1 / 39

Aetiology and Pathology of Inflammatory Bowel Disease.

Aetiology and Pathology of Inflammatory Bowel Disease. Dr Bryan F Warren Consultant Gastrointestinal Pathologist, John Radcliffe Hospital, Oxford, UK M62 Course 2004. Lecture planning!. Aetiology and Pathology in 15 minutes!. Aetiology of IBD. Genetics vs environment

Download Presentation

Aetiology and Pathology of Inflammatory Bowel Disease.

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Aetiology and Pathology of Inflammatory Bowel Disease. Dr Bryan F Warren Consultant Gastrointestinal Pathologist, John Radcliffe Hospital, Oxford, UK M62 Course 2004

  2. Lecture planning! Aetiology and Pathology in 15 minutes!

  3. Aetiology of IBD • Genetics vs environment • Liverpool family studies

  4. Crohn’s disease 8-12% patients have affected 1º relative Sibling risk of disease: s 15-35 Monozygotic twins vs. Dizygotic twins higher disease concordance No simple mendelian inheritance pattern Genetic predisposition?

  5. Complex trait – genetics and environment Blood Group Lung Cancer IBD Car crash Eye Colour Diabetes Cystic Fibrosis Malaria 100% Environment (multiple factors) 100% Genetic (multiple mutations)

  6. Nature 2001 Discovery of the NOD2/CARD15 gene

  7. Risk of developing Crohn’s disease 11 studies, 3616 Crohn’s / 3055 controls Non-Jewish Caucasian Single mutation OR 2.7 [2.3 – 3.3] Double mutationOR 20.5[11.9 – 35.4] Economou 2004

  8. Carriage of one or more NOD2 mutation PHENOTYPE Familial Small bowel Stenosing 1.0 2.0 4.0 Odds ratio, Susceptibility for Crohn’s disease Small bowel disease (Oxford study) 100% carriers of 2 mutations - ileal disease 56% ileal disease - no NOD2 mutation Economou 2004 Lesage 2002 Ahmad 2002

  9. NOD2 : Crohn’s phenotype Weak association • earlier age at diagnosis No association with • Disease severity, need for surgery • Extraintestinal manifestations • Drug response (inc. infliximab)

  10. Doesn’t get Crohn’s disease… Protected against endotoxin challenge (iv) Pauleau Mol Cell Biol 2003 NOD2: knockout mouse

  11. NOD2: more questions than conclusions • What is the physiological function of NOD2 in vivo? • intracellular recognition of bacteria? • Why do mutations in NOD2 cause Crohn’s disease? • Which bacteria are important? • a quarter of UK Crohn’s disease • tends toward stenotic small bowel phenotype

  12. Potential environmental factors in the pathogenesis of IBD Early environmental factors: • Maternal infection • Measles • Mumps • Whooping cough • Birth order • Breast feeding (protects) • Early weaning • Poor household amentities

  13. Potential environmental factors in the pathogenesis of IBD At all ages • Luminal bacteria (normal/abnormal) • Diet • Smoking • Tonsillectomy • Appendicectomy • NSAIDs (Jersey)

  14. Potential pathogenesis of IBD • Cytokine imbalance • Intestinal mucus barrier function-structure/sulphationetc • Leucocyte endothelial interactions(integrins etc)

  15. Why differentiate CD colitis and UC? • Previously - good to know for prognosis. • Now - crucial for selection for pouch surgery.

  16. When is it difficult to differentiate CD colitis and UC? • Fulminant colitis • After treatment of UC • When rare variants of Uc are not recognised.

  17. 1/9/2003

  18. Colectomy-quiescent UC – restorative proctocolectomy for intermittent but severe symptoms

  19. Fulminant UC- emergency colectomy.

  20. Fulminant UC Diffuse changes: when the mucosa is ulcerated away, diffuse, deeper ulceration occurs. Catch: mucin is often strikingly well preserved.

  21. Biopsy pathology UC • Crypt architectural distortion takes 6 weeks • Diffuse changes- • Architecture, mucin depletion, chronic inflammation, acute inflammation • Rectum most severe • Distribution of changes in a biopsy and in a biopsy series. • Catch-patchiness-post treatment or at junction of diseased and normal, or in caecal patch. UC after treatment Early disease-diffuse Chronic inflammation and basal plasma cells

  22. CMV in UC Beware of superimposed infection After immunosuppressive treatment.

  23. Quiescent UC Polyp Flat mucosa May have only architectural distortion, =/-paneth cells, may return to ‘normal’-review original biopsies ? Infection.

  24. Diversion in UC • Transmural inflammation • Granulomas • PMC like change • Mimics Crohn’s • It is UC and not a contraindication to pouch surgery. • Seen as part of the three stage pouch procedure. • Comforting if this occurs-helps confirm pouch has been made in UC!

  25. UC DALMs

  26. Crohn’s disease

  27. Crohn’s large bowel biopsy. • May be normal • May mimic UC • Patchiness is most reproducible feature • Mucosal granulomas – may mislead

  28. Definition of a granuloma 2 • “>/= 5 epithelioid macrophages in aggregation” Guidelines for initial biopsy diagnosis of suspected chronic inflammatory bowel disease. Jenkins D et al BSG group. J Clin Pathol 1997; February

  29. Crohn’s colitis Schiller KFR, Cockel R, Hunt RH, Warren BF. 2001 An atlas of gastrointestinal endoscopy and related pathology

  30. Crohn’s colitis Focal erosions and Focal inflammation Aphthous ulcer Perineural chronic inflammation and granuloma.

  31. Crohn’s colitis Transmural inflammation in the form of lymphoid aggregates

  32. Ileal Crohn’s disease –fat wrapping

  33. Crohn’s colitis-terminal ileal disease.

  34. When does ulcerative colitis mimic Crohn’s colitis? • Granulomas in response to crypt damage • Patchiness of disease after treatment • Resolution of histological changes after treatment • Fulminant colitis • Diversion proctitis in UC • SKIP LESIONS • Caecal patch • Appendix

  35. Granuloma in response to crypt damage-neutrophils and mucin.

  36. Skip lesions in UC Acceptable ones: • Appendix –Davison and Dixon • Caecal patch – D‘Haens Not contraindications to pouch surgery.

  37. Caecal patch in UC Courtesy of Dr Axel von Herbay

  38. Diverted Crohn’s colitis

  39. IBD: aetiology and pathology. Conclusions Genetics of IBD now providing more information about phenotype and risk. Clear diagnosis needed: UC, CD, indeterminate There are pathological’catches’. Help your pathologist-tell him what you have done.

More Related