Inflammatory Bowel Disease Overview

Inflammatory Bowel Disease (IBD)

• IBD is a chronic inflammation of the GI tract, cycling between remission and exacerbation.
• Classified as Crohn's disease or ulcerative colitis (UC).
• Affects approximately 1.3 million Americans, typically beginning in teenage years or early adulthood, with a second peak in the 6th decade.

Etiology and Pathophysiology

• Exact cause unknown; thought to be an autoimmune disorder with an overactive immune response to the intestinal tract.
• Likely triggered by environmental and bacterial factors in genetically susceptible individuals.
• Inflammation leads to tissue damage.
• Incidence varies geographically; high rates in Northern Hemisphere industrialized nations, urban areas, and those of White and Ashkenazic Jewish descent.
• Family history is a significant risk factor.
• Lifestyle factors (diet, smoking, stress) influence GI microbial flora and contribute to IBD development; high refined sugar, total fats, polyunsaturated fatty acids (PUFAs), and omega-6 fatty acids show association with increased risk; conversely, raw fruits/veggies, omega-3-rich foods, and fiber decrease risk.
• Use of NSAIDs, antibiotics, and oral contraceptives increase risk.

Genetic Link

• IBD is more common in family members, especially identical twins.
• Over 200 genes associated with IBD; different mutations linked to Crohn's, UC, or both.
• Genes involved in intestinal protection and immune system function (especially T cell maturation).
• Variations in genes may explain differing responses to therapies.
• Key genes in Crohn's include NOD2, ATG16L1, IL23R, and IRGM; involved in immune response to GI tract bacteria.
• NOD2 gene changes associated with ileum-affecting Crohn's disease in groups of northern European descent, impacting normal immune response.

Pattern of Inflammation

• Crohn's disease: affects any part of the GI tract (most common in distal ileum/proximal colon), with interspersed healthy tissue (skip lesions). Transmural inflammation (all layers of the bowel wall). Deep longitudinal ulcerations, creating cobblestone appearance. Strictures can cause obstructions. Higher risk for abscesses/peritonitis due to leaks through the entire wall. Fistulas common.
• Ulcerative colitis: colon and rectum are usually affected, inflammation starts in rectum and moves toward cecum with mild possible ileum involvement. Mucosal layer only is involved; minimal risk of fistulas/abscesses. Diarrhea with significant fluid/electrolyte loss is a common symptom. Breakdown of intestinal cells leads to protein loss. Mucosal inflammation creates pseudopolyps.

Clinical Manifestations

• Both Crohn's and UC involve chronic disorders with unpredictable exacerbations.
• Similar symptoms in both (diarrhea, weight loss, abdominal pain, fever, fatigue).
• Crohn's disease: common diarrhea and cramping abdominal pain; small intestine involvement leads to malabsorption/ weight loss; sometimes rectal bleeding.
• UC: primarily bloody diarrhea and abdominal pain (vary from mild lower abdominal cramping to severe acute pain); different severities based on stool frequency/blood/mucus content and systemic symptoms (fever, malaise, anemia, anorexia).

Complications

• IBD complications are local (GI tract) or systemic (extraintestinal).
• GI tract: hemorrhage, strictures, perforation (leading to peritonitis), abscesses, fistulas, Clostridium difficile infection (CDI), and toxic megacolon.
• Toxic megacolon is more common with UC. IBD increases risk of colorectal cancer (CRC), with higher risk in Crohn's for small intestinal cancer. Regular cancer screenings are important.
• Systemic: multiple sclerosis, ankylosing spondylitis, malabsorption, liver disease (like primary sclerosing cholangitis - necessitating liver function tests), and osteoporosis. Routine bone density scans are recommended.

Diagnostic Studies

• IBD diagnosis involves excluding similar conditions, differentiating between Crohn's and UC.
• Diagnostic tools identify disease severity and complications.
• Laboratory findings may include anemia from blood loss, high WBC count (suggestive of toxic megacolon or perforation), electrolyte imbalances (due to diarrhea, vomiting), and hypoalbuminemia (severe disease).
• Elevated inflammatory markers (ESR, CRP, WBC) signify inflammation.
• Stool tests detect blood, pus, and mucus, and infection.
• Imaging (double-contrast barium enema, small bowel series, ultrasound, CT, MRI) help diagnose.
• Colonoscopy enables full large intestine and sometimes distal ileum examination for inflammation, ulcerations, pseudopolyps, strictures and tissue biopsies.
• Capsule endoscopy may be necessary for small intestine involvement in Crohn's, as colonoscopies cannot reach this area.