Definition/General
Introduction:
Pseudomembranous colitis is an antibiotic-associated inflammatory condition characterized by adherent pseudomembranes
Most commonly caused by Clostridium difficile
Results from disruption of normal colonic flora
Shows characteristic volcano-like lesions with pseudomembrane formation.
Origin:
Caused by C
difficile toxins (toxin A and B)
Results from antibiotic disruption of normal flora
Leads to C
difficile overgrowth
Toxins cause epithelial damage and inflammatory response
Shows pseudomembrane formation.
Classification:
Antibiotic-associated diarrhea (mild form)
Antibiotic-associated colitis (moderate)
Pseudomembranous colitis (severe form)
Fulminant colitis (life-threatening)
Recurrent C
difficile infection.
Epidemiology:
Peak incidence in hospitalized elderly patients
Increasing incidence with broad-spectrum antibiotic use
Healthcare-associated infection
Community-acquired cases increasing
Indian hospitals showing rising prevalence.
Clinical Features
Presentation:
Watery diarrhea (most common - >90%)
Abdominal pain and cramping
Fever (60-80% cases)
Leukocytosis
Recent antibiotic use (weeks to months)
Dehydration.
Symptoms:
Profuse watery diarrhea (3-15 stools/day)
Lower abdominal cramping
Fever (38-40°C)
Nausea and vomiting
Malaise
Rarely bloody stools (fulminant cases).
Risk Factors:
Antibiotic exposure (clindamycin, fluoroquinolones, cephalosporins)
Advanced age (>65 years)
Hospitalization
Inflammatory bowel disease
Immunosuppression
Proton pump inhibitors.
Screening:
C
difficile toxin assay
Polymerase chain reaction (C
difficile genes)
Enzyme immunoassay
Stool culture
CT scan (complications)
Colonoscopy (severe cases).
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Gross Description
Appearance:
Yellow-white plaques adherent to mucosa
Pseudomembranes 2-10mm diameter
Underlying mucosal erythema
Confluent pseudomembranes (severe cases)
Normal intervening mucosa
Colonic distention (toxic megacolon).
Characteristics:
Adherent pseudomembranes difficult to remove
Underlying ulcerated mucosa
Yellow-green exudate
Edematous bowel wall
Serosal congestion
Minimal bleeding.
Size Location:
Pan-colonic involvement (typical)
Rectosigmoid most severely affected
Cecum and ascending colon (antibiotic-associated)
Rectal sparing (some cases)
Small bowel involvement (rare).
Multifocality:
Diffuse colonic involvement
Variable density of pseudomembranes
Segmental involvement (mild cases)
Progressive spread
Rectal involvement variable.
Microscopic Description
Histological Features:
Pseudomembrane formation (pathognomonic)
Surface epithelial necrosis
Acute inflammatory exudate
Volcano-like lesions
Neutrophilic infiltrate
Submucosal edema.
Cellular Characteristics:
Surface epithelial loss
Neutrophils in lamina propria
Fibrin and cellular debris
Mucin pools
Capillary congestion
Endothelial swelling.
Architectural Patterns:
Mushroom-shaped pseudomembranes
Volcano lesions (pseudomembrane over crypt opening)
Surface ulceration
Preserved crypt architecture
Summit lesions (between crypts)
Minimal chronic changes.
Grading Criteria:
Mild: few pseudomembranes, minimal inflammation
Moderate: confluent pseudomembranes, active inflammation
Severe: extensive pseudomembranes, mucosal necrosis
Fulminant: transmural necrosis, perforation risk.
Immunohistochemistry
Positive Markers:
C
difficile toxin A (tissue detection)
C
difficile toxin B
CD68 (macrophages)
Myeloperoxidase (neutrophils)
Fibrinogen (pseudomembranes).
Negative Markers:
Other bacterial antigens
Viral inclusions (CMV, HSV)
Parasitic forms
Malignancy markers
IBD-associated markers.
Diagnostic Utility:
C
difficile toxin detection (tissue-based)
Confirms bacterial etiology
Excludes other infectious causes
Tissue-based diagnosis when stool testing negative
Research applications.
Molecular Subtypes:
Toxin A+B+ strains (most common)
Toxin A-B+ strains
Binary toxin-positive (NAP1/027 strain)
Hypervirulent strains
Antibiotic-resistant strains.
Molecular/Genetic
Genetic Mutations:
C
difficile toxin genes (tcdA, tcdB)
Binary toxin genes (cdtA, cdtB)
Regulatory genes (tcdC mutations)
Resistance genes
Virulence factors.
Molecular Markers:
Toxin A (enterotoxin)
Toxin B (cytotoxin)
Binary toxin (hypervirulent strains)
Surface layer proteins
Adhesion factors.
Prognostic Significance:
Strain virulence (027/NAP1 worse prognosis)
Age (elderly worse outcome)
Comorbidities
White blood cell count (>15,000 poor prognostic factor)
Serum creatinine elevation.
Therapeutic Targets:
Metronidazole (mild cases)
Oral vancomycin (severe cases)
Fidaxomicin (recurrent cases)
Fecal microbiota transplant
Bezlotoxumab (monoclonal antibody).
Differential Diagnosis
Similar Entities:
Inflammatory bowel disease
Ischemic colitis
Other infectious colitis (Salmonella, Shigella)
Drug-induced colitis
Neutropenic colitis.
Distinguishing Features:
Pseudomembranous colitis: Pseudomembranes, antibiotic history, C
difficile toxin
IBD: Chronic changes, younger age
Ischemic: Watershed zones, vascular disease
Other infectious: Specific organisms
Drug-induced: Specific drug history.
Diagnostic Challenges:
Distinguishing from other antibiotic-associated colitis
Recognizing atypical presentations
Differentiating from IBD flare
Identifying complications
Stool testing correlation.
Rare Variants:
Small bowel involvement
Rectal sparing
Right-sided predominance
Fulminant colitis
Recurrent infection.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type] from [anatomical location]
Clinical Information
Recent antibiotic use: [yes/no]. Duration of symptoms: [days/weeks]
Pseudomembrane Features
Pseudomembranes: [present/absent]. Distribution: [focal/diffuse]. Morphology: [volcano lesions/mushroom-shaped]
Epithelial Changes
Surface epithelial necrosis: [present/absent]. Crypt architecture: [preserved/distorted]
Inflammatory Features
Acute inflammation: [mild/moderate/severe]. Neutrophilic infiltrate: [present/absent]
Complications
Mucosal necrosis: [present/absent]. Perforation risk: [low/high]
Special Studies
C. difficile toxin testing: [recommended/performed]. Results: [positive/negative/pending]
Final Diagnosis
Pseudomembranous Colitis, consistent with C. difficile infection