Collagenous Colitis

Julianne K. Purdy, MD

Key Facts

Clinical Issues

Microscopic Pathology

Patchy subepithelial increased collagen
- Most reliable biopsies from transverse colon
- Irregular collagen band extends entraps capillaries, inflammatory cells, and fibroblast nuclei
Increased intraepithelial lymphocytes (IELs)
- > 10-20 IELs/100 surface epithelial cells
Chronic or mixed inflammation in lamina propria
- Increased eosinophils (may be marked)
Detachment of surface epithelial cells from collagen band
Normal crypt size and shape; rare distortion
Rarely giant cells or focal IBD-like changes (Paneth cell metaplasia, cryptitis, crypt abscesses, branched crypts)

Top Differential Diagnoses

Lymphocytic colitis
- No increased subepithelial collagen
Inflammatory bowel disease
- Erosion/ulceration, crypt architectural distortion, basal plasmacytosis
Amyloidosis
- Stains with Congo red, not trichrome
- Tangential sectioning
Ischemic/radiation colitis
- No ↑ intraepithelial or lamina propria lymphocytes
Entities mimicking thickened collagen
- Tangential sectioning of tissue, hyperplastic polyp

Hematoxylin & eosin shows increased intraepithelial lymphocytes

, a band of subepithelial collagen

, and chronic inflammation in the lamina propria (plasma cells, lymphocytes).

Hematoxylin & eosin shows sloughing surface epithelium

, entrapment of capillaries and inflammatory cells

by collagen, increased lamina propria plasma cells, and focal Paneth cell metaplasia

TERMINOLOGY

Abbreviations

Definitions

Form of microscopic colitis with abnormal subepithelial collagen deposition and normal colonoscopy

ETIOLOGY/PATHOGENESIS

Environmental Exposure

Abnormal immunologic response to intraluminal bacteria/toxin in predisposed individuals
- Ileostomy with diversion of fecal stream → cessation of symptoms and histologic remission
Infection
- Antibodies to Yersinia more common in CC patients
- Development after C. difficile infection
- No definite infectious agent identified
Drugs: NSAIDs, lansoprazole, cimetidine, ticlopidine, simvastatin
- NSAID use: 39% of CC patients
- Mechanisms not elucidated
Prior ulceration/inflammation → stimulation of collagen synthesis or resulting defect in regulation

Genetic Factors

Autoimmune Pathogenesis

Often coexisting autoimmune disease (17-40%)
- Celiac disease (8-17%), thyroid disorders, diabetes, collagen vascular diseases
Causality not proven
- Responds to steroids but no immune complex deposits identified

Abnormal Collagen Metabolism

Impaired degradation of extracellular matrix (vs. increased fibrogenesis) → increased collagen accumulation
↑ pericryptal fibroblast turnover and activation → increased/premature collagen formation
↑ expression of fibrogenic genes by myofibroblasts
Transforming growth factor β-1 (TGF-β-1) and vascular endothelial growth factor (VEGF) alter balance of fibrogenesis and fibrinolysis
Possibly ↑ basic fibroblast growth factor → differentiation of fibroblasts

Unknown Etiology