炎癥性腸病的診療進(jìn)展

1、炎癥性腸病的研究進(jìn)展,消化內(nèi)科張文俊,IBD 概述,CD和UC是一種疾病的兩個(gè)階段或兩種疾病目前尚無(wú)定論,inflammatory bowel diseases,Crohn disease,Ulcerative colitis,,,,,,Undeterminated colitis,,CH/10/30,,,炎癥性腸病的復(fù)雜性,,對(duì)病因和發(fā)病機(jī)制進(jìn)一步研究有助于預(yù)防和指導(dǎo)治療,IBD 現(xiàn)狀,病因尚不清楚 治療措施有限包括非特異性抗

2、炎和免疫抑制治療,,Epidemiology of IBD,1-2 million IBD patients in the U.S.Equal incidence of ulcerative colitis and Crohn’s diseaseApproximately 10,000 new cases diagnosed annually*,*Hanauer S. Inflammatory Bowel Disease. N En

3、gl J Med. 1996;334(13):841-8,VariableFindingTime trends in incidenceIncreased 1960s–80swith recent plateauIncidence (per 100,000)5-7Peak age at onset (y)15-30Female-to-male ratio1.1 to 1.8:1Racial/ethnic inci

4、denceHigh in whites, Jews,Epidemiology of IBD: Overview,,,Andres PG et al. Gastroenterol Clin N Am. 1999;28:255.,Age and Sex Incidence of IBD,IBD 病因,遺傳易感性,環(huán)境促發(fā)因素,精神因素免疫因素,IBD,GENETIC SUSCEPTIBILITY,種族的影響,Basu, D; Am

5、J Gastroenterology 100:2254-2261, 2005,A,Whites had stronger family history of IBD and colorectal cancer.African Americans with CD had higher incidence of arthritis. Disease severity similar across all groups. P-anca

6、 served as a sensitive maker for Mexican Americans as 100% with UC were positive compared with 40% in whites,識(shí)別的第一個(gè)IBD基因 –CARD15/NOD2,,,,,,,,,糖多肽,CD14,TLR4,TRAF6,NOD2,NF-kB,細(xì)胞核,,,,,,,,,,,,,,,炎癥,單核細(xì)胞,C-插入突

7、變 終止碼, NF-kB的異常激活,,,,IBD相關(guān)基因,Bamias. Ann Intern Med, 2005,143(12):895-904,IBD常見(jiàn)的免疫遺傳異常,p-ANCA (Peri-Nuclear Anti-Neutrophil Cytoplasmic Antibodies) ASCA (Anti-Saccharomyces cerevisiae antibodies) UC:

8、+p-ANCA, -ASCASens=57 Spec=97 CD: -p-ANCA, +ASCASens=47 Spec=97,pANCA 70% of UC,6% of CD；ASCA 50-60% of CD,基因型與IBD的關(guān)系,不同基因型不同IBD分型,,疾病易感性不同對(duì)藥物治療的反應(yīng)不同,No contribution of NOD2,NOD2 contributes,NOD2 major factor

9、,,,M. CROHN AND NOD2/CARD15,CP/06/23,Environmental Triggers,Infections,NSAIDs,Stress,Smoking,Diet,Antibiotics,IBD,,,飲食因素,明確危險(xiǎn)因素:過(guò)量攝入糖類(lèi)，尤其是CD 可能危險(xiǎn)因素:巧克力和可樂(lè)類(lèi)飲料,高脂 可能保護(hù)因素:高纖維食物,水果和蔬菜 其他：丁酸，硫化物，谷氨酸鹽,Meta分析: 吸煙者發(fā)病危險(xiǎn)性為從不吸煙者

10、的2倍吸煙增加CD復(fù)發(fā)可能性，女性多見(jiàn)（ 4倍）,過(guò)量吸煙,CD的危險(xiǎn)因素，UC的保護(hù)因素,對(duì)于CD：,長(zhǎng)期吸煙者發(fā)病危險(xiǎn)性高 戒煙者患病的危險(xiǎn)性為從不吸煙者的1.7倍 戒煙者重新吸煙(45％)可改善癥狀 尼古丁治療可增加活動(dòng)期UC的癥狀緩解率,對(duì)于UC：,感染,外源性感染：沙門(mén)氏菌,志賀氏菌,副結(jié)核分枝桿菌, 產(chǎn)單核細(xì)胞的李斯特菌屬,纏繞桿菌屬,

11、 酵母菌,彎曲桿菌屬,耶爾森菌屬； 阿米巴; 麻疹病毒內(nèi)源性細(xì)菌：大腸桿菌E.coli ?,微生物因素,微生物因素在IBD發(fā)生中的作用尚存在爭(zhēng)議缺乏足夠證據(jù)證明IBD的特異性病原體現(xiàn)有研究表明:病原微生物可能是本病的促發(fā)因素,J. Nutr. 1995;125:1401-12,The Human Gut Flora,Rapidly colonises gu

12、t after birth Comprises more than 1014 organisms Weighs 1-2 kgMore than 400 speciesAn individuals flora is immunologically distinctSymbiotic relationship with hostProbiotics,BALANCE OF COMMENSAL BACTERIAL COMPONE

13、NTS,,,,無(wú)菌腸道環(huán)境,細(xì)菌感染,未見(jiàn)炎癥,結(jié)腸炎癥,,免疫激活,基因易感宿主,No Bacteria, No IBD ？,麻疹病毒感染與IBD的相關(guān)研究,Ekbom A. Lancet 1996; 348. Lawrenson R. BMJ 1998; 316. Nielsen LLW. BMJ 1998; 316. Afzal MA. Lancet 1998; 351. Haga Y. Gut 1996; 38. Chad

14、wick N. J Med Virol 1998: 55.,假說(shuō)一：持續(xù)麻疹病毒感染與CD相關(guān),來(lái)自瑞士的研究: 麻疹流行期出生者CD患病率高在CD病人腸道組織中發(fā)現(xiàn)麻疹病毒蛋白和DNA,證據(jù),研究者Wakefield后續(xù)的研究不支持自己前期研究 當(dāng)時(shí)檢測(cè)麻疹病毒的技術(shù)不夠可靠 來(lái)自英、美、日等國(guó)的研究存在分歧 血清中未檢測(cè)到抗麻疹病毒抗體,反證據(jù),麻疹病毒感染與IBD的相關(guān)研究,Thomspon NP. Lancet 1

15、995; 345. Gilat T. Scan J Gastroenterology 1987; 22.Pebody RG. BMJ 1998; 316. Feeney M. Lancet 1997; 350.,假說(shuō)二：麻疹疫苗(非MMR)接種與CD相關(guān),麻疹疫苗接種者IBD發(fā)病率較未接種者高,證據(jù),來(lái)自歐洲的病例對(duì)照研究不支持上述觀點(diǎn) 英國(guó)和芬蘭的研究顯示CD與疫苗接種無(wú)關(guān),反證據(jù),麻疹病毒感染與IBD的相關(guān)研究,Montgom

16、ery SM. Gastroenterology 1999, 116; 796-803.Davids RL et al. Archives of Pediatric and Adolescent Medicine 2001; 155: 354-9.,假說(shuō)三：IBD可能與早期病毒性腮腺炎有關(guān),基于對(duì)70年代出生兒童的調(diào)查IBD與2歲前野生腮腺炎病毒或與麻疹病毒聯(lián)合感染相關(guān),證據(jù),上述結(jié)果依據(jù)雙親對(duì)幼年時(shí)期患病的回憶調(diào)查

17、 （而病毒性腮腺炎多無(wú)癥狀） IBD患者未檢測(cè)到腮腺炎病毒或抗體 MMR疫苗接種后IBD發(fā)病率未見(jiàn)明顯升高,反證據(jù),,大腸桿菌與IBD的相關(guān)研究,假說(shuō)：鞭毛蛋白在IBD中啟動(dòng)獲得性免疫機(jī)制,,E. Coli,Flagella,,,,,,,,,,,,,,,,,,大腸桿菌與IBD的相關(guān)研究,假說(shuō)：鞭毛蛋白在IBD中啟動(dòng)獲得性免疫機(jī)制,常規(guī)革蘭染色陰性的鞭毛蛋白單體（如大腸桿菌）

18、 在CD中可作為抗原激發(fā)獲得性免疫反應(yīng) 這種獲得性免疫反應(yīng)受TLR5介導(dǎo)的先天性免疫調(diào)節(jié) 粘膜組織中可檢測(cè)到 非造血細(xì)胞產(chǎn)生的細(xì)胞因子（如IL-6和TNFa) 獲得性免疫與CD發(fā)生發(fā)展相關(guān),大腸桿菌與IBD的相關(guān)研究,社會(huì)心理因素,45%的IBD患者認(rèn)為應(yīng)激促發(fā)IBD 胃腸病學(xué)專(zhuān)家認(rèn)為 社會(huì)心理因素在IBD中起重要作用,“Stress…h(huán)as been positively co

19、rrelated with exacerbation of disease”,,依據(jù)：應(yīng)激增強(qiáng)動(dòng)物模型腸粘膜炎癥反應(yīng),Qui. Nature Med. 1999.,依據(jù)：無(wú)癥狀UC中應(yīng)激與直腸炎癥有關(guān),Levenstein S, et al. Am J Gastroenterol 1994;89:1219-25.,依據(jù)：應(yīng)激對(duì)UC病情影響與持續(xù)時(shí)間有關(guān),Levenstein S, et al. Am J Gastroenterol 20

20、00;95(5):1213-20.,Levenstein S, et al. Am J Gastroenterol 2000;95(5):1213-20.,依據(jù)：應(yīng)激對(duì)UC病情影響與應(yīng)激程度有關(guān),不同IBD分型應(yīng)激的影響不同,Maunder R. Dig Dis Sci 2000;45(11):2127-32.,機(jī)制：應(yīng)激與循環(huán)遞質(zhì),機(jī)制：應(yīng)激與腸壁通透性,Wilson LM. Microcirculation 1999;6:189.

21、.Meddings JB. Gastroent 2000;119:1019.,機(jī)制：應(yīng)激與腸道局部介質(zhì),Soderholm JD. Am J Physiol Gastrointest Liver Physiol 2001;280:G7–G13.,Mawdsley J E. Gut. 2005,54(10):1481-91.,應(yīng)激對(duì)胃腸道影響的多通路機(jī)制,Mawdsley J E. Gut. 2005,54(10):1481-91.,應(yīng)激

22、與IBD,精神神經(jīng)免疫學(xué)機(jī)制,IBD處于血栓前狀態(tài) 凝血參數(shù)大多增高 血栓栓塞發(fā)生時(shí)給予抗凝治療 可同時(shí)改善IBD病情 血栓栓塞是IBD的嚴(yán)重并發(fā)癥 多發(fā)生于年輕患者急性期； 深靜脈血栓和肺栓塞常見(jiàn)； 動(dòng)脈栓塞和其他

23、則少見(jiàn),凝血和抗凝平衡紊亂,Schapira M. Acta Gastroenterol Belg. 1999, 62:182.Alfredo Guglielmi. World J Gastroenterol, 2005,7;11:2035.,凝血狀態(tài)異常是IBD的病因還是結(jié)果尚不確定,,UC患者腸系膜靜脈和門(mén)靜脈血栓形成,IBD 發(fā)病機(jī)制 (Pathogenesis),損傷機(jī)理： 粘膜屏障受損

24、 粘膜免疫異常 系統(tǒng)免疫失衡 IBD發(fā)病機(jī)制研究進(jìn)展： 先天性免疫在IBD中的作用 IBD免疫效應(yīng)分型－－Th1/Th2 CD是免疫亢進(jìn)或免疫缺陷

25、 細(xì)胞因子及免疫遞質(zhì)研究進(jìn)展,ETIOLOGIC HYPOTHESES,,Pathogenesis of IBD,,,,,,,,,NSAIDsAntibioticsInfectionsViralBacterialParasitic,Luminal antigensFood antigensBacteriaBacterial productsFMLPLPSPGPS,,IL-2IFN-?IL-12T

26、NF-?IL-1TGF-? IL-4IL-5IL-10etc.,Translocation of luminal contents,InitiatingEvents,MucosalDamage,AbnormalImmune Response,ChronicInflammation,,Courtesy of R Baldassano, 2000.,Chronic Inflammation: Imbalance Bet

27、ween Mediators,,,,Pro-inflammatory,Anti-inflammatory,TNF-a,,IL-1b,,IL-8,,IL-12,,IFN-g,,TGF-b,,IL-10,,IL-1ra,,IL-4/IL-13,,,,,,,,,,,,,,,,,,,,,,"Target“,,PG,LTB,PAF,H2O2,Indirect,destruction,InterleukinschemokinesTNF

28、a,Release of factors,,,,,,,Virus,Bac-teria,Protein,,,,,Lymphocytes,Uncontrolled reactionto antigen,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Macrophages,PMN´s,Recruitment of cells,,,,,MHC,,,,4,,,,,,CP/03/48,PRINCIPLES

29、OF PATHOPHYSIOLOGY OF IBD,APC,Effector T-cell,Uncontrolled T-Cell Responses Induce Chronic Gut Inflammation,,,正常腸壁有生理性抗炎功能 IBD腸壁滲透性增加 損害腸粘膜屏障的因素： 遺傳易感性 環(huán)境促發(fā)因素,機(jī)制一：粘膜屏障受損,Mucosal Immune Syste

30、m,機(jī)制二：粘膜免疫失衡,腔內(nèi)抗原浸潤(rùn)并激活MC 效應(yīng)細(xì)胞產(chǎn)生促炎細(xì)胞因子 減少調(diào)節(jié)性細(xì)胞因子產(chǎn)生 級(jí)聯(lián)反應(yīng)促使炎癥反應(yīng)擴(kuò)大,粘膜免疫中的腸道微環(huán)境和相關(guān)基因,機(jī)制三：系統(tǒng)免疫失衡,遺傳、環(huán)境及社會(huì)心理等因素共同作用于免疫系統(tǒng),,先天性免疫是非特異性防御病原體的機(jī)制 —— 是機(jī)體的第一道防線(xiàn) 主要針對(duì)抗原產(chǎn)生的化學(xué)物質(zhì)(而非抗原本身) 針對(duì)抗原的某種免

31、疫細(xì)胞選擇性增殖,The Role of the Innate Immune System in IBD,獲得性免疫與先天性免疫在IBD中的作用,傳統(tǒng)觀點(diǎn)認(rèn)為 Acquired immune system IBD是獲得性免疫系統(tǒng)細(xì)胞介導(dǎo)的炎癥反應(yīng),主要識(shí)別抗原本身效應(yīng)T細(xì)胞 (Teff) 和調(diào)節(jié)T細(xì)胞 (Treg),Defects in the innate immune system may play

32、an equal or even more important role in IBD,IBD可有原發(fā)性的調(diào)節(jié)性淋巴細(xì)胞和細(xì)胞因子 功能失調(diào)，如:IL-10、TGF-β,導(dǎo)致炎癥控制失靈 CD中存在激活的T細(xì)胞調(diào)亡抵抗,這些現(xiàn)象無(wú)法用現(xiàn)有的獲得性免疫機(jī)制解釋,,先天性免疫缺陷可能在IBD中起更重要的作用,進(jìn)一步研究提示,Ann Intern Med, Volume 143(12).December 20, 2005.895

33、-904,NOD2蛋白是細(xì)胞內(nèi)受體主要識(shí)別細(xì)菌胞壁成分在先天免疫中起作用被認(rèn)為是IBD的易感基因NOD2突變見(jiàn)于1/3的CD而在UC不是危險(xiǎn)因素,支持先天性免疫的證據(jù),先天性免疫中介導(dǎo)微生物-宿主反應(yīng)的信號(hào)通路基因,膜耦聯(lián)受體 TLRs（toll-like receptors ） 識(shí)別脂多糖等微生物結(jié)構(gòu)組分 細(xì)胞質(zhì)蛋白家族成員： NBS/LRR (Nod1 and N

34、od2) 特異性識(shí)別肽聚糖,MediatesInnate Immune Defense,,IBD免疫效應(yīng)分型－－Th1/Th2 paradigm,傳統(tǒng)觀點(diǎn)認(rèn)為: CD為T(mén)h1優(yōu)勢(shì)反應(yīng) IL-12 和 IFN-γ等分泌增多,抗IL-12治療可減少固有層MC分泌細(xì)胞因子,傳統(tǒng)觀點(diǎn)認(rèn)為: UC為T(mén)h2優(yōu)勢(shì)反應(yīng)

35、 IL-5 和 IL-13等分泌增多,抗IL-13治療有助于改善結(jié)腸炎癥,,,,,,,,Th1,,Th2,Crohn’s Disease,BACTERIA,This will mean something unique to everyone. The bottom line is this: We’re sure that you’ll have a positive experience with DanActive and th

36、at you’ll be completely satisfied with it. We’re also confident that you’ll want to make DanActive a part of your family’s daily wellness routine.,Th1/Th2 新觀點(diǎn)的提出,UC和CD的研究發(fā)現(xiàn)Th1,Th2免疫分型界限不明顯各種細(xì)胞因子表達(dá)與原有分型差異甚至完全相反基于傳統(tǒng)Th1/T

37、h2觀點(diǎn)提出 抗TNF單克隆抗體 (Infliximab) 用于CD治療； 目前的研究發(fā)現(xiàn) Infliximab 對(duì)重癥UC同樣有效； 而對(duì)部分CD不能誘導(dǎo)緩解 抗IL-10的制劑不能誘導(dǎo)CD患者緩解,IBD存在免疫反應(yīng)差異性,這些現(xiàn)象無(wú)法用傳統(tǒng)的Th1/Th2模式解釋,,其他T細(xì)胞免疫效應(yīng)途徑,Am J Gastroenterol.2002,97:2820.

38、N Engl J Med,2002,347:417. Nat Rev Immunol,2003,3:521. J Exp Med,2002,195:1129. J Clin Invest. 2004;113:1490.,Th3 /Tr1與口服耐受相關(guān),IBD病程不同免疫分型不同,急性期Th1為主,慢性期Th1/Th2混合型,自身免疫機(jī)制是CD發(fā)病的關(guān)鍵 遺傳易感的宿主對(duì)細(xì)菌抗原的免疫耐受終止 免疫過(guò)度激活導(dǎo)致慢性透壁性炎癥,CD

39、是免疫亢進(jìn)或免疫缺陷,Sands, B E. Inflamm Bowel Dis,  2006,12(2),S 2:p S1,傳統(tǒng)觀點(diǎn):IBD包括CD免疫亢進(jìn)是其主要機(jī)制,細(xì)菌與腸粘膜粘附性增強(qiáng) defensins表達(dá)降低 defensins治療有效 IBD存在體液,細(xì)胞免疫缺陷 NOD2/CARD15基因突變 損害細(xì)胞因子的轉(zhuǎn)錄表達(dá)GM-

40、CSF治療有效,支持CD存在免疫缺陷的證據(jù),Christian F. Eur J Gastroenterol Hepatol 2003 15:621–626,集落刺激因子改善粒細(xì)胞功能缺陷,KORZENIK JR. Dig Dis Sci, 2000 , 45, 6 :1121.,G-CSF and GM-CSF,KORZENIK JR. New Engl J Med, 2005, 352, 21 :2193.,Sargramostim

41、作為一種GM-CSF刺激腸道先天性免疫系統(tǒng)細(xì)胞,過(guò)氧化物酶增殖活化受體 PPAR- ?,Lewis, AJG 2001. Dubuquoy, Gastro 2003,,治療應(yīng)用,外源物質(zhì)代謝與IBD密切相關(guān) Pregnane X receptor (PXR) 是配體激活的 轉(zhuǎn)錄因子家族成員 PXR可啟動(dòng)外源物質(zhì)代謝 PXR可被多種內(nèi)源性或外源性物質(zhì)激活， 如:激素，膽汁酸，抗生素

42、PXR 編碼基因NR1I2多態(tài)性與IBD相關(guān),Pregnane X receptor and IBD,Dring MM. Gastrol, 2006, 130:341–348.,Vitamin D 和 IBD,Lim WC. J Gastro & Hepatol, 2005, 2:308.,Clinical Findings,,,,CD/05/105,STRICTURING STENOSIS AT THE ILEOCECAL

43、 BORDER,Presentation of UC,DiarrheaBleedingNO abdominal pain (cramps)Extraintestinal manifestations,Ulcerative Colitis: Bleeding,101402.7 Lindenbaum - On-screen 80,Complications of UC,Toxic MegacolonColonic Perforati

44、onDysplasia or CancerGrowth failure (pediatrics)Extraintestinal disorders(eg, arthritis, and dermatologic, musculoskeletal, ocular, renal, and hepatic disorders),Clinical Vignette: Ulcerative Colitis,22 yo mal

45、e presents with 15-20 bloody liquid bowel movements a day.He recently quit cigarette smokingHis mother has Crohn’s diseaseHe takes ibuprofen for left knee arthritisStool cultures are negative and colonoscopy reveals

46、colitis from the rectum to cecum.,Presentation of CD,DiarrheaChronic abdominal pain and tendernessLoss of appetite and weight lossFeverPerianal diseaseComplications such as fistulasExtraintestinal manifestations,Co

47、mplications of CD,FistulasAbscessesStricturesGrowth failure (pediatrics)MalnutritionExtraintestinal disorders,Crohn’s Disease Complications: Fistulas,A tunnel between two sections of the intestines or between the

48、intestines and other organs, including the skin,SmallIntestine,LargeIntestine(Colon),Fistula,,,,Fistula,,Crohn’s Disease Complications: Abscesses,A localized collection of pus within the tissue of the GI tract,Stom

49、ach,,SmallIntestine,LargeIntestine(Colon),,,Abscess froma fissure in thesmall intestineinto the peritoneal cavity,,Complications of CD: Fistulas,,,Abdominal Fistula,Perianal Fistula,Differential Diagnosis of IBD,L

50、ymphomaInfectious etiologiesAppendicitisDiverticulitisCarcinomaIschemic ColitisCeliac disease,Significant factorsUCCDAnatomic location Colon/rectumAny part of GI tractDistributionDiffuseFocal with “skip” ar

51、easFistula or abscessRareCommonStricturesUncommonCommonCurrent smokerRareCommonBloody diarrheaCommonRare,,Adapted from Surawicz CM. Contemp Intern Med. 1991;3:17.,,Differential Diagnosis,,Severe Crohn’s Colit

52、is,Reprinted by permission of Blackwell Science, Inc. Marion JF et al. In: Di Marino AJ, Benjamin SB (eds). Gastrointestinal Disease: An Endoscopic Approach. 1997:511.,Pseudopolyps in CD,Reprinted by permission of Black

53、well Science, Inc. Marion JF et al. In: Di Marino AJ, Benjamin SB (eds).Gastrointestinal Disease: An Endoscopic Approach. 1997:511.,Fibrostenosis in CD,Courtesy of J-F Colombel, MD.,Intestinal Complications of Ulcerativ

54、e Colitis Toxicity,101402.7 Lindenbaum - On-screen 95,Granuloma of the Ileum in CD,Courtesy of J-F Colombel, MD and K Geboes, MD.,Crypt Abscesses in IBD,Courtesy of J-F Colombel, MD.,ExtraintestinalManifestations,,Extra

55、intestinal Manifestations of IBD,Skin disordersErythema nodosumPyoderma gangrenosumJoint disordersPeripheral arthritisSacroiliitisAnkylosing spondylitisOcular disordersIritis, uveitis, and episcleritis,Extraintes

56、tinal Manifestations of IBD,HepatobiliaryGallstonesSclerosing cholangitisCholangiocarcinomaRenalRenal stonesAmyloidosisOther manifestationsAphthous stomatitisHypercoagulable state,Erythema Nodosum in IBD,Courtes

57、y of J-F Colombel, MD.,Pyoderma Gangrenosum in IBD,Courtesy of J-F Colombel, MD.,Pyoderma Gangrenosum in CD,Sacroiliitis in IBD,Courtesy of J-F Colombel, MD.,Reprinted from the Clinical Slide Collection on the Rheumatic

58、Diseases, copyright 1991, 1995, 1997.Used by permission of the American College of Rheumatology.,Ankylosing Spondylitis,Scleritis in IBD,Courtesy of J-F Colombel, MD.,Aphthous Stomatitis in IBD,Courtesy of J-F Colombel,

59、 MD.,Sclerosing Cholangitis in IBD,Courtesy of J-F Colombel, MD.,,CD/05/76,,SMALL LESIONS IN THE COLON IN CD – INVISIBLE IN MRI,,,CD/05/62,,WCE INSMALL BOWELCROHN´S DISEASE,,CD/05/97,CT-ENTEROCLYSIS – CROHN´

60、S DISEASE WITH STENOSIS AND PRESTENOTIC DILATATION,,n=41,*p<0.007,,,CD/05/73,COMPARISON OF WIRELESS CAPSULE ENDOS-COPY (WCE) – CT-ENTEROCLYSIS (CTE) IN IBD,Voderholzer, 2005,,,CD/06/22,,,DIAGNOSTIC ALGORITHM IN IBD,La

61、b test (blood count, CRP, lipase),microbiology, abdominal ultrasound,Inflammatory constellationpersistence of complaints,Ileocolonoscopysmall bowel X-ray / MRE / CTE,,Esophagogastroduodenoscopy,Goals of Treatment,Indu

62、ce response/remissionMaintain response/remissionHeal mucosal liningPrevent or cure complications (eg, fistulas)Improve quality of lifeRestore and maintain nutritionLimit surgery,Conventional Treatments for IBD,Amin

63、osalicylates (5-ASA)Glucocorticosteroids (GCS)ImmunosuppressantsAntibiotics (Cipro and Flagyl),Traditional Treatment Pyramid Based on Severity of CD,,SurgeryBowel restCyclosporineCorticosteroidsAzathioprine6-merc

64、aptopurineMethotrexateCorticosteroidsAntibioticsAminosalicylates,Disease Severity,,Mild,Moderate,Severe,Initial Treatment: Oral 5-ASA therapyTopical TherapyDisease Flare or Progression: Oral 5-ASA at higher do

65、se (>4g/d)CorticosteroidsImmunomodulatorsSteroid Dependent or Refractory or Severe Colitis:CyclosporineSurgery,Approach to Medical Treatment of UC,Early or Mild Disease: 5-ASA agents Antibiotics (Flagyl or C

66、ipro)Moderate to Severe Disease: Corticosteroids Immunomodulators Biologic Response Modifiers: Remicade Fistulizing Crohn’s Disease: Antibiotics: Flagyl, Cipro Immunomodulators: 6-MP/Imuran Remicade,Approach

67、 to Medical Treatment of Crohn’s disease,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,SASP,5-ASA,top. SASP/ASA,Prednisolone,Steroid Enema,0,20,40,60,80,100,% Success,,Drug,Placebo,,,,,TA,39%,TA,41%,TA,56%,TA,56%,TA,45%,,,CUT/03/21,META

68、-ANALYSIS OF DRUG TREATMENT OF ULCERATIVE COLITIS,Kornbluth, 1993,,,CUT/01/11,DOSE FINDING FOR 5-ASA IN ACTIVE ULCERATIVE COLITIS,Kruis, AGA 2000,8 weeks3 x 0.5 g3 x 1.0 g3 x 1.5 g(n = 104) (n = 104) (n = 104)R