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IBD
Inflammatory bowel disease is caused by inappropriate activation of the immune system in response to normal gut bacteria. The two main types are Crohn's disease and ulcerative colitis. Crohn's disease can affect any part of the gastrointestinal tract and often involves transmural inflammation. Ulcerative colitis only involves the colon and rectum in a continuous manner. Both have a genetic component and involve defects in the epithelial barrier and immune response to gut microbiota. Common symptoms include abdominal pain, diarrhea, and weight loss.
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IBD
- 1. INFLAMMATORY BOWEL DISEASE Moderator – Dr. Poonam Nanwani Speaker – Dr. Sourabh Mandwariya
- 2. INTRODUCTION Group of inflammatory disorders thought to be result of inappropriate activation of mucosal immune system driven by the presence of normal luminal flora. Ulcerative Crohn‘s Two disorders Colitis Disease 1. Crohn‘s disease 2. Ulcerative colitis INDETERMINATE COLITIS
- 3. EPIDEMIOLOGY Common in Female Age group – Teens and early 20s Common in western world Prevalence increasing in developing nations
- 4. EPIDEMIOLOGY Improved food storage Decreased food contamination Hygiene Reduced frequency of enteric infection Hypothes is Inadequate development of mucosal immune response regulatory process Excessive response to self limited diseases Chronic inflammatory disease
- 5. EPIDEMIOLOGY Hygiene hypothesis supported by Low incidence of IBD in the helminthes infection prevalent areas IBD may precedes by an episode of acute infectious gastroenteritis
- 6. PATHOGENESIS Idiopathic Intestinal Epithelial disorder Dysfuncti on Aberrant Defect in Mucosal Host Immune Interaction Respons with e Intestinal Microbiota
- 7. PATHOGENESIS 1. Genetic factors 2. Mucosal immune responses 3. Epithelial defects 4. Microbiota
- 8. PATHOGENESIS 1. Genetic factors More dominant in Crohn‘s disease Concordance rate in monozygotic twins Crohn's disease – 50 % (Similar regions and with in 2 yr of each other) Ulcerative colitis – 16 % Concordance rate in Dizygotic twins – 10 % (Both) HLA-DR associated familial predisposition HLA-DR2 – Ulcerative colitis
- 9. PATHOGENESIS 1. Genetic factors Crohn's disease NOD2 (Nucleotide oligomerization binding domain 2) Gene; Chromosome 16q12 Regulate immune response – prevent excessive activation by luminal microbes Four fold increase in Crohn's disease risk <10% individual with mutation develop disease
- 10. PATHOGENESIS NOD2 (Nucleotide oligomerization binding domain 2) Gene Binds to intracellular bacterial peptidoglycans Activates NF-kB In NOD2 Mutation Luminal microbes are less effectively recognized Microbes enter to lamina propria Trigger inflammatory responses
- 12. PATHOGENESIS ATG16L1 (Autophagy-related 16-like) and IRGM (Immunity-related GTPase M) Gene Involved in autophagy and clearance of intracellular bacteria None of these genes are associated with ulcerative colitis
- 13. PATHOGENESIS 2. Mucosal immuneresponses Activation of mucosal immunity and suppression of immunoregulation
- 17.
- 18. PATHOGENESIS Transepitheli al flux of luminal bacterial components Activation Increase of innate flux of and luminal adaptive material immunity Increase Secretion of TNF tight and inflammatory junction mediator (In permeabilit genetically y susceptible Host)
- 19. PATHOGENESIS 3. Epithelial defects– Critical component Crohn's disease Defects in intestinal epithelial tight junction barrier function Associated with NOD2 Mutation Mutation of organic cation transporter SLC22A4 Defect in secreted mucin
- 20. PATHOGENESIS 3. Epithelial defects Ulcerative colitis ECM1 (Extracellular matrix protein 1) polymorphism Inhibition of matrix metalloproteinase 9
- 21. PATHOGENESIS 4. Microbiota Varies between individuals and modified by diet Probiotic may combat disease Metronidazole and other antibiotics are useful
- 22. PATHOGENESIS 4. Microbiota Implicated causative agent 1. Mycobacterium (Particularly M. Paratuberculosis) 2. E. Coli 3. Yersinia 4. Streptococcus 5. Viruses (Including measles)
- 23. PATHOGENESIS 6. Other Factors An episode of appendicitis – Reduce risk of ulcerative colitis Smoking – Reduces risk of ulcerative colitis - Increases risk of Crohn's's disease
- 24. CROHN'S DISEASE In 850 AD King Alfred, "England's Darling” had a GI illness that began at age 20 yr At the time the illness was thought to be due to punishment for the King's infidelities. It is now thought to be Crohn's disease Louis XIII of France (1601-1643)
- 25. CROHN'S DISEASE 1913 Dr. Dalziel - Described transmural intestinal inflammation in 13 autopsied patients. First fully described and published by – Crohn's, Ginzburg, Oppenheimer (1932) Regional enteritis or Granulomatous colitis
- 26. CROHN'S DISEASE Equal frequency in both sexes Common in twenties to thirties Can manifest in any age from childhood to old age May occur in any area of GI tract Most common sites – Terminal ileum - Iliocecal valve - Cecum
- 27. Crohn's’s Disease: CROHN'S DISEASE Anatomic Distribution Small bowel alone (33%) Ileocolic (45%) Colon alone Freq of involvement (20%) Most Least
- 28. CROHN'S DISEASE Gross features Earliest Crohn's disease lesion – Aphthoid ulcers Pinpoint reddish purple erosions of mucosa Progress to elongated serpentine ulcers
- 29. CROHN'S DISEASE Gross features - Sharp demarcation between normal and abnormal areas
- 30. CROHN'S DISEASE Skip lesions – multiple, separate sharply delineated areas of disease
- 31. CROHN'S DISEASE Occasionally entire length of small bowel will be evolved ( Diffuse jejunoileitis) Soggy feeling of small bowel Edema, fibrosis and loss of normal mucosal architecture Intramural abscess formation
- 32. CROHN'S DISEASE Transmural involvement
- 33. CROHN'S DISEASE Cobblestone appearance – Diseased tissue is depressed below the level of normal mucosa
- 34. CROHN'S DISEASE Gross features Cobblestone appearance
- 35. CROHN'S DISEASE Gross features Fissures Fistula tracts Perforation
- 36. CROHN'S DISEASE Gross features Perforation
- 37. CROHN'S DISEASE Gross features Creeping fat – In extensive transmural disease extension of mesenteric fat around the serosal surface
- 38. CROHN'S DISEASE Gross features Thickened and rubbery intestinal wall – Due to transmural edema, inflammation, submucosal fibrosis, hypertrophy of muscularis propria
- 39. CROHN'S DISEASE Strictures are common – Marked narrowing of lumen along with dilatation and hypertrophy of proximal segment
- 40. CROHN'S DISEASE Microscopic features Submucosal lymphedema – Earliest change Active disease – Marked infiltration of neutrophils and destruction of crypt epithelium Mucosal ulceration, necrosis and atrophy with loss of crypts
- 41. CROHN'S DISEASE Microscopic features Distortion of mucosal architecture – By repeated cycles of destruction and regeneration
- 42. CROHN'S DISEASE Microscopic features Lymphoid hyperplasia – Lamina propria and submucosa Chronic inflammatory cell infiltrate Edema, lymphatic dilation, hyperemia along with hyperplasia of muscularis mucosa
- 43. CROHN'S DISEASE Microscopic features Transmural involvement
- 44. CROHN'S DISEASE Microscopic features Transmural involvement
- 45. CROHN'S DISEASE Microscopic features Noncaseating granulomas Hallmark of Crohn's disease (60% cases) Sarcoid – like – with in center of lymphoid follicle Composed of epithelioid cells and multinucleated giant cells with absent or minimal necrosis
- 46. CROHN'S DISEASE Microscopic features
- 47. CROHN'S DISEASE Microscopic features Noncaseating granulomas – May present anywhere in the wall of bowel, lymph node, blood vessels (Granulomatous vasculitis)
- 48. CROHN'S DISEASE Microscopic features Fissures – Slit like spaces with sharp edges and narrow lumina, arranged perpendicularly to the mucosa and extending deeply into the submucosa or even upto the muscularis externa
- 49. CROHN'S DISEASE Microscopic features Obliterative muscularization Increase in number of smooth muscle fibers in submucosa Stricture formation Tenascin – Involved in morphogenesis of muscle tissue and wound healing Enteritis cystica profunda – Cystically dilated
- 50. CROHN'S DISEASE Microscopic features Disproportionate inflammation – Well defined focus of inflammatory cells surrounded by noninflamed and histologically normal mucosa Mesenteric lymph nodes – May show granuloma formation Metastatic Crohn's disease – Formation of cutaneous granuloma
- 51. CROHN'S DISEASE Clinical features Intermittent attacks of abdominal pain, fever and mild bloody diarrhea Mimic acute appendicitis or bowel perforation Active disease period is interrupted by asymptomatic periods for weeks to many months Undulating yet progressive course
- 53. CROHN'S DISEASE Clinical features Reactivation is associated with – Emotional stress - Specific dietary items - Smoking
- 55. CROHN'S DISEASE Other associated clinical features Small bowel disease – Malabsorption - Sever protein loss - Hypoalbuminemia - Vit. B12 deficiency, Colonic disease - Iron deficiency anemia
- 56. CROHN'S DISEASE Clinical features Extra intestinal manifestation (25%) – Ocular manifestation – Uveitis Musculoskeletal system - Migratory polyarthritis - Osteoporosis - Ankylosing spondylitis Skin involvement - Hidradenitis suppurativa - Clubbing of finger tips
- 57. CROHN'S DISEASE Clinical features Extra intestinal manifestation (25%) – Skin involvement - Erythema nodosum - Perianal abscess and fistula formation - Erythema multiforme - Aphthous ulcer - Cutaneous vasculitis
- 58. CROHN'S DISEASE Clinical features Extra intestinal manifestation (25%) – Hepatobiliary system – Pericolangitis - Primary sclerosing cholangitis
- 59. CROHN'S DISEASE Differential diagnosis Tuberculosis – Multiple circumferential ulcers - Caseous necrosis Sarcidosis - Rarely involve small intestine - Associated with other systemic features
- 60. CROHN'S DISEASE Differential diagnosis Yersiniosis – Colonies of gram negative bacteria beneath the ulcers - Identification of organism in stool, lymph node, blood and peritoneal fluid Eosinophilic enteritis – Peripheral eosinophilia with
- 61. ULCERATIVE COLITIS Greek physician Soranus - 130 AD First officially described by Wilks and Moxon in 1875 Before this discovery, all diarrheal diseases were believed to be caused by infectious agents and bacteria
- 62. ULCERATIVE COLITIS Severe ulcerating inflammatory disease limited to colon and rectum Involves only mucosa and submucosa Common age group – 20 to 30 yr and 70 to 80 yr
- 63. ULCERATIVE COLITIS Gross features Always involves rectum Extends proximally in continuous fashion to involve colon Limited disease – Ulcerative proctitis - Ulcerative proctosigmoiditis - Left sided colitis - Pancolitis
- 64. ULCERATIVE COLITIS Gross features - Backwash ileitis – Involvement of distal ileum
- 65. Farmer RG, EasleyKA, Ranking GB. Dig Dis Sci 1993;38(6):1137-1146. ULCERATIVE COLITIS 37% 46% 17% Farmer RG, Easley KA, Ranking GB. Dig Dis Sci 1993;38(6):1137-1146
- 66. ULCERATIVE COLITIS Gross features Mucosa – Red and granular with petechial hemorrhages
- 67. ULCERATIVE COLITIS Gross features Active disease (left) atrophic changes(Right)
- 68. ULCERATIVE COLITIS Gross features Sharp demarcation between active ulcerative colitis and normal area
- 69. ULCERATIVE COLITIS Gross features Broad based ulcer with various size
- 70. ULCERATIVE COLITIS Gross features Pseudopolyps – Elevated small multiple sessile reddish nodule due to isolated islands of mucosal ulceration
- 71. ULCERATIVE COLITIS Gross features Pseudopolyps
- 72. ULCERATIVE COLITIS Gross features Pseudopolyps and cobblestone appearance
- 73. ULCERATIVE COLITIS Gross features Mucosal bridges – Fusion of tips of Pseudopolyps
- 74. ULCERATIVE COLITIS Gross features Chronic disease – Mucosal atrophy (Flat and smooth
- 75. ULCERATIVE COLITIS Gross features Submucosal fat deposition Fibrotic, narrowed and shortened bowel
- 76. ULCERATIVE COLITIS Gross features Toxic megacolon – Due to destruction of muscularis propria and disturbed neuromuscular function due to inflammation and inflammatory mediators - Significant risk of perforation
- 77. ULCERATIVE COLITIS Gross features No stricture formation No mural thickening Normal serosal surface
- 78. ULCERATIVE COLITIS Microscopic features Mucosal and submucosal involvement
- 79. ULCERATIVE COLITIS Microscopic features Acute phase – Inflammatory cell infiltrate in lamina propria Progressive destruction of glands
- 80. ULCERATIVE COLITIS Microscopic features Crypt abscess – Collection of neutrophils in glandular lumen
- 81. ULCERATIVE COLITIS Microscopic features - Crypt abscess
- 82. ULCERATIVE COLITIS Microscopic features Atrophic and regenerative changes present together Stromal inflammatory cell infiltrate
- 83. ULCERATIVE COLITIS Microscopic features Pseudopolyps formation - Composed of granulation tissue mixed with inflamed and hyperemic mucosa Duplication of muscularis mucosa Obliterative endarteritis with dilation and thrombosis of blood vessels Accumulation of mast cells at the line of demarcation between normal and abnormal
- 84. ULCERATIVE COLITIS Microscopic features Pseudo pyloric metaplasia - Presence of gastric antral appearing glands
- 85. ULCERATIVE COLITIS Clinical features Relapsing and remitting course Episode of Mucoid bloody diarrhea, lower abdominal pain and cramp may last for days to months Relived by defecation Triggering factors – Infectious enteritis,
- 86. ULCERATIVE COLITIS Clinical features Extra intestinal manifestations – Ocular manifestation – Uveitis - Musculoskeletal system - Migratory polyarthritis - Ankylosing spondylitis - Skin lesions - Pyoderma gangrenosus - Perianal abscess
- 87. ULCERATIVE COLITIS Clinical features Extra intestinal manifestations – Hepatobiliary system - Fatty infiltration - Liver abscess - Cirrhosis - Pericolangitis - Primary sclerosing cholangitis - Carcinoma of biliary tract
- 88. ULCERATIVE COLITIS Differential diagnosis Nonspecific bacterial colitis – Acute inflammation out of proportion of chronic inflammation - Absence of crypt distortion Allergic colitis and proctitis – Mucosal edema and eosinophilic infiltration - Common in infants and children
- 89. ULCERATIVE COLITIS Differential diagnosis Pseudomembranous colitis – Presence of yellow white mucosal plaques - Focal explosive mucosal lesion Cytomegalovirus colitis – inclusion bodies - Common in immunocompromised patient
- 90.
- 91. SEROLOGICAL STUDIES Anti - neutrophil cytoplasmic antibodies – Ulcerative colitis (75% cases) - Crohn's disease (11% cases) Anti Saccharomyces cerevisiae antibodies - IgA and IgG against cell wall of Sac. cerevisiae – Crohn's disease (60% cases)
- 92. SEROLOGICAL STUDIES Anti-OmpC* Anti-Cbir1 Anti-I2 Anti-Glycan Abs Anti pancreatic Ab (PAB) Anti-laminaribocide Ab (ALCA) Anti-chitobioside (ACCA)
- 93. INDETERMINATE COLITIS Definitive diagnosis is not possible in 10 % of cases Pathological and clinical overlap between Ulcerative colitis and Crohn's disease Colonic disease in contentious pattern – Suggestive of ulcerative colitis Patchy histological disease, fissure, family history of Crohn's disease, onset after initiating use of cigarette – Against Ulcerative colitis
- 94. IBD ASSOCIATED NEOPLASM Long term complication Risk factors Risk increase after 8 to 10 years of disease initiation Patient with Pancolitis are at greater risk Greater frequency and severity of active inflammation – increase risk (presence of neutrophils)
- 95. IBD ASSOCIATED NEOPLASM Begins with dysplasia and develop into invasive carcinomas Categories for dysplasia 1. Negative for dysplasia 2. Indefinite for dysplasia, probably negative 3. Indefinite for dysplasia, unknown 4. Indefinite for dysplasia, probably positive
- 96. IBD ASSOCIATED NEOPLASM Indefinite for dysplasia
- 97. IBD ASSOCIATED NEOPLASM 5.Positive for dysplasia, low grade
- 98. IBD ASSOCIATED NEOPLASM 6.Positive for dysplasia, high grade
- 99.
- 100. IBD ASSOCIATED NEOPLASM Adenocarcinoma Carcinoid tumor Anaplastic carcinomas Carcinosarcomas Malignant lymphomas Colonic adenomas may also occur Regular follow-up with mucosal biopsy
- 101. TREATMENT Medical – Immunosuppression - Elemental diet - Total parenteral nutrition Surgical management – Resection of involved bowel segment
- 102. CROHN'S DISEASE V/SULCERATIVE COLITIS Features Crohn's disease Ulcerative colitis Clinical Rectal bleeding Inconspicuous Common Perforation 4% 12% Colon carcinomaVery rare 5%-10% Anal 75 %; Fissure, Rare; Minor complications Fistulas, Ulceration Abdominal mass 10%-15% Practically never Abdominal pain Usually right- Usually left side sided
- 103. CROHN'S DISEASE V/SULCERATIVE COLITIS Features Crohn's disease Ulcerative colitis Radiographic Sparing of 90 % Exceptional rectum Involvement of Common; Rare; Dilated ileum Constricted (Backwash ileitis) Strictures Often present Absent Skip areas Common Absent Internal fistulas May be present Absent Longitudinal and Common Exceptional transverse ulcer
- 104. CROHN'S DISEASE V/SULCERATIVE COLITIS Features Crohn's disease Ulcerative colitis Morphologic Distribution of Transmural Mucosal and involvement submucosal Mucosal atrophy Minimal Marked and regeneration Cytoplasmic Preserved Diminish mucin Lymphoid Common Rare aggregates Edema Marked Minimal
- 105. CROHN'S DISEASE V/SULCERATIVE COLITIS Features Crohn's disease Ulcerative colitis Morphologic Hyperemia Minimal May be extreme Crypt abscesses Rare Common Rectal 50 % Practically involvement always Granulomas Present in 60% Absent Fissuring Present Absent Lymph nodes May contain Reactive granulomas hyperplasia
- 106. REFERENCES Rosai and Ackerman’s; surgical pathology Robbins and Cotran: pathological Basis of Disease An atlas of gross pathology; C D M Fletcher & P H McKee New Concepts in the Pathophysiology of Inflammatory Bowel Disease ; Annals of Internal Medicine Harsh Mohan ; Textbook of Pathology Various internet link
- 109. CROHN'S DISEASE Microscopic features Fissures
- 110.
- 111.
Editor's Notes
- #92 ASCA:Sacch=brewer’s yeastSimple ELISA, standardized, easy to runPoor correlation with mucosal S. cerevesiaeMallant-Hent RC, et al. World J Gastroenterol 2006;12:292 ANCA:ANCA IgG, pANCA IIF, DNASE senspANCA IIFResults variable based on assay, personnel experience. ELISA+IFE--?60%, IFE alone0-40%