ibd與結(jié)核 ppt課件

1、克羅恩病與腸結(jié)核的鑒別,王 新第四軍醫(yī)大學(xué)西京消化病醫(yī)院2010-06-23,——現(xiàn)狀與挑戰(zhàn),It’s reported 21% of patients eventually diagnosed with CD were initially thought of ITB (J Gastroenterol Hepatol, 1998),In China, Liu reported up

2、to 65% of CD had been misdiagnosed as ITB (Zhonghua Nei Ke Za Zhi, 1981),The delay in diagnosis affect both the patient individually and the society

3、 (Am J Gastroenterol, 2003),Diagnostic Challenge for ITB and CD,Marker for differential diagnosis of ITB and CD!!!,A major concern when treating patients with CD using anti-TNF agents is the development o

4、f TB, even more so when the diagnosis is not definite,Epidemiology of CD,Epidemiology of ITB,Both intestinal tuberculosis (ITB) and Crohn’s disease (CD) are chronic granulomatous disorder with a lot of similarities,Cha

5、nge in epidemiology of ITB and CD make it more difficult in discriminating the two diseases,ITB and CD,(Am J Gastroenterol,2009),克羅恩病 (Crohn’s disease, CD),Burrill Crohn在1932年最早描述該病, 1973年WHO將其定為Crohn病是一種病因尚不十分明確的腸道慢性炎癥

6、性肉芽腫性疾病歐美國(guó)家發(fā)病率高, 近幾年我國(guó)發(fā)病率呈增加趨勢(shì)臨床表現(xiàn)呈多樣性內(nèi)鏡下主要特點(diǎn)為縱行潰瘍、鋪路石樣外觀和非干酪性肉芽腫次要特點(diǎn)為線樣、阿弗他潰瘍樣改變。,腸結(jié)核 (Intestinal tuberculosis, ITB),由結(jié)核分枝桿菌侵犯腸道引起的慢性特異性感染我國(guó)常見(jiàn)病之一，發(fā)病率較高主要臨床表現(xiàn)為腹痛、排便習(xí)慣改變、腹部包塊和低熱、盜汗、消瘦等全身癥狀診斷金標(biāo)準(zhǔn)：病原學(xué)檢查和病變組織干酪樣壞死部分腸結(jié)

7、核與CD患者臨床表現(xiàn)、內(nèi)鏡及病理學(xué)改變極為相似，鑒別診斷十分困難兩種疾病相互誤診率達(dá)50%～70%,鑒別診斷,ITB內(nèi)鏡下改變,橫向潰瘍包繞腸腔,回盲瓣多發(fā)潰瘍瘢痕形成,,,CD內(nèi)鏡下表現(xiàn),粘膜鵝卵石樣改變,,直腸口瘡樣粘膜潰瘍,,CD？ITB？,CD患者內(nèi)鏡下橫向潰瘍,ITB患者鵝卵石樣改變,ITB患者直腸口瘡樣潰瘍,ITB病理學(xué)表現(xiàn),肉芽腫形成,干酪樣壞死肉芽腫,淋巴肉芽腫,上皮組織基底潰瘍,CD病理學(xué)表現(xiàn),模糊的肉芽腫形成,小

8、肉芽腫形成,Caseous necrosis,﹖,TB最突出的特征： 肉芽腫最大直徑大于400μm； 每個(gè)活檢位點(diǎn)多于四處炎性肉芽腫； 裂隙樣潰瘍(cessation)； 潰瘍基底部上皮樣巨噬細(xì)胞帶；回盲部肉芽腫CD最突出的特征： 無(wú)上述肉芽腫特點(diǎn)；局限性結(jié)腸炎加重； 隱窩旁炎性

9、肉芽腫；存在組織結(jié)構(gòu)改變/慢性炎癥無(wú)肉芽腫的病灶 臨近部位的深大潰瘍 CD肉芽腫比TB更常見(jiàn)于結(jié)直腸,病理學(xué)特征分析的鑒別診斷價(jià)值,Pulimood AB, et al. J Gastroenterol Hepatol. 2005;20(5):688-96,對(duì)疑似腸結(jié)核患者回腸末段和回盲部大體表現(xiàn)正常的粘膜組織行活檢標(biāo)本組織病理學(xué)檢查有助于不可忽略的一小部分患者明確診斷,Misra SP, et al. Endo

10、scopy. 2004;36(7):612-6,回顧性分析臨床、影像學(xué)和組織學(xué)確診的CD (n=25, 104塊) 和腸結(jié)核(n=18, 41塊)結(jié)腸鏡活檢標(biāo)本,Kirsch R, et al. J Clin Pathol. 2006;59(8):840-4,,,,,病理學(xué)特征分析的鑒別診斷價(jià)值,110例確診胃腸道結(jié)核患者納入研究，觀察全形態(tài)學(xué)表現(xiàn)譜 (entire morphological spectrum)結(jié)果：除了典型的結(jié)核

11、病灶如橫向潰瘍、狹窄、 增生性病損和漿膜結(jié)節(jié)，腸穿孔發(fā)生頻率高(32.6%)，并存在腸缺血(7.3%)組織病理學(xué)：干酪樣、非干酪樣、融合型、散在型甚至化膿性肉芽腫等各種類(lèi)型的上皮樣細(xì)胞肉芽腫均可見(jiàn)同一病例中出現(xiàn)不同類(lèi)型肉芽腫并存的現(xiàn)象是重要發(fā)現(xiàn)多達(dá)44.5%的病例粘膜下層可見(jiàn)肉芽腫病灶85.5%病例的粘膜固有層炎癥類(lèi)型為淋巴漿細(xì)胞型,Tripathi PB, et al. Trop Gastroenterol. 2009;30(

12、1):35-9,病理學(xué)特征分析的鑒別診斷價(jià)值,30例初發(fā)內(nèi)鏡活檢疑似CD并后續(xù)行腸切除的成人患者（25例CD/3例結(jié)核/2例憩室并發(fā)炎癥），長(zhǎng)期隨訪內(nèi)鏡活檢。標(biāo)本經(jīng)三位病理學(xué)醫(yī)生盲評(píng)以下指標(biāo)：粘膜結(jié)構(gòu)改變、上皮異常、慢性活動(dòng)性炎癥和粘膜下層及粘膜基層改變結(jié)果：主要表現(xiàn)為活動(dòng)性慢性回結(jié)腸炎粘膜固有層的慢性炎癥，敏感性最好（92.7%），活動(dòng)性炎癥、基層漿細(xì)胞增多、結(jié)構(gòu)改變、上皮異常也具有較好的敏感性肉芽腫可見(jiàn)于部分CD患者和所有

13、腸結(jié)核患者CD患者的肉芽腫較小、致密、邊界清晰；TB為大而融合型肉芽腫,病理學(xué)特征分析的鑒別診斷價(jià)值,Kumarasinghe MP, et al. Pathology. 2010;42(2):131-7,Clinical, endoscopic, and histological features aid in the differentiation,(Am J Gastroenterol,2009),,,,,,Serologica

14、l Tests and Culture,ESR CRP,p-ANCA and c-ANCA,IgA and IgC subtypes of anti-Saccharomyces cerevisiae antibodies,Most reliable-- evidence of M. tuberculosis in the intestinal tissues,Acid-fast bacilli staining lacks sensit

15、ivity and specificity!,Biopsy culture for M. tuberculosis is time consuming (3-8weeks),Results are frequently negative (accuracy 25-35%),(Word J Gastroenterol,2008;Dig Dis Sci, 2007;… …),(Am J Gastroenterol,2009),Fetal

16、 Biomarkers,Lactoferrin (Am J Gastroenterol, 1998),Calprotectin,No difference between IBS (Am J Gastroenterol,2003),Controversy in predictive

17、 value of UC versus CD (Gut,2005),S100A12 (Gut, 2007),Mostly done in children patients, need more for verification

18、 (Gut,2009),Multi-marker panelsCommercial available panel: “IBD first-step” pANCA a

19、nd ASCA; Pilot study: anti-OmpW, anti-I2, and ASCA,Proteomic approaches for biomarkers,,,(Inflamm Bowel Dis 2010 [ahead of print]),Proteomic approaches for biomarkers,,(Inflamm Bowel Dis 2010 [ahead of print]),The tuber

20、culin skin test (TST),The PPD skin test has been extensively studied in cases of pulmonary TB. - e value of this test is unknown for ITB, but from these studies we can conclude that diagnostic value of this test varies a

21、ccording to the population that is being tested.,(Am J Gastroenterol,2009),Promising New Approach,TB-PCR (World J Gastroenterol, 2008),Amplification of insertion elemen

22、t IS6110 that is specific for the M. tuberculosis (J Clin Microbiol, 2006),In situ PCR (Am J Clin Pathol, 2008),方法：

23、原位PCR法檢測(cè)粘膜活檢標(biāo)本：結(jié)核分枝桿菌復(fù)合物特異性引物檢測(cè)IS6110結(jié)果：陽(yáng)性率：腸結(jié)核30%(6/20); CD 5%(1/20)結(jié)論：如檢測(cè)敏感性得到提高，原位PCR可有助于區(qū)分ITB和CD,Pulimood AB, et al. Am J Clin Pathol. 2008;129(6):846-51,PCR檢測(cè)腸黏膜結(jié)核桿菌DNA的鑒別診斷價(jià)值,,,,,,,,Image Studies,Chest X-ra

24、y,Negative can not exclude ITB,MRI,Not helpful in discriminating CD from ITB— Cannot detect small calcification within node or masses,CT,Helpful,(Am J Gastroenterol, 2009),Anti-TB medication trial,The use of anti

25、-TB medications comes with the risk of signifcant side effects and morbidity and can cause unnecessary delay in the management of patients with CD.,(Am J Gastroenterol,2009),Quantiferon-TB gold (QFT-G),QFT-G is a blood

26、test that uses an IFN-r-release assay to measure release of IFN after stimulation in vitro by M. tuberculosis antigen Approved by FDA for diagnosis of latent TB in 2005 May

27、 (MMWR Recomm Rep, 2005),ESAT-6,即6kDa早期分泌性抗原，是從結(jié)核分枝桿菌短期培養(yǎng)濾液中分離純化出的一種低分子量分泌性蛋白，具有較強(qiáng)的細(xì)胞免疫活性，在抗結(jié)核感染的免疫回憶應(yīng)答中起重要作

28、用。ESAT-6僅存在于致病性分枝桿菌中，包括人型結(jié)核桿菌、牛型結(jié)核桿菌、非洲分枝桿菌以及蘇爾加分枝桿菌、海水分枝桿菌和堪薩斯分枝桿菌等非典型分枝桿菌，BCG及其他非致病性分枝桿菌缺失。,CFP-10,即培養(yǎng)濾液蛋白10，與ESAT-6位于同一基因簇上，兩者分布相同，都是RDl區(qū)編碼的。ESAT-6和CFP10能刺激機(jī)體產(chǎn)生特異性IgG，利用ESAT-6和CFP10蛋白抗原能與結(jié)核分枝桿菌感染者血中特異性 IgG結(jié)合的特點(diǎn)，

29、采用ELISA等方法可特異性區(qū)分是真正的結(jié)核分枝桿菌感染或是接種BCG后所致敏，該方法明顯優(yōu)于PPD作包被抗原的ELISA法。,,Quantiferon®TB金標(biāo)法（QFT-G）PPD:純化的蛋白衍生物酶聯(lián)免疫斑點(diǎn)(Elispot)檢測(cè)外周血中結(jié)核分枝桿菌性抗原特異性γ干擾素(IFN-γ)水平 結(jié)核菌素皮內(nèi)測(cè)試(TST)特異性較低，而QFT-G和結(jié)核感染T細(xì)胞斑點(diǎn)試驗(yàn) (T-SPOT.TB)是基于干擾素-Gamma

30、對(duì)于結(jié)核分枝桿菌特異性抗原的反應(yīng)。,How Quantiferon? Is Performed,QFT vs. TST,In vitroMultiple antigensNo boosting1 patient visitMinimal inter-reader variability Results in 1 dayStimulate < 12 hrs,In vivoSingle anti

31、gen Boosting2 patient visitsInter-reader variability Results in 2 - 3 daysRead in 48 - 72 hrs,結(jié)核感染T細(xì)胞斑點(diǎn)實(shí)驗(yàn),陰性對(duì)照,抗原A,抗原B,陽(yáng)性對(duì)照,陽(yáng)性樣本,陰性樣本,結(jié)果分析,通常陰性對(duì)照沒(méi)有或僅有很少斑點(diǎn)。? 根據(jù)抗原A或/和抗原B孔的反應(yīng)判斷結(jié)果:陰性對(duì)照孔斑點(diǎn)數(shù)為0~5, 陽(yáng)性樣本應(yīng)為:(抗原A 或抗原B 斑點(diǎn)數(shù))

32、 – (陰性對(duì)照孔斑點(diǎn)數(shù)) ≥6.當(dāng)陰性對(duì)照孔斑點(diǎn)數(shù)≥6 spots, 陽(yáng)性樣本應(yīng)為:(抗原A 或抗原B 斑點(diǎn)數(shù)) ≥2x (陰性對(duì)照孔斑點(diǎn)數(shù)).如果陽(yáng)性對(duì)照孔結(jié)果良好，但抗原A或抗原B均達(dá)不到陽(yáng)性樣本判斷標(biāo)準(zhǔn)，則結(jié)果為陰性。陽(yáng)性結(jié)果說(shuō)明患者體內(nèi)存在針對(duì)結(jié)核桿菌的效應(yīng)T淋巴細(xì)胞。陰性結(jié)果提示患者可能不含針對(duì)結(jié)核桿菌的效應(yīng)T淋巴細(xì)胞。,回結(jié)腸炎癥中非干酪性肉芽腫或組織活檢中無(wú)抗酸桿菌,非可疑腸結(jié)核,無(wú)腸結(jié)核證據(jù),SUM

33、MARY,Although there are many proposed distinguishing clinical,radiological, endoscopic and histological features betweenthe two diseases, we believe the most important step for making the correct diagnosis is having a hi