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

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%)

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 2-2.4 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

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.

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

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

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

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

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

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

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

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

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

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%)