Editorial: Examining Perianal Fistulising Crohn's Disease Through the Lens of Wound Repair

Abstract

Perianal fistulising Crohn's disease (PFCD), a chronic debilitating condition affecting a third of patients with CD [1], carries substantial associated morbidity and negatively impacts quality of life (QoL). The three basic tenets of PFCD management have been to drain sepsis, control inflammation and heal the fistula, if appropriate. The caveat is attached to the third tenet because not all Crohn's fistulas are suitable for curative treatment; the principal focus of management is QoL, driven by the patient's expectations, as formally recognised in the recent comprehensive classification of PFCD [2].

Control of inflammation in PFCD improved greatly with biologic medications and, since the ACCENT trials [3], anti-TNFa therapy has been the mainstay of treatment. While newer medical therapies show promise in PFCD, none has matched its efficacy. Despite this, response rates to medical therapy are incomplete and recurrences common, and long-term fistula healing rates remain low [4].

McCurdy et al. have addressed reasons for these failures, challenging us to consider PFCD management through the lens of the phases of wound repair: localised inflammation, cell recruitment and tissue remodelling. These three phases lead to the possible outcomes of healing, tract epithelialisation or persistent chronic wounds. Consideration of the molecular and structural mechanisms operating in these phases provides a rationale for different treatment strategies, particularly for some where controversy persists [5].

For instance, the inflammatory phase is characterised by the presence of specific bacteria and pathogen-associated mucosal patterns that support the use of antibiotics in this phase and during the induction of anti-TNFa therapy [6]. Wound repair involves tightly controlled homeostatic mechanisms; under- or over-activity of these leads to dysfunctional repair, very evident in the epithelialisation of PFCD tracts. While re-epithelialisation is crucial for healing of open wounds, its extension into tubular structures such as fistulas impairs healing. In many cryptoglandular fistulas, this can be circumvented by fistulotomy, but this is usually not possible in PFCD.

This makes timing of seton removal crucial—targeting the point where inflammation is controlled but tract epithelialisation is yet to occur. While the recommendation of removing setons after the second induction dose of infliximab often appears too soon to control inflammation, the median of 8 months reported in many centres may well be too long and impair, rather than facilitate, healing [7].

To prevent epithelialisation and persistent inflammatory stimulus in the fistula, control of the internal opening remains key. Both PISA II [8] and ADMIRE-CDII [9], that utilised the ‘scrape and close’ technique, supported surgical intervention in addition to seton removal where possible.

Attempts to heal fistulas in CD are possible only if inflammation is controlled. Persistent proctitis remains a contraindication to definitive surgical procedures and an exclusion in clinical trials. This reinforces that, while all three tenets of PFCD treatment are important, success is driven by our ability to control inflammation. Hence, the work of McCurdy et al., integrating molecular inflammatory mechanisms with management, plays a crucial role in improving outcomes in PFCD.

Tim Eglinton: conceptualization, writing – original draft, writing – review and editing.

The author declares no conflicts of interest.

This article is linked to McCurdy et al paper. To view this article, visit https://doi.org/10.1111/apt.18466.