STUDIES IN THE AETIOLOGY, INVESTIGATION AND TREATMENT OF PERIANAL FISTULA
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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.
Authors
Haddow, James BoydCollections
- Theses [4099]