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Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis

BMJ 2010; 341 doi: (Published 15 July 2010) Cite this as: BMJ 2010;341:c3369

calprotectin is a good screening test to increase the likelihood of IBD, including ileal Crohn’s disease

We appreciate the response from Roblin and Phelip, which allows us to
clear up a misunderstanding. In our meta-analysis (1) we evaluated whether
including a test for faecal calprotectin in the diagnostic pathway is
beneficial for patients with suspected but unconfirmed inflammatory bowel
disease. We concluded that the numbers of false negatives (missed cases)
and false positives (cases without inflammatory bowel disease who go on to
have endoscopy) are acceptable when faecal calprotectin is used as
screening test. In the “new” diagnostic pathway only patients with a
calprotectin value above the cut-point continue for endoscopy.

Roblin and Phelip suggest that the diagnostic accuracy of
calprotectin may be lower in a subgroup of patients with undiagnosed ileal
Crohn’s disease. This suggestion implies that the number of missed cases
is higher when the inflammation is located in the ileum. Roblin and Phelip
refer to two papers that were excluded from our meta-analysis based on
wrong patient spectrum and poor methodological quality (2, 3). Both papers
reported the recruitment of patients with confirmed inflammatory bowel
disease and evaluated the value of calprotectin to predict relapse. In
neither of the studies was relapse confirmed with endoscopy. We only
included studies that recruited patients with suspected inflammatory bowel
disease and that compared faecal calprotectin levels with the results of
endoscopy (reference standard).

Triggered by the letter of Roblin and Phelip we searched for other
diagnostic studies published in Medline that reported the location of
Crohn’s disease in combination with endoscopy and calprotectin testing. We
identified six studies with a fully paired design and better
methodological quality than the two cited by Roblin and Phelip. Five
studies recruited patients with confirmed Crohn’s disease (4-8), and one
recruited patients with suspected inflammatory bowel disease (9). The
latter was also included in our meta-analysis. No study showed a
statistically significant difference in calprotectin levels between
proximal and distal sites of Crohn’s disease, although there was a trend
towards a higher degree of faecal calprotectin increase in colonic

In our meta-analysis we recommend that in the “new” diagnostic
pathway only patients with a calprotectin value above the cut-point (>
50 to 150 ìg/g) continue for endoscopy. Every increase above the cut-point
(irrespective of the magnitude) indicates a higher likelihood of
inflammatory bowel disease and justifies endoscopic evaluation. A
calprotectin value of 600 instead of 900 ìg/g makes no difference for the
sensitivity and specificity. There is no evidence to support the
suggestion of Roblin and Phelip that patients with ileal Crohn’s disease
will be wrongly excluded from endoscopy when faecal calprotectin is used
for screening. Including a test for faecal calprotectin in the
investigation of suspected inflammatory bowel disease reduces the number
of adults requiring endoscopy by 67%, and the number of children and
teenagers requiring endoscopy with 35%. The backside of this screening
strategy is that diagnosing IBD may be delayed in a small proportion of
the affected patients. We conclude that measuring faecal calprotectin is a
good screening test to increase the likelihood of inflammatory bowel
disease, including ileal Crohn’s disease.

1. van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for
screening of patients with suspected inflammatory bowel disease:
diagnostic meta-analysis. BMJ. 2010;341:c3369.

2. Costa F, Mumolo MG, Ceccarelli L, Bellini M, Romano MR, Sterpi C
et al. Calprotectin is a stronger predictive marker of relapse in
ulcerative colitis than in Crohn's disease. Gut 2005;54:364-8.

3. D'Inca R, Dal Pont E, Di Leo V, Benazzato L, Martinato M,
Lamboglia F et al. Can calprotectin predict relapse risk in inflammatory
bowel disease? Am J Gastroenterol 2008;103: 2007-14.

4. Sipponen T, Karkkainen P, Savilahti E, Kolho KL, Nuutinen H,
TurunenU, et al. Correlation of faecal calprotectin and lactoferrin with
an endoscopic score for Crohn’s disease and histological findings. Aliment
Pharmacol Ther 2008;28:1221-9.

5. Kaiser T, Langhorst J,Wittkowski H, Becker K, FriedrichAW, Rueffer
A, et al. Faecal S100A12 as a non-invasive marker distinguishing
inflammatory bowel disease from irritable bowel syndrome. Gut

6. Bremner A, Roked S, Robinson R, Phillips I, Beattie M. Faecal
calprotectin in children with chronic gastrointestinal symptoms. Acta
Paediatr 2005;94:1855-8.

7. Leach ST, Yang Z, Messina I, et al. Serum and mucosal S100
proteins, calprotectin (S100A8 ⁄ S100A9) and S100A12, are elevated
at diagnosis in children with inflammatory bowel disease. Scand J
Gastroenterol 2007; 42: 1321–31.

8. Schoepfer AM, Beglinger C, Straumann A, Trummler M, Vavricka SR,
Bruegger LE, Seibold F. Fecal calprotectin correlates more closely with
the Simple Endoscopic Score for Crohn's disease (SES-CD) than CRP, blood
leukocytes, and the CDAI. Am J Gastroenterol. 2010 Jan;105(1):162-9.

9. Schroder O, Naumann M, Shastri Y, Povse N, Stein J. Prospective
evaluation of faecal neutrophil-derived proteins in identifying intestinal
inflammation: combination of parameters does not
improve diagnostic accuracy of calprotectin. Aliment Pharmacol Ther

Competing interests:
None declared

Competing interests: No competing interests

25 August 2010
Patrick F van Rheenen
paediatric gastroenterologist
Els Van de Vijver, and Vaclav Fidler
Beatrix Children's Hospital - UMCG, PO Box 30001, 9700 RB Groningen, Netherlands