Diagnosis and differentiation of intestinal tuberculosis and Crohn's disease by use of faecal and serum calprotectin.

Abstract

BACKGROUND: The incidence of both intestinal tuberculosis (ITB) and Crohn's disease (CD) increases worldwide. ITB may easily be confounded with CD, a mimicry that may pose diagnostic challenges. Misdiagnosing a patient with ITB as CD may be lethal given the immunosuppressive nature of CD therapy. Empiric ITB treatment may delay therapy of CD or make it difficult to confirm ITB at a later stage. Currently, differentiating between ITB and CD is time consuming, labour intensive and costly. Knowledge of ITB is largely based on a few studies in populations with low TB prevalence and is of limited use in TB endemic regions. There is a need for simple, inexpensive and rapid ways to diagnose ITB, applicable in both TB endemic areas and in areas of low TB prevalence. Calprotectin is a protein released from neutrophils and macrophages in response to inflammation. Faecal calprotectin is markedly elevated in patients with active CD. As both ITB and CD are chronic granulomatous inflammations, it is suggested that increased calprotectin levels may be found in ITB too. The aim of this study is to establish the levels of faecal and serum calprotectin in patients with ITB. METHODS: Blood and faecal samples from 35 healthy controls and 17 newly diagnosed ITB patients in India have been analysed since October 2009. The calprotecin levels have been established by use of conventional ELISA and by Point Of Care rapid tests (Bühlmann Laboratories AG, Switzerland). RESULTS: Median faecal (F-) calprotecin concentration was 15 lg/g (n=35) in the control subjects and 310 lg/g (n=17) in the ITB patiens. The distribution of F-calprotectin in the ITB patients was >300 lg/g in 9/17; 200-299 in 1/17; 100-199 in 2/17 and < 100 in 5/17. A good correlation was found between the ELISA method and the lateral flow rapid tests analysed by the POC device (r=0.921, p<0.0001). Median serum(S-) calprotectin concentration was 4,0 lg/ml (n=35) in the control subjects and 8,5 lg/ml (n=15) in the ITB patients. The median F-/Scalprotectin ratio was 3,9 (95% CI, 3.7-10.6) in the control group and 28,6 (95% CI, 18.7-115.5) in the ITB group. CONCLUSION: As per August 2010, results show that F-calprotectin and S-calprotectin are moderately elevated in patients with active ITB. F-calprotectin was lower than we expected. Elevated S-calprotectin may be used as a diagnostic tool for ITB in TB endemic areas when analysed in conjunction with F-calprotectin and TB specific parameters; the F-/S-calprotectin ratio may be used to discriminate between ITB and healthy subjects. Furthermore, as patients with active CD have a markedly high Fcalprotectin level and a normal S-calprotectin level, the F-/S-calprotectin ratio may be used to differentiate CD from ITB. We therefore propose that the F-/S-calprotectin ratio may be used to differentiate between CD, ITB and healthy subjects, and that calprotectin analysis may be established as a simple and inexpensive tool in this regard.