Pathogenesis of Perianal Fistulising Crohn's Disease: Current Knowledge, Gaps in Understanding, and Future Research Directions

Fistulising perianal involvement is a common presentation of Crohn's disease. Perianal Crohn's disease dramatically impairs patients' social and sexual life and its management remains a critical challenge in field of inflammatory bowel disease. No medical therapy is specifically designed for the treatment of perianal Crohn's disease, largely due to the poorly understood pathophysiology. Limited evidence from preclinical and clinical studies suggests that the initiation, progression, and maintenance of Crohn's disease-associated perianal fistulas involves complex interactions between host, microbial, and environmental factors. This review intends to discuss the possible roles of genetic predisposition, mucosal immunity, and gut microbiome in perianal Crohn's disease, and considers how epithelial-to-mesenchymal transition may contribute to the pathogenesis. It also summarises recent advances on the development of animal models and new therapies for perianal Crohn's disease. At the end, we discussed future directions in basic, translational, and clinical research that may dramatically improve our understanding of perianal Crohn's disease and open avenues for novel therapeutic strategies with a multidisciplinary approach. Overall, this review aims to identify current gaps in understanding of perianal fistulising Crohn's disease and to explore future research priorities for this debilitating condition.

Automated summary

Perianal Crohn's disease is a common and debilitating presentation of the disease, and its treatment remains a challenge due to the lack of understanding of its pathophysiology. This review discusses the potential roles of genetic predisposition, mucosal immunity, and gut microbiome in the disease, as well as the contribution of epithelial-to-mesenchymal transition to its pathogenesis. Recent advances in animal models and new therapies are also summarized. Future research directions are proposed to improve our understanding and develop novel therapeutic strategies for this condition.