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1、Inflammatory Bowel Disease,Hongyu Ren,MD Division of GI, Xiehe Hospital, Wuhan,Overview,Introduction/Epidemiology Pathogenesis Clinical Manifestations Conventional Therapies Prognosis,Introduction,Definition: Chronic autoimmune inflammatory disorders, involving some or all layers of the gut wall.,Ul
2、cerative Colitis (UC) Mucosal / submucosal only,Crohns Disease (CD) All layers of wall at risk,Ulcerative Colitis,Crohns Disease,Endoscopic Appearance,Normal colon,Friability Exudate bleeding,Diffuse ulceration,Cobblestoning,Focal ulceration,Histology/Depth of IBD,Mucosal and submucosal only No gran
3、ulomas seen,* Transmural disease * Granulomas occasionally seen,Ulcerative Colitis,Crohns Disease,Ulcerative Colitis vs Crohns Disease,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: Crohns di
4、sease: Slight female predominance Ulcerative Colitis: Slight male predominance Age incidence - Bimodal distribution Peak onset: 15 to 25 years of age Second peak incidence: 50 to 65 years of age,Anti-inflammatory,Pro-inflammatory,TNF IL-1b IL-12 / IL-18 IFNg,IL-4 / IL-13 IL-1Ra TGFb IL-10 PGE2,Patho
5、genesis,Pathogenesis of Inflammatory Bowel Disease,Immune Dysregulation,IBD,GeneticSusceptibility,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
6、 paucity of 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,Possible Oral contraceptives Diet: sugar, fat Breastfeeding (protective) Childhood infections Measles
7、 infection Mycobacterium paratuberculosis infection,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 as 67% for Crohns disease but only 13% to 20% for ulc
8、erative colitis,Genetics,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 Concordance CD (58%) UC (6%) Genome search loci on chromosomes 3, 5, 6, 12, 14, 16, 19
9、,Luminal antigen,Mucosal immune System (APC),Th2,Th1,T-supp/T-reg cells,TNF-, IFN-,IL-4 IL-5 IL-10,Humoral immune response B-cell, plasma cell expansion Increased Ig secretion,Th1 vs Th2 response,Crohns Disease,Cytokine production,Resistance to normal downregulation,Tissue injury Ineffective repair,
10、Ulcerative Colitis,Healthy Colon,Cell-mediated immune response,Immune Dysregulation,Pathology,Macroscopic Features Early lesion-aphthous ulcer Later Findings-Linear or serpiginous ulcers may form in a longitudinal direction. Irregular thickening of the bowel wall and, along with hypertrophy of the m
11、uscularis mucosa. Microscopic level The transmural nature of the inflammation. The presence of granulomas.,Clinical Manifestations,History,Exam,Laboratory,Endoscopy,Stool Studies,Clinical Presentation,Signs Mild or moderate disease usually look well Severe attacks: fever tachycardia abdominal tender
12、ness distension decreased bowel sounds Clubbing,Lab evaluation Acute phase reactants: ESR, CRP elevation Leukocytosis Anemia Reduced serum albumin Hypokalemia Abnormal LFTs Stool: leukocytes, RBCs,Symptoms,Crohns Disease Diarrhea (non-bloody) Weight loss Fever Perianal drainage/pus Right lower quadr
13、ant pain,Ulcerative Colitis Rectal bleeding Fecal urgency / tenesmus Diarrhea (bloody) Lower abdominal cramping,Disease Distribution,Ulcerative Colitis Rectum Cecum Confluent / Contiguous Ileal involvement uncommon No perianal disease,Crohns Disease Anywhere from “mouth to anus” Segmental / Skip Les
14、ions Rectum usually spared Ileal involvement common Perianal disease common,Ulcerative Colitis distribution,Mild,Severe,30%,40%,30%,Crohns Disease distribution,Liver,Eyes,Skin,Joints,Blood,Heart,Mouth,Extraintestinal IBD,Complication-UC,Massive hemorrhage Perforation acute dilatation of the colon (t
15、oxic megacolon) strictures pseudopolyps colonic cancer,Complication-CD,Stricture Fistula and Abscess perforation and bleeding cholelithiasis,Complications of Crohns Disease,Crohns Strictures,Complications of Crohns Disease,Crohns Fistulae,Perianal fistula,Complications of Crohns Disease,Crohns Fistu
16、lae,Entero-enteral fistula,Assessment of Disease Severity,Mildfewer than four stools daily, with or without blood, with no systemic disturbance and a normal erythrocyte sedimentation rate (ESR). Moderatemore than four stools daily but with minimal systemic disturbance. Severemore than six stools dai
17、ly with blood and with evidence of systemic disturbance, as shown by fever, tachycardia, anemia, or an ESR greater than 30.,Treatment Goals,Diagnosis and prompt therapeutic response Induction of complete remission Low side-effect profile to enhance compliance Maintenance of clinical remission Medica
18、l vs. surgical remission Steroid sparing Education and improvement of quality of life,Treatment,Conventional therapies: 5-ASA/SASP Corticosteroids/Budesonide Immunomodulators Antibiotics Anti-metabolites Biologic Modifiers,Prognosis,Ulcerative colitis 80% have intermittent attacks of their disease F
19、rom 10% to 15% of patients pursue a chronic continuous course,Crohn Disease Over a 4-year, 22% of patients remain in remission, 25% experience active symptoms, and 53% between active and inactive disease. The risk of colorectal cancer in Crohns disease above the general population as high as 26.6,END,