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Pseudomembranous colitis: C. difficile toxins and the volcano lesion

  • Lesion

After antibiotics disturb the normal gut bacteria, C. difficile overgrows and its toxins coat the colon with grey-yellow plaques.

Updated

What it is

Pseudomembranous colitis is generally caused by Clostridioides (formerly Clostridium) difficile and is also called antibiotic-associated colitis. Antibiotics disrupt the colonic microbiota, letting C. difficile overgrow. Its toxins A and B glucosylate small GTPases such as Rho, collapsing the cytoskeleton, opening tight junctions and killing epithelial cells; neutrophil-rich exudate erupts from injured crypts. Hospitals are the main reservoir.

Structure

  • Gross: grey-yellow plaques on a red mucosa, mostly in the colon.
  • Micro: denuded surface, neutrophils in the superficial lamina propria, fibrin thrombi in capillaries.
  • Mushroom- or volcano-shaped exudate from crypts spreading to form the pseudomembrane.

Step by step

  1. Antibiotics reduce the diversity of the colonic microbiota.
  2. C. difficile spores germinate and the organism overgrows.
  3. Toxins A and B inactivate Rho GTPases in epithelial cells.
  4. The cytoskeleton and tight junctions fail; cells die and cytokines are released.
  5. Neutrophils and fibrin pour out of crypts and coalesce into pseudomembranes.

Clinical notes

  • Fever, leukocytosis, cramps and watery diarrhoea, usually not grossly bloody.
  • Hypervirulent strains and up to two in five recurrence rates make prevention and hand hygiene essential.

Test yourself

Think of the answer, then tap the question to see it.

How do C. difficile toxins injure colonic epithelium?

They inactivate small GTPases such as Rho, disrupting the cytoskeleton and tight junctions and causing cell death and inflammation.

What is the volcano lesion?

A plume of neutrophils, mucus and fibrin erupting from a damaged crypt, which coalesces into pseudomembranes.

Are pseudomembranes specific to C. difficile?

No; ischaemia and necrotizing infections can also form them, but volcano lesions in the right setting are characteristic.

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: About C. diff (Centers for Disease Control and Prevention, 2024).

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Representative model, for educational purposes only.