内科学课件：炎症性肠病IBDe
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Concordance – CD (58%) > UC (6%) ➢ Genome search – loci on chromosomes 3, 5, 6, 12, 14, 16, 19
Immune Dysregulation
Healthy Colon
Luminal antigen
Crohn’s disease: Slight female predominance Ulcerative Colitis: Slight male predominance ➢ Age incidence -- Bimodal distribution Peak onse来自百度文库: 15 to 25 years of age Second peak incidence: 50 to 65 years of age
10 40
Ulcerative Colitis
Crohn's Disease
50
Indeterminate Colitis
Epidemiology
➢ Incidence: 5-29 per 100,000 people per year ➢ Prevalence: ~ 1.3 million persons ➢ New cases: estimated 20,000-100,000 per year* ➢ Gender distribution:
Possible
➢ Oral contraceptives ➢ Diet: sugar, fat ➢ Breastfeeding (protective) ➢ Childhood infections ➢ Measles infection ➢ Mycobacterium
paratuberculosis infection
fresh fruits and vegetables in the diet • Smoking • Stress
Risk Factors
Known
➢ Family history of IBD ➢ Cigarette smoking
Risk for CD Protective for UC ➢ Appendectomy Risk for CD Protective for UC
Inflammatory Bowel Disease
Overview
➢ Introduction/Epidemiology ➢ Pathogenesis ➢ Clinical Manifestations ➢ Conventional Therapies ➢ Prognosis
Introduction
as 67% for Crohn's disease but only 13% to 20% for ulcerative colitis
Genetics
➢ 10-25% of patients have a 1st degree relative with IBD ➢ Lifetime risk for siblings and offspring of IBD patients: ~10% ➢ Monozygotic twins – often share disease pattern and age of onset
Endoscopic Appearance
Ulcerative Colitis
Crohn’s Disease
Friability Exudate bleeding
Diffuse ulceration
Normal colon
Cobblestoning
Focal ulceration
Histology/Depth of IBD
Immune Dysregulation
IBD
Genetic Susceptibility
Environmental Triggers
Environment
Risk factors: • Occupations associated with outdoor physical labor • Higher socioeconomic status • Women who use oral contraceptives • Increased intake of refined sugars and a paucity of
Ulcerative Colitis
Mucosal and submucosal only No granulomas seen
Crohn’s Disease
* Transmural disease * Granulomas occasionally seen
Ulcerative Colitis vs Crohn’s Disease
Genetics
➢ The relative risk among first-degree relatives is 14 to 15 times higher than that of the general population
➢ Ethnicity plays a role as well ➢ The concordance rate among monozygotic twins is as high
Pathogenesis
Pro-inflammatory
TNF IL-1b IL-12 / IL-18 IFNg
Anti-inflammatory
IL-4 / IL-13 IL-1Ra TGFb IL-10 PGE2
Pathogenesis of Inflammatory Bowel Disease
Definition: Chronic autoimmune inflammatory disorders, involving some or all layers of the gut wall.
Ulcerative Colitis (UC) Mucosal / submucosal only
Crohn’s Disease (CD) All layers of wall at risk
Immune Dysregulation
Healthy Colon
Luminal antigen
Crohn’s disease: Slight female predominance Ulcerative Colitis: Slight male predominance ➢ Age incidence -- Bimodal distribution Peak onse来自百度文库: 15 to 25 years of age Second peak incidence: 50 to 65 years of age
10 40
Ulcerative Colitis
Crohn's Disease
50
Indeterminate Colitis
Epidemiology
➢ Incidence: 5-29 per 100,000 people per year ➢ Prevalence: ~ 1.3 million persons ➢ New cases: estimated 20,000-100,000 per year* ➢ Gender distribution:
Possible
➢ Oral contraceptives ➢ Diet: sugar, fat ➢ Breastfeeding (protective) ➢ Childhood infections ➢ Measles infection ➢ Mycobacterium
paratuberculosis infection
fresh fruits and vegetables in the diet • Smoking • Stress
Risk Factors
Known
➢ Family history of IBD ➢ Cigarette smoking
Risk for CD Protective for UC ➢ Appendectomy Risk for CD Protective for UC
Inflammatory Bowel Disease
Overview
➢ Introduction/Epidemiology ➢ Pathogenesis ➢ Clinical Manifestations ➢ Conventional Therapies ➢ Prognosis
Introduction
as 67% for Crohn's disease but only 13% to 20% for ulcerative colitis
Genetics
➢ 10-25% of patients have a 1st degree relative with IBD ➢ Lifetime risk for siblings and offspring of IBD patients: ~10% ➢ Monozygotic twins – often share disease pattern and age of onset
Endoscopic Appearance
Ulcerative Colitis
Crohn’s Disease
Friability Exudate bleeding
Diffuse ulceration
Normal colon
Cobblestoning
Focal ulceration
Histology/Depth of IBD
Immune Dysregulation
IBD
Genetic Susceptibility
Environmental Triggers
Environment
Risk factors: • Occupations associated with outdoor physical labor • Higher socioeconomic status • Women who use oral contraceptives • Increased intake of refined sugars and a paucity of
Ulcerative Colitis
Mucosal and submucosal only No granulomas seen
Crohn’s Disease
* Transmural disease * Granulomas occasionally seen
Ulcerative Colitis vs Crohn’s Disease
Genetics
➢ The relative risk among first-degree relatives is 14 to 15 times higher than that of the general population
➢ Ethnicity plays a role as well ➢ The concordance rate among monozygotic twins is as high
Pathogenesis
Pro-inflammatory
TNF IL-1b IL-12 / IL-18 IFNg
Anti-inflammatory
IL-4 / IL-13 IL-1Ra TGFb IL-10 PGE2
Pathogenesis of Inflammatory Bowel Disease
Definition: Chronic autoimmune inflammatory disorders, involving some or all layers of the gut wall.
Ulcerative Colitis (UC) Mucosal / submucosal only
Crohn’s Disease (CD) All layers of wall at risk