STUDIES IN THE AETIOLOGY, INVESTIGATION AND TREATMENT OF PERIANAL FISTULA

Abstract

Background: Perianal fistulae are common and cause significant symptoms and psychosocial morbidity. Current theory suggests two distinct types: idiopathic (no established cause) and secondary, which usually arise from Crohn’s disease. Research to date has assumed that idiopathic and Crohn’s perianal fistulae differ in their pathogenesis and pathophysiology. This fundamental hypothesis has not yet been adequately tested. We therefore aimed to test the broad hypothesis that idiopathic and Crohn’s perianal fistulae differ in their pathogenesis and pathophysiology. Methods: We prospectively recruited a cohort of 61 participants (48 idiopathic, 13 Crohn’s disease) and phenotyped them in detail using clinical assessment, Perineal Disease Activity Index, EQ-5D-5L, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), operative assessment, biopsy, and clinical follow-up. We interrogated the biopsy samples in the laboratory to characterize their profiles for 30 cytokines and 39 phosphoproteins. Over 12,000 clinical and 23,500 laboratory measurements were made. Results: We found no clear differences in the clinical characteristics or the overall cytokine or phosphoprotein profiles between idiopathic and Crohn’s perianal fistulae. We also found no differences in the DCE-MRI measurements between the groups. Conclusions: We did not find good evidence to support our hypothesis. The alternative hypothesis offers a shift in the current research paradigm: idiopathic and Crohn’s perianal fistulae are the same pathology on a spectrum across which the pathogenic and pathophysiological features are distributed in a skewed manner. This may be the key to unravelling our understanding of the disease’s aetiology. It would also be a construct within which trials of biological therapy, such as infliximab, could be justified for idiopathic disease.