What is the etiology of colitis?

Etiology of Colitis

Colitis has multiple etiologies including infectious agents, inflammatory bowel disease (IBD), medications, and genetic factors, with the consensus being that IBD-related colitis results from environmental triggers in genetically susceptible individuals. 1, 2

Major Categories of Colitis

1. Infectious Colitis

• Bacterial pathogens:
  • Clostridium difficile (most common healthcare-associated)
  • Campylobacter, Salmonella, Shigella, Escherichia coli (especially STEC)
  • Yersinia 1, 3, 4
• Transmission: Primarily fecal-oral route and ingestion of contaminated food/water 4
• Clinical features: Acute onset, bloody diarrhea, fever, abdominal pain, tenesmus 3
• Diagnostic approach: Stool culture, toxin assays (for C. difficile), inflammatory markers 3

2. Inflammatory Bowel Disease (IBD)

• Ulcerative Colitis (UC):

  • Characterized by diffuse mucosal inflammation limited to the colon
  • Continuous inflammation pattern
  • Lower genetic component compared to Crohn's disease
  • Higher risk of colorectal cancer 1, 2

• Crohn's Disease (CD):

  • Patchy, transmural inflammation that can affect any part of the GI tract
  • Stronger genetic component
  • Associated with higher risk of complications 1, 2

• Indeterminate Colitis (IC):

  • Approximately 5% of IBD patients have features of both UC and CD
  • Diagnosis based on overlapping features or absence of clear diagnostic pattern 1

3. Microscopic Colitis

• Types: Collagenous colitis and lymphocytic colitis
• Clinical presentation: Chronic watery (non-bloody) diarrhea
• Endoscopic appearance: Normal or near-normal
• Diagnosis: Distinct histologic pattern on biopsy 1
• Triggers: Medications (NSAIDs, PPIs, SSRIs, statins), particularly in susceptible individuals 2

Pathogenesis Factors

Genetic Factors

• Family history: Increases risk of IBD (incidence rate ratio 4.08 for first-degree relatives) 2
• Genetic mutations:
  • CARD15/NOD2 mutations associated with small intestinal CD in white populations
  • OCTN1, OCTN2, and DLG5 genes also implicated in CD 1
• Monogenic disorders: Over 40 monogenic defects can present with IBD-like intestinal inflammation 5

Environmental Triggers

• Infections: May trigger onset of IBD or cause disease flares 1
• Smoking:
  • Protective effect against UC but increases risk of CD
  • Ex-smokers have approximately 70% higher risk of developing UC 2
• Appendectomy: For confirmed appendicitis before adulthood reduces UC risk 2
• Medications: Can trigger microscopic colitis 2

Immunological Factors

• Dysregulated immune response: Failure of proper down-regulation of inflammation in the bowel wall 6
• Auto-immune processes: Self-perpetuating inflammatory cycle 6

Risk Factors for Colitis

• Age: Bimodal distribution with peaks in 10-40 years and >60 years 1
• Ethnicity: Higher incidence in certain groups (e.g., Ashkenazi Jews) 1, 6
• Immunosuppression: Increases risk of infectious and other forms of colitis 2
• Comorbidities: Including primary sclerosing cholangitis (PSC), which significantly increases colorectal cancer risk in IBD patients 2

Diagnostic Approach

• Laboratory tests: CBC, inflammatory markers, stool studies for pathogens and inflammatory markers 2
• Endoscopy with histology: Essential for differentiating between types of colitis 1, 2
• Clinical history: Recent travel, medication use, family history of IBD 2

Treatment Considerations

• Infectious colitis: Pathogen-specific antimicrobial therapy (except for STEC) 3
• Medication-induced colitis: Discontinuation of suspected triggering medication 2
• IBD: Anti-inflammatory agents, immunomodulators, biologics 7
• Antibiotics in IBD: May induce remission in active CD and UC through effects on gut microbiota 7

The multifactorial nature of colitis requires careful diagnostic evaluation to determine the specific etiology, which is essential for appropriate management and improved outcomes.