Sunday, December 30, 2012

IBD Blood Tests for Diagnosis


IBD Blood Diagnostics


Crohn’s disease and Ulcerative colitis are the abnormal inflammation of the intestinal wall, resulting in ulcerations, that is not related to an otherwise identified reason (e.g. colon cancer).  Crohn’s disease can occur in bands and can be anywhere in the intestinal tract, whereas UC occurs exclusively in the large intestine* in a defined region.  Additionally, Crohns is a full thickness disease – it impacts all layers of the intestinal wall while UC impacts the surface layer.

Diagnosing IBD is generally a multi-stage process.  First, a detailed patient history is examined for symptoms consistent with IBD, including, but not limited to, chronic diarrhea, abdominal pain, blood in the stool, weight loss, and fatigue.  If the patient presents with possible IBD, the doctor may order imaging tests, ranging from barium swallow MRI tests to CT scans.  Next, direct observation of the suspected area through endoscopy, sigmoidoscopy, or colonoscopy is performed.  Finally, tissue samples of the affected area are biopsied.

What role does blood testing play in the diagnosis of IBD?  Blood testing is relatively harmless and can be used to identify signs of IBD initially and as an ongoing monitor of health in already diagnosed patients.  Blood tests look for a few things – markers of inflammation (such as C-Reactive Protein), vitamin and mineral levels (to look for things line iron deficiencies indicative of bleeding or vitamin deficiencies that may pinpoint disease areas), and other functional markers (such as liver function).

What about blood tests like the Prometheus IBD Serology 7 (now in the 4th generation with the IBD sgi Diagnostic)?  Prometheus, to its credit, identifies the test as aiding, not making the diagnosis, but more than a few doctors have misunderstood this claim:

The new Prometheus IBD sgi Diagnostic is the 4th-generation IBD diagnostic test and the first and only test to combine serologic, genetic, and inflammation markers in the proprietary Smart Diagnostic Algorithm for added diagnostic clairty. This test will aid healthcare providers in differentiating IBD vs non-IBD, and CD vs UC, in one comprehensive blood test. (1)

While including other factors (including inflammation and genetics), the serum marker test Prometheus Labs does is a probabilistic test, but the sensitivity and specificity are fairly low to be saying it diagnoses IBD well.  For example, if we look at one of the larger preliminary reviews of the serological component, we will see that there is a sensitivity of 65% and a specificity of 94% on the primary components of the test.(2)  In a more recent and larger study, the sensitivity and specificity of the Prometheus IBD testing was 80% and 61.5%, respectively.  What does that mean?

Sensitivity is the percentage of sick people who are correctly identified as having the condition. Specificity is the percentage of healthy people who are correctly identified as not having the condition.  80% sounds a lot better than chance, right?  The problems come when you do the math related to prevalence.  The positive prediction value and negative prediction value are what the patient is really interested in.  Looking at the second article’s raw numbers we get the following:

True Positive:  23
True Negative:  45
False Positive:   7
False Negative:  19

Positive Prediction Value = True Positive/(True Positive + False Positive) = 23/(23+7)= 77%
Negative Prediction Value = True Negative/(True Negative + False Negative) = 45/(45+19) = 70%

In non-mathematical terms, this means that 23% of the people who are diagnosed with Crohn’s disease by the test don’t actually have, and 30% of the people that are diagnosed as not having Crohn’s disease do have it.  The test has other uses – including differentiation of Crohn’s and UC, but the numbers above don’t show tremendous diagnostic ability.  The numbers above also represent a sample of individuals that already presented with the symptoms of IBD – if more fringe cases are tested, the numbers would be expected to get worse.  Although not marketed this way, if this test were presented to the US population as a whole, based on expected prevalence of IBD, we’d get the following results:

Positive Predictive Value = (Sensitivity)(Prevalence)/((Sensitivity)(Prevalence) + (1-Specificity)(1-Prevalence)) = (.8)(.005)/((.8)(.005) + (.385)(.995)) = 1%
Negative Predictive Value = (Specificity)(1-Prevalence)/((Specificity)(1-Prevalence)+(1-Sensitivity)(Prevalence)) = (.615)(.995)/((.615)(.995)+(.2)(.005)) = 99.8%

This means the test falls victim to the base rate fallacy – because IBD is rare enough, the test gets skewed based on the prevalence.  While no one is advocating mass screenings using this blood test, overzealous physicians may (and have) misused it with individuals that don’t meet the other diagnostic criteria (e.g. sending everyone with repeated boughts of diarrhea for IBD serological testing), leading to misdiagnoses in both directions.

The folks at Prometheus are doing great work in identifying markers of IBD, and hopefully they will keep it up and continue refining their tests.  Right now, their tests can provide probabilistic differentiation, but are not, in of themselves, a diagnosis.

Note:  I welcome anyone to check my math - lots of numbers in the probability calculations and I wouldn't object to a confirmation or correction!

* The terminal ileum can be impacted in rare cases.

Bottom Line:

  • Serological testing can be an adjunct to traditional diagnostics and assist in differentiating IBD.
  • Serological tests, including the Prometheus Serum 7 and Prometheus IBD sgi Diagnostic cannot be used exclusively to diagnosis IBD.




  1. http://www.prometheuspatients.com/Products_Diagnostics.asp, retrieved 12/24/2012. 
  2. Anna Zholudev MPH, David Zurakowski PhD, Wes Young BA, Alan Leichtner MD and Athos Bousvaros MD, MPHSerologic Testing with ANCA, ASCA, and Anti-OmpC in Children and Young Adults with Crohn's Disease and Ulcerative Colitis: Diagnostic Value and Correlation with Disease Phenotype.  The American Journal of Gastroenterology, 2004. 
  3. F. Rashid, M.L. Bechtold, S.R. Puli, J.D. Bragg: Utility of IBD Serology Tests: Experience of an Academic Center. The Internet Journal of Gastroenterology. 2011.

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