1、炎症性肠病炎症性肠病Inflammatory Bowel DiseaseInflammatory Bowel Disease附属一院内科附属一院内科 陈旻湖陈旻湖炎症性肠病炎症性肠病（Inflammatory Bowel Disease，IBD）溃疡性结肠炎（ulcerative colitis，UC)克罗恩病（Crohn disease,CD)Distribution of IBD:pre-World War IIDistribution of IBD:1950-1970Distribution of IBD:1970-1990Distribution of IBD:1990-present
2、2,8313,5184,0984,8565,7156,6097,7028,8629,98011,33712,64513,99715,44016,89118,03619,65121,06105,00010,00015,00020,00025,00085 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 0111,60213,61316,03718,07220,81323,20026,60329,66133,11436,97941,24346,21551,47757,07860,63166,71472,672010,00020,00030,00040,000
3、50,00060,00070,00080,00085 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01Cumulative number of IBD patients registered in JapanUlcerative colitisCrohns diseaseCourtesy of Dr.H.Ogata108642193019401950196019701980Year of DiagnosisUSA Ulcerative colitisUK Ulcerative colitisUSA Crohns diseaseUK Crohns d
4、iseaseIBD:Comparing East&West19902000Asian Ulcerative colitisAsian Crohns diseaseIncidence per 105 Inflammatory Bowel Disorders Specific etiologyinfectious（bacterial;tuberculosis,virus,parasite,fungus）dug-related（acute hemorrhagic colitis,pseudomembranous colitis）vascular（ischemic colitis,radiation
5、exposure）systemic（collagen disease、uremic toxic syndrome）IdiopathicCrohns diseaseUlcerative Colitisothers（Behet disease、non-specific multiple ulcers in small bowel）Inflammatory Bowel Disease：IBD？systemic disease infection drug mechanical stimulation vascular Pathophysiological Background of IBDGenet
6、ic factorsEnvironmental factorsImmunological abnormalities Intestinal inflammationEnteric floraEnvironmental factorsGenesImmunesystemSmokingSmokingDietDietDrugsDrugsGeography and social statusGeography and social statusStressStressMicrobes andMicrobes andenteric floraenteric floraPermeabilityPermeab
7、ilityAppendectomyAppendectomyInflammatoryInflammatorybowel diseasebowel diseaseHygiene hypothesis:Hygiene hypothesis:postulated mechanismspostulated mechanisms“Clean”lifestyle“Clean”lifestyleMatricardi&Bonini Clin Exp Allergy 2000“Dirty”lifestyle“Dirty”lifestyleHigh allergyLow allergyTh1Th1Th2Th2Hay
8、 feverHay feverAsthmaAsthmaAtopicAtopic eczema eczemaFood allergyFood allergyLow microbialexposureWeak immunestimulationCrohnsCrohnsdiseasediseaseStrong immunestimulationWeak regulatory network:low IL-10 and TGF-Weak regulatory network:low IL-10 and TGF-b b b bHigh microbialexposureA.Levine,2002Acut
9、e Acute inflammation inflammation(Host defense)(Host defense)Physiologic/”controlled”inflammationReturn to Return to tolerancetolerancePathologic/uncontrolled inflammation(IBD)Loss of Loss of tolerancetolerancePatterns of intestinal immune responsesFoodFloraEnteric floraEnteric floraT cell activatio
10、nT cell activationProliferationProliferationApoptosisApoptosisDefective apoptosisDefective apoptosisCrohns diseaseCrohns diseaseProliferationProliferationApoptosisApoptosisT cell activationT cell activationIncreased apoptosisIncreased apoptosisControlled inflammationControlled inflammationT cell act
11、ivationT cell activationProliferationProliferationApoptosisApoptosisNormal apoptosisNormal apoptosisPhysiological inflammationPhysiological inflammationPathogensPathogensDietary antigensDietary antigens Crohns diseaseOnly small bowel25 30%Onlycolon20 25%Anorectal disease(anal fistulae,ascesses)30 40
12、Small boweland colon40 55%EsophagusStomachDuodenum3 5%Involvement of rectum11 26%Distribution of inflammatory bowel diseasesProctosigmoiditis30 50%(Sub-)total colitis15 20%back-washileitis“Ulcerative colitisUCUCUCCD临床表现临床表现腹痛腹痛腹泻、血便腹泻、血便腹部包腹部包块体重下降体重下降瘘管形成瘘管形成肛周肛周脓肿发热肠外表外表现“非典型”改变：阿弗他溃疡诊断手段常规大肠镜、钡灌
13、肠常规大肠镜、钡灌肠“典型”改变：节段性病灶、纵行溃疡、鹅卵石 样改变，肠腔狭窄 EndoscopyFlat ulcersUlcerative colitisCrohns diseaseDeep longitudinal ulcers,cobblestone mucosa Crohns DiseaseTypical linear ulcers in the sigmoid(left)and aphtoid lesion in normal mucosa(right)HistologyUMSMMSMFUlcerative colitisMucosal inflammation only(M)Ul
14、cers(U)Crohns disease Transmural inflammation mucosa(M)and submucisa(SM)Ulcers Fissures(F)HistologyUlcerative colitis Crypt abscesses(A)with granulocytes highly specific Crohns disease epitheloid cell granuloma (arrows)highly specific but only in 40%of patients AOur mission is to be the global Our m
15、ission is to be the global leader in providing innovative,leader in providing innovative,world-class diagnostic solutions for world-class diagnostic solutions for the gastrointestinal community.the gastrointestinal community.GivenGivenis GI focusedis GI focused26胶囊内镜胶囊内镜CAPSULE ENDOSCOPY(CE)THE GIVE
16、N DIAGNOSTIC IMAGING SYSTEMAmbulatory data recorder on a beltRAPID Software for image processing and viewingM2A Capsule1126mmInside the M2ATM Capsule1.Optical dome2.Lens holder3.Lens4.Illuminating LEDs(Light-Emitting Diode)s.CMOS(Complementary Metal Oxide Semiconductor)Imager6.Battery7.ASIC(Applicat
17、ion-Specific Integrated Circuit)transmitter8.AntennaRAPID Main ScreenVideo SectionThumbnailSectionTime barVideo ControlsCommentSMALL INTESTINE IMAGING IN 3 EASY STEPS 检查三步骤1.Ingesting the capsule（吞吞胶囊）胶囊）2.Undergoing the procedure（数据数据记录）记录）3.Viewing the results（读读结果）结果）AngiodysplasiaSB TumorCrohns
18、diseaseCeliac-Sprue双气囊全小肠镜C22A 男 18岁，反复腹痛伴发热1年余小肠Crohns 病Evolution of IBD therapy:Evolution of IBD therapy:the result of understanding IBD pathogenesisthe result of understanding IBD pathogenesis1940s1940s SulfasalazineSulfasalazine1950s1950s Cortisone,ACTHCortisone,ACTH1960s1960s Azathioprine Azath
19、ioprine 1970s1970s 5-ASA5-ASA1980s1980s 6-MP,metronidazole,6-MP,metronidazole,elemental dietselemental diets1990s(early)1990s(early)Cyclosporine,budenoside,Cyclosporine,budenoside,methotrexate,antibioticsmethotrexate,antibiotics1990s(late)1990s(late)Biologicals,probiotics,Biologicals,probiotics,leuk
20、apheresisleukapheresis2000s2000sCombination therapiesCombination therapies炎症性肠病的治疗炎症性肠病的治疗生物治疗生物治疗10-20%20-40%50-70%免疫抑制剂免疫抑制剂治疗治疗传统治疗传统治疗:皮质激素皮质激素 5-ASAChronic gut inflammation:imbalance of immune mediatorsPro-inflammatoryPro-inflammatoryAnti-inflammatoryAnti-inflammatoryTNF-TNF-a a a aIL-1IL-1b b
21、b bIL-8IL-8IL-12IL-12IFN-IFN-g g g gTGF-TGF-b b b bIL-10IL-10IL-1raIL-1raIL-4/13IL-4/13TNF-TNF-a a a aIL-1IL-1b b b b IL-8IL-8IL-12IL-12IFN-IFN-g g g gTGF-TGF-b b b b IL-10IL-10IL-1raIL-1raIL-4/13IL-4/13Recombinant cytokine-basedtherapy for IBDPro-Pro-inflammatoryinflammatoryAnti-Anti-inflammatoryinflammatoryPro-Pro-inflammatoryinflammatoryAnti-Anti-inflammatoryinflammatoryAnti-cytokine antibody-basedtherapy for IBDTNF-TNF-a a a aIL-1IL-1b b b b IL-8IL-8IL-12IL-12IFN-IFN-g g g gTGF-TGF-b b b b IL-10IL-10IL-1raIL-1raIL-4/13IL-4/13
