Statement 5 Upper gastrointestinal endoscopy should be routinely done in all patients of Crohn’s Disease

Why ? Disease Mapping ? Does it help in patients with indeterminate colitis ? Any typical histological finding ?

Halme L, Karkkainen P, Rautelin H, et al. High frequency of Helicobacter pylori-negative gastritis in patients with Crohn’s disease. Gut 1996;38:379–83. Oberhuber G, Puspok A, Oesterreicher C, et al. Focally enhanced gastritis: A frequent type of gastritis in patients with Crohn’s disease. Gastroenterology 1997;112:698 –706. Focally enhanced gastritis was observed in 76% of H. pylori–negative patients with Crohn’s disease and in 0.8% of controls

Whether these focal inflammatory infiltrates are exclusive to CD ? In H. pylori- negative patients, FEG was found in 8 of 27 patients (29.6%) of CD patients 6 of 27 (22.2%) patients with UC 2 of 9 (10.5%) of non-IBD control group (p=0.324) Hung HC et al, Korean J Gastroenterol 2009;53:23-28

Morphologic Findings in Upper Gastrointestinal Biopsies of Patients With Ulcerative Colitis A Controlled Study Jingmei Lin, MD, PhD, Barbara J. McKenna, MD, and Henry D. Appelman, MD (Am J Surg Pathol 2010;34:1672–1677)

CD involving the upper gastrointestinal tract is almost invariably accompanied by small or large bowel involvement Rutgeerts P, Onette E, Vantrappen G, Geboes K, Broeckaert L, Talloen L. Crohn's disease of the stomach and duodenum: A clinical study with emphasis on the value of endoscopy and endoscopic biopsies. Endoscopy 1980;12(6):288–94. Wagtmans MJ, van Hogezand RA, Griffioen G, Verspaget HW, Lamers CB. Crohn's disease of the upper gastrointestinal tract. Neth J Med 1997;50(2):S2–S7. Witte AM, Veenendaal RA, van Hogezand RA, Verspaget HW, Lamers CB. Crohn's disease of the upper gastrointestinal tract: the value of endoscopic examination. Scand J Gastroenterol Suppl 1998;100-5:100–5.

Upper gastrointestinal tract involvement reportedly occurs in 5% to 70% of patients with CD Korelitz BI, Waye JD, Kreuning J, et al. Crohn’s disease in endoscopic biopsies of the gastric antrum and duodenum. Am J Gastroenterol 1981;76:103–9. Maki M, Vaajalahti P, Arajarvi P, et al. Upper gastrointestinal endoscopic findings in childhood Crohn’s disease. Acta Paediatr Scand 1985;322(suppl):30. Kirschner BS. Gastroduodenal Crohn’s disease in childhood. J Pediatr Gastroenterol Nutr 1989;9:138–40. Cameron DJS. Upper and lower gastrointestinal endoscopy in children and adolescents with Crohn’s disease: A prospective study. J Gastroenterol Hepatol 1991;6:355–8. Lenaerts C, Roy CC, Vaillancourt M, et al. High incidence of upper gastrointestinal tract involvement in children with Crohn’s disease. Pediatrics 1989;83:777–81. Mashako MNL, Cezard JP, Navarro J, et al. Crohn’s disease lesions in the upper gastrointestinal tract: Correlation between clinical, radiological, endoscopic, and histological features in adolescents and children. J Pediatr Gastroenterol Nutr 1989;8:442–6. Griffiths AM, Alemayehu E, Sherman P. Clinical features of gastroduodenal Crohn’s disease in adolescents. J Pediatr Gastroenterol Nutr 1989;8:166–71.

The Role of Esophagogastroduodenoscopy in the Initial Evaluation of Childhood Inflammatory Bowel Disease: A 7-Year Study JPGN 39:257–261, 2004 Gastric biopsies may be useful in colitis unclassified, as focal active gastritis in the absence of ulceration may be a feature of CD Histology of UGI tract biopsies may confirm diagnosis of CD that would be otherwise missed. Granulomas, confirming the diagnosis of CD, were found in the upper gastrointestinal tracts of 28% of our patients with Crohn disease. In some cases, granulomas were found solely in the upper gastrointestinal tracts

Upper gastrointestinal inflammation was seen in 29 of 54 (22 CD; 7 UC ). Upper gastrointestinal tract endoscopy should be part of the first-line investigation in all new cases suspected of IBD. Absence of specific upper gastrointestinal symptoms do not preclude presence of upper gastrointestinal inflammation. Diagnostic Role of Upper Gastrointestinal Endoscopy in Pediatric Inflammatory Bowel Disease JPGN 39:257–261, 2004.

ESPGHAN’s Porto working group has recommended routine upper endoscopy at initial presentation to aid in the diagnosis of pediatric IBD Inflammatory Bowel Disease Working Group of ESPGHAN.Inflammatory bowel disease in children and adolescents:recommendations for diagnosis–the Porto criteria. J Pediatr Gastroenterol Nutr 2005; 41:1–7

ESPGHAN’s Porto working group has recommended routine upper endoscopy at initial presentation to aid in the diagnosis of pediatric IBD

Why ? Disease Mapping ? Yes Does it help in patients with indeterminate colitis ? Probably Yes Any typical histological finding ?Probably Yes Does it help in investigating for celiac ? Yes Is it more useful in a particular age group ? Yes

Upper Gastrointestinal endoscopy should be routinely done in all patients of Crohn’s Disease Comments: There is no indication for upper gi endoscopy in all Crohn's patients With suspected upper GI involvement Only in paediatrics If patients present with upper gastrointestinal manifestations, upper GI endoscopy should be indicated. Upper GI involvement uncommon to warrent rountine int. As a baseline test it should be done and need not be repeated indicated for patients with UGI symptoms "Pediatrics yes. Adults-not as well validated " Should be limited to patients with upper GI symptoms. I will do it when symptom suggest upper GI involvement

Statement 5 Upper gastrointestinal endoscopy is advisable in subgroups of Crohn’s disease : a) pediatric age group b) indeterminate colitis

Statement 6 Wireless capsule endoscopy is not indicated in all patients with Crohn’s disease. It is indicated if suspicion of Crohn’s Disease still remains despite a negative ileocolonoscopy and CT or MR enteroclysis

Capsule Endoscopy Has a Significantly Higher Diagnostic Yield in Patients With Suspected and Established Small- Bowel Crohn ’ s Disease: A Meta-Analysis Am J Gastroenterol 2010; 105:1240–1248 The yield of capsule endoscopy is superior to small- bowel radiography, computed tomography enterography, and colonoscopy with ileoscopy in the diagnosis of suspected small-bowel Crohn ’ s disease. CE is also a more effective diagnostic tool in established CD patients compared with SBR, CTE, and PE.

Am J Gastroenterol 2010; 105:1240–1248

Impact of Capsule Endoscopy on Management of Inflammatory Bowel Disease: A Single Tertiary Care Center Experience (Inflamm Bowel Dis 2011;17:1855–1862) Patients with CD 61.6% : Change in medication in the 3 months after the CE 39.5% : initiating a new IBD medication 12.8% : underwent surgery Severe findings on CE in patients with CD, as compared to no/minimal findings, resulted in significant differences in medication changes (73.2% versus 51.1%) addition of medications (58.5% versus 22.2%, P < 0.01), and surgeries (21.9% versus 4.4%, P=0.01).

Impact of Capsule Endoscopy on Management of Inflammatory Bowel Disease: A Single Tertiary Care Center Experience (Inflamm Bowel Dis 2011;17:1855–1862) CE results in management changes in the majority of cases of symptomatic IBD

J Crohns Colitis.J Crohns Colitis Apr;5(2): Small bowel capsule endoscopy vs conventional techniques in patients with symptoms highly compatible with Crohn's disease 30 cases SBCE may detect lesions compatible with small bowel CD in almost one third of patients with symptoms highly compatible with CD and no conclusive diagnosis by using conventional techniques ( Barium studies, Ileocolonoscopy, contrast USG)

Wireless capsule endoscopy in not indicated in all patients with Crohn’s disease. It is indicated if the suspicion of Crohn’s disease still remains despite a negative ileocolonoscopy and CT or MR enteroclysis. Comments: Agree with first sentence. CT should not be encouraged due to DMR. Enteroclysis is not necessary with CT or MRI in most patients and is often poorly tolerated. MR enterography is as good as mr enteroclysis (same for CT) when performed by specialist radiologists What about strictures causing retained capsule? Cautious with retained capsule CT/MR enterography and in patients without stricture lesions. Reined sound statement

A normal SBCE examination has a very high negative predictive value, essentially ruling out small bowel CD. However, the use of SBCE in cases of suspicion of small bowel CD is limited by a lack of specificity. CD associated lesions described by SBCE need more precise definition. Over 10% of healthy subjects demonstrate mucosal breaks and erosions in their SB. Thus, SBCE findings of mucosal lesions of the small bowel are not alone sufficient to establish a diagnosis of CD.

Statement 7 Serum ASCA and ANCA have no role in diagnosing Crohn’s Disease

The prevalence and diagnostic value of p ANCA and ASCA in patients with inflammatory bowel disease in mainland China. Zhou F. Clinica Chimica Acta 411 (2010) 1461–1465

The prevalence and diagnostic value of p ANCA and ASCA in patients with inflammatory bowel disease in mainland China. Zhou F. Clinica Chimica Acta 411 (2010) 1461–1465 Detection of pANCA and ASCA is useful in confirming the diagnosis of IBD, but plays a limited role in the differentiation between UC and CD in a central Chinese population.

pANCA and ASCA are not specific in identification of UC and CD in Canadian patients Can J Gastroenterol 2008 Low sensitivity Cannot replace existing diagnostic tools May be useful in indeterminate colitis

Clinical significance of anti-Saccharomyces cerevisiae antibody (ASCA) in Korean patients with Crohn’s disease and its relationship to the disease clinical course Kim et al, Digestive and Liver Disease 39 (2007) 610–616 A more severe clinical course and thus often required more aggressive medical treatment

Ghoshal UC, Ghoshal U, Singh H, Tiwari S. Anti-Saccharomyces cerevisiae antibody is not useful to differentiate between Crohn's disease and intestinal tuberculosis in India. J Postgrad Med Jul-Sep;53(3): Makharia GK, Sachdev V, Gupta R, Lal S, Pandey RM. Anti-Saccharomyces cerevisiae antibody does not differentiate between Crohn's disease and intestinal tuberculosis. Dig Dis Sci Jan;52(1):33-9. ITB vs CD

What Is the Role of Serological Markers in IBD? Pediatric and Adult Data Marla Dubinsky Pediatric IBD Center, Cedars-Sinai Medical Center, David Geffen School of Medicine, Los Angeles, Calif., USA Dig Dis 2009;27:259–268 Newer antiglycan antibodies The search for novel diagnostic approaches that accurately distinguishes a group of patients with IBD from those unaffected by the disease has become a focus in IBD research.

Serum ASCA and ANCA antibodies have no role in diagnosing Crohn’s disease. Comments: May be for research benchmark "May in occasions, help differentiate Crohn's disease from ulcerative colitis" "There are some reports against this statement. Such as Zhou F et al. Clin Chim Acta 2010, Oct 9, 416 (19-20)" Can be helpful in differentiating UC from CD In cases of indeterrminate colitis, the serological tests may help in distinguishing Crogn's disease from Ulcerative colitis These are sometimes useful for differential diagnosis. more data are necessary to confirm its accuracy Its not curcil for diagnosis but helps in differentiation of difficult cases of Crohn's and UC In the west, in CD 2/3 are ASCA+, 1/3 ANCA+. ASCA+ and ANCA- combination may help differentaing CD from UC. Can we use another word rather than "no role" such as "limited role".

Statement 7 Serum ASCA and ANCA have a limited role in diagnosing Crohn’s Disease, particularly in differentiating indeterminate colitis

Statement 8 Genetic testing is not routinely recommended for work up of Crohn’s Disease patients

Genetic testing is not routinely recommended for work up of Crohn’s disease patients Comments: "For Diagnosis of Crohn's Disease" In future, the development in genomic test may change in scenario.

Statement 14 Starting concomitant therapy for CD while the patient is on anti TB therapy should be discouraged in patients that are indeterminate for ITB and CD

Timer Period –Response CD (n=109)N(%) ITB(n=25)N(% ) P value At 1 month(n=109) Complete response1 (0.9)p<0.001 Partial response9 (8.3)21 (84) No response99 (90.8)4 (16) At 2 months( n=109) Complete response3 (2.8)4 (16)p<0.001 Partial response14 (12.8)20 (80) No response90 (82.6)1 (4) Worsened2 (1.8) At 3 months(n=109) Complete response5 (4.6)17 (68)p<0.001 Partial response38 (34.9)8 (32) No response63 (57.8) Worsened/relapsed3 (2.7) At 6 months(n=87) Complete response15 (17.4)23 (92)p<0.001 Partial response29 (33.7)2 (8) No response35 (39.6) Worsened/relapsed8 (9.3)

Case Scenarios A patient has completed 5 months of ATT and then shows lack of response ? Drug resistant tuberculosis