Inflammatory Bowel Disease

Description

• Inflammatory bowel disease (IBD) includes two separate clinical entities: ulcerative colitis (UC) and Crohn disease (CD). UC and CD are both uncontrolled immune-mediated inflammatory responses.
• UC: relapsing and remitting course; inflammation is limited to mucosal layer. UC always involves the colon (spectrum of proctitis > left-sided colitis > pancolitis) ± extracolonic manifestations. Hallmarks: bloody diarrhea and abdominal pain
• CD: Transmural inflammation involving any part of alimentary canal, commonly affects small bowel (80% of cases), almost always involves the terminal ileum. Hallmarks: skip lesions (spared areas of inflammation), fibrosis/strictures, intra-abdominal abscesses, and fistulas

Epidemiology

Incidence

• Approximately 1.5 million North Americans are affected with IBD; increasing incidence over time, specifically in developed countries (1)
• CD—20.2/100,000 person-years in North America and 12.7/100,000 person-years in Europe
• UC—19.2/100,000 person-years in North America and 24.3/100,000 person-years in Europe

Prevalence
Increasing; Europe > Americas

• CD—319/100,000 persons in North America and 322/100,000 persons in Europe
• UC—249/100,000 in North America and 505/100,000 in Europe

Etiology and Pathophysiology

• Pathogenesis not well understood. Multifactorial: genetic susceptibility; gut flora dysbiosis; external environment/geography; lifestyle AND diet; alterations in immune response
• High levels of HLA II/activated macrophages secrete increased proinflammatory cytokines (IL-1, 6, 8 and TNF-α) in conjunction with decreased production of downregulatory cytokines (IL-2, 10 and TNF-β) (1).

Genetics
There are 163 IBD-associated gene loci (110 for both UC and CD, 30 CD-specific, and 23 UC-specific).

Risk Factors

• Cigarette smoking doubles risk of CD (1).
• Age—bimodal peaks for UC (larger peak at 30 to 40 years old and smaller peak 60 to 70 years old); CD diagnosis peaks in 3rd decade (1).
• Alterations in gut microbiome; disruption of intestinal mucosa
• Diets high in sugar, omega-6 fatty acids, unsaturated fatty acids, and meat may be risk factors (1).
• Family history/genetics; up to 15% of patients also have a first-degree relative with IBD.
• More often in Ashkenazi Jews; less often in African American or Hispanic populations

General Prevention

No prevention of primary disease. Treatment focus is prevention of remission and comorbid conditions.

Commonly Associated Conditions

• Extraintestinal manifestations: erythema nodosum, pyoderma gangrenosum, psoriasis, episcleritis, uveitis, scleritis, ankylosing spondylitis, sacroiliitis, osteoporosis, nephrolithiasis, deep venous thrombosis, primary sclerosing cholangitis ± cirrhosis, cholangiocarcinoma, chronic bronchitis, bronchiectasis, malabsorption, vitamin deficiency
• Metastatic CD (MCD), colorectal cancer (CRC)