Diagnosing a condition with abdominal pain, nausea, diarrhea
Pseudomembranous Colitis: Causes, Pathophysiology, Diagnosis, and Management
Introduction
Pseudomembranous colitis (PMC) is an inflammatory condition of the colon, most commonly caused by an overgrowth of Clostridioides difficile (formerly Clostridium difficile), a Gram-positive, spore-forming bacterium. The disease is characterized by the presence of pseudomembranes—yellowish plaques composed of fibrin, inflammatory cells, and necrotic epithelial cells—lining the colonic mucosa.
While PMC is most often associated with recent antibiotic use, it can also occur in immunocompromised patients, after gastrointestinal surgery, or in individuals with disrupted gut microbiota. Without timely intervention, it can progress to severe complications such as toxic megacolon, perforation, and sepsis.
Etiology
The primary cause of pseudomembranous colitis is infection by C. difficile. This bacterium can exist harmlessly in the intestinal tract of some individuals but becomes pathogenic under certain conditions.
Common causes and risk factors include:
- Antibiotic therapy: Especially broad-spectrum antibiotics such as clindamycin, ampicillin, cephalosporins, and fluoroquinolones.
- Hospitalization: Prolonged stays increase exposure risk.
- Advanced age: Reduced immune resilience.
- Immunosuppression: From diseases like HIV/AIDS or therapies such as chemotherapy and corticosteroids.
- Gastrointestinal surgery: Alters gut flora balance.
- Use of proton pump inhibitors (PPIs): May increase susceptibility by altering gastric acidity.
Pathophysiology
PMC develops when the normal gut microbiota is disrupted, often due to antibiotics. This reduction in microbial diversity allows C. difficile spores, which resist antibiotic destruction, to germinate and proliferate.
The bacterium produces two main exotoxins:
- Toxin A (Enterotoxin): Increases intestinal permeability, stimulates secretion, and causes inflammation.
- Toxin B (Cytotoxin): Directly damages colonic epithelial cells by depolymerizing actin filaments.
The combined effects lead to:
- Epithelial cell death.
- Inflammatory exudation of fibrin, mucus, and neutrophils.
- Formation of characteristic pseudomembranes on the mucosal surface.
Clinical Features
Symptoms vary in severity from mild diarrhea to fulminant colitis.
Typical signs and symptoms include:
- Profuse watery diarrhea (often foul-smelling)
- Abdominal pain and cramping
- Fever
- Nausea and loss of appetite
- Dehydration
- Leukocytosis (often marked)
In severe cases: - Ileus
- Hypotension and shock
- Toxic megacolon
Diagnosis
Diagnosis is based on a combination of clinical presentation, laboratory findings, and endoscopic appearance.
Investigations include:
- Stool testing for C. difficile toxins A and B (enzyme immunoassay or PCR).
- Complete blood count: Leukocytosis is common.
- Electrolyte panel: To assess dehydration and metabolic imbalance.
- Sigmoidoscopy or colonoscopy: Reveals raised yellow-white plaques (pseudomembranes) over an erythematous mucosa.
- CT scan: May show colonic wall thickening in severe disease.
Management
Treatment involves eradicating C. difficile, restoring gut flora, and preventing complications.
General measures:
- Discontinue the inciting antibiotic whenever possible.
- Provide supportive care with fluids, electrolytes, and nutrition.
Specific antimicrobial therapy:
- First-line: Oral vancomycin.
- Alternative: Fidaxomicin (especially for recurrence).
- For mild cases: Metronidazole may be used if first-line agents are unavailable.
Severe or complicated cases:
- Surgical consultation for toxic megacolon or perforation (may require subtotal colectomy).
- Fecal microbiota transplantation (FMT) for recurrent infections.
Complications
If untreated, PMC can progress to:
- Severe dehydration and electrolyte imbalance
- Toxic megacolon
- Colonic perforation
- Sepsis and multiorgan failure
- High mortality in severe cases
Prevention
- Rational use of antibiotics (antimicrobial stewardship).
- Hand hygiene with soap and water (alcohol-based sanitizers are less effective against spores).
- Environmental disinfection with sporicidal agents.
- Isolation of infected patients in healthcare settings.
Prognosis
Most patients respond well to timely treatment, but recurrence occurs in approximately 20–25% of cases. Risk of recurrence increases with age, immunosuppression, and continued exposure to risk factors.
Conclusion
Pseudomembranous colitis remains a significant healthcare-associated infection worldwide, driven largely by C. difficile. Prevention relies heavily on infection control measures and prudent antibiotic use. Early recognition and appropriate therapy can dramatically reduce morbidity and mortality, making clinician awareness critical.
