Serologic markers in the diagnosis of irritable bowel disease
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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 l.jpg

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 l.jpg
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 l.jpg
IBD diagnosis of 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 l.jpg
IBD – consensus criteria diagnosis of IBD

  • Chief symptom: abdominal pain with altered bowel habits

  • Rome criteria


Ibd rome iii criteria l.jpg
IBD - Rome III criteria diagnosis of IBD

  • Rule out “Alarm” feature


Epidemiology of ibd l.jpg
Epidemiology of IBD diagnosis of IBD


Uc vs cd l.jpg
UC vs CD diagnosis of IBD


Pathophysiology l.jpg
Pathophysiology diagnosis of IBD

  • 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


Hypothesized etiologies l.jpg
Hypothesized Etiologies diagnosis of IBD


Differential diagnosis l.jpg
Differential Diagnosis diagnosis of IBD


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Antibodies in IBD diagnosis of IBD


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IBD Serologies diagnosis of IBD

  • 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 l.jpg
pANCA diagnosis of IBD

  • 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


Anca immunofluorescence l.jpg
ANCA immunofluorescence diagnosis of IBD


Asca elisa l.jpg
ASCA ELISA diagnosis of IBD

  • ASCA – anti-Saccharomyces cerevisiae antibody

    • Usually measured with IgA or IgG

    • Increased titers indicates ileal involvement

    • Crohn Disease 50-60%


Serologic associations l.jpg
Serologic associations diagnosis of IBD


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Serologic associations diagnosis of IBD


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IBD SCREENING TEST diagnosis of IBD

  • 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 l.jpg
Serology in CD diagnosis of IBD

  • 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 l.jpg
UptoDate diagnosis of IBD


Prometheus l.jpg
Prometheus diagnosis of IBD


Uptodate re prometheus l.jpg
UptoDate – re: Prometheus diagnosis of IBD

  • 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 l.jpg
    Correlations I diagnosis of IBD

    • 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 l.jpg
    Correlations II diagnosis of IBD

    • 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 l.jpg
    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 l.jpg
    Diagnosis of IBD diagnosis of IBD

    • History & physical

    • Radiological evidence

    • Endoscopy

      • IBD inclusion – CD vs UC discrimination

    Pathology


    Pathology l.jpg
    Pathology diagnosis of IBD

    • 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 l.jpg
    Pathology diagnosis of IBD

    • 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 l.jpg
    Viewpoints diagnosis of IBD

    Rutgeerts, Vermeire

    Hoffenberg, Fidanza,

    Sauaia

    Canani et al

    Lerner, Schoenfeld


    The insurance angle l.jpg
    The Insurance angle diagnosis of IBD

    • Position echoed on four insurance policy statements


    Case history rmd request for prometheus ibd panel l.jpg
    Case history – RMD request for Prometheus IBD panel diagnosis of IBD

    • 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 l.jpg
    Case history – continued diagnosis of IBD

    • 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 l.jpg
    Case history – continued diagnosis of IBD

    • Case sent for Prometheus panel


    Case history conclusion l.jpg
    Case history – conclusion diagnosis of IBD


    Differential diagnosis36 l.jpg
    Differential Diagnosis diagnosis of IBD


    Final dx l.jpg
    Final Dx diagnosis of IBD

    • It looks like a duck, walks like a duck, quacks like a duck

    (see comment)

    Comment: favor duck; correlate with serologies


    Bibliography l.jpg
    Bibliography diagnosis of IBD

    • 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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