Perianal fistulizing Crohn's disease: pathogenesis, diagnosis and therapy

Key Points Factors involved in fistulizing perianal disease pathogenesis include a genetically determined altered immune response with increased production of cytokines, leading to upregulation of matrix metalloproteinases and epithelial-to-mesenchymal transition Essential evaluation of fistulas includes a clinical assessment of external openings, endoscopic assessment of proctitis and MRI to determine the anatomy of fistula tracts and presence of abscesses A top-down approach with medical therapy might provide maximal benefit for treatment of this aggressive manifestation of Crohn's disease Local injection of mesenchymal stem cells can induce remission in patients not responding to medical therapies, or avoid the exposure to systemic immunosuppression Surgery is still required in a high proportion of patients and should not be delayed when criteria of drug failure is met Perianal fistulizing Crohn's disease has a major negative effect on a patient's quality of life and is a predictor of poor long-term outcome. Here, the authors provide an up-to-date overview on the pathogenesis and diagnosis of fistulizing Crohn's disease, as well as therapeutic strategies. Perianal fistulizing Crohn's disease has a major negative effect on patient quality of life and is a predictor of poor long-term outcomes. Factors involved in the pathogenesis of perianal fistulizing Crohn's disease include an increased production of transforming growth factor β, TNF and IL-13 in the inflammatory infiltrate that induce epithelial-to-mesenchymal transition and upregulation of matrix metalloproteinases, leading to tissue remodelling and fistula formation. Care of patients with perianal Crohn's disease requires a multidisciplinary approach. A complete assessment of fistula characteristics is the basis for optimal management and must include the clinical evaluation of fistula openings, endoscopic assessment of the presence of proctitis, and MRI to determine the anatomy of fistula tracts and presence of abscesses. Local injection of mesenchymal stem cells can induce remission in patients not responding to medical therapies, or to avoid the exposure to systemic immunosuppression in patients naive to biologics in the absence of active luminal disease. Surgery is still required in a high proportion of patients and should not be delayed when criteria for drug failure is met. In this Review, we provide an up-to-date overview on the pathogenesis and diagnosis of fistulizing Crohn's disease, as we