炎癥性腸病的診療

InflammatoryBowelDisease

炎癥性腸病Overview

Introduction/EpidemiologyPathogenesisClinicalManifestationsConventionalTherapiesPrognosisIntroductionDefinition:

Chronicautoimmuneinflammatorydisorders,involvingsomeoralllayersofthegutwall.UlcerativeColitis(UC)Mucosal/submucosalonlyCrohn’sDisease(CD)AlllayersofwallatriskUlcerativeColitisCrohn’sDiseaseEndoscopicAppearanceNormalcolonFriabilityExudatebleedingDiffuseulcerationCobblestoningFocalulcerationHistology/DepthofIBDMucosalandsubmucosalonlyNogranulomasseen*Transmuraldisease*GranulomasoccasionallyseenUlcerativeColitisCrohn’sDiseaseUlcerativeColitisvsCrohn’sDiseaseEpidemiologyIncidence:5-29per100,000peopleperyearPrevalence:~1.3millionpersonsNewcases:estimated20,000-100,000peryear*Genderdistribution:

Crohn’sdisease:Slightfemalepredominance

UlcerativeColitis:SlightmalepredominanceAgeincidence--Bimodaldistribution

Peakonset:15to25yearsofage

Secondpeakincidence:50to65yearsofageAnti-inflammatoryPro-inflammatoryTNFIL-1bIL-12/IL-18IFNgIL-4/IL-13IL-1RaTGFbIL-10PGE2PathogenesisPathogenesisofInflammatoryBowelDiseaseImmuneDysregulationIBDGenetic

SusceptibilityEnvironmental

TriggersEnvironmentRiskfactors:OccupationsassociatedwithoutdoorphysicallaborHighersocioeconomicstatusWomenwhouseoralcontraceptivesIncreasedintakeofrefinedsugarsandapaucityoffreshfruitsandvegetablesinthedietSmokingStressRiskFactorsKnownFamilyhistoryofIBDCigarettesmoking

RiskforCD

ProtectiveforUCAppendectomy

RiskforCD

ProtectiveforUCPossibleOralcontraceptivesDiet:sugar,fatBreastfeeding(protective)ChildhoodinfectionsMeaslesinfectionMycobacteriumparatuberculosisinfectionTherelativeriskamongfirst-degreerelativesis14to15timeshigherthanthatofthegeneralpopulationEthnicityplaysaroleaswellTheconcordancerateamongmonozygotictwinsisashighas67%forCrohn'sdiseasebutonly13%to20%forulcerativecolitisGeneticsGenetics10-25%ofpatientshavea1stdegreerelativewithIBDLifetimeriskforsiblingsandoffspringofIBDpatients:~10%Monozygotictwins–oftensharediseasepatternandageofonsetConcordance–CD(58%)>UC(6%)Genomesearch–locionchromosomes3,5,6,12,14,16,19LuminalantigenMucosalimmuneSystem(APC)Th2Th1T-supp/T-regcellsTNF-

,IFN-IL-4IL-5IL-10HumoralimmuneresponseB-cell,plasmacellexpansionIncreasedIgsecretionTh1vsTh2responseCrohn’sDiseaseCytokineproductionResistancetonormaldownregulationTissueinjuryIneffectiverepairUlcerativeColitisHealthyColonCell-mediatedimmuneresponseImmuneDysregulationPathologyMacroscopicFeatures

Earlylesion-aphthousulcer

LaterFindings-Linearorserpiginousulcersmayforminalongitudinaldirection.Irregularthickeningofthebowelwalland,alongwithhypertrophyofthemuscularismucosa.Microscopiclevel

Thetransmuralnatureoftheinflammation.

Thepresenceofgranulomas.

ClinicalManifestationsHistoryExamLaboratoryEndoscopyStoolStudiesClinicalPresentationSignsMildormoderatediseaseusuallylookwellSevereattacks:fevertachycardiaabdominaltendernessdistensiondecreasedbowelsoundsClubbingLabevaluationAcutephasereactants:ESR,CRPelevationLeukocytosisAnemiaReducedserumalbuminHypokalemiaAbnormalLFT’sStool:leukocytes,RBC’sSymptomsCrohn’sDiseaseDiarrhea(non-bloody)WeightlossFeverPerianaldrainage/pusRightlowerquadrantpainUlcerativeColitisRectalbleedingFecalurgency/tenesmusDiarrhea(bloody)LowerabdominalcrampingDiseaseDistributionUlcerativeColitisRectum

CecumConfluent/ContiguousIlealinvolvementuncommonNoperianaldiseaseCrohn’sDiseaseAnywherefrom“mouthtoanus”Segmental/SkipLesionsRectumusuallysparedIlealinvolvementcommonPerianaldiseasecommonUlcerativeColitis–distributionMildSevere30%40%30%Crohn’sDisease–distributionLiverEyesSkinJointsBloodHeartMouthExtraintestinalIBDComplication-UCMassivehemorrhagePerforationacutedilatationofthecolon("toxicmegacolon")stricturespseudopolypscoloniccancerComplication-CDStrictureFistulaandAbscessperforationandbleedingcholelithiasisComplicationsofCrohn’sDiseaseCrohn’sStricturesComplicationsofCrohn’sDiseaseCrohn’sFistulaePerianalfistulaComplicationsofCrohn’sDiseaseCrohn’sFistulaeEntero-enteralfistulaAssessmentofDiseaseSeverityMild—fewerthanfourstoolsdaily,withorwithoutblood,withnosystemicdisturbanceandanormalerythrocytesedimentationrate(ESR).Moderate—morethanfourstoolsdailybutwithminimalsystemicdisturbance.Severe—morethansixstoolsdailywithbloodandwithevidenceofsystemicdisturbance,asshownbyfever,tachycardia,anemia,oranESRgreaterthan30.TreatmentGoalsDiagnosisandprompttherapeuticresponseInductionofcompleteremissionLowside-effectprofiletoenhancecomplianceMaintenanceofclinicalremissionMedicalvs.surgicalremissionSteroidsparingEducationandimprovementofqualityoflifeTreatmentConventionaltherapies:5-ASA/SASPCorticosteroids/BudesonideImmunomodulatorsAntibioticsAnti-metabolitesBiologicModifiersPrognosisUlcerativecolitis80%haveintermittentattacksoftheirdiseaseFrom10%to15%o