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  • 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 alone0-40%
  • IBD

    1. 1. INFLAMMATORY BOWEL DISEASE Moderator – Dr. Poonam Nanwani Speaker – Dr. Sourabh Mandwariya
    2. 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 Disease1. Crohn‘s disease2. Ulcerative colitis INDETERMINATE COLITIS
    3. 3. EPIDEMIOLOGY Common in Female Age group – Teens and early 20s Common in western world Prevalence increasing in developing nations
    4. 4. EPIDEMIOLOGY Improved food storage Decreased food contaminationHygiene Reduced frequency of enteric infectionHypothes is Inadequate development of mucosal immune response regulatory process Excessive response to self limited diseases Chronic inflammatory disease
    5. 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. 6. PATHOGENESIS Idiopathic Intestinal Epithelial disorder Dysfuncti on Aberrant Defect in Mucosal Host Immune Interaction Respons with e Intestinal Microbiota
    7. 7. PATHOGENESIS1. Genetic factors2. Mucosal immune responses3. Epithelial defects4. Microbiota
    8. 8. PATHOGENESIS1. Genetic factors  More dominant in Crohn‘s disease  Concordance rate in monozygotic twins  Crohns 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. 9. PATHOGENESIS1. Genetic factors  Crohns disease  NOD2 (Nucleotide oligomerization binding domain 2) Gene; Chromosome 16q12  Regulate immune response – prevent excessive activation by luminal microbes  Four fold increase in Crohns disease risk  <10% individual with mutation develop disease
    10. 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
    11. 11. 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
    12. 12. PATHOGENESIS2. Mucosal immune responses  Activation of mucosal immunity and suppression of immunoregulation
    13. 13. PATHOGENESIS
    14. 14. PATHOGENESIS Transepitheli al flux of luminal bacterial components ActivationIncrease of innate flux of and luminal adaptivematerial immunity Increase Secretion of TNF tight and inflammatory junction mediator (In permeabilit genetically y susceptible Host)
    15. 15. PATHOGENESIS3. Epithelial defects – Critical component  Crohns disease  Defects in intestinal epithelial tight junction barrier function  Associated with NOD2 Mutation  Mutation of organic cation transporter SLC22A4  Defect in secreted mucin
    16. 16. PATHOGENESIS3. Epithelial defects  Ulcerative colitis  ECM1 (Extracellular matrix protein 1) polymorphism  Inhibition of matrix metalloproteinase 9
    17. 17. PATHOGENESIS4. Microbiota  Varies between individuals and modified by diet  Probiotic may combat disease  Metronidazole and other antibiotics are useful
    18. 18. PATHOGENESIS4. Microbiota  Implicated causative agent 1. Mycobacterium (Particularly M. Paratuberculosis) 2. E. Coli 3. Yersinia 4. Streptococcus 5. Viruses (Including measles)
    19. 19. PATHOGENESIS6. Other Factors An episode of appendicitis – Reduce risk of ulcerative colitis Smoking – Reduces risk of ulcerative colitis - Increases risk of Crohnss disease
    20. 20. CROHNS DISEASE In 850 AD King Alfred, "Englands 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 Kings infidelities. It is now thought to be Crohns disease Louis XIII of France (1601-1643)
    21. 21. CROHNS DISEASE 1913 Dr. Dalziel - Described transmural intestinal inflammation in 13 autopsied patients. First fully described and published by – Crohns, Ginzburg, Oppenheimer (1932) Regional enteritis or Granulomatous colitis
    22. 22. CROHNS 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
    23. 23. Crohns’s Disease: CROHNS DISEASE Anatomic Distribution Small bowel alone (33%) Ileocolic (45%) Colon alone Freq of involvement (20%)Most Least
    24. 24. CROHNS DISEASE Gross features Earliest Crohns disease lesion – Aphthoid ulcers  Pinpoint reddish purple erosions of mucosa Progress to elongated serpentine ulcers
    25. 25. CROHNS DISEASE Gross features - Sharp demarcation between normal and abnormal areas
    26. 26. CROHNS DISEASE Skip lesions – multiple, separate sharply delineated areas of disease
    27. 27. CROHNS 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
    28. 28. CROHNS DISEASE Transmural involvement
    29. 29. CROHNS DISEASE Cobblestone appearance – Diseased tissue is depressed below the level of normal mucosa
    30. 30. CROHNS DISEASE Gross features Cobblestone appearance
    31. 31. CROHNS DISEASE Gross features Fissures  Fistula tracts  Perforation
    32. 32. CROHNS DISEASE Gross features Perforation
    33. 33. CROHNS DISEASE Gross features Creeping fat – In extensive transmural disease extension of mesenteric fat around the serosal surface
    34. 34. CROHNS DISEASE Gross features Thickened and rubbery intestinal wall – Due to transmural edema, inflammation, submucosal fibrosis, hypertrophy of muscularis propria
    35. 35. CROHNS DISEASE Strictures are common – Marked narrowing of lumen along with dilatation and hypertrophy of proximal segment
    36. 36. CROHNS 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
    37. 37. CROHNS DISEASE Microscopic features Distortion of mucosal architecture – By repeated cycles of destruction and regeneration
    38. 38. CROHNS DISEASE Microscopic features Lymphoid hyperplasia – Lamina propria and submucosa Chronic inflammatory cell infiltrate Edema, lymphatic dilation, hyperemia along with hyperplasia of muscularis mucosa
    39. 39. CROHNS DISEASE Microscopic features Transmural involvement
    40. 40. CROHNS DISEASE Microscopic features Transmural involvement
    41. 41. CROHNS DISEASE Microscopic features Noncaseating granulomas  Hallmark of Crohns disease (60% cases)  Sarcoid – like – with in center of lymphoid follicle  Composed of epithelioid cells and multinucleated giant cells with absent or minimal necrosis
    42. 42. CROHNS DISEASE Microscopic features
    43. 43. CROHNS DISEASE Microscopic features Noncaseating granulomas – May present anywhere in the wall of bowel, lymph node, blood vessels (Granulomatous vasculitis)
    44. 44. CROHNS 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
    45. 45. CROHNS 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
    46. 46. CROHNS 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 Crohns disease – Formation of cutaneous granuloma
    47. 47. CROHNS 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
    48. 48. CROHNS DISEASE Clinical features Reactivation is associated with – Emotional stress - Specific dietary items - Smoking
    49. 49. CROHNS DISEASE Other associated clinical features Small bowel disease – Malabsorption - Sever protein loss - Hypoalbuminemia - Vit. B12 deficiency, Colonic disease - Iron deficiency anemia
    50. 50. CROHNS 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
    51. 51. CROHNS DISEASE Clinical features Extra intestinal manifestation (25%) –  Skin involvement - Erythema nodosum - Perianal abscess and fistula formation - Erythema multiforme - Aphthous ulcer - Cutaneous vasculitis
    52. 52. CROHNS DISEASE Clinical features Extra intestinal manifestation (25%) –  Hepatobiliary system – Pericolangitis - Primary sclerosing cholangitis
    53. 53. CROHNS DISEASE Differential diagnosis Tuberculosis – Multiple circumferential ulcers - Caseous necrosis Sarcidosis - Rarely involve small intestine - Associated with other systemic features
    54. 54. CROHNS 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
    55. 55. 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
    56. 56. 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
    57. 57. 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
    58. 58. ULCERATIVE COLITIS Gross features - Backwash ileitis – Involvement of distal ileum
    59. 59. Farmer RG, Easley KA, 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
    60. 60. ULCERATIVE COLITIS Gross features Mucosa – Red and granular with petechial hemorrhages
    61. 61. ULCERATIVE COLITIS Gross features Active disease (left) atrophic changes(Right)
    62. 62. ULCERATIVE COLITIS Gross features Sharp demarcation between active ulcerative colitis and normal area
    63. 63. ULCERATIVE COLITIS Gross features Broad based ulcer with various size
    64. 64. ULCERATIVE COLITIS Gross features Pseudopolyps – Elevated small multiple sessile reddish nodule due to isolated islands of mucosal ulceration
    65. 65. ULCERATIVE COLITIS Gross features Pseudopolyps
    66. 66. ULCERATIVE COLITIS Gross features Pseudopolyps and cobblestone appearance
    67. 67. ULCERATIVE COLITIS Gross features Mucosal bridges – Fusion of tips of Pseudopolyps
    68. 68. ULCERATIVE COLITIS Gross features Chronic disease – Mucosal atrophy (Flat and smooth
    69. 69. ULCERATIVE COLITIS Gross features Submucosal fat deposition Fibrotic, narrowed and shortened bowel
    70. 70. 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
    71. 71. ULCERATIVE COLITIS Gross features No stricture formation No mural thickening Normal serosal surface
    72. 72. ULCERATIVE COLITIS Microscopic features Mucosal and submucosal involvement
    73. 73. ULCERATIVE COLITIS Microscopic features Acute phase – Inflammatory cell infiltrate in lamina propria Progressive destruction of glands
    74. 74. ULCERATIVE COLITIS Microscopic features Crypt abscess – Collection of neutrophils in glandular lumen
    75. 75. ULCERATIVE COLITIS Microscopic features - Crypt abscess
    76. 76. ULCERATIVE COLITIS Microscopic features Atrophic and regenerative changes present together Stromal inflammatory cell infiltrate
    77. 77. 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
    78. 78. ULCERATIVE COLITIS Microscopic features Pseudo pyloric metaplasia - Presence of gastric antral appearing glands
    79. 79. 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,
    80. 80. ULCERATIVE COLITIS Clinical features Extra intestinal manifestations – Ocular manifestation – Uveitis - Musculoskeletal system - Migratory polyarthritis - Ankylosing spondylitis - Skin lesions - Pyoderma gangrenosus - Perianal abscess
    81. 81. ULCERATIVE COLITIS Clinical features Extra intestinal manifestations – Hepatobiliary system - Fatty infiltration - Liver abscess - Cirrhosis - Pericolangitis - Primary sclerosing cholangitis - Carcinoma of biliary tract
    82. 82. 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
    83. 83. ULCERATIVE COLITIS Differential diagnosis Pseudomembranous colitis – Presence of yellow white mucosal plaques - Focal explosive mucosal lesion Cytomegalovirus colitis – inclusion bodies - Common in immunocompromised patient
    85. 85. SEROLOGICAL STUDIES Anti - neutrophil cytoplasmic antibodies – Ulcerative colitis (75% cases) - Crohns disease (11% cases) Anti Saccharomyces cerevisiae antibodies - IgA and IgG against cell wall of Sac. cerevisiae – Crohns disease (60% cases)
    86. 86. SEROLOGICAL STUDIES Anti-OmpC* Anti-Cbir1 Anti-I2 Anti-Glycan Abs Anti pancreatic Ab (PAB) Anti-laminaribocide Ab (ALCA) Anti-chitobioside (ACCA)
    87. 87. INDETERMINATE COLITIS Definitive diagnosis is not possible in 10 % of cases Pathological and clinical overlap between Ulcerative colitis and Crohns disease Colonic disease in contentious pattern – Suggestive of ulcerative colitis Patchy histological disease, fissure, family history of Crohns disease, onset after initiating use of cigarette – Against Ulcerative colitis
    88. 88. 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)
    89. 89. IBD ASSOCIATED NEOPLASM Begins with dysplasia and develop into invasive carcinomas Categories for dysplasia1. Negative for dysplasia2. Indefinite for dysplasia, probably negative3. Indefinite for dysplasia, unknown4. Indefinite for dysplasia, probably positive
    90. 90. IBD ASSOCIATED NEOPLASM Indefinite for dysplasia
    91. 91. IBD ASSOCIATED NEOPLASM5. Positive for dysplasia, low grade
    92. 92. IBD ASSOCIATED NEOPLASM6. Positive for dysplasia, high grade
    94. 94. IBD ASSOCIATED NEOPLASM Adenocarcinoma Carcinoid tumor Anaplastic carcinomas Carcinosarcomas Malignant lymphomas Colonic adenomas may also occur Regular follow-up with mucosal biopsy
    95. 95. TREATMENT Medical – Immunosuppression - Elemental diet - Total parenteral nutrition Surgical management – Resection of involved bowel segment
    96. 96. CROHNS DISEASE V/S ULCERATIVE COLITISFeatures Crohns disease Ulcerative colitis ClinicalRectal bleeding Inconspicuous CommonPerforation 4% 12%Colon carcinomaVery rare 5%-10%Anal 75 %; Fissure, Rare; Minorcomplications Fistulas, UlcerationAbdominal mass 10%-15% Practically neverAbdominal pain Usually right- Usually left side sided
    97. 97. CROHNS DISEASE V/S ULCERATIVE COLITISFeatures Crohns disease Ulcerative colitis RadiographicSparing of 90 % ExceptionalrectumInvolvement of Common; Rare; Dilatedileum Constricted (Backwash ileitis)Strictures Often present AbsentSkip areas Common AbsentInternal fistulas May be present AbsentLongitudinal and Common Exceptionaltransverse ulcer
    98. 98. CROHNS DISEASE V/S ULCERATIVE COLITISFeatures Crohns disease Ulcerative colitisMorphologicDistribution of Transmural Mucosal andinvolvement submucosalMucosal atrophy Minimal Markedand regenerationCytoplasmic Preserved DiminishmucinLymphoid Common RareaggregatesEdema Marked Minimal
    99. 99. CROHNS DISEASE V/S ULCERATIVE COLITISFeatures Crohns disease Ulcerative colitis MorphologicHyperemia Minimal May be extremeCrypt abscesses Rare CommonRectal 50 % Practicallyinvolvement alwaysGranulomas Present in 60% AbsentFissuring Present AbsentLymph nodes May contain Reactive granulomas hyperplasia
    100. 100. 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
    101. 101. CROHNS DISEASE Microscopic features Fissures
    102. 102. THANK YOU
    103. 103. THANKS