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
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Dr Bryan F Warren
Consultant Gastrointestinal Pathologist,
John Radcliffe Hospital, Oxford, UK
M62 Course 2004
Aetiology and Pathology in
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 patternGenetic predisposition?
11 studies, 3616 Crohn’s / 3055 controls
Single mutation OR 2.7 [2.3 – 3.3]
Double mutationOR 20.5[11.9 – 35.4]
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
No association with
Protected against endotoxin challenge (iv)
Pauleau Mol Cell Biol 2003NOD2: knockout mouse
Early environmental factors:
At all ages
Diffuse changes: when the mucosa is ulcerated away,
diffuse, deeper ulceration occurs.
Catch: mucin is often strikingly well preserved.
UC after treatment
and basal plasma cells
CMV in UC intermittent but severe symptoms
Beware of superimposed infection
After immunosuppressive treatment.
May have only architectural distortion, =/-paneth cells,
may return to ‘normal’-review original biopsies ? Infection.
UC DALMs intermittent but severe symptoms
Guidelines for initial biopsy diagnosis of suspected chronic inflammatory bowel disease.
Jenkins D et al BSG group. J Clin Pathol 1997; February
Schiller KFR, Cockel R, Hunt RH, Warren BF. 2001
An atlas of gastrointestinal endoscopy and related pathology
Focal erosions and
Perineural chronic inflammation
Transmural inflammation in the form of lymphoid aggregates
Not contraindications to pouch surgery.
Courtesy of Dr Axel von Herbay
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.