Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sjögren's syndrome and rheumatoid arthritis

Abstract

Introduction: Faecal calprotectin (FC) has been proposed to be a biomarker of gastrointestinal (GI) disease in systemic sclerosis (SSc). The purpose of this study was to extend cross-sectional observations and prospectively assess the variability of FC over time in SSc patients. We also aimed to examine FC in relation to immunosuppressive therapy. Finally we wanted to analyse FC in other rheumatic diseases to evaluate the specificity of FC for SSc GI disease.

Methods: FC was measured in consecutive patients with SSc, primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA) and in healthy hospital workers. The intraindividual variability of FC in SSc was assessed with intra class correlation (ICC) and κ statistics. Associations between FC and objective markers of GI disease and immunosuppressive medication were investigated.

Results: FC was associated with micronutrient deficiency and GI pathology as assessed by cineradiography confirming our previous results. FC showed only a limited intra-individual variation in SSc, ICC = 0.69 (95% confidence interval, CI: 0.57-0.78) and κ = 0.64 (95% CI: 0.56-0.73). Generalised immunosuppression did not have any significant impact on FC. FC was significantly higher in SSc patients compared to patients with pSS or RA as well as compared to healthy subjects.

Conclusions: FC is a promising non-invasive biomarker for GI disease in SSc. In view of stable levels over time, FC could be a useful marker when novel, more specific drugs targeting the GI tract in SSc will be introduced.

Figure 1

In systemic sclerosis, faecal calprotectin is associated with pathological cineradiograhy. Individual and median faecal calprotectin levels in systemic sclerosis patients with different degrees of pathological cineradiographies. 1-way analysis of variance, P = 0.007. Please note the logarithmic scale on the y-axis.

Figure 2

In systemic sclerosis, faecal calprotectin is associated with micronutrient deficiency. Individual and median faecal calprotectin levels in systemic sclerosis patients with different degrees of micronutrient deficiency. 1-way analysis of variance, P = 0.005. Please note the logarithmic scale on the y-axis. Patients were subject to analysis of the following micronutrient deficiencies by laboratory examination of serum or plasma: iron, vitamin B₁₂, zinc and folic acid. Subjects with pathological testing according to local laboratory standards were regarded as micronutrient deficient. Patients with pathological testing for more than one of the aforementioned micronutrients were categorised as having multiple deficiencies.

Figure 3

Repeated testing of faecal calprotectin in systemic sclerosis. Faecal calprotectin at time point 2 as a function of faecal calprotectin at time point 1 in 93 SSc patients. ICC = 0.69 (95% CI: 0.57 to 0.78). Please note the logarithmic scale on the x- and y-axis. CI, confidence interval; ICC, intra class correlation.

Figure 4

Faecal calprotectin in different patient groups. Individual and median levels of faecal calprotectin in patients with systemic sclerosis (SSc) n = 93, primary Sjögren’s syndrome (pSS) n = 44, rheumatoid arthritis (RA) n = 24 and healthy controls n = 21. Please note the logarithmic scale on the y-axis.