MICROSCOPIC COLITIS AND CELIAC DISEASE

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MICROSCOPIC COLITIS AND CELIAC DISEASE

• JEFFREY M. ARON, M.D.
• California Pacific Medical Center
• San Francisco
• August 31, 2005

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OVERVIEW

• A MUCOSAL INFLAMMATORY AND COLLAGENOUS RESPONSE
  THAT OCCURS CONCOMITANTLY IN SEVERAL SITES OF THE
  GUT
• STOMACH
• SMALL INTESTINE
• COLON

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DEFINITION
MICROSCOPIC COLITIS
Lymphocytic colitis
Collagenous colitis
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HISTOLOGY

• NORMAL MUCOSA
• LYMPHOCYTIC COLITIS

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HISTOLOGY COLLAGENOUS COLITIS
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HISTOLOGY
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CLINICAL PRESENTATION

• CHRONIC WATERY DIARRHEA (all pathogens and
  abnormal humoral causes excluded)
• RARELY CONSTIPATION
• OVERWHELMINGLY FEMALE
• ELDERLY (peak incid 70, but Veress et. al.
  reported 30 cases age onset 36-44, with ave
  duration of symptx 11-20 yrs)

Veress B et al Gut 199536 880-6
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CLINICAL COURSE

• INSIDIOUS ONSET
• USUALLY BENIGN WITH PROLONGED REMISSIONS AND
  RELAPSES
• RARELY PROTRACTED AND SEVERE-MORE OFTEN IN
  COLLAGENOUS THAN IN MICROSCOPIC COLITIS
• ABD PAIN IS CRAMPING AND INTERMITTENT

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LABORATORY FINDINGS

• STOOLS NEGATIVE FOR ALL PATHOGENS
• RARELY OCCAS WBCs
• NEGATIVE INVESTIGATION FOR ALL HUMORAL FACTORS(
  gastrin, VIP, thyroid)

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ENDOSCOPY

• COLONOSCOPY TO T.I. USUALLY NORMAL
• MILD, NON-SPECIFIC ERYTHEMA HAS BEEN RARELY NOTED
  IN COLLAGENOUS COLITIS
• BIOPSIES OF NORMAL-APPEARING MUCOSA FROM TI TO
  RECTUM ARE MANDATORY
• 2 each from TI, asc, prox transv, dist transv,
  desc, sigmoid and rectum
• Stain for CD3, CD25 and mast cells

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ENDOSCOPY

• EGD MANDATORY
• BIOPSY DUODENUM (8-10 bxs from transverse back to
  post -bulbar)
• BIOPSY STOMACH
• STAIN FOR CD3 CELLS-count /100 epith cells in
  mucosa gt20-25/100 abnormal

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RELATION TO CELIAC DISEASE

• 28 OF CELIACS HAVE MICROSCOPIC COLITIS
• SIMILAR TO LYMPHOCYTIC COLITIS, BUT WITH LESS PAN
  MUCOSAL LYMPHOCYTOSIS (Fine KD et al Hum Pathol
  1998291433.)
• 67 OF REFRACTORY SPRUE PATIENTS HAVE MICROSCOPIC
  COLITIS (Fine KD et al Am J Gastro 2000 951974)
• HIGHER PERCENTAGE OF COLLAGENOUS COLITIS, BUT
  LYMPHOCYTIC COLITIS ALSO COMMON

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CELIAC

• 98 OF CELIACS ARE HLA-DQ2 AND HLA-DQ8 POSITIVE
• 43 OF MICROSCOPIC COLITIS ARE POSITIVE FOR THESE
  MARKERS VS. 18 OF CONTROLS (p000000008, OR 6.7)

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CELIAC

• 70 OF ALL MICROSCOPIC COLITIS PTS HAD AN
  ABNORMAL SM BOWEL BX
• 43 HAD A MARSH I LESION (normal villi but gt20
  CD3/100epith)
• 14 HAD A MARSH II (partial villous atrophy,
  lamina propria lymphocytosis)
• 14 MARSH III (subtotal atrophy, l.p. lymphs)
• 100 HAD BOTH HLA MARKERS
• ONLY 27 AND 7 HAD EITHER AGA OR AEA

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RELATION WITH CELIAC DISEASE

• CELIAC DISEASE OCCURS IN OVER 20 OF MICROSCOPIC
  COLITIS (Freeman HJ J Clin Gastroenterol.
  200438664)
• All cases had collagenous colitis
• All small intestinal bxs returned to normal after
  a g-f diet
• 3/8 reversed collagenous changes on repeat
  colonoscopic bxs
• 5/8 had no change, and had associated autoimmune
  disease and lymphoma

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• THIS STRONG ASSOCIATION MANDATES A THOROUGH
  SEARCH FOR CELIAC DISEASE IN ALL PATIENTS WITH
  MICROSCOIC COLITIS

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OTHER ETIOLOGIES

• DRUG-INDUCED MICROSCOPIC COLITIS
• Collagenous lansoprazole, NSAIDS, cimetidine
• Lymphocytic lansoprazole, ranitidine,
  ticlodipine, flutamide, vinburine, tardyferon,
  acarbose,levodopa-benserazide, carbamazepine
• INFECTIOUS
• Yersinia, C diff, Campylobacter
• ? HORMONAL

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• MICROSCOPIC COLITIS CAN BE CURED BY DIVERTING
  ILEOSTOMY, BUT PROMPTLY RECURS WITH
  RE-ANASTOMOSIS
• (Janerot G et al Gastroenterlogy 1995
  109449-455.)

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• SOUND FAMILIAR????
• Enteric disease is a phenotypic expression of an
  interaction of lumenal (environmental) factors
  and a genotypically-controlled immune/inflammatory
  response

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A MODEL FOR DISEASE CONTROL OF THE LINE OF
SCRIMMAGE
X X X X X X X X X X X
Defense
Offense
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SPECTRUM OF DIGESTIVE DISEASE
GERD
FD
IBS D C P
Celiac
microcolitis
IBD
UC
Crohns
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TREATMENT

• ASSESS DRUG HISTORY
• TRIAL OF ANTIDIARRHEALS
• BISMUTH SUBSALICYLATE
• 3 TABS TID FOR 8 WKS
• BUDESONIDE
• 9mg/day for 6-8weeks, taper optional
• BILE ACID BINDING AGENTS-symptx only
• ( best controlled trials, collagenous disease
  only COCHRANE DATABASE AJG 2004992459-65.)

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TREATMENT

• GLUTEN-FREE DIET
• 5-ASAs uncontrolled trials
• Prednisolone not effective
• Immunomodulators uncontrolled trials
• Biologics no data, only in refractory sprue
• Surgery-a last resort