the IL-31 receptor α subunit involved in atopic dermatitis (AD) pathogenesis. Objective: We sought to evaluate a new dosing strategy of nemolizumab in patients with AD. Methods: We performed a 24-week, randomized, double-blind, multicenter study of nemolizumab (10, 30, and 90 mg) subcutaneous injections every 4 weeks versus placebo, with topical corticosteroids in adults with moderate-to-severe AD, severe pruritus, and inadequate control with topical treatment (n = 226). The Eczema Area and Severity Index (EASI), the peak pruritus (PP) numeric rating scale (NRS), and the Investigator's Global Assessment (IGA) were assessed. Standard safety assessments were performed. Results: Nemolizumab improved EASI, IGA, and/or NRS-itch scores, with the 30-mg dose being most effective. Nemolizumab (30 mg) reduced EASI scores versus placebo at week 24 (-68.8% vs -52.1%, P = .016); significant differences were observed by week 8 (P ≤ .01). With significant improvement (P = .028) as early as week 4, IGA 0/1 rates were higher for 30 mg of nemolizumab versus placebo at week 16 (33.3% vs 12.3%, P = .008) but not week 24 because of an increased placebo/topical corticosteroid effect (36.8% vs 21.1%, P = .06). PP-NRS scores were improved for 30 mg of nemolizumab versus placebo at week 16 (-68.6% vs -34.3%, P < .0001) and week 24 (-67.3% vs -35.8%, P < .0001), with a difference by week 1 (P < .001). NRS response rates (≥4-point decrease) were greater for 30 mg of nemolizumab versus placebo at week 16 (P ≤ .001) and week 24 (P ≤ .01). Nemolizumab was safe and well tolerated. The most common adverse events were nasopharyngitis and upper respiratory tract infection. Conclusions: Nemolizumab resulted in rapid and sustained improvements in cutaneous signs of inflammation and pruritus in patients with AD, with maximal efficacy observed at 30 mg. Nemolizumab had an acceptable safety profile.
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Research has investigated 25-hydroxyvitamin D (25(OH)D) levels in the Atopic Dermatitis (AD) population, as well as changes in AD severity after vitamin D (VitD) supplementation. We performed an up-to-date systematic review and meta-analysis of these findings. Electronic searches of MEDLINE, EMBASE and COCHRANE up to February 2018 were performed. Observational studies comparing 25(OH)D between AD patients and controls, as well as trials documenting baseline serum 25(OH)D levels and clinical severity by either SCORAD/EASI scores, were included. Of the 1085 articles retrieved, sixteen were included. A meta-analysis of eleven studies of AD patients vs. healthy controls (HC) found a mean difference of −14 nmol/L (95% CI −25 to −2) for all studies and −16 nmol/L (95% CI −31 to −1) for the paediatric studies alone. A meta-analysis of three VitD supplementation trials found lower SCORAD by −11 points (95% CI −13 to −9, p < 0.00001). This surpasses the Minimal Clinical Important Difference for AD of 9.0 points (by 22%). There were greater improvements in trials lasting three months and the mean weighted dose of all trials was 1500–1600 IU/daily. Overall, the AD population, especially the paediatric subset, may be at high-risk for lower serum 25(OH)D. Supplementation with around 1600 IU/daily results in a clinically meaningful AD severity reduction.
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Background Two phase 3 trials with identical design, LIBERTY AD SOLO 1 (NCT02277743) and LIBERTY AD SOLO 2 (NCT02277769), confirmed dupilumab efficacy and safety versus placebo in adults with moderate-to-severe atopic dermatitis (AD). Objectives To report a pooled analysis of these trials to further explore dupilumab’s effects on AD clinical parameters, patient-reported outcomes (PROs), symptoms of anxiety/depression, health-related quality of life (HRQoL), and safety. Methods A pooled analysis of two 16-week phase 3 studies in adults with moderate-to-severe AD (N = 1379) inadequately controlled with/inadvisable for topical medications, randomized to dupilumab 300 mg once weekly (qw), every 2 weeks (q2w), or placebo. Results Dupilumab significantly improved all pre-specified efficacy endpoints versus placebo (P < 0.0001), including clinical severity outcomes and PROs, symptoms of anxiety/depression, and HRQoL, consistent with previously published results. In post-hoc analyses, among patients reporting at least some baseline pain/discomfort on the EuroQoL-5D, no pain/discomfort at Week 16 was reported by 43%/46%/14% of dupilumab qw/q2w/placebo-treated patients (P < 0.0001). The distribution of dupilumab-treated patients within pre-defined score categories on the Investigator’s Global Assessment (0–1/2/3/4) and Eczema Area and Severity Index (≥90%/≥75–<90%/≥50–<75%/<50%) steadily and consistently improved over time versus marginal changes with placebo. Dupilumab significantly improved pruritus within 1–3 days of treatment initiation. No new safety signals were observed. Injection-site reactions and conjunctivitis were more common with dupilumab; AD exacerbation and non-herpetic skin infections more frequent with placebo. Conclusions Dupilumab versus placebo significantly improved objective AD signs, subjective PROs, symptoms of anxiety/depression, and HRQoL, with a favorable benefit-risk profile in adults with moderate-to-severe AD.
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Background In the US, an Investigator's Global Assessment (IGA) score of ≤ 1 (clear/almost clear skin) has been the regulatory outcome standard measure for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. Objective To evaluate the treatment effect of dupilumab in patients with IGA>1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. Methods LIBERTY AD SOLO 1 and 2 were two 16‐week, randomized, double‐blind trials enrolling adult patients with moderate‐to‐severe AD (IGA≥3) inadequately controlled with topical treatment. We performed a post‐hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA>1 included Eczema Area and Severity Index (EASI), pruritus Numerical Rating Scale (NRS), affected Body Surface Area (BSA), Patient‐Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). Results At Week 16, 278/449 dupilumab q2w‐treated patients (median age 36·0 years) and 396/443 placebo‐treated patients had IGA>1. Among patients with IGA>1 at Week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (–48·9% vs. –11·3%, P<0·001), pruritus NRS (–35·2% vs. –9·1%, P < 0·001), BSA affected (–23·1% vs. –4·5%, P<0·001), POEM score ≥ 4‐point improvement (57·4% vs. 21·0%, P<0·001), and DLQI score ≥ 4‐point improvement (59·3% vs. 24·4%, P<0·001). Conclusions In patients with IGA>1 at Week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures versus placebo. The IGA≤1 endpoint significantly underestimates clinically relevant dupilumab treatment effects. This article is protected by copyright. All rights reserved.
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Background Vitamin D has immunomodulatory effects both in the innate and adaptive immune systems, and there is growing scientific evidence demonstrating its relevance in inflammatory processes such as AD. Hypothesis If vitamin D3 promotes the skin immune system, then it should improve the response to treatment of patients with AD. Methods A randomized, double‐blind placebo‐controlled clinical trial was conducted, which included 65 patients with AD according to Hanifin–Rajka criteria and the severity scale (SCORAD). The patients were divided into two groups to receive either vitamin D3 5000 IU/day (n = 33) or placebo (n = 32), plus baseline therapy (topical steroid, soap substitute, and emollient) during 3 months. Results Fifty‐eight of the 65 enrolled subjects were included in the analysis. At the end of the intervention, the treated group achieved higher levels of 25(OH)D (P < 0.001). At week 12, those patients who registered serum levels of 25(OH)D ≥20 ng/ml, regardless of whether or not they had received supplementation, showed a lower SCORAD compared to those with levels <20 ng/ml (P < 0.001). Eighty percent of the patients with serum levels <20 ng/ml (n = 9) had moderate–severe AD despite standard treatment. Vitamin D levels ≥20 ng/ml associated with baseline therapy strongly favored remission of atopic dermatitis (P = 0.03). No significant differences were found between patients with serum levels of ≥20 ng/ml vs. ≥30 ng/ml. Conclusions Reaching serum levels of 25(OH)D > 20 ng/ml in conjunction with standard therapy is sufficient to achieve a reduction in severity (SCORAD) in patients with AD.
Acne vulgaris is one of the most common chronic inflammatory skin disorder affecting millions of people worldwide. Vitamin D deficiency has a role in various inflammatory skin diseases as acne. This study aimed to investigate the serum level of 25 hydroxy vitamin D in acne patients and to assess the efficacy and safety of active vitamin D in management of acne. This study was conducted on 100 patients with acne and 100 healthy controls, then the 100 acne patients were randomized to either the study group that received 0.25ug alfacalcidol daily or the placebo group that received oral placebo during the 3 months study period. Serum levels of 25-hydroxy-vitamin D were significantly lower in acne patients than in healthy control and were inversely correlated to the severity of acne. After alfacalcidol administration, the study group showed significant higher level of 25(OH) D levels (P <0.05) compared to placebo group. In addition, median serum level of IL6 and TNFα significantly decreased (p < 0.05) in the study group in comparison to placebo group and as compared to their baseline results. Acne patients are more commonly to have vitamin D deficiency as compared to healthy people and hence, alfacalcidol might have a beneficial role in the acne management with no reported side effects.
Background: Vitamin D is a regulatory factor for immunity and skin barrier functions. It is hypothesized to be linked to atopic dermatitis (AD) which is characterized by interaction between epidermal barrier dysfunction and dysregulation of skin immune functions. Methods: One hundred AD patients and one hundred and one normal controls were collected from outpatient clinic based on their clinical condition, both had measurement of 25-hydroxyvitamin D [25(OH)D]. We assessed the relationship between 25(OH)D deficiency and AD prevalence using adjusted Poisson regression model. Results: Serum 25(OH)D levels were significantly lower in cases than controls (mean 35.1 vs 22.6 ng/mL, p < 0.001). The unadjusted prevalence ratios (PRs) (95% CI) for AD for comparing participants with intermediate and deficient vitamin D levels to those with optimal levels were 3.11 (1.91, 5.06) and 4.77 (2.99, 7.60), respectively. The association didn’t materially change after adjusting for potential confounders. In the fully adjusted analysis stratified by gender, PRs for AD for comparing male participants with intermediate and deficient vitamin D levels to those with optimal levels were 3.38 (1.21, 9.40) and 5.20 (1.91, 14.13), respectively, whereas in the female participants were 1.32 (0.96, 1.83) and 1.49 (1.04, 2.14), respectively (p-interaction <0.001). Conclusion: In this case-control study in children, we found a statistically significant dose-response association between vitamin D deficiency and AD. We also observed a statistically significant effect modification of this association by gender. Further research is recommended to study this association longitudinally, and to examine whether treating vitamin D deficiency may potentially improve AD.
Atopic dermatitis (AD), also known as atopic eczema, is a chronic relapsing inflammatory skin condition. Incidence of AD has increased 2- to 3-fold in industrialized nations, impacting approximately 15% to 20% of children and 1% to 3% of adults worldwide. AD has a wide-ranging impact on a patient's quality of life and the burden from direct and indirect costs (approximately $37.7 billion in out-of-pocket costs) is shared by the families and caregivers of patients with AD. This article reviews the epidemiology, burden of disease, pathophysiology, and diagnostic criteria important for early diagnosis and treatment. New insights related to the genetic, immunologic, and environmental impacts of AD have created new treatment opportunities. Nonpharmacologic and pharmacologic interventions are discussed, with an emphasis on emerging treatments for AD. Healthcare providers play an important role in the management of AD to improve economic and clinical outcomes. Treatment strategies need to be individualized with a strong emphasis on patient education and self-management strategies to optimize outcomes and reduce unnecessary costs associated with the management of AD.