Fecal calprotectin in systemic sclerosis: Light and shade of a promising tool

We read with great interest the study by Marie et al, who investigated the relationship between fecal calprotectin (FC) and gastrointestinal involvement in an unselected population of patients affected by systemic sclerosis (SSc). In their series and according to current literature, 74% of patients were affected by severe esophageal motor impairment, 51.7% had delayed gastric emptying and 35% had interstitial lung disease. Moreover, the authors reported that about two thirds of patients referred for testing had abnormal FC levels (>50mcg/g), whose increase was directly related to the severity of gastrointestinal symptoms, evaluated by means of the Global Symptom Score (GSS), and with the impairment of esophageal and gastric motility. Finally, prevalence of Small Intestinal Bacterial Overgrowth (SIBO), as assessed by means of glucose H2/CH4 breath test, was about 35%. Highly elevated levels of FC (>200 mcg/g) strictly related with the presence of SIBO reaching its highest diagnostic accuracy for values > 275mcg/g (ROC 0.97±0.0001). We really appreciated this work which underlines the utility of a non-invasive fecal test to identify patients with gastro-intestinal involvement in SSc. Moreover, the correlation between fecal calprotectin levels and response to therapy provides additional confirmation to this diagnostic approach. Nevertheless, we believe that the strength of their findings should be considered with caution because of the following considerations: 1. the criteria employed to diagnose SIBO by Glucose Breath Test (GBT). the lack of oral-cecal transit time (OCTT) measurements. It is well known that methane production is higher and more frequently found in subjects with constipation and its concentration in breath samples, when increased, is usually constant during the test. Moreover, it has been also reported that SSc patients often present prolonged OCTT. Accordingly, the decision to consider an increase of CH4 > 10 ppm on two consecutive measurements within the 2 h of the examination as a positive GBT for SIBO may have led to over diagnose a proportion of SSc patients with constipation as affected by SIBO. At this regard, the assessment of OCTT rather than gastric emptying would have provided more valuable information to the study. In fact, about 2/3 of the patients they studied had severe esophageal motility impairment and it has been shown that this occurs often in association with an intestinal involvement. This aspect might have also affected the relative low eradication rate (9/22; 41%) the Authors achieved, despite 3 months of rotating courses of antibiotics. In a recent study by our group, indeed, eradication of SIBO was obtained in 73% of SSc patients with a single 10-day course of rifaximin 1200mg/d, with a significant reduction of symptoms in 73% of them. In a further study conducted in patient with SIBO, we showed that the association of rifaximin with soluble fibers, rather than the use of antibiotics alone, increased the eradication rate from 62% to 87%. In our opinion, similar approaches should be preferred to increasing the dosage or prolonging the administration of antibiotics. In conclusion, the study by Marie et al provides new approaches to the management of SSc patients. The dosage of fecal calprotectin alone or in combination with other tests might be able to identify patients with gastrointestinal involvement, such as impaired gastro-esophageal motility, which, in turn, may favor malnutrition and interstitial lung disease, as well as SIBO with its complications (i.e. abdominal symptoms, malabsorption and ultimately body wasting). These comorbidities should be always carefully investigated with appropriate tests that must be accurately interpreted, because they are highly common in scleroderma and may severely impact the quality of life of these patients.