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Overview of Inflammatory Bowel Disease (IBD) 5-000-487.

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Presentation on theme: "Overview of Inflammatory Bowel Disease (IBD) 5-000-487."— Presentation transcript:

1 Overview of Inflammatory Bowel Disease (IBD) 5-000-487

2 Inflammatory Bowel Disease Group of chronic inflammatory diseases of the GI tract Main subtypes are Ulcerative Colitis (UC) - involves the large intestine (colon) and rectum Crohn’s Disease (CD) - may involve the entire GI tract Indeterminate Colitis (IC) - indeterminate Crohn’s & Colitis Foundation of America. http://www.ccfa.org/info/about/.

3 Ulcerative Colitis and Crohn’s Disease: Distinct Diseases With Similar Symptoms Crohn’s & Colitis Foundation of America Web site. http://www.ccfa.org/info/about/. Friedman S et al. In: Fauci AS, et al, eds. Harrison’s Principles of Internal Medicine. 17th ed. Columbus, OH: McGraw-Hill; 2008:1886-1898. Ulcerative Colitis Crohn’s Disease UC CD Inflammation Healthy bowel Ulcers Terminal ileum Stricture Patchy inflammation Healthy bowel Inflammation

4 Crohn’s Disease CD and UC have many overlapping features and several distinctive differences In a considerable number of patients, diagnosis may change during follow-up CD has transmural and segmental inflammation patterns and has the potential to involve any part of the GI tract, including the peri-anal area CD has a tendency to be complicated by fistulae, abscesses, and strictures CD has a lower propensity to develop into colorectal malignancy Lichtenstein GR. The Clinician’s Guide to Inflammatory Bowel Disease. Thorofare, NJ: Slack Publications; 2003:16-17.

5 Crohn’s Disease (continued) CD has a unique pattern of mucosal involvement Early stages develop aphthous ulcers As the disease progresses, these superficial ulcers enlarge and combine to become long and linear Larger ulcers can deepen throughout the bowel wall—possibly complicated with fistula and abscess formation Longitudinal and transverse linear ulcers can cross over normal, non-ulcerated mucosa to form a cobblestone appearance Transmural inflammation can heal, forming scars that lead to strictures

6 Ulcerative Colitis UC is a relapsing and remitting disease Almost every patient with UC has diarrhea, often with blood and mucus Anal lesions, fever, and weight loss are less frequent in UC than in CD, and there are rarely symptoms of obstruction General markers of inflammation (erythrocyte sedimentation rate and C-reactive protein) are less frequently found to be elevated in UC and rise to a lesser extent than in CD UC extends continuously from distal to proximal and almost always involves the rectum Satsangi J, Sutherland LR, eds. Inflammatory Bowel Disease. New York, NY: Churchill Livingstone; 2003.

7 Indeterminate Colitis No definitive diagnostic criteria for IC A diagnosis of IC is made when the criteria for either UC or CD cannot be definitively established on the basis of endoscopy or histologic and radiologic findings 10%-15% of cases diagnosed as IC at initial evaluation >50% will be diagnosed as UC or CD over time—majority as UC 4%-5% of all IBD will be left with a diagnosis of IC, with an uncertain treatment course More severe course with greater chance of colectomy and pouch failure Optimal treatment regimen is unknown Current evidence supports the premise that IC may be a separate entity; however, more studies are needed Burakoff R. J Clin Gastroenterol. 2004;38 (5 suppl):S41-S43.

8 Pediatric Considerations Diagnosis of CD in pediatric patients can be difficult with conventional modalities 1 Distinguishing between UC and CD is difficult with colonoscopy with ileoscopy (C+I) alone because of lack of definitive lesions 2 Pediatric patients more likely than adult patients to have disease involving the proximal small-bowel 3 FDA-cleared diagnostic tool for children ≥ 2 years of age 4 Main indications: Obscure GI bleeding and suspected CD 4 1. Seidman et al. Techniques in Gastrointestinal Endoscopy. 2006;8:149-153. 2. Castellaneta SP et al. J Pediatr Gastroenterol Nutr. 2004;39(3):257-261. 3. Cuffari C. Minerva Pediatr. 2006;58(2):139-157. 4. Shamir R et al. World J Gastroenterol. 2008;14(26):4152-4155.

9 Pediatric Considerations (continued) Pediatric studies report that the extent of small bowel involvement was better delineated by CE than by small bowel follow-through, CT scan, or standard upper endoscopy 1 Capsule endoscopy led to reclassification of disease (UC/IC to CD) in 5 of 7 (71%) patients studied 1 13 of 21 (62%) patients with CD had more extensive small bowel involvement 1 CE findings led to reclassification of disease (UC/IC to CD) in 5 of 7 patients (71.4%) 1 Resulted in change in medical management for all 5 patients Procedure is free of anesthesia and is non-invasive, patient-friendly, safe, and well-tolerated Main limitation is swallowing large capsule 2 Capsule can be introduced to the duodenum via standard endoscopy Main adverse event is capsule retention due to strictures 2 1. Cohen SA et al. J Pediatric Gastroenterol Nutr. 2008;47(1):31-36. 2. Shamir R et al. World J Gastroenterol. 2008;14(26):4152-4155.

10 CE was undertaken in 20 children with suspected Crohn’s disease; age range of 5.0 – 7.9 years 11/20 (55%) had positive findings consistent with IBD; 8 had small bowel Crohn’s disease and 3 had Crohn’s colitis Upper and lower endoscopy failed to provide a diagnosis in these children The finings in the 11 positive studies varied from diffuse aphthous ulcerations throughout the small bowel to fissuring with terminal ileus All 11 had evidence of acute active disease 9/20 (45%) had normal studies This study demonstrates that CE is useful and equally as safe in young children as it is in adults Fritscher-Ravens et al. Gut 2009;58(11):1467-1472. Pediatric Considerations (continued)

11 Cost and Burden of Care in Crohn’s Disease Hospitalization, surgery, work loss, and impaired quality of life contribute to the cost and burden of care 1 Major determinants of cost are inpatient hospitalization/surgery (>50%), outpatient services, physician visits, and prescription medications 2 Aggregate global costs for the first year are ~$8,295 for newly diagnosed patients who are medically managed; for those requiring aggressive medical management, including anti-TNF therapy, the cost is $29,508; and for patients requiring hospitalization, the cost is $49,074 3 Diagnostic costs for CD can be considerable, especially given the cycle of repeat testing due to low diagnostic yield of certain modalities and the inability of current diagnostic procedures to image the entire small bowel 4 1. Lichtenstein GR et al. Am J Gastroenterol. 2004;99(1):91-96. 2. Feagan BG et al. Am J Gastroenterol. 2000;95(8):1955-1960. 3. Leighton JA et al. Gastroenterology. 2009;136(suppl 1): Abstract W1084. 4. Goldfarb NI et al. Dis Manag. 2004;7(4):292-304.

12 CE is helpful in patients following ileocolonic resection for Crohn’s Disease (CD) to monitor the recurrence of active disease 1 Crohn’s disease typically recurs at the site of removal of macroscopic lesions and extends to the neoterminal ileum following the same initial pattern 1 In a study of 30 patients with post operative recurrence of Crohn’s disease, Involvement of the small intestine occurred in 21/30 (70%) of patients operated on less than 6 months before 1 CE is shown to be a useful tool for detecting CD recurrence and previously undetected small bowel involvement 2 CE exploration is of great use in the evaluation and treatment management of recurrent CD 2 1.Bourreille A et al. Gut 2006;55(7):978-983 2.Pons Beltran V et al. Gastrointest Endosc 2007;66:533-40 Managing the Relapse of Crohn’s Disease

13 Therapeutic Goal: Remission In a study by Lichtenstein et al., Crohn’s Disease Activity Index (CDAI) remission was associated with reduced hospitalization and surgeries, increased employment, and normalized quality of life 1 573 patients with moderate to severe Crohn’s disease were studied at week 54, after infliximab was administered, to determine the long term efficacy and safety of the therapy Patients in remission at week 54 were employed, and had better mental and physical functioning than those not in remission Hospitalization and surgery rates decreased as the percentage of time patients were in CDAI remission increased 1. Lichtenstein GR et al. Am J Gastroenterol. 2004;99(1):91-96.

14 Therapeutic Goal: Remission Current body of evidence supports the use of mucosal healing as an objective biological parameter of short- term efficacy in CD 1 Clinical improvement with infliximab correlates with improvement in the endoscopic severity index Systematic 8 week maintenance treatment with infliximab induces mucosal healing, as long as the therapy is continued This body of evidence supporting the use of mucosal healing as an objective biological parameter of short-term efficacy in CD is sufficient to consider endoscopy as an essential component of clinical trial outcomes 1. Van Assche G et al. Tech Gastrointest Endosc. 2004;6:138-143.

15 Crohn’s Disease and Small Bowel Evaluation CD is a debilitating, progressive, inflammatory disease for which there is no cure CD most commonly affects the ileum in 70% of patients, with up to 30% of patients presenting with disease limited to the small bowel 1 Complete assessment of the small bowel is necessary Comprehensive evaluation of the entire small bowel—not just the colon and ileum—is needed to: Make a definitive diagnosis of CD Determine extent and severity of disease Determine baseline (disease activity) to serve as a comparator for monitoring and surveillance of disease Colonoscopy at the terminal ileum can miss CD located proximally to the ileum Patchy pattern of diseased and normal bowel may increase the potential of missing diseased areas during C+I 1. Lashner BA. Clinical features, laboratory findings, and course of Crohn’s disease. In: Kirsner JB, ed. Inflammatory Bowel Disease. 5th ed. Philadelphia, PA: Saunders; 2000:305-314.

16 Is Location of Disease Important? In 70% of Crohn’s disease patients, the small bowel is involved In the right colon, another 15% of CD is identified In the descending and transverse colon, 15% of CD is identified CD can occur in patchy patterns - diseased areas followed by normal areas Colonoscopy at the terminal ileum can miss Crohn’s located proximally to the ileum Engstrom et al. “Diagnosis and Management of Bowel Diseases” Prof. Communications Publisher 1999. 40% 30%

17 Small Bowel Involvement in Crohn’s Disease A prospective study by Voderholzer et. al. showed that small intestinal involvement in CD occurs more frequently than previously considered 1 CE showed significantly more findings in the small bowel (jejunal and ileocecal involvement) than CTE (61% CE vs. 32% CTE) 1 The results of CE provided explanations for the symptoms of patients and gave a rationale for the therapeutic decision 1 1. Voderholzer WA et al. Gut. 2005;54(3):369-373.

18 Small Bowel Involvement in Crohn’s Disease (continued) Small Bowel Segment Examination (n) Patients With Small Lesions Patients With Large Lesions Upper GI tract OGD (41) CE (41) 17 14 0000 Small intestine CTE (41) CE (41) 10 23 5858 Neoterminal ileum C+I (40) CTE (41) CE (32) 23 14 24 13 10 Frequency of lesions (n) in patients who underwent CE Voderholzer WA et al. Gut. 2005;54(3):369-373. OGD = oesophagogastroduodenoscopy; CE = capsule endoscopy; CTE = computed tomography enteroclysis; C+I = colonoscopy with ileoscopy.

19 Importance of Small Bowel Evaluation in Crohn’s Disease Comprehensive evaluation of the entire small bowel — not just the colon and ileum — is needed to: Make a definitive diagnosis of CD Determine extent and severity of disease Determine baseline (disease activity) to serve as a comparator for monitoring of disease Colonoscopy at the terminal ileum can miss CD located proximally to the ileum Patchy pattern of diseased and normal bowel may increase the potential of missing diseased areas during C+I


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