Patho Basic Chronic Inflammatory Bowel Diseases. Jürg Vosbeck Pathology

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1 Patho Basic Chronic Inflammatory Bowel Diseases Jürg Vosbeck Pathology

2 General Group of chronic relapsing diseases with chronic bloody or watery diarrhea Usually ulcerative colitis (UC) or Crohn s disease (CD) Some cases of «indeterminate colitis»

3 Ulcerative colitis IBD of the large intestine Almost always begins in rectum May stay limited to rectum (ulcerative proctitis) or may extend to the entire colon in continuous fashion Maximum activity usually in distal colon

4 Ulcerative colitis Clinical course characterized by periods of exacerbation and remission («UC flares») Rarely continuous low grade activity or initial single attack Involvement of terminal Ileum may occur in patients with pancolitis («backwash ileitis»), 5 25 cm, 10% total colectomies

5 Ulcerative colitis Primarily inflammation of mucosa (DD Crohn s), but may involve deep layers in severe disease Classically diffuse distribution, however: false segmental distribution possible esp. in treated patients Cecal or periappendiceal patch

6 Aetiology unknown Ulcerative colitis One or more genetic factors in association with external factors and altered host immunology (failure to downregulate normal immune reaction?) Interplay microbes < > immune system

7 Ulcerative colitis Appendectomy may be protective of UC (mechanism?) Smoking seems to be preventive! Abnormality of colonic mucus?

8 Ulcerative colitis Peak in 3rd decade, range all ages M<F Anglo-Saxon origin (N Europe, N America), Jews

9 UC Macro Frail erythematous mucosa, hemorrhagic bowel content (F: rectocolite ulcérohémorrhagique, RCUH) Relative rectal sparing in treated patients

10 UC Macro Relatively little fibrosis, mostly of rectal submucosa Inflammatory polyps/mucosal tags and mucosal islands common

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15 Histology: UC Histo Active, resolving, in remission Active: Neutrophils, cryptitis, crypt abscesses «basal plasmocytosis», sometimes very large numbers of Eos or Mast cells

16 UC Histo Granulomas possible! But: Mucin-granulomas, reaction to damaged crypts («cryptolytic granulomas»). Location important; genuine sarcoid-type basally oriented granulomas don t occur in UC.

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21 Resolving: UC Histo Changes in crypt architecture Submucosal fibrosis Duplication of muscularis mucosae May occur in different rates depending on site -> false impression of segmental disease

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23 Ulcerative colitis Extraintestinal manifestations: Primary sclerosing cholangitis (5% of all UC patients; 70% of PSC patients have UC) Arthritis, ankylosing spondylitis, Erythema nodosum, Uveitis...

24 Drugs: 1st line: UC Treatment 5-ASA (aminosalicylic acid), Steroids Refractory disease: Azathioprine, 6-Mercaptopurine, Tacrolimus, MTX Novel therapies: Probiotics (alter bacterial flora); «stool transplantation»

25 Surgery: Colectomy UC Treatment Urgent in fulminant colitis, toxic megacolon, intractable bleeding Elective in refractory disease Ileoanal pouch Potentially curative

26 UC Prognosis Chronic, usually unrelenting Colonic adenocarcinoma in 3-5% of patients Risk: total colitis +/- backwash ileitis, early onset disease, > 8 years duration (some suggest > 5 yrs), PSC, family history Extensive disease: 19 fold risk compared to no Left sided disease: 4 fold risk

27 IBD Dysplasia Adenomas just like in healthy colon DALM concept outdated (dysplasia associated lesion or mass -> colectomy) Adenoma resected endoscopically + biopsies taken around the base Biopsies w/o dysplasia -> no further actions Biopsies with dysplasia -> EMR, ESD, colectomy

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30 Crohn s Disease 1932, «regional enteritis» (terminal Ileitis) Involves any part of the gut, mouth to anus Restricted to colon in 15-30% of patients Rectum macroscopically normal in 50% of cases

31 Crohn s Disease

32 Crohn s Disease Incidence continues to increase (UC has reached plateau in 1990s) Peak 3rd decade, wide range Aetiology remains mystery Genetic Immunological Deficiency of innate intestinal mucosal barrier? No autoimmunity involved Environmental: Smoking is strong risk factor (<-> UC) Appendectomy < 20 yrs. is a risk factor (<-> UC) Microbes (sustained alterations of gut flora through dietary habits, increased use of antibiotics)

33 Crohn s Disease Macro Segmental disease Ulceration, strictures, thickening of gut wall Small aphthous lesions to complete loss of mucosa in extensive disease Cobblestone appearance as result of intercommunicating fissures Transmural extension, expansion to neighboring organs (abscesses, fistulae)

34 Crohn s Disease Macro Esophageal: rare (<1%) Gastric: typically antral Duodenal: usually concomitant distal ileal or colonic disease Oral: 20-50%! Vesicles, aphthous ulcers

35 Crohn s Disease Macro Nonalimentary tract: 25% Arthritis, sacroileitis, ankylos. spondylitis Erythema nodosum, vasculitis Uveitis, conjunctivitis Rarely PSC

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40 Biopsy: Crohn s Disease Histo Discontinuity of inflammation Granulomas Architectural abnormalities Terminal ileoscopic biopsies: Focal active inflammation, sometimes granulomas DD: NSAIDs, Yersiniosis, Behçet, UC...

41 Surgical specimen: Crohn s Disease Focal ulceration, transmural inflammation with lymphoid aggregates, granulomas Hyperplasia of nerve fibers (submucosal and myenteric plexus)

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47 DD «diverticular colitis»

48 Drugs: Crohn s Disease Treatment Aminosalicylates ( -salazines) Cyclosporin, steroids Azathioprine, Mercaptopurine Metronidazol, Ciprofloxacin Surgery: >60% repeated OPs, risk of short bowel syndrome

49 Crohn s Disease Prognosis Recurrences in 95% Less prone to pre-cancerous and malignant changes in colon thank UC Risk of carcinoma in small bowel 10-20x compared to normal

50 Indeterminate colitis Term widely used with variety of definitions Aetiology and type of colitis can t be identified properly Confusion: «Uncertainty whether or not IBD» «Patients with IBD but unsure if UC or Crohn s» -> clinical diagnosis of indeterminate colitis doesn t necessarily mean that the patient has an IBD!

51 Indeterminate colitis Strict definition (Montreal classification): Colectomy has been performed and pathologists are unable to make a definitive diagnosis of either UC or Crohn s In practice, distinction only of major importance if ileal pouch is considered (Crohn s -> no ileal pouch)

52 Indeterminate colitis Temporary «diagnosis» Most cases will behave like UC (80-90%) -> ileal pouch not contraindicated Never use term on biopsy (inflammatory bowel disease of undetermined aetiology, IBDU, instead)

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55 Summary Chronic inflammatory disease of colon (and small bowel) with many overlapping clinical and histological features -> interdisciplinary approach to correct patient handling Context, context, context!

56 Picture credits: Thank you

57 Thank you

58 Colectomy: UC Crohn s Indeterminate colitis «severe fulminant colitis without features of ulcerative colitis or Crohn s disease» = indeterminate colitis

59 Indeterminate colitis Overlapping histological features of UC and Crohn s Relative rectal sparing in UC

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