CollagenousCollagenous ColitisColitis

Richard M. Wardrop, IIIRichard M. Wardrop, IIIAM Report 10/20/03AM Report 10/20/03

Department of Internal Medicine and PediatricsUNC College of Medicine

HistoryHistory

CollagenousCollagenous colitis (CC) was first described by Lindstrom colitis (CC) was first described by Lindstrom in a case report in 1976 of a woman with chronic watery in a case report in 1976 of a woman with chronic watery diarrhea, normal mucosa macroscopically, with a diarrhea, normal mucosa macroscopically, with a thickened subthickened sub--epithelial collagen band seen epithelial collagen band seen microscopically.microscopically.

Subsequently clustered with Subsequently clustered with lymphocyticlymphocytic colitis (LC) into colitis (LC) into the entity termed Microscopic Colitis.the entity termed Microscopic Colitis.

These two These two colitidescolitides are viewed as atypical IBD in some are viewed as atypical IBD in some reviews and may represent the same disease process reviews and may represent the same disease process because they share so many features. because they share so many features.

DefinitionDefinition

““The term The term collagenouscollagenous colitis and colitis and lymphocyticlymphocyticcolitis are now used to denote the association colitis are now used to denote the association of chronic watery diarrhea with normal or near of chronic watery diarrhea with normal or near normal normal endoscopicendoscopic findings, combined with findings, combined with characteristic characteristic histopathalogicalhistopathalogical inflammatory inflammatory changes.”changes.”

LymphocyticLymphocytic and and collagenouscollagenous colitis may be colitis may be viewed as microscopic colitis with or without viewed as microscopic colitis with or without collagen thickening. collagen thickening.

Epidemiology Epidemiology -- CCCC

Females predominate numbers of cases; from case Females predominate numbers of cases; from case series range from 2.7:1 to 15:1 female : male ratio.series range from 2.7:1 to 15:1 female : male ratio.

Mean age from early fifties to mid sixties but reports in Mean age from early fifties to mid sixties but reports in children do exist.children do exist.

Incidence is estimated at 1.1 per 100,000 (Spain) Incidence is estimated at 1.1 per 100,000 (Spain) persons and 4.1 per 100,000 (Iceland).persons and 4.1 per 100,000 (Iceland).

Prevalence among those with watery diarrhea who get Prevalence among those with watery diarrhea who get colonoscopy is 9.5%.colonoscopy is 9.5%.

Clinical Presentation Clinical Presentation

Cardinal clinical manifestation is watery, nonCardinal clinical manifestation is watery, non--bloody diarrhea bloody diarrhea ––sometimes insidious (58%) and sometimes with sudden onset sometimes insidious (58%) and sometimes with sudden onset (42%) often confusing it with infectious causes.(42%) often confusing it with infectious causes.

Average of six “bowel actions” per day but may have as many as Average of six “bowel actions” per day but may have as many as 20.20.

The presence of nocturnal diarrhea may help distinguish from IBSThe presence of nocturnal diarrhea may help distinguish from IBS..

Also cramping (41%), anorexia, mild weight loss (42%), urgency, Also cramping (41%), anorexia, mild weight loss (42%), urgency, fatigue (24%), and incontinence.fatigue (24%), and incontinence.

MalabsorptionMalabsorption is rare but protein losing is rare but protein losing enteropathyenteropathy may be may be associated.associated.

Associated ConditionsAssociated Conditions

Celiac disease (estimated at 3.8Celiac disease (estimated at 3.8--5.0%)5.0%)

Autoimmune diseases such as Autoimmune diseases such as thyroiditisthyroiditis, , RA, DMRA, DM--I, I, sarcoidsarcoid, pernicious anemia, , pernicious anemia, sclerodermascleroderma, CREST, , CREST, Sjogren’sSjogren’s

NonNon--ersosiveersosive seronegativeseronegative arthtitisarthtitis in 10%in 10%

Diagnostic StudiesDiagnostic Studies

Colonoscopy with Colonoscopy with biospybiospy is diagnostic is diagnostic –– important to sample right important to sample right and left colon as the left side may have less diagnostic utilityand left colon as the left side may have less diagnostic utilitycompared to the right.compared to the right.

U/S U/S –– not generally that useful.not generally that useful.

Stool Studies Stool Studies –– to diagnose to diagnose secretorysecretory diarrhea; stool diarrhea; stool osmolarosmolar gap gap < 50 < 50 –– indicates a indicates a secretorysecretory diarrhea. diarrhea.

Studies to rule out or rule in celiac disease may be useful espeStudies to rule out or rule in celiac disease may be useful especially cially in persons under 50.in persons under 50.

Stool may have fecal WBC (50%) and obviously no parasites.Stool may have fecal WBC (50%) and obviously no parasites.

ESR may be slightly elevated and total ESR may be slightly elevated and total IgMIgM may be elevated.may be elevated.

PathologyPathology

At At endoscopyendoscopy the colon typically appears the colon typically appears normal.normal.May have mild patchy May have mild patchy erythemaerythema, edema, and , edema, and superficial erosions.superficial erosions.Hallmarks include:Hallmarks include:

Increased density of IEL.Increased density of IEL.Epithelial injury.Epithelial injury.Mononuclear cell infiltrate in LP Mononuclear cell infiltrate in LP –– amount correlate with amount correlate with diarrhea severity.diarrhea severity.Thickened Thickened subepithelialsubepithelial collagen band.collagen band.Sparing of crypt architecture.Sparing of crypt architecture.

CC, LC, IBD CharacteristicsCC, LC, IBD Characteristics

* > or = 10* > or = 10µµmm

----++++++**--SubepithelialSubepithelial collagencollagen

--+++++++/+++/++++Lamina Lamina PropriaPropriamononuclear cellsmononuclear cells

++++--++++++++++Surface damageSurface damage

--++++++----Crypt distortionCrypt distortion

++++------InterepithelialInterepithelial PMN’sPMN’s

----+/+++/++++++++InterepithelialInterepithelial lymphslymphs

Acute Acute ColitisColitis

IBDIBDCCCCLCLC

Adapted from Adapted from TagkalidiTagkalidi et. al, et. al, Microscopic ColitisMicroscopic Colitis. 2002.. 2002.

CollagenousCollagenous Colitis (CC) vs. Colitis (CC) vs. LymphocyticLymphocyticColitis (LC)Colitis (LC)

From Up to Date, “Microscopic colitis”From Up to Date, “Microscopic colitis”

HistopathologyHistopathology

From Up to Date, “Microscopic colitis”From Up to Date, “Microscopic colitis”

Pathology Pathology –– via U/Svia U/S

From Up to Date, “Microscopic colitis”From Up to Date, “Microscopic colitis”

PathogenesisPathogenesis

Generally viewed as an abnormal immune and Generally viewed as an abnormal immune and tissue response to some luminal substance. tissue response to some luminal substance.

This is supported by:This is supported by:Cases where Cases where ileostomyileostomy caused remission and subsequent caused remission and subsequent relapse with relapse with ileostomyileostomy takedowntakedown

Effects of binders such as colloidal bismuth and Effects of binders such as colloidal bismuth and cholestyraminecholestyramine–– putative role for binding bacterial products.putative role for binding bacterial products.

Fecal toxicity on epithelial Fecal toxicity on epithelial monolayersmonolayers in vitroin vitro. Reversal of this . Reversal of this phenomenon with phenomenon with cholestyraminecholestyramine..

TreatmentTreatment

Avoidance of suspected inciting agents:Avoidance of suspected inciting agents:Glutens Glutens –– only if celiac disease is present.only if celiac disease is present.NSAIDS, ranitidine, NSAIDS, ranitidine, carbamazepinecarbamazepine, , simvistatinsimvistatin, , lansoprazolelansoprazole all implicated.all implicated.

Treat with specific drugs in a progressionTreat with specific drugs in a progressionAntiAnti--motility agents.motility agents.Colloidal bismuth, Colloidal bismuth, cholestyraminecholestyramine, , sulfasalazinesulfasalazine, , mesalazinemesalazine..If these fail then If these fail then budesonidebudesonide, , prednisoloneprednisolone..If these fail then MTX, If these fail then MTX, azathiopreneazathioprene..In severe refractory cases elemental diet and In severe refractory cases elemental diet and iliostomyiliostomy..

Prognosis Prognosis Limited longLimited long--term studies exist to assess the natural term studies exist to assess the natural history of CC and to a lesser extent LC.history of CC and to a lesser extent LC.

No link to increased in colon CA as in other forms of IBDNo link to increased in colon CA as in other forms of IBD

Most cases are chronic intermittent in nature with periods of noMost cases are chronic intermittent in nature with periods of normal rmal function function

One study of LC showed diarrhea cessation in 93%, return to normOne study of LC showed diarrhea cessation in 93%, return to normal al histology in 82%, and no progression to histology in 82%, and no progression to collagenouscollagenous colitiscolitis

Another series of CC patient showed significant improvements in Another series of CC patient showed significant improvements in diarrhea in 74% of patientsdiarrhea in 74% of patients

The good news is the disease is not associated with increased moThe good news is the disease is not associated with increased mortality rtality or severe deterioration.or severe deterioration.

ReferencesReferences

TagkalidiTagkalidi, P., , P., BhathalBhathal, P., and Peter Gibson. , P., and Peter Gibson. Microscopic ColitisMicroscopic Colitis. . Journal of Gastroenterology and Journal of Gastroenterology and HepatologyHepatology. Volume 17, 2002, pp. . Volume 17, 2002, pp. 236236--248.248.

Up to DateUp to Date, , “Microscopic colitis”“Microscopic colitis”

Fiedler et. al. Fiedler et. al. Treatment Responses in Treatment Responses in CollagenousCollagenous ColitisColitis. . The The American Journal of GastroenterologyAmerican Journal of Gastroenterology. Volume 96, No. 3, 2001, pp. . Volume 96, No. 3, 2001, pp. 817817--821.821.