Tunnel vision: rethinking local therapy for perianal fistulas in Crohn's disease

Local therapies involving direct delivery of agents to fistula tracts in perianal fistulizing Crohn's disease (PFCD) have been explored but are not standard in clinical practice. We aimed to conduct a systematic review of local therapies for PFCD to evaluate their role in fistula closure, considering current pathophysiological insights and contemporary surgical and medical expertise.

We performed a systematic review assessing the efficacy of local therapies for PFCD, excluding mesenchymal stem cell therapies, which have been reviewed elsewhere. The reporting quality of the studies was assessed using a validated checklist.

The systematic review included 31 studies evaluating fibrin glue (n = 11), fistula plugs (n = 11), locally injected medications (n = 5), ointments (n = 3), and platelet-rich plasma (n = 2). Fibrin glue showed short-term success (healing rates 30%-91%) but poor long-term outcomes (26%-57%). Fistula plugs had variable success rates (15%-85%) with minimal benefit from repeated applications. Locally injected biologics achieved healing rates of over 60%, often with durable responses. Metronidazole ointment had only short-term efficacy, while tacrolimus had no significant benefit. A potential approach to improving the efficacy and durability of local therapies for PFCD may involve surgical preconditioning (through curettage and internal orifice closure) and the efficient delivery of agents into fistula tracts that modulate microbial communities, inflammation, and, ultimately, wound healing.

There is an unmet need to generate novel local therapies that achieve long-lasting fistula closure. To facilitate their development, the delineation of host and microbial pathways contributing to PFCD pathogenesis and research in drug delivery systems are needed.