Inflammatory Bowel Disease¶
Chapter 337 | Part 10: Disorders of the Gastrointestinal System
KEY CLINICAL POINTS¶
- IBD includes ulcerative colitis (UC) and Crohn’s disease (CD), with global incidence rising in urbanized regions due to environmental factors.
- Genetic factors (e.g., NOD2, ATG16L1) and environmental triggers (diet, microbiome, smoking) interact to drive pathogenesis.
- Differential diagnosis includes infectious causes (e.g., C. difficile, TB) and non-IBD conditions like ischemic colitis or diverticulitis.
- Biologic therapies (anti-TNF, IL-12/23 inhibitors) are first-line for moderate-to-severe IBD, with surgical options for complications like strictures or fistulas.
- Pregnancy management requires careful medication selection (e.g., avoiding methotrexate) and endoscopic surveillance for dysplasia/cancer.
1. DEFINITION & OVERVIEW¶
Inflammatory bowel disease (IBD) encompasses ulcerative colitis (UC) and Crohn’s disease (CD), characterized by chronic inflammation of the gastrointestinal tract. IBD is a multifactorial condition involving genetic susceptibility, environmental triggers, and immune dysregulation. The disease spectrum includes both localized and transmural inflammation, with distinct clinical and histopathologic features.
Table 337-1: IBD Epidemiology¶
| UC | CD |
|---|---|
| Age of onset: 2nd-4th decades; 7th-9th decades | Age of onset: 2nd-4th decades; 7th-9th decades |
| Ethnicity: White > Black > Latinx > Asian | Ethnicity: White > Black > Latinx > Asian |
| Smoking: protective for UC, risk factor for CD | Smoking: risk factor for CD |
| Oral contraceptives: no increased risk for UC | Oral contraceptives: hazard ratio 2.82 for CD |
| Appendectomy: protective for UC | Appendectomy: modestly associated with CD |
| Monozygotic twins: 6-18% concordance for UC | Monozygotic twins: 38-58% concordance for CD |
1.1 Global Epidemiology¶
IBD prevalence is highest in North America (UC: 286/100,000; CD: 319/100,000), Europe (UC: 505/100,000; CD: 322/100,000), and Oceania. Incidence has increased in developing countries, with annual increases of 4-14% in Asia/Pacific regions. Urbanization and Western dietary patterns correlate with rising IBD rates.
1.2 Ethnic and Demographic Trends¶
Whites have highest prevalence; Latinx, Black, and Asian populations show increasing rates. Female-to-male ratios: UC (0.51-1.58), CD (0.34-1.65). Pediatric IBD (20-25% of cases) includes early-onset (VEO) and infantile IBD with genetic mutations (e.g., NOD2, ATG16L1).
2. EPIDEMIOLOGY¶
IBD affects 1-2% of the global population, with rising incidence in urbanized regions. The global prevalence is 0.3-0.5%, with higher rates in Western countries. Environmental factors (diet, hygiene, antibiotic use) and genetic predisposition interact to influence disease risk.
Table 337-2: Primary Genetic Disorders¶
| Name | Genetic Association | Phenotype |
|---|---|---|
| Turner’s syndrome | X chromosome deletion | UC and colonic CD |
| Wiskott-Aldrich syndrome | X-linked recessive | Colitis, immunodeficiency, thrombocytopenia |
| Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) | Loss of FoxP3 transcription factor | UC-like autoimmune enteropathy |
| Deficient IL-10/IL-10R | IL-10 receptor dysfunction | Severe, refractory IBD |
2.1 Incidence Trends¶
Annual incidence rates: CD (4-14% increase), UC (4-10% increase). Asia-Pacific regions show highest incidence (1.5-3.6 cases/100,000). Urbanization and Western dietary patterns correlate with rising IBD rates.
2.2 Risk Factors¶
Smoking: protective for UC, risk factor for CD. Appendectomy: protective for UC. Oral contraceptives: increased risk for CD. Genetic factors (NOD2, ATG16L1, IL23R) contribute to susceptibility.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
IBD results from complex interactions between genetic predisposition, environmental triggers, and immune dysregulation. The gut microbiome and host immune responses play critical roles in disease pathogenesis.
Table 337-3: Genetic Loci in IBD¶
| Locus | Associated Gene | Function |
|---|---|---|
| IBD1 | NOD2 | Nucleotide-binding oligomerization domain 2 |
| IBD2 | ATG16L1 | Autophagy-related protein 16-like 1 |
| IBD3 | IL23R | Interleukin 23 receptor |
| IBD4 | IRGM | Immunity-related GTPase family M |
3.1 Genetic Factors¶
Genetic loci include Norpion (NOD2), ATG16L1, IL23R, and IRGM. Mutations in these genes disrupt innate immunity and autophagy, increasing susceptibility to inflammation.
3.2 Microbiome and Immune Dysregulation¶
Dysbiosis and altered gut microbiota contribute to inflammation. The microbiome interacts with host genetics to influence disease severity. Immune responses involving Th1/Th17 cells and cytokines (TNF- α , IL-12/23) drive inflammation.
3.3 Environmental Triggers¶
Diet, smoking, antibiotic use, and gut permeability influence disease development. Western diets high in processed foods and low in fiber are associated with increased risk.
4. CLINICAL FEATURES¶
IBD presents with diverse symptoms depending on disease location and extent. UC typically involves continuous rectal involvement, while CD can affect any GI tract segment with transmural inflammation.
Table 337-4: Montreal Classification for UC¶
| Location | Behavior | Coprology |
|---|---|---|
| Proctitis | Continuous | Mucous |
| Left-sided colitis | Continuous | Mucous |
| Pancolitis | Continuous | Mucous |
| Proctosigmoiditis | Continuous | Mucous |
| Proctitis | Patchy | Mucous |
| Left-sided colitis | Patchy | Mucous |
| Pancolitis | Patchy | Mucous |
4.1 Ulcerative Colitis¶
Continuous inflammation of the colon, starting in the rectum. Symptoms include diarrhea, rectal bleeding, urgency, and abdominal pain. Extraintestinal manifestations include arthritis, skin lesions, and uveitis.
4.2 Crohn’s Disease¶
Transmural inflammation of any GI tract segment. Presents with abdominal pain, diarrhea, weight loss, and perianal disease. Complications include strictures, fistulas, and abscesses.
4.3 Complications¶
Toxic megacolon, perforation, strictures, fistulas, malnutrition, and increased cancer risk (especially in UC).
5. INVESTIGATIONS¶
Diagnostic workup includes endoscopy, imaging, and laboratory tests to confirm IBD and differentiate from other conditions.
Table 337-5: Diagnostic Criteria for IBD¶
| Criteria | UC | CD |
|---|---|---|
| Location | Continuous rectal involvement | Any GI tract segment |
| Behavior | Continuous inflammation | Transmural inflammation |
| Endoscopic appearance | Continuous mucosal inflammation | Skip lesions, strictures |
| Criteria | UC | CD |
|---|---|---|
| Histology | Cryptitis, crypt abscesses | Granulomas, transmural inflammation |
5.1 Endoscopic Findings¶
UC shows continuous mucosal inflammation with pseudopolyps and ulceration. CD presents with transmural inflammation, strictures, and fistulas.
5.2 Imaging¶
CT/MRI for CD to assess bowel wall thickening, strictures, and fistulas. Barium enema for UC to show continuous inflammation.
5.3 Laboratory Tests¶
Elevated CRP/ESR, anemia, and electrolyte imbalances. Calprotectin in stool helps differentiate IBD from infection.
6. MANAGEMENT¶
Treatment is tailored to disease severity, location, and complications. Includes medical therapy, biologics, and surgery for refractory cases.
Table 337-6: 5-ASA Preparations¶
| Preparation | Formulation | Delivery | Dosing |
|---|---|---|---|
| Sulfasalazine | Sulfapyridine-5-ASA | Colon | 3-6g (acute), 2-4g (maintenance) |
| Balsalazide | Aminobenzoyl-b-alanine–5 -ASA | Colon | 6.75-9g |
| Mesalamine (Delzicol) | Ethylcellulose microgranules | Distal ileum-colon | 2.4-4.8g (acute), 1.6-4.8g (maintenance) |
| Mesalamine (Lialda) | Multi-Matrix System | Ileum-colon | 2.4-4.8g |
6.1 Medical Therapy¶
5-ASA for mild-to-moderate UC. Corticosteroids for acute flares. Immunosuppressants (azathioprine, methotrexate) for maintenance. Biologics (anti-TNF, IL-12/23 inhibitors) for refractory disease.
6.2 Biologic Therapies¶
Anti-TNF agents (infliximab, adalimumab) are first-line for moderate-to-severe IBD. IL-12/23 inhibitors (ustekinumab) and integrin inhibitors (vedolizumab) are alternatives. JAK inhibitors (tofacitinib) are used for refractory cases.
6.3 Surgical Indications¶
Total proctocolectomy with ileostomy for UC with dysplasia/cancer. Resection for CD with strictures/fistulas. IPAA for selected UC patients.
7. SPECIAL CONSIDERATIONS¶
Management of IBD in pregnancy, cancer risk, and drug interactions require careful planning.
Table 337-7: Extraintestinal Manifestations¶
| Category | Clinical Course | Treatment |
|---|---|---|
| Rheumatologic Disorders | Peripheral arthritis (asymmetric, migratory) | Reduce bowel inflammation |
| Ankylosing Spondylitis | Spinal involvement, HLA-B27 positive | Physical therapy, steroids, anti-TNF |
| Ocular Disorders | Uveitis, episcleritis | Topical steroids, systemic steroids |
| Hepatobiliary Disorders | Primary sclerosing cholangitis (PSC) | Cholecystectomy, ERCP, antifibrotic agents |
7.1 Pregnancy¶
Quiescent IBD has normal fertility. Avoid MTX and anti-TNF agents in first trimester. Use corticosteroids and 5-ASA safely. Cesarean delivery may be needed for anorectal disease.
7.2 Cancer Risk¶
UC patients with >10 years of disease have 1.5-2x higher CRC risk. CD patients with extensive disease have increased risk of colorectal and small bowel cancer. Endoscopic surveillance recommended.
7.3 Drug Interactions¶
Anti-TNF agents increase infection risk. JAK inhibitors and biologics may increase cancer risk. Avoid corticosteroids in elderly patients.