Etiology of perianal Crohn's disease: role of genetic, microbiological, and immunological factors.

Perianal fistulation is a common complication of Crohn's disease (CD). Fistulating perianal CD appears to represent a distinct phenotype of CD, separate from luminal fistulating disease, with differing disease behavior and which often requires different therapeutic strategies. The etiology of Crohn's perianal fistulae appears to have genetic, microbiological, and immunological components. Relationships with IBD5, which codes for the organic/cation transporter and IRGM, important in the autophagy pathway, have been identified but further genetic associations remain elusive. The partially efficacious use of antibiotics and fecal diversion imply a microbiological component and, similarly, the partial efficacy of immunosuppressants and anti-tumor necrosis factor alpha (TNFalpha) treatments suggest not only that an immunological process is taking place, but also that microbiota alone cannot account for the pathogenesis. Recent work implicates failures in the tissue injury/repair process with myofibroblasts, matrix metalloproteinases, and an epithelial-to-mesenchymal transition being possible culprits. We examine these areas in a review of the current understanding of the etiology of Crohn's perianal fistulae.