7/9/2017 CrohnDiseaseTreatment&Management:ApproachConsiderations,PharmacologicTherapyforDiarrhea,AntiinflammatoryandImmunosuppressantTh

CrohnDiseaseTreatment&Management
Updated:Jan06,2017
Author:LeylaJGhazi,MDChiefEditor:PraveenKRoy,MD,AGAFmore...

TREATMENT

ApproachConsiderations
ThegeneralgoalsoftreatmentforCrohndiseaseareasfollows:

Toachievethebestpossibleclinical,laboratory,andhistologiccontroloftheinflammatorydiseasewiththe
leastadverseeffectsfrommedication
Topermitthepatienttofunctionasnormallyaspossible
Inchildren,topromotegrowthwithadequatenutrition

TreatmentofCrohndiseasehaschangedoverthepastfewyears,reflectingnewtherapiesthatcantargetspecific
locationsinthegastrointestinal(GI)tractandspecificcytokines.Thedevelopmentofbiologicantitumornecrosis
factor(antiTNF)agents(eg,infliximab,adalimumab,certolizumabpegol,andnatalizumab)hassignificantly
advancedthetreatmentofCrohndiseaseandimprovedtheinductionandmaintenanceofclinicalremissionin
patientswithmoderatetoseveredisease,especiallyinthosewhoarecorticosteroiddependent.[81]

IfmedicaltherapyforactiveCrohndiseasefails,surgicalresectionoftheinflamedbowel,withrestorationof
continuity,isindicated.Urgentsurgerymayberequiredinrarecasesofsustainedorrecurrenthemorrhage,
perforation,abscess,andtoxicmegacolon.Partialsmallbowelobstructionorintraabdominalabscessmay
sometimesbetreatedconservativelywithintravenous(IV)hydration,nasogastricsuction,andparenteralnutritionif
thereisnoevidenceofischemia.[2,82]

In2013,thefirstrandomizedcontrolledtrialofstemcelltransplantationintreatmentresistantCrohndiseasewas
performedin45patientswithmoderatelytoseverelyactivedisease.Allpatientsunderwentstemcellmobilization
withcyclophosphamideandfilgrastimandwerethenrandomlyassignedtoimmediatestemcelltransplantation(at1
month)ordelayedtransplantation(at13monthscontrolgroup).At1yearfollowup,objectiveendoscopicfindings
weresubstantiallybetterinthetreatmentgroupontheSimpleEndoscopicScoreforCrohn'sDisease(SESCD),the
meanlowergastrointestinalscorefellfrom13to4inthetreatmentgroupbutremainedunchangedinthecontrol
group.ThetreatmentgroupalsoshowedagreaterdecreasethanthecontrolgroupinmedianCrohn'sDisease
ActivityIndexscore(approximately165vs50points).Twothirdsofthetreatmentgroupwereabletodiscontinue
immunosuppressivedrugsandsteroidsat1year,comparedwith15%ofthecontrolgroup.[83]

About7%oflargebowelstricturesinpatientswithlongstandingCrohndiseasearemalignanttheseshouldbe
surveyedwithmultiplebiopsiesandcytologicbrushingforneoplastictransformation.[7]Resectionisgenerally
performedwhenstricturescannotbeappropriatelysurveyed,ifneoplasticchangesareobserved,orobstructionis
persistent.[7]

Outpatientvsinpatientmanagement
ManypatientswithanexacerbationofCrohndiseasecanbetreatedonanoutpatientbasis.However,ifaserious
complicationofCrohndisease(eg,obstruction,perforation,abscess,orhemorrhage)isaconcernorifoutpatient
treatmentfails,IVtherapy(eg,corticosteroids,antibiotics,ortotalparenteralnutrition[TPN])mayberequired,and
hospitalizationiswarranted.

Patientsshouldbeexaminedonaregularbasis,withthefrequencyofexaminationdependingontheseverityand
activityoftheirdisease.Followuplaboratoryworkupanddiagnostictestingshouldbeperformedregularlyas
neededtomonitorthesafetyandsuccessoftherapy.

Stepupvstopdownapproach
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TherapyformildCrohndiseaseistypicallyadministeredinasequentialstepupapproach,inwhichlessaggressive
andlesstoxictreatmentsareinitiatedfirst,followedbymorepotentmedicationsorproceduresiftheinitialtherapy
fails.Patientsaretreatedwithpreparationsof5aminosalicylicacid(5ASA),antibiotics,andnutritionaltherapy.
However,theuseof5ASAforthetreatmentofCrohndiseaseiscontroversialonlyasmallsubsetofpatientsmay
benefitfromthisagent.

Ifnoresponseoccursorifthediseaseismoreseverethaninitiallythought,corticosteroidsandinhibitorsofDNA
synthesis(ie,immunomodulators)with6mercaptopurine(6MP)/azathioprineormethotrexateareadministered.
Finally,biologicagents(infliximab,adalimumab,certolizumabpegol,andnatalizumab)andsurgicaltherapiescanbe
useful.

ForthetreatmentofmoderatetosevereCrohndisease,currentrecommendationsincludethetopdownapproach,
whichdiffersfromtheconventionalstepupapproachinthatmorepotentagentsareadministeredinitially.Topdown
therapiesincludebiologicagentsandsteroidsasneededversuscombinationtherapywithbothbiologicdrugsand
immunomodulatoragents.

Randomizedtrialshaveshownthatthecombinationofazathioprineor6MPwithabiologicagentismoreeffectivein
theinductionofremission,steroidfreeremission,andmucosalhealingthaneitherazathioprine/6MPaloneora
biologicagentalone.[84]However,itisunclearwhetherthesefindingsholdtrueinclinicalpracticethus,physicians
mustconsidertherisksandbenefitsoftherapytoavoidovertreatment.

Atpresent,itisclearthatasubsetofpatientswithCrohndiseaseisatahigherriskforcomplicationsofthedisease
theseindividualsshouldbeconsideredfortopdowntherapy.Poorprognosticindicatorsincludeyoungageat
diagnosis,perianaldisease,upperGItractinvolvement,multipleextraintestinalmanifestations(EIMs),active
tobaccouse,andperforating(ie,fistulizing)disease.

PharmacologicTherapyforDiarrhea
Diarrheamaydevelopasaresultofactivedisease.Otherpossiblecausesincludeacuteinfection(ie,Cdifficile),
bacterialovergrowth,lossofileocecalvalve,shortbowelsyndrome,lactasedeficiency,concomitantceliacdisease,
andfunctionalbowelsyndrome.ChronicdiarrheainCrohndiseaserespondswelltoantidiarrhealagentssuchas
loperamide,bileacidbinders(forbileaciddiarrhea),diphenoxylatewithatropine,andtinctureofopium.Suchagents
shouldbeconsideredwithcareinactivecolitisbecauseoftheriskoftoxicmegacolon.

Patientswithterminalilealdiseaseorpreviousterminalilealresectionmaynotabsorbbileacidsnormally,andthis
abnormalitycanleadtosecretorydiarrheainthecolon.Thesepatientsmaybenefitfrombileacidsequestrants(eg,
cholestyramineorcolestipol).Thosewhohaveextensiveilealdiseaseorhaveundergoneresectionofmorethan
100cmoftheileumhavedefectivebilesaltabsorptionanddevelopsteatorrheatheybenefitfromalowfatdietand
mediumchaintriglyceridepreparations.Bilesequestrantsexacerbatethistypeofdiarrhea.

Abdominalcrampsmaybereducedwithantispasmagentssuchaspropantheline,dicyclomine,orhyoscyamine.
However,thesedrugsshouldnotbeusedifthereisthepossibilityofbowelobstruction.[2,82]

AntiinflammatoryandImmunosuppressantTherapyforActiveCrohn
Disease
ForcolonandsmallbowelinflammationinCrohndisease,antiinflammatorydrugsorantibioticsarehelpful.
Sulfasalazineisusefulmainlyincolonicdiseasetheactivecompound5ASAisreleasedinthelargebowelby
bacterialdegradationoftheparentcompound.Sulfasalazinedoesnotalleviatesmallboweldiseaseandhasno
additiveeffectorsteroidsparingeffectwhenusedtogetherwithcorticosteroids.Inaddition,incontrasttoitsactionin
ulcerativecolitis,sulfasalazineseemsnottomaintainremissioninCrohndisease.[85]

Productssuchasmesalamine,whichrelease5ASAinthedistalsmallbowelwhentriggeredbypHchanges,are
moreusefulinpatientswithsmallbowelCrohndisease.Longtermmaintenancewithmesalaminemaydelayclinical
relapse.Controlledreleaseofmesalamineisthoughttobeginatthepylorusandtocontinueataconstantrate
throughoutthesmallbowelandcolonconsequently,thisdrugissometimesusedwhenproximalintestinaland
gastricCrohndiseaseisfound.

5ASAprovidesonlymodestbenefitinpreventingrelapseofCrohndiseaseinremissionaftersurgery.Itcanbe
consideredformildCrohndiseasewhenimmunosuppressivetherapyiseithernotwarrantedorcontraindicated.
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Ashortcourseofcorticosteroidtherapyisindicatedinpatientswithseveresystemicsymptoms(eg,fever,nausea,or
weightloss)andinthosewhoseconditiondoesnotrespondtoantiinflammatoryagents.Prednisoneisgenerally
helpfulinacuteinflammationwithoutsignsofobviousinfection.Inpatientswithatender,palpablemass,the
possibilityofanunderlyingabscessshouldbeexcludedbeforesteroidsarestarted.Addingantibioticssuchas
ciprofloxacinormetronidazoleisalwaysbeneficialifcoexistinginfectionexists.

Steroidsarenotindicatedformaintenance,becauseofseriouscomplications(eg,asepticnecrosisofthehip,
osteoporosis,cataract,diabetes,andhypertension).Accordingly,onceremissionisachieved,theagentisslowly
tapered.Itshouldbenotedthatsteroidsdonotmodifydiseaseorinducesustainedmucosalhealing.

Entericcoatedilealreleasepreparationswithdecreasedsystemiceffects(eg,budesonide)havebeendevelopedto
treatilealandcecalCrohndisease.BudesonideinducesremissioninactiveCrohndiseasebutislesseffectivethan
otherstandardglucocorticosteroidsandisofnobenefitinpreventingrelapse.[86]Forrelapseaftersteroid
withdrawal,othertreatmentoptionsarerequired.

Ifsteroidwithdrawalprovesdifficult,immunosuppressantssuchasazathioprineoritsactivemetabolite6MPmaybe
considered.Treatmentresponseisusuallyobservedwithin36months.Becauseoftheriskofbonemarrow
suppression,carefulsupervisionisneeded.

Beforetheinitiationoftherapy,thiopurinemethyltransferase(TPMT)activityshouldbemeasuredtoidentifypatients
predisposedtoaltereddrugmetabolism,whichincreasestheriskofearlyleukopenia.Measurementof6thioguanine
nucleotide(6TG)metabolitesishelpfulinassessingcomplianceandadjustingdosing.

MethotrexateiseffectiveininducingandmaintainingremissioninCrohndiseaseinadultsithasalsobeenshownto
beeffectiveandwelltoleratedformaintenanceofremissioninchildren.[87]Theonsetofactionisshorterfor
methotrexatethanfor6MP,andtheonceweeklydosingissometimespreferred.Whetheroraltherapyisas
effectiveasparenteraltherapyisunclear.

AsystemicreviewoftheefficacyofbiologictherapiesinIBD(seebelow)confirmedthatplaceboisinferiorto
antiTNFantibodiesandnatalizumabininducingremissionofactiveCrohndisease.[88]

BiologicTherapy
Tumornecrosisfactor(TNF),akeyinflammatorycytokineandmediatorofintestinalinflammation,isexpressed
prominentlyininflammatoryboweldisease(IBD).PatientslikelytobenefitfromantiTNFtherapyincludethe
following[81]:

PatientswhohavemoderatetoseveredebilitatingsymptomsofCrohndisease,whohavedocumentedactive
inflammation,orwhoaredependentoncorticosteroidsandunabletotapertheseagentswithoutreturnof
symptoms
PatientswhodonotshowevidenceofactivebowelinfectionasacauseofGIsymptoms

BeforeadministeringantiTNFagents,cliniciansshouldscreenpatientsforMycobacteriumtuberculosis.Inaddition,
cautionisadvisedifapatientisahepatitisBviruscarrier.[81]

InSeptember2011,theUSFoodandDrugAdministration(FDA)issuedanotificationregardingupdatestotheBlack
BoxWarningfortheentireclassofTNFblockers.[89]TheadvisoryaddressedtheriskofLegionellaandListeria
infections,aswellastheconsistencyoftheinformationintheBoxedWarningandWarningsandPrecautions
sectionsregardingtheriskofseriousinfectionsandtheassociateddiseasecausingorganisms.[89]

AnotherareaofconcernwiththeuseoftheseantiTNFmedicationsisthatseveralpatientshavebeenreportedto
developararehepatosplenicTcelllymphomawhentreatedwithdualtherapyof6MPorazathioprineaswellasa
TNFinhibitor.Althoughthishasbeenararecomplication,allreportedcaseshavebeeninadolescentsandyoung
adults.

Infliximab
InfliximabisachimericmousehumanmonoclonalantibodyagainstTNFthathasshownpromiseinCrohndisease
treatmentitblocksTNFintheserumandatthecellsurface,leadingtothelysisofTNFproducingmacrophages
andTcells.InfliximabhasalsobeenapprovedforthetreatmentofpediatricCrohndisease.
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AccordingtotheAmericanGastroenterologicalAssociation(AGA),infliximabisindicatedforthefollowing:

TreatmentofpatientswithCrohndiseasewhodonotachieveadequateclinicalresponsedespitetreatment
withconventionaltherapy(ie,acorticosteroidoranimmunosuppressiveagent)
TreatmentoffistulizingCrohndiseasethatisrefractorytoconventionaltherapy(ie,antibiotics,surgical
drainagewithexaminationunderanesthesia,immunosuppressivetherapy,orcombinationsthereof)[90]

Patientswhorespondtoinductiontherapywithinfliximabshouldreceivemaintenancetherapy.[90]

Inonestudy,nearly65%ofrefractorycasesofCrohndiseaserespondedwelltotreatmentwithinfliximab(5mg/kg),
andonethirdwentintocompleteremission.[91]Patientswhorelapsedaftertheinitialresponserespondedagainto
furtherinfusions.

Infliximabisalsoeffectiveinpatientswhohaverefractoryperianalandenterocutaneousfistulae.Currentclinical
practiceistogive5mg/kgIVat0weeks,2weeks,and6weeks,followedbymaintenanceIVinfusionsevery8
weeks.Onaverage,theeffectlastsfor12weeks.

Importantadverseeffectsincludethedevelopmentofalupuslikesyndrome,multiplesclerosis,psoriasiformrash,
andopportunisticorfungalinfections(eg,Pneumocystisjirovecipneumoniaorhistoplasmosis).Antidouble
strandedDNAisnotalwaysassociatedwithclinicallupus.Anaddedbenefitofinfliximabtreatmentisthepotential
abilitytotapersteroids,whichwilldecreasefurtheradverseeffects.[92,93]

Inastudyof115patientswithCrohndiseasewhoweretreatedfor1yearwithinfliximabandanantimetabolite,with
atleast6monthsofcorticosteroidfreeremission,andthenfollowedupat1year(median,28months),nearlyhalf
(52/11545.2%)experiencedarelapse.[94]The1yearrelapseratewas43.9%.

Inthisstudy,riskfactorsforrelapseincludedmalesex,leukocytecounthigherthan6.0109/L,Creactiveprotein
(CRP)levelof5.0mg/Lorhigher,andfecalcalprotectinlevelof300g/gorhigher.[94]However,retreatmentwith
infliximabwaseffectivein88%ofpatientswitharelapseandwaswelltolerated.

Unfortunately,infliximabisimmunogenic,andlongholidaysbetweeninfusionsmayresultinthedevelopmentof
antibodiestoinfliximabthatleadtoinfusionreactions,lossofefficacy,anddelayedhypersensitivityreactions.[95]

Adalimumabandcertolizumabpegol
TwootherantiTNFagents,adalimumabandcertolizumabpegol,maybelessimmunogenicthaninfliximaband
haveshownefficacyinthetreatmentofCrohndiseasethatisrefractorytothestandardmedicaltreatmentof
corticosteroidsandinhibitorsofDNAsynthesis.[95]

Adalimumabisarecombinanthumanimmunoglobulin(Ig)G1monoclonalantibodythatbindswithahighaffinityand
specificitytohumansolubleTNFbutnottolymphotoxin(TNF).Studyresultshaveshownthatthe
immunogenicityofadalimumabislowcomparedwiththatofthechimericagentinfliximab.[95]

Twoplacebocontrolledtrials,CLASSICIandII(CLinicalassessmentofAdalimumabSafetyandefficacyStudiedas
InductiontherapyinCrohnsdisease),showedthatadalimumabwaseffectiveforbothinductionandmaintenanceof
remissioninpatientswhowerepreviouslynaivetoantiTNFtherapy.[25,96]

TheCHARM(CrohnstrialofthefullyHumanantibodyAdalimumabforRemissionMaintenance)trialdemonstrated
thesameeffectinamixedpopulationofpatientswhowereeithernaivetoinfliximabtherapyorwhohadpreviously
beenoninfliximabtherapy.[97]Inpatientswhohadlostresponsetoorbecomeintolerantofinfliximab,theGAIN
(GaugingAdalimumabefficacyinInfliximabNonresponders)trialresultsshowedabenefitfromadalimumabtherapy
inductionwithremissionat4weeks.[98]

Furthermore,anopenlabelstudyconductedinFrancethatassessedthelongtermefficacyandsafetyof
adalimumabmaintenancetherapyinthispopulationshowedthatitwaswelltoleratedandeffectiveinmaintaining
clinicalremissioninpatientswhohadCrohndiseasewithalostresponsetoorintoleranceofinfliximab.[25,99,100]

AreviewofrandomizedclinicaltrialsusingadalimumabinthetreatmentofCrohndiseaserecommendedinitiating
adalimumabasaloadingdoseof160/80mgsubcutaneouslyatweek0/week2,followedby40mgeveryotherweek

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asamaintenancedoseinordertodeterminewhetherthereisaresponse.[81]

InthePRECISE(PegylatedAntibodyFragmentEvaluationinCrohnsDisease:SafetyandEfficacy)trials,
certolizumabpegol,ahumanizedFabantibodyfragmentconjugatedtopolyethyleneglycol,demonstratedefficacyin
maintainingremissioninpatientswithmoderatelytoseverelyactiveCrohndisease.

InPRECISE1,certolizumabyieldedgreaterclinicalresponse(37%)inpatientswithhighCRPlevels(10mg/L)at
week6thanplacebo(26%),aswellasgreaterpersistenceofresponseat6months(22%vs12%,respectively).[101]
Remissionratesdidnotdifferbetweentreatmentandplacebogroups.InPRECISE2,whenweek6responderswere
randomizedtodrugorplacebo,certolizumabyieldedclinicalremissionin36%andclinicalresponsein63%.[102]In
PRECISE3,41%ofpatientsachievedremissionat12monthsand36%at18months.[103]

Natalizumab
Natalizumabisahumanizedmonoclonalantibodythatpreventstheaccumulationoflymphocytesinthediseased
bowelbybinding47integrin(gutspecific).Italsobindsto41integrin(CNSspecific).Clinicaldataindicatethat
thisdrugiseffectiveininducingclinicalresponseandremissionofactivemoderatetosevereCrohndisease.Itis
administeredinasingle300mgdoseevery4weeksupto12weeks,atwhichtimeitmaybestoppedifitisnot
effective.

Thisdrugwasinitiallytakenoffofthemarketin2005asaresultofreportedcasesofprogressivemultifocal
leukoencephalopathy(PML)inpatientswithmultiplesclerosis[2]itwasthenreintroducedintothemarketwith
restrictionsfortheindicationofrefractorymultiplesclerosisin2006andCrohndiseasein2008.

PMLisanopportunisticinfectioncausedbytheJCvirusthattypicallyonlyoccursinpatientswhoare
immunocompromised.AsofAugust1,2012,therewere271confirmedcasesofPMLworldwideinindividuals
treatedwithnatalizumab,onewasapatientwithCrohndiseasewhowasreceiving35infusionsofnatalizumab.[104]
Individualsatriskincludethosewiththefollowing[105]:

JCvirusantibodypositivity
Previousexposuretoimmunosuppressanttherapy
Morethan2yearsoftreatmentwithnatalizumab

TheriskofdevelopingPMLislessthan1in1000users,butitincreasesto11per1000usersifall3riskfactorsare
present.[105]

NatalizumabtherapyiscurrentlyreservedforindividualswithmoderatetosevereCrohndiseasewhoareintolerant
oforhavelostresponsetootherbiologicorimmunosuppressanttherapies.TheENACT(EvaluationofNatalizumab
AsContinuousTherapy)[106]andENCORE(EfficacyofNatalizumabinCrohnsDiseaseResponseandRemission)
[107] trialsevaluatedtheefficacyofnatalizumabintheinductionofresponse(ENACT1andENCORE)and
maintenanceofresponse(ENACT2)inpatientswithactiveCrohndisease.

InENACT1,natalizumabinducedclinicalresponseatweek10inpatientswithanelevatedCRPlevel.[106]
ENCOREfounda48%clinicalresponserateand26%clinicalremissionrateatweek8.[107]InENACT2,ofpatients
fromENACT1whohadhadaclinicalresponsetonatalizumabandwhowerererandomizedtomaintenancetherapy
withnatalizumab300mgorplaceboevery4weeksfor1year,61%ofpatientsinthenatalizumabgroupmaintained
response,and44%achievedremissionthroughweeks36and60.[106]

Vedolizumab

Vedolizumab,anotherintegrinantagonist,isapprovedforCrohndiseaseandulcerativecolitis.Itisspecificfor47
integrin.Approvalwasbasedonalargephase3clinicaltrialconductedtosimultaneouslyevaluatevedolizumabfor
bothUCandCDthatincludedseveralclinicalstudiesinvolving2,700patientsinnearly40countries.

AmongpatientswithCDwhohadaresponsetoinductiontherapywithvedolizumab,39.0%ofthoseassignedto
vedolizumabevery8weekswereinclinicalremissionatweek52,comparedwith21.6%assignedtoplacebo(P<
0.001).[108]

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Ustekinumab

Ustekinumabinhibitsinterleukin(IL)12andIL23cytokines,whichplayakeyroleininflammatoryandimmune
responses.InSeptember2016,theFDAapprovedustekinumabforadultswithmoderatelytoseverelyactiveCrohn
diseasewhohave[109,110]:

Failedorwereintoleranttoimmunomodulatorsorcorticosteroids,butneverfailedtreatmentwithaTNF
blocker,OR
Failedorwereintoleranttotreatmentwith1ormoreTNFblockers

FDAapprovalwasbasedonthreephase3studies(UNITI1,UNITI2,IMUNITI)inmorethan1300patients.[109,
110] Ofpatientswhowereeithernewto,experiencedwith,orfailedbiologictherapy(TNFblockers),between34%
(UNITI1study)and56%(UNITI2study)ofpatientsexperiencedreliefofsymptomswithin6weeksafterreceiving
ustekinumabasaonetimeIVinfusion.Noticeableimprovementwasobservedasearlyas3weeks.Amajorityof
thosewhorespondedtoinductiondosingandcontinuedtreatmentwithsubcutaneous(SC)maintenancedoses
every8weekswereinremissionattheendof44weeks(52weeksfromtheinitiationoftheinductiondose).[111,112,
113]

Otheragents

TacrolimusmaybeeffectiveintreatingCrohndisease.Asystematicreviewoftheroleoftacrolimusfoundremission
ratesof44.3%forpatientswithluminalCrohndiseaseand28.6%forpatientswithperianaldiseasewhenthisagent
wasusedsystemically.[114]Thereviewnotedthatinstudiesoftopicaluseoftacrolimus,35.7%ofpatientsachieved
remissionand28.6%apartialresponse.[114]

Sideeffectsincludedtremor,paresthesia,andheadacherecurrentnephrotoxicityoccurredin16%ofpatients.[114]
Althoughthisreviewappearstosupporttheuseoftacrolimus,theinvestigatorsnotedthatrandomizedcontrolled
trialsareneeded.

MycophenolatemofetilhasbeenusedintheshortandlongtermtreatmentofdifficultIBD.Thisagentinhibitsade
novopathwayofpurinesynthesisinlymphocytes,leadingtointracellulardepletionofguanosinemonophosphate
andresultinginthesuppressionofcytotoxicTcellsandtheformationofantibodiesbyactivatedBcells.Adoseof
500mgtwicedailyin2divideddosesiswelltoleratedbypatientsandcanbeusedtoreducethesteroiddose.[2,82]

EarlystudieshavesuggestedtheuseofthehelminthTrichurissuisforthetreatmentofCrohndisease.This
suggestionisbasedontheobservationthatthediseaseiscommoninhighlyindustrializedWesterncountries,where
helminthsarerare,butuncommoninlessdevelopedareasoftheworld,wheremostpeoplecarrytheworms.Itis
believedthathelminthsdiminishimmuneresponsivenessinnaturallycolonizedhumansandreduceinflammationin
experimentalcolitis.StudiesevaluatingtheuseofTsuiseggsforthispurposeareunderway.

EvidencesupportingtheefficacyoflowdoseoralnaltrexoneforthetreatmentofCrohndiseaseislimitedthe2main
studieshadsmallpatientcohortsandshortdurationoffollowup.Thus,atpresent,thereisnoclearindicationforthe
useoflowdoseoralnaltrexoneforCrohndisease.However,asmallsubpopulationmaybenefitfromtreatment.
Further,largerstudiesmaybewarranted.

ManagementofFistulae
Fistulaebetweenbowelloops(ileoileal,ileocecal,ileosigmoid,enterovesicular,enterocutaneous,cologastric,and
coloduodenal)canoccurinpatientswithprogressiveCrohndisease.Surgicalinterventionmayberequiredleft
untreated,fistulaecancausecomplicationssuchasunexplaineddiarrhea,abdominalpain,orabscessformation.
Occasionally,medicalmanagementwithoralmetronidazoleorciprofloxacincanbeusedtotreatunderlying
infectionsandsymptomsuntilmoredefinitivemedicalorsurgicalplanningcanbeestablished.

Ingeneral,localizedandsystemicsepsisdonotoccurinfistulaethatoriginateindiseasedbowelandinvolveother
intraabdominalorgansortheskin.[7]However,thepresenceofsepsisnecessitatestheinitiationofbroadspectrum
antibioticagents.Radiologicstudiesshouldbeperformedtoruleoutconcomitantabscesses,whichshouldbe
drainedwhenpresent.Incasesofpersistentsepsis,thediseasedbowelisgenerallyexcised,whetheranabscessis
presentornot(seeSurgicalIntervention).

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PerianalfistulaecanbeadebilitatingcomplicationofCrohndisease.Amultidisciplinaryandtopdownapproachmay
berequiredtoinduceremissionofmorecomplexfistulae.Asmallstudydemonstratedthatthecombinationof
ciprofloxacinandmetronidazolein14patientswithperianalfistulaehealedthefistulaein3patientsandimproved
theconditionof85%ofthepatients.[115]

Thereisgoodevidencethatthecombinationofantibiotics,currentmedicaltherapy(antiTNFagentswithor
withoutazathioprine/6MP)andsurgicaldrainageofabscessesfollowedbysetonplacementisofgreatestefficacyin
improvingtheoutcomeofperianalfistulizingdisease.[79]

Inaddition,theuseofendoscopicultrasonography(EUS),magneticresonanceimaging(MRI),orbothtoidentifythe
anatomyandmonitorfistulaactivityinconjunctionwiththeabovementionedmanagementapproachhasbeen
showntohelpinthemaintenanceoffistulaclosure.[79]

NutritionalTherapyandDietModification
Nutritionaltherapyisanotherimportantmodalityforthetreatmentofdisease,malnutrition,andgrowthfailurein
Crohndisease.Althoughineffectiveasaprimarytherapy,nutritionalmanipulationsthatfacilitatebowelrestcanbe
effectiveadjunctsinthetreatmentofactiveCrohndisease.Adramaticreversalofmalnutritionandachangein
growthvelocitycanbeexpectedinallchildrentreatedwithadequatenutritioninconjunctionwithmedicaltherapyto
controlsymptomsofCrohndisease.

Bothparenteralandenteralnutritionareeffective.Additionally,exclusiveenteralnutrition(EEN)hasbeenshownto
beaseffectiveascorticosteroidsfortheinductionofremissionandmightpromotebetterGItractmucosalhealing.
[116] Consumptionofatleast1200kcal/dayhasbeenassociatedwithlowerratesofdiseaserelapse,butpatients

frequentlyrelapseafterinitiationofanormaldiet.[117,118,119]

Becausemostpatientshaveappetitesuppression,overnightnasogastricfeedsareoftenusedinchildren.Nighttime
supplementalenteralnutritionwithoutdaytimedietaryrestrictionshasbeenshowntobebeneficialinmaintaining
diseaseremission.Althoughtheexactmechanismofactionisunknown,beneficialeffectscouldbeduetoanaltered
intestinalflora,areducedantigenload,anddecreasedinflammatorycytokinelevels.

PatientswithCrohndiseaserequireabalanceddiet.Fibersupplementationissaidtobebeneficialforpatientswith
colonicdisease,inthatdietaryfibercanbeconvertedtoshortchainfattyacids,whichprovidefuelforcolonic
mucosalhealingalowroughagedietisusuallyindicatedforpatientswithobstructivesymptoms.

BecausepatientswithCrohndiseaseofthesmallintestineareoftenlactoseintolerant,avoidanceofdairyproducts
maybeindicated.However,calciumsupplementationmayberequired.Osteoporosisisacommonnutritional
complication,resultingnotonlyfromdecreasedcalciumabsorptioninthosewithactivesmallboweldiseasebutalso
fromthereleaseofcytokinesfrominflammatorycells,whichstimulateosteoclastactivityandleadtoincreasedbone
breakdown.Corticosteroiduseisanotherriskfactorforosteoporosis.[117,118,119]

AninternationalsurveyofenteralnutritionformulaprotocolsforchildrenwithCrohndiseasefoundthatthemost
commondurationofEENadministrationwas68weeksandthat90%ofcentersusedpolymericformulaswitha
varietyofflavoringsadded.[120]ThemostcommonrecommendationforthereintroductionoffoodafterEENwas
graduallyintroducingfoodastheuseofformulawasdecreased(52%)orbeginningalowfiberdiet(26%).[120]

Patientswhoundergoextensiveresectionoftheterminalportionoftheileummaybenefitfromalowfatdietwiththe
additionofmediumchaintriglyceridepreparations.

SelectedpatientsmayrequireTPN.ShorttermuseofTPN(givenpreoperatively)isappropriateforpatientswith
activeinflammation,abscesses,fistulae,andseveremalnutrition.LongtermTPNissuitableforpatientswhohave
undergoneextensiveintestinalresection,resultinginshortbowelsyndrome.[82]

SurgicalIntervention
Indications
SurgeryplaysanintegralroleincontrollingthesymptomsandtreatingthecomplicationsofCrohndisease,but
operativeresectionisnotcurative.Becauseofthehighrateofdiseaserecurrenceaftersegmentalbowelresection,
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theguidingprincipleofsurgicalmanagementofCrohndiseaseispreservationofintestinallengthandfunction.[1]
Recommendedindicationsforsurgicalinterventionincludethefollowing[1]:

Persistentsymptomsdespitehighdosecorticosteroidtherapy
Treatmentrelatedcomplications,includingintraabdominalabscesses
Medicallyintractablefistulae
Fibroticstrictureswithobstructivesymptoms
Toxicmegacolon
Intractablehemorrhage
Perforation
Cancer

In2007,theStandardsPracticeTaskForceoftheAmericanSocietyofColonandRectalSurgeons(ASCRS)
publishedrecommendationsforsurgeryinpatientswithCrohndisease(seeTable2,below).[7]

Table2.ASCRSIndicationsforSurgicalManagementofCrohnDisease(OpenTableinanewwindow)

OperativeIndication FactorsforConsideringSurgery

Presenceofdiseaserelatedsymptomsnotresponsiveto
medicalmanagementconditiondemonstratesan
inadequateresponse
Whenfirstandsecondlinetherapiesdonotinduce
Failedmedicaltherapy remissionsafelyinseveredisease
Beforeescalatingmedicaltherapyinsevereorsteroid
dependentdiseasewithlimitedextent(eg,diseasewith
stricturingbehavior,patientswhohavecontraindications
orriskfactorsforfurthermedicaltherapy)

Presenceofsymptomsorsignsoffreeperforation
Immediateresectionofperforatedsegment(hasa
relativelyhighmortality)
Perforation
Aftersmallbowelresectionorperforation,other
procedurescanbeperformed,asneeded(eg,endstoma,
divertedornondivertedanastomosis)

Whenlargeanteroparietal,interloop,
intramesenteric,orretroperitoneal
abscessescannotbeorare
unsuccessfullymanagedwithantibiotics
andpercutaneousdrainage
Performsurgicaldrainageinsuch
cases,withorwithoutresection

Persistententericfistulaeand
symptomsorsignsoflocalizedor
systemicsepsisdespiteappropriate
medicalmanagement
Persistentsepsiswarrantsexcisionof
thediseasedbowel,whetherornotan
abscessispresent

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Fortargetorinnocentbystanderorgans,
diseasedbowelistypicallyresected,
noninflamedbowelprimarilyclosed,and
otherinternalorgansprimarilyclosedor
allowedtohealbysecondaryintention

Note:Operativeinterventionmaybeavoided
forasymptomaticinternalfistulae

Presenceofsymptomaticstricturesinregionsnot
Obstruction
amenableorresponsivetomedicaltherapy

Presenceofasymptomaticcolonic
stricturesthatcannotbeadequately
surveyedbybiopsyorcytology
brushing

Presenceofacutecolitisandsymptomsorsignsof
impendingoractualperforation(eg,transversecolon
distention>6cmonabdominalxrayorpersistent
Inflammation gaseouscolonicdistentionindicatetoxicmegacolon,
pneumatosiscoli,evolvinglocalperitonitis,multipleorgan
failure)
Presenceofsevereorfulminantcolitis

Worseningacutecolitisorfailureto
significantlyimprovedespite4896
hoursofappropriatemedicaltherapy

Presenceofmassivehemorrhagingofanyoriginthat(1)
cannotbeorfailstobemanagedwithinterventionalor
endoscopictechniquesand(2)occursin
hemodynamicallyunstablepatients
Hemorrhage Mesentericangiographywithembolizationmaybeattempted
whenadequateendoscopicvisualizationisnotpossibleor
whenthebleedingsourcecannotbeidentifiedifthistechnique
isnotsuccessfulorthepatientishemodynamicallyunstable,
laparotomywithorwithoutintraoperativeendoscopyand
resectionoftheresponsiblebowelsegmentmayberequired

PresenceofchronicCrohndiseaseoftheileocolonor
Neoplasia colon(endoscopicsurveillance)
Presenceofadenomatousappearingpolyps(excision)

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Presenceofcarcinoma,DALM,high
gradedysplasia,multifocalcolonicor
rectallowgradedysplasia(resection)

PresenceofchronicCrohndiseaseof
theterminalileum,ileocolon,orupper
GIregion

Presenceofsignificantgrowthretardationinprepubertal
GrowthretardationandEIMs
patientsdespiteappropriatemedicaltherapy

Presenceofsymptomaticdermatologic,
oral,ophthalmologic,orjointdisorders
refractorytomedicaltherapy(resection
ofdiseasedintestine)

ASCRS=AmericanSocietyofColonand
RectalSurgeonsDALM=dysplasia
associatedlesionormassEIM=
extraintestinalmanifestationGI=
gastrointestinal.

Source:StrongSA,KoltunWA,HymanNH,
BuieWD,fortheStandardsPracticeTask
ForceofTheAmericanSocietyofColonand
RectalSurgeons.Practiceparametersforthe
surgicalmanagementofCrohnsdisease.Dis
ColonRectum.200750(11):173546.[7]

Recommendedprocedures

Unlikeulcerativecolitis,Crohndiseasehasnosurgicalcure.MostpatientswithCrohndiseaserequiresurgical
interventionduringtheirlifetime.Within15yearsofdiagnosis,70%ofpatientswithCrohndiseasehaverequired1or
moresurgicalprocedures,andmanyrequiremultipleprocedures.[41]

Approximately8590%ofpatientsdevelopdiseaserecurrencewithinthefirstpostoperativeyear.Therefore,every
attemptatconservingthesmallbowelshouldbemadeinthesurgicalapproachtoCrohndisease.However,
repeatedintestinalresectionforCrohndiseaseisamajorcauseofshortbowelsyndrome.Severalagentshavebeen
showntodecreasethelikelihoodofdiseaserecurrenceinindividualswhohavehadileocolicresections,including
antibiotics,azathioprine/6MP,andbiologicagents.[121,122,123,124,125]

TheASCRShasidentifiedrecommendedsurgicalproceduresforsitespecificCrohndisease(seeTable3,below).
[7]

Table3.ASCRSRecommendationsforSiteSpecificOperativeManagementofCrohnDisease(OpenTableinanew
window)

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Site SurgicalIntervention

Resectionoftheaffectedbowelfor
jejunal,proximalileal,terminalileal,
orileocolicdiseaseintheabsenceof
existingorimpendingshortbowel
syndrome
Ileocolostomyorproximalloop
ileostomyincaseswherethereis
Terminalileum,ileocolon,upperGItract
concernaboutdamageto
nondiseasedbowel,superior
mesentericvessels,retroperitoneal
structures
Drainageofanysepticfociwithlater
definitiveresection(afterseveral
monthsdelay)

Strictureplastyfornonphlegmonousjejunal,ileal,orileocolic
stricturesintheabsenceofexistingorimpendingshort
bowelsyndrome
Strictureplastywhenmultiplejejunalorproximal/terminal
ileumstricturesarepresent

Bypassorstrictureplastyforsymptomaticgastricor
duodenaldisease

Endoscopicdilatationofsymptomatic,accessiblestrictures
oftheintestinaltract

Note:Surgicalservicesshouldbeavailableincaseofperforation

Subtotalortotalcolectomywithend
ileostomyforcolonicdisease
Colon requiringemergencyorurgent
surgery(vialaparoscopicoropen
approach)

Segmentalortotalcolectomywithorwithoutprimary
anastomosisforcolonicdiseaserequiringelectivesurgery

Totalproctocolectomyorproctectomywithstomacreationfor
rectaldiseaserequiringsurgery

ASCRS=AmericanSocietyofColonandRectalSurgeonsGI=
gastrointestinal.

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Source:StrongSA,KoltunWA,HymanNH,BuieWD,forthe
StandardsPracticeTaskForceofTheAmericanSocietyofColon
andRectalSurgeons.Practiceparametersforthesurgical
managementofCrohnsdisease.DisColonRectum.
200750(11):173546.[7]

ThemostcommoncomplicationofCrohndisease,occurringin3050%ofpatients,issmallbowelobstruction.
Typically,itisduetointestinalstricturesfromrepeatedboutsofinflammationandsubsequentfibrosis.Forapartialor
completeobstructionrefractorytononsurgicalmanagement,surgicalinterventionisrequired.Surgicaloptions
includeresectionofthestricturedbowelandstrictureplasty.Forlong(>12cm)stricturesormultiplestricturesin
closeproximity,surgicalresectionwithprimaryanastomosisisoftenrequired.

Strictureplastyformultipleshorterstrictureshasthebenefitofconservingthebowel.AFoleycatheter(inflatedto25
mm)canbepassedthroughthelumentodetectadditionaldistalstrictures.Thestricturedbowelisincised
longitudinallytoapoint12cmbeyondthenarrowingandthenclosedtransverselywithoutresection.

Forlongormultipleconfluentstrictures,astricturoplastythatresemblesaFinneysidetosidepyloroplasty
(essentiallyasidetosidegastroduodenostomy[126]orasidetosideanastomosisofantrumandduodenumthat
doesnotexcludethepyloricarea[127])canbeusedtoconservebowellength.

Hydrostaticballoondilatationofileocolicstrictureshasbeenperformed,butitseffectsmaynotbelonglasting.
Bypassproceduresareusuallyreservedforduodenalobstructions.[128,129]

OthercomplicationsofCrohndiseasethatmayrequireoperativeinterventionincludefreeperforation,abscesses,
fistulae,toxicmegacolon,andmassivehemorrhage.Morethan10%ofpatientswithCrohndiseasehaveanintra
abdominalorpelvicabscessduringtheirlifetime.Unfortunately,manypatientsatriskforperforationorabscesswill
beoncorticosteroids,whichareknowntosuppressperitonealsignsandfeverandmaskthepresentingsignsof
infection.Computedtomography(CT)helpsconfirmthediagnosis.

Abscessesmustbedrained,eithersurgicallyorpercutaneously,andtreatedwithbroadspectrumantibiotics.
Althoughsurgicaldrainageismoreoftensuccessful,attemptingpercutaneousdrainagefirstmaysparesome
patientsanoperation.[130]

Enteroenteric,enterocutaneous,enterovesical,andrectovaginalfistulaeareoftentreatedinitiallyaccordingtothe
principlesoffistulahealingandmedicaltherapy.Ifmedicaltherapyisunsuccessful,resectionoftheinvolvedbowel
isrequiredinsymptomaticpatients.

Toxicmegacolonandmassivehemorrhagearemuchlesscommoncomplicationsbutmayrequireurgentbowel
resectionwhenpresent.TotalabdominalcolectomywithaHartmannpouchhasbeenadvocatedforfulminanttoxic
megacolonthisallowsfuturerestorationofbowelcontinuitywithasphincterpreservingileorectalanastomosis.
However,apermanentileostomymayultimatelyberequiredtotreatrecurrentrectaldisease.[131]

Inastudycomprisingastrictlydefinedcohortofpatients,Kiranetalwerenotabletoidentifysegmentalbowel
resectionasanindependentriskfactorforrecurrenceorstomaformationadditionally,theyfoundnoreductionin
qualityoflifescorestosuggestanadverseeffectofrecurrence.[132]Nevertheless,segmentalcolectomyprovides
goodfunction,andthedatasupportpracticeofaconservativeapproachwithanastomosisinanatomicallylinked
Crohndisease.

PerianalCrohndiseasepresentsaparticularlydifficultmanagementchallenge.Fissures,fistulae,andabscessmay
bemultipleandrecurrent,andrepeatoperationsmayleadtosphincterdamageandincontinence.

Trueabscessrequiresdrainage.Whenafistulatractcanbeidentified,asetoncanbeusedtopreventpremature
skinclosureandrecurrentabscesses.Theseindwellingsetonsshouldbeleftinplaceforanextendedperiod(upto
612months)toallowcompleteepithelializationofthetractasvisualizedbyMRIorEUS.Thisapproachleadstoa
chronicallydrainingfistulatract.Incaseswheresevereperianaldiseasehasdestroyedthesphincter,proctectomy
withpermanentileostomymaybenecessary.[77,133,134,135]
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Laparoscopicversusopenresection

ThelaparoscopicapproachtoCrohndiseasehasbeenshowntobefeasibleaswellassafe.[136,137]Complications
ofCrohndiseasesuchasabscesses,phlegmons,andrecurrentdiseasehavebeensafelytreatedlaparoscopically
andarenotcontraindicationstolaparoscopyinthesepatients.

Althoughopenresectionisstillperformedbymanysurgeonsandshouldbeconsideredthecriterionstandard,the
laparoscopicapproachisbeingemployedwithincreasingfrequency.Inchildren,laparoscopicintestinalresections
havebeenusedforproctectomyandpullthroughproceduresinHirschsprungdiseaseformorethanadecade.[138]
SegmentalintestinalresectionsinCrohndiseasecaneasilybeaccomplishedaswell.

Nodifferenceinrecurrencerateshasbeenfoundinadultsundergoinglaparoscopicasopposedtoopenileocolic
resection,andthelaparoscopicapproachhasbeenfoundtoshortenthedurationofpostoperativeileussignificantly.
[139,140] Adultpatientswhoundergolaparoscopicileocecectomytendtoexperienceabetterqualityoflifethanthose
whoundergotheequivalentopenprocedure.Inaddition,patientsundergoinglaparoscopicresectionreportthatthey
aremoresatisfiedwiththephysicalappearanceoftheirsurgicalscar.[141]

Astudycomparinglaparoscopicileocolicresectionwithinfliximabinthetreatmentofdistalileitisisinprogressinthe
Netherlands.Theprimaryoutcomesofthestudyarequalityoflifeandcosts,withrecurrencebeingasecondary
outcome.[142]Todate,nodatahavebeenpublishedonrecurrenceratesinchildrenundergoingopenversus
laparoscopicresection.

Preparationforresection

Preoperatively,arecentevaluationoftheextentofintestinaldiseasewithappropriateradiologicandendoscopic
studiesisessential.Steroidsaretaperedasmuchasistolerable,andthepatientsnutritionalstatusisoptimized.

Incaseswherestomasmayberequired,preoperativecounselingbetterpreparesthepatientsandtheirfamiliesfor
thispossibility.Astomaltherapistornurseshouldbeinvolvedwithpatientcarebeforethesurgicalprocedure.
Patientsshouldalsobecounseledabouttheexpectationsofsurgery,becausefuturerecurrencesarelikely.

Mostpatientswillhavereceivedcorticosteroidsrecently.Therefore,perioperativesteroiddosingwilllikelybe
required.

Perianal,rectal,andsigmoidoscopicexaminationsareoftenperformedwhilethepatientisunderanesthesiato
determinethepresenceandextentofperianaldisease.

Thegoalofsurgicalresectionistoremovethegrosslyinvolvedbowelmicroscopicdiseaseatresectionmarginsis
acceptable.Primaryanastomosisofbowelcanusuallybeachieved.Occasionally,aproximalfunctioningstomaor
Brookeileostomyisrequiredinpatientsinwhomananastomosiswouldbeunsafe.

Operativesteps:laparoscopicresection

Afterthepatientisplacedundergeneralendotrachealanesthesiaandaurinarycatheterisintroduced,theabdomen
ispreparedanddrapedwidely.A12mmincisionismadeintheumbilicus,throughwhicha12mmcannulais
introducedforfutureinsertionoftheendoscopicstaplingdevice.Two5mmincisionsaremade,oneintheleftmid
abdomenandtheotherintheleftsuprapubicregionthroughthese,graspingforcepsareinsertedforretraction.

Thefinalport(ifnecessary)isinitially5or10mminlengthandisplacedintherightlowerabdomeninalocation
similartoanopenappendectomyincision.Thisincisionissubsequentlyenlargedtoapproximately2cm,andthe
specimenisextractedfromtheabdominalcavitythroughthisincision(seetheimagebelow).Inaddition,the2ends
oftheintestinetobeanastomosedareexteriorizedthroughthisincision,anda2layerextracorporealanastomosisis
created.

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Thispostoperativephotographdepictsincisionsusedforlaparoscopicileocolectomyina14yearoldmaleadolescentwith
obstructionofterminalileum.Note2cmincisioninrightlowerabdomen,throughwhichthespecimenwasextractedand
extracorporealanastomosisperformed.12mmumbilicalincisionisnicelyhiddeninthedepthsoftheumbilicus.5mmincisionis
visibleinleftlowerabdomen,andanotherisinleftsuprapubicregionjustabovethetopofthepants.
ViewMediaGallery

Thefirststepintheoperationisligationanddivisionoftheproximalileumwiththeendoscopicstapler.Next,with
eitheranUltraCisionHarmonicScalpel(EthiconEndosurgery,Cincinnati,OH)oraLigaSuredevice(ValleyLab,
Boulder,CO),themesenteryoftheproximalrightcoloniscoagulatedandtransected(seetheimagebelow).Then,
therightlowerabdominalincisionisenlargedto2cmandthespecimenisexteriorized.

Onthislaparoscopicphotograph,themesenteryoftheterminalileumisbeingcoagulatedwithasealingdevice(LigaSureValley
Lab,Boulder,Colo).Notethattheligationofthemesenteryproceedsneartheborderoftheileumratherthanatthebaseofthe
mesentery.
ViewMediaGallery

Alternatively,theumbilicalincisionmaybeenlargedtoallowexteriorizationofthespecimen.Withthistechnique,the
distalmarginofresectionismorepreciselydetermined,andthedistalresectionmargincanbedividedwiththe
surgicalstapler.Thisproceduremayalsobeperformedintracorporeallywithanendoscopicstapler.

Oncetheresectedspecimenisremoved,theproximalsmallintestineisdeliveredthroughtherightlowerabdominal
incision(ortheenlargedumbilicalincision),anda2layerextracorporealanastomosisiscreatedbetweenthe
proximalanddistalmargins.Thebowelisthenreturnedtotheabdominalcavity,andallincisionsareclosed.

Postoperativemanagement
Postoperatively,steroidsaretaperedappropriately.Patientswhowerereceivinglowdoseorshorttermsteroids
preoperativelymaybetreatedwithamorerapidtaper.Often,patientswhohavereceivedlongtermsteroidtherapy
willbegivensocalledstressdosesteroidsintraoperativelytopreventadrenalinsufficiencyduringatimewhenthe
bodyisunderhighstress(asisthecaseinsurgery).Thisstressdoseistaperedrapidly.Parenteralnutritionisoften
continueduntilbowelfunctionreturns.

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Complicationsofsurgery

ThemostcommoncomplicationofsurgicaltreatmentofCrohndiseaseisthedevelopmentofintraperitoneal
adhesions.PatientswithCrohndiseaseundergoingabdominalsurgeryarealsoatincreasedriskforthe
developmentofenterocutaneousfistulaeasaresultoftheirsurgery.Thosewhoarebeingtreatedwithsteroidsor
immunosuppressiveagentsmaybeatincreasedriskofwoundorintraabdominalinfections.

Consultations
Crohndiseaseisachronicdiseasethatrequirestreatmentbyateamofexpertsconsistingofprimarycareproviders,
gastroenterologists,psychologists,nutritionists,socialworkers,andnurses.Amultidisciplinaryapproachinvolving
theparticipationofspecialistssuchassurgeons,dermatologists,rheumatologists,endocrinologists,and
obstetriciansisoftennecessarytomanagecomplicationsofthedisease,aswellaspotentialsideeffectsoftherapy,
iftheseoccurunexpectedly.

AcriticalfactorinthesuccessfulmanagementofCrohndiseaseisthewillingnessofthepatienttoparticipateand
cooperatewiththeteam.Adherencetotherapyandthemanagementplanisessentialinimprovingoutcomes.
Patientsandparentsmustbeeducatedandreceivesupporttotreatthisdisordereffectively.

Medication

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metaanalysis.AmJGastroenterol.2011Apr.106(4):66173.[Medline].

144.FeaganBG,RutgeertsPJ,SandsBE,etal.Inductiontherapyforulcerativecolitis:resultsofGEMINII,a
randomized,placebocontrolled,doubleblind,multicenterphase3trial[abstract943b].Gastroenterology.
2012.142(5):S16061.

145.SakurabaA,KeyashianK,CorreiaC,etal.NatalizumabinCrohn'sdisease:resultsfromaUStertiary
inflammatoryboweldiseasecenter.InflammBowelDis.2013Mar.19(3):6216.[Medline].

146.SavarinoE,BodiniG,DulbeccoP,etal.Adalimumabismoreeffectivethanazathioprineandmesalamineat
preventingpostoperativerecurrenceofCrohn'sdisease:arandomizedcontrolledtrial.AmJGastroenterol.
2013Nov.108(11):173142.[Medline].[FullText].

147.ValentineJF,FedorakRN,FeaganB,etal.Steroidsparingpropertiesofsargramostiminpatientswith
corticosteroiddependentCrohn'sdisease:arandomised,doubleblind,placebocontrolled,phase2study.Gut.
2009Oct.58(10):135462.[Medline].

MediaGallery

Colonoscopicimageofalargeulcerandinflammationofthedescendingcolonina12yearoldboywithCrohn
disease.
Laparoscopicviewdepictscreepingfatalongthemesenteryoftheterminalileum.
Onthislaparoscopicphotograph,themesenteryoftheterminalileumisbeingcoagulatedwithasealingdevice
(LigaSureValleyLab,Boulder,Colo).Notethattheligationofthemesenteryproceedsneartheborderofthe
ileumratherthanatthebaseofthemesentery.
Thispostoperativephotographdepictsincisionsusedforlaparoscopicileocolectomyina14yearoldmale
adolescentwithobstructionofterminalileum.Note2cmincisioninrightlowerabdomen,throughwhichthe
specimenwasextractedandextracorporealanastomosisperformed.12mmumbilicalincisionisnicelyhidden
inthedepthsoftheumbilicus.5mmincisionisvisibleinleftlowerabdomen,andanotherisinleftsuprapubic
regionjustabovethetopofthepants.
ColonicgranulomainpatientwithCrohndisease.Hematoxylineosinstaining.ImagecourtesyofDrE.
Ruchelli.
Aphthousulcers.DoublecontrastbariumenemaexaminationinCrohncolitisdemonstratesnumerous
aphthousulcers.
Doublecontrastbariumenemastudydemonstratesmarkedulceration,inflammatorychanges,andnarrowing
ofrightcoloninpatientwithCrohncolitis.
CobblestoninginCrohndisease.Spotviewoftheterminalileumfromasmallbowelfollowthroughstudy
demonstrateslinearlongitudinalandtransverseulcerationsthatcreateacobblestoneappearance.Also,note
therelativelygreaterinvolvementofthemesentericsideoftheterminalileumandthedisplacementofthe
involvedloopawayfromthenormalsmallbowelsecondarytomesentericinflammationandfibrofatty
proliferation.
Crohndiseaseofterminalileum.Smallbowelfollowthroughstudydemonstratesthestringsigninterminal
ileum.Also,notepseudodiverticulaoftheantimesentericwallofterminalileum,secondarytogreater
distensibilityofthislessinvolvedwallsegment.
SpotviewoftheterminalileumfromasmallbowelfollowthroughstudyinapatientwithCrohndisease
demonstratesthestringsign,consistentwithnarrowingandstricturing.Also,noteasinustractoriginatingfrom
themedialwalloftheterminalileumandtheinvolvementofthemedialwallofthececum.
EnterocolicfistulainpatientwithCrohndisease.Doublecontrastbariumenemastudydemonstratesmultiple
fistuloustractsbetweenterminalileumandrightcolonadjacenttotheileocecalvalve(socalleddouble
trackingofileocecalvalve).
ActivesmallbowelinflammationinapatientwithCrohndisease.ThisCTscandemonstratessmallbowelwall
thickening,mesentericinflammatorystranding,andmesentericadenopathy.
ThiscomputedtomographyscanfromapatientwithterminalilealCrohndiseaseshowsanenteroenteral
fistula(arrow)betweenloopsofdiseasedsmallintestine.

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AteenagedpatientwithCrohndiseaseunderwentcontrastenhanceduppergastrointestinalCTwithsmall
bowelfollowthrough.Severalloopsofsmallbowelareinthepelvis.Noteloopofdistalbowelwiththickened
wall(solidarrow),whichiscontrastedwithlessinvolvedloopofbowelinwhichintestinalwallisnotthickened
atall(dottedarrow).
CTscandepictsCrohndiseaseinfundusofstomach.
MRIdemonstratesinflamedterminalileumin10yearoldgirlwithCrohndisease.
GranulomainmucosaofapatientwithCrohndisease.

of17

Tables

Table1.CharacteristicsDifferentiatingCrohnDiseaseandUlcerativeColitis
Table2.ASCRSIndicationsforSurgicalManagementofCrohnDisease
Table3.ASCRSRecommendationsforSiteSpecificOperativeManagementofCrohnDisease

Table1.CharacteristicsDifferentiatingCrohnDiseaseandUlcerativeColitis

Characteristic

Crohn
UlcerativeColitis
Disease

Entire
Distribution gastrointestinal Colononly,thoughgastritisisrecognized
tract

Continuous
involvement
Skiplesions
proximally
fromrectum

Pathology Fullthickness Mucosaonly

Granulomas(1530%
inbiopsyspecimens No
4060%insurgically granulomas
resectedbowel)

Entire
Radiology gastrointestinal Colononly
tract

Continuous
involvement
Skiplesions
proximally
fromrectum

Fistulae,abscesses, Mucosal
fibroticstrictures diseaseonly

Estimatedtobe3%at10years,8%at30years,and18%at30
Cancerrisk Increased yearsafterdiagnosis[46]riskishigherinpatientswithprimary
sclerosingcholangitisandlongstandingcolitis(>810y)maybe
lowerinsubsequentstudies(seeIntestinalManifestations).

Presentation

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Crohn UlcerativeColitis
Disease

Bleeding Occasional Verycommon

Obstruction Common Uncommon

Fistulae Common None

Weightloss Common Uncommon

Perianaldisease Common Rare

Table2.ASCRSIndicationsforSurgicalManagementofCrohnDisease

OperativeIndication FactorsforConsideringSurgery

Presenceofdiseaserelatedsymptomsnotresponsiveto
medicalmanagementconditiondemonstratesan
inadequateresponse
Whenfirstandsecondlinetherapiesdonotinduce
Failedmedicaltherapy remissionsafelyinseveredisease
Beforeescalatingmedicaltherapyinsevereorsteroid
dependentdiseasewithlimitedextent(eg,diseasewith
stricturingbehavior,patientswhohavecontraindications
orriskfactorsforfurthermedicaltherapy)

Presenceofsymptomsorsignsoffreeperforation
Immediateresectionofperforatedsegment(hasa
relativelyhighmortality)
Perforation
Aftersmallbowelresectionorperforation,other
procedurescanbeperformed,asneeded(eg,endstoma,
divertedornondivertedanastomosis)

Whenlargeanteroparietal,interloop,
intramesenteric,orretroperitoneal
abscessescannotbeorare
unsuccessfullymanagedwithantibiotics
andpercutaneousdrainage
Performsurgicaldrainageinsuch
cases,withorwithoutresection

Persistententericfistulaeand
symptomsorsignsoflocalizedor
systemicsepsisdespiteappropriate
medicalmanagement
Persistentsepsiswarrantsexcisionof
thediseasedbowel,whetherornotan
abscessispresent

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Fortargetorinnocentbystanderorgans,
diseasedbowelistypicallyresected,
noninflamedbowelprimarilyclosed,and
otherinternalorgansprimarilyclosedor
allowedtohealbysecondaryintention

Note:Operativeinterventionmaybeavoided
forasymptomaticinternalfistulae

Presenceofsymptomaticstricturesinregionsnot
Obstruction
amenableorresponsivetomedicaltherapy

Presenceofasymptomaticcolonic
stricturesthatcannotbeadequately
surveyedbybiopsyorcytology
brushing

Presenceofacutecolitisandsymptomsorsignsof
impendingoractualperforation(eg,transversecolon
distention>6cmonabdominalxrayorpersistent
Inflammation gaseouscolonicdistentionindicatetoxicmegacolon,
pneumatosiscoli,evolvinglocalperitonitis,multipleorgan
failure)
Presenceofsevereorfulminantcolitis

Worseningacutecolitisorfailureto
significantlyimprovedespite4896
hoursofappropriatemedicaltherapy

Presenceofmassivehemorrhagingofanyoriginthat(1)
cannotbeorfailstobemanagedwithinterventionalor
endoscopictechniquesand(2)occursin
hemodynamicallyunstablepatients
Hemorrhage Mesentericangiographywithembolizationmaybeattempted
whenadequateendoscopicvisualizationisnotpossibleor
whenthebleedingsourcecannotbeidentifiedifthistechnique
isnotsuccessfulorthepatientishemodynamicallyunstable,
laparotomywithorwithoutintraoperativeendoscopyand
resectionoftheresponsiblebowelsegmentmayberequired

PresenceofchronicCrohndiseaseoftheileocolonor
Neoplasia colon(endoscopicsurveillance)
Presenceofadenomatousappearingpolyps(excision)

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Presenceofcarcinoma,DALM,high
gradedysplasia,multifocalcolonicor
rectallowgradedysplasia(resection)

PresenceofchronicCrohndiseaseof
theterminalileum,ileocolon,orupper
GIregion

Presenceofsignificantgrowthretardationinprepubertal
GrowthretardationandEIMs
patientsdespiteappropriatemedicaltherapy

Presenceofsymptomaticdermatologic,
oral,ophthalmologic,orjointdisorders
refractorytomedicaltherapy(resection
ofdiseasedintestine)

ASCRS=AmericanSocietyofColonand
RectalSurgeonsDALM=dysplasia
associatedlesionormassEIM=
extraintestinalmanifestationGI=
gastrointestinal.

Source:StrongSA,KoltunWA,HymanNH,
BuieWD,fortheStandardsPracticeTask
ForceofTheAmericanSocietyofColonand
RectalSurgeons.Practiceparametersforthe
surgicalmanagementofCrohnsdisease.Dis
ColonRectum.200750(11):173546.[7]

Table3.ASCRSRecommendationsforSiteSpecificOperativeManagementofCrohnDisease

Site SurgicalIntervention

Terminalileum,ileocolon,upperGItract
Resectionoftheaffectedbowelfor
jejunal,proximalileal,terminalileal,
orileocolicdiseaseintheabsenceof
existingorimpendingshortbowel
syndrome
Ileocolostomyorproximalloop
ileostomyincaseswherethereis
concernaboutdamageto
nondiseasedbowel,superior
mesentericvessels,retroperitoneal
structures

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Drainageofanysepticfociwithlater
definitiveresection(afterseveral
monthsdelay)

Strictureplastyfornonphlegmonousjejunal,ileal,orileocolic
stricturesintheabsenceofexistingorimpendingshort
bowelsyndrome
Strictureplastywhenmultiplejejunalorproximal/terminal
ileumstricturesarepresent

Bypassorstrictureplastyforsymptomaticgastricor
duodenaldisease

Endoscopicdilatationofsymptomatic,accessiblestrictures
oftheintestinaltract

Note:Surgicalservicesshouldbeavailableincaseofperforation

Subtotalortotalcolectomywithend
ileostomyforcolonicdisease
Colon requiringemergencyorurgent
surgery(vialaparoscopicoropen
approach)

Segmentalortotalcolectomywithorwithoutprimary
anastomosisforcolonicdiseaserequiringelectivesurgery

Totalproctocolectomyorproctectomywithstomacreationfor
rectaldiseaserequiringsurgery

ASCRS=AmericanSocietyofColonandRectalSurgeonsGI=
gastrointestinal.

Source:StrongSA,KoltunWA,HymanNH,BuieWD,forthe
StandardsPracticeTaskForceofTheAmericanSocietyofColon
andRectalSurgeons.Practiceparametersforthesurgical
managementofCrohnsdisease.DisColonRectum.
200750(11):173546.[7]

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ContributorInformationandDisclosures

Author

LeylaJGhazi,MDAssistantProfessor,DepartmentofMedicine,AssociateProgramDirector,Divisionof
GastroenterologyandHepatology,UniversityofMarylandSchoolofMedicine

LeylaJGhazi,MDisamemberofthefollowingmedicalsocieties:AmericanCollegeofGastroenterology,American
GastroenterologicalAssociation,AmericanSocietyforGastrointestinalEndoscopy,Crohn'sandColitisFoundationof
America

Disclosure:Nothingtodisclose.

SpecialtyEditorBoard

BSAnand,MDProfessor,DepartmentofInternalMedicine,DivisionofGastroenterology,BaylorCollegeof
Medicine

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AmericanCollegeofGastroenterology,AmericanGastroenterologicalAssociation,AmericanSocietyfor
GastrointestinalEndoscopy

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ChiefEditor

PraveenKRoy,MD,AGAFChiefofGastroenterology,PresbyterianHospitalMedicalDirectorofEndoscopy,
PresbyterianMedicalGroupAdjunctAssociateResearchScientist,LovelaceRespiratoryResearchInstitute

PraveenKRoy,MD,AGAFisamemberofthefollowingmedicalsocieties:AmericanGastroenterological
Association,AmericanSocietyforGastrointestinalEndoscopy

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Acknowledgements

BSAnand,MDProfessor,DepartmentofInternalMedicine,DivisionofGastroenterology,BaylorCollegeof
Medicine

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AmericanCollegeofGastroenterology,AmericanGastroenterologicalAssociation,andAmericanSocietyfor
GastrointestinalEndoscopy

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TulaneUniversitySchoolofMedicine

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DivisionofGastroenterology,BaylorCollegeofMedicineandVeteransAffairsMedicalCenter

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