Clinical relevance of calprotectin in patients with perianal fistulas in Crohn's disease and cryptoglandular fistulas.

Background and aims: Previous literature suggests that faecal calprotectin (FC) discriminates Crohn's disease perianal fistulas from cryptoglandular fistulas, irrespective of luminal disease. This study aims to prospectively validate this and analyse if increased local fistula calprotectin levels are associated with fistula characteristics.

Methods: In this prospective study, all consecutive patients with an active perianal fistula undergoing examination under anaesthesia were included. Faecal and fistula tract scraping calprotectin levels were determined. The primary objective was to analyse whether FC levels could be used to differentiate between Crohn's disease and cryptoglandular perianal fistulas. Secondary outcome parameters were the levels of local calprotectin in fistula scrapings and their correlation with fistula characteristics.

Results: Sixty-three patients were included in this study (perianal Crohn's disease; 45, cryptoglandular; 18). Faecal calprotectin levels were significantly higher in Crohn's disease patients compared with cryptoglandular fistula (354.3 [58.8-1076.3] vs. 47.3 [14.6-233.6] μg/g, p = 0.003). Faecal calprotectin could accurately discriminate Crohn's disease patients with active luminal disease from patients without luminal disease (median [interquartile range]) (1167.0 [557.0-2806.3] vs. 93.0 [47.5-571.6] μg/g, p = 0.001). Faecal calprotectin was not related to calprotectin levels in fistula scrapings. No fistula characteristic was found to be correlated to scraping calprotectin, but a correlation was found with the TOpCLASS classification system, which stratifies fistulas according to disease severity and outcome: class 2a (amenable for repair), class 2b (symptom control) and class 2c (gradually debilitating disease): 140[31.0-149.0]) μg/g versus 706[198.5-1936] μg/g versus 4000[1337-5894] μg/g, p < 0.001). Scraping calprotectin was also related to pronounced hyperintensity of the fistula tract on MRI in Crohn's disease patients: (69.0[30.0-821.0] vs. 1284.0[204.3-4185.5]; p = 0.01)) and cryptoglandular patients: (30.0[13.5-80.5] vs. 3012.0 [923.8-5021.0]; p = 0.002).

Conclusion: Crohn's disease and cryptoglandular perianal fistulas differ in FC levels. Local fistula calprotectin production did not explain this difference, implying FC reflects the luminal condition. A correlation exists between scraping calprotectin levels and Crohn's disease fistula severity, which could be clinically relevant for prognostic cohorts and tailored treatment.