1. Overview of Inflammatory Bowel Disease (IBD)

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
Reference
CCFA: Crohn’s & Colitis Foundation of America Web site. Accessed July 9, 2009.
Crohn’s & Colitis Foundation of America.

3. Ulcerative Colitis and Crohn’s Disease: Distinct Diseases With Similar Symptoms
Ulcerative Colitis Crohn’s Disease
UC CD
Stricture
Healthy bowel
Healthy bowel
Inflammation
Inflammation
Terminal ileum
Ulcerative Colitis and Crohn’s Disease: Distinct Diseases With Similar Symptoms
Although ulcerative colitis (UC) and Crohn’s disease (CD) have similar symptoms (ie, diarrhea, urgency, rectal bleeding, crampy abdominal pain), they are 2 very distinct diseases1
Symptoms of CD may include weight loss, joint pain, oral/skin lesions/problems, fever, and stunted growth in children1
Laboratory findings may include iron-deficiency anemia, elevated erythrocyte sedimentation rate and/or C-reactive protein, and hypoalbuminemia
CD most commonly affects the end of the small intestine and the beginning of the large intestine but can appear anywhere in the gastrointestinal (GI) tract, whereas UC is limited to the large intestine, including the rectum1
In CD, the entire thickness of the bowel wall may be involved, whereas only the innermost layer is affected in UC1
In CD, healthy bowel may be found between patches of inflamed bowel; these healthy sections of bowel are known as “skip” areas; however, in UC, inflammation extends up the colon in a continuous manner1
Contrary to UC, strictures and fistulas are frequently present in CD2
Blood in the stool is common in UC but occurs only occasionally in CD2
References
1. CCFA: Crohn’s & Colitis Foundation of America Web site. Accessed July 9, 2009.
2. Friedman S, Blumberg RS. Inflammatory bowel disease. In: Fauci AS, Braunwald E, Kasper DL, et al, eds. Harrison’s Principles of Internal Medicine. 17th ed. Columbus, OH: McGraw-Hill; 2008:
Patchy
inflammation
Ulcers
Crohn’s & Colitis Foundation of America Web site.
Friedman S et al. In: Fauci AS, et al, eds. Harrison’s Principles of Internal Medicine. 17th ed. Columbus, OH: McGraw-Hill; 2008:

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
Reference
Lichtenstein GR. The Clinician’s Guide to Inflammatory Bowel Disease. Thorofare, NJ: Slack Publications; 2003:16-17.
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
Reference
Satsangi J, Sutherland LR, eds. Inflammatory Bowel Disease. New York, NY: Churchill Livingstone; 2003.
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
Supplemental Information
The World Health Organization ratified revisions (October 2005), and the diagnosis, indeterminate colitis K52.3, was added to the ICD-10 in January 2009.
Reference
Burakoff R. Indeterminate colitis: clinical spectrum of disease. J Clin Gastroenterol. 2004;38(suppl 5):S41-S43.
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 modalities1
Distinguishing between UC and CD is difficult with colonoscopy with ileoscopy (C+I) alone because of lack of definitive lesions2
Pediatric patients more likely than adult patients to have disease involving the proximal small-bowel3
FDA-cleared diagnostic tool for children ≥ 2 years of age4
Main indications: Obscure GI bleeding and suspected CD4
References
Seidman E, Costea F, Dirks M. Performing capsule endoscopy in pediatric patients. Tech Gastrointest Endosc. 2006;8:
Castellaneta SP, Afzal NA, Greenberg M, et al. Diagnostic role of upper gastrointestinal endoscopy in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2004;39(3):
Cuffari C. Inflammatory bowel disease in children: a pediatrician's perspective. Minerva Pediatr. 2006;58(2):
Shamir R, Eliakim R. Capsule endoscopy in pediatric patients. World J Gastroenterol. 2008;14(26):
1. Seidman et al. Techniques in Gastrointestinal Endoscopy. 2006;8:
2. Castellaneta SP et al. J Pediatr Gastroenterol Nutr. 2004;39(3):
3. Cuffari C. Minerva Pediatr. 2006;58(2):
4. Shamir R et al. World J Gastroenterol. 2008;14(26):

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 endoscopy1
Capsule endoscopy led to reclassification of disease (UC/IC to CD) in 5 of 7 (71%) patients studied1
13 of 21 (62%) patients with CD had more extensive small bowel involvement1
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 capsule2
Capsule can be introduced to the duodenum via standard endoscopy
Main adverse event is capsule retention due to strictures2
References
Cohen SA, Gralnek IM, Ephrath H, et al. Capsule endoscopy may reclassify pediatric inflammatory bowel disease: a historical analysis. J Pediatric Gastroenterol Nutr. 2008;47(1):31-36.
Shamir R, Eliakim R. Capsule endoscopy in pediatric patients. World J Gastroenterol. 2008;14(26):
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):

10. Pediatric Considerations (continued)
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):

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 care1
Major determinants of cost are inpatient hospitalization/surgery (>50%), outpatient services, physician visits, and prescription medications2
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 $49,0743
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 bowel4
References
Lichtenstein GR, Yan S, Bala M, Hanauer S. Remission in patients with Crohn’s disease is associated with improvement in employment and quality of life and a decrease in hospitalization and surgeries. Am J Gastroenterol. 2004;99(1):91-96.
Feagan BG, Vreeland MG, Larson LR, et al. Annual cost of care for Crohn’s disease: a payor perspective. Am J Gastroenterol. 2000;95(8):
Leighton JA, Gralnek IM, Richner RE, Lacey MJ, Papatheofanis FJ. Capsule endoscopy (CE) in “suspected” small bowel (SB) Crohn’s disease (CD): economic impact of disease diagnosis and treatment. Gastroenterology. 2009;136(suppl 1): Abstract W1084.
1. Lichtenstein GR et al. Am J Gastroenterol. 2004;99(1):91-96.
2. Feagan BG et al. Am J Gastroenterol. 2000;95(8):
3. Leighton JA et al. Gastroenterology. 2009;136(suppl 1): Abstract W1084.
4. Goldfarb NI et al. Dis Manag. 2004;7(4):

12. Managing the Relapse of Crohn’s Disease
CE is helpful in patients following ileocolonic resection for Crohn’s Disease (CD) to monitor the recurrence of active disease1
Crohn’s disease typically recurs at the site of removal of macroscopic lesions and extends to the neoterminal ileum following the same initial pattern1
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 before1
CE is shown to be a useful tool for detecting CD recurrence and previously undetected small bowel involvement2
CE exploration is of great use in the evaluation and treatment management of recurrent CD2
Bourreille A et al. Gut 2006;55(7):
Pons Beltran V et al. Gastrointest Endosc 2007;66:533-40

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 life1
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
References
Lichtenstein GR, Yan S, Bala M, Hanauer S. Remission in patients with Crohn’s disease is associated with improvement in employment and quality of life and a decrease in hospitalization and surgeries. Am J Gastroenterol. 2004;99(1):91-96.
Van Assche G, Ferrante M, Vermeire S, Rutgeerts P. The role and importance of endoscopic mucosal healing in Crohn’s disease. Tech Gastrointest Endosc. 2004;6:
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 CD1
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:

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 bowel1
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: 15

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
40%
30%
30%
Engstrom et al. “Diagnosis and Management of Bowel Diseases” Prof. Communications Publisher 1999.

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 considered1
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 decision1
References
Voderholzer WA, Beinhoelzl J, Rogalla P, et al. Small bowel involvement in Crohn's disease: a prospective comparison of wireless capsule endoscopy and computed tomography enteroclysis. Gut. 2005;54(3):
1. Voderholzer WA et al. Gut. 2005;54(3):

18. Small Bowel Involvement in Crohn’s Disease (continued)
Frequency of lesions (n) in patients who underwent CE
Small Bowel Segment
Examination (n)
Patients With Small Lesions
Patients With Large Lesions
Upper GI tract
OGD (41)
CE (41) 17 14
Small intestine
CTE (41) 10 23 5 8
Neoterminal ileum
C+I (40)
CE (32) 24 13
Frequency of lesions (n) occurring in CD in 41 patients who underwent the capsule examination
Data were stratified with respect to the different examination techniques and the small-bowel segments
Small lesions were defined as patchy erythema, villous denudation, and aphthoid ulcerations
Large lesions were defined as large/fissural ulcers, cobblestoning, and stenosis
Small and large lesions can occur in the same patient (P = .007 vs computed tomography enterography [CTE]) (McNemar test)
Ten capsules did not reach the colon, implying that the terminal ileum was not reached; in 1 patient, the colonoscope could not be passed into the terminal ileum
Reference
Voderholzer WA, Beinhoelzl J, Rogalla P, et al. Small bowel involvement in Crohn's disease: a prospective comparison of wireless capsule endoscopy and computed tomography enteroclysis. Gut. 2005;54(3):
OGD = oesophagogastroduodenoscopy; CE = capsule endoscopy;
CTE = computed tomography enteroclysis; C+I = colonoscopy with ileoscopy.
Voderholzer WA et al. Gut. 2005;54(3):

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