Pseudomembranous Colitis

Description

Pseudomembranous colitis is an acute inflammatory condition of the colon caused by Clostridioides difficile (C. difficile) infection. This condition is often associated with recent antibiotic use, which disrupts normal gut flora and allows for the overgrowth of C. difficile. The disease is characterised by the formation of pseudomembranes, which are yellowish plaques composed of inflammatory cells, fibrin, and necrotic debris adherent to the colonic mucosa.

Pathogenesis

The pathogenesis of pseudomembranous colitis involves the production of toxins by C. difficile, leading to inflammation and damage to the colonic mucosa. The colon is a major site for water absorption and waste processing. Antibiotics disrupt the balance of the gut microbiota, allowing C. difficile to proliferate. C. difficile produces two main toxins, TcdA and TcdB, which cause mucosal damage, inflammation, and pseudomembrane formation.

Subtypes

There are no distinct subtypes of pseudomembranous colitis, but the severity can vary from mild diarrhoea to life-threatening fulminant colitis.

Epidemiology, Risk Factors & Associations

• Affects approximately 500,000 individuals annually in the United States.
• More common in older adults and hospitalised patients.

Risk factors:

• Recent antibiotic use (particularly clindamycin, cephalosporins, fluoroquinolones).
• Hospitalisation or long-term care facility residence.
• Immunosuppression.
• Proton pump inhibitor use.
• Inflammatory bowel disease (IBD).

Clinical Features

• Profuse, watery diarrhoea (often foul-smelling).
• Abdominal pain and cramping.
• Fever.
• Nausea and vomiting.
• Dehydration and electrolyte imbalances.
• In severe cases, signs of toxic megacolon or perforation.

Complications

• Toxic megacolon.
• Colonic perforation.
• Sepsis and multi-organ failure.
• Recurrence of C. difficile infection.
• Death, especially in severe untreated cases.

Pathological Features

Histopathology

• Macroscopic: Pseudomembranes, which are yellowish plaques, often visible on colonoscopy.
• Microscopic: Inflammatory infiltrate composed of neutrophils and fibrin. Necrotic debris and damaged colonic epithelium.

Serology

• Not used in diagnosis.

Biochemistry

• Elevated white blood cell count (leukocytosis).
• Hypoalbuminaemia in severe cases.

Radiological Features

General Features

• First-line investigation: Contrast-enhanced abdominal CT is the imaging modality of choice in suspected pseudomembranous colitis, particularly in moderate-to-severe cases or when complications such as toxic megacolon or perforation are suspected.
• Gold standard: Colonoscopy, which allows for direct mucosal visualisation and biopsy, confirming the presence of characteristic pseudomembranes. However, colonoscopy carries risk of perforation in severely inflamed bowel and is typically reserved for unclear or refractory cases.
• While the disease commonly begins in the rectosigmoid colon and extends proximally, in some patients it may be isolated to the right colon, particularly in elderly or immunosuppressed individuals, making imaging essential for complete assessment.
• Imaging may reveal:
  • Diffuse or segmental colonic wall thickening, most pronounced in the descending colon, sigmoid, and rectum.
  • Submucosal oedema, manifesting as the classic accordion sign.
  • Variable degrees of colonic dilatation, often with preserved haustration.
  • Pericolonic fat stranding may be present in more advanced or transmural involvement.

XR

• Limited sensitivity, but may show late or severe manifestations:
  • Colonic dilatation, particularly if progressing to toxic megacolon (transverse colon >6 cm)
  • Thumbprinting due to submucosal oedema
  • Pneumatosis coli in rare, severe cases
  • Free subdiaphragmatic air indicating perforation
• Upright chest or left lateral decubitus abdominal films may detect small pneumoperitoneum

CT

Non-contrast

• Diffuse colonic wall thickening: Symmetric, often up to 1.5 cm; most prominent in the left colon
• Shaggy mucosal contour: Irregular ill-defined mucosal-luminal interface reflecting disrupted mucosal integrity due to pseudomembrane formation, sloughing and oedema.
• Free intraperitoneal fluid: Small-volume ascites may be seen in the pelvis or pericolic gutters
• Minimal pericolonic fat stranding: As this is predominantly a mucosal and submucosal process, the pericolic fat is often relatively spared in early or moderate disease

C+ Arterial

• Not routinely performed for pseudomembranous colitis
• May show mild mucosal hyperenhancement, but lacks diagnostic specificity
• Occasionally performed when evaluating for other causes of colitis or concurrent vascular pathology

C+ Portal Venous

• Enhancement pattern:
  • Mucosal hyperenhancement due to inflammation
  • Submucosal hypodensity from oedema or haemorrhage
• Accordion sign:
  • Alternating layers of high attenuation (enhancing mucosa) and low attenuation (oedematous haustra filled with intraluminal fluid or contrast)
  • Best seen in the transverse and descending colon
• May demonstrate pericolonic vascular congestion and reactive mesenteric lymphadenopathy in severe cases
• Evaluate for complications:
  • Toxic megacolon: Colonic diameter >6 cm with loss of haustration, wall thinning
  • Perforation: Pneumoperitoneum, extraluminal fluid or air
  • Pneumatosis intestinalis: Rare, but concerning if present

MRI

• Not routinely utilised in the acute setting due to time constraints and limited availability in unstable patients
• May be used in paediatric or pregnant populations
• T2-weighted sequences may show hyperintense submucosal oedema
• Post-contrast sequences can demonstrate layered mural enhancement akin to CT
• Diffusion-weighted imaging (DWI) may reveal restricted diffusion in areas of severe inflammation or necrosis

US

B-mode

• Limited by bowel gas and patient body habitus
• Thickened bowel wall, typically >4 mm, most evident in the left colon
• Loss of normal wall stratification in severe inflammation
• Presence of luminal debris or fluid
• May detect free fluid or early complications in paediatric or thin patients

Colour Doppler

• Increased mural vascularity may be seen in early inflammatory stages
• Diminished or absent flow in segments of necrosis or transmural involvement
• Can aid in assessing bowel wall perfusion, particularly when evaluating for possible ischaemic changes or necrosis

NM

Not typically used in the evaluation of pseudomembranous colitis

Grading and Staging

There is no specific grading or staging system for pseudomembranous colitis, but severity can be classified based on clinical presentation and complications:

• Mild: Watery diarrhoea with minimal systemic symptoms.
• Moderate: Diarrhoea with significant abdominal pain, fever, and leukocytosis.
• Severe: Severe abdominal pain, high fever, marked leukocytosis, signs of toxic megacolon or perforation.

Diagnosis

Diagnosis is primarily clinical, supported by:

• Stool tests for C. difficile toxins or PCR for C. difficile DNA.
• Colonoscopy showing pseudomembranes.
• Abdominal CT scan showing colonic wall thickening and pericolonic fat stranding.

Differential Diagnosis

• Ulcerative colitis: Chronic inflammatory bowel disease with continuous colonic involvement and bloody diarrhoea. Predilection for rectum and distal colon.
• Crohn’s disease: Transmural inflammation with skip lesions and potential involvement of any part of the gastrointestinal tract.
• Ischaemic colitis: Typically in older adults with vascular risk factors. Would rarely cause a pancolitis. The rectum is rarely involved due to rich anastomotic blood supply.
• Infectious colitis: Caused by other pathogens (e.g., Salmonella, Shigella), typically with a history of recent travel or foodborne exposure. Can occur from multiple pathogens in immunocompromised patients. Focal, segmental, or pancolitis with wall oedema and pericolonic inflammation are typical features.
• Drug-induced colitis: Associated with medications like NSAIDs, presenting with similar symptoms.

Management

• Initial management: Discontinuation of the inciting antibiotic. Oral or intravenous fluid replacement. Electrolyte correction.
• Definitive treatment: Oral vancomycin or fidaxomicin for 10-14 days. Metronidazole as an alternative or adjunct in mild to moderate cases. Faecal microbiota transplantation for recurrent C. difficile infection.
• Supportive care: Monitoring for complications such as toxic megacolon and perforation. Surgical consultation for severe cases with complications