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Medically reviewed by Dr. Shani S. Saks, D.O. on August 2, 2023

Anti-tumor necrosis factor therapy and surgical treatment are recommended for recurrent fistulas in the absence of luminal inflammation.

Perianal fistula is characterized by pathological connections between the perianal skin and the anorectal canal. The majority are cryptoglandular fistulas that develop from infected anal glands, whereas others arise from malignancies, Crohn’s disease (CD), or trauma.

This review article describes the similarities and differences between cryptoglandular fistulas and CD-associated fistulas based on clinical management, epidemiological characteristics, and pathogenesis. These findings are published in the Journal of Clinical Medicine.

Epidemiological Characteristics of Cryptoglandular and CD-Associated Fistulas

There is a variable incidence of cryptoglandular fistulas across countries. The incidence of CD-associated fistulas is associated with the duration of prolonged disease, and it may decrease following the administration of biologics in the form of anti-TNF-α. There is a male predominance in either type of fistula.

Pathogenesis of Cryptoglandular and CD-Associated Fistulas

Multiple factors contribute to the pathogenesis of perianal fistulas, including anal gland inflammation, intestinal inflammation, epithelial-mesenchymal transition (EMT), and disturbed microbiota. In cryptoglandular fistulas, the acute infection initially involves the perianal glands, followed by abscess formation leading to a draining tract and fistula. Pro-inflammatory cytokines continue to cause tissue damage in patients with cryptoglandular fistulas, whereas the microbiota contributes to the development and persistence of inflammation. 

On the contrary, in CD-associated fistulas, the pathogenesis involves chronic intestinal inflammation, abundant release of cytokines, and epithelial defects, which cumulatively result in epithelial–mesenchymal transition. The matrix metalloproteinases contribute to tissue damage, inflammation, and fistula formation, whereas the disturbed microbiota leads to inflammation and epithelial–mesenchymal transition.

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Treatment and Clinical Distinction of Cryptoglandular and CD-Associated Fistulas

Given that the therapeutic measures for cryptoglandular and CD-associated fistulas are different, clinicians need to distinguish between the two pathologies at the earliest possible time. Patients presenting with recurrent fistulas that are not associated with luminal inflammation should receive anti-tumor necrosis factor α therapy and surgical treatment.


Zhou, Z., Ouboter, L., Peeters, K., Hawinkels, L. J., Holman, F. A., Pascutti, M. F., Barnhoorn, M. C., & Van Der Meulen-De Jong, A. E. (2023). Crohn’s Disease-Associated and Cryptoglandular fistulas: Differences and similarities. Journal of Clinical Medicine, 12(2), 466. https://doi.org/10.3390/jcm12020466