Microscopic colitis is a chronic inflammatory condition of the colon characterized by watery diarrhea, normal or near-normal endoscopic findings, and distinctive histologic features. First recognized as a distinct entity in 1980, it comprises two primary subtypes: collagenous colitis (defined by a thickened subepithelial collagen band) and lymphocytic colitis (marked by intraepithelial lymphocytosis). Diagnosis hinges on histologic examination, as endoscopy often appears unremarkable. This review synthesizes current knowledge on microscopic colitis, emphasizing its histopathologic hallmarks, pathogenesis, clinical mimics, and management strategies.
Epidemiology and Clinical Presentation
Incidence: 4.14–4.85 cases per 100,000 persons, with collagenous colitis showing a stronger female predominance (female-to-male ratio up to 9:1).
Symptoms: Chronic, non-bloody watery diarrhea (≥15 episodes/day in severe cases), fecal urgency, abdominal pain, and weight loss.
Diagnostic Challenge: Requires exclusion of mimics like celiac disease, IBD, and infections via endoscopy, serology (e.g., anti-tTG antibodies), and stool studies.
Pathogenesis
Microscopic colitis arises from a complex interplay of genetic, autoimmune, and environmental factors:
Genetic Predisposition:
HLA-DQ2/DQ3 haplotypes (shared with celiac disease) and IL-6-174 polymorphisms promote chronic inflammation.
Autoimmunity:
Overexpression of pro-inflammatory cytokines (TNF-α, IL-1, TGF-β1) drives collagen deposition in collagenous colitis.
Environmental Triggers:
Medications (NSAIDs, PPIs), infections (C. difficile, Yersinia), and microbiome dysbiosis contribute to disease onset.
Histopathologic Features
Collagenous Colitis:
Key Finding: Irregular subepithelial collagen band ≥10 μm (trichrome stain highlights entrapped capillaries and fibroblasts).
Inflammation: Mixed lymphoplasmacytic infiltrate in lamina propria; Paneth cell metaplasia may occur.
Architecture: Preserved crypts, though rare branching/dilation may be seen.
Lymphocytic Colitis:
Key Finding: >20 intraepithelial lymphocytes/100 epithelial cells (vs. 5 in normal mucosa).
Inflammation: "Top-heavy" lymphoplasmacytic infiltrate in superficial lamina propria.
Histologic Mimickers and Differentiation
Amyloidosis:
Hallmark: Congo red-positive amyloid deposits in submucosa/vessels (apple-green birefringence under polarized light).
Clinical Clue: Systemic symptoms (e.g., proteinuria, cardiomyopathy).
Radiation Colitis:
Acute: Crypt atrophy, nuclear atypia, eosinophil-rich inflammation.
Chronic: Submucosal fibrosis and hyalinized vessels.
Ischemic Colitis:
Features: Mucosal withering, lamina propria hyalinization, vascular congestion.
Key Differentiator: Absence of marked epithelial atypia or eosinophils.
Management
First-line: Budesonide (8–12 weeks, then taper) induces remission in >80% of patients.
Refractory Cases: Anti-TNF agents (e.g., infliximab) or surgery (ileostomy/colectomy).
Supportive Care: Antidiarrheals (loperamide) for symptom control.
Key Highlights
Diagnostic Triad: Chronic diarrhea + normal endoscopy + histologic inflammation (collagen band or lymphocytes).
Mimickers: Amyloidosis, radiation colitis, and ischemic colitis require Congo red staining and clinical history for distinction.
Pathogenesis: Autoimmune mechanisms (HLA-DQ2/DQ3) and microbiome dysbiosis are central to disease development.
Treatment: Budesonide is highly effective; refractory cases may need biologics.
Future Directions
Further research is needed to clarify:
The role of gluten sensitivity (given shared HLA haplotypes with celiac disease).
Microbiome modulation as a therapeutic target.
Long-term outcomes of biologic therapies.
Conclusion
Microscopic colitis remains a clinicopathologic diagnosis requiring meticulous histologic evaluation and exclusion of mimics. Understanding its genetic and autoimmune underpinnings, alongside accurate histopathologic assessment, is critical for optimal patient management. Emerging insights into microbiome dysbiosis may pave the way for novel therapies.
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