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Asia Pacific Working Party on Crohn’s Disease

Asia Pacific Working Party on Crohn’s Disease. Vineet Ahuja Dept of Gastroenterology All India Institute of Medical Sciences New Delhi, India. Statement 9.

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Asia Pacific Working Party on Crohn’s Disease

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  1. Asia Pacific Working Party on Crohn’s Disease Vineet Ahuja Dept of Gastroenterology All India Institute of Medical Sciences New Delhi, India

  2. Statement 9 It is important to differentiate Crohn’s disease from Intestinal tuberculosis. Behcet’s disease should be excluded in areas of high prevalence.

  3. Behcet’s Disease Prevalence of Behcet’s disease is higher in middle and east Asia, including Japan, Korea, and China, especially in areas along the “Silk Road’’ BD is a multisystem vasculitis with systemic involvement which features mucocutaneous, ocular, articular, vascular, intestinal, urogenital, and neurologic involvement • Intestinal involvement is uncommon : 5-25% • High frequency of complications : • intestinal perforation, fistula formation, • and, occasionally, massive hemorrhage

  4. Development and Validation of Novel Diagnostic Criteria for Intestinal Behçet’s disease in Korean Patients With Ileocolonic Ulcers. Am J Gastroenterol 2009; 104:2492–2499; Longitudinal ulcers with a cobblestone appearance : CD Round and oval ‘punched-out’ ulcers : BD Most common site : ileocaecal area

  5. Development and Validation of Novel Diagnostic Criteria for Intestinal Behçet’s disease in Korean Patients With Ileocolonic Ulcers. Am J Gastroenterol 2009; 104:2492–2499;

  6. Differential diagnosis of intestinal Behcet’s disease and Crohn’s disease by colonoscopic findings.S. K. Lee*, B. K. Kim*, T. I. Kim,W. H. Kim Endoscopy 2009; 41: 9-16

  7. 115–BD 135 -CD Differential diagnosis of intestinal Behcet’s disease and Crohn’s disease by colonoscopic findings S. K. Lee*, B. K. Kim*, T. I. Kim,W. H. Kim Endoscopy 2009; 41: 9-16

  8. Anti-Saccharomycescerevisiae Antibody in Intestinal Behcet’s Disease Patients: Relation to Clinical Course Chang Hwan Choi, Dis Colon Rectum 2006; 49: 1849–1859

  9. A case of Behçet’s disease accompanied by colitis with longitudinal ulcers and granuloma JGH (2002) 17, 105–108

  10. Guideline Statements for Diagnosis of Intestinal Behcet’s Disease (Japan) Diagnosis of Intestinal Behcet’s disease can be made if A. There is a typical oval-shaped large ulcer in the terminal ileum, OR B. There are ulcerations or inflammation in the small or large intestine, AND clinical findings meet the diagnostic criteria of Behcet’s disease Diagnostic Criteria (International Study Group for Behçet’s Disease, 1990) Recurrent oral Uleration + 2 of the following : Recurrent genital ulceration Eye lesions : uveitis Skin lesions : Erythema nodosum Positive Pathergy test Cheon JH, Korean J Gastroenterol 2009;53:187-193

  11. Intestinal Tuberculosis • Li X, Liu X, Zou Y, Ouyang C, Wu X, Zhou M, Chen L, Ye L, Lu F. Predictors of • Clinical and Endoscopic Findings in Differentiating Crohn's Disease from • Intestinal Tuberculosis. Dig Dis Sci. 2010 May 14. [Epub ahead of print] • Makharia GK, Srivastava S, Das P, Goswami P, Singh U, Tripathi M, Deo V, • Aggarwal A, Tiwari RP, Sreenivas V, Gupta SD. Clinical, endoscopic, and • histological differentiations between Crohn's disease and intestinal • tuberculosis. Am J Gastroenterol. 2010 Mar;105(3):642-51. • Amarapurkar DN, Patel ND, Rane PS. Diagnosis of Crohn's disease in India • where tuberculosis is widely prevalent. World J Gastroenterol. 2008 Feb • 7;14(5):741-6. • Differentiation of Crohn’s disease from intestinal tuberculosis in India in 2010.World J Gastroenterol 2011 January 28; 17(4): 433-443 • Zhou ZY, Luo HS. Differential diagnosis between Crohn's disease and • intestinal tuberculosis in China. Int J Clin Pract. 2006 Feb;60(2):212-4. • Kumarasinghe MP, Quek TP, Chau CY, Mustapha NR, Luman W, Ooi CJ. Endoscopic • biopsy features and diagnostic challenges of adult Crohn's disease at initial • presentation. Pathology. 2010 Feb;42(2):131-7. • Almadi MA, Ghosh S, Aljebreen AM. Differentiating intestinal tuberculosis from • Crohn's disease: a diagnostic challenge. Am J Gastroenterol. 2009 • Apr;104(4):1003-12.

  12. Statement 10 The colonoscopic features which suggest a diagnosis of CD include anorectal lesions, longitudinal ulcers, aphthous ulcers, cobblestone appearance. Features suggestive of ITB include transverse ulcers, involvement of fewer than four segments and a patulous ileocaecal valve

  13. Analysis of Colonoscopic Findings in the Differential Diagnosis Between Intestinal Tuberculosis and Crohn’s Disease . Lee YJ et al Endoscopy 2006; 38 (6): 592–597

  14. A score of + 1 was assigned to the four endoscopic parameters (anorectal lesions, longitudinal ulcers, aphthous ulcers, and cobblestone appearance) that are characteristic of Crohn’s disease, and a score of –1 was given to the other four parameters (involvement of fewer than four segments, a patulous ileocecal valve, transverse ulcers, and scars or pseudopolyps) that are characteristic of intestinal tuberculosis. The mean value of the scores for the eight parameters was 1.61 in patients with Crohn’s disease and –1.95 in patients with intestinal tuberculosis (P < 0.001).

  15. Analysis of Colonoscopic Findings in the Differential Diagnosis Between Intestinal Tuberculosis and Crohn’s Disease . Lee YJ et al Endoscopy 2006; 38 (6): 592–597

  16. Limitations of endoscopic findings • Overlap not Exclusive findings • Small sample size • No single finding is diagnostic • Correct diagnosis in 90% of cases by scoring system • No validation studies in different geographical locations • Scoring system not useful if colon not involved

  17. Statement 11 When granulomas are seen, features which favour ITB are necrosis (caseating), confluence, multiplicity, large size and submucosal location of granulomas and disproportionate degree of submucosal inflammation. The granulomas seen in CD are usually scant and tiny ( microgranulomas).

  18. Resected specimens: Distinguishing features of intestinal tuberculosis and Crohn’s disease Macroscopic • TB(n=159) • transverse, circumferential ulcers • short strictures • serosal nodules • CD(n=10) • longitudinal, serpiginous ulcers along the mesenteric attachment • cobble stone mucosa • fissuring ulcers • submucosal widening • long strictures • frequent presence of fistulae and anal lesions Tandon and Prakash, Gut 1972; Tonghua et al, Chin Med J, 1981

  19. Resected specimens: Distinguishing features of intestinal tuberculosis and Crohn’s disease Microscopic • TB: • large, confluent, usually caseating granulomas surrounded by an inflammatory cuff and fibrosis • pyloric gland metaplasia • fibrosis of the muscularis propria • CD: • Discrete, small granulomas without a cuff of inflammatory cells or peripheral fibrosis • transmural lymphoid follicles • lymphangiectasia • subserosal fibrosis Tandon and Prakash, Gut 1972; Tonghua et al, Chin Med J, 1981

  20. ? Applicability to mucosal biopsies • Changes below superficial submucosa cannot be evaluated • transmural lymphoid follicles, submucosal widening, serosal nodules, fibrosis of the muscularis propria and even fissuring ulcers • granulomas found exclusively in regional lymph nodes and not in the intestinal wall in 6 to 24% of resected specimens! • Quantity of tissue limited: ?Sampling error • Hoon et al 1950 - 44 cases; Anand SS 1956 - 50 cases; Tandon et al 1972 – 159 cases

  21. TB versus Crohn’s on Mucosal Biopsies • Only clinically confirmed cases with histological findings • Total of 100 cases (50 of TB and 50 of Crohn’s) • Granulomas: size, number, location • Other lesions • Segmental distribution of changes Pulimood et al, Gut 1999; Pulimood et al, J Gastroenterol Hepatol, 2005

  22. TB versus Crohn’s on Mucosal Biopsies Tuberculosis: • Caseation • Confluence • Lymphoid cuff • Granulomas larger than 400 micrometer • 5 or more granulomas in biopsies from one segment • Granulomas located in the submucosa or granulation tissue: often with palisaded histiocytes • Disproportionate submucosal inflammation Pulimood et al, Gut 1999; Pulimood et al, J Gastroenterol Hepatol, 2005

  23. TB versus Crohn’s on Mucosal Biopsies Crohn’s disease: Granulomas • Small (<200 micrometer) • Discrete • Very few / single • Poorly organised • Commonly located in the mucosa • “microgranulomas”: aggregates of histiocytes • Crypt-centric inflammation: pericryptal granulomas and focally enhanced colitis Pulimood et al, Gut 1999; Pulimood et al, J Gastroenterol Hepatol, 2005

  24. TB versus Crohn’s on Mucosal Biopsies Histological features that were not useful • Aphthous ulcers • Chronic inflammation • Architectural alteration • Patchy inflammation • Skip lesions

  25. Segmental Distribution of Lesions in Intestinal Tuberculosis and Crohn’s Disease Granulomatous Inflammation Crohn’s disease (n=33 cases) Tuberculosis (n=31 cases)

  26. Role of mucosal biopsies in the differentiation of intestinal tuberculosis from Crohn’s disease • Certainly useful, but have their limitations • Need to explore the use of complementary techniques like molecular studies to improve the diagnostic yield

  27. Statements 12 and 13 • A trial of 8-12 weeks anti TB therapy is reasonable in patients where it is not possible to confidently differentiate ITB from CD • In patients showing no or partial symptom response at 8-12 weeks, a repeat colonoscopy should be done. • To differentiate ITB from CD, a colonoscopy is suggested to document mucosal healing at the completion of ATT.

  28. Colonoscopy evaluation after short-term anti-tuberculosis treatment in nonspecific ulcers on the ileocecal area Park et al, World J Gastroenterol 2008 ; 14(32):5051-5058 18 patients with nonspecific ulcers on the ileocecal area 7 patients of confirmed tuberculous colitis The follow-up colonoscopy was performed after 2-3 months of ATT

  29. Colonoscopy evaluation after short-term anti-tuberculosis treatment in nonspecific ulcers on the ileocecal area Park et al, World J Gastroenterol 2008 ; 14(32):5051-5058 If there were healing of active ulcers similar to tuberculous colitis on follow up colonoscopy findings, the patients were classified as “suspicious tuberculous colitis group”, If there were still active ulcers or extension of the lesion, classified as “suspicious IBD group”. Mean duration for short-term follow up was 107.3 days

  30. Colonoscopy evaluation after short-term anti-tuberculosis treatment in nonspecific ulcers on the ileocecal area Park et al, World J Gastroenterol 2008 ; 14(32):5051-5058

  31. Colonoscopy evaluation after short-term anti-tuberculosis treatment in nonspecific ulcers on the ileocecal area Park et al, World J Gastroenterol 2008 ; 14(32):5051-5058 2-mo to 3-months trial of ATT and colonoscopy follow-up are very useful for differential diagnosis of tuberculous colitis with other inflammatory bowel diseases

  32. Response to trial of antitubercular therapy in patients with ulceroconstrictive intestinal disease and an eventual diagnosis of Crohn’s disease Khushboo Munot1 , Ashwin N Ananthakrishnan2, Vikas Singla1, Jaya Benjamin1, Saurabh Kedia1, Rajan Dhingra1, Govind Makharia1, Vineet Ahuja1 1Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India, 2 Gastrointestinal Unit, Massachusetts General Hospital, Boston, USA

  33. Objectives Evaluating a) clinical response b) temporal profile of nonresponse/relapse c) mucosal response to anti-tubercular therapy in patients with ulceroconstrictive intestinal disease and an eventual diagnosis of Crohn’s disease

  34. Ulceroconstrictive Small or large intestine disease ATT trial : 2 months of INH, rifampicin,pyrizinamide, ethambutol 4-7 months of INH, rifampicin For comparison of symptom response: 25 confirmed cases of ITB Patient follow up : 1 , 2 , 3 and 6 months Every 6 months thereafter Final diagnosis of CD made : Loss of response following ATT with response to steroids

  35. Outcome Measures • Global symptomatic response : on a visual analogue scale at 1,2, 3, 6 and > 6 months following ATT initiation • Individual symptom response of weight loss, abdominal pain, diarrhea, subacute intestinal obstruction (SAIO) and hematochezia • Colonoscopy changes at end of therapy were compared to baseline colonoscopy

  36. 50% response 75% response Visual Analog Scale 100% response Complete Response Partial Response No Response Relapse

  37. Patient Flow chart 380 patients with Crohn’s disease 115 (30.26%) patients received a trial of anti tubercular therapy before being eventually diagnosed as Crohn’s disease 6 patients Longitudinal records not available 109 CD patients were included in the study

  38. Overall response to ATT : Temporal Profile Figures denote percentages N= 109 N=109 N=109 N =87 N =63

  39. Comparison of Individual symptom profile in patients with CD and ITB on ATT P<0.001 Abdominal pain Figures denote percentages P<0.001 Weight Loss

  40. Comparison of Individual symptom profile in patients with CD and ITB on ATT Figures denote percentages Diarrhoea P=0.013 P=0.065 SAIO Hematochezia P=0.001

  41. Changes observed on colonoscopy before starting ATT and after ATT trial in patients with Crohn’s Disease N=62 Figures denote percentages

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