INFLAMMATORY BOWEL DISEASE. Jean-Paul Achkar, MD Center for Inflammatory Bowel Disease Cleveland Clinic

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1 INFLAMMATORY BOWEL DISEASE Jean-Paul Achkar, MD Center for Inflammatory Bowel Disease Cleveland Clinic

2 WHAT IS INFLAMMATORY BOWEL DISEASE (IBD)? Chronic inflammation of the intestinal tract Two related but different diseases: Ulcerative colitis Crohn s disease

3 WHAT IBD IS NOT IBD is sometimes confused with: Irritable bowel syndrome (IBS) Diverticulitis Colitis

4 INTESTINES: NORMAL STATE Protective immune cells are present in intestinal wall Immune system turns on and off to fight harmful substances like bacteria and viruses that pass through intestines

5 Microflora distribution in the GI tract Oral cavity to 10 8 Stomach - 0 to 10 3 Duodenum - < 10 8 Jejunum - < 10 3 to 10 5 Ileum - < 10 5 to 10 7 Large intestine to Oral cavity Esophagus Stomach Large intestine Small intestine Stool to 10 12

6 WHAT HAPPENS IN IBD? The immune system is activated by some unidentified factor The immune system does not turn off: Uncontrolled inflammation Attack on normal intestinal cells

7 Multifactorial Basis of IBD Immune factors Nonspecific inflammation Tissue injury Genetic factors Environmental factors Restitution and repair Elson CO et al. In: Proceedings of V International Symposium on Inflammatory Bowel Diseases, 1998.

8 Chronic Inflammation: Imbalance Between Mediators IFN-γ IL-12 IL-1β TNF-α IL-8 IL-1ra IL-4/IL-13 IL-10 TGF-β Pro-inflammatory Anti-inflammatory

9 HOW COMMON IS IBD? More than 1 million cases estimated in the United States: Ulcerative colitis: 50% Crohn s disease: 50% New cases diagnosed at a rate of 10 cases per 100,000 people

10 SCOPE OF THE PROBLEM Chronic lifelong diseases Periods of active disease alternating with periods of disease control: Other conditions can cause symptoms that mimic those of IBD Complications can develop Surgery frequently required

11 ULCERATIVE COLITIS Inflammation of the inner lining of the colon (mucosa) Only the colon is involved- starts in the rectum and spreads up the colon in continuous pattern Curable by surgery- removal of the colon

12 Gastrointestinal Tract Esophagus Small Intestine Stomach Colon Appendix Rectum

13 Disease Distribution at Presentation n= % 46% 17% Farmer RG, Easley KA, Ranking GB. Dig Dis Sci 1993;38(6):

14 ULCERATIVE COLITIS: SYMPTOMS Diarrhea Rectal bleeding Rectal urgency Abdominal cramps Fever

15 Normal Colonic Mucosa

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17 UC: Transition Point

18 Disease Distribution at Presentation n= % 46% 17% Farmer RG, Easley KA, Ranking GB. Dig Dis Sci 1993;38(6):

19 ULCERATIVE COLITIS: SYMPTOMS Diarrhea Rectal bleeding Rectal urgency Abdominal cramps Fever

20 UC Natural History Patients with UC (%). 100% 80% 60% 40% 20% Moderate-High Activity (20%) Low Activity (30%) No Symptoms (50%) Colectomy Rate (%) 40% 30% 20% 10% 10% 23% 31% 0% Disease Activity 0% Years Hendriksen C, Kreiner S, Binder V. Gut 1985;26:

21 CROHN S DISEASE Inflammation can involve all layers of the intestinal wall Can involve any part of the intestines from mouth to rectum with skip lesions- areas in between disease can be normal Usually comes back after surgery

22 Gastrointestinal Tract Esophagus Small Intestine Stomach Colon Appendix Rectum

23 Locations in the GI Tract Most Often Affected 40% Large and small intestine 25% Large intestine only 30% Small intestine only 5% Stomach and small intestine

24 CROHN S DISEASE: SYMPTOMS Same as those for ulcerative colitis Weight loss Fistulas- abnormal connection between intestine and other organs Abscess- collection of pus Strictures- areas of narrowing

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27 Crohn s Disease Complications: Fistulas Small Intestine Fistula Colon Fistula A tunnel between two sections of the intestines or between the intestines and other organs, including the skin

28 Crohn s Disease Complications: Abscesses A localized collection of pus within the tissue of the GI tract Stomach Large Intestine (Colon) Abscess from a fissure in the small intestine into the peritoneal cavity Small Intestine

29 Complications of CD: Fistulas Abdominal Fistula Perianal Fistula

30 Cumulative Probability of Surgical Intervention in CD Probability (%) ±2 SD 0 0 D Years Events (no.) Munkholm P, et al. Gastroenterology. 1993;105:1716.

31 Extraintestinal Manifestations Skin disorders: Erythema nodosum Pyoderma gangrenosum Joint disorders: Peripheral arthritis Sacroiliitis Ankylosing spondylitis Ocular disorders: Iritis, uveitis, and episcleritis

32 Extraintestinal Manifestations Hepatobiliary: Gallstones Primary sclerosing cholangitis (PSC) Cholangiocarcinoma Renal: Renal stones Amyloidosis Other manifestations: Aphthous stomatitis Hypercoagulable state

33 Episcleritis

34 Peripheral Arthritis

35 Erythema Nodosum

36 Pyoderma Gangrenosum

37 Treatment of IBD

38 Goals of Treatment Induce response/remission Maintain response/remission Heal mucosal lining Prevent or cure complications (eg, fistulas) Improve quality of life Restore and maintain nutrition Limit surgery

39 Treatment Options for IBD 5-ASA agents Antibiotics Steroids Immunomodulators: 6-MP/azathioprine Methotrexate Biologic agents: Anti-TNF agents Natalizumab