Brigham Young University Brigham Young University

BYU ScholarsArchive BYU ScholarsArchive

Student Works

2016-07-27

Differentiating Celiac Disease, Lactose Intolerance, and Irritable Differentiating Celiac Disease, Lactose Intolerance, and Irritable

Bowel Syndrome in the Primary Care Setting Bowel Syndrome in the Primary Care Setting

Sophia M. Larimer Brigham Young University - Provo, sgalgiani@gmail.com

Donna Freeborn

Karlen E. Luthy Brigham Young University - Provo

Follow this and additional works at: https://scholarsarchive.byu.edu/studentpub

The College of Nursing showcases some of our best evidence based scholarly papers from

graduate students in the Family Nurse Practitioner Program. The papers address relevant

clinical problems for advance practice nurses and are based on the best evidence available.

Using a systematic approach students critically analyze and synthesize the research studies to

determine the strength of the evidence regarding the clinical problem. Based on the findings,

recommendations are made for clinical practice. The papers are published in professional

journals and presented at professional meetings.

BYU ScholarsArchive Citation BYU ScholarsArchive Citation Larimer, Sophia M.; Freeborn, Donna; and Luthy, Karlen E., "Differentiating Celiac Disease, Lactose Intolerance, and Irritable Bowel Syndrome in the Primary Care Setting" (2016). Student Works. 182. https://scholarsarchive.byu.edu/studentpub/182

This Master's Project is brought to you for free and open access by BYU ScholarsArchive. It has been accepted for inclusion in Student Works by an authorized administrator of BYU ScholarsArchive. For more information, please contact scholarsarchive@byu.edu, ellen_amatangelo@byu.edu.

DifferentiatingCeliacDisease,LactoseIntolerance,and

IrritableBowelSyndromeinthe

PrimaryCareSetting

SophiaLarimer

Anevidencebasedscholarlypapersubmittedtothefacultyof

BrighamYoungUniversity

inpartialfulfillmentoftherequirementsforthedegreeof

MasterofScience

DonnaFreeborn,ChairKarlenE.Luthy

CollegeofNursing

BrighamYoungUniversity

July2016

Copyright©2016SophiaLarimer

ABSTRACT

DifferentiatingCeliacDisease,LactoseIntolerance,andIrritableBowelSyndromeinthe

PrimaryCareSetting

SophiaM.LarimerCollegeofNursing

BYUMasterofScience

Thepurposeofthispaperistoassistnursepractitioners(NPs)andotherprimarycare

providersindifferentiatingbetweenceliacdisease(CD),lactoseintolerance(LI),and

irritablebowelsyndrome(IBS)inadults.TheHealthSource:Nursing/AcademicEdition,

CINAHL,MEDLINE(EBSCO)searchengineswereutilizedtoaccesssystematicreviewsand

primaryresearcharticlespublishedbetween2009–2016.Currentliteraturesupportsthat

athoroughhistoryandphysicalmustbeconductedandalarmingsymptomsmustbe

investigatedtoruleoutworrisomediagnoses.Basedonsubtlecharacteristicsgathered

fromthehistoryandphysical,theNP’sexaminationandtestingwillhelpdistinguishCD,LI,

andIBS.Nursepractitionersshoulduseasequentialprocessofexaminationandtesting

(seeFigure-1)todistinguishgastrointestinaldisordersthatsharecommonsymptoms.

Keywords:celiacdisease,lactoseintolerance,irritablebowelsyndrome,diarrhea

TABLEOFCONTENTS

DifferentiatingCeliacDisease,LactoseIntolerance,andIrritableBowelSyndromeinthe

PrimaryCareSetting………………………………………………………………………………………………….……1

Methods…………………………………………………………….…………………………………………………………..2

BackgroundInformationonCD,LI,andIBS……………….……………………………….……………………2

CeliacDisease…………………..…………………………………………………………..………………………2

LactoseIntolerance…………………………………………………..………………………………………….4

IrritableBowelSyndrome.…………………………………………………..……..…………………………5

CurrentRecommendationsforDiagnosingCD……….……….………………..……….……………………..6

SerologicalTesting…………………..…………..…………………………………………………………….…6

Endoscopy…………..…………………..…………..…………………………………………………………….…7

AlternativeTestingforCD…………..………..…………………………………………………………….…8

CurrentRecommendationsforDiagnosingLI…………………………..…………………….………………..9

CurrentRecommendationsforDiagnosingIBS-D…………………..………………....…………..………..10

Discussion………………………………………..………………………………………..…………………..……………..12

Limitations……….…………………………………………........…………………………………….…………12

Conclusion……………………………………………….………..…………………………………………………………13

References……………………………….…………...………………………………………………………………………14

Tables…………………..…………..…………………………………………………………………………………………..20

Figures…………………………………………...………………………………………………………………….………..21

1

DifferentiatingCeliacDisease,LactoseIntolerance,

andIrritableBowelSyndromeinthePrimaryCareSetting

Gastrointestinal(GI)disordersarefrequentlyseeninprimarycaresettingsand

commonlyincludeceliacdisease(CD),lactoseintolerance(LI),andirritablebowel

syndrome(IBS).However,thesedisordersareoftendifficulttodifferentiatebecauseeach

conditionsharecommonsymptomssuchasabdominalpain,bloating,gas,anddiarrhea.

Theseoftenvagueandcommonplacesymptomsmakethediagnosisdifficultandcontribute

todelayindiagnosis.PatientswhodevelopCDasadultsgraduallyexperienceabnormal

symptomsofdiarrheaandsteatorrhea,andasaresultthesepatientsmayperceivetheir

symptomsasbeingnormal(Brody&Murray,2014).Forexample,ittakesapproximately

oneyear(andsometimesevenaslongas10years)forpatientswithCDtobediagnosed

afterGIsymptomsappear(Fordetal.,2009;Fuchsetal.,2014).Likewise,10–15%ofthe

populationintheUnitedStatesisaffectedbyIBS,butonly5–7%areactuallydiagnosed

(NationalDigestiveDiseasesInformationClearinghouse,2013),andusuallyonlyaftertheir

primarycareprovider(PCP)hasreferredthemtoagastroenterologist(El-Salhy,Lomholt-

Beck,&Gundersen,2011).

Abdominalcomplaintscomprise30–50%ofreportedcasesintheprimarycaresetting;

therefore,nursepractitioners(NPs)mustbewellversedinGI-relateddisorders.Although

CD,LI,andIBSpresentwithsimilarsymptoms,thepathologydiffers,and,ifmisdiagnosed,

irreversibleGIdamageandnutritionaldeficienciesmightresult.AccordingtoPirontietal.

(2010),patientscomplainingofchronicdiarrheaand/orabdominalpainsufferfrom

microscopicdamageduetoanunderlyingpathologicalprocess81%ofthetime.Therefore,

itisimperativethatNPsmakeaccurateandtimelydiagnosesnotonlytoprevent

2

pathologicaldiseaseprocessesfromensuing,buttoimprovetheirpatient’squalityoflife

(Schuppan&Zimmer,2013;Strauch&Cotter,2011;Thom,Longo,Running,&

Ashley2009).Accordingly,thepurposeofthispaperistointroduceNPstoasystematic

approachforsuccessfullydifferentiatingCD,LI,andIBSinadults.

Methods

Collectively,therearefewsystematicreviewsandmeta-analysespublishedon

distinguishingCD,IBS,andLI;thereare,however,avarietyofresearchstudiesavailableon

thesetopicsindividually.Datawereaccessedthroughseveralsearchengines.First,the

CochraneDatabasewasaccessedtoidentifyanymeta-analysesstudyingthesedisorders

conjointly.Next,theHealthSource:Nursing/AcademicEdition,CINAHL,MEDLINE(EBSCO)

searchengineswereusedtoaccessarticlespublishedinEnglishbetween2009–2015.

Searchtermsincluded“celiac,”“CD,”“lactoseintolerance,”“LI,”“irritablebowel,”“IBS,”and

“diagnose.”

BackgroundInformationonCD,LI,andIBS

CeliacDisease

Affecting0.5–1%ofpeopleworldwide,CDisageneticallyorautoimmunebasedchronic

enteropathyofthesmallintestinethatiscausedbyanintolerancetogluten(Mehdi,

Sakineh,Mohammad,Mansour,&Alireza,2012;Schuppan&Zimmer,2013).Glutenisa

complexofwater-solubleproteinthatisacomponentinwheat,barley,bulgur,durum,rye,

andspelt.Otherfoodscontainingglutenthatpatientsmightbeunfamiliarwith,include

beer,candy,gravies,imitationmeatsorseafood,processedluncheonmeats,salad

dressings,soysauce,self-bastingpoultry,andsomesoups(TheMayoFoundation,2013).

PeoplewhohavethegeneticpredispositionforCDtypicallycarrytheHLA-DQ2orHLA-

3

DQ8genes(90%and10%,respectively)(Schuppan&Zimmer,2013;Strauch&Cotter,

2011).Patientswithgenetic-basedandautoimmunediseases(especiallyTurnersyndrome,

Downsyndrome,typeIdiabetesmellitus[DM1],andthyroiddisease),aswellasfirst-

degreerelativesofpatientswithCD,areconsideredtobehighriskfordevelopingCD.This

geneticlinkcausesclassIIhumanleukocyteantigenstoproduceautoantibodiesagainstthe

enzymetissuetransglutaminase(tTG),whichbecomesactivatedinthepresenceofgluten

(Schuppan&Zimmer,2013;Strauch&Cotter,2011).Asthisautoimmuneprocess

proceeds,itdamagesthevilliliningthemucosaofthesmallintestineandaltersthe

environmentwherenutrientsareabsorbed(Leffler&Schuppan,2010).Oncediagnosed,

thisinflammationcanbemanagedsimplybyexcludingglutenfromthediet(El-Salhyetal.,

2011;Fordetal.,2009).

Celiacdiseaseinvolvesavarietyofsymptomswithbothgastrointestinalandsystemic

manifestations,usuallylastinglongerthan3months.Apatienttypicallypresentswith

diarrhea,unexplainedweightloss,abdominaldistention,bloating,dyspepsia,and

flatulence(Schuppan&Zimmer,2013).Itisnotuncommonforpaintobespecifically

locatedintherightlowerabdomen,andevenaccompaniedbyapalpablemass,raising

suspicionsofappendicitisorCrohn’sdisease(Gikas&Triantafillidis,2014).Systemic

manifestationsofCDincludemigraines,chronicfatigue,depression,irritability,Duhring’s

dermatitisherpetiformis,oralaphthousulcers,lossofdentalenamel,iron-deficiency

anemia,anorexia,osteoporosis,jointpain,growthfailure,shortstature,delayedpuberty,

amenorrhea,earlymenopause,reducedfertility,andepilepsy(Boettcher&Crowe,2013;

Kurppaetal.,2009;Rubio-Tapia,Hill,Ciarán,Calderwood,&Murray,2013;Strauch&

Cotter,2011).Patientswhopresentedwithcoexistingmusculoskeletalorneurological

4

disorders,diarrhea,abdominalpain,iron-deficiencyanemia,orfemale,werefoundtohave

experienceadiagnosticdelaybeforebeingdiagnosedwithCD(Fuchsetal.,2014).Itis

importantforNPstorecognizethesesystemicmanifestationstodistinguishCDfromother

boweldisorders.

LactoseIntolerance

Lactoseintoleranceisthemostcommonmetabolicfoodsensitivity,affecting60–70%of

peopleworldwide.Approximately20%ofthoseaffectedareEuropeansandAmericans

(Carter&Attel,2013;Peretsetal.,2014).Primarylactosedeficiencyisthemostcommon

causeofLIandisfoundmostfrequentlyinSouthAmerica,Africa,Asia,anddescendants

fromthoseareas.Secondarylactosedeficiencyresultsfrominjuryandinflammationofthe

brushborderofthesmallintestine,andcanalsobecausedbybacterialovergrowth,

gastroenteritis,CD,anddisordersthatcauserapidgastrointestinalmotility(Carter&Attel,

2013;Yangetal.,2013).Lactoseintoleranceusuallybeginsinchildhood,butitismost

prevalentinadulthood,becausethelactaseenzymeprogressivelydecreasesoverthe

lifespan(Boettcher&Crowe,2013;Furnarietal.,2013;Peretsetal.,2014).Lactase

persistenceisatermusedtodescribethecapabilityofbeingabletodigestlactoseasan

adult.Abouttwothirdsofpeopleintheworlddonotcarrythegeneticmakeupthatallows

forlactaseproduction,andarethereforelactasenon-persistent.Genetictestingisavailable

toidentifypeoplewhoarelactasenon-persistent,andcanbescreenedfortheC/C(-13910)

genotype(sensitivity93%andspecificity100%).AdditionaltestingisavailablefortheT/C

(-13910)gene,butthesepatientscaneitherbelactasepersistentornon-persistent

(Baffour-Awuahetal.,2015).

5

Lactoseisadisaccharidesugarfoundindairyproductssuchasmilk,yogurt,andcheese

thatrequiresthelactaseenzymetobreakitdownintoglucoseandgalactose.Inadequate

levelsofthelactaseenzymeresultinabdominaldiscomfort,bloating,gas,anddiarrhea,

becauseundigestedlactoseinthecolonisfermentedbybacteria(Boettcher&Crowe,2013;

Campbelletal.,2010;Carter&Attel,2013).PeoplewithLIcangenerallytolerate12grams

oflactose(1cupofmilk)withsymptomstypicallybeginningwhen40gramsoflactoseare

ingested.However,ifminuteamountsoflactosecausedistressingsymptoms,arare

disordercalledcongenitallactasedeficiencyshouldbeconsidered(Bolin2009;Campbellet

al.,2010;Yangetal.,2013).Studieshaveshownthatdiarrheapre-dominantIBS(IBS-D)

patientsreleasegreateramountsofinflammatorycellsafterlactoseingestioncomparedto

theaverageperson,andfindsymptomreliefwithalactose-freediet(Yangetal.,2014).

Althoughlactoseintoleranceisquitecommon,itcanbedifficulttodifferentiatewhenit

coexistswithotherdisorders,suchasIBSandCD.

IrritableBowelSyndrome

Irritablebowelsyndromeaffects10–15%oftheworld’spopulation(butmostcasesare

concentratedinNorthAmerica),isasetofGIsymptomsresultingfromirregularrelaxation

andcontractionofthebowel(NationalDigestiveDiseasesInformationClearinghouse,

2013).Thesesymptomsarethoughttooriginatefromanalterationintheneuromuscular

functionofthesmoothmuscleliningofthelargebowel,whichnormallyrelaxesand

contractsinacoordinatedrhythm(Bolin,2009;Fordetal.,2009;MayoFoundationfor

MedicalEducationandResearch,2011).Evidencehassupportedtheideathattheremaybe

aconnectionbetweenexcessivemicroflorainthegut,aswellasexcessiveinflammation

andcytokineactivity(Simsek,2011;Yangetal.,2014).RiskfactorsforIBSincludefemale

6

gender,beingbetweentheagesof20–40,andhavingpsychosocialissuessuchasanxiety,

depression,personalitydisorders,andabuse(Chapman,Chen,&Leaver,2015;Simsek,

2011).ThefoursubtypesofIBSareIBSwithdiarrhea(IBS-D),IBSwithconstipation(IBS-

C),mixedIBS(IBS-M),andunsubtypedIBS(IBS-U).ItisnotablethatIBS-Disthesubtype

mostfrequentlyconfusedwithotherboweldisorders.Thesepatientstypicallyexperience

diarrheaandabdominalcrampingthatmainlyoccursinthemorningsandaftermeals.

Othercomplaintsincludemucusinthestool,fecalincontinence,feelingsofincomplete

evacuation,andpainrelievedbydefecation(Yangetal.,2013;Yangetal.,2014).Anorexia,

steatorrhea,nocturnalpainordiarrhea,progressivepain,andbloodystoolsareabnormal

andconsideredinconsistentwiththediagnosisofIBS-D,thusrequiringfurthertesting

(Chapmanetal.,2015).Irritablebowelsyndromedoesnotcausepermanentdamagetothe

colonorincreasetheriskforcolorectalcancer,althoughitdoesseverelyimpactpatients’

qualityoflife.ThereisapossibilitythatCDandIBS-Dcancoexistsimultaneously,butthere

areconflictingresultssupportingroutinescreeningoftheseconcurrently(Bakhshipouret

al.,2012;Cash,2011;El-Salhyetal.,2011;Shahbazkhanietal.,2003).

CurrentRecommendationsforDiagnosingCD

SerologicalTesting

DiagnosisofCDfirstbeginswithserologicalscreeningforantibodies(Kurppaetal.,

2009;Tortoraetal.,2014).Thefirst-lineserologicaltestisthetissuetransglutaminase

antibody(IgAa-tTG),whichhashighsensitivity(90–98%)andspecificity(95–97%),is

inexpensive,reliable,andeasytointerpret.A“TotalIgA”levelshouldbetested

simultaneouslybecause2%ofpeoplewithCDhaveanIgAdeficiencyand,therefore,might

falselytestnegativeforIgAa-tTG.PatientswhohaveanIgAdeficiencywiththeinitial

7

testingforthe“IgAa-tTG”and“TotalIgAlevels”shouldinsteadbetestedfortheIgGanti-

DGPserumantibody(Brody&Murray,2014;Fordetal.,2009;Leffler&Schuppan,2010;

Schuppan&Zimmer,2013;Thometal.,2009).Itisimperativethatpatientsarenotona

gluten-freedietatthetimeoflabworkbecausetheabsenceofgluteninthedietgives

falselynormaltestresults.Patientswhohavenegativeserologyasaresultofbeingona

gluten-freedietcanbescreenedviatheIgAa-tTGandIgGanti-DGP,and,ifeitherserology

ispositive,canproceedtoupperendoscopywithsmallbowelbiopsy.Ifthesepatientswere

onagluten-freedietandtheirserologytestsarenegative,theycanbescreenedforHLA-

DQ2/DQ8genes.Ifthesegeneticmarkersarenegative,itcanbeassumedthattheydonot

haveCD.Ontheotherhand,iftheyarepositive,thesepatientsshouldparticipateina

glutenchallengediet.Glutenshouldbepresentinthedietforatleast2weeks(optimally8

weeks),afterwhichserologicaltestingcanbeperformed.Ifserologyisnegative,thenthe

patientshouldcontinueaglutendietfor6moreweeksandberetestedfortheIgAa-

tTG,TotalIgA,andIgGanti-DGPserumantibodies(Brookes&Murray,2014;Schuppan&

Zimmer,2013).

Endoscopy

Ifserologyispositive,orifthereisahighprobabilityofCD,patientsshouldbereferred

toagastroenterologistforanupperendoscopyandsmallbowelbiopsy(Kurppaetal.,

2009;Rubio-Tapiaetal.,2013).Asmentionedearlier,CDriskfactorsincludehavingafirst-

degreerelativewithCD;anautoimmunepredisposition,especiallytype1diabetesmellitus

andthyroiddisease;orDownsyndrome.Apersonwithseverediarrhea,weightloss,and

anemiaisatmoderatetohighriskforhavingCD(Leffler&Schuppan,2010).During

endoscopy,atleastfourbiopsiesfromtheduodenum,andatleasttwobiopsiesfromthe

8

duodenalbulbmustbeobtainedforaccurateresults.Thesesamplesaregradedaccording

totheMARSHIIIcriteria,whichcategorizestheseverityofthepatchy,inflamedlesionsof

thesmallbowel.Debateexistsregardingothernon-invasiveapproachestoconfirmCD,but

endoscopywithduodenalbiopsyisconsideredthe“goldstandard”fordiagnosis(Kurppaet

al.,2009;Schuppan&Zimmer,2013;Strauch&Cotter,2011).

AlternativeTestingforCD

Currenttrendsincludetheuseofalternative,less-invasivemethodstoruleoutCD,

especiallyfortheelderlyandhigh-riskpopulationswhomightnottolerateendoscopy.

Capsuleendoscopy,whereanencapsulatedcameraisingestedandpassedthroughtheGI

tract,maybeperformedifthepatientrefusesendoscopyandnoalarmsymptomsare

present.Anotheroption,althoughnotthepreferredmethod,istouseacombinationof

antibodytiterstopredicttheamountofdamagecausedtothesmallintestine.Tortoraand

histeam(2014)foundthatthepresenceofa-tTGlevels(>62.4)accompaniedbyelevated

EMAlevels(>45U/mL)werediagnosticforsmallboweldamage.RapidCDtestsare

availableover-the-counter,butthereislittleevidencethattheyarediagnosticforCD.

Korkutetal.(2010)reportedthattherapidBioCardCeliacTestwasaccurateinidentifying

allpatientswhohadbiopsy-provenCD.However,moreresearchmustbeconductedto

determineiftheserapidtestswillbefeasibleforuseinprimarycareclinics.Ultimately,

endoscopyisthemosteffectivewaytodiagnoseCD,butcapsuleendoscopy,antibodytiters,

andrapidCDtestsarealternativeoptionsinanon-compliantpatient(Bolin,2009;

Schuppan&Zimmer,2013;Strauch&Cotter,2011).

9

CurrentRecommendationsforDiagnosingLI

ThediagnosisofLItypicallyinvolveseliminatingdietarylactosefor2weeksto

determineifsymptomsimprove.ItissufficienttodiagnoseapatientwithLIifGI

complaintsresolvewithalactosefree-diet.However,patientswhorefusetoadheretoa

trialoflactoseeliminationshouldproceedwiththeLactoseHydrogenBreathTest(HBT)

(sensitivity[69–100%]andspecificity[89–100%]),whichisnon-invasiveandcost-

effective.DuringtheHBT,individualsaregiven2g/kgoflactoseandaretestedfor

hydrogendetectedintheirbreathatbaseline(fastingforatleast12hours)andin30-

minuteintervalsfor3hours.Participantswhohaveapersistentriseintheirhydrogen

breathlevelby20ppmareconsideredHBTpositive(Ghoshal,Kumar,Chourasia,&Misra,

2009;Peretsetal.,2014;Yangetal.,2013).EfficacyoftestingforLIusingtheHBTwas

foundtobedependentonwhethertherewasadequatepreparation.Falsepositiveresults

areseenwithinadequatepretestfastingorrecentsmoking(within6hoursoftesting),and

falsenegativeresultsoccurwithantibioticuse,diabetes,bacterialovergrowthofthesmall

intestine,gastricemptyingissues,orunderlyingpulmonarydisordersbecausethesefactors

canaffecttheamountofhydrogenlevelsdetectedinthebreathofpatients(Carter&Attel,

2013).AnalternativeoptiontotheHBTistheLactoseToleranceTest(LTT),buttheLTT

hasalowersensitivity(77–96%)andspecificity(76–94%).TheHBTisalsomore

convenientbecauseitmonitorsthepresenceofhydrogen,whichisabyproductof

undigestedlactose,whereastheLTTrequiresconsecutivebloodsamplestomonitorfor

glucoseabsorptioninthebloodtoindicatewhetherornotlactoseisbeingbrokendownin

thesmallbowel(Furnarietal.,2013).

10

ApatientwhohasanegativeHBTorLTTbutcontinuestodisplayabnormalGI

symptomsafterconsuminglactosemayreceivegenetictestingorundergoabiopsy-based

LactoseIntoleranceQuickTest(LIQT),whichhasasensitivity,specificity,andpositive

predictivevaluenearing100%.Abiopsysample,takenduringendoscopy,fromthe

duodenumisincubatedwithlactosefor20minutesandobservedforareaction.However,

becauseofitshighcostandinvasiveness,thePCPshouldorderLIQTtestingvery

conservatively.GenetictestingoftheC/C(-13910)andT/C(-13910)genesisan

alternativeoption,butisalsocostly(Carter&Attel,2013;Furnarietal.,2013;Peretsetal.,

2013).

CurrentRecommendationsforDiagnosingIBS-D

Unfortunately,therearenospecificteststhatdirectlydetectIBS-D;thediagnosisismade

onlyafterrulingoutotherdiseasesthathavesimilarGIsymptoms(El-Salhyetal.,2011).

Alarmsymptomssuchasrectalbleeding,anemia,andweightlossareconsistentwitha

pathologicalillness,andshouldbeinvestigatedaggressively.Thisinvestigationshould

includeinvasivetestingsuchasendoscopyandcolonoscopyandaconsultationwith

gastroenterology.Forcasesofchronicdiarrhea(lastinglongerthan2to4weeks)themost

basicserologicaltestsshouldincludeacompletebloodcount,C-reactiveprotein,andCD

serology(Chapmanetal.,2015).Additionaltestsincludestoolstudies,especiallyifthe

patienthasrecentlytraveledabroadorbeenhospitalized.Essentially,thepatient’sspecific

clinicalhistoryandbackgroundshoulddictatetheprovider’schoiceoftesting(Bolin,2009;

Ford,2009;NationalDigestiveDiseasesInformationClearinghouse,2013).

Iftherearenoalarmsymptomsthatneedtobeinvestigated,theROMEIIIcriteria

questionnairesprovideapositiveapproachtodiagnoseIBS.Aftertheexclusionofother

11

diagnoses,theROMEIIIcriteriacanbeusedtosubstantiateadiagnosisofIBS.Examplesof

theROMEIIIcriteriaincludethepresenceofrecurrentabdominalpainordiscomfortforat

least3days/monthinthelast3monthsthatisassociatedwithtwoormoreofthe

following:Improvementwithdefecation,onsetassociatedwithachangeinfrequencyof

stool,orachangeinformorappearanceofstool(Chapmanetal.,2015;Gikas&

Triantafillidis,2014;RomeFoundation,2006).ApositiveRomeIIIscreeningcorrelates

withathree-foldgreaterlikelihoodofhavingIBS(Fordetal.,2013).

Ontheotherhand,thereiscontroversyregardingtheuseofsubjectivequestionnairesto

substantiateafinaldiagnosisofIBS-D.Researchhasshownthatquestionnaires,including

theROMEIIIcriteria,haveasensitivityandspecificityofapproximately70%.Thisis

attributedtothefactthatsuchquestionnairesaresolelybasedonpatient-reported

symptoms(Bolin,2009;Chapmanetal.,2015).Infact,20–50%ofpatientswithconfirmed

CDmeettheROMEcriteriaforIBS,highlightingthepotentialinaccuracyofquestionnaires

(Korkutetal.,2010;Rubio-Tapiaetal.,2013).InordertoaddressgapsintheROMEIII

criteria,Pimenteletal.(2010)developedaquestionnairethatfocusesonirregularbowel

patterns,suchasmonitoringintensityofsymptomsandtheirchangesovertime.Itincludes

questionsregardingunpredictablebowelhabitsthatoccurredonadailybasis,andwere

correlatedmostspecificallywiththreeormoreweeklyvariablestoolforms(Pimenteletal.,

2010).BecauseIBS-Distechnicallyadiagnosisofexclusion,thekeyfactorisfirsttoexclude

life-threateningillnessesandtokeepCDandLIinthedifferentialwhenassessingapatient

forIBS-D.

12

Discussion

Numerousgastrointestinalissuesexist,andevenassignsandsymptomsmanifest

themselves,identifyingthespecificissuecanbecomplicated.Complaintsofabdominal

pain,bloating,gas,anddiarrheaareoftenpresentinCD,LI,andIBSandcontributetoa

delayindiagnosis.Forexample,orderingaseriesofstoolstudiesisappropriateifthe

patienthasrecentlytraveledinternationallyorhasbeenhospitalized.Likewise,whenCDis

thetopdifferential,itiscrucialthattheNPscreensforafamilyhistoryofCDandother

autoimmunediseases.TheNPmustalsothoroughlyevaluatethepatientforsystemic

manifestationsofCDsuchasanemia,dermatitisherpetiformis,dentalenameldefects,

aphthousulcers,infertility,andosteoporosis.WhenIBS-Dishighlysuspected,atthevery

leastaCBC,CRP,andCDserologyshouldbeanalyzed.Ontheotherhand,itispossiblefor

differentcombinationsofCD,LI,andIBStocoexist.

Limitations

Thereareseverallimitationsofthisliteraturereview,manyofwhichareattributableto

thefactthatsomeinformationwasgatheredfromstudiesperformedworldwide.Celiac

disease,LI,andIBSeachhaveaneffectonspecificinternationalpopulations,and

synthesizingdataintoonecompositionofevidencecouldinfluencetheresultsthatwere

obtained.ManyofthestudiesthatwerepertinenttoLIinvolvedpersonsofAsiandescent.

Themajorityofthesestudieswereperformedonadultsages18–75,andresultsmightnot

beasvaluableinassistingNPsinaddressingGIissuesinthepediatricpopulation.There

wasnopersonalbenefit,bias,ormonetarygainintheprocessofcollectingpublished

literature.

13

Conclusion

Celiacdisease,LI,andIBSpresentwithsimilarcommonsymptoms,whichcanbe

misleadingandcontributetoadelayindiagnosis.TheNPmustbeexceptionallythorough

inobtainingthepatient’shistoryandperformingthephysicalexaminationinorderto

identifysubtlecluesthatwoulddirecthimorhertowardthecorrectdiagnosis.Apatient’s

age,ethnicity,gender,familyhistory,psychosocialhistory,recenttraveland

hospitalization,diet,andtimingofsymptomsshouldbeaddressed.Itiscriticalthat

patientswithalarmsymptoms(fatigue,weightloss,nocturnaldiarrhea,andbloodinthe

stool)arereferredtogastroenterologyformoreaggressivetesting,whichwouldlikely

involveendoscopy.TheNPcanusethealgorithm(Figure-1)andtable(Table-1)provided

whenheorsheencounterspatientspresentingwithsymptomssuchasabdominalpain,

bloating,gas,anddiarrhea.Theseshouldbereferencedandutilizedinaccordancewiththe

patient’sclinicalhistoryandphysicalexamination.However,theNPshouldalsoconsider

otherdifferentialsandorderadditionaltestingthatwouldbeappropriateforthe

individual’spresentation.ThepurposeofthispaperistoprepareNPstoidentifypatients

whoareaffectedbyCD,LI,orIBSinordertoquicklyandefficientlyprovidetreatment

optionsandimprovetheirpatients’qualityoflife.Therefore,itiscriticalforNPstobe

preparedwithaprocesstodistinguishboweldisorders,prioritizedifferentialdiagnosis,

andorderappropriateteststhatwouldguidethemintheirdiagnosisofCD,LI,andIBS,and

furthermorepreparethemwithteststhatconsultingspecialistsmightanticipate.

14

References

Bakhshipour,A.,Nezam,S.K.,Zakeri,Z.,Gharibi,R.,Bahari,A.,&Kaykhaei,M.A.(2012).

Coeliacdiseaseinirritablebowelsyndrome(romeIII)insoutheastiran.Arab

JournalofGastroenterology:TheOfficialPublicationofthePan-ArabAssociationof

Gastroenterology,13(1),24–27.doi:10.1016/j.ajg.2012.03.003

Baffour-Awuah,N.Y.,Fleet,S.,Montgomery,R.K.,Baker,S.S.,Butler,J.L.,Campbell,C.,

Tischfield,S.,...Hirschhorn,J.N.(2015).Functionalsignificanceofsinglenucleotide

polymorphismsinthelactasegeneindiverseUSpatientsandevidenceforanovel

lactasepersistencealleleat13909inthoseofeuropeanancestry.JournalofPediatric

GastroenterologyandNutrition,60(2),182–91.doi:10.1097/MPG.0000000000000595

Boettcher,E.,&Crowe,S.E.(2013).Dietaryproteinsandfunctionalgastrointestinal

disorders.TheAmericanJournalOfGastroenterology,108(5),728–736.doi:

10.1038/ajg.2013.97

Bolin,T.(2009).IBSorintolerance?AustralianFamilyPhysician,38(12),962–965.

Retrievedfromhttp://www.racgp.org.au/publications/afp/

Brody,J.(Interviewer)&Dr.Murray,J.(Interviewee).(2014).CeliacDisease,aCommon,but

Elusive,Diagnosis.RetrievedfromtheCeliacDiseaseFoundationWebSite:

https://celiac.org/blog/2014/09/29/cdf-medical-advisory-board-member-dr-

joseph-murray-quoted-new-york-times-article-celiac-disease-diagnosis/

Brookes,L.(Interviewer)&Murray,J.(Interviewee).(2014).DiagnosingandManaging

CeliacDiseaseinPrimaryCare:ApplicationofCurrentGuidelines[Interview

Transcript].RetrievedfromMedscapeWebSite:

http://www.medscape.com/viewarticle/820397

15

Campbell,A.K.,Matthews,S.B.,Vassel,N.,Cox,C.D.,Naseem,R.,Chaichi,J.,...Wann,K.T.

(2010).Bacterialmetabolic'toxins':anewmechanismforlactoseandfood

intolerance,andirritablebowelsyndrome.Toxicology,278(3),268–276.doi:

10.1016/j.tox.2010.09.001

Carter,S.L.,&Attel,S.(2013).Thediagnosisandmanagementofpatientswithlactose-

intolerance.TheNursePractitioner,38(7),23–28.

doi:10.1097/01.NPR.0000429894.03255.80

Cash,B.D.,Rubenstein,J.H.,Young,P.E.,Gentry,A.,Nojkov,B.,Lee,D.,...Chey,W.D.

(2011).Theprevalenceofceliacdiseaseamongpatientswithnonconstipated

irritablebowelsyndromeissimilartocontrols.Gastroenterology,141(4),1187–

1193.doi:10.1053/j.gastro.2011.06.084

Chapman,T.P.,Chen,L.Y.,&Leaver,L.(2015).Investigatingyoungadultswithchronic

diarrhoeainprimarycare.BMJ(ClinicalResearchEd.),350,h573,1-4.

doi:10.1136/bmj.h573

El-Salhy,M.,Lomholt-Beck,B.,&Gundersen,D.(2011).Theprevalenceofceliacdiseasein

patientswithirritablebowelsyndrome.MolecularMedicineReports,4(3),403–405.

doi:10.3892/mmr.2011.466

Ford,A.C.,Chey,W.D.,Talley,N.J.,Malhotra,A.,Spiegel,B.M.R.,&Moayyedi,P.(2009).

Yieldofdiagnostictestsforceliacdiseaseinindividualswithsymptomssuggestive

ofirritablebowelsyndrome:systematicreviewandmeta-analysis.Archivesof

InternalMedicine,169(7),651–658.doi:10.1001/archinternmed.2009.22

Ford,A.C.,Bercik,P.,Morgan,D.G.,Bolino,C.,Pintos-Sanchez,M.I.,&Moayyedi,P.(2013).

ValidationoftheromeIIIcriteriaforthediagnosisofirritablebowelsyndromein

16

secondarycare.Gastroenterology,145(6),1262–1270.e1261.doi:

10.1053/j.gastro.2013.08.048

Fuchs,V.,Kurppa,K.,Huhtala,H.,Collin,P.,Mäki,M.,&Kaukinen,K.(2014).Factors

associatedwithlongdiagnosticdelayinceliacdisease.ScandinavianJournalof

Gastroenterology,49(11),1304–1310.doi:10.3109/00365521.2014.923502

Furnari,M.,Bonfanti,D.,Parodi,A.,Franzè,J.,Savarino,E.,Bruzzone,L.,...Savarino,V.

(2013).Acomparisonbetweenlactosebreathtestandquicktestonduodenalbiopsies

fordiagnosinglactasedeficiencyinpatientswithself-reportedlactoseintolerance.

JournalofClinicalGastroenterology,47(2),148–152.

doi:10.1097/MCG.0b013e31824e9132

Ghoshal,U.C.,Kumar,S.,Chourasia,D.,&Misra,A.(2009).Lactosehydrogenbreathtest

versuslactosetolerancetestinthetropics:doespositivelactosetolerancetest

reflectmoreseverelactosemalabsorption?TropicalGastroenterology:Official

JournalofTheDigestiveDiseasesFoundation,30(2),86–90.

Gikas,A.,&Triantafillidis,J.K.(2014).Theroleofprimarycarephysiciansinearly

diagnosisandtreatmentofchronicgastrointestinaldiseases.InternationalJournalof

GeneralMedicine,7,159–173.doi:10.2147/IJGM.S58888

Korkut,E.,Bektas,M.,Oztas,E.,Kurt,M.,Cetinkaya,H.,&Ozden,A.(2010).Theprevalence

ofceliacdiseaseinpatientsfulfillingromeIIIcriteriaforirritablebowelsyndrome.

EuropeanJournalofInternalMedicine,21(5),389–392.

doi:10.1016/j.ajem.2010.06.004

17

Kurppa,K.,Collin,P.,Viljamaa,M.,Haimila,K.,Saavalainen,P.,Partanen,J.,...Kaukinen,K.

(2009).Diagnosingmildenteropathyceliacdisease:arandomized,controlled

clinicalstudy.Gastroenterology,136(3),816–823.doi:10.1053/j.gastro.2008.11.040

Leffler,D.A.&Schuppan,D.(2010).Updateonserologictestinginceliacdisease.The

AmericanJournalofGastroenterology105,2520–2524doi:10.1038/ajg.2010.276

MayoFoundationforMedicalEducationandResearch.(2011).IrritableBowelSyndrome.

Retrievedfromhttp://www.mayoclinic.org/diseases-conditions/irritable-bowel-

syndrome/basics/definition/con-20024578.

Mehdi,Z.,Sakineh,E.,Mohammad,F.,Mansour,R.,&Alireza,A.(2012).Celiacdisease:

Serologicalprevalenceinpatientswithirritablebowelsyndrome.Journalof

ResearchinMedicalSciences :TheOfficialJournalofIsfahanUniversityofMedical

Sciences,17(9),839–842.

NationalDigestiveDiseasesInformationClearinghouse.(2013).IrritableBowelSyndrome.

Retrievedfromhttp://digestive.niddk.nih.gov/ddiseases/pubs/ibs/.

Perets,T.T.,Shporn,E.,Aizic,S.,Kelner,E.,Levy,S.,Bareli,Y.,...Dickman,R.(2014).A

diagnosticapproachtopatientswithsuspectedlactosemalabsorption.Digestive

DiseasesandSciences,59(5),1012–1016.doi:10.1007/s10620-013-2980-7

Pimentel,M.,Hwang,L.,Melmed,G.Y.,Low,K.,Vasiliauskas,E.,Ippoliti,A.,...Sahakian,A.

(2010).NewclinicalmethodfordistinguishingD-IBSfromothergastrointestinal

conditionscausingdiarrhea:TheLA/IBSdiagnosticstrategy.DigestiveDiseasesand

Sciences,55(1),145–149.doi:10.1007/s10620-008-0694-z

Pironti,A.,Tadeu,V.,Pedroni,A.,Porcu,A.,Manca,A.,Massarelli,G.,Dore,M.P.(2010).Role

ofroutinesmallintestinalbiopsyinadultpatientwithirritablebowelsyndrome-like

symptoms.MinervaMedica,101(3),129–134.

18

RomeFoundation.(2006).RomeIIIDiagnosticCriteriaforFunctionalGastrointestinal

Disorders.Retrievedfrom

http://www.romecriteria.org/assets/pdf/19_RomeIII_apA_885–898.pdf.

Rubio-Tapia,A.,Hill,A.D.,Ciarán,K.P.,Calderwood,A.H,&Murray,J.A.(2013).Diagnosis

andmanagementofceliacdisease.AmJGastroenterol.2013;108:656–676;

doi:10.1038/ajg.2013.79

Schuppan,D.,&Zimmer,K.P.(2013).Thediagnosisandtreatmentofceliacdisease.

DeutschesÄrzteblattInternational,110(49),835–846.

doi:10.3238/arztebl.2013.0835

Shahbazkhani,B.,Forootan,M.,Merat,S.,Akbari,M.R.,Nasserimoghadam,S.,Vahedi,H.,&

Malekzadeh,R.(2003).Coeliacdiseasepresentingwithsymptomsofirritablebowel

syndrome.AlimentaryPharmacology&Therapeutics,18(2),231–235.

doi:10.1046/j.1365-2036.2003.01666.x

Simsek,I.(2011).Irritablebowelsyndromeandotherfunctionalgastrointestinaldisorders.

JournalOfClinicalGastroenterology,45Suppl,S86–S88.doi:

10.1097/MCG.0b013e31821fbd6f

Strauch,K.,A.,&Cotter,V.,T.(2011).Celiacdisease:Anoverviewandmanagementfor

primarycarenursepractitioners.JournalforNursePractitioners,7(7),588–599.

doi:10.1016/j.nurpra.2011.03.003

Thom,S.,Longo,B.M.,Running,A.F.,&Ashley,J.M.(2009).Celiacdisease:Aguideto

successfuldiagnosisandtreatment.JournalforNursePractitioners,5(4),244–253

Tortora,R.,Imperatore,N.,Capone,P.,DePalma,G.D.,DeStefano,G.,Gerbino,N.,...Rispo,

A.(2014).Thepresenceofanti-endomysialantibodiesandthelevelofanti-tissue

transglutaminasescanbeusedtodiagnoseadultcoeliacdiseasewithoutduodenal

19

biopsy.AlimentaryPharmacology&Therapeutics,40(10),1223–1229.

doi:10.1111/apt.12970

Yang,J.,Deng,Y.,Chu,H.,Cong,Y.,Zhao,J.,Pohl,D.,...Fox,M.(2013).Prevalenceand

presentationoflactoseintoleranceandeffectsondairyproductintakeinhealthy

subjectsandpatientswithirritablebowelsyndrome.ClinicalGastroenterologyand

Hepatology:TheOfficialClinicalPracticeJournalofTheAmericanGastroenterological

Association,11(3),262–268.e261.doi:10.1016/j.cgh.2012.11.034

Yang,J.,Fox,M.,Cong,Y.,Chu,H.,Zheng,X.,Long,Y.,...Dai,N.(2014).Lactoseintolerance

inirritablebowelsyndromepatientswithdiarrhoea:Therolesofanxiety,activationof

theinnatemucosalimmunesystemandvisceralsensitivity.AlimentaryPharmacology

&Therapeutics,39(3),302–311.doi:10.1111/apt.12582

20

Table-1.CharacteristicsdifferentiatingCD,LI,andIBS

DiseaseType

Population

RiskFactors

Signs&Symptoms

Timing

ofSymptoms

Tests

CeliacDisease

1%ofworldMalesandfemalesAllagesAllethnicities,butmostprevalentinEuropeans

Genetics:HLA-DQ2&DQ8genes1°or2°relativewithCDHavinganotherautoimmunedisease

Typicalsymptoms:Anorexia

Diarrhea

BloatingAbdominalpain

Systemicsymptoms*

DailySymptomspresentgraduallySymptomshavebeenpresentlongerthan3mos.

IgA-tTG&TotalIgA.IfTotalIgAisdeficient,thentesttheIgGanti-DGPIfserologyispositive,proceedwithendoscopy&duodenalbiopsy

IrritableBowelSyndrome

10–15%worldwideFemalesAges20–40NorthAmerica

Mentalhealthhistory(anxiety,depression,personalitydisorders,historyofabuse)

Familyhistory

Painrelievedbydefecation

Varyingstoolforms(>3/wk)

Mucusinthestool

Bloating

AbdominalPain

Cramping

Diarrhea

Usually>3mos.

Wakinghours(morningsandaftermeals)

Processofelimination.CBC,CRP,and(IgA-tTG/TotalIgA)RomeIIICriteria

LactoseIntolerance

60–70%worldwideIncreaseswithageAllethnicities,butmostcommoninAsians,AfricanAmericans,Indians,Hispanics

Genetics:C/C(-13910)&T/C(-13910)Injuryordiseasesaffectingthesmallintestine:(i.e.,bacterialovergrowth,CD,post-surgeryorchemotherapyetc.)

Diarrhea

Nausea

Bloating

AbdominalCramping

Flatulence

Vomiting

Post-lactoseingestion(usually1–2haftermeals)

LactoseEliminationdietfor2wks.HydrogenBreathTestLactoseIntoleranceQuickTestGeneticTestingC/C(-13910)&T/C(-13910)

*Systemic Symptoms for CD: Iron-deficiency anemia, lactose intolerance, chronic fatigue, joint pain,osteoporosis, migraines, depression, irritability, epilepsy, vitamin deficiencies, protein-caloriemalnutrition,shortstature,failuretothrive,delayedpuberty/earlymenopause,infertility,dentalenameldefects,recurrentaphthousstomatits,dermatitisherpetiformis,andotherautoimmunedisorders.

21

Figure-1.SystematicApproachforDifferentiatingCD,LIandIBS