INFLAMMATORY BOWEL DISEASE

Jean-Paul Achkar, MDCenter for Inflammatory Bowel Disease

Cleveland Clinic

WHAT IS INFLAMMATORY BOWEL DISEASE (IBD)?

• Chronic inflammation of the intestinal tract

• Two related but different diseases:– Ulcerative colitis– Crohn’s disease

WHAT IBD IS NOT

• IBD is sometimes confused with:

– Irritable bowel syndrome (IBS)– Diverticulitis– “Colitis”

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

Microflora distribution in the GI tract

Oral cavity - 107 to 108

Stomach - 0 to 103

Duodenum - < 108

Jejunum - < 103 to 105

Ileum - < 105 to 107

Large intestine - 1010 to 1012

Stool - 1010 to 1012

Stomach

Smallintestine

Esophagus

Oral cavity

Largeintestine

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

Nonspecific inflammation

Tissue injury

Restitution and repair

Multifactorial Basis of IBD

Elson CO et al. In: Proceedings of V International Symposium on Inflammatory Bowel Diseases, 1998.

Genetic Environmentalfactors factors

Immune factors

Chronic Inflammation: Imbalance Between Mediators

Pro-inflammatoryAnti-inflammatory

TNF-αTNF-αIL-1βIL-1β

IL-8IL-8IL-12IL-12

IFN-γIFN-γTGF-βTGF-β

IL-10IL-10IL-1raIL-1ra

IL-4/IL-13IL-4/IL-13

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

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

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

Gastrointestinal Tract

SmallIntestine

Colon

Appendix

Esophagus

Stomach

Rectum

Farmer RG, Easley KA, Ranking GB. Dig Dis Sci 1993;38(6):1137-1146.

Disease Distribution at PresentationDisease Distribution at Presentation

n=1116n=1116

37%37%

17%17%

46%46%

ULCERATIVE COLITIS: SYMPTOMS

• Diarrhea• Rectal bleeding• Rectal urgency• Abdominal cramps • Fever

Normal Colonic Mucosa

UC: Transition Point

Farmer RG, Easley KA, Ranking GB. Dig Dis Sci 1993;38(6):1137-1146.

Disease Distribution at PresentationDisease Distribution at Presentation

n=1116n=1116

37%37%

17%17%

46%46%

ULCERATIVE COLITIS: SYMPTOMS

• Diarrhea• Rectal bleeding• Rectal urgency• Abdominal cramps • Fever

Hendriksen C, Kreiner S, Binder V. Gut 1985;26:158-163.

UC Natural HistoryUC Natural History

0%

10%

20%

30%

40%

0 5 10 15 20Years

Col

ecto

my

Rat

e (%

)

0%

20%

40%

60%

80%

100%

Disease Activity

Patie

nts w

ith U

C (%

) .

No SymptomsNo Symptoms(50%)(50%)

Low ActivityLow Activity(30%)(30%)

ModerateModerate--High High Activity (20%)Activity (20%)

10%10%

23%23%

31%31%

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

Gastrointestinal Tract

SmallIntestine

Colon

Appendix

Esophagus

Stomach

Rectum

Locations in the GI Tract Most Often Affected

40%Large and

small intestine

25%Large

intestineonly

30%Small

intestine only 5%

Stomach and small intestine

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

Crohn’s Disease Complications: Fistulas

• A tunnel between two sections of the intestines or between the intestines and other organs, including the skin

SmallIntestine

Colon

Fistula

Fistula

Crohn’s Disease Complications: Abscesses

• A localized collection of pus within the tissue of the GI tract Stomach

SmallIntestine

LargeIntestine(Colon)

Abscess froma fissure in thesmall intestineinto the peritoneal cavity

Complications of CD: Fistulas

Abdominal Fistula Perianal Fistula

Cumulative Probability of Surgical Intervention in CD

Munkholm P, et al. Gastroenterology. 1993;105:1716.

Years

Prob

abili

ty (%

)

Events (no.) 122 26 15 7 7 4 8 1 8 2 2 2 3 2 1

0

20

40

60

80

100

0 2 5 8 11 14 17 20

±2 SD

D

Extraintestinal Manifestations

• Skin disorders:– Erythema nodosum– Pyoderma gangrenosum

• Joint disorders:– Peripheral arthritis– Sacroiliitis– Ankylosing spondylitis

• Ocular disorders:– Iritis, uveitis, and episcleritis

Extraintestinal Manifestations

• Hepatobiliary:– Gallstones– Primary sclerosing cholangitis (PSC)– Cholangiocarcinoma

• Renal:– Renal stones– Amyloidosis

• Other manifestations:– Aphthous stomatitis– Hypercoagulable state

Episcleritis

Peripheral Arthritis

Erythema Nodosum

Pyoderma Gangrenosum

Treatment of IBD

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

Treatment Options for IBD

• 5-ASA agents• Antibiotics• Steroids• Immunomodulators:

– 6-MP/azathioprine– Methotrexate

• Biologic agents:– Anti-TNF agents– Natalizumab