Aetiology and pathology of inflammatory bowel disease
Download
1 / 39

Aetiology and Pathology of Inflammatory Bowel Disease. - PowerPoint PPT Presentation


  • 105 Views
  • Uploaded on

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

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Aetiology and Pathology of Inflammatory Bowel Disease.' - gabriella-consuela


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.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
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


Aetiology and pathology of inflammatory bowel disease

Lecture planning!

Aetiology and Pathology in

15 minutes!


Aetiology of ibd
Aetiology of IBD

  • Genetics vs environment

  • Liverpool family studies


Genetic predisposition

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?


Complex trait genetics and environment
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)


Discovery of the nod2 card15 gene

Nature 2001

Discovery of the NOD2/CARD15 gene


Aetiology and pathology of inflammatory bowel disease

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


Aetiology and pathology of inflammatory bowel disease

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


Nod2 crohn s phenotype
NOD2 : Crohn’s phenotype

Weak association

  • earlier age at diagnosis

    No association with

  • Disease severity, need for surgery

  • Extraintestinal manifestations

  • Drug response (inc. infliximab)


Nod2 knockout mouse

Doesn’t get Crohn’s disease…

Protected against endotoxin challenge (iv)

Pauleau Mol Cell Biol 2003

NOD2: knockout mouse


Nod2 more questions than conclusions
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


Potential environmental factors in the pathogenesis of ibd
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


Potential environmental factors in the pathogenesis of ibd1
Potential environmental factors in the pathogenesis of IBD

At all ages

  • Luminal bacteria (normal/abnormal)

  • Diet

  • Smoking

  • Tonsillectomy

  • Appendicectomy

  • NSAIDs (Jersey)


Potential pathogenesis of ibd
Potential pathogenesis of IBD

  • Cytokine imbalance

  • Intestinal mucus barrier function-structure/sulphationetc

  • Leucocyte endothelial interactions(integrins etc)


Why differentiate cd colitis and uc
Why differentiate CD colitis and UC?

  • Previously - good to know for prognosis.

  • Now - crucial for selection for pouch surgery.


When is it difficult to differentiate cd colitis and uc
When is it difficult to differentiate CD colitis and UC?

  • Fulminant colitis

  • After treatment of UC

  • When rare variants of Uc are not recognised.




Fulminant uc emergency colectomy
Fulminant UC- emergency colectomy. intermittent but severe symptoms


Fulminant uc
Fulminant UC intermittent but severe symptoms

Diffuse changes: when the mucosa is ulcerated away,

diffuse, deeper ulceration occurs.

Catch: mucin is often strikingly well preserved.


Biopsy pathology uc
Biopsy pathology UC intermittent but severe symptoms

  • 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


Aetiology and pathology of inflammatory bowel disease

CMV in UC intermittent but severe symptoms

Beware of superimposed infection

After immunosuppressive treatment.


Quiescent uc
Quiescent UC intermittent but severe symptoms

Polyp

Flat mucosa

May have only architectural distortion, =/-paneth cells,

may return to ‘normal’-review original biopsies ? Infection.


Diversion in uc
Diversion in UC intermittent but severe symptoms

  • 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!


Aetiology and pathology of inflammatory bowel disease

UC DALMs intermittent but severe symptoms


Crohn s disease
Crohn’s disease intermittent but severe symptoms


Crohn s large bowel biopsy
Crohn’s large bowel biopsy. intermittent but severe symptoms

  • May be normal

  • May mimic UC

  • Patchiness is most reproducible feature

  • Mucosal granulomas – may mislead


Definition of a granuloma 2
Definition of a granuloma 2 intermittent but severe symptoms

  • “>/= 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


Crohn s colitis
Crohn’s colitis intermittent but severe symptoms

Schiller KFR, Cockel R, Hunt RH, Warren BF. 2001

An atlas of gastrointestinal endoscopy and related pathology


Crohn s colitis1
Crohn’s colitis intermittent but severe symptoms

Focal erosions and

Focal inflammation

Aphthous ulcer

Perineural chronic inflammation

and granuloma.


Crohn s colitis2
Crohn’s colitis intermittent but severe symptoms

Transmural inflammation in the form of lymphoid aggregates


Ileal crohn s disease fat wrapping
Ileal Crohn’s disease –fat wrapping intermittent but severe symptoms


Crohn s colitis terminal ileal disease
Crohn’s colitis-terminal ileal disease. intermittent but severe symptoms


When does ulcerative colitis mimic crohn s colitis
When does ulcerative colitis mimic Crohn’s colitis? intermittent but severe symptoms

  • 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



Skip lesions in uc
Skip lesions in UC intermittent but severe symptoms

Acceptable ones:

  • Appendix –Davison and Dixon

  • Caecal patch – D‘Haens

    Not contraindications to pouch surgery.


Caecal patch in uc
Caecal patch in UC intermittent but severe symptoms

Courtesy of Dr Axel von Herbay


Diverted crohn s colitis
Diverted Crohn’s colitis intermittent but severe symptoms


Ibd aetiology and pathology
IBD: aetiology and pathology. intermittent but severe symptoms

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.