2 Inflammatory Bowel Disease Group of chronic inflammatory diseases of the GI tractMain subtypes areUlcerative Colitis (UC) - involves the large intestine (colon) and rectumCrohn’s Disease (CD) - may involve the entire GI tractIndeterminate Colitis (IC) - indeterminateReferenceCCFA: 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 DiseaseUC CDStrictureHealthy bowelHealthy bowelInflammationInflammationTerminal ileumUlcerative Colitis and Crohn’s Disease: Distinct Diseases With Similar SymptomsAlthough ulcerative colitis (UC) and Crohn’s disease (CD) have similar symptoms (ie, diarrhea, urgency, rectal bleeding, crampy abdominal pain), they are 2 very distinct diseases1Symptoms of CD may include weight loss, joint pain, oral/skin lesions/problems, fever, and stunted growth in children1Laboratory findings may include iron-deficiency anemia, elevated erythrocyte sedimentation rate and/or C-reactive protein, and hypoalbuminemiaCD 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 rectum1In CD, the entire thickness of the bowel wall may be involved, whereas only the innermost layer is affected in UC1In 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 manner1Contrary to UC, strictures and fistulas are frequently present in CD2Blood in the stool is common in UC but occurs only occasionally in CD2References1. 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:PatchyinflammationUlcersCrohn’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 DiseaseCD and UC have many overlapping features and several distinctive differencesIn a considerable number of patients, diagnosis may change during follow-upCD has transmural and segmental inflammation patterns and has the potential to involve any part of the GI tract, including the peri-anal areaCD has a tendency to be complicated by fistulae, abscesses, and stricturesCD has a lower propensity to develop into colorectal malignancyReferenceLichtenstein 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 involvementEarly stages develop aphthous ulcersAs the disease progresses, these superficial ulcers enlarge and combine to become long and linearLarger ulcers can deepen throughout the bowel wall—possibly complicated with fistula and abscess formationLongitudinal and transverse linear ulcers can cross over normal, non-ulcerated mucosa to form a cobblestone appearanceTransmural 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 mucusAnal lesions, fever, and weight loss are less frequent in UC than in CD, and there are rarely symptoms of obstructionGeneral 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 CDUC extends continuously from distal to proximal and almost always involves the rectumReferenceSatsangi 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 ICA 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 findings10%-15% of cases diagnosed as IC at initial evaluation>50% will be diagnosed as UC or CD over time—majority as UC4%-5% of all IBD will be left with a diagnosis of IC, with an uncertain treatment courseMore severe course with greater chance of colectomy and pouch failureOptimal treatment regimen is unknownCurrent evidence supports the premise that IC may be a separate entity; however, more studies are neededSupplemental InformationThe World Health Organization ratified revisions (October 2005), and the diagnosis, indeterminate colitis K52.3, was added to the ICD-10 in January 2009.ReferenceBurakoff 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 modalities1Distinguishing between UC and CD is difficult with colonoscopy with ileoscopy (C+I) alone because of lack of definitive lesions2Pediatric patients more likely than adult patients to have disease involving the proximal small-bowel3FDA-cleared diagnostic tool for children ≥ 2 years of age4Main indications: Obscure GI bleeding and suspected CD4ReferencesSeidman 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 endoscopy1Capsule endoscopy led to reclassification of disease (UC/IC to CD) in 5 of 7 (71%) patients studied113 of 21 (62%) patients with CD had more extensive small bowel involvement1CE findings led to reclassification of disease (UC/IC to CD) in 5 of 7 patients (71.4%)1Resulted in change in medical management for all 5 patientsProcedure is free of anesthesia and is non-invasive, patient-friendly, safe, and well-toleratedMain limitation is swallowing large capsule2Capsule can be introduced to the duodenum via standard endoscopyMain adverse event is capsule retention due to strictures2ReferencesCohen 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 years11/20 (55%) had positive findings consistent with IBD; 8 had small bowel Crohn’s disease and 3 had Crohn’s colitisUpper and lower endoscopy failed to provide a diagnosis in these childrenThe finings in the 11 positive studies varied from diffuse aphthous ulcerations throughout the small bowel to fissuring with terminal ileusAll 11 had evidence of acute active disease9/20 (45%) had normal studiesThis study demonstrates that CE is useful and equally as safe in young children as it is in adultsFritscher-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 care1Major determinants of cost are inpatient hospitalization/surgery (>50%), outpatient services, physician visits, and prescription medications2Aggregate 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 $49,0743Diagnostic 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 bowel4ReferencesLichtenstein 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 disease1Crohn’s disease typically recurs at the site of removal of macroscopic lesions and extends to the neoterminal ileum following the same initial pattern1In 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 before1CE is shown to be a useful tool for detecting CD recurrence and previously undetected small bowel involvement2CE exploration is of great use in the evaluation and treatment management of recurrent CD2Bourreille 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 life1573 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 therapyPatients in remission at week 54 were employed, and had better mental and physical functioning than those not in remissionHospitalization and surgery rates decreased as the percentage of time patients were in CDAI remission increasedReferencesLichtenstein 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 CD1Clinical improvement with infliximab correlates with improvement in the endoscopic severity indexSystematic 8 week maintenance treatment with infliximab induces mucosal healing, as long as the therapy is continuedThis 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 outcomes1. 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 cureCD most commonly affects the ileum in 70% of patients, with up to 30% of patients presenting with disease limited to the small bowel1Complete assessment of the small bowel is necessaryComprehensive evaluation of the entire small bowel—not just the colon and ileum—is needed to:Make a definitive diagnosis of CDDetermine extent and severity of diseaseDetermine baseline (disease activity) to serve as a comparator for monitoring and surveillance of diseaseColonoscopy at the terminal ileum can miss CD located proximally to the ileumPatchy pattern of diseased and normal bowel may increase the potential of missing diseased areas during C+I1. 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 involvedIn the right colon, another 15% of CD is identifiedIn the descending and transverse colon, 15% of CD is identifiedCD can occur in patchy patterns - diseased areas followed by normal areasColonoscopy at the terminal ileum can miss Crohn’s located proximally to the ileum40%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 considered1CE showed significantly more findings in the small bowel (jejunal and ileocecal involvement) than CTE (61% CE vs. 32% CTE)1The results of CE provided explanations for the symptoms of patients and gave a rationale for the therapeutic decision1ReferencesVoderholzer 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 CESmall Bowel SegmentExamination (n)Patients With Small LesionsPatients With Large LesionsUpper GI tractOGD (41)CE (41)1714Small intestineCTE (41)102358Neoterminal ileumC+I (40)CE (32)2413Frequency of lesions (n) occurring in CD in 41 patients who underwent the capsule examinationData were stratified with respect to the different examination techniques and the small-bowel segmentsSmall lesions were defined as patchy erythema, villous denudation, and aphthoid ulcerationsLarge lesions were defined as large/fissural ulcers, cobblestoning, and stenosisSmall 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 ileumReferenceVoderholzer 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 CDDetermine extent and severity of diseaseDetermine baseline (disease activity) to serve as a comparator for monitoring of diseaseColonoscopy at the terminal ileum can miss CD located proximally to the ileumPatchy pattern of diseased and normal bowel may increase the potential of missing diseased areas during C+I