Inflammatory Bowel Disease (IBD)

• Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn’s disease (CD), as well as diversion colitis, diverticular colitis, and colitis caused by radiation, drugs, infections, or ischemia.

Prevalence

• CD prevalence is approximately 27-106 per 100,000.
• UC prevalence is about 80-150 per 100,000.
• Highest prevalence is in Northern Europe and North America.

Etiology

• The precise cause of IBD remains unknown.
• Both conditions involve a Th1 cell-type inflammatory response in the gut.

Risk Factors

• Family history of IBD is the most significant independent risk factor, suggesting a genetic predisposition (e.g., CARD 15 gene).
• Environmental factors: Good domestic hygiene may be linked to CD development but not UC.
• Nutritional factors like high glucose intake may contribute.
• Smoking has contrasting effects: Protective against UC but increases the risk of CD.
• NSAID use and stress can play a role in IBD development.

Pathogenesis

• Involves a defective mucosal immune response, leading to an inappropriate reaction to luminal antigens.
• Gut bacteria stimulate an inflammatory response (via dendritic cells), resulting in a Th1 helper T cell response.
• Macrophages are also stimulated, leading to severe tissue damage and further inflammatory cell recruitment.

Ulcerative Colitis (UC)

• UC is an inflammatory disorder affecting the rectum and extending proximally in a continuous manner to involve varying extents of the colon.
• Backwash ileitis, inflammation of the distal terminal ileum, occurs in some instances.
• High incidence in the US, UK, and northern Europe, typically presenting in young adults and more commonly in females.
• Symptoms include rectal bleeding, diarrhea, and abdominal pain.

Crohn's Disease (CD)

• CD is a chronic inflammatory condition that can affect any part of the GI tract, from mouth to anus, with a predilection for the terminal ileum and ascending colon.
• Can affect one or multiple areas of the GI tract, with normal bowel segments in between (skip lesions).
• Incidence peaks at 15-30 years and again at 60 years.
• Th1 cells dominate the mucosa, producing Interferon Gamma (IFN-g) and IL-2.

Investigations for IBD

• Colonoscopy and biopsies of involved mucosa to check for ulceration.
• Stool analysis to check for parasites, Clostridium difficile toxin, and culture.
• Barium radiographs.
• CT scan.
• Capsule endoscopy.
• Plain X-ray if bowel obstruction or perforation is suspected.

Macroscopic Changes in CD

• Involved small bowel becomes thickened and narrowed (stenosis is common).
• Inflammation extends through all bowel layers (transmural), causing deep ulcers and fissures, resulting in a cobblestone appearance.
• Early signs include apthoid ulceration, which can progress to deeper ulcers.
• Fistulae can develop between bowel loops, or between the bowel and bladder/skin.

Macroscopic Changes in UC

• Mucosa appears reddened, inflamed, and bleeds easily.
• Severe disease shows extensive ulceration with inflammatory (pseudo) polyps.

Extra-Gastrointestinal Manifestations in IBD

• Joint complications are most common.
• Other problems can affect the eyes, skin, liver, and cause venous thrombosis.

Microscopic Changes in CD

• Transmural inflammation (through all layers of the bowel).
• Increase in chronic inflammatory cells.
• Lymphoid hyperplasia.
• Granulomas (50%).

Microscopic Changes in UC

• Superficial inflammation.
• Chronic inflammatory cell infiltrate in the lamina propria.
• Crypt abscesses.
• Goblet cell depletion.

Feature Comparison: UC vs. CD

• Depth of Inflammation: UC is mucosal, CD is transmural.
• Pattern of Disease: UC is continuous, CD has skip areas.
• Location: UC affects the colorectum, CD can affect the mouth to anus.
• Rectal Involvement: Usual in UC, less common in CD.
• Ileal Disease: Backwash ileitis in UC (15-20%), common in CD.
• Fistulas: Rare in UC, common in CD.
• Perianal Disease: Rare in UC, common in CD.
• Granulomas: Unlikely in UC, present in 50-60% of CD patients.
• Overt Bleeding: Usual in UC, less common in CD.
• Malnutrition: Unlikely in UC, more common in CD.
• Cancer Risk: Colorectal cancer in UC; colorectal and small bowel cancer in CD (depending on location).
• Tobacco Use: Protective in UC, harmful in CD.
• Radiology: Collar button ulcers in UC, String sign of Kantor in CD.

Diagnostic Difficulties

• Distinguishing between UC and CD impacts treatment, timing of surgery, prognosis, and disease course.
• Indeterminate colitis (IC) or Colitis of Undetermined Type and Etiology (CUTE) is diagnosed when differentiation is not possible, particularly in acute phases.
• Serological testing for anti-neutrophil cytoplasmic antibodies (ANCA) in UC and anti-Saccharomyces cerevisiae antibodies (ASCA) in CD can help.
• Sometimes, a diagnosis can only be made after examining a surgical colectomy specimen.

Crohn's Disease Presentation

• Symptoms depend on the disease location.
  • Upper GI involvement: Nausea, vomiting, low-grade fever, dyspepsia.
  • Small bowel obstruction: Anorexia, weight loss, loose stools.
  • Colonic Disease: Diarrhea, steatorrhea, passage of obvious blood.
  • Terminal ileum involvement: Anemia due to poor Vitamin B12 absorption.