Review article: pathogenesis of Crohn's perianal fistula-understanding factors impacting on success and failure of treatment strategies.

Background: Evidence from groups who have studied fistula aetiology and extrapolation from interventional studies supports a multifactorial hypothesis of Crohn's perianal fistula, with several pathophysiological elements that may contribute to fistula formation, persistence and resistance to treatment.

Aim: An evidence synthesis of current understanding of pathophysiological factors underlying Crohn's perianal fistula is presented, exploring the fundamental reasons why some treatments succeed and others fail, as a means of focussing clinical knowledge on improving treatment of Crohn's perianal fistula.

Methods: Evidence to support this review was gathered via the Pubmed database. Studies discussing pathophysiological factors underpinning perianal fistula, particularly in Crohn's disease, were reviewed and cross-referenced for additional reports.

Results: Pathophysiological factors that impact on success or failure of interventions for Crohn's perianal fistulae include the high-pressure zone, obliterating the dead space, disconnecting the track from the anus, removing epithelialisation, eradicating sepsis and by-products of bacterial colonisation, correcting abnormalities in wound repair and removing the pro-inflammatory environment which allows fistula persistence. Most current interventions for Crohn's perianal fistulae tend to focus on a single, or at best two, aspects of the pathophysiology of Crohn's anal fistulae; as a result, failure to heal fully is common.

Conclusions: For an intervention or combination of interventions to succeed, multiple factors must be addressed. We hypothesise that correct, timely and complete attention to all of these factors in a multimodal approach represents a new direction that may enable the creation of an effective treatment algorithm for Crohn's anal fistula.