1. Anna Giles, Surgical Registrar POWH
Crohn’s Disease
Anna Giles, Surgical Registrar POWH

2. Orientation to Crohn’s
A chronic transmural inflammatory process that can affect the GIT anywhere from mouth to anus +/- extra-intestinal manifestations
Prevalence of 0.1% (5-6/100,000) and increasing
Females > males
Symptoms include diarrhoea (70-90%), weight loss (65-75%), abdominal pain (45-65%), rectal bleeding (30%) and perianal disease (10%)

3. Proposed Aetiological Factors in Crohn’s and UC -1
Interplay between genetic and environmental factors
Smoking and OCP
Smoking increases the relative risk of Crohn’s by times (cf. UC where smoking has a protective effect)
OCP may be associated with a small increase in risk but no effect on disease activity. Data conflicting and most information relates to Crohn’s
NSAIDS
Use may be associated with IBD in humans
Diet
No causative dietary factor identified
Lactose intolerance can accompany UC, but this is rare

4. Proposed Aetiological Factors in Crohn’s and UC -2
Infection
Mycobacterium paratuberculosis causes a granulomatous inflammatory disorder in the intestine of cattle (Johne’s disease)
Maybe Crohn’s is the human form of this disease
Conflicting evidence
Nil evidence to suggest that measles virus infection or vaccination may cause the granulomatous vasculitis seen in Crohn’s
Some patients with UC have a history of infective proctocolitis.

5. Proposed Aetiological Factors in Crohn’s and UC -3
Genetic
Likely that IBD results from a genetic predisposition to an abnormal interaction between the immune system and environmental factors
2-22% of patients with Crohn’s have a FDR with IBD
Greater concordance in monozygotic (36%) compared with dizygotic (4%) twin pairs
Early onset disease has a higher familial prevalence rate
Clinical patterns of IBD in affected parent/child and sibling pairs are concordant for each of disease type, extent and extra-intestinal manifestations in large part

6. Proposed Aetiological Factors in Crohn’s and UC -4
The CARD theory
Crohn’s and UC seem polygenetic disorders with some shared susceptibility genes
9 loci (IBD1-9) have been implicated in susceptibility to IBD
All variants of IBD1 (caspase recruitment domain family member 15 or CARD15) gene have generated interest in regard to Crohn’s
CARD15 encodes NOD2 which is associated with ileal disease and displays ethnic variation
CARD15 variants appear to impair the innate immune system at mucosal level, limiting the ability of the intestinal epithelium to deal with pathogens or components of them in the gut microbiota

7. Histological and Macroscopic appearance of Crohn’s - 1
Distribution
Small bowel alone 30-35%
Colon alone 25-35%
Small bowel and colon 30-50% (usually ileocolic)
Perianal lesions >50% (a strong clue to Crohn’s)
Stomach and duodenum 5% (minor subclinical abnormalities in 50%)
Skip lesions (areas of disease separated by normal bowel) strongly suggest Crohn’s

8. Histological and Macroscopic appearance of Crohn’s - 2
Stiff, thick walled segment of bowel with fat wrapping
Can be fibrinous exudate and adhesions on the serosal surface, reflecting transmural inflammation
“Cobblestone” appearance – narrow serpiginous ulcers with intervening islands of oedematous mucosa
May be fistulas associated with the ulceration
Inflammatory polyps frequently found in the involved colon
Strictures can vary from 1-30cm in length and can be multiple and associated with obstruction and proximal dilatation
Fistulas, sinuses and abscesses often present in the ileocaecal region and can communicate with other loops of bowel, stomach, bladder, vagina, skin or intra-abdominal abscess cavities

9. Histological and Macroscopic appearance of Crohn’s - 3
Microscopy
Full thickness of the bowel wall is involved
Neutrophilia, then mucosal lymphoid aggregates then overlying ulceration
Relative preservation of goblet cell mucin
Connective tissue changes occur in all layers of the bowel wall as the disease progresses – submucosal fibrosis and muscularisation
Three diagnostic “hallmarks”
Deep non caseating granulomas
Intralymphatic granulomas
Granulomatous vasculitis

10. Histological and Macroscopic appearance of UC
Inflammation is confined to the large intestine
The rectum is always involved
The inflammation is diffuse without intervening normal mucosa and extends proximally a variable length
“Backwash itelitis” occurs only in cases with colonic extention to the ileocaecal junction
At endoscopy
Loss of vascular pattern – opaque appearance to mucosa
“granular” appearance
Erythema, contact bleeding, ulceration
Mucosal regeneration nodules or pseudopolyps may be seen

11. Histological and Macroscopic appearance of UC -2
Microscopically
Mucosal thickening
Infiltration of lamina propria with neutrophils, plasma cells, lymphocytes, eosinophils and mast cells
Goblet cell depletion
Crypt abscesses – the number correlates with the severity of the disease
Loss of crypts
Branching of crypts associated with attempts at regeneration

12. Summary slide UC Crohn’s Distribution Rectum Anal disease
Malignant risk
Intestinal fistula
Stricture (non neoplastic)
Colon and rectum
Involved
Rare
10% at 20 years
Never
GIT
Often spared
Common
Probably similar (LB)
Bowel wall involvement
Granulomas
Mucous secretion
Fissuring
Crypt abscesses
Mucosa and submucosa
None
Impaired
Absent
Full thickness
60-70%
Slightly impaired

13. Extraintestinal Manifestations of Crohn’s and UC-1
In Crohn’s, these are more common in association with Crohn’s colitis than isolated small bowel disease
In UC, up to one third of patients will develop at least one extra alimentary manifestation during the course of the illness
In general
Divided into related or not related to disease activity
Arthropathy is the commonest extra-alimentary manifestation
AS does not respond to proctocolectomy
PSC is more often seen in UC than Crohn’s and there is no relation between duration of disease and disease activity and it progresses to liver failure
Erythema nodusum is the commonest cutaneous manifestation of IBD - it occurs more often in Crohn’s and is activity related. Proctocolectomy is associated with healing in about 50% of cases.
Uveitis is rare and not related to disease activity; episcleritis is activity related and occurs more often in Crohn’s
Extraintestinal (and systemic manifestations) become more important in the paediatric population – about 15% have arthralgia and arthritis that precedes bowel symptoms by months or years

14. Extraintestinal manifestations of Crohn’s and UC-2
Related to disease activity
Aphthous ulceration (10%)
Erythema nodosum (5-10%)
Pyoderma gangrenosum (0.5%)
Acute arthropathy (20% in UC; 6-12% in Crohn’s)
Eye complications (3-10%)
Amyloidosis (1%)
Unrelated to disease activity
Sacroiliitis (10-15%)
Ankolosing spondylitis (1-2%)
Primary sclerosing cholangitis (rare)
Chronic active hepatitis (2-3%)
Gallstones (15-30%)
Renal calculi (5-10%)