Inflammatory Bowel Disease Epidemiology

IBD Pathogenesis

• Targeted disruption of genes for T-cell receptor and cytokine IL-2 in mice results in GI tract disease resembling ulcerative colitis

Neonatal Period

• Patterning activity of the immune system during the neonatal period influences immune responses in adulthood
• Early exposure to intestinal microbiota may contribute to IBD pathogenesis
• Maternal effects, including transmission of intestinal microbiota, are thought to contribute to GI disease

Crohn's Disease

• Clinical manifestations:
  • Intermitent attacks of diarrhea, fever, and abdominal pain
  • 20% of patients present acutely with RLQ pain, fever, and bloody diarrhea
  • Periods of active disease are interrupted by asymptomatic periods
  • Disease reactivation can be associated with physical or emotional stress, dietary items, and cigarette smoking
  • Iron deficiency anemia can occur due to blood loss in colonic disease

Epidemiology

• Exact causes of IBD are unknown
• Hygiene hypothesis suggests that changes in gut microbiome composition contribute to IBD
• Some mucosa-associated microbes trigger persistent inflammation in susceptible hosts
• Other potential explanations include preservatives in processed foods inducing low-grade mucosal damage

IBD Pathogenesis

• Combination of genetic risk and environmental factors contributes to IBD
  • Genetic risk includes abnormalities in immune regulation, host-microbiome interactions, and epithelial barrier functions
  • Environmental factors include pathogenic microorganisms, dietary factors, smoking, and defective immune responses

Crohn's Disease Pathophysiology

• Defective modulation of inflammatory responses to dietary and microbial antigens may contribute to uncontrolled inflammation
• Mice lacking interleukin-10 develop spontaneous intestinal inflammation, which can be reduced by monoclonal antibodies to tumor necrosis factor alpha (TNFa)

Complications

• Frequent complications include perforation, fistula formation, abscess formation, and small intestinal obstruction
• Fibrosing strictures, particularly of the terminal ileum, are common and require surgical resection
• Fistulae can develop between loops of bowel and involve the urinary bladder, vagina, and abdominal or perianal skin

Extraintestinal Manifestations

• Cutaneous nodules formed by granulomas
• Uveitis, iritis
• Migratory polyarthritis, sacroileitis, ankylosing spondylitis
• Erythema nodosum, cutaneous granulomas
• Autoimmune chronic active hepatitis, sclerosing cholangitis
• Clubbing of the fingertips
• Renal disorders, especially nephrolithiasis
• Amyloidosis