潰瘍性結(jié)腸炎的方方面面

潰瘍性結(jié)腸炎的方方面面第1頁/共86頁潰瘍性結(jié)腸炎第2頁/共86頁Introduction

IBD是一種病因尚不十分清楚的慢性非特異性腸道炎癥，包括UC和CD

。其發(fā)病率呈逐年上升趨勢，且多為青壯年發(fā)病，臨床表現(xiàn)復雜，并發(fā)癥嚴重，腸外表現(xiàn)多樣，嚴重影響個人生活質(zhì)量和社會生產(chǎn)力。此外，因其有癌變的風險，備受廣大醫(yī)生的重視。近年來在國內(nèi)外IBD基礎與臨床研究高潮迭起，基礎研究的成果直接指向臨床治療，取得了劃時代的進展。探討和摸索適合國人的治療方案以降低重癥UC的并發(fā)癥和死亡率顯得十分重要。第3頁/共86頁Introduction

Ulcerativecolitisischaracterizedbymucosalinflammation

ofthecolon.Thepathologyisinflammatoryandthe

diseasecourseisrelapsingandremittingwithintermittent

symptomsofrectalbleedinganddiarrhea.Approximately

25%ofpatientsdevelopachronicactiveorarapidlyfulminate

diseasecourse.Chronicinflammationcanleadto

dysplasiaandcancer.Approximately20%ofpatientsrequire

colectomywithileoanalpouchorstoma.VelayosFS,TerdimanJP,WalshJM.Effectof5-aminosalicylate

useoncolorectalcanceranddysplasiarisk:asystematicreview

andmetaanalysisofobservationalstudies.AmJGastroenterol

2005;100:1345–1353.第4頁/共86頁ConsensusStangeEF,TravisSP,VermeireS,ReinischW,GeboesK,BarakauskieneA,etal.Europeanevidence-basedConsensusonthediagnosisandmanagementofulcerativecolitis:definitionsanddiagnosis.JCrohnsColitis2008;2:1–23.VanAsscheG，DignassA，PanesJ，eta1．ThesecondEuropeanevidence-basedConsensusonthediagnosisandmanagementofulcerativecolitis：Definitionsanddiagnosis．JCrohnsColitis，2010·4：727．MowatC,ColeA,WindsorA,AhmadT,ArnottI,DriscollR,etal.Guidelinesforthemanagementofinflammatoryboweldiseaseinadults.Gut2011;60:571–607.TurnerD,LevineA,EscherJC,GriffithsAM,RussellRK,DignassA,etal.Managementofpediatriculcerativecolitis:ajointECCOandESPGHANevidence-basedconsensusguidelines.JPediatrGastroenterolNutr2012.TurnerD,TravisSP,GriffithsAM,RuemmeleFM,LevineA,BenchimolEI,etal.Consensusformanagingacutesevereulcerativecolitisinchildren:asystematicreviewandjointstatementfromECCO,ESPGHAN,andthePortoIBDWorkingGroupofESPGHAN.AmJGastroenterol2011;106:574–88.第5頁/共86頁Managementconsensusofinflammatoryboweldiseasefor

theAsia–Pacificregion2006

Abstract:Atthepresenttherearenolarge-scaleepidemiologicdataoninflammatoryboweldisease(IBD)intheAsia–Pacificregion,butseveralstudieshaveshownanincreasedincidenceandprevalenceofIBDinthisregion.ComparedtotheWest,thereappearstoexistatimelagphenomenon.WithregardtothetwomainformsofIBD,ulcerativecolitis(UC)ismoreprevalentthanCrohn’sdisease(CD).Inadditiontogeographicdifferences,ethnicdifferenceshavebeenobservedinthemultiracialAsiancountries.Moreover,thegeneticbackgroundsaredifferentintheAsiancomparedtoWesternpatients.Forinstance,NOD2/CARD15variantshavenotbeenfoundinAsianCDpatients.Ingeneral,theclinicalcourseofIBDseemstobelesssevereintheAsia–PacificregionthaninWesterncountries.DiagnosisofIBDinthisregionposesspecialproblems.ThelackofagoldstandardforthediagnosisofIBD,andtheexistenceofavarietyofinfectiousenterocolitiswithsimilarmanifestationstothoseofIBDmakethedifferentialdiagnosisparticularlydifficult.Sofar,WesterndiagnosticcriteriahavebeenintroducedforthediagnosisofIBD.Astepwiseapproachtoexcludenon-IBDenterocolitisalsomustbeintroduced,andadefinitediagnosismustincludetypicalhistologicalfeatures.Insomepatients,followupandtherapeutictrialsmightbenecessarytoobtainadefinitivediagnosis.AbetterunderstandingofthepathogenesisofIBDwillallowthedevelopmentofbetterdiagnosticmarkers.ThemanagementofIBDalsoposessomespecialproblemsintheAsia–PacificRegion.ThereisoftenadelayinusingpropermedicationsforIBD,andalternativelocalremediesarestillwidelyused.WithacombinationofWesternguidelinesandregionalexperiences,similarprinciplescanbeusedforinductionandmaintenanceofremission.Astepwiseselectionofmedicationsisadvocateddependingontheextent,activityandseverityofthedisease.ComprehensiveandindividualizedapproachesaresuggestedfordifferentIBDpatients.DeeperunderstandingofdiseasepathogenesisandtheuniquecharacteristicsofIBDintheAsia–Pacificregion,combinedwithreasonableandpracticalguidelinesfordrugmanagementandthefutureuseofbiologicalagentswouldimprovethetherapeuticoutlookofIBDinthisregion.第6頁/共86頁TheAsia-Pacificconsensusonulcerativecolitis2010

第7頁/共86頁Europeanevidence-basedconsensusonthediagnosis/managementofulcerativecolitis2008ThisdocumentsetsoutthecurrentEuropeanConsensusonthediagnosisandmanagementofUC,reachedbytheEuropeanCrohn'sandColitisOrganisation(ECCO)atameetingheldinBerlinon20thOctober2006.ECCOisaforumforspecialistsininflammatoryboweldiseasefrom23Europeancountries.LiketheinitialConsensusonthemanagementofCrohn'sdisease,thecurrentConsensusisgroupedintothreeparts:definitionsanddiagnosis;currentmanagement;andmanagementofspecialsituations.Thisfirstsectionconcernsaims,methodsanddefinitionsoftheConsensus,aswellasclassification,diagnosis,imagingandpathologyofUC.Thesecondsectiononcurrentmanagementincludestreatmentofactivedisease,maintenanceofmedically-inducedremissionandsurgeryofUC.Thethirdsectiononspecialsituationsincludespouchdisorders,cancersurveillance,pregnancy,paediatrics,psychosomatics,extra-intestinalmanifestationsandalternativetherapy.第8頁/共86頁2ndEuropeanevidence-basedconsensusonthediagnosis/managementofulcerativecolitis2012ThisdocumentupdatesthepreviousEuropeanConsensusonthediagnosisandmanagementofUC,andwasfinalisedbytheEuropeanCrohn'sandColitisOrganisation(ECCO)atameetingheldinDublininFebruary2011.ECCOisaforumforspecialistsininflammatoryboweldiseasefrom31Europeancountries.LiketheinitialConsensusonthediagnosisandmanagementofulcerativecolitis,6–8thisupdatedConsensusisgroupedintothreeparts:definitionsanddiagnosis;currentmanagement;andmanagementofspecialsituations.Previouslyincludedchaptersonpregnancyandpediatricsarenolongerincludedinthisguideline,asspecificECCOConsensusGuidelinesonReproductionandPregnancyandPediatricUC(togetherwithESPGHAN)coverthesetopicsextensively.第9頁/共86頁Background

潰瘍性結(jié)腸炎（UC）1859年由Wilks首先描述，1920年被醫(yī)學界公認，我國于1956年首次報道?！短匕l(fā)性潰瘍性結(jié)腸炎診斷及治療標準（草案）》（1978年杭州）《潰瘍性結(jié)腸炎的診斷及療效標準》（1993年太原）《對潰瘍性結(jié)腸炎診斷治療規(guī)范的建議》（2000年杭州）《對我國炎癥性腸病診斷治療規(guī)范的共識意見》（2007年濟南）《炎癥性腸病診斷與治療的共識意見》（2012年廣州）從中可以看出每一次補充和修改都反映了我國對該病認識的逐步提高，治療逐漸規(guī)范化。第10頁/共86頁第九屆中華消化病學分會炎癥性腸病學組成員名單

名譽組長：歐陽欽

組長：胡品津

副組長：錢家嗚夏冰吳開春冉志華

秘書：王玉芳高翔

核心成員：胡品津歐陽欽鄭家駒錢家嗚夏冰

吳開春冉志華劉占舉鐘捷吳小平

陳旻湖胡仁偉

組員：歐陽欽鄭家駒鄧長生劉新光胡品津

錢家鳴夏冰吳開春李俊霞呂愈敏

顧芳劉玉蘭王曉娣韓英朱峰

冉志華劉占舉鄭萍鐘捷龐智

曹茜陳旻湖智發(fā)朝姜泊張亞歷

鐘英強沙衛(wèi)紅胡仁偉王玉芳甘華田

鄒開芳吳小平繆應蕾江學良于成功

梅俏王承黨郭長存盧雪峰高翔

霍麗娟第11頁/共86頁UlcerativecolitisinChina:Retrospectiveanalysisof3100

hospitalizedpatientsBackground&Aims:Thisretrospectivestudyanalyzedtheclinicalcharacteristicsofhospitalizedpatientswithulcerativecolitis(UC)inChina.Methods:Atotalof3100hospitalizedpatientswithUCadmittedto23hospitalsinChinafrom1990to2003wereretrospectivelyinvestigatedandtheirclinicalcharacteristicswereanalyzed.Results:Amale/femaleratioof1.34/1.00wasfoundinthe3100patients,whohadanaverageageof4415.1yearsatdiagnosis.Ofthepatients,2972(95.9%)hadactiveUC.ActiveUCwasmildin35.4%ofthe2972patients,moderatein42.9%andseverein21.7%.Ofthe2726patientswithadescriptionoftheirlesionextent,14.8%hadproctitis,26.4%hadproctosigmoiditis,25.0%hadleft-sidedcolitis,6.3%hadextensivecolitis,25.8%hadpancolitisand1.7%hadregionalcolitis.ThepredominantcomplaintsofthepatientswithUCwerebloodydiarrhea(48.2%),abdominalpain(67.3%)andmucusstools(58.4%).Amongthesepatients,13.6%hadextraintestinalmanifestationsand9.6%hadrelatedcomplications.Adifferentialdiagnosiswasdifficulttomake,astherewere19varietiesofthedisease;infectiousenterocolitishadamisdiagnosisrateof22.9%beforeadmission.ThemainmedicationsforUCinChinawereaminosalicylates(66.8%)andsteroids(42.8%).Only94(3%)ofthepatientsrequiredcolectomyandonly19(0.6%)diedofUC.Conclusions:ComparedwithUCinWesterncountries,ulcerativecolitisinChinahassomedifferencesinclinicalcharacteristics.Therefore,afurtherpopulation-basedepidemiologicalstudyisrequiredtodeterminetheprevalenceandincidenceratesofUCinChina.OuyangQ．APDW2004ChineseIBDworkinggroup．JGastroenterolHepatol.2007．第12頁/共86頁EpidemiolgyTheincidenceofUCrangedfrom1.0to2.0per100000personyears.TheprevalenceofUChasrangedfrom4.0to44.3per100000.Inarecentstudy,thespeculatedprevalencewas11.6/100000inChina.ComparedtotimetrendsintheWest,thereappearstobeatimelagphenomenoninvolvingincidenceandandprevalenceofIBDwithregardtotheAsianexperience.OuyangQ,TandonR,GohKLetal.Managementconsensusof

inflammatoryboweldiseasefortheAsia-Pacificregion.J

Gastroenterol.Hepatol.2006;21:1772–82.Lennrd-JonesJE.IncidenceofinfammatoryboweldiseaseacrossEurope:isthereadifferencebetweennorthandsouth?.Gut1996;39:690-697.第13頁/共86頁EtiologyandPathogenesis目前對IBD病因和發(fā)病機制的認識可概括為：環(huán)境因素作用于遺傳易感者，在腸道菌群叢的參與下，啟動了腸道免疫系統(tǒng)及非免疫系統(tǒng)，最終導致免疫反應和炎癥過程?？赡苁怯捎诳乖某掷m(xù)刺激或（及）免疫調(diào)節(jié)紊亂，這種免疫炎癥反應表現(xiàn)為過度亢進或難于自限。BaumgartDC,CardingSR.Inflammatoryboweldisease:causeandimmunobiology.Lancet2007;369:1627–1640.BrownSJ，MayerI．Theimmuneresponseininflammatoryboweldisease．AmJGastroenterol，2007，102：2058—2069．BernsteinCN，ShanahanF．Disordersofamodernlifestylelreconcilingtheepidemiologyofinflammatoryboweldiseases．Gut，2008，57：1185-1191．第14頁/共86頁菌群失調(diào)IBD患者腸遭細菌存在菌群失調(diào)，正常細菌數(shù)量減少，而致病菌、條件致病菌數(shù)量明顯增多。Duchmann等發(fā)現(xiàn)。正常人對其體內(nèi)腸道菌群及抗原物質(zhì)耐受，而IBD患者腸黏膜免疫細胞對失調(diào)的腸道菌群及抗原物質(zhì)失去了耐受。這一發(fā)現(xiàn)證實了IBD患者腸道菌群及抗原物質(zhì)能誘導腸黏膜異常免疫反應。Frank等發(fā)現(xiàn)IBD患者腸道菌群中擬桿菌、厚壁菌類減少，而變形桿菌及放線菌等增多。由于在腸道內(nèi)，擬桿菌、厚壁菌是主要的裂解食物纖維產(chǎn)生丁酸鹽和其他短鏈脂肪酸的細菌，這些細菌數(shù)量減少，導致維持腸上皮細胞生長和代謝的丁酸鹽和其他短鏈脂肪酸等營養(yǎng)物質(zhì)減少。同時。潰瘍性結(jié)腸炎患者腸道內(nèi)產(chǎn)硫化氫的細菌增多，硫化氫具有抑制丁酸鹽和其他短鏈脂肪酸等營養(yǎng)物質(zhì)生存．及直接影響腸上皮細胞新陳代謝的功能。上述細菌菌群失調(diào)導致腸上皮細胞營養(yǎng)缺乏，影響了腸黏膜屏障功能。DuchmannR。KaiserI，HermannE，eta1．Toleranceexiststowardsresidentintestinalflorabutisbrokeninactiveinflammatoryboweldisease(IBD)．ClinExpImmunol，1995．102：448—455．FrankDN，StAmandAL，F(xiàn)eldmanRA，eta1．Molecularphylogeneticcharacterizationofmicrobialcommunityimbalancesinhumaninflammatoryboweldiseases．ProcNatlAcadSciUSA，2007，104：13780—13785．第15頁/共86頁FamilyhistoryKitahoraetal.foundastrongfamilialoccurrenceinUCamongJapanesepatients.InaKoreanstudy,asimilarfamilialaggregationwasalsoreported.KitahoraT,UtsunomiyaT,YokotaA.EpidemiologicalstudyofulcerativecolitisinJapan:incidenceandfamilialoccurrence.TheEpidemiologyGroupoftheResearchCommitteeofInflammatoryBowelDiseaseinJapan.J.Gastroenterol.1995;30(Suppl.8):5–8.ParkER,YangSK,MyungSJetal.FamilialoccurrenceofulcerativecolitisinKorea.KoreanJ.Gastroenterol.2000;36:770–4.第16頁/共86頁RiskfactorsObjectiveToscreentheriskfactorsofinflammatoryboweldisease(IBD)bycaseinvestigation．Methords72determinedIBDpatientsand72pairedhealthysubjectsweresurveyedwithanorganizedinventorycomprisingofrelevantitemstoIBD．COXregressionmethodwasusedtoscreenthestatisticallysignificantriskfactorsforIBD．ResultsCOXregressionindicatedthestatisticalsignificanceinstress．milkandfriedfoodovertheotherpostulatedriskfactorsforIBD．ConclusionStress，milkandfriedfoodarethepotentialriskfactorsforIBD．KaichunWuetal.Investigationontheriskfactorsofinflammatoryboweldisease：Apairedstudyof72cases.ChinJGastroenterolHepatol.2006,15(2):161-162第17頁/共86頁ProtectivefactorsAstudyfromJapanfoundaprotectiveeffectofsmokingforUC.Nametal.foundthatappendectomywasprotectiveagainstUCintheirgroupofKoreanpatients.Acase-controlstudyofulcerativecolitisinrelationtodietaryandotherfactorsinJapan.TheEpidemiologyGroupoftheResearchCommitteeofInflammatoryBowelDiseaseinJapan.JGastroenterol.1995;30(Suppl.8):9–12.NamSW,YangSK,JungHYetal.Appendectomyandtheriskofdevelopingulcerativecolitis:resultsaftercontrolofsmokingfactor.KoreanJ.Gastroenterol.1998;32:55–60.VleggaarFP,LutgensMW,ClaessenMM.Reviewarticle:the

relevanceofsurveillanceendoscopyinlong-lastinginflammatory

boweldisease.Aliment.Pharmacol.Ther.2007;26(Suppl.2):

47–52.第18頁/共86頁ClinicalPresentationIntestinalSymptoms70%ofpatientswithUCreport>5bowelmovementsduringacutephases.Themainreason

fordiarrheaiscolonicinflammation,butbileacidand

foodmalabsorptionsecondarytoinflammationinthe

terminalileumortheproximalsmallbowelcancontribute

tothissymptom.Ahistoryofsurgicalresectionscan

beseminalinexplainingsymptoms.AcutephasesofUC

almostalwayspresentwithbloodydiarrhea(“hematochezia”).Activeinflammatoryanorectallesions

resultinurgencyofdefecationandcrampsarounddefecation

(“tenesmus”).UCpatientsoftencomplainof

lowerleftquadrantpain.ExtraintestinalManifestationsWafikEl-DieryandDavidMetz,SectionEditors．DiagnosticsofInflammatoryBowelDisease．Gastroenterology，2007;133:1670–1689．第19頁/共86頁腸外表現(xiàn)(Extraintestinal

manifestations)腸外表現(xiàn)包括：皮膚黏膜表現(xiàn)(如口腔潰瘍、結(jié)節(jié)性紅斑和壞疽性膿皮病)關節(jié)損害(如外周關節(jié)炎、脊柱關節(jié)炎等)眼部病變(如虹膜炎、鞏膜炎、葡萄膜炎等)、肝膽疾病(如脂肪肝、原發(fā)性硬化性膽管炎、膽石癥等)血栓栓塞性疾病等。

MendozaJL,LanaR,TaxoneraCetal.Extraintestinal

manifestationsininflammatoryboweldisease:differencesbetween

Crohn’sdiseaseandulcerativecolitis.Med.Clin.(Barc.)2005;125:

297–300.第20頁/共86頁并發(fā)癥(Complications)并發(fā)癥包括：中毒性巨結(jié)腸（toxicmegacolon）腸穿孔下消化道大出血上皮內(nèi)瘤變和癌變錢家鳴,等.潰瘍性結(jié)腸炎合并中毒性巨結(jié)腸六例及文獻復習.中華內(nèi)科雜志[J].2012，51(9):694-697/ChowDK，LeongRW，TsoiKK,eta1．Long—termfollow—up

ofulcerativecolitisintheChinesepopulation．AmJ

Gastroenterol，2009，104：647-654．第21頁/共86頁Serologicalmarkers

Thetwomostwidelystudiedserologicalmarkersin

inflammatoryboweldiseaseinrecentyearshavebeen

p-ANCAandASCA.Theclinicalutilityofp-ANCAorASCA

testinginthediagnosisofinflammatoryboweldisease,in

patientswithnon-specificgastrointestinalsymptoms,is

limitedbecauseofthevaryingseroprevalenceofthese

antibodiesinpatientswithinflammatoryboweldiseaseand

theinadequatesensitivityoftheassays.LawranceIC,MurrayK,HallA,SungJJ,LeongR.Aprospective

comparativestudyofASCAandpANCAinChineseandCaucasian

IBDpatients.Am.J.Gastroenterol.2004;99:2186–94ReeseGE,ConstantinidesVA,SimillisCetal.Diagnosticprecision

ofanti-Saccharomycescerevisiaeantibodiesandperinuclear

antineutrophilcytoplasmicantibodiesininflammatorybowel

disease.AmJGastroenterol.2006(Oct);101(10):2410–22.BossuytX．Serologicmarkersininflammatofyboweldisease．C1in

Chem2006：52：171一181．第22頁/共86頁Serumproteins

目的應用蛋白質(zhì)組學尋找潰瘍性結(jié)腸炎(UC)血清差異蛋白，初步探索UC可能的生物標志物。方法收集UC患者30例和健康對照者30名的血清標本，雙向凝膠電泳(2-DE)分離等量混合血清的蛋白質(zhì)，運用圖像分析軟件進行比較和分析，識別差異表達蛋白質(zhì)。應用基質(zhì)輔助激光解吸／電離飛行時間質(zhì)譜(MAI，DI-TOF-MS)鑒定部分差異蛋白質(zhì)點。結(jié)果UC組和對照組之間年齡、體重指數(shù)、吸煙情況和飲滔量的差異均無統(tǒng)計學意義(P值均>o．05)。初步篩選出UC患者與健康對照者存在明顯差異的39個蛋白點，選擇其中9個點。經(jīng)質(zhì)譜分析發(fā)現(xiàn)觸珠蛋白，熱休克轉(zhuǎn)錄因子2，受體酪氨酸激酶、醛脫氫酶、載脂蛋白c一Ⅲ、中心粒旁物質(zhì)l在UC患者中表達水平升高，角蛋白1，細絲蛋白A結(jié)合蛋白1、肌球蛋白3在UC患者中表達水平降低。結(jié)論采用蛋白質(zhì)組學2-DE和質(zhì)譜技術，篩選并鑒定出與UC相關的9個血清蛋白質(zhì)，為提供新的UC生物學行為研究分子標志物奠定基礎。繆應雷，等.潰瘍性結(jié)腸炎血清差異蛋白的篩選研究.中華消化雜志.2010,30(12):898-901.尿白蛋白

目的：探討炎癥性腸病患者尿中白蛋白的臨床意義。方法：對臨床確診的32例IBD患者（UC27例，CD5例)在疾病的不同時期，用免疫放射比濁法測定尿中白蛋白，并結(jié)合臨床Harvey和Bradshaw指數(shù)進行綜合分析，選取25例健康人為正常對照。結(jié)果：患者尿白蛋白活動期比緩解期明顯增高（0.002），Harvey和Bradshaw指數(shù)呈正相關（活動期r=0.76,P<0.001；靜止期r=0.73,P<0.001）。患者尿中白蛋白明顯高于正常人（活動期P<0.001,緩解期,P<0.005）。結(jié)論：患者尿中白蛋白可作為判斷患者疾病活動情況的指標。鄧長生.炎癥性腸病患者尿白蛋白的臨床意義.武漢大學學報.2002，23(1)：88-89.第24頁/共86頁巨細胞病毒(CMV)巨細胞病毒(CMV)屬皰疹病毒科B屬雙鏈DNA病毒，近年隨著IBD與CMV研究的深入，發(fā)現(xiàn)CMV在IBD的發(fā)生和疾病進展中起一定作用，且對IBD的臨床診治亦有一定指導價值。Pfau等發(fā)現(xiàn)CMV更易感染肉芽組織生長細胞．CMV對炎癥的趨向性使IBD患者感染CMV的風險增加。結(jié)腸活檢組織的炎癥和潰瘍部位可見CMV包涵體,且研究發(fā)現(xiàn)生長旺盛的細胞如肉芽組織或潰瘍深部．更易發(fā)現(xiàn)CMV感染．推測CMV可通過單核細胞到達炎癥黏膜．并可在黏膜內(nèi)增殖．且對炎癥黏膜具有特殊親和力。CMV急性感染可顯著提高血清和腸道自然殺傷細胞、白細胞介素(IL)．6、TNF-a、IFN．1水平．提示CMV感染可改變黏膜免疫．提高宿主對炎癥的易感性．CMV感染可激活原癌基因、激酶、轉(zhuǎn)錄因子致腫瘤發(fā)生?？赡苁荌BD患者結(jié)直腸癌發(fā)病率較高的原因之一例。MatsuokaK,1waoY，MoriT，eta1．Cytomegalovirusisfrequentlyreactivatedanddisappearswithoutantiviralagentsinulcerativecolitispatients．AmJGastroenterol，2007，102：331-337．第25頁/共86頁難辨梭狀芽孢桿菌（Clostridiumdifficile）目的通過對炎癥性腸病(IBD)患者糞便中難辨梭狀芽孢桿菌(Cd)的檢測,了解IBD患者中該菌的感染情況及其與IBD的關系.方法收集2009年12月至2011年1月上海交通大學醫(yī)學院附屬瑞金醫(yī)院消化科確診的IBD患者130例,包括潰瘍性結(jié)腸炎(UC)患者60例及克羅恩病(CD)患者70例.同時收集腸易激綜合征(IBS)患者及無腸道疾患的健康人群各60例為對照.通過聚合酶鏈反應(PCR)和Cd毒素快速測試試劑盒(CDTK)方法對糞便樣本中毒素A、毒素B基因進行檢測,采用SPSS軟件進行統(tǒng)計分析.結(jié)果納入研究的130例IBD患者中,Cd感染者16例(12.3％),其中UC10例(16.7％),CD6例(8.6％)；對照組中未發(fā)現(xiàn)Cd感染者(x2=15.779,P=0.000).處于活動期的IBD患者Cd感染率顯著高于非活動期患者(x2=10.092,P=0.001).結(jié)腸型CD患者的感染率為4/14,顯著高于其他類型的CD患者(x2=13.125,P=0.001).輕度UC患者Cd感染率為4.5％、中度為14.3％、重度為6/17(x2=6.667,P=0.037)；輕度CD患者的Cd感染率為0％、中度為4.2％、重度為5/16,感染率隨疾病嚴重程度的上升而增高(x2=13.907,P=0.000).使用廣譜抗生素的患者與未使用者其Cd感染率差異無統(tǒng)計學意義(x2=1.414,p=0.378);免疫抑制劑與廣譜抗生素同時使用者和單用廣譜抗生素者Cd感染率差異亦無統(tǒng)計學意義(x2=0.330,P=0.962).結(jié)論IBD患者中存在著一定的Cd感染率,尤其是處于疾病活動期的患者,感染率隨IBD疾病嚴重程度的上升而增高.袁耀宗，等.

難辨梭狀芽孢桿菌與炎癥性腸病關系的初步研究.中華消化雜志.2012，32(4)：88-89.第26頁/共86頁FecalmarkersCalprotectin(FCP),aheterocomplexofS100A8andS100A9,isacalcium-bindingproteinwithantimicrobialprotectivepropertiesderivedpredominatelyfromneutrophils,andtoalesserextent,frommonocytesandreactivemacrophages.Itconstitutesapproximately5%ofthetotalproteinandupto60%ofthecytosolicproteininhumanneutrophils.Assuch,thefecalcalprotectinconcentrationisproportionaltotheinfluxofneutrophilsintotheintestinaltract,ahallmarkofactiveIBD.Lactoferrinisaniron-bindingglycoproteinidentifiedinthesecretionsoverlyingmostmucosalsurfacesthatinteractdirectlywithexternalpathogens,includingsaliva,tears,vaginalsecretions,feces,synovialfluid,andmammalianbreastmilk.Itisamajorcomponentofthesecondarygranulesofpolymorphonuclearneutrophilsandisshowntobeaprimaryfactorintheacuteinflammatoryresponse.Intheintestinallumen,fecallactoferrinlevelsquicklyincreasewiththeinfluxofneutrophilsduringinflammation.Sugiandcolleaguesinvestigatedlactoferrin,polymorphonuclearneutrophil(PMN)elastase,andlysozymetogetherwithmyeloperoxidaseinfecalmaterialandwhole-gutlavagefluidfromIBDpatients.LanghorstJ,ElsenbruchS,MuellerTetal.Comparisonof4neutrophil-derivedproteinsinfecesasindicatorsofdiseaseactivityinulcerativecolitis.Inflamm.BowelDis.2005;11:1085–91.第27頁/共86頁Fecalmarkers

JuddTA，DayAS，LembergDA，eta1．Updateoffecalmarkersofinflammationininflammatoryboweldisease．JGastroenterolHepat01．2011，26：1493—1499．第28頁/共86頁Fecalmarkers

第29頁/共86頁鋇劑灌腸檢查所見的主要改變?yōu)椋?1)黏膜粗亂和(或)顆粒樣改變；(2)腸管邊緣呈鋸齒狀或毛刺樣，腸壁有多發(fā)性小充盈缺損；(3)腸管短縮，袋囊消失呈鉛管樣。第30頁/共86頁CTUlcerativecolitiswithbackwashileitis.AxialCTenterographicsectionsshowcontinuousinvolvementofthelargebowel(whitearrrows)andbackwashileitis(blackarrowinb).ElsayesKM，AI—HawaryMM，JagdishJ，eta1．CTenterography：principles，trends，andinterpretationoffindings．Radiographics，2010，30：1955—1970．第31頁/共86頁結(jié)腸鏡檢查DaneseS，F(xiàn)iocehiC．Ulcerativecolitis．NEnglJMed，2011．365：17131725．結(jié)腸鏡檢查并活組織檢查(后文簡稱活檢)是UC診斷的主要依據(jù)。結(jié)腸鏡下UC病變多從直腸開始，呈連續(xù)性、彌漫性分布，表現(xiàn)為：(1)黏膜血管紋理模糊、紊亂或消失，黏膜充血、水腫、質(zhì)脆、自發(fā)或接觸出血和膿性分泌物附著，亦常見黏膜粗糙、呈細顆粒狀；(2)病變明顯處可見彌漫性、多發(fā)性糜爛或潰瘍；(3)可見結(jié)腸袋變淺、變鈍或消失以及假息肉、橋黏膜等。第32頁/共86頁Typicalendoscopicfindings

(A)UCwithmildinflammationandreducedhaustration,vasculartransparencyis

missing.(B)Moderateinflammationwithreducedhaustration.Themucosaisedematous,coveredwithfibrin,andshowsmultipleerosions.(C)

Severeinflammationwithinflammatorynarrowingofthelumenthroughpseudopolyps.第33頁/共86頁放大內(nèi)鏡(Confocalmicroscopy)

內(nèi)鏡下黏膜染色技術能提高內(nèi)鏡對黏膜病變的識別能力，結(jié)合放大內(nèi)鏡技術，通過對黏膜微細結(jié)構(gòu)的觀察和病變特征的判別，有助UC診斷，姜泊，等．放大內(nèi)鏡結(jié)合黏膜染色技術診斷潰瘍性結(jié)腸炎附116例放大內(nèi)鏡形態(tài)分析．現(xiàn)代消化及介入診療，2005，10：116—118．第34頁/共86頁small-bowelcapsuleendoscopy(SBCE).

Crohn’sdiseaseandulcerativecolitisarelifelong

diseases.Bothdiseasesaremarkedbyfrequentrelapsesandpatientsoftenundergorepeatedinvestigationstodefinetheextentofthedisease,assesstheseverityofrelapse,oridentifycomplications.Whereasulcerativecolitisisachronicinflammatoryconditioncausingdiffuseandcontinuousmucosalinflammationofthecolon,Crohn’sdiseaseisaheterogeneousentitycomprisedofseveraldifferentphenotypes,butcanaffecttheentiregastrointestinaltract.Theuseofcapsuleendoscopyasafilterforpush?and?pullenteroscopy(PPE)isoccasionallynecessaryinpatientswithestablishedulcerativecolitiswhenthediagnosisisquestioned,especiallybeforesurgery.CapsuleendoscopycanalsodirectthechoiceofrouteofPPE.第35頁/共86頁SBCE

Subtlelesionsasseenatsmall-bowelcapsuleendoscopyBourreilleA，IgnjatovicA，AabakkenL，eta1．Roleofsmall—bowelendoscopyinthemanagementofpatientswithinflammatoryboweldisease：aninternationalOMED-ECCOconsensus．Endoscopy，2009，41：618—637．第36頁/共86頁黏膜活檢組織學檢查

組織學可見以下主要改變?；顒悠冢?1)固有膜內(nèi)彌漫性急慢性炎性細胞浸潤，包括中性粒細胞、淋巴細胞、漿細胞和嗜酸粒細胞等，尤其是上皮細胞間中性粒細胞浸潤及隱窩炎，乃至形成隱窩膿腫；(2)隱窩結(jié)構(gòu)改變：隱窩大小、形態(tài)不規(guī)則，排列紊亂，杯狀細胞減少等；(3)可見黏膜表面糜爛，淺潰瘍形成和肉芽組織增生。緩解期：(1)黏膜糜爛或潰瘍愈合；(2)固有膜內(nèi)中性粒細胞浸潤減少或消失，慢性炎性細胞浸潤減少；(3)隱窩結(jié)構(gòu)改變：隱窩結(jié)構(gòu)改變可加重，如隱窩減少、萎縮，可見潘氏細胞化生(結(jié)腸脾曲以遠)。UC活檢標本的病理診斷：活檢病變符合上述活動期或緩解期改變，結(jié)合臨床，可報告符合UC病理改變。宜注明為活動期或緩解期。如有隱窩上皮異型增生(上皮內(nèi)瘤變)或癌變，應予注明。RileySA,ManiV,GoodmanMJ,etal.Microscopicactivityinulcerativecolitis:whatdoesitmean?Gut.1991;32:174–178.第37頁/共86頁Microscopicfindingsinbiopsies

(D,E)CryptabscessinUC.(F)Pseudopolypformation.L,lymphfollicle.NikolausS，SchreiberS．Diagnosticsofinflammatorybowel

disease．Gastroenterology，2007，133：1670—1689．第38頁/共86頁診斷要點

在排除其他疾病基礎上，可按下列要點診斷：(1)具有上述典型臨床表現(xiàn)者為I臨床疑診(spicious)，安排進一步檢查；(2)同時具備上述結(jié)腸鏡和(或)放射影像特征者，可臨床擬診(probable)；(3)如再加上上述黏膜活檢和(或)手術切除標本組織病理學特征者，可以確診(definite)；(4)初發(fā)病例如I臨床表現(xiàn)、結(jié)腸鏡及活檢組織學改變不典型者，暫不確診UC，應予隨訪(follow-up)。Lennard-JonesJE.Classificationofinflammatoryboweldisease.ScandJGastroenterol.Suppl.1989;170:2–6;discussion16–19.第39頁/共86頁Diagnosticcriteria

VariousdiagnosticclassificationsofIBDareavailable,includingMendeloff’scriteria,theLennard-Jonescriteria,theinternationalmulticentrescoringsystemoftheOrganizationMondialedeGastroenterologie(OMGE),andthediagnosticcriteriaofJapaneseResearchSocietyonIBD.ModifiedMendeloffcriteriapluskeypointsoftheLennard-Jonescriteria,commonlyusedcriteria,arepresentedhere.MyrenJ,BouchierIA,WatkinsonG,SoftleyA,ClampSE,deDombalFT.TheOMGEmultinationalinflammatoryboweldiseasesurvey1976–1986.Afurtherreporton3175cases.ScandJGastroenterol.Suppl.1988;144:11–19.第40頁/共86頁鑒別診斷

1．急性感染性腸炎：各種細菌感染，如志賀菌、空腸彎曲菌、沙門菌、產(chǎn)氣單孢菌、大腸埃希菌、耶爾森菌等。常有流行病學特點(如不潔食物史或疫區(qū)接觸史)，急性起病常伴發(fā)熱和腹痛，具自限性(病程一般數(shù)天至1周，不超過6周)；抗菌藥物治療有效；糞便檢出病原體可確診。2．阿米巴腸病3．腸道血吸蟲病4．其他：腸結(jié)核、真菌性腸炎、抗生素相關性腸炎(包括假膜性腸炎)、缺血性結(jié)腸炎、放射性腸炎、嗜酸粒細胞性腸炎、過敏性紫癜、膠原性結(jié)腸炎、白塞病、結(jié)腸息肉病、結(jié)腸憩室炎以及人類免疫缺陷病毒(HIV)感染合并的結(jié)腸病變應與本病鑒別。第41頁/共86頁Differentiatediagnosis

第42頁/共86頁Differentiatediagnosis

夏冰，等.缺血性結(jié)腸炎與潰瘍性結(jié)腸炎的臨床鑒別診斷.胃腸病學.2010，15(11)：681-683.第43頁/共86頁InternationalStudyGroupforBehcet’sdisease.Criteriaforthe

diagnosisofBehcet’sdisease.Lancet1990;335:1078–1080.

第44頁/共86頁Evaluationandassessment

Beforestartingtreatment,patientsneedtobere-evaluatedforcorrectdiagnosis,andtoensurethatothercolitisandcoloniclesionshavebeenexcluded.Theanatomicallocationandextentofinflammation,severityanddiseaseactivity,presenceofextraintestinalmanifestationsandcomplicationsetc.shouldbescrutinizedtodecidethebestformoftreatment.Itisessentialtorememberthatacorrectdiagnosisisbasedonthecombinationofclinical,endoscopic,radiologicalandhistologicaldata.2ndEuropeanevidence-basedconsensusonthediagnosis/managementofulcerativecolitis2012第45頁/共86頁ClinicalSubtype1、根據(jù)病程經(jīng)過初發(fā)型慢性反復發(fā)作型慢性持續(xù)型急性爆發(fā)型(Acutefulminantcolitis)初發(fā)型慢性復發(fā)型2、根據(jù)病變部位和范圍直腸炎和直乙結(jié)腸炎左半結(jié)腸炎右半結(jié)腸炎區(qū)域性結(jié)腸炎全結(jié)腸炎直腸炎左半結(jié)腸炎廣泛結(jié)腸炎3、根據(jù)病情輕度中度重度4、根據(jù)病情分期活動期緩解期《炎癥性腸病診斷與治療的共識意見》（2012年廣州）第46頁/共86頁TrueloveandWittsSeverityIndexTrueloveSC,WittsLJ.Cortisoneinulcerativecolitis.Finalreport

onatherapeutictrial.BMJ1955;2:1041–1048.第47頁/共86頁MontrealclassificationAccordingtoDiseaseExtentSatsangiJ，SilverbergMS，VermeireS，eta1．TheMontrealclassificationofinflammatoryboweldisease：controversies，consensus，andimplications．Gut．2006，55：749—753．第48頁/共86頁MontrealclassificationAccordingtoDiseaseSeverity

SatsangiJ，SilverbergMS，VermeireS，eta1．TheMontrealclassificationofinflammatoryboweldisease：controversies，consensus，andimplications．Gut．2006，55：749—753．第49頁/共86頁SutherlandIndex（DAI）第50頁/共86頁MayoScore

第51頁/共86頁SutherlandIndex(alsocalledMayoscores)SchroederKW,TremaineWJ,IlstrupDM.Coatedoral5-aminosalicylicacidtherapyformildlytomoderatelyactiveulcerativecolitis,arandomizedstudy.NEnglJMed1987;317:1625–9.SutherlandLR,MartinF,GreerS,etal.5-Aminosalicylicacidenemainthetreatmentofdistalulcerativecolitis,proctosigmoiditis,andproctitis.Gastroenterology1987;92:1894–8.第52頁/共86頁EndoscopicscoresStangeEF，TravisSP，VermeireS，etal，Europeanevidence-basedConsensusonthediagnosisandmanagementofulcerativecolitis：definitionsanddiagnosis．JCrohnsColitis，2008，2：1—23．第53頁/共86頁BaronendoscopicscoresBaronJH．ConnellAM．Lennard-JonesJE．Variationbetweenobserversindescribingmucosalappearancesinproctocolitis．BrMedJ.1964。1：89—92．第54頁/共86頁Endoscopicscores(UCEI