A simple method for assessing intestinal inflammation in Crohn's disease

Abstract

Background and aims: Assessing the presence and degree of intestinal inflammation objectively, simply, and reliably is a significant problem in gastroenterology. We assessed faecal excretion of calprotectin, a stable neutrophil specific marker, as an index of intestinal inflammation and its potential use as a screening test to discriminate between patients with Crohn's disease and those with irritable bowel syndrome.

Methods: The validity of faecal calprotectin as a marker of intestinal inflammation was assessed in 22 patients with Crohn's disease (35 studies) by comparing faecal excretions and concentrations using four day faecal excretion of (111)indium white cells. A cross sectional study assessed the sensitivity of faecal calprotectin concentration for the detection of established Crohn's disease (n=116). A prospective study assessed the value of faecal calprotectin in discriminating between patients with Crohn's disease and irritable bowel syndrome in 220 patients referred to a gastroenterology clinic.

Results: Four day faecal excretion of (111)indium (median 8.7%; 95% confidence interval (CI) 7-17%; normal <1.0%) correlated significantly (p<0.0001) with daily (median ranged from 39 to 47 mg; normal <3 mg; r=0.76-0.82) and four day faecal calprotectin excretion (median 101 mg; 95% CI 45-168 mg; normal <11 mg; r=0.80) and single stool calprotectin concentrations (median 118 mg/l; 95% CI 36-175 mg/l; normal <10 mg/l; r=0.70) in patients with Crohn's disease. The cross sectional study showed a sensitivity of 96% for calprotectin in discriminating between normal subjects (2 mg/l; 95% CI 2-3 mg/l) and those with Crohn's disease (91 mg/l; 95% CI 59-105 mg/l). With a cut off point of 30 mg/l faecal calprotectin has 100% sensitivity and 97% specificity in discriminating between active Crohn's disease and irritable bowel syndrome.

Conclusion: The calprotectin method may be a useful adjuvant for discriminating between patients with Crohn's disease and irritable bowel syndrome.

Figure 1

(A) Four day faecal excretion of ¹¹¹indium labelled white cells (% dose) plotted against four day faecal excretion (mg) of calprotectin (r=0.80, p<0.001). (B) Four day faecal excretion of ¹¹¹indium white cells plotted against single stool calprotectin concentrations (mg/l) (r=0.70, p<0.001) in patients with Crohn's disease.

Figure 2

Concentrations of calprotectin (on a logarithmic scale) in faeces in 116 patients with Crohn's disease compared with controls. The horizontal line indicates the upper normal limit (+2SD) for calprotectin concentrations.

Figure 3

Concentrations of calprotectin (on a logarithmic scale) in faeces in patients subsequently diagnosed as having Crohn's disease, irritable bowel syndrome (IBS), and miscellaneous diseases. The upper normal limit (+2SD) for calprotectin concentrations is 10 mg/l.

Figure 4

Serum C reactive protein levels in patients subsequently diagnosed as having Crohn's disease, irritable bowel syndrome (IBS), and miscellaneous disease. The upper limit of normal, which had previously been established at the Department of Immunology, King's College Hospital, for C reactive protein is 5 mg/l.

Figure 5

Receiver operating characteristic analysis of the ability of calprotectin, C reactive protein (CRP), and erythrocyte sedimentation rate (ESR) to discriminate between patients with Crohn's disease and the irritable bowel syndrome. The unbroken line ("no discrimination") indicates values that have no discriminatory value. Note that on the vertical axis, the scale is from no (0) to complete (1 or 100%) sensitivity. The horizontal axis is a reciprocal scale (1−specificity). The optimum performance of a test is determined either as the highest sum of the specificity and sensitivity or at an acceptable level of sensitivity for the given disease. A cut off value of 30 mg/l for faecal calprotectin gives 100% sensitivity and 97% specificity for discriminating between patients with Crohn's disease and the irritable bowel syndrome.