Definition/General
Introduction:
Collagenous colitis is a form of microscopic colitis characterized by thickened subepithelial collagen band and chronic watery diarrhea
Shows normal endoscopic appearance with characteristic histologic changes
Part of microscopic colitis spectrum
Collagen band >10 micrometers diagnostic.
Origin:
Results from abnormal collagen deposition beneath surface epithelium
Associated with myofibroblast activation
Shows increased collagen synthesis
Linked to chronic inflammatory process
Drug-induced cases common
Autoimmune mechanisms implicated.
Classification:
Collagenous colitis (thickened collagen band >10 μm)
Lymphocytic colitis (increased intraepithelial lymphocytes)
Incomplete microscopic colitis (partial features)
Drug-induced microscopic colitis
WHO classification recognizes distinct entities.
Epidemiology:
Peak incidence in elderly women (60-80 years)
Strong female predominance (10:1 ratio)
Higher prevalence than lymphocytic colitis
Association with autoimmune diseases
Increasing recognition worldwide including India.
Clinical Features
Presentation:
Chronic watery diarrhea (defining symptom)
Normal colonoscopy
Abdominal cramping
Fecal incontinence
Weight loss (variable)
No blood or mucus in stools.
Symptoms:
Large-volume watery stools (5-20 per day)
Nocturnal diarrhea (50-60% cases)
Urgency and incontinence
Crampy abdominal pain
Dehydration
Electrolyte imbalance.
Risk Factors:
Female gender (strong association)
Advanced age (>60 years)
Medications (NSAIDs, PPIs, statins, ACE inhibitors)
Autoimmune diseases
Smoking cessation
Celiac disease association.
Screening:
Colonoscopy with biopsy (mandatory)
Normal endoscopic mucosa
Multiple site biopsies
Trichrome stain for collagen
Stool analysis (exclude infection)
Medication review.
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Gross Description
Appearance:
Normal gross appearance at colonoscopy
No visible mucosal abnormalities
Normal vascular pattern
No ulceration or erosions
Pseudomelanosis coli (laxative abuse)
Biopsy sites only gross finding.
Characteristics:
Macroscopically unremarkable colonic mucosa
No inflammatory changes visible
Normal colonic haustrations
No mass lesions
Normal mucosal color and texture.
Size Location:
Pan-colonic involvement (microscopic)
Right-sided predominance (clinical symptoms)
Cecum to rectum affected
Uniform distribution
Small bowel typically spared.
Multifocality:
Diffuse colonic involvement
Consistent changes throughout colon
No segmental variation
Both right and left colon
Rectal involvement universal.
Microscopic Description
Histological Features:
Thickened subepithelial collagen band (>10 micrometers)
Surface epithelial damage
Chronic inflammation in lamina propria
Increased intraepithelial lymphocytes (variable)
Normal crypt architecture.
Cellular Characteristics:
Subepithelial myofibroblasts
Chronic inflammatory cells (lymphocytes, plasma cells)
Surface epithelial flattening
Intraepithelial lymphocytes (increased)
Minimal neutrophils.
Architectural Patterns:
Preserved crypt architecture
Homogeneous eosinophilic collagen band
Surface epithelial denudation
Normal goblet cell population
Entrapped capillaries in collagen band.
Grading Criteria:
Collagen band thickness (>10 μm diagnostic, >20 μm typical)
Surface epithelial damage degree
Inflammatory cell density
Intraepithelial lymphocyte count
No formal grading system.
Immunohistochemistry
Positive Markers:
Smooth muscle actin (myofibroblasts in collagen band)
CD68 (macrophages)
CD3 (T lymphocytes)
Collagen IV (basement membrane)
Cytokeratin (epithelium).
Negative Markers:
Desmin (myofibroblasts negative)
S-100 (myofibroblasts negative)
Specific infectious agents
Malignancy markers
Neuroendocrine markers.
Diagnostic Utility:
Smooth muscle actin highlights myofibroblasts
Confirms collagen nature of thickening
Usually morphology sufficient
Trichrome stain more useful than IHC
Research applications.
Molecular Subtypes:
Drug-induced subtype (reversible)
Idiopathic subtype (most common)
Autoimmune-associated
Post-infectious
Genetic predisposition subtypes.
Molecular/Genetic
Genetic Mutations:
No specific genetic mutations
HLA associations (DQ2, DQ8)
TNF gene polymorphisms
TGF-β pathway genes
Collagen gene variants
Multifactorial inheritance.
Molecular Markers:
TGF-β1 (fibroblast activation)
PDGF (myofibroblast proliferation)
Type I and III collagen
Matrix metalloproteinases
TIMP-1 (tissue inhibitor).
Prognostic Significance:
Chronic relapsing course
Variable treatment response
Drug withdrawal may improve symptoms
Spontaneous remission (20-30% cases)
No malignant transformation.
Therapeutic Targets:
Budesonide (first-line treatment)
Cholestyramine (bile acid binding)
Anti-diarrheal agents
Prednisolone (refractory cases)
Immunosuppressants (severe disease).
Differential Diagnosis
Similar Entities:
Lymphocytic colitis (normal collagen band)
Ischemic colitis (hyalinized stroma)
Amyloidosis (amyloid deposits)
Drug-induced colitis (specific agents)
Normal aging changes.
Distinguishing Features:
Collagenous colitis: Thick homogeneous collagen band >10 μm
Lymphocytic colitis: Normal collagen, increased lymphocytes
Ischemic colitis: Hyalinized stroma, vascular changes
Amyloidosis: Apple-green birefringence
Aging: Collagen <10 μm.
Diagnostic Challenges:
Distinguishing from lymphocytic colitis (collagen band measurement)
Differentiating from normal aging (thickness criteria)
Recognizing drug-induced cases
Measuring collagen band accurately
Trichrome staining essential.
Rare Variants:
Incomplete collagenous colitis (thin band 7-10 μm)
Drug-induced collagenous colitis
Collagenous sprue (small bowel involvement)
Collagenous gastritis
Nodular collagenous colitis.
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
Chronic watery diarrhea. Normal colonoscopy. Drug history: [specify medications]
Collagen Band Assessment
Subepithelial collagen band thickness: [X] micrometers (diagnostic >10 μm, typical >20 μm)
Epithelial Changes
Surface epithelial damage: [present/absent]. Epithelial flattening and denudation noted
Inflammatory Features
Chronic inflammation in lamina propria: [mild/moderate]. Intraepithelial lymphocytes: [increased/normal]
Special Stains
Trichrome stain: Highlights thickened blue collagen band beneath surface epithelium
Crypt Architecture
Crypt architecture: [preserved]. No significant architectural distortion
Final Diagnosis
Collagenous Colitis - Microscopic colitis with thickened subepithelial collagen band