Sunday, September 8, 2013

Fecal Calprotectin as an IBD Diagnostic Tool

Monitoring IBD and Fecal Calprotectin

One of the less used tests for gauging the status of inflammatory bowel disease is fecal calprotectin.  Most have never heard of it – its less commonly used than C-Reactive Protein and other testing, and it’s not cited as frequently as lifestyle scores like CDAI.  What is fecal calprotectin and what can it tell us about IBD?

Calprotectin is a protein strongly correlated with intestinal inflammation.  It is measured through fecal testing at a standard lab.  Because it only involves proving a stool sample (and waiting up to 2 weeks), the testing is non-invasive. Additionally, it is a marker of inflammation and is not elevated in those with irritable bowel syndrome.(1) 

The first area of interest in the fecal calprotectin test is for use in diagnosing IBD.  While the test alone cannot provide the location and complications related to IBD, it can help in rule out IBD without resorting to colonoscopy or other more invasive measures.  In a 2010 meta-analysis, Van Rheenen et al looked at individuals showing symptoms of IBD and found that the sensitivity was .93 and the specificity was .96 in adults, with lower values for teenagers and children.  This means, in practical terms, that 7% of adults with IBD will not register on the initial testing and will not be diagnosed, and 4% of those diagnosed will not have IBD.  Because the next step in screening for those with a positive fecal calprotectin is a more invasive procedure (colonoscopy, endoscopy, small bowel study, etc.), the 4% can be largely ignored in the analysis (without the test they would have undergone the invasive testing anyway).  That leaves 7% that are undiagnosed by the testing but actually have IBD.  That is, in general, a reasonable tradeoff.  The 7% that are undiagnosed are likely to be watched for followup, and an invasive procedure performed several months later if symptoms do not abate (or another fecal calprotectin test performed – the study did not look at the impact of successive testing).

The second area of interest is in monitoring the activity of Crohn’s and Ulcerative Colitis.  Smaller, earlier studies showed a strong correlation between fecal calprotectin score and the likelihood of relapse in Ulcerative Colitis (but not Crohn’s).(3)  Further review showed that it was predictive in certain types f Crohn’s disease, namely ileocolonic and colonic, but not upper GI-centric Cronhn’s.(4)  While not predictive of relapse in Crohn’s it was found to be strongly correlated to the Simple Endoscopic Score, better than CRP, the CDAI, and other testing.  A 2010 analysis found that:

The SES-CD correlated closest with calprotectin (Spearman's rank correlation coefficient r=0.75), followed by CRP (r=0.53), blood leukocytes (r=0.42), and the CDAI (r=0.38)

Additionally, the testing found a response curve where the fecal calprotectin level corresponded with the severity of the disease (mild, moderate, or severe).(5)
Fecal calprotectin isn’t the only game in town – other markers, such as fecal lactoferrin, show promise as well (though with cost and stability issues).  Additionally, further biomarkers for differentiating Crohn’s and Ulcerative Colitis are being investigated, and may result in fewer invasive procedures for diagnosis and monitoring.  The fecal calprotectin testing is inexpensive (though not all insurance may yet cover it), and it is fairly new for doctors, but the evidence shows that it should be used more frequently at all stages of IBD analysis.

Bottom Line

·         Fecal calprotectin is a better measure for predicting IBD than traditional test like C-Reactive Protein tests.
·         Fecal calprotectin is correlated strongly with the level of disease activity, and can be used as part of monitoring.
·         The evidence shows that fecal calprotectin testing should be incorporated into both initial diagnostic and ongoing monitoring testing regimes.

1.       Costa, F., M. G. Mumolo, M. al Bellini, M. R. Romano, L. Ceccarelli, P. Arpe, C. Sterpi, S. Marchi, and G. Maltinti. "Role of faecal calprotectin as non-invasive marker of intestinal inflammation." Digestive and liver disease 35, no. 9 (2003): 642-647.
2.       Van Rheenen, Patrick F., Els Van de Vijver, and Vaclav Fidler. "Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis." BMJ: British Medical Journal 341 (2010).
3.       Costa, F., M. G. Mumolo, L. Ceccarelli, M. Bellini, M. R. Romano, C. Sterpi, A. Ricchiuti, S. Marchi, and M. Bottai. "Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease." Gut 54, no. 3 (2005): 364-368.
4.       Mao, Ren, Yinglian Xiao, Xiang Gao, Baili Chen, Yao He, Li Yang, Pinjin Hu, and Minhu Chen. "Fecal calprotectin in predicting relapse of inflammatory bowel diseases: A metaanalysis of prospective studies." Inflammatory Bowel Diseases 18, no. 10 (2012): 1894-1899.

5.       Schoepfer, Alain M., Christoph Beglinger, Alex Straumann, Michael Trummler, Stephan R. Vavricka, Lukas E. Bruegger, and Frank Seibold. "Fecal calprotectin correlates more closely with the Simple Endoscopic Score for Crohn's disease (SES-CD) than CRP, blood leukocytes, and the CDAI." The American journal of gastroenterology 105, no. 1 (2009): 162-169.

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