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Serologic markers in the diagnosis of irritable bowel disease. 7 September 2006 Roni J Bollag. To evaluate the utility of serologic markers in the diagnosis of IBD. Background on IBD Current criteria for IBD diagnosis Evidence for serology in IBD Case study at MCG

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serologic markers in the diagnosis of irritable bowel disease

Serologic markers in the diagnosis of irritable bowel disease

7 September 2006

Roni J Bollag

to evaluate the utility of serologic markers in the diagnosis of ibd
To evaluate the utility of serologic markers in the diagnosis of IBD
  • Background on IBD
  • Current criteria for IBD diagnosis
  • Evidence for serology in IBD
  • Case study at MCG
  • Serology: adjunct or screening tool
  • Conclusion
slide3
IBD
  • Spectrum of chronic relapsing disorders affecting GI tract
    • Crohn disease
    • Ulcerative colitis
    • Indeterminate colitis
  • Lifelong disease beginning in youth (15-30)
  • Prevalence: 15 -20% (North America)
  • Immunologically mediated disease in genetically susceptible hosts
ibd consensus criteria
IBD – consensus criteria
  • Chief symptom: abdominal pain with altered bowel habits
  • Rome criteria
ibd rome iii criteria
IBD - Rome III criteria
  • Rule out “Alarm” feature
pathophysiology
Pathophysiology
  • Aberrant immune response with loss of tolerance to normal GI flora leading to chronic inflammation of the GI tract
  • Genetic susceptibility: multifactorial CARD15/NOD2 in Crohn - increased severity: fibrostenotic small bowel
  • IBD5, DLG5
  • Chr 1, 3, 5, 7, 10, 12, 16
ibd serologies
IBD Serologies
  • ANCA – antineutrophilic cytoplasmic abx
    • pANCA, cANCA (Wegener’s)
    • Atypical pANCA = not myeloperoxidase
  • ASCA – anti-Saccharomyces cerevisiae abx
    • IgG, IgA
    • Increased titers indicates ileal involvement
  • Antibodies against bacterial antigens (E. coli)
    • OmpC, Hup-B
  • I2 (bacterial sequence in CD)
  • PAB (antibodies to pancreatic antigens)

Lee: IBD2006

panca
pANCA
  • Produced by B-cells in IBD patients
  • 70% UC patients pANCA positive
  • 30% Crohn disease pANCA positive
    • Left sided colonic disease requiring colectomy
    • Reduced rate of response to anti-TNF

Lee: IBD2006

asca elisa
ASCA ELISA
  • ASCA – anti-Saccharomyces cerevisiae antibody
    • Usually measured with IgA or IgG
    • Increased titers indicates ileal involvement
    • Crohn Disease 50-60%
ibd screening test
IBD SCREENING TEST
  • Modified ANCA / ASCA - lowered threshold
  • Positive test confirmed by higher titer test
  • 95% non-IBD patients negative (74 patients)
  • 69% of IBD patients positive (54 patients)
    • False negatives will continue with symptoms
    • Positives confirmed with imaging / scoping
    • Important in indeterminate colitis - pouch

Lee: IBD2006

serology in cd
Serology in CD
  • Prospective study in children with CD
  • Children with more severe (internal penetrating / stricturing) disease had increased levels of antibodies
  • Anti-OmpC, anti I2, anti-CBir1,ASCA,
uptodate re prometheus
UptoDate – re: Prometheus
  • accuracy and predictive value in diagnosis of IBD unclear
  • prevalence of antibodies in patients with a variety of inflammatory diseases affecting the gut not well studied
  • ASCA present in 50 % of patients with celiac disease
      • may reflect a non-specific immune response in small bowel disease
      • ASCA association with cystic fibrosis
  • at the present time antibody tests should only be used as an adjunct to conventional testing and clinical diagnosis.
correlations i
Correlations I
  • P-ANCA+/ASCA-  UC
  • P-ANCA-/ASCA+  CD
  • Positive IBD panel modestly increases pre-test probability for IBD
  • Positivity for multiple serological markers correlates with disease severity
  • Negative IBD panel has no clinical relevance
correlations ii
Correlations II
  • Strongest risk factor for IBD is having a relative with disease – good correlation with serology
    • Possibility as ‘pre-clinical’ markers in familial IBD
  • Correlation of ASCA levels with increased severity in CD
  • No correlation between ANCA levels and UC severity
diagnosis of ibd
Diagnosis of IBD
  • IBD was once a diagnosis of exclusion
  • With symptom-based approach, IBD now a diagnosis of inclusion
  • Role of serology?
diagnosis of ibd27
Diagnosis of IBD
  • History & physical
  • Radiological evidence
  • Endoscopy
    • IBD inclusion – CD vs UC discrimination

Pathology

pathology
Pathology
  • Time honored diagnostic criteria for ulcerative colitis are being questioned
    • Rectal involvement
    • Contiguous disease
  • Non-contiguous UC
  • Rectal sparing, especially in children

Lee IBD2006

pathology29
Pathology
  • Non-contiguous distribution in UC
  • Rectal sparing not uncommon (peds)
  • One colonoscopy with biopsies should not establish the extent of disease
  • UC skip lesions do not warrant a diagnosis change to Crohn disease

Lee: IBD2006

viewpoints
Viewpoints

Rutgeerts, Vermeire

Hoffenberg, Fidanza,

Sauaia

Canani et al

Lerner, Schoenfeld

the insurance angle
The Insurance angle
  • Position echoed on four insurance policy statements
case history rmd request for prometheus ibd panel
Case history – RMD request for Prometheus IBD panel
  • 11-year-old male with weight loss and diarrhea who developed an intra-abdominal abscess
  • patient underwent a small-bowel resection at an outside institution
  • per report specimen was not diagnostic for CD
  • Peds GI unable to scope the patient due to his recent surgery and requested the Prometheus panel in the interim.  
  • Patient kept in-house; endoscopy after 4 days
case history continued
Case history – continued
  • Case deferred for pathology …

PATHOLOGY

  • Specimen A: The findings are suggestive, but not diagnostic of celiac disease. Repeat biopsy after a trial of gluten-free diet may be helpful.
  • Specimens D-E: While inflammatory bowel disease is a possible cause of the chronic active colitis, the histologic features are not diagnostic of this disease. No granulomas are identified.
case history continued34
Case history – continued
  • Case sent for Prometheus panel
final dx
Final Dx
  • It looks like a duck, walks like a duck, quacks like a duck

(see comment)

Comment: favor duck; correlate with serologies

bibliography
Bibliography
  • Bossuyt, X.(2006) Clin. Chem 52:171-181
  • Abreu, M.T. (2002) Inflamm Bowel Dis 8:224-6
  • Canani, R.B et al. (2006) J Ped Gastroenterol Nutr 42:9-15
  • Reumaux. D. et al. (2003) Best Pract Res Clin Gastroenterol 17:19-35
  • Dubinsky , M et al. (2006) Am J Gastroenterol 101:360-367
  • Ruemmele et al. (1998) Gastroenterology 115:822-829
  • Hoffenberg et al. (1999) J. Pediatr. 134:447-452
  • Lerner, A., Schoenfeld, Y. (2002) Eur J. Gastroentero Hepat 14:103-105
  • Malagelada, J-R (2005) Int J Clin Pract 60:57-63
  • Cash, B.D., Chey, W.D. (2004) Aliment Pharmacol Ther 19:1235-1245
  • Lee, J.L. (2006) IBD2006 (powerpoint)
  • Medscape
  • UptoDate
  • Harrison’s Principles of Internal Medicine, 15th ed., 2005
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