What causes pseudomembranous colitis?

Causes of Pseudomembranous Colitis

Pseudomembranous colitis is primarily caused by Clostridioides difficile (C. difficile) infection, which typically occurs following antibiotic use that disrupts the normal intestinal flora, allowing C. difficile to proliferate and produce toxins that damage the colonic mucosa. 1

Pathophysiology

Pseudomembranous colitis develops through the following mechanism:

1. Disruption of normal gut flora:

   • Most commonly due to antibiotic therapy
   • Almost any antibiotic can cause this condition, but clindamycin, cephalosporins, and ampicillin/amoxicillin are most frequently implicated 2
   • Even vancomycin and metronidazole (used to treat C. difficile) can paradoxically cause pseudomembranous colitis when administered parenterally 2

2. C. difficile proliferation:

   • When normal gut flora is disrupted, C. difficile can overgrow in the colon
   • C. difficile produces toxins (primarily toxin A and toxin B) that damage the colonic mucosa 3
   • These toxins have cytopathic and hypersecretory effects on the intestinal mucosa 2

3. Formation of pseudomembranes:

   • The toxins cause inflammation and damage to the colonic epithelium
   • This leads to the formation of characteristic yellowish-white plaques (pseudomembranes) on the colonic mucosa 4
   • These pseudomembranes consist of fibrin, mucus, inflammatory cells, and cellular debris

Risk Factors

• Antibiotic exposure (primary risk factor) 5
• Advanced age (elderly patients are more susceptible) 2
• Hospitalization or healthcare facility residence (nosocomial acquisition) 2
• Immunosuppression
• Recent gastrointestinal surgery
• Prolonged hospital stay
• Use of proton pump inhibitors (PPI) 1

Clinical Manifestations

• Diarrhea (≥3 liquid stools in 24 hours) - primary symptom 5
• Abdominal pain and cramping 5
• Fever (body temperature >38.5°C) 5
• Leukocytosis (>15 x 10^9/L) 5
• Hypoalbuminemia 2
• In severe cases: toxic megacolon, ileus, peritonitis, or septic shock 5

Diagnostic Considerations

• Diagnosis requires diarrhea plus either:

  • Positive stool test for toxigenic C. difficile or its toxins
  • Colonoscopic/histopathological findings demonstrating pseudomembranous colitis 5

• Endoscopy may reveal characteristic pseudomembranes, but these are only present in 71% of severe cases and 23% of mild cases 5

• Timing of onset can be during antibiotic treatment or up to 2-3 weeks after completion 5

Important Clinical Pearls

1. Pseudomembrane formation requires neutrophils - in neutropenic patients, typical pseudomembranes may not be visible despite active C. difficile infection 1

2. Atypical presentations - some patients, especially postoperative ones, may present with ileus or toxic megacolon without diarrhea 5

3. Diagnostic imaging - CT findings may include colonic wall thickening, dilation, peri-colonic stranding, "accordion sign," and "double-halo sign" 1

4. Recurrence risk - C. difficile infection has a high recurrence rate (20-50%) after initial treatment 3

5. Non-C. difficile causes - While rare, other infectious agents can occasionally cause pseudomembranous colitis, including cytomegalovirus (CMV) in immunocompromised patients 1

By understanding the primary cause and pathophysiology of pseudomembranous colitis, clinicians can better diagnose and manage this potentially serious condition, which if left untreated can lead to severe complications including hypovolemic shock, toxic megacolon, intestinal perforation, and death.