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w w w . j c o l . o r g . b r

Journal

of

Coloproctology

Original

Article

Association

between

vitamin

D

deficiency

and

anemia

in

inflammatory

bowel

disease

patients

with

ileostomy

Andre

Fialho

a

,

Andrea

Fialho

a

,

Gursimran

Kochhar

b

,

Bo

Shen

b,∗ aDepartmentofInternalMedicine,TheClevelandClinicFoundation,Cleveland,UnitedStates

bDepartmentofGastroenterologyandHepatology,TheClevelandClinicFoundation,Cleveland,UnitedStates

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received13May2015

Accepted8June2015

Availableonline2July2015

Keywords:

Anemia Ileostomy

VitaminDdeficiency

a

b

s

t

r

a

c

t

Background:VitaminDdeficiencyiscommonlyseeninpatientswithinflammatorybowel

disease(IBD).VitaminDdeficiencyinIBDpatientswithileostomyhasnotbeensystemically

studied.Theaimofthestudywastoassessthefrequencyandriskfactorsassociatedwith

low25(OH)D3levelsinthosepatients.

Methods:112eligibleIBDpatientswithileostomywerestudied.Demographic,clinical,and

endoscopicvariableswereanalyzed.VitaminDlevelsbeforeandafterileostomywere

com-paredwhenavailable.Levelsofserum25(OH)D3<20ng/mLwereclassedasbeingdeficient.

Results:112 eligible ileostomy patients were included. The mean vitamin D level was

21.47±1.08ng/dl.LowlevelsofvitaminD(<30ng/dl)werepresentin92patients(82%).

Vita-minDdeficiency(<20ng/dL)wasseenin55patients(49%).Therewasnodifferencebetween

patientswithorwithoutvitaminDdeficiencyregardingdemographicvariables,medication

useanddurationofileostomy.Neo-ilealinflammationonendoscopywasnotassociated

withvitaminDdeficiency(p=0.155).Lowerlevelsofphosphorus(p=0.020)orhemoglobin

(p=0.019)andshorterdurationofIBD(p=0.047)werefoundinpatientswithvitaminD

deficiency.Inmultivariateanalysis,lowerlevelsofphosphorus(oddsratio[OR]:1.83,95%

confidenceinterval[CI]:1.16–2.89,p=0.009)andhemoglobin(OR:1.32,95%CI:1.08–1.60,

p=0.006)remainedsignificantlyassociatedwithvitaminDdeficiency.

Conclusion: VitaminDdeficiencyiscommoninIBDpatientswithileostomyandisassociated

withlowhemoglobinlevels.FurtherstudiesareneededtoevaluatevitaminD

supplemen-tationasapossibleadjuvantinthetreatmentofanemiaofchronicdiseaseinIBDpatients.

©2015SociedadeBrasileiradeColoproctologia.PublishedbyElsevierEditoraLtda.All

rightsreserved.

Correspondingauthor.

E-mail:shenb@ccf.org(B.Shen).

http://dx.doi.org/10.1016/j.jcol.2015.06.004

(2)

Associac¸ão

entre

deficiência

de

vitamina

D

e

anemia

em

pacientes

com

doenc¸a

inflamatória

intestinal

submetidos

a

ileostomia

Palavras-chave:

Anemia Ileostomia

DeficiênciadeVitaminaD

r

e

s

u

m

o

Introduc¸ão: AdeficiênciadevitaminaDempacientescomdoenc¸ainflamatóriaintestinal

submetidosaileostomianãofoiestudadasistematicamente.Oobjetivodesseestudofoi

avaliarafrequênciaeosfatoresderiscoassociadoscomadeficiênciadevitaminaDnesses

pacientes.

Resultados: 112pacienteselegíveisforam incluídos.Amédia dosníveisde vitaminaD

napopulac¸ãoestudadafoide21.47±1.08ng/dl.NíveisdevitaminaDabaixodonormal

(<30ng/dl)edeficiênciadevitaminaD(<20ng/dL)foramencontradosem92pacientes(82%)

eem55pacientes(49%)respectivamente.Encontrou-seumaassociac¸ãoentredeficiência

devitaminaDeníveismaisbaixosdefosforo(p=0.020),hemoglobina(p=0.019)edurac¸ão

dadoenc¸ainflamatóriaintestinal(p=0.047).Naanálisemultivariada,níveismaisbaixosde

fósforo(oddsratio[OR]:1.83,95%confidenceinterval[CI]:1.16–2.89,p=0.009)ehemoglobina

(OR:1.32,95%CI:1.08–1.60,p=0.006)permaneceramassociadoscomdeficiênciadevitamina

D.

Conclusão: AdeficiênciadevitaminaDécomumempacientescomdoenc¸ainflamatória

intestinal submetidosaileostomiae estáassociadacomníveisbaixosdehemoglobina.

Maisestudossãonecessáriosparaavaliarseasuplementac¸ãodevitaminaDpodeserum

adjuvantenotratamentodeanemiadadoenc¸acrônicanessespacientes.

©2015SociedadeBrasileiradeColoproctologia.PublicadoporElsevierEditoraLtda.

Todososdireitosreservados.

Introduction

Vitamin D is a steroid hormone responsible for calcium

hemostasis and metabolism. It also has

immunoregula-tory functions and anti-inflammatory effects.1 The main

source of vitamin D derives from the conversion of

7-dehydrocholesterol in the skin to cholecalciferol (D3) by

sunlight.VitaminDisalsoacquired fromthedietandit is

absorbedintheduodenumandjejunum.Asaliposoluble

vita-min,itdependsonbileacidsforitsabsorption.Thebileacid

poolismaintainedbytheenterohepaticcirculationandrelays

ontheabsorptionofbileacidsintheterminalileum.

VitaminDdeficiencyiscommonworldwide.IntheUnited

States, the reported frequency of vitamin D deficiency is

18–40%inadultfemalesand11–26%inadultmales,with

vari-ationdependingonage,seasonandgeographicallocation.2

Vitamin D deficiency has a significant impact on health,

includinglowbonemineraldensity,increasedriskoffractures

andfalls.3Inaddition,adequatebloodvitaminDlevelsand

intakeofvitaminDmaydecreasetheriskofcancer,4typeI

diabetes,5multiplesclerosis6andrheumatoidarthritis.7

LowvitaminDlevelsarecommoninpatientswith

inflam-matory bowel disease (IBD), occurring in 45–63% of the

patients.8,9 ThemechanismsforvitaminDdeficiencyinIBD

patientsare multifactorial.PatientswithIBDaresubject to

surgery,particularlyilealresectionforCrohn’sdisease,and

maybeatincreasedriskofvitaminDdeficiency.IBDpatients

oftenrequiresurgeryduringthecourseoftheirdisease10and

ileostomyisperformed in asubset ofpatients withCD or

ulcerativecolitis(UC).11

Surgicalproceduressuchasileostomymayposean

addi-tionalriskforvitaminDdeficiencyinIBDpatients.Studies

evaluatingtheratesandassociatedriskfactorsofvitaminD

deficiencyinthispopulationarelacking.Thustheaimsofthis

studyweretoevaluatethefrequencyofvitaminDdeficiency

inIBDpatientswithanileostomyandtoidentifyriskfactors

forvitaminDdeficiencyinthesepatients.

Patients

and

methods

Patients

ThisstudywasapprovedbytheClevelandClinicInstitutional

Review Board (IRB). Three hundred IBD patients with

per-manent ileostomy were retrospectively identified from the

electronicmedicalrecords.Atotalof112patientswithIBD

andatleastoneserum25(OH)D3levelaftertheconstructionof

ileostomywereincludedinthestudy.Inclusioncriteriawere:

(1) diagnosisofIBD;(2)thepresenceofpermanent or

tem-poraryileostomy;and(3)atleastoneserum25(OH)D3 level

measuredaftertheostomy.Exclusioncriteriawereileostomy

forbowelmalignancyorforfamilialadenomatouspolyposis

oretiologiesotherthanIBD.

Variables

Atotalof32demographic,clinicalandendoscopicvariables

were studied.Demographic variables included age, gender,

race,bodymassindex(BMI),smokingstatusandgeographical

location(Northvs.South).TheNorthernlocationwasdefined

aslocationabovethelatitudeof37degreesNorth.The

South-ernlocationwasdefinedasalocationbelowthelatitudeof37

(3)

Thefollowingclinicalvariableswereincluded:durationof

disease,duration ofdisease until submission to ileostomy,

duration of ileostomy, season when vitamin D was

mea-suredandclinicalindicationforileostomyandbloodlevels

of25(OH)D3,albumin,hemoglobin(Hb),calcium,parathyroid

hormone (PTH), alkaline phosphatase and C-reactive

pro-tein(CRP).Historyofuse ofcalcium supplements, vitamin

supplements,corticosteroid,immunomodulators,anti-tumor

necrosisfactor (TNF)biologics, antibiotics or non-steroidal

anti-inflammatorydrugs(NSAID)werealsoevaluated.

Endo-scopic variables included the presence or absence of any

mucosalinflammationonileoscopy.

Vitamin D status was assessed by measuringthe most

recent25(OH)D3level.VitaminDlevels≥30ng/mLwere

con-sidered normal. Alow vitamin D was definedas the level

below30ng/mL.LowvitaminDlevelswerefurthercategorized

intovitaminDinsufficiencywhenlevelswerebetween20and

29ng/dlandvitaminDdeficiencywhenlevelswerelessthan

20ng/dl.

Toevaluatethepresenceofanemia,themostrecentHb

levelwithin6monthsofvitaminDlevelmeasurementwas

takenintoaccount.AnemiawasdefinedasHb<12.0g/dLin

femalesandHb<13g/dLinmales.Thepresenceofiron

defi-ciencyanemia(IDA)andanemiaofchronicdisease(ACD)was

definedbased onserum ironlevels, transferrin,transferrin

saturationand ferritin.ThedefinitionofACDand IDAwas

asfollowsaccordingtoWeissandGoodough12:(1)transferrin

saturation<16%withnormalorelevatedserumferritin

lev-els(>100ng/mL)characterizedasACD;(2)lowlevelsofboth

transferrinsaturation(<16%)andserumferritin(<30ng/mL)

characterizedas IDA.Transferrinsaturation <16%,reduced

transferrinconcentration,andserum ferritin>30ng/mLbut

<100ng/mLcharacterizedamixedpatternofIDAandACD.

Outcomemeasurements

Theprimaryoutcomeswerethefrequencyandriskfactorsof

vitaminDdeficiencyinIBDpatientswithileostomy.

Statisticalanalysis

AllstatisticalanalyseswereperformedusingSPSSsoftware

version22(IBMCorp.,Armonk,NY).Mean±SDorn%wasused

topresentcontinuousvariables.Toidentifypotentialrisk

fac-torsforvitaminDdeficiency,univariableanalysiswasused.

Student’sttest(orWilcoxonranksumtestwhen

appropri-ate)wasusedforcontinuousvariables,whileChi-squaretest

(orFishersexact test, whenappropriate) wasused for

cat-egoricalvariables.Variablesthatwere significantly(p<0.05)

associatedwithvitaminDdeficiencyonunivariateanalysis

wereincluded inthemultivariateanalysis alongwith

vari-ablespreviouslyshownintheliteraturetoaffectvitaminD

levels.

Results

Atotalof112eligiblepatientswithIBDandileostomywere

includedinthisstudy,ofwhich107hadCD and5had UC.

Themeanageofthecohortstudiedwas53.4±1.3years(range

24–91years)and70(62.5%)patientswerefemales.Themean

duration of IBD diagnosis was 24.6±1.2 years (range 2–60

years) and the mean duration of ileostomy was 12.7±0.9

years(range2–45years).Themainindicationsforileostomy

inthecohortwerefailureofmedicaltherapyin90patients

(80.4%)andbowelobstructionin22(19.6%).Inthesubgroup

ofpatientswithUC,themainindicationforendileostomy

wascomplicationsoftheilealpouch(3/5).Fivepatientshad

temporaryileostomyand107hadpermanentileostomy.

FrequencyofvitaminDdeficiency

The mean vitamin D level of the whole cohort was

21.47±1.08ng/dl. Low vitamin D (<30ng/dl) levels were

presentin92(82.1%)patients.Thirty-sevenpatients(33.0%)

were classified as having vitamin D insufficiency (level

between20and29ng/dl)and55(49.1%)asvitaminDdeficiency

(<20ng/dl).

We performed a subanalysis of the trend of vitamin D

status before and after ileostomy, based on available data

in 26 (23.2%) of the 112 patients. The mean level of

vita-minDwassignificantlyhigherafterileostomycomparedto

beforeileostomy(22.4±1.8ng/dL,vs.17.5±1.8ng/dL,p=0.007)

asshowninFig.1.

UnivariateassessmentofriskfactorsforvitaminD deficiency

The112patientsweredividedintothosewithvitaminD

defi-ciency (<20ng/mL) and those without vitaminD deficiency

(>20ng/mL)toanalyzetheriskfactorsassociatedwithvitamin

Ddeficiency.

Intheunivariateanalysis,levelsofphosphoruswere

sig-nificantlylowerinthevitaminDdeficiencygroup(p<0.020).

NumericallylowerlevelsofcalciumandhigherlevelsofPTH

werealsofoundinthesepatientsalthoughthisdidnotreach

statisticalsignificance(Table1).

Inaddition,Hblevelsweresignificantlylowerinthe

vita-minDdeficiencygroup(p=0.019)(Table1).Atotalof47(42.0%)

ofthe112werefoundtohaveanemia,definedasHb<12ng/dL

infemalesandHb<13ng/dLinmales.Amongthe47patients

withdiagnosisofanemia,37hadironstudiesincludingiron

levels,transferrin,transferrinsaturationandferritin.ACDwas

detectedin21(63.6%)patients,IDAwasdetectedin6(18.2%)

patients andmixed patternanemia wasalsodetectedin6

(18.2%)patients.Nostatisticaldifferencewasfoundbetween

patientswithandwithoutvitaminDdeficiencyregardingthe

prevalenceofthedifferenttypesofanemia(ACDvs.IDAvs.

mixedpatternanemia)(p=0.204,Table1).

PatientswithvitaminDdeficiencyhadIBDdiagnosisfora

shorterperiodoftime(p=0.047),butnosignificantdifferences

werefoundneitherinthedurationofileostomy(p=0.080),the

intervalbetweenIBDdiagnosis(p=0.819)andileostomynor

thepresenceofinflammationonileoscopy(p=0.155)asshown

inTable1.

Therewasnodifferenceinage,gender,race,BMI,

smok-ing status, geographical location, season when vitamin D

was measured, albumin, alkaline phosphatase, CRP, the

use ofcalciumsupplements,vitaminsupplements,steroid,

(4)

Table1–Demographic,clinical,endoscopicandhistologiccharacteristicsofileostomypatientswithandwithoutvitamin Ddeficiency.

Variables Allcases(total

112)

Vitamin deficiency (<20ng/mL)n=55

NovitaminD deficiency (≥20ng/mL)n=57

p-value

Meanage,years 53.39±1.32 52.04±1.87 54.87±1.87 0.317a

Malegender 42 18(32.7%) 24(42.1%) 0.203b

BMI 26.19±0.58 26.46±0.94 25.94±0.70 0.659a

Race,n%

Non-Hispanic 27 14(25.5%) 13(22.8%) 0.827b

Caucasian 85 41(74.5%) 44(77.2%)

Northstatelocation 105 51(92.7%) 54(94.7%) 0.480b

Season,n%

Spring 26 11(20.0%) 15(26.3%)

0.598b

Summer 30 15(27.3%) 15(26.3%)

Fall 31 14(25.5%) 17(29.8%)

Winter 25 15(27.3%) 10(17.5%)

Smoking,n%

Current 21 14(25.5%) 7(12.3%)

0.146b

Quit 33 13(23.6%) 20(35.1%)

Never 58 28(50.9%) 30(52.6%)

Excessiveuseofalcohol,n% 37 15(27.3%) 22(38.6%) 0.232b

Indicationforstoma

RefractoryIBD 90 43(78.2%) 47(82.5%)

0.971b

Mechanicalobstruction 22 12(21.8%) 10(17.5%)

YearsfromIBDdiagnosis 24.60±1.24 22.09±1.84 27.02±1.62 0.047a

Yearsafterileostomy 12.72±0.91 12.50±1.37 12.92±1.92 0.819a

Yearsbetweendiagnosisandileostomy 11.18±1.07 9.27±1.44 13.02±1.54 0.080a

Ilealinflammation(ileoscopy) 26 10(18.2%) 16(28.1%) 0.266b

Useofsteroids 83 39(70.9%) 44(77.2%) 0.520b

Useofaspirin 43 23(41.8%) 20(35.1%) 0.295b

Useofantibiotics 107 52(94.5%) 55(96.5%) 0.483b

UseofNSAIDS 62 31(56.4%) 31(54.4%) 0.492b

Useofbiologics 49 20(36.4%) 29(50.9%) 0.132b

Useofimmunomodulators 63 28(50.9%) 35(61.4%) 0.177b

Useofcalcium 78 35(63.6%) 43(75.4%) 0.125b

UseofvitaminD 88 40(72.7%) 48(84.2%) 0.105b

Calcium 81.25±1.83 77.75±2.86 84.63±2.23 0.060c

PTH 103.11±14.01 111.64±21.73 87.23±16.78 0.512c

Phosphorus 3.35±0.10 3.08±0.10 3.58±0.17 0.020c

Alkalinephosphatase 132.36±9.06 143.73±16.06 117.53±8.46 0.096c

Hemoglobin 10.92±0.22 10.38±0.32 11.42±0.30 0.019c

Anemiatyped

Chronicdisease 21 15(75.0%) 6(46.2%)

0.204b,c

Irondeficiency 6 2(10.0%) 4(30.8%)

Mixedpattern 6 3(15.0%) 3(23.1%)

Albumin 3.47±0.08 3.37±0.13 3.55±0.15 0.429a

CRP>1e 66 37(67.3%) 29(50.9%) 0.073b,c

BMI,bodymassindex;5ASA,5-aminosalicylicacid;NSAID,non-steroidalanti-inflammatorydrugs;PTH,parathyroidhormone.

a Thepvaluewascalculatedbyt-test. b Thepvaluewascalculatedbychi-squaretest.

c Somevariablesmayhavelessthan112duetomissingdata.

(5)

.00 10.00 20.00 30.00

V

itamin D level ng/dl

40.00 50.00

p=0.007

Period of measurement

After ileostomy Before ileostomy

Fig.1–BoxplotdistributionofvitaminDlevelsbeforeandafterileostomy(N=26).

non-steroidalanti-inflammatorydrugs(NSAID),betweenthe

studyandcontrolgroups(Table1).

MultivariateanalysisofriskfactorsforvitaminD deficiency

LowHb, low phosphoruslevel and shorterduration ofIBD

diagnosisweresignificantlyassociatedwithvitaminD

defi-ciencyintheunivariateanalysisandthuswereincludedinthe

multivariableanalysis.Whentheeffectofthesevariableswas

analyzedtogetherinthelogisticregression,lowHb(oddsratio

[OR]:1.32, 95% confidence interval [CI]: 1.08–1.60, p=0.006)

and low phosphorus (OR: 1.83, 95% CI: 1.16–2.89, p=0.009)

remainedindependentlyassociatedwithvitaminDdeficiency

(Table2).

Discussion

Inthisstudy,wefoundthatthelowvitaminDlevels(vitaminD

deficiencyorinsufficiency)werecommoninIBDpatientswith

ileostomy,with afrequency of82.1% (92/112). Surprisingly,

vitaminDstatusimprovedafterileostomy,whencompared

withpre-ileostomystatus,basedonthedatain26patients

with sequential measurements of serum vitamin D level.

VitaminD deficiencywasfoundtobeassociatedwith

ane-mia(p=0.009),suggestingthattheremaybealinkbetween

vitaminDdeficiencyandanemiainthesepatients.Inthe33

patientswhohadavailabledataforanemiatypeidentification,

ACDwasmoreprevalentinpatientswithvitaminDdeficiency

thancontrols(66.7%vs.33.3%),althoughthisfindingdidnot

reachstatisticalsignificance(p=0.204).Therewasno

associ-ationbetweenvitaminDdeficiencyandileuminflammation

onileoscopy(p=0.155).

LowvitaminDlevelsarecommoninpatientswithIBDin

general.7Upto63%ofpatientswithCDhavevitaminD

defi-ciency [39],whileinpatientswithUC vitaminDdeficiency

hasbeenshowntooccurin45%ofthecases.7InbothCDand

UC,severityofdiseasewasfoundtobeassociatedwith

vita-minDdeficiency.13,14SincevitaminDhasbeenshowntohave

anti-inflammatoryproperties,itslowerlevelmaypredispose

togreaterinflammationanddiseaseactivityinbothCDand

UC,creatingaviciouscircle.15,16 Ourstudyshowedthatthe

creationofanileostomymayhelpboostthelevelofserum

vitaminD,presumablyduetothebypassorresectionofthe

diseasedboweldownstream.

ThecauseofvitaminDdeficiencyinIBDpatientsappears

tobemultifactorial,includingdecreasedsunexposure17and

decreased dietary vitamin D intake due to the disease.18

In patients with CD, additional culprits are vitamin D

Table2–MultivariateanalysisofriskfactorsassociatedwithvitaminDdeficiencyinIBDpatientswithileostomy.

Variables OR CI p-value

Lowphosphorus 1.83 1.16–2.89 0.009

Lowhemoglobin 1.32 1.08–1.60 0.006

YearsfromIBDdiagnosis 1.04 1.00–1.07 0.051

(6)

malabsorptionand proteinlosing enteropathy causing loss

ofvitaminDbindingprotein.19Terminalileumresectionin

patientsCDhasalsobeenproposedasacontributorto

vita-minDdeficiencyduetodecreasedenterohepaticcirculation

ofbileacids.20

Surgical approach in patients with IBD such as end

ileostomyimposesadditionalmetabolicconsequencestoan

alreadyburdenedpopulation.InIBDpatientswithileostomy,

our group has previously shown a high prevalence oflow

bonemineraldensity,furthercomplicatedbyincreasedrisk

offractures.21TheremaybeanincreasedriskofvitaminB12

deficiencyinthesepatients,althoughthisseemstobemore

commonwhensignificantamountsofileumareresected.22

Inaddition,thereisanincreasedfecalexcretionof

choles-terolandbileacidsinpatientswithileostomy,whichhasbeen

showntoimprovecholesterolprofileinthesepatients,while

itmayfurtherimpairbileacidenterocirculation.23The

associ-ationbetweenvitaminDdeficiencyandanemia,ontheother

hand,hasnotbeenestablishedinthispopulation.

Toourknowledge,this isthefirst studyevaluating

vita-min D deficiency and its risk factors in IBD patients with

ileostomy.Kennedy et al.24 studiedcalcium metabolism in

49 patients with ileostomyand mentioned that the levels

ofvitaminDinthesepatientsvariedfrom21.4±9.5nmol/L

inthewinterto46.4±19.2nmol/Linthesummer.However,

riskfactorsforvitaminDdeficiencywerenotevaluated.In

thepresentstudy,vitaminDdeficiencywascommoninIBD

patients submitted to ileostomy.The exact

etiopathogene-sisforvitaminDdeficiency inIBDpatients withileostomy

isunknown.Wepostulatethatitmay berelated toaltered

intestinaltransittimeandilealresectioninthispopulation.

SomeIBDpatientswithileostomymayhaveextensive

inflam-mationorstrictures,whichleadstostasisoffecalcontentin

thesmallbowelandbacterialovergrowth.25Inturn,bacterial

overgrowthcausesdeconjugationofbileacidsanddecreases

theabsorptionoffatsolublevitaminssuchasvitaminD.26

IleostomywithilealresectioninCDmayleadtoimpairedbile

acidenterohepaticcirculation.InpatientswithilealCD,lower

vitaminDlevelsseemtobemorecommon.20

Tobetterunderstandtheexactburdenthatileostomyposes

towardvitaminDdeficiency,wecomparedthelevelsof

vita-minDbeforeandafterileostomyin26patientswithavailable

data. Surprisingly,the mean level ofvitaminDwas

signif-icantly lower before ileostomythan afterileostomy. These

findings may be a consequence of better disease control

orlessinflammationleadingtonutritionalimprovementin

IBDpatientsafterileostomy.Inaddition,aftersurgerythese

patientsmayhaveimprovedoralintakeandincreasedquality

oflifewithmoreoutdooractivity.

Interestingly,wefoundasignificantassociationbetween

lowvitaminDandHbinbothunivariableandmultivariate

analyses.Thisfinding,along withthe similaronereported

in patients with ileal pouch-anal anastomosis (IPAA),27

promptedourhypothesisthatthelinkbetweenvitaminD

defi-ciencyandanemiaisnotacoincidence.Thisassociationhas

notyetbeenstudiedinIBDpatientswithoutileostomyorIPAA.

Atotalof37patientshadavailablelaboratorydatatofurther

categorizethesubtypeofanemiaintoACD,IDAormixed

pat-tern.ACDwasthemostcommontypeofanemiainthecohort,

occurringin21patients(66.6%).AlthoughACDoccurredmore

frequentlyinpatientswithvitaminDdeficiency,thisdidnot

reachstatisticalsignificance(75.0%vs.46.2%,p=0.204),

prob-ablyduetothesmallsamplesize.

TheassociationofvitaminDdeficiencywithanemiahas

beendemonstratedinpatientswithandwithoutchronic

kid-neydisease.28,29Intheelderly,vitaminDdeficiencyseemsto

beassociatedwithACD,butnotwithothertypesofanemia,

pointingtowardapossibleroleofvitaminDininflammation

suppression.28VitaminDdeficiencywassignificantly

associ-atedwithahighhepcidinlevel,apro-inflammatorymediator

andaplayerinironmetabolism.Hepcidinmayplayarolein

ACDinCD.30Wethereforeattemptedtoconnectthedots.We

postulatethatvitaminDdeficiencyislinkedtoanemiainIBD

patients,specificallyACD,throughtheinflammation-hepcidin

axis.WhethervitaminDdeficiencycontributestoincreased

inflammation leading to ACD or whether both vitamin D

deficiencyandanemiaareacommonendofachronic

inflam-matorystateisunknown.Prospective,longitudinalstudiesare

neededtofurthersortouttheassociationorcausal

relation-ship.

Althoughthepresenceofinflammationintheileum

diag-nosed byileoscopycould potentially bepredisposedtolow

vitaminDlevelsbyfurtherimpairingabsorptionofbileacids

and vitaminD throughthe inflamed mucosa,this wasnot

confirmedinbyourstudy.Thismayindicatethatthemost

importantfactor forvitaminDdeficiency inthesepatients

isdisruptionoftheanatomy.Similarfindingsoflowvitamin

DlevelsinIBDpatientswithIPAAwithoutcorrelationwith

inflammationonendoscopyorhistologyhavebeendescribed

in the literature.27 Alternatively, this may imply that

con-ditions such as ileostomy and IPAA cause a reset of the

immunostat,interferingwithnutritionandmetabolism.

There areseveral clinicalimplications ofthe findingsin

thisstudy.VitaminDdeficiencyiscommoninpatientswith

ileostomyandvitaminDlevelsshouldberoutinelymeasured

inthesepatients.Inaddition,wesuggestthatHblevelsshould

becheckedwhenvitaminDdeficiencyisencounteredandvice

versa.Inaddition,theremaybearoleforvitaminD

supple-mentationthroughimmunomodulationinthe treatmentof

ACDinthispatientpopulation,warrantingfuturestudiesfor

confirmation.

Thisstudyhaslimitations.First,thesamplesizemaylimit

thepower ofthestudy,particularlythe analysisofanemia.

Second,therateofvitaminDdeficiencymayreflectgreater

diseaseseverityoftheIBDpatientpopulationinourtertiary

centerandmaynotrepresenttheIBDpopulationingeneral,

resultinginreferralbias.Becausethisisaretrospectivestudy,

dataonlevelsofvitaminDandanemiabeforeandafterthe

ileostomywerelackinginsomepatients,ascheckingof

vita-minDbeforeileostomyhasnotbeenapartofroutineclinical

practice.Furtherstudiesconfirmingtheassociationofvitamin

DdeficiencywithanemiasubtypesinIBDpatients

indepen-dentofsurgicalstatusmaybeofinterest.Inaddition,itmay

beinterestingtocomparedifferentdosesofvitaminD

supple-mentationinpatientswithileostomyinthefuturetoestablish

if vitamin D supplementationcan ameliorate notonly the

vitamin Ddeficiency but alsoanemia inIBD patientswith

ileostomy.

In conclusion, vitamin D deficiency is common in IBD

(7)

endoscopy or histology and is associated with anemia,

PatientswithIBDand anemiashouldberoutinelyscreened

forvitaminDdeficiencyandviceversa.VitaminDdeficiency

mayplayaroleinACD.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgement

Dr.BoShenissupportedbytheEdandJoeyStoryEndowed

Chair.

r

e

f

e

r

e

n

c

e

s

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Imagem

Table 1 – Demographic, clinical, endoscopic and histologic characteristics of ileostomy patients with and without vitamin D deficiency.
Fig. 1 – Box plot distribution of vitamin D levels before and after ileostomy ( N = 26).

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