溃疡性结肠炎诊治全集

1、溃疡性结肠炎的诊治进展,Introduction,IBD是一种病因尚不十分清楚的慢性非特异性肠道炎症，包括UC和CD 。 其发病率呈逐年上升趋势，且多为青壮年发病，临床表现复杂，并发症严重，肠外表现多样，严重影响个人生活质量和社会生产力。 此外，因其有癌变的风险，备受广大医生的重视。 近年来在国内外IBD基础与临床研究高潮迭起，基础研究的成果直接指向临床治疗，取得了划时代的进展。 探讨和摸索适合国人的治疗方案以降低重症UC的并发症和死亡率显得十分重要,Introduction,Ulcerative colitis is characterized by mucosal inflammation

2、 of the colon. The pathology is inflammatory and the disease course is relapsing and remitting with intermittent symptoms of rectal bleeding and diarrhea. Approximately 25% of patients develop a chronic active or a rapidly fulminate disease course. Chronic inflammation can lead to dysplasia and canc

3、er. Approximately 20% of patients require colectomy with ileoanal pouch or stoma. Velayos FS, Terdiman JP, Walsh JM. Effect of 5-aminosalicylate use on colorectal cancer and dysplasia risk: a systematic review and metaanalysis of observational studies. Am J Gastroenterol 2005;100:13451353,Consensus,

4、Stange EF, Travis SP, Vermeire S, Reinisch W, Geboes K, Barakauskiene A, et al. European evidence-based Consensus on the diagnosis and management of ulcerative colitis: definitions and diagnosis. J Crohns Colitis 2008;2:123. Van Assche G，Dignass A，Panes J，et a1The second European evidence-based Cons

5、ensus on the diagnosis and management of ulcerative colitis：Definitions and diagnosisJ Crohns Colitis，20104：7 27 Mowat C, Cole A, Windsor A, Ahmad T, Arnott I, Driscoll R, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut 2011;60:571607. Turner D, Levine A, Escher JC,

6、 Griffiths AM, Russell RK, Dignass A, et al. Management of pediatric ulcerative colitis: a joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nutr 2012. Turner D, Travis SP, Griffiths AM, Ruemmele FM, Levine A, Benchimol EI, et al. Consensus for managing acute severe

7、 ulcerative colitis in children: a systematic review and joint statement from ECCO, ESPGHAN, and the Porto IBD Working Group of ESPGHAN. Am J Gastroenterol 2011;106:57488,Management consensus of inflammatory bowel disease forthe AsiaPacific region 2006,Abstract: At the present there are no large-sca

8、le epidemiologic data on inflammatory bowel disease (IBD) in the AsiaPacific region, but several studies have shown an increased incidence and prevalence of IBD in this region. Compared to the West, there appears to exist a time lag phenomenon. With regard to the two main forms of IBD, ulcerative co

9、litis (UC) is more prevalent than Crohns disease (CD). In addition to geographic differences, ethnic differences have been observed in the multiracial Asian countries. Moreover, the genetic backgrounds are different in the Asian compared to Western patients. For instance, NOD2/CARD15 variants have n

10、ot been found in Asian CD patients. In general, the clinical course of IBD seems to be less severe in the AsiaPacific region than in Western countries. Diagnosis of IBD in this region poses special problems. The lack of a gold standard for the diagnosis of IBD, and the existence of a variety of infe

11、ctious enterocolitis with similar manifestations to those of IBD make the differential diagnosis particularly difficult. So far, Western diagnostic criteria have been introduced for the diagnosis of IBD. A stepwise approach to exclude non-IBD enterocolitis also must be introduced, and a definite dia

12、gnosis must include typical histological features. In some patients, follow up and therapeutic trials might be necessary to obtain a definitive diagnosis. A better understanding of the pathogenesis of IBD will allow the development of better diagnostic markers. The management of IBD also poses some

13、special problems in the AsiaPacific Region. There is often a delay in using proper medications for IBD, and alternative local remedies are still widely used. With a combination ofWestern guidelines and regional experiences, similar principles can be used for induction and maintenance of remission.A

14、stepwise selection of medications is advocated depending on the extent, activity and severity of the disease. Comprehensive and individualized approaches are suggested for different IBD patients. Deeper understanding of disease pathogenesis and the unique characteristics of IBD in the AsiaPacific re

15、gion, combined with reasonable and practical guidelines for drug management and the future use of biological agents would improve the therapeutic outlook of IBD in this region,The Asia-Pacific consensus on ulcerative colitis 2010,European evidence-based consensus on the diagnosis/management of ulcer

16、ative colitis 2008,This document sets out the current European Consensus on the diagnosis andmanagement of UC, reached by the European Crohns and Colitis Organisation (ECCO) at a meeting held in Berlin on 20th October 2006. ECCO is a forum for specialists in inflammatory bowel disease from 23 Europe

17、an countries. Like the initial Consensus on the management of Crohns disease, the current Consensus is grouped into three parts: definitions and diagnosis; current management; and management of special situations. This first section concerns aims, methods and definitions of the Consensus, as well as

18、 classification, diagnosis, imaging and pathology of UC. The second section on current management includes treatment of active disease, maintenance ofmedically-induced remission and surgery of UC. The third section on special situations includes pouch disorders, cancer surveillance, pregnancy, paedi

19、atrics, psychosomatics, extra-intestinal manifestations and alternative therapy,2nd European evidence-based consensus on the diagnosis/management of ulcerative colitis 2012,This document updates the previous European Consensus on the diagnosis and management of UC, and was finalised by the European

20、Crohns and Colitis Organisation (ECCO) at a meeting held in Dublin in February 2011. ECCO is a forum for specialists in inflammatory bowel disease from 31 European countries. Like the initial Consensus on the diagnosis and management of ulcerative colitis,68 this updated Consensus is grouped into th

21、ree parts: definitions and diagnosis; current management; and management of special situations. Previously included chapters on pregnancy and pediatrics are no longer included in this guideline, as specific ECCO Consensus Guidelines on Reproduction and Pregnancy and Pediatric UC (together with ESPGH

22、AN) cover these topics extensively,Background,溃疡性结肠炎（UC）1859年由Wilks首先描述，1920年被医学界公认，我国于1956年首次报道。 特发性溃疡性结肠炎诊断及治疗标准（草案）（1978年杭州） 溃疡性结肠炎的诊断及疗效标准（1993年太原） 对溃疡性结肠炎诊断治疗规范的建议（2000年杭州） 对我国炎症性肠病诊断治疗规范的共识意见（2007年济南） 炎症性肠病诊断与治疗的共识意见（2012年广州） 从中可以看出每一次补充和修改都反映了我国对该病认识的逐步提高，治疗逐渐规范化,第九届中华消化病学分会炎症性肠病学组成员名单,名誉组长：欧

23、阳钦 组长：胡品津 副组长：钱家呜 夏 冰 吴开春 冉志华 秘书：王玉芳 高 翔 核心成员：胡品津 欧阳钦 郑家驹 钱家呜 夏 冰吴开春 冉志华 刘占举 钟 捷 吴小平陈旻湖 胡仁伟 组员：欧阳钦 郑家驹 邓长生 刘新光 胡品津钱家鸣 夏 冰 吴开春 李俊霞 吕愈敏顾 芳 刘玉兰 王晓娣 韩 英 朱 峰冉志华 刘占举 郑 萍 钟 捷 庞 智曹 茜 陈旻湖 智发朝 姜 泊 张亚历钟英强 沙卫红胡仁伟 王玉芳 甘华田邹开芳 吴小平 缪应蕾 江学良 于成功梅 俏 王承党 郭长存 卢雪峰 高 翔霍丽娟,Ulcerative colitis in China: Retrospective analysi

24、s of 3100hospitalized patients,Background infectious enterocolitis had a misdiagnosis rate of 22.9% before admission. The main medications for UC in China were aminosalicylates (66.8%) and steroids (42.8%). Only 94 (3%) of the patients required colectomy and only 19 (0.6%) died of UC. Conclusions: C

25、ompared with UC in Western countries, ulcerative colitis in China has some differences in clinical characteristics. Therefore, a further population-based epidemiological study is required to determine the prevalence and incidence rates of UC in China,Ouyang QAPDW 2004 Chinese IBD working groupJ Gast

26、roenterol Hepatol. 2007,Epidemiolgy,The incidence of UC ranged from 1.0 to 2.0 per 100 000 person years. The prevalence of UC has ranged from 4.0 to 44.3 per 100 000. In a recent study, the speculated prevalence was 11.6/100 000 in China. Compared to time trends in the West, there appears to be a ti

27、me lag phenomenon involving incidence and and prevalence of IBD with regard to the Asian experience. Ouyang Q, Tandon R, Goh KL et al. Management consensus of inflammatory bowel disease for the Asia-Pacific region. J Gastroenterol. Hepatol. 2006; 21: 177282. Lennrd-Jones JE. Incidence of infammatory

28、 bowel disease across Europe:is there a difference between north and south?. Gut 1996; 39: 690-697,Etiology and Pathogenesis,目前对IBD病因和发病机制的认识可概括为： 环境因素作用于遗传易感者，在肠道菌群丛的参与下，启动了肠道免疫系统及非免疫系统，最终导致免疫反应和炎症过程。 可能是由于抗原的持续刺激或（及）免疫调节紊乱，这种免疫炎症反应表现为过度亢进或难于自限。 Baumgart DC, Carding SR. Inflammatory bowel disease:

29、cause and immunobiology. Lancet 2007;369:16271640. Brown SJ，Mayer IThe immune response in inflammatory bowel diseaseAm J Gastroenterol，2007，102：20582069 Bernstein CN，Shanahan FDisorders of a modern lifestylel reconciling the epidemiology of inflammatory bowel diseasesGut，2008，57：1185-1191,菌群失调,IBD患者

30、肠遭细菌存在菌群失调，正常细菌数量减少，而致病菌、条件致病菌数量明显增多。 Duchmann等 发现。正常人对其体内肠道菌群及抗原物质耐受，而IBD患者肠黏膜免疫细胞对失调的肠道菌群及抗原物质失去了耐受。这一发现证实了IBD患者肠道菌群及抗原物质能诱导肠黏膜异常免疫反应。 Frank等 发现IBD患者肠道菌群中拟杆菌、厚壁菌类减少，而变形杆菌及放线菌等增多。由于在肠道内，拟杆菌、厚壁菌是主要的裂解食物纤维产生丁酸盐和其他短链脂肪酸的细菌，这些细菌数量减少，导致维持肠上皮细胞生长和代谢的丁酸盐和其他短链脂肪酸等营养物质减少。同时。溃疡性结肠炎患者肠道内产硫化氢的细菌增多，硫化氢具有抑制丁酸盐和其

31、他短链脂肪酸等营养物质生存及直接影响肠上皮细胞新陈代谢的功能。 上述细菌菌群失调导致肠上皮细胞营养缺乏，影响了肠黏膜屏障功能。 Duchmann R。Kaiser I，Hermann E，et a1Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD)Clin Exp Immunol，1995102：448455 Frank DN， St Amand AL， Feldman RA， et a1Molecularphylogenetic

32、characterization of microbial community imbalances in human inflammatory bowel diseasesProc Natl Acad Sci USA，2007，104：1378013785,Family history,Kitahora et al. found a strong familial occurrence in UC among Japanese patients. In a Korean study, a similar familial aggregation was also reported. Kita

33、hora T, Utsunomiya T, Yokota A. Epidemiological study of ulcerative colitis in Japan: incidence and familial occurrence. The Epidemiology Group of the Research Committee of Inflammatory Bowel Disease in Japan. J. Gastroenterol. 1995; 30 (Suppl. 8): 58. Park ER, Yang SK, Myung SJ et al. Familial occu

34、rrence of ulcerative colitis in Korea. Korean J. Gastroenterol. 2000; 36: 7704,Risk factors,Objective To screen the risk factors of inflammatory bowel disease(IBD)by case investigation Methords 72 determined IBD patients and 72 paired healthy subjects were surveyed with an organized inventory compri

35、sing of relevant items to IBDCOX regression method was used to screen the statistically significant risk factors for IBD Results COX regression indicated the statistical significance in stressmilk and fried food over the other postulated risk factorsfor IBD Conclusion Stress，milk and fried food are

36、the potential risk factors for IBD Kaichun Wu et al. Investigation on the risk factors of inflammatory bowel disease：A paired study of 72 cases. Chin J Gastroenterol Hepatol. 2006, 15(2): 161-162,Protective factors,A study from Japan found a protective effect of smoking for UC. Nam et al. found that

37、 appendectomy was protective against UC in their group of Korean patients. A case-control study of ulcerative colitis in relation to dietary and other factors in Japan. The Epidemiology Group of the Research Committee of Inflammatory Bowel Disease in Japan. J Gastroenterol. 1995; 30 (Suppl. 8): 912.

38、 Nam SW, Yang SK, Jung HY et al. Appendectomy and the risk of developing ulcerative colitis: results after control of smoking factor. Korean J. Gastroenterol. 1998; 32: 5560. Vleggaar FP, Lutgens MW, Claessen MM. Review article: the relevance of surveillance endoscopy in long-lasting inflammatory bo

39、wel disease. Aliment. Pharmacol. Ther. 2007; 26 (Suppl. 2): 4752,Clinical Presentation,Intestinal Symptoms 70% of patients with UC report 5 bowel movements during acute phases. The main reason for diarrhea is colonic inflammation, but bile acid and food malabsorption secondary to inflammation in the

40、 terminal ileum or the proximal small bowel can contribute to this symptom. A history of surgical resections can be seminal in explaining symptoms. Acute phases of UC almost always present with bloody diarrhea (“hematochezia”). Active inflammatory anorectal lesions result in urgency of defecation an

41、d cramps around defecation (“tenesmus”). UC patients often complain of lower left quadrant pain. Extraintestinal Manifestations,Wafik El-Diery and David Metz, Section EditorsDiagnostics of Inflammatory Bowel DiseaseGastroenterology，2007;133:16701689,肠外表现(Extraintestinal manifestations,肠外表现包括： 皮肤黏膜表现

42、(如口腔溃疡、结节性红斑和坏疽性脓皮病) 关节损害(如外周关节炎、脊柱关节炎等) 眼部病变(如虹膜炎、巩膜炎、葡萄膜炎等)、 肝胆疾病(如脂肪肝、原发性硬化性胆管炎、胆石症等) 血栓栓塞性疾病等。 Mendoza JL, Lana R, Taxonera C et al. Extraintestinal manifestations in inflammatory bowel disease: differences between Crohns disease and ulcerative colitis. Med. Clin. (Barc.) 2005; 125: 297300,并发症(C

43、omplications,并发症包括： 中毒性巨结肠 （toxic megacolon） 肠穿孔 下消化道大出血 上皮内瘤变和癌变 钱家鸣, 等.溃疡性结肠炎合并中毒性巨结肠六例及文献复习. 中华内科杂志J. 2012，51(9): 694-697/ Chow DK，Leong RW，Tsoi KK, et a1Longterm followup of ulcerative colitis in the Chinese populationAm J Gastroenterol，2009，104：647-654,Serological markers,The two most widely st

44、udied serological markers in inflammatory bowel disease in recent years have been p-ANCA and ASCA. The clinical utility of p-ANCA or ASCA testing in the diagnosis of inflammatory bowel disease, in patients with non-specific gastrointestinal symptoms, is limited because of the varying seroprevalence

45、of these antibodies in patients with inflammatory bowel disease and the inadequate sensitivity of the assays. Lawrance IC, Murray K, Hall A, Sung JJ, Leong R. A prospective comparative study of ASCA and pANCA in Chinese and Caucasian IBD patients. Am. J. Gastroenterol. 2004; 99: 218694 Reese GE, Con

46、stantinides VA, Simillis C et al. Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease. Am J Gastroenterol. 2006 (Oct); 101 (10): 241022. Bossuyt XSerologic markers in inflammatofy bowel diseaseC1in Chem

47、2006：52：171一181,Serum proteins,目的 应用蛋白质组学寻找溃疡性结肠炎(UC)血清差异蛋白，初步探索UC可能的生物标志物。 方法 收集UC患者30例和健康对照者30名的血清标本，双向凝胶电泳(2-DE)分离等量混合血清的蛋白质，运用图像分析软件进行比较和分析，识别差异表达蛋白质。应用基质辅助激光解吸电离飞行时间质谱(MAI，DI-TOF-MS)鉴定部分差异蛋白质点。 结果 UC组和对照组之间年龄、体重指数、吸烟情况和饮滔量的差异均无统计学意义(P值均o05)。初步筛选出UC患者与健康对照者存在明显差异的39个蛋白点，选择其中9个点。经质谱分析发现触珠蛋白，热休克转录

48、因子2，受体酪氨酸激酶、醛脱氢酶、载脂蛋白c一、中心粒旁物质l在UC患者中表达水平升高，角蛋白1，细丝蛋白A结合蛋白1、肌球蛋白3在UC患者中表达水平降低。 结论 采用蛋白质组学2-DE和质谱技术，筛选并鉴定出与UC相关的9个血清蛋白质，为提供新的UC生物学行为研究分子标志物奠定基础。 缪应雷，等. 溃疡性结肠炎血清差异蛋白的筛选研究. 中华消化杂志. 2010 , 30 (12): 898-901,尿白蛋白,目的： 探讨炎症性肠病患者尿中白蛋白的临床意义。 方法：对临床确诊的32例IBD患者（UC 27例，CD 5 例 ) 在疾病的不同时期，用免疫放射比浊法测定尿中白蛋白，并结合临床 Har

49、vey 和 Bradshaw 指数进行综合分析，选取25例健康人为正常对照。 结果：患者尿白蛋白活动期比缓解期明显增高（0.002）， Harvey 和 Bradshaw 指数呈正相关（活动期 r=0.76, P0.001；静止期 r=0.73, P0.001）。患者尿中白蛋白明显高于正常人（活动期 P0.001, 缓解期, P0.005）。 结论： 患者尿中白蛋白可作为判断患者疾病活动情况的指标。 邓长生. 炎症性肠病患者尿白蛋白的临床意义. 武汉大学学报. 2002， 23 (1)： 88-89,巨细胞病毒(CMV,巨细胞病毒(CMV)属疱疹病毒科B属双链DNA病毒，近年随着IBD与CMV

50、研究的深入，发现CMV在IBD的发生和疾病进展中起一定作用，且对IBD的临床诊治亦有一定指导价值。 Pfau 等发现CMV更易感染肉芽组织生长细胞CMV对炎症的趋向性使IBD患者感染CMV的风险增加。结肠活检组织的炎症和溃疡部位可见CMV包涵体, 且研究发现生长旺盛的细胞如肉芽组织或溃疡深部更易发现CMV感染推测CMV可通过单核细胞到达炎症黏膜并可在黏膜内增殖且对炎症黏膜具有特殊亲和力。 CMV急性感染可显著提高血清和肠道自然杀伤细胞、白细胞介素(IL)6、TNF-a、IFN1水平提示CMV感染可改变黏膜免疫提高宿主对炎症的易感性 CMV感染可激活原癌基因、激酶、转录因子致肿瘤发生。可能是IB

51、D患者结直肠癌发病率较高的原因之一例。 Matsuoka K, 1wao Y，Mori T，et a1Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patientsAm J Gastroenterol，2007，102：331-337,难辨梭状芽孢杆菌 （Clostridium difficile,目的 通过对炎症性肠病(IBD)患者粪便中难辨梭状芽孢杆菌(Cd)的检测,了解IBD患者中该菌的感染情况及其与IBD的关系. 方法 收集2

52、009年12月至2011年1月上海交通大学医学院附属瑞金医院消化科确诊的IBD患者130例,包括溃疡性结肠炎(UC)患者60例及克罗恩病(CD)患者70例.同时收集肠易激综合征(IBS)患者及无肠道疾患的健康人群各60例为对照.通过聚合酶链反应( PCR)和Cd毒素快速测试试剂盒(CDTK)方法对粪便样本中毒素A、毒素B基因进行检测,采用SPSS软件进行统计分析. 结果 纳入研究的130例IBD患者中,Cd感染者16例(12.3),其中UC 10例(16.7),CD 6例(8.6)；对照组中未发现Cd感染者(x2=15.779,P=0.000).处于活动期的IBD患者Cd感染率显著高于非活动期

53、患者(x2=10.092,P=0.001).结肠型CD患者的感染率为4/14,显著高于其他类型的CD患者(x2=13.125,P=0.001).轻度UC患者Cd感染率为4.5、中度为14.3、重度为6/17(x2=6.667,P=0.037)；轻度CD患者的Cd感染率为0、中度为4.2、重度为5/16,感染率随疾病严重程度的上升而增高(x2=13.907,P=0.000).使用广谱抗生素的患者与未使用者其Cd感染率差异无统计学意义(x2=1.414,p=0.378);免疫抑制剂与广谱抗生素同时使用者和单用广谱抗生素者Cd感染率差异亦无统计学意义(x2=0.330,P=0.962). 结论 IB

54、D患者中存在着一定的Cd感染率,尤其是处于疾病活动期的患者,感染率随IBD疾病严重程度的上升而增高. 袁耀宗，等. 难辨梭状芽孢杆菌与炎症性肠病关系的初步研究. 中华消化杂志. 2012， 32 (4)： 88-89,Fecal markers,Calprotectin (FCP), a heterocomplex of S100A8 and S100A9, is a calcium-binding protein with antimicrobial protective properties derived predominately from neutrophils, and to a

55、lesser extent, from monocytes and reactive macrophages. It constitutes approximately 5% of the total protein and up to 60% of the cytosolic protein in human neutrophils. As such, the fecal calprotectin concentration is proportional to the influx of neutrophils into the intestinal tract, a hallmark o

56、f active IBD. Lactoferrin is an iron-binding glycoprotein identified in the secretions overlying most mucosal surfaces that interact directly with external pathogens, including saliva, tears, vaginal secretions, feces, synovial fluid, and mammalian breast milk. It is a major component of the seconda

57、ry granules of polymorphonuclear neutrophils and is shown to be a primary factor in the acute inflammatory response. In the intestinal lumen, fecal lactoferrin levels quickly increase with the influx of neutrophils during inflammation. Sugi and colleagues investigated lactoferrin, polymorphonuclear

58、neutrophil (PMN) elastase, and lysozyme together with myeloperoxidase in fecal material and whole-gut lavage fluid from IBD patients. Langhorst J, Elsenbruch S, Mueller T et al. Comparison of 4 neutrophil-derived proteins in feces as indicators of disease activity in ulcerative colitis. Inflamm. Bow

59、el Dis. 2005; 11: 108591,Fecal markers,Judd TA，Day AS，Lemberg DA，et a1Update of fecal markers of inflammation in inflammatory bowel diseaseJ Gastroenterol Hepat012011，26：14931499,Fecal markers,钡剂灌肠,检查所见的主要改变为： (1)黏膜粗乱和(或)颗粒样改变； (2)肠管边缘呈锯齿状或毛刺样，肠壁有多发性小充盈缺损； (3)肠管短缩，袋囊消失呈铅管样,CT,Ulcerative colitis with

60、 backwash ileitis. Axial CT enterographic sections show continuous involvement of the large bowel (white arrrows) and backwash ileitis (black arrow in b). Elsayes KM，AIHawary MM，Jagdish J，et a1CT enterography：principles，trends，and interpretation of findingsRadiographics，2010，30：19551970,结肠镜检查,Danese