Post on 20-Jun-2020
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