Crohn's disease - Wikipedia

2024-11-24

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Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. ... Symptoms often include abdominal pain ... Crohn'sdisease FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Typeofinflammatoryboweldisease MedicalconditionCrohn'sdiseaseOthernamesCrohndisease,Crohnsyndrome,granulomatousenteritis,regionalenteritis,Leśniowski-CrohndiseaseThethreemostcommonsitesofintestinalinvolvementinCrohn'sdisease(left)comparedtotheareasaffectedbycolitisulcerosa(right).SpecialtyGastroenterologySymptomsAbdominalpain,diarrhoea(maybebloody),fever,weightloss[1]ComplicationsAnemia,skinrashes,arthritis,bowelcancer[1]Usualonset20to30[2]DurationLongterm[1]RiskfactorsTobaccosmoking[3]DiagnosticmethodBiopsy,medicalimaging[1]DifferentialdiagnosisIrritablebowelsyndrome,celiacdisease,Behçet'sdisease,nonsteroidalanti-inflammatorydrugenteropathy,intestinaltuberculosis[1][4]MedicationCorticosteroids,biologicaltherapy,immunosuppressantssuchasazathioprine,methotrexate[1]PrognosisSlightlyincreasedriskofdeath[5]Frequency3.2per1,000(developedworld)[6] Crohn'sdiseaseisatypeofinflammatoryboweldisease(IBD)thatmayaffectanysegmentofthegastrointestinaltract.[2]Symptomsoftenincludeabdominalpain,diarrhea(whichmaybebloodyifinflammationissevere),fever,abdominaldistension,andweightloss.[1][2]Complicationsoutsideofthegastrointestinaltractmayincludeanemia,skinrashes,arthritis,inflammationoftheeye,andfatigue.[1]Theskinrashesmaybeduetoinfectionsaswellaspyodermagangrenosumorerythemanodosum.[1]Bowelobstructionmayoccurasacomplicationofchronicinflammation,andthosewiththediseaseareatgreaterriskofcoloncancerandsmallbowelcancer.[1] WhiletheprecisecausesofCrohn'sdisease(CD)areunknown,itisbelievedtobecausedbyacombinationofenvironmental,immune,andbacterialfactorsingeneticallysusceptibleindividuals.[2][7][8][9]Itresultsinachronicinflammatorydisorder,inwhichthebody'simmunesystemdefendsthegastrointestinaltract,possiblytargetingmicrobialantigens.[8][10]WhileCrohn'sisanimmune-relateddisease,itdoesnotappeartobeanautoimmunedisease(inthattheimmunesystemisnotbeingtriggeredbythebodyitself).[11]Theexactunderlyingimmuneproblemisnotclear;however,itmaybeanimmunodeficiencystate.[10][12][13] Abouthalfoftheoverallriskisrelatedtogenetics,withmorethan70geneshavingbeenfoundtobeinvolved.[1][14]TobaccosmokersaretwiceaslikelytodevelopCrohn'sdiseaseasnonsmokers.[3]Italsooftenbeginsaftergastroenteritis.[1]Diagnosisisbasedonanumberoffindings,includingbiopsyandappearanceofthebowelwall,medicalimaging,anddescriptionofthedisease.[1]OtherconditionsthatcanpresentsimilarlyincludeirritablebowelsyndromeandBehçet'sdisease.[1] ThereisnoknowncureforCrohn'sdisease.[1][2]Treatmentoptionsareintendedtohelpwithsymptoms,maintainremission,andpreventrelapse.[1]Inthosenewlydiagnosed,acorticosteroidmaybeusedforabriefperiodoftimetorapidlyimprovesymptoms,alongsideanothermedicationsuchaseithermethotrexateorathiopurineusedtopreventrecurrence.[1]StoppingsmokingisrecommendedinpeoplewithCrohn'sdisease.[1]Oneinfivepeoplewiththediseaseisadmittedtothehospitaleachyear,andhalfofthosewiththediseasewillrequiresurgeryforthediseaseatsomepointoveraten-yearperiod.[1]Whilesurgeryshouldbeusedaslittleaspossible,itisnecessarytoaddresssomeabscesses,certainbowelobstructions,andcancers.[1]Checkingforbowelcancerviacolonoscopyisrecommendedeveryfewyears,startingeightyearsafterthediseasehasbegun.[1] Crohn'sdiseaseaffectsabout3.2per1,000peopleinEuropeandNorthAmerica,[6]andaround1.54in1000intheUK.[15]ItislesscommoninAsiaandAfrica.[16][17]Ithashistoricallybeenmorecommoninthedevelopedworld.[18]Rateshave,however,beenincreasing,particularlyinthedevelopingworld,sincethe1970s.[17][18]Inflammatoryboweldiseaseresultedin47,400deathsin2015,[19]andthosewithCrohn'sdiseasehaveaslightlyreducedlifeexpectancy.[1]Ittendstostartintheteensandtwenties,thoughitcanoccuratanyage.[1][2][20]Malesandfemalesareequallyaffected.[2] Contents 1Name 2Signsandsymptoms 2.1Gastrointestinal 2.2Perianal 2.3Intestines 2.4StomachandEsophagus 2.5Oropharynx(Mouth) 2.6Systemic 2.7Extraintestinal 2.8Complications 2.8.1IntestinalDamage 2.8.2Cancer 2.8.3Majorcomplications 2.8.4OtherComplications 2.8.5Pregnancy 2.8.6Ostomy-relatedcomplications 3Etiology 3.1Autoinflammatorytheory 3.2Immunodeficiencytheory 4Causes 4.1Genetics 4.2Immunesystem 4.3Microbes 4.4Environmentalfactors 5Pathophysiology 6Diagnosis 6.1Classification 6.2Endoscopy 6.3Radiologictests 6.4Bloodtests 6.5Comparisonwithulcerativecolitis 6.6Differentialdiagnosis 7Management 7.1Lifestylechanges 7.2Medication 7.3Surgery 7.4Mentalhealth 7.5Alternativemedicine 8Prognosis 9Epidemiology 10History 11Research 12References 13Furtherreading 14Externallinks Name[edit] ThediseasewasnamedaftergastroenterologistBurrillBernardCrohn,whoin1932,togetherwithtwocolleaguesatMountSinaiHospitalinNewYork,describedaseriesofpatientswithinflammationoftheterminalileumofthesmallintestine,theareamostcommonlyaffectedbytheillness.[21] Signsandsymptoms[edit] Signsandsymptoms Crohn'sdisease Ulcerativecolitis Defecation Oftenporridge-like,[22]sometimessteatorrhea Oftenmucus-likeandwithblood[22] Tenesmus Lesscommon[22] Morecommon[22] Fever Common[22] Indicatesseveredisease[22] Fistulae Common[23] Seldom Weightloss Often Moreseldom Gastrointestinal[edit] AnaphthousulceronthemucousmembraneofthemouthinCrohn'sdisease. ManypeoplewithCrohn'sdiseasehavesymptomsforyearsbeforethediagnosis.[24]Theusualonsetisintheteensandtwenties,butcanoccuratanyage.[20][1]Becauseofthe'patchy'natureofthegastrointestinaldiseaseandthedepthoftissueinvolvement,initialsymptomscanbemoresubtlethanthoseofulcerativecolitis.PeoplewithCrohn'sdiseaseexperiencechronicrecurringperiodsofflare-upsandremission.[25]Thesymptomsexperiencedcanchangeovertimeasinflammationincreasesandspreads.Symptomscanalsobedifferentdependingonwhichorgansareinvolved.ItisgenerallythoughtthatthepresentationofCrohn'sdiseaseisdifferentforeachpatientduetothehighvariabilityofsymptoms,organinvolvement,andinitialpresentation. Perianal[edit] PerianaldiscomfortmayalsobeprominentinCrohn'sdisease.Itchinessorpainaroundtheanusmaybesuggestiveofinflammationoftheanus,orperianalcomplicationssuchasanalfissures,fistulae,orabscessesaroundtheanalarea.[1]PerianalskintagsarealsocommoninCrohn'sdisease,andmayappearwithorwithoutthepresenceofcolorectalpolyps.[26]FecalincontinencemayaccompanyperianalCrohn'sdisease. Intestines[edit] Theintestines,especiallythecolonandterminalileum,arethemostcommonlyaffectedareasofthebody.AbdominalpainisacommoninitialsymptomofCrohn'sdisease,[2]especiallyinthelowerrightabdomen.[27]Flatulence,bloating,andabdominaldistensionareadditionalsymptomsandmayalsoaddtotheintestinaldiscomfort.Painisoftenaccompaniedbydiarrhea,whichmayormaynotbebloody.Inflammationindifferentareasoftheintestinaltractcanaffectthequalityofthefeces.Ileitistypicallyresultsinlarge-volume,wateryfeces,whilecolitismayresultinasmallervolumeoffecesofhigherfrequency.Fecalconsistencymayrangefromsolidtowatery.Inseverecases,anindividualmayhavemorethan20bowelmovementsperday,andmayneedtoawakenatnighttodefecate.[1][28][29][30]VisiblebleedinginthefecesislesscommoninCrohn'sdiseasethaninulcerativecolitis,butisnotunusual.[1]Bloodybowelmovementsareusuallyintermittent,andmaybebrightred,darkmaroon,orevenblackincolor.Thecolorofbloodystooldependsonthelocationofthebleed.InsevereCrohn'scolitis,bleedingmaybecopious.[28] StomachandEsophagus[edit] ThestomachisrarelythesoleorpredominantsiteofCD.TodatethereareonlyafewdocumentedcasereportsofadultswithisolatedgastricCDandnoreportsinthepediatricpopulation.Isolatedstomachinvolvementisveryunusualpresentationaccountingforlessthan0.07%ofallgastrointestinalCD.[31]Rarely,theesophagusandstomachmaybeinvolvedinCrohn'sdisease.Thesecancausesymptomsincludingdifficultyswallowing(dysphagia),upperabdominalpain,andvomiting.[32] Oropharynx(Mouth)[edit] Themouthmaybeaffectedbyrecurrentsores(aphthousulcers).Recurrentaphthousulcersarecommon;however,itisnotclearwhetherthisisduetoCrohn'sdiseaseorsimplythattheyarecommoninthegeneralpopulation.Otherfindingsmayincludediffuseornodularswellingofthemouth,acobblestoneappearanceinsidethemouth,granulomatousulcers,orpyostomatitisvegetans.MedicationsthatarecommonlyprescribedtotreatCD,suchasanti-inflammatoryandsulfa-containingdrugs,maycauselichenoiddrugreactionsinthemouth.Fungalinfectionsuchascandidiasisisalsocommonduetotheimmunosuppressionrequiredinthetreatmentofthedisease.Signsofanemiasuchaspallorandangularcheilitisorglossitisarealsocommonduetonutritionalmalabsorption.[33] PeoplewithCrohn'sdiseasearealsosusceptibletoAngularStomatitis,aninflammationofthecornersofthemouth,andPyostomatitisVegetans.[34] Systemic[edit] Likemanyotherchronic,inflammatorydiseases,Crohn'sdiseasecancauseavarietyofsystemicsymptoms.[1]Amongchildren,growthfailureiscommon.ManychildrenarefirstdiagnosedwithCrohn'sdiseasebasedoninabilitytomaintaingrowth.[35]Asitmaymanifestatthetimeofthegrowthspurtinpuberty,upto30%ofchildrenwithCrohn'sdiseasemayhaveretardationofgrowth.[36]Fevermayalsobepresent,thoughfeversgreaterthan38.5 °C(101.3 °F)areuncommonunlessthereisacomplicationsuchasanabscess.[1]Amongolderindividuals,Crohn'sdiseasemaymanifestasweightloss,usuallyrelatedtodecreasedfoodintake,sinceindividualswithintestinalsymptomsfromCrohn'sdiseaseoftenfeelbetterwhentheydonoteatandmightlosetheirappetite.[35]Peoplewithextensivesmallintestinediseasemayalsohavemalabsorptionofcarbohydratesorlipids,whichcanfurtherexacerbateweightloss.[37] Extraintestinal[edit] Crohn'sdiseasecanaffectmanyorgansystemsbeyondthegastrointestinaltract.[38] Complications Crohn'sdisease Ulcerativecolitis Nutrientdeficiency Higherrisk Coloncancerrisk Slight Considerable Prevalenceofextraintestinalcomplications[39][40][41] Iritis/uveitis Females 2.2% 3.2% Males 1.3% 0.9% Primarysclerosingcholangitis Females 0.3% 1% Males 0.4% 3% Ankylosingspondylitis Females 0.7% 0.8% Males 2.7% 1.5% Pyodermagangrenosum Females 1.2% 0.8% Males 1.3% 0.7% Erythemanodosum Females 1.9% 2% Males 0.6% 0.7% Visual Inflammationoftheinteriorportionoftheeye,knownasuveitis,cancauseblurredvisionandeyepain,especiallywhenexposedtolight(photophobia).[42]Uveitiscanleadtolossofvisionifuntreated.[38] Inflammationmayalsoinvolvethewhitepartoftheeye(sclera)ortheoverlyingconnectivetissue(episclera),whichcausesconditionscalledscleritisandepiscleritis,respectively.[42] Otherveryrareophthalmologicalmanifestationsinclude:conjunctivitis,glaucoma,andretinalvasculardisease.[43] GallbladderandLiver Crohn'sdiseasethataffectstheileummayresultinanincreasedriskofgallstones.Thisisduetoadecreaseinbileacidresorptionintheileum,andthebilegetsexcretedinthestool.Asaresult,thecholesterol/bileratioincreasesinthegallbladder,resultinginanincreasedriskforgallstones.[42]Althoughtheassociationisgreaterinthecontextofulcerativecolitis,Crohn'sdiseasemayalsobeassociatedwithprimarysclerosingcholangitis,atypeofinflammationofthebileducts.[44] LiverinvolvementofCrohn'sdiseasecanincludecirrhosisandsteatosis.Nonalcoholicfattyliverdisease(NAFLD)andnonalcoholicsteatohepatitis(NASH)arerelativelycommonandcanslowlyprogresstoend-stageliverdisease.NAFLDsensitizesthelivertoinjuryandincreasestheriskofdevelopingacuteorchronicliverfailurefollowinganotherliverinjury.[43] OtherrarehepatobiliarymanifestationsofCrohn'sdiseaseinclude:cholangiocarcinoma,granulomatoushepatitis,cholelithiasis,autoimmunehepatitis,hepaticabscess,andpericholangitis.[43] RenalandUrological Nephrolithiasis,obstructiveuropathy,andfistulizationoftheurinarytractdirectlyresultfromtheunderlyingdiseaseprocess.Nephrolithiasisisduetocalciumoxalateoruricacidstones.CalciumoxalateisduetohyperoxaluriatypicallyassociatedwitheitherdistalilealCDorilealresection.Oxalateabsorptionincreasesinthepresenceofunabsorbedfattyacidsinthecolon.Thefattyacidscompetewithoxalatetobindcalcium,displacingtheoxalate,whichcanthenbeabsorbedasunboundsodiumoxalateacrosscolonocytesandexcretedintotheurine.Becausesodiumoxalateonlyisabsorbedinthecolon,calcium-oxalatestonesformonlyinpatientswithanintactcolon.Patientswithanileostomyarepronetoformationofuric-acidstonesbecauseoffrequentdehydration.Thesuddenonsetofsevereabdominal,back,orflankpaininpatientswithIBD,particularlyifdifferentfromtheusualdiscomfort,shouldleadtoinclusionofarenalstoneinthedifferentialdiagnosis.[43] UrologicalmanifestationsinpatientswithIBDmayincludeureteralcalculi,enterovesicalfistula,perivesicalinfection,perinephricabscess,andobstructiveuropathywithhydronephrosis.Ureteralcompressionisassociatedwithretroperitonealextensionofthephlegmonousinflammatoryprocessinvolvingtheterminalileumandcecum,andmayresultinhydronephrosissevereenoughtocausehypertension.[43] ImmunecomplexglomerulonephritispresentingwithproteinuriaandhematuriahasbeendescribedinchildrenandadultswithCDorUC.Diagnosisisbyrenalbiopsy,andtreatmentparallelstheunderlyingIBD.[43] Amyloidosis(seeendocrinologicalinvolvement)secondarytoCrohn'sdiseasehasbeendescribedandisknowntoaffectthekidneys.[43] Pancreatic PancreatitismaybeassociatedwithbothUCandCD.ThemostcommoncauseisiatrogenicandinvolvessensitivitytomedicationsusedtotreatIBD(3%ofpatients),includingsulfasalazine,mesalamine,6-mercaptopurine,andazathioprine.Pancreatitismaypresentassymptomatic(in2%)ormorecommonlyasymptomatic(8–21%)diseaseinadultswithIBD.[43] CardiovascularandCirculatory ChildrenandadultswithIBDhavebeenrarely(<1%)reporteddevelopingpleuropericarditiseitheratinitialpresentationorduringactiveorquiescentdisease.Thepathogenesisofpleuropericarditisisunknown,althoughcertainmedications(eg,sulfasalazineandmesalaminederivatives)havebeenimplicatedinsomecases.Theclinicalpresentationmayincludechestpain,dyspnea,orinseverecasespericardialtamponaderequiringrapiddrainage.Nonsteroidalanti-inflammatorydrugshavebeenusedastherapy,althoughthisshouldbeweighedagainstthehypotheticalriskofexacerbatingtheunderlyingIBD.[43] Inrarecases,cardiomyopathy,endocarditis,andmyocarditishavebeendescribed.[43] Crohn'sdiseasealsoincreasestheriskofbloodclots;[42]painfulswellingofthelowerlegscanbeasignofdeepvenousthrombosis,whiledifficultybreathingmaybearesultofpulmonaryembolism. Respiratory Laryngealinvolvementininflammatoryboweldiseaseisextremelyrare.Only12casesoflaryngealinvolvementinCrohndiseasehavebeenreporteduntilnow.Moreover,onlyonecaseoflaryngealmanifestationsinulcerativecolitishasbeenreportedsofar.[45]9patientscomplainedofdifficultyinbreathingduetoedemaandulcerationfromthelarynxtothehypopharynx[46]Hoarseness,sorethroat,andodynophagiaareothersymptomsoflaryngealinvolvementofCrohn'sdisease.[47] ConsideringextraintestinalmanifestationsofCD,thoseinvolvingthelungarerelativelyrare.However,thereisawidearrayoflungmanifestations,rangingfromsubclinicalalterations,airwaydiseasesandlungparenchymaldiseasestopleuraldiseasesanddrug-relateddiseases.Themostfrequentmanifestationisbronchialinflammationandsuppurationwithorwithoutbronchiectasis.ThereareanumberofmechanismsbywhichthelungsmaybecomeinvolvedinCD.Theseincludethesameembryologicaloriginofthelungandgastrointestinaltractbyancestralintestine,similarimmunesystemsinthepulmonaryandintestinalmucosa,thepresenceofcirculatingimmunecomplexesandauto-antibodies,andtheadversepulmonaryeffectsofsomedrugs.[48]Acompletelistofknownpulmonarymanifestationsinclude:Fibrosingalveolitis,Pulmonaryvasculitis,Apicalfibrosis,Bronchiectasis,Bronchitis,Bronchiolitis,Trachealstenosis,Granulomatouslungdisease,andAbnormalpulmonaryfunction.[43] Musculoskeletal Crohn'sdiseaseisassociatedwithatypeofrheumatologicdiseaseknownasseronegativespondyloarthropathy.[42]Thisgroupofdiseasesischaracterizedbyinflammationofoneormorejoints(arthritis)ormuscleinsertions(enthesitis).[42]ThearthritisinCrohn'sdiseasecanbedividedintotwotypes.Thefirsttypeaffectslargerweight-bearingjointssuchastheknee(mostcommon),hips,shoulders,wrists,orelbows.[42]Thesecondtypesymmetricallyinvolvesfiveormoreofthesmalljointsofthehandsandfeet.[42]Thearthritismayalsoinvolvethespine,leadingtoankylosingspondylitisiftheentirespineisinvolved,orsimplysacroiliitisifonlythesacroiliacjointisinvolved.[42]Thesymptomsofarthritisincludepainful,warm,swollen,stiffjoints,andlossofjointmobilityorfunction.[49] Crohn'sdiseaseincreasestheriskofosteoporosisorthinningofthebones.[42]Individualswithosteoporosisareatincreasedriskofbonefractures.[50] Asinglelesionoferythemanodosum Dermatological Crohn'sdiseasemayalsoinvolvetheskin,blood,andendocrinesystem.Erythemanodosumisthemostcommontypeofskinproblem,occurringinaround8%ofpeoplewithCrohn'sdisease,producingraised,tenderrednodulesusuallyappearingontheshins.[42][51][52]Erythemanodosumisduetoinflammationoftheunderlyingsubcutaneoustissue,andischaracterizedbyseptalpanniculitis.[51] Pyodermagangrenosumisalesscommonskinproblem,occurringinunder2%,[52]andistypicallyapainfululceratingnodule.[51][38] Clubbing,adeformityoftheendsofthefingers,mayalsobearesultofCrohn'sdisease. Otherveryraredermatologicalmanifestationsinclude:Pyostomatitisvegetans,Psoriasis,Erythemamultiforme,Epidermolysisbullosaacquista(describedinacasereport),andMetastaticCD(thespreadofCrohn'sinflammationtotheskin[34]).[43]ItisunknownifSweet'sSyndromeisconnectedtoCrohn'sdisease.[43] Neurological Crohn'sdiseasecanalsocauseneurologicalcomplications(reportedlyinupto15%).[53]Themostcommonoftheseareseizures,stroke,myopathy,peripheralneuropathy,headache,anddepression.[53] CentralandperipheralneurologicaldisordersaredescribedinpatientswithIBDandincludeperipheralneuropathies,myopathies,focalcentralnervoussystemdefects,convulsions,confusionalepisodes,meningitis,syncope,opticneuritis,andsensorineuralloss.AutoimmunemechanismsareproposedforinvolvementwithIBD.Nutritionaldeficienciesassociatedwithneurologicalmanifestations,suchasvitaminB12deficiency,shouldbeinvestigated.Spinalabscesshasbeenreportedinbothachildandanadultwithinitialcomplaintsofseverebackpainduetoextensionofapsoasabscessfromtheepiduralspacetothesubarachnoidspace.[43] Psychiatricandpsychological Crohn'sdiseaseislinkedtomanypsychologicaldisorders,includingdepressionandanxiety,denialofyourdisease,theneedfordependenceordependentbehaviors,feelingoverwhelmed,andhavingapoorself-image.[54] EndocrinologicalorHematological Autoimmunehemolyticanemia,aconditioninwhichtheimmunesystemattackstheredbloodcells,isalsomorecommoninCrohn'sdiseaseandmaycausefatigue,apaleappearance,andothersymptomscommoninanemia. Secondaryamyloidosis(AA)isanotherrarebutseriouscomplicationofinflammatoryboweldisease(IBD),generallyseeninCrohn'sdisease.Atleast1%ofpatientswithCrohn'sdiseasedevelopamyloidosis.Intheliterature,thetimelapsebetweentheonsetofCrohn'sdiseaseandthediagnosisofamyloidosishasbeenreportedtorangefromoneto21years. Leukocytosisandthrombocytopeniaareusuallyduetoimmunosuppressanttreatmentsorsulfasalazine.PlasmaerythropoietinlevelsoftenarelowerinpatientswithIBDthanexpected,inconjunctionwithsevereanemia.[43] ThrombocytosisandthromboemboliceventsresultingfromahypercoagulablestateinpatientswithIBDcanleadtopulmonaryembolismorthrombosiselsewhereinthebody.Thrombosishasbeenreportedin1.8%ofpatientswithUCand3.1%ofpatientswithCD.Thromboembolismandthrombosisarelessfrequentlyreportedamongpediatricpatients,with3patientswithUCand1withCDdescribedincasereports.[43] Inrarecases,hypercoagulationdisordersandportalveinthrombosishavebeendescribed.[43] MalnutritionSymptoms PeoplewithCrohn'sdiseasemaydevelopanemiaduetovitaminB12,folate,irondeficiency,orduetoanemiaofchronicdisease.[55][56]Themostcommonisirondeficiencyanemia[55]fromchronicbloodloss,reduceddietaryintake,andpersistentinflammationleadingtoincreasedhepcidinlevels,restrictingironabsorptionintheduodenum.[56]AsCrohn'sdiseasemostcommonlyaffectstheterminalileumwherethevitaminB12/intrinsicfactorcomplexisabsorbed,B12deficiencymaybeseen.[56]Thisisparticularlycommonaftersurgerytoremovetheileum.[55]Involvementoftheduodenumandjejunumcanimpairtheabsorptionofmanyothernutrientsincludingfolate.PeoplewithCrohn'softenalsohaveissueswithsmallbowelbacterialovergrowthsyndrome,whichcanproducemicronutrientdeficiencies.[57][58] Complications[edit] IntestinalDamage[edit] Crohn'sdiseasecanleadtoseveralmechanicalcomplicationswithintheintestines,includingobstruction,[59]fistulae,[60]andabscesses.[61]Obstructiontypicallyoccursfromstricturesoradhesionsthatnarrowthelumen,blockingthepassageoftheintestinalcontents.Afistulacandevelopbetweentwoloopsofbowel,betweenthebowelandbladder,betweenthebowelandvagina,andbetweenthebowelandskin.Abscessesarewalled-offconcentrationsofinfection,whichcanoccurintheabdomenorintheperianalarea.Crohn'sisresponsiblefor10%ofvesicoentericfistulae,andisthemostcommoncauseofileovesicalfistulae.[62] Symptomscausedbyintestinalstenosis,orthetighteningandnarrowingofthebowel,arealsocommoninCrohn'sdisease.Abdominalpainisoftenmostsevereinareasofthebowelwithstenosis.Persistentvomitingandnauseamayindicatestenosisfromsmallbowelobstructionordiseaseinvolvingthestomach,pylorus,orduodenum.[28] Intestinalgranulomasareawalled-offportionsoftheintestinebymacrophagesinordertoisolateinfections.Granulomaformationismoreoftenseeninyoungerpatients,andmainlyinthesevere,activepenetratingdisease.[63]GranulomaisconsideredthehallmarkofmicroscopicdiagnosisinCrohn’sdisease(CD),butgranulomascanbedetectedinonly21-60%ofCDpatients.[63] Cancer[edit] Crohn'sdiseasealsoincreasestheriskofcancerintheareaofinflammation.Forexample,individualswithCrohn'sdiseaseinvolvingthesmallbowelareathigherriskforsmallintestinalcancer.[64]Similarly,peoplewithCrohn'scolitishavearelativeriskof5.6fordevelopingcoloncancer.[65]ScreeningforcoloncancerwithcolonoscopyisrecommendedforanyonewhohashadCrohn'scolitisforatleasteightyears.[66] SomestudiessuggestthereisaroleforchemoprotectioninthepreventionofcolorectalcancerinCrohn'sinvolvingthecolon;twoagentshavebeensuggested,folateandmesalaminepreparations.[67]Also,immunomodulatorsandbiologicagentsusedtotreatthisdiseasemaypromotedevelopingextra-intestinalcancers.[68] Somecancers,suchasAcuteMyelocyticLeukaemiahavebeendescribedincasesofCrohn'sdisease.[43]HepatosplenicT-celllymphoma(HSTCL)isarare,lethaldiseasegenerallyseeninyoungmalepatientswithinflammatoryboweldisease.TNF-αInhibitortreatments(infliximab,adalimumab,certolizumab,natalizumab,andetanercept)arethoughttobethecauseofthisraredisease.[69] EndoscopicimageofcoloncanceridentifiedinthesigmoidcolononscreeningcolonoscopyforCrohn'sdisease Majorcomplications[edit] MajorcomplicationsofCrohn'sdiseaseincludebowelobstruction,abscesses,freeperforation,andhemorrhage,whichinrarecasesmaybefatal.[70][71] OtherComplications[edit] IndividualswithCrohn'sdiseaseareatriskofmalnutritionformanyreasons,includingdecreasedfoodintakeandmalabsorption.Theriskincreasesfollowingresectionofthesmallbowel.Suchindividualsmayrequireoralsupplementstoincreasetheircaloricintake,orinseverecases,totalparenteralnutrition(TPN).MostpeoplewithmoderateorsevereCrohn'sdiseasearereferredtoadietitianforassistanceinnutrition.[72] Smallintestinalbacterialovergrowth(SIBO)ischaracterizedbyexcessiveproliferationofcolonicbacterialspeciesinthesmallbowel.PotentialcausesofSIBOincludefistulae,strictures,ormotilitydisturbances.Hence,patientswithCrohn'sdiseaseareespeciallypredisposedtodevelopSIBO.Asresult,CDpatientsmayexperiencemalabsorptionandreportsymptomssuchasweightloss,waterydiarrhea,meteorism,flatulence,andabdominalpain,mimickingacuteflareinthesepatients.[58] Pregnancy[edit] Crohn'sdiseasecanbeproblematicduringpregnancy,andsomemedicationscancauseadverseoutcomesforthefetusormother.ConsultationwithanobstetricianandgastroenterologistaboutCrohn'sdiseaseandallmedicationsfacilitatespreventivemeasures.Insomecases,remissionoccursduringpregnancy.Certainmedicationscanalsolowerspermcountorotherwiseadverselyaffectaman'sfertility.[73] Ostomy-relatedcomplications[edit] Commoncomplicationsofanostomy(acommonsurgeryinCrohn'sdisease)are:Mucosaledema,Peristomaldermatitis,Retraction,Ostomyprolapse,Mucosal/skindetachment,Hematoma,Necrosis,Parastomalhernia,andStenosis.[74] Etiology[edit] TheetiologyofCrohn'sdiseaseisunknown.Manytheorieshavebeendisputed,withfourmaintheorieshypothesizedtobetheprimarymechanismofCrohn'sdisease.Inautoimmunediseases,antibodiesandTlymphocytesaretheprimarymodeofinflammation.Thesecellsandbodiesarepartoftheadaptiveimmunesystem,orthepartoftheimmunesystemthatlearnstofightforeignbodieswhenfirstidentified.[75]Autoinflammatorydiseasesarediseaseswheretheinnateimmunesystem,ortheimmunesystemwearegeneticallycodedwith,isdesignedtoattackourowncells.[76]Crohn'sdiseaselikelyhasinvolvementofboththeadaptiveandinnateimmunesystems.[77] Autoinflammatorytheory[edit] Crohn'sdiseasecanbedescribedasamultifactorialautoinflammatorydisease.TheetiopathogenesisofCrohn’sdiseaseisstillunknown.Inanyevent,alossoftheregulatorycapacityoftheimmuneapparatuswouldbeimplicatedintheonsetofthedisease.Inthisrespectinterestinglyenough,asforBlau’sdisease(amonogenicautoinflammatorydisease),theNOD2genemutationshavebeenlinkedtoCrohn’sdisease.However,inCrohn’sdisease,NOD2mutationsactasariskfactor,beingmorecommonamongCrohn’sdiseasepatientsthanthebackgroundpopulation,whileinBlau’sdiseaseNOD2mutationsarelinkeddirectlytothissyndrome,asitisanautosomal-dominantdisease.AllthisnewknowledgeinthepathogenesisofCrohn’sdiseaseallowsustoputthismultifactorialdiseaseinthegroupofautoinflammatorysyndromes.[76] Someexamplesofhowtheinnateimmunesystemaffectsbowelinflammationhavebeendescribed.[77]Ameta-analysisofCDgenome-wideassociationstudiesrevealed71distinctCD-susceptibilityloci.Interestingly,threeveryimportantCD-susceptibilitygenes(theintracellularpathogen-recognitionreceptor,NOD2;theautophagy-related16-like1,ATG16L1andtheimmunity-relatedGTPaseM,IRGM)areinvolvedininnateimmuneresponsesagainstgutmicrobiota,whileone(theX-boxbindingprotein1)isinvolvedinregulationofthe[adaptive]immunepathwayviaMHCclassII,[78]resultinginautoinflammatoryinflammation.StudieshavealsofoundthatincreasedILC3canoverexpressmajorhistocompatibilitycomplex(MHC)II.MHCclassIIcaninduceCD4+Tcellapoptosis,thusavoidingtheTcellresponsetonormalbowelmicrobacteria.FurtherstudiesofIBDpatientscomparedwithnon-IBDpatientsfoundthattheexpressionofMHCIIbyILC3wassignificantlyreducedinIBDpatients,thuscausinganimmunereactionagainstintestinalcellsornormalbowelbacteriaanddamagingtheintestines.Thiscanalsomaketheintestinesmoresusceptibletoenvironmentalfactors,suchasfoodorbacteria.[77] Thethinkingis,thatbecauseCrohn'sdiseasehasstronginnateimmunesysteminvolvementandhasNOD2mutationsasapredisposition,Crohn'sdiseaseismorelikelyanautoinflammatorydiseasethananautoimmunedisease.[77] Immunodeficiencytheory[edit] AsubstantialbodyofdatahasemergedinrecentyearstosuggestthattheprimarydefectinCrohn’sdiseaseisactuallyoneofrelativeimmunodeficiency.[79]Thisviewhasbeenbolsteredrecentlybynovelimmunologicalandclinicalstudiesthathaveconfirmedgrossaberrationsinthisearlyresponse,consistentwithsubsequentgeneticstudiesthathighlightedmoleculesimportantforinnateimmunefunction.ThesuggestionthereforeisthatCrohn’spathogenesisactuallyresultsfrompartialimmunodeficiency,atheorythatcoincideswiththefrequentrecognitionofavirtuallyidentical,non-infectiousinflammatoryboweldiseasearisinginpatientswithcongenitalmonogenicdisordersimpairingphagocytefunction.[79] Causes[edit] Risk factors Crohn'sdisease Ulcerativecolitis Smoking Higherriskforsmokers Lowerriskforsmokers[80] Age Usualonsetbetween15and30years[81] Peakincidencebetween15and25years Whiletheexactcauseorcausesareunknown,Crohn'sdiseaseseemstobeduetoacombinationofenvironmentalfactorsandgeneticpredisposition.[82]Crohn'sisthefirstgeneticallycomplexdiseaseinwhichtherelationshipbetweengeneticriskfactorsandtheimmunesystemisunderstoodinconsiderabledetail.[83]EachindividualriskmutationmakesasmallcontributiontotheoverallriskofCrohn's(approximately1:200).Thegeneticdata,anddirectassessmentofimmunity,indicatesamalfunctionintheinnateimmunesystem.[84]Inthisview,thechronicinflammationofCrohn'siscausedwhentheadaptiveimmunesystemtriestocompensateforadeficientinnateimmunesystem.[85] Genetics[edit] NOD2proteinmodelwithschematicdiagram.TwoN-terminalCARDdomains(red)connectedviahelicallinker(blue)withcentralNBDdomain(green).AtC-terminusLRRdomain(cyan)islocated.Additionally,somemutationswhichareassociatedwithcertaindiseasepatternsinCrohn'sdiseasearemarkedinredwirerepresentation.[86] Crohn'shasageneticcomponent.[87]Becauseofthis,siblingsofknownpeoplewithCrohn'sare30timesmorelikelytodevelopCrohn'sthanthegeneralpopulation.[88] ThefirstmutationfoundtobeassociatedwithCrohn'swasaframeshiftintheNOD2gene(alsoknownastheCARD15gene),[89]followedbythediscoveryofpointmutations.[90]Over30geneshavebeenassociatedwithCrohn's;abiologicalfunctionisknownformostofthem.Forexample,oneassociationiswithmutationsintheXBP1gene,whichisinvolvedintheunfoldedproteinresponsepathwayoftheendoplasmicreticulum.[91][92]ThegenevariantsofNOD2/CARD15seemtoberelatedwithsmall-bowelinvolvement.[93]OtherwelldocumentedgeneswhichincreasetheriskofdevelopingCrohn'sdiseaseareATG16L1,[94]IL23R,[95]IRGM,[96]andSLC11A1.[97] ThereisconsiderableoverlapbetweensusceptibilitylociforIBDandmycobacterialinfections.[98]Genome-wideassociationstudieshaveshownthatCrohn'sdiseaseisgeneticallylinkedtocoeliacdisease.[99] Crohn'shasbeenlinkedtothegeneLRRK2withonevariantpotentiallyincreasingtheriskofdevelopingthediseaseby70%,whileanotherlowersitby25%.Thegeneisresponsibleformakingaprotein,whichcollectsandeliminateswasteproductincells,andisalsoassociatedwithParkinson'sdisease.[100] Immunesystem[edit] TherewasaprevailingviewthatCrohn'sdiseaseisaprimaryTcellautoimmunedisorder;however,anewertheoryhypothesizesthatCrohn'sresultsfromanimpairedinnateimmunity.[101]Thelaterhypothesisdescribesimpairedcytokinesecretionbymacrophages,whichcontributestoimpairedinnateimmunityandleadstoasustainedmicrobial-inducedinflammatoryresponseinthecolon,wherethebacterialloadishigh.[8][84]AnothertheoryisthattheinflammationofCrohn'swascausedbyanoveractiveTh1andTh17cytokineresponse.[102][103] In2007,theATG16L1genewasimplicatedinCrohn'sdisease,whichmayinduceautophagyandhinderthebody'sabilitytoattackinvasivebacteria.[94]Anotherstudytheorizedthatthehumanimmunesystemtraditionallyevolvedwiththepresenceofparasitesinsidethebodyandthatthelackthereofduetomodernhygienestandardshasweakenedtheimmunesystem.Testsubjectswerereintroducedtoharmlessparasites,withpositiveresponses.[104] Microbes[edit] ItishypothesizedthatmaintenanceofcommensalmicroorganismgrowthintheGItractisdysregulated,eitherasaresultorcauseofimmunedysregulation.[105][106] ThereisanapparentconnectionbetweenCrohn'sdisease,Mycobacterium,otherpathogenicbacteria,andgeneticmarkers.[107][108]AnumberofstudieshavesuggestedacausalroleforMycobacteriumaviumsubspeciesparatuberculosis(MAP),whichcausesasimilardisease,Johne'sdisease,incattle.[109][110]Inmanyindividuals,geneticfactorspredisposeindividualstoMycobacteriumaviumsubsp.paratuberculosisinfection.Thisbacteriummayproducecertaincompoundscontainingmannose,whichmayprotectbothitselfandvariousotherbacteriafromphagocytosis,therebypossiblycausingavarietyofsecondaryinfections.[111] NOD2isageneinvolvedinCrohn'sgeneticsusceptibility.Itisassociatedwithmacrophages'diminishedabilitytophagocytizeMAP.ThissamegenemayreduceinnateandadaptiveimmunityingastrointestinaltissueandimpairtheabilitytoresistinfectionbytheMAPbacterium.[112]MacrophagesthatingesttheMAPbacteriumareassociatedwithhighproductionofTNF-α.[113][114] OtherstudieshavelinkedspecificstrainsofenteroadherentE.colitothedisease.[115]Adherent-invasiveEscherichiacoli(AIEC),aremorecommoninpeoplewithCD,[116][117][115]havetheabilitytomakestrongbiofilmscomparedtonon-AIECstrainscorrelatingwithhighadhesionandinvasionindices[118][119]ofneutrophilsandtheabilitytoblockautophagyattheautolysosomalstep,whichallowsforintracellularsurvivalofthebacteriaandinductionofinflammation.[120]InflammationdrivestheproliferationofAIECanddysbiosisintheileum,irrespectiveofgenotype.[121]AIECstrainsreplicateextensivelyinsidemacrophagesinducingthesecretionofverylargeamountsofTNF-α.[122] MousestudieshavesuggestedsomesymptomsofCrohn'sdisease,ulcerativecolitis,andirritablebowelsyndromehavethesameunderlyingcause.Biopsysamplestakenfromthecolonsofallthreepatientgroupswerefoundtoproduceelevatedlevelsofaserineprotease.[123]Experimentalintroductionoftheserineproteaseintomicehasbeenfoundtoproducewidespreadpainassociatedwithirritablebowelsyndrome,aswellascolitis,whichisassociatedwithallthreediseases.[124]RegionalandtemporalvariationsinthoseillnessesfollowthoseassociatedwithinfectionwiththeprotozoanBlastocystis.[125] The"cold-chain"hypothesisisthatpsychrotrophicbacteriasuchasYersiniaandListeriaspeciescontributetothedisease.AstatisticalcorrelationwasfoundbetweentheadventoftheuseofrefrigerationintheUnitedStatesandvariouspartsofEuropeandtheriseofthedisease.[126][127][128] ThereisalsoatentativeassociationbetweenCandidacolonizationandCrohn'sdisease.[129] Still,theserelationshipsbetweenspecificpathogensandCrohn'sdiseaseremainunclear.[130][131] Environmentalfactors[edit] TheincreasedincidenceofCrohn'sintheindustrializedworldindicatesanenvironmentalcomponent.Crohn'sisassociatedwithanincreasedintakeofanimalprotein,milkprotein,andanincreasedratioofomega-6toomega-3polyunsaturatedfattyacids.[132] ThosewhoconsumevegetableproteinsappeartohavealowerincidenceofCrohn'sdisease.Consumptionoffishproteinhasnoassociation.[132] Smokingincreasestheriskofthereturnofactivedisease(flares).[3]TheintroductionofhormonalcontraceptionintheUnitedStatesinthe1960sisassociatedwithadramaticincreaseinincidence,andonehypothesisisthatthesedrugsworkonthedigestivesysteminwayssimilartosmoking.[133]IsotretinoinisassociatedwithCrohn's.[134][135][136] AlthoughstressissometimesclaimedtoexacerbateCrohn'sdisease,thereisnoconcreteevidencetosupportsuchclaim.[2]Dietarymicroparticles,suchasthosefoundintoothpaste,havebeenstudiedastheyproduceeffectsonimmunity,buttheywerenotconsumedingreateramountsinpatientswithCrohn's.[137][138]Theuseofdoxycyclinehasalsobeenassociatedwithincreasedriskofdevelopinginflammatoryboweldiseases.[139][140][141]Inonelargeretrospectivestudy,patientswhowereprescribeddoxycyclinefortheiracnehada2.25-foldgreaterriskofdevelopingCrohn'sdisease.[140] Pathophysiology[edit] Pathophysiology Crohn'sdisease Ulcerativecolitis Cytokineresponse AssociatedwithTh17[142] VaguelyassociatedwithTh2 Duringacolonoscopy,biopsiesofthecolonareoftentakentoconfirmthediagnosis.CertaincharacteristicfeaturesofthepathologyseenpointtowardCrohn'sdisease;itshowsatransmuralpatternofinflammation,meaningtheinflammationmayspantheentiredepthoftheintestinalwall.[1]Ulcerationisanoutcomeseeninhighlyactivedisease.Thereisusuallyanabrupttransitionbetweenunaffectedtissueandtheulcer—acharacteristicsignknownasskiplesions.Underamicroscope,biopsiesoftheaffectedcolonmayshowmucosalinflammation,characterizedbyfocalinfiltrationofneutrophils,atypeofinflammatorycell,intotheepithelium.Thistypicallyoccursintheareaoverlyinglymphoidaggregates.Theseneutrophils,alongwithmononuclearcells,mayinfiltratethecrypts,leadingtoinflammation(crypititis)orabscess(cryptabscess).[citationneeded] Granulomas,aggregatesofmacrophagederivativesknownasgiantcells,arefoundin50%ofcasesandaremostspecificforCrohn'sdisease.ThegranulomasofCrohn'sdiseasedonotshow"caseation",acheese-likeappearanceonmicroscopicexaminationcharacteristicofgranulomasassociatedwithinfections,suchastuberculosis.Biopsiesmayalsoshowchronicmucosaldamage,asevidencedbybluntingoftheintestinalvilli,atypicalbranchingofthecrypts,andachangeinthetissuetype(metaplasia).Oneexampleofsuchmetaplasia,Panethcellmetaplasia,involvesthedevelopmentofPanethcells(typicallyfoundinthesmallintestineandakeyregulatorofintestinalmicrobiota)inotherpartsofthegastrointestinalsystem.[143][144] Diagnosis[edit] ThediagnosisofCrohn'sdiseasecansometimesbechallenging,[24]andmanytestsareoftenrequiredtoassistthephysicianinmakingthediagnosis.[28]Evenwithafullbatteryoftests,itmaynotbepossibletodiagnoseCrohn'swithcompletecertainty;acolonoscopyisapproximately70%effectiveindiagnosingthedisease,withfurthertestsbeinglesseffective.Diseaseinthesmallbowelisparticularlydifficulttodiagnose,asatraditionalcolonoscopyallowsaccesstoonlythecolonandlowerportionsofthesmallintestines;introductionofthecapsuleendoscopy[145]aidsinendoscopicdiagnosis.Giant(multinucleate)cells,acommonfindinginthelesionsofCrohn'sdisease,arelesscommoninthelesionsoflichennitidus.[146] EndoscopicimageofCrohn'scolitisshowingdeepulceration CTscanshowingCrohn'sdiseaseinthefundusofthestomach EndoscopicbiopsyshowinggranulomatousinflammationofthecoloninacaseofCrohn'sdisease. Sectionofcolectomyshowingtransmuralinflammation ResectedileumfromapersonwithCrohn'sdisease Classification[edit] DistributionofgastrointestinalCrohn'sdisease. Crohn'sdiseaseisonetypeofinflammatoryboweldisease(IBD).Ittypicallymanifestsinthegastrointestinaltractandcanbecategorizedbythespecifictractregionaffected.Adiseaseofboththeileum(thelastpartofthesmallintestinethatconnectstothelargeintestine),andthelargeintestine,IleocolicCrohn'saccountsforfiftypercentofcases.Crohn'sileitis,manifestintheileumonly,accountsforthirtypercentofcases,whileCrohn'scolitis,ofthelargeintestine,accountsfortheremainingtwentypercentofcasesandmaybeparticularlydifficulttodistinguishfromulcerativecolitis.[citationneeded] GastroduodenalCrohn'sdiseasecausesinflammationinthestomachandthefirstpartofthesmallintestinecalledtheduodenum.Jejunoileitiscausesspottypatchesofinflammationinthetophalfofthesmallintestine,calledthejejunum.[147]Thediseasecanattackanypartofthedigestivetract,frommouthtoanus.However,individualsaffectedbythediseaserarelyfalloutsidethesethreeclassifications,withpresentationsinotherareas.[1] Crohn'sdiseasemayalsobecategorizedbythebehaviorofdiseaseasitprogresses.ThesecategorizationsformalizedintheViennaclassificationofthedisease.[148]TherearethreecategoriesofdiseasepresentationinCrohn'sdisease:stricturing,penetrating,andinflammatory.Stricturingdiseasecausesnarrowingofthebowelthatmayleadtobowelobstructionorchangesinthecaliberofthefeces.Penetratingdiseasecreatesabnormalpassageways(fistulae)betweenthebowelandotherstructures,suchastheskin.Inflammatorydisease(ornonstricturing,nonpenetratingdisease)causesinflammationwithoutcausingstricturesorfistulae.[148][149] Endoscopy[edit] AcolonoscopyisthebesttestformakingthediagnosisofCrohn'sdisease,asitallowsdirectvisualizationofthecolonandtheterminalileum,identifyingthepatternofdiseaseinvolvement.Onoccasion,thecolonoscopecantravelpasttheterminalileum,butitvariesfrompersontoperson.Duringtheprocedure,thegastroenterologistcanalsoperformabiopsy,takingsmallsamplesoftissueforlaboratoryanalysis,whichmayhelpconfirmadiagnosis.As30%ofCrohn'sdiseaseinvolvesonlytheileum,[1]cannulationoftheterminalileumisrequiredinmakingthediagnosis.Findingapatchydistributionofdisease,withinvolvementofthecolonorileum,butnottherectum,issuggestiveofCrohn'sdisease,asareotherendoscopicstigmata.[150] Theutilityofcapsuleendoscopyforthis,however,isstilluncertain.[151]A"cobblestone"-likeappearanceisseeninapproximately40%ofcasesofCrohn'sdiseaseuponcolonoscopy,representingareasofulcerationseparatedbynarrowareasofhealthytissue.[citationneeded] Radiologictests[edit] Asmallbowelfollow-throughmaysuggestthediagnosisofCrohn'sdiseaseandisusefulwhenthediseaseinvolvesonlythesmallintestine.Becausecolonoscopyandgastroscopyallowdirectvisualizationofonlytheterminalileumandbeginningoftheduodenum,theycannotbeusedtoevaluatetheremainderofthesmallintestine.Asaresult,abariumfollow-throughX-ray,whereinbariumsulfatesuspensionisingestedandfluoroscopicimagesofthebowelaretakenovertime,isusefulforlookingforinflammationandnarrowingofthesmallbowel.[150][152]Bariumenemas,inwhichbariumisinsertedintotherectumandfluoroscopyisusedtoimagethebowel,arerarelyusedinthework-upofCrohn'sdiseaseduetotheadventofcolonoscopy.Theyremainusefulforidentifyinganatomicalabnormalitieswhenstricturesofthecolonaretoosmallforacolonoscopetopassthrough,orinthedetectionofcolonicfistulae(inthiscasecontrastshouldbeperformedwithiodatesubstances).[153] CTandMRIscansareusefulforevaluatingthesmallbowelwithenteroclysisprotocols.[154]Theyarealsousefulforlookingforintra-abdominalcomplicationsofCrohn'sdisease,suchasabscesses,smallbowelobstructions,orfistulae.[155]Magneticresonanceimaging(MRI)isanotheroptionforimagingthesmallbowelaswellaslookingforcomplications,thoughitismoreexpensiveandlessreadilyavailable.[156]MRItechniquessuchasdiffusion-weightedimagingandhigh-resolutionimagingaremoresensitiveindetectingulcerationandinflammationcomparedtoCT.[157][158] Bloodtests[edit] Acompletebloodcountmayrevealanemia,whichcommonlyiscausedbybloodlossleadingtoirondeficiencyorbyvitaminB12deficiency,usuallycausedbyilealdiseaseimpairingvitaminB12absorption.Rarelyautoimmunehemolysismayoccur.[159]Ferritinlevelshelpassessifirondeficiencyiscontributingtotheanemia.Erythrocytesedimentationrate(ESR)andC-reactiveproteinhelpassessthedegreeofinflammation,whichisimportantasferritincanalsoberaisedininflammation.[160]Serumiron,totalironbindingcapacityandtransferrinsaturationmaybemoreeasilyinterpretedininflammation.Anemiaofchronicdiseaseresultsinanormocyticanemia.[citationneeded] Othercausesofanemiaincludemedicationusedintreatmentofinflammatoryboweldisease,likeazathioprine,whichcanleadtocytopenia,andsulfasalazine,whichcanalsoresultinfolatedeficiency.TestingforSaccharomycescerevisiaeantibodies(ASCA)andantineutrophilcytoplasmicantibodies(ANCA)hasbeenevaluatedtoidentifyinflammatorydiseasesoftheintestine[161]andtodifferentiateCrohn'sdiseasefromulcerativecolitis.[162]Furthermore,increasingamountsandlevelsofserologicalantibodiessuchasASCA,antilaminaribioside[Glc(β1,3)Glb(β);ALCA],antichitobioside[GlcNAc(β1,4)GlcNAc(β);ACCA],antimannobioside[Man(α1,3)Man(α)AMCA],antiLaminarin[(Glc(β1,3))3n(Glc(β1,6))n;anti-L]andantichitin[GlcNAc(β1,4)n;anti-C]associatewithdiseasebehaviorandsurgery,andmayaidintheprognosisofCrohn'sdisease.[163][164][165][166] LowserumlevelsofvitaminDareassociatedwithCrohn'sdisease.[167]Furtherstudiesarerequiredtodeterminethesignificanceofthisassociation.[167] Comparisonwithulcerativecolitis[edit] ThemostcommondiseasethatmimicsthesymptomsofCrohn'sdiseaseisulcerativecolitis,asbothareinflammatoryboweldiseasesthatcanaffectthecolonwithsimilarsymptoms.Itisimportanttodifferentiatethesediseases,sincethecourseofthediseasesandtreatmentsmaybedifferent.Insomecases,however,itmaynotbepossibletotellthedifference,inwhichcasethediseaseisclassifiedasindeterminatecolitis.[1][28][29] Diagnosticfindings Crohn'sdisease Ulcerativecolitis Terminalileuminvolvement Commonly Seldom Coloninvolvement Usually Always Rectuminvolvement Seldom Usually(95%)[80] Involvementaroundtheanus Common[168] Seldom Bileductinvolvement Noincreaseinrateofprimarysclerosingcholangitis Higherrate[169] Distributionofdisease Patchyareasofinflammation(skiplesions) Continuousareaofinflammation[80] Endoscopy Deepgeographicandserpiginous(snake-like)ulcers Continuousulcer Depthofinflammation Maybetransmural,deepintotissues[168][170] Shallow,mucosal Stenosis Common Seldom Granulomasonbiopsy Mayhavenon-necrotizingnon-peri-intestinalcryptgranulomas[168][171][172] Non-peri-intestinalcryptgranulomasnotseen[173] Differentialdiagnosis[edit] OtherconditionswithsimilarsymptomsasCrohn'sdiseaseincludesintestinaltuberculosis,Behçet'sdisease,ulcerativecolitis,nonsteroidalanti-inflammatorydrugenteropathy,irritablebowelsyndromeandceliacdisease.[4]Irritablebowelsyndromeisexcludedwhenthereareinflammatorychanges.[4]Celiacdiseasecannotbeexcludedifspecificantibodies(anti-transglutaminaseantibodies)arenegative,[174][175]norinabsenceofintestinalvilliatrophy.[176][177] Management[edit] Mainarticle:ManagementofCrohn'sdisease Management Crohn'sdisease Ulcerativecolitis Mesalazine Lessuseful[178] Moreuseful[178] Antibiotics Effectiveinlong-term[179] Generallynotuseful[180] Surgery Oftenreturnsfollowingremovalofaffectedpart Usuallycuredbyremovalofcolon ThereisnocureforCrohn'sdiseaseandremissionmaynotbepossibleorprolongedifachieved.Incaseswhereremissionispossible,relapsecanbepreventedandsymptomscontrolledwithmedication,lifestyleanddietarychanges,changestoeatinghabits(eatingsmalleramountsmoreoften),reductionofstress,moderateactivity,andexercise.Surgeryisgenerallycontraindicatedandhasnotbeenshowntopreventrelapse.Adequatelycontrolled,Crohn'sdiseasemaynotsignificantlyrestrictdailyliving.[181]TreatmentforCrohn'sdiseaseisonlywhensymptomsareactiveandinvolvefirsttreatingtheacuteproblem,thenmaintainingremission. Lifestylechanges[edit] Certainlifestylechangescanreducesymptoms,includingdietaryadjustments,elementaldiet,properhydration,andsmokingcessation.Dietsthatincludehigherlevelsoffiberandfruitareassociatedwithreducedrisk,whiledietsrichintotalfats,polyunsaturatedfattyacids,meat,andomega-6fattyacidsmayincreasetheriskofCrohn's.[182]Maintainingabalanceddietwithproperportioncontrolcanhelpmanagesymptomsofthedisease.Eatingsmallmealsfrequentlyinsteadofbigmealsmayalsohelpwithalowappetite.Afooddiarymayhelpwithidentifyingfoodsthattriggersymptoms.Somepeopleshouldfollowalowfiberdiettocontrolacutesymptomsespeciallyiffibrousfoodscausesymptoms.[181]Somefindreliefineliminatingcasein(aproteinfoundincow'smilk)andgluten(aproteinfoundinwheat,ryeandbarley)fromtheirdiets.Theymayhavespecificdietaryintolerances(notallergies).[183]Fatiguecanbehelpedwithregularexercise,ahealthydiet,andenoughsleep.Smokingmayworsensymptoms,andstoppingisrecommended.[181] Medication[edit] Acutetreatmentusesmedicationstotreatanyinfection(normallyantibiotics)andtoreduceinflammation(normallyaminosalicylateanti-inflammatorydrugsandcorticosteroids).Whensymptomsareinremission,treatmententersmaintenance,withagoalofavoidingtherecurrenceofsymptoms.Prolongeduseofcorticosteroidshassignificantside-effects;asaresult,theyare,ingeneral,notusedforlong-termtreatment.Alternativesincludeaminosalicylatesalone,thoughonlyaminorityareabletomaintainthetreatment,andmanyrequireimmunosuppressivedrugs.[168]Ithasbeenalsosuggestedthatantibioticschangetheentericflora,andtheircontinuoususemayposetheriskofovergrowthwithpathogenssuchasClostridiumdifficile.[184] MedicationsusedtotreatthesymptomsofCrohn'sdiseaseinclude5-aminosalicylicacid(5-ASA)formulations,prednisone,immunomodulatorssuchasazathioprine(givenastheprodrugfor6-mercaptopurine),methotrexate,[185]infliximab,adalimumab,[29]certolizumab,[186]vedolizumab,ustekinumab,[187]andnatalizumab.[188][189]HydrocortisoneshouldbeusedinsevereattacksofCrohn'sdisease.[190]Biologicaltherapiesaremedicationsusedtoavoidlong-termsteroiduse,decreaseinflammation,andtreatpeoplewhohavefistulaswithabscesses.[27]Themonoclonalantibodyustekinumabappearstobeasafetreatmentoption,andmayhelppeoplewithmoderatetosevereactiveCrohn'sdisease.[191]Thelongtermsafetyandeffectivenessofmonoclonalantibodytreatmentisnotknown.[191]ThemonoclonalantibodybriakinumabisnoteffectiveforpeoplewithactiveCrohn'sdiseaseanditisnolongerbeingmanufactured.[191] Thegraduallossofbloodfromthegastrointestinaltract,aswellaschronicinflammation,oftenleadstoanemia,andprofessionalguidelinessuggestroutinelymonitoringforthis.[192][193][194]Adequatediseasecontrolusuallyimprovesanemiaofchronicdisease,butirondeficiencymayrequiretreatmentwithironsupplements.Guidelinesvaryastohowironshouldbeadministered.Besides,otherproblemsincludealimitationinpossibledailyresorptionandanincreasedgrowthofintestinalbacteria.Some[194]adviseparenteralironasfirstlineasitworksfaster,hasfewergastrointestinalsideeffects,andisunaffectedbyinflammationreducingenteralabsorption. Otherguidelines[193]adviseoralironasfirst-linewithparenteralironreservedforthosethatfailtoadequatelyrespondasoralironisconsiderablycheaper.Allagreethatsevereanemia(hemoglobinunder10g/dL)shouldbetreatedwithparenteraliron.Bloodtransfusionshouldbereservedforthosewhoarecardiovascularlyunstable,duetoitsrelativelypoorsafetyprofile,lackoflong-termefficacy,andcost.[193] Surgery[edit] Crohn'scannotbecuredbysurgery,asthediseaseeventuallyrecurs,thoughitisusedinthecaseofpartialorfullblockageoftheintestine.[195]Surgerymayalsoberequiredforcomplicationssuchasobstructions,fistulas,orabscesses,orifthediseasedoesnotrespondtodrugs.Afterthefirstsurgery,Crohn'susuallycomesbackatthesitewherethediseasedintestinewasremovedandthehealthyendswererejoined;itcanalsocomebackinotherlocations.Afteraresection,scartissuebuildsup,whichcancausestrictures,whichformwhentheintestinesbecometoosmalltoallowexcrementtopassthrougheasily,whichcanleadtoablockage.Afterthefirstresection,anotherresectionmaybenecessarywithinfiveyears.[196]Forpatientswithanobstructionduetoastricture,twooptionsfortreatmentarestrictureplastyandresectionofthatportionofbowel.Thereisnostatisticalsignificancebetweenstrictureplastyaloneversusstrictureplastyandresectionincasesofduodenalinvolvement.Inthesecases,re-operationrateswere31%and27%,respectively,indicatingthatstrictureplastyisasafeandeffectivetreatmentforselectedpeoplewithduodenalinvolvement.[197] PostsurgicalrecurrenceofCrohn'sdiseaseisrelativelycommon.Crohn'slesionsarenearlyalwaysfoundatthesiteoftheresectedbowel.Thejoin(oranastomosis)aftersurgerymaybeinspected,usuallyduringacolonoscopy,anddiseaseactivitygraded.The"Rutgeert'sscore"isanendoscopicscoringsystemforpostoperativediseaserecurrenceinCrohn'sdisease.MildpostsurgicalrecurrencesofCrohn'sdiseasearegradedi1andi2,moderatetosevererecurrencesaregradedi3andi4.[198]Fewerlesionsresultinalowergrade.Basedonthescore,treatmentplanscanbedesignedtogivethepatientthebestchanceofmanagingtherecurrenceofthedisease.[199] Shortbowelsyndrome(SBS,alsoshortgutsyndromeorsimplyshortgut)iscausedbythesurgicalremovalofpartofthesmallintestine.Itusuallydevelopsinthosepatientswhohavehadhalformoreoftheirsmallintestinesremoved.[200]Diarrheaisthemainsymptom,butothersmayincludeweightloss,cramping,bloating,andheartburn.Shortbowelsyndromeistreatedwithchangesindiet,intravenousfeeding,vitaminandmineralsupplements,andtreatmentwithmedications.InsomecasesofSBS,intestinaltransplantsurgerymaybeconsidered;thoughthenumberoftransplantcentresofferingthisprocedureisquitesmallanditcomeswithahighriskduetothechanceofinfectionandrejectionofthetransplantedintestine.[201] BileaciddiarrheaisanothercomplicationfollowingsurgeryforCrohn'sdiseaseinwhichtheterminalileumhasbeenremoved.Thisleadstothedevelopmentofexcessivewaterydiarrhea.Itisusuallythoughttobeduetoaninabilityoftheileumtoreabsorbbileacidsafterresectionoftheterminalileumandwasthefirsttypeofbileacidmalabsorptionrecognized.[202] Mentalhealth[edit] Crohn'smayresultinanxietyormooddisorders,especiallyinyoungpeoplewhomayhavestuntedgrowthorembarrassmentfromfecalincontinence.[203]Counsellingaswellasantidepressantoranxiolyticmedicationmayhelpsomepeoplemanage.[203] Asof2017[update]thereisasmallamountofresearchlookingatmindfulness-basedtherapies,hypnotherapy,andcognitivebehaviouraltherapy.[204] Alternativemedicine[edit] ItiscommonforpeoplewithCrohn'sdiseasetotrycomplementaryoralternativetherapy.[205]Theseincludediets,probiotics,fishoil,andotherherbalandnutritionalsupplements. AcupunctureisusedtotreatinflammatoryboweldiseaseinChina,andisbeingusedmorefrequentlyinWesternsociety.[206]Atthistime,evidenceisinsufficienttorecommendtheuseofacupuncture.[205] A2006surveyinGermanyfoundthatabouthalfofpeoplewithIBDusedsomeformofalternativemedicine,withthemostcommonbeinghomeopathy,andastudyinFrancefoundthatabout30%usedalternativemedicine.[207]Homeopathicpreparationsarenotprovenwiththisoranyothercondition,[208][209][210]withlarge-scalestudiesfindingthemtobenomoreeffectivethanaplacebo.[211][212][213] Therearecontradictingstudiesregardingtheeffectofmedicalcannabisoninflammatoryboweldisease,[214]anditseffectsonmanagementareuncertain.[215] Prognosis[edit] Crohn'sdiseaseisachronicconditionforwhichthereisnoknowncure.Itischaracterisedbyperiodsofimprovementfollowedbyepisodeswhensymptomsflareup.Withtreatment,mostpeopleachieveahealthyweight,andthemortalityrateforthediseaseisrelativelylow.Itcanvaryfrombeingbenigntoverysevere,andpeoplewithCDcouldexperiencejustoneepisodeorhavecontinuoussymptoms.Itusuallyreoccurs,althoughsomepeoplecanremaindisease-freeforyearsordecades.Upto80%ofpeoplewithCrohn'sdiseasearehospitalizedatsomepointduringthecourseoftheirdisease,withthehighestrateoccurringinthefirstyearafterdiagnosis.[5]MostpeoplewithCrohn'sliveanormallifespan.[216]However,Crohn'sdiseaseisassociatedwithasmallincreaseinriskofsmallbowelandcolorectalcarcinoma(bowelcancer).[217] Epidemiology[edit] ThepercentageofpeoplewithCrohn'sdiseasehasbeendeterminedinNorwayandtheUnitedStatesandissimilarat6to7.1:100,000.TheCrohn'sandColitisFoundationofAmericacitesthisnumberasapprox149:100,000;NIHcites28to199per100,000.[218][219]Crohn'sdiseaseismorecommoninnortherncountries,andwithhigherratesstillinthenorthernareasofthesecountries.[220]TheincidenceofCrohn'sdiseaseisthoughttobesimilarinEuropebutlowerinAsiaandAfrica.[218]ItalsohasahigherincidenceinAshkenaziJews[1][221]andsmokers.[222] Crohn'sdiseasebeginsmostcommonlyinpeopleintheirteensand20s,andpeopleintheir50sthroughtotheir70s.[1][28][20]Itisrarelydiagnosedinearlychildhood.Itusuallyaffectsfemalechildrenmoreseverelythanmales.[223]However,onlyslightlymorewomenthanmenhaveCrohn'sdisease.[224]Parents,siblingsorchildrenofpeoplewithCrohn'sdiseaseare3to20timesmorelikelytodevelopthedisease.[225]Twinstudiesfindthatifonehasthediseasethereisa55%chancetheotherwilltoo.[226] TheincidenceofCrohn'sdiseaseisincreasinginEurope[227]andinnewlyindustrialisedcountries.[228]Forexample,inBrazil,therehasbeenanannualincreaseof11%intheincidenceofCrohn'sdiseasesince1990.[228] History[edit] Mainarticle:ListofpeoplediagnosedwithCrohn'sdisease InflammatoryboweldiseasesweredescribedbyGiovanniBattistaMorgagni(1682–1771)andbyScottishphysicianTKennedyDalzielin1913.[229] IleitisterminaliswasfirstdescribedbyPolishsurgeonAntoniLeśniowskiin1904,althoughitwasnotconclusivelydistinguishedfromintestinaltuberculosis.[230]InPoland,itisstillcalledLeśniowski-Crohn'sdisease(Polish:chorobaLeśniowskiego-Crohna).BurrillBernardCrohn,anAmericangastroenterologistatNewYorkCity'sMountSinaiHospital,describedfourteencasesin1932,andsubmittedthemtotheAmericanMedicalAssociationundertherubricof"Terminalileitis:Anewclinicalentity".Laterthatyear,he,alongwithcolleaguesLeonGinzburgandGordonOppenheimer,publishedthecaseseries"Regionalileitis:apathologicandclinicalentity".However,duetotheprecedenceofCrohn'snameinthealphabet,itlaterbecameknownintheworldwideliteratureasCrohn'sdisease.[21] Research[edit] SomeevidencesupportsthehypothesisthatthebacteriumMycobacteriumaviumsubspeciesparatuberculosis(MAP)isacauseofCrohn'sdisease(seealsoJohne'sdisease).Asaresult,researchersarelookingattheeradicationofMAPasatherapeuticoption.[231]TheCrohnsMAPVaccineisanexperimentalvaccinebasedonthishypothesis.[232]TreatingMAPusingspecificantibioticsthatMAPmaybesusceptibletohasbeenexaminedandtheresultsareunclearbuttentativelybeneficial.[233][234] Crohn'siscommoninpartsoftheworldwherehelminthiccolonisationisrareanduncommoninthoseareaswheremostpeoplecarryworms.Infectionswithhelminthsmayaltertheautoimmuneresponsethatcausesthedisease.TrialsofextractsfromthewormTrichurissuisshowedpromisingresultswhenusedinpeoplewithIBD.[235][236][237]However,thesetrials(TRUST-I&TRUST-II)failedinPhase2clinicaltrialsandwerethendiscontinuedafterconsistentfailureinbothNorthAmericaandEurope.[238][239] Thereisnogoodevidencethatthalidomideorlenalidomideisusefultobringaboutormaintainremission.[240][241] References[edit] 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^CoronadoBiosciences(November7,2013)."CoronadoBiosciencesAnnouncesIndependentDataMonitoringCommitteeRecommendationtoDiscontinueFalkPhase2TrialofTSOinCrohn'sDisease".ArchivedfromtheoriginalonAugust16,2016.RetrievedAugust16,2016. ^SrinivasanR,AkobengAK(April2009)."ThalidomideandthalidomideanaloguesforinductionofremissioninCrohn'sdisease".TheCochraneDatabaseofSystematicReviews(2):CD007350.doi:10.1002/14651858.CD007350.pub2.PMID 19370684. ^AkobengAK,StokkersPC(April2009)."ThalidomideandthalidomideanaloguesformaintenanceofremissioninCrohn'sdisease".TheCochraneDatabaseofSystematicReviews(2):CD007351.doi:10.1002/14651858.CD007351.pub2.PMC 7207562.PMID 19370685. Furtherreading[edit] LichtensteinGR,LoftusEV,IsaacsKL,RegueiroMD,GersonLB,SandsBE(April2018)."ACGClinicalGuideline:ManagementofCrohn'sDiseaseinAdults".Am.J.Gastroenterol.113(4):481–517.doi:10.1038/ajg.2018.27.PMID 29610508. Externallinks[edit] "Crohn'sdisease".MedlinePlus.U.S.NationalLibraryofMedicine. ClassificationDICD-10:K50ICD-9-CM:555OMIM:266600MeSH:D003424DiseasesDB:3178ExternalresourcesMedlinePlus:000249eMedicine:med/477ped/507radio/197PatientUK:Crohn'sdisease WikimediaCommonshasmediarelatedtoCrohn'sdisease. vteInflammatoryboweldisease:Crohn'sdiseaseandulcerativecolitisMain Crohn'sDiseaseActivityIndex Treatment Biologicaltherapy Crohn'sdisease Complications Abdominalpain Analabscess Erythemanodosum Fistula Granuloma Ileum Ileitis Malabsorption Proctitis Proteinlosingenteropathy Pyodermagangrenosum Sacroiliitis Shortbowelsyndrome Smallbowelobstruction Stenosis History GiovanniBattistaMorgagni BurrillBernardCrohn Organizations Crohn'sandColitisFoundationofAmerica DigestiveDisordersFoundation NationalSocietyforColitisandCrohn'sDisease Crohn'sandColitisCanada People ListofpeoplediagnosedwithCrohn'sdisease Listofpeoplediagnosedwithulcerativecolitis DeathsfromCrohn'sdisease vteDiseasesofthedigestivesystemUpperGItractEsophagus Esophagitis Candidal Eosinophilic Herpetiform Rupture Boerhaavesyndrome Mallory–Weisssyndrome UES Zenker'sdiverticulum LES Barrett'sesophagus Esophagealmotilitydisorder Nutcrackeresophagus Achalasia Esophagogastricjunctionoutflowobstruction Diffuseesophagealspasm Gastroesophagealrefluxdisease(GERD) Laryngopharyngealreflux(LPR) Esophagealstricture Megaesophagus Esophagealintramuralpseudodiverticulosis Acuteesophagealnecrosis Stomach Gastritis Atrophic Ménétrier'sdisease Gastroenteritis Peptic(gastric)ulcer Cushingulcer Dieulafoy'slesion Dyspepsia Pyloricstenosis Achlorhydria Gastroparesis Gastroptosis Portalhypertensivegastropathy Gastricantralvascularectasia Gastricdumpingsyndrome Gastricvolvulus Buriedbumpersyndrome Gastrinoma Zollinger–Ellisonsyndrome LowerGItractEnteropathySmallintestine(Duodenum/Jejunum/Ileum) Enteritis Duodenitis Jejunitis Ileitis Peptic(duodenal)ulcer Curling'sulcer Malabsorption:Coeliac Tropicalsprue Blindloopsyndrome Smallintestinalbacterialovergrowth Whipple's Shortbowelsyndrome Steatorrhea Milroydisease Bileacidmalabsorption Largeintestine(Appendix/Colon) Appendicitis Colitis Pseudomembranous Ulcerative Ischemic Microscopic Collagenous Lymphocytic Functionalcolonicdisease IBS Intestinalpseudoobstruction /Ogilviesyndrome Megacolon /Toxicmegacolon Diverticulitis/Diverticulosis/SCAD Largeand/orsmall Enterocolitis Necrotizing Gastroenterocolitis IBD Crohn'sdisease Vascular:Abdominalangina Mesentericischemia Angiodysplasia Bowelobstruction:Ileus Intussusception Volvulus Fecalimpaction Constipation Diarrhea Infectious Intestinaladhesions Rectum Proctitis Radiationproctitis Proctalgiafugax Rectalprolapse Anismus Analcanal Analfissure/Analfistula Analabscess Hemorrhoid Analdysplasia Pruritusani GIbleeding Bloodinstool Upper Hematemesis Melena Lower Hematochezia AccessoryLiver Hepatitis Viralhepatitis Autoimmunehepatitis Alcoholichepatitis Cirrhosis PBC Fattyliver NASH Vascular Budd–Chiarisyndrome Hepaticveno-occlusivedisease Portalhypertension Nutmegliver Alcoholicliverdisease Liverfailure Hepaticencephalopathy Acuteliverfailure Liverabscess Pyogenic Amoebic Hepatorenalsyndrome Peliosishepatis Metabolicdisorders Wilson'sdisease Hemochromatosis Gallbladder Cholecystitis Gallstone/Cholelithiasis Cholesterolosis Adenomyomatosis Postcholecystectomysyndrome Porcelaingallbladder Bileduct/Otherbiliarytree Cholangitis Primarysclerosingcholangitis Secondarysclerosingcholangitis Ascending Cholestasis/Mirizzi'ssyndrome Biliaryfistula Haemobilia Commonbileduct Choledocholithiasis Biliarydyskinesia SphincterofOddidysfunction Pancreatic Pancreatitis Acute Chronic Hereditary Pancreaticabscess Pancreaticpseudocyst Exocrinepancreaticinsufficiency Pancreaticfistula OtherHernia Diaphragmatic Congenital Hiatus Inguinal Indirect Direct Umbilical Femoral Obturator Spigelian Lumbar Petit's Grynfeltt-Lesshaft Undefinedlocation Incisional Internalhernia Richter's Peritoneal Peritonitis Spontaneousbacterialperitonitis Hemoperitoneum Pneumoperitoneum vteOralandmaxillofacialpathologyLips Cheilitis Actinic Angular Plasmacell Cleftlip Congenitallippit Eclabium Herpeslabialis Macrocheilia Microcheilia Nasolabialcyst Sunpoisoning Trumpeter'swart Tongue Ankyloglossia Blackhairytongue Caviartongue Crenatedtongue Cunnilingustongue Fissuredtongue Foliatepapillitis Glossitis Geographictongue Medianrhomboidglossitis Transientlingualpapillitis Glossoptosis Hypoglossia Lingualthyroid Macroglossia Microglossia Rhabdomyoma Palate Bednar'saphthae Cleftpalate High-archedpalate Palatalcystsofthenewborn Inflammatorypapillaryhyperplasia Stomatitisnicotina Toruspalatinus Oralmucosa–Liningofmouth Amalgamtattoo Anginabullosahaemorrhagica Behçet'sdisease Bohn'snodules Burningmouthsyndrome Candidiasis Condylomaacuminatum Darier'sdisease Epulisfissuratum Erythemamultiforme Erythroplakia Fibroma Giant-cell Focalepithelialhyperplasia Fordycespots Hairyleukoplakia Hand,footandmouthdisease Hereditarybenignintraepithelialdyskeratosis Herpangina Herpeszoster Intraoraldentalsinus Leukoedema Leukoplakia Lichenplanus Lineaalba Lupuserythematosus Melanocyticnevus Melanocyticorallesion Molluscumcontagiosum Morsicatiobuccarum Oralcancer Benign:Squamouscellpapilloma Keratoacanthoma Malignant:Adenosquamouscarcinoma Basaloidsquamouscarcinoma Mucosalmelanoma Spindlecellcarcinoma Squamouscellcarcinoma Verrucouscarcinoma Oralfloridpapillomatosis Oralmelanosis Smoker'smelanosis Pemphigoid Benignmucousmembrane Pemphigus Plasmoacanthoma Stomatitis Aphthous Denture-related Herpetic Smokelesstobaccokeratosis Submucousfibrosis Ulceration Riga–Fededisease Verrucavulgaris Verruciformxanthoma Whitespongenevus Teeth(pulp,dentin,enamel) Amelogenesisimperfecta Ankylosis Anodontia Caries Earlychildhoodcaries Concrescence Failureoferuptionofteeth Densevaginatus Taloncusp Dentindysplasia Dentinhypersensitivity Dentinogenesisimperfecta Dilaceration Discoloration Ectopicenamel Enamelhypocalcification Enamelhypoplasia Turner'shypoplasia Enamelpearl Fluorosis Fusion Gemination Hyperdontia Hypodontia Maxillarylateralincisoragenesis Impaction Wisdomtoothimpaction Macrodontia Methmouth Microdontia Odontogenictumors Keratocysticodontogenictumour Odontoma Densindente Opencontact Prematureeruption Neonatalteeth Pulpcalcification Pulpstone Pulpcanalobliteration Pulpnecrosis Pulppolyp Pulpitis Regionalodontodysplasia Resorption Shovel-shapedincisors Supernumeraryroot Taurodontism Trauma Avulsion Crackedtoothsyndrome Verticalrootfracture Occlusal Toothloss Edentulism Toothwear Abrasion Abfraction Aciderosion Attrition Periodontium(gingiva,periodontalligament,cementum,alveolus)–Gumsandtooth-supportingstructures Cementicle Cementoblastoma Gigantiform Cementoma Eruptioncyst Epulis Pyogenicgranuloma Congenitalepulis Gingivalenlargement Gingivalcystoftheadult Gingivalcystofthenewborn Gingivitis Desquamative Granulomatous Plasmacell Hereditarygingivalfibromatosis Hypercementosis Hypocementosis Lineargingivalerythema Necrotizingperiodontaldiseases Acutenecrotizingulcerativegingivitis Pericoronitis Peri-implantitis Periodontalabscess Periodontaltrauma Periodontitis Aggressive Asamanifestationofsystemicdisease Chronic Perio-endolesion Teething Periapical,mandibularandmaxillaryhardtissues–Bonesofjaws Agnathia Alveolarosteitis Buccalexostosis Cherubism Idiopathicosteosclerosis Mandibularfracture Microgenia Micrognathia Intraosseouscysts Odontogenic:periapical Dentigerous Buccalbifurcation Lateralperiodontal Globulomaxillary Calcifyingodontogenic Glandularodontogenic Non-odontogenic:Nasopalatineduct Medianmandibular Medianpalatal Traumaticbone Osteoma Osteomyelitis Osteonecrosis Bisphosphonate-associated Neuralgia-inducingcavitationalosteonecrosis Osteoradionecrosis Osteoporoticbonemarrowdefect Paget'sdiseaseofbone Periapicalabscess Phoenixabscess Periapicalperiodontitis Stafnedefect Torusmandibularis Temporomandibularjoints,musclesofmasticationandmalocclusions–Jawjoints,chewingmusclesandbiteabnormalities Bruxism Condylarresorption Mandibulardislocation Malocclusion Crossbite Openbite Overbite Overeruption Overjet Prognathia Retrognathia Scissorbite Maxillaryhypoplasia Temporomandibularjointdysfunction Salivaryglands Benignlymphoepitheliallesion Ectopicsalivaryglandtissue Frey'ssyndrome HIVsalivaryglanddisease Necrotizingsialometaplasia Mucocele Ranula Pneumoparotitis Salivaryductstricture Salivaryglandaplasia Salivaryglandatresia Salivaryglanddiverticulum Salivaryglandfistula Salivaryglandhyperplasia Salivaryglandhypoplasia Salivaryglandneoplasms Benign:Basalcelladenoma Canalicularadenoma Ductalpapilloma Monomorphicadenoma Myoepithelioma Oncocytoma Papillarycystadenomalymphomatosum Pleomorphicadenoma Sebaceousadenoma Malignant:Aciniccellcarcinoma Adenocarcinoma Adenoidcysticcarcinoma Carcinomaexpleomorphicadenoma Lymphoma Mucoepidermoidcarcinoma Sclerosingpolycysticadenosis Sialadenitis Parotitis Chronicsclerosingsialadenitis Sialectasis Sialocele Sialodochitis Sialosis Sialolithiasis Sjögren'ssyndrome Orofacialsofttissues–Softtissuesaroundthemouth Actinomycosis Angioedema Basalcellcarcinoma Cutaneoussinusofdentalorigin Cystichygroma Gnathophyma Ludwig'sangina Macrostomia Melkersson–Rosenthalsyndrome Microstomia Noma OralCrohn'sdisease Orofacialgranulomatosis Perioraldermatitis Pyostomatitisvegetans Other Eaglesyndrome Hemifacialhypertrophy Facialhemiatrophy Oralmanifestationsofsystemicdisease Authoritycontrol:Nationallibraries Japan Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Crohn%27s_disease&oldid=1084467384" Categories:AbdominalpainAutoimmunediseasesInflammationsMembranetransportproteindisordersNoninfectiveenteritisandcolitisSteroid-responsiveinflammatoryconditionsHiddencategories:CS1maint:DOIinactiveasofFebruary2022WebarchivetemplatewaybacklinksCS1Spanish-languagesources(es)ArticleswithshortdescriptionShortdescriptionmatchesWikidataUsemdydatesfromNovember2021ShortdescriptionisdifferentfromWikidataAllarticleswithunsourcedstatementsArticleswithunsourcedstatementsfromSeptember2021Articlescontainingpotentiallydatedstatementsfrom2017AllarticlescontainingpotentiallydatedstatementsArticlescontainingPolish-languagetextCommonscategorylinkfromWikidataArticleswithNDLidentifiersGoodarticlesArticlescontainingvideoclipsWikipediamedicinearticlesreadytotranslateWikipediaemergencymedicinearticlesreadytotranslate Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk English Views ReadEditViewhistory More Search Navigation 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