What causes colitis?

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Causes of Colitis

Colitis is primarily caused by environmental triggers (infections, drugs, or other agents) in genetically susceptible individuals, with different types having distinct pathophysiological mechanisms. 1

Types and Causes of Colitis

Inflammatory Bowel Disease (IBD)

  • Ulcerative Colitis (UC)

    • Environmental triggers in genetically susceptible individuals 1
    • Genetic component present but weaker than in Crohn's disease 1
    • Smoking paradoxically decreases risk (opposite effect compared to Crohn's) 1
    • Characterized by superficial mucosal ulceration limited to the colon 2
    • Affects the colon in a retrograde and continuous fashion starting from the rectum 2

  • Crohn's Disease (Colonic form)

    • Stronger genetic component than UC 1
    • Smoking increases risk 1
    • Characterized by patchy, transmural inflammation 1
    • Can affect any part of the gastrointestinal tract 1
    • Mutations in CARD15/NOD2 gene (Chr 16) associated with small intestinal Crohn's in white populations 1

Microscopic Colitis

  • Medication-induced triggers:

    • Non-steroidal anti-inflammatory drugs (NSAIDs) 3
    • Proton pump inhibitors (PPIs) 3
    • Selective serotonin reuptake inhibitors (SSRIs) 3
    • Statins 3

  • Risk factors:

    • Female sex, age ≥50 years 3
    • Coexistent autoimmune disease 3, 4
    • History of nocturnal or severe watery diarrhea 3

Immune Checkpoint Inhibitor (ICPi) Colitis

  • Caused by immune checkpoint inhibitor therapy 1
  • Often affects descending colon more than other parts 1
  • Histologically shows more inflammatory changes than classic IBD 1
  • Characterized by marked mixed inflammatory cell infiltrates 1

Infectious Colitis

  • Common pathogens to exclude:
    • Clostridium difficile (particularly in healthcare settings) 1
    • Cytomegalovirus (especially in immunocompromised patients) 1
    • Other bacterial, parasitic, and viral pathogens 1

Pathophysiological Mechanisms

Immune-Mediated Processes

  • Loss of tolerance against indigenous enteric flora is the central event in IBD pathogenesis 5
  • Abnormalities in humoral and cell-mediated immunity 5
  • Enhanced reactivity against intestinal bacterial antigens 5
  • Defects in regulatory T-cell function 5
  • Excessive stimulation of mucosal dendritic cells 5

Inflammatory Pathways

  • NF-κB pathway involvement 6
  • PI3K/Akt signaling pathway 6
  • JAK/STAT signaling pathway 6

Autoimmune Components

  • Presence of serum and mucosal autoantibodies against intestinal epithelial cells 5
  • Perinuclear antineutrophil cytoplasmic antibodies (pANCA) common in UC 5
  • Antibodies against Saccharomyces cerevisiae (ASCA) frequently found in Crohn's disease 5

Risk Factors for Opportunistic Infections in IBD

  • Immunosuppressive treatments (particularly in combination) 1
  • Malnutrition and obese BMI 1
  • Comorbidities 1
  • Active disease 1
  • Older age 1
  • Combination therapies (especially thiopurines plus steroids or thiopurines plus steroids plus infliximab) 1

Clinical Evaluation for Suspected Colitis

Key History Elements

  • Onset of symptoms, rectal bleeding, stool consistency and frequency 1
  • Urgency, tenesmus, abdominal pain, incontinence, nocturnal diarrhea 1
  • Recent travel, possible infectious exposures 1
  • Medication history (antibiotics, NSAIDs, immunosuppressants) 1, 3
  • Smoking status 1
  • Family history of IBD or colorectal cancer 1

Initial Investigations

  • Full blood count, inflammatory markers (CRP, ESR) 1
  • Electrolytes and liver function tests 1
  • Stool samples for microbiological analysis (including C. difficile toxin) 1
  • Faecal calprotectin (accurate marker of colonic inflammation) 1
  • Endoscopy with histological analysis 1

Important Clinical Considerations

  • No single "gold standard" exists for diagnosing colitis - diagnosis is established by clinical, laboratory, imaging, and endoscopic parameters 1
  • Infectious causes must always be excluded before confirming inflammatory colitis 1
  • Autoimmune diseases are significantly associated with microscopic colitis (22% vs 11% in controls) 4
  • Combination immunosuppressive therapies significantly increase risk of opportunistic infections 1
  • Microscopic colitis can coexist with other conditions like bile acid diarrhea 3

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

3
Guideline

Microscopic Colitis Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

5
Research

Inflammatory bowel disease: autoimmune or immune-mediated pathogenesis?

Clinical & developmental immunology, 2004

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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