Tutorial 14: Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a group of chronic relapsing inflammatory conditions of the gastrointestinal tract. The two principal forms are Crohn's disease (CD) and ulcerative colitis (UC). Together they affect approximately 0.3% of Western populations, with peak incidence in the second to third decades of life. The aetiology involves complex interactions between genetic susceptibility (over 200 susceptibility loci identified, including NOD2 in Crohn's disease), environmental triggers (diet, gut microbiome alterations, smoking, antibiotics), and dysregulated immune responses in a genetically predisposed host.

Crohn's disease can affect any part of the gastrointestinal tract from mouth to anus, but most commonly involves the terminal ileum and ileocaecal region. The inflammation is transmural (involving all layers of the bowel wall) and discontinuous — segmental involvement with normal intervening "skip lesions" separating areas of disease. Characteristic macroscopic features include: "cobblestone" mucosal appearance (intersecting linear fissuring ulcers separated by oedematous mucosa), "fat wrapping" (mesenteric fat encroaches onto the bowel wall), stricture formation (transmural fibrosis → luminal narrowing → obstructive symptoms), and sinus tracts — infected tracts leading from deep-seated inflammation and discharging pus to adjacent structures or the skin surface. Fistulae occur when transmural inflammation creates pathological connections between the bowel and adjacent organs or skin (entero-enteric, entero-vesical causing pneumaturia, entero-cutaneous, perianal). Histologically: non-caseating granulomas are found in the bowel wall and mesenteric lymph nodes in approximately 60% of cases; these are pathognomonic of Crohn's disease when present. The inflammatory infiltrate includes lymphoid aggregates (collections of lymphocytes and plasma cells) throughout all layers. Crypts are relatively preserved compared to UC.

Ulcerative colitis involves only the colon and rectum, beginning at the rectum and extending continuously proximally. The inflammation is confined to the mucosa and submucosa — it is never transmural. Macroscopic features: diffuse mucosal erythema, oedema, granularity, and fragility; in active disease, mucosal ulceration and pseudopolyps (islands of regenerating mucosa between ulcerated areas) are seen. There is no cobblestoning, no skip lesions, no fistulae, no transmural involvement. Histologically: crypt architectural distortion (branching, shortening, atrophy of crypts) is a hallmark of chronicity; active disease shows cryptitis (neutrophils invading crypt epithelium) and crypt abscesses (neutrophils within the crypt lumen). Goblet cell depletion is characteristic.

Complications of IBD. Crohn's: obstruction (strictures), fistulae, abscesses, malabsorption (especially terminal ileum disease → B12 and fat-soluble vitamin deficiency), bile salt malabsorption → cholesterol gallstones and oxalate kidney stones, short bowel syndrome post-resection. UC: toxic megacolon (life-threatening dilatation of the colon from transmural inflammation in a severe attack — risk of perforation), primary sclerosing cholangitis (PSC — associated with UC in ~5% of patients), and significantly increased risk of colorectal adenocarcinoma (risk proportional to duration and extent of disease; surveillance colonoscopy recommended from 8–10 years).

Extra-intestinal manifestations (EIM) affect both CD and UC: joints (seronegative arthropathy — peripheral arthritis mirroring bowel disease activity; axial arthritis independent of bowel activity), skin (erythema nodosum — tender red nodules on shins, associated with disease activity; pyoderma gangrenosum — ulcerating necrotic skin lesions), eye (uveitis, episcleritis), liver (PSC — predominantly UC; autoimmune hepatitis — CD). PSC is characterised by progressive fibrosis of intrahepatic and extrahepatic bile ducts, causing cholestatic jaundice and dramatically increased risk of cholangiocarcinoma.

Treatment: 5-aminosalicylates (mesalazine) are effective in mild-moderate UC but have limited efficacy in CD. Corticosteroids (prednisolone) induce remission in moderate-severe flares. Immunomodulators (azathioprine, 6-mercaptopurine) maintain remission. Anti-TNF biologics (infliximab, adalimumab) are effective in moderate-severe CD and UC. Surgery: UC is potentially curable by proctocolectomy (total colectomy with ileal pouch-anal anastomosis — IPAA); CD surgery addresses complications (strictures, abscesses, fistulae) but is not curative.