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Treatment of perianal manifestations of Crohn's disease

https://doi.org/10.31146/1682-8658-ecg-234-2-187-193

Abstract

Currently, the treatment of patients with perianal manifestations of Crohn's disease is a complex task that requires an integrated approach. Existing methods of surgical correction are often only temporary, the rate of relapse of the disease remains high. Unsatisfactory treatment results, especially in the late postoperative period, a small number of clinical observations in published scientific papers devoted to the treatment of perianal fistulas against the background of Crohn's disease, the lack of a unified treatment strategy for these patients, as well as the low reliability of the results, determine the need for further research.

About the Authors

I. A. Nikitina
Moscow Clinical Scientific Center named after Loginov MHD
Russian Federation


A. V. Leontyev
Moscow Clinical Scientific Center named after Loginov MHD; Moscow Financial and Industrial University «Synergy»
Russian Federation


V. V. Sytkov
Russian University of Medicine; Federal Scientific and Clinical Center for Children and Adolescents of the Federal Medical and Biological Agency
Russian Federation


M. A. Danilov
Moscow Clinical Scientific Center named after Loginov MHD
Russian Federation


A. I. Khavkin
Belgorod State Research University. Ministry of Science and Higher Education of the Russian Federation; Research Clinical Institute of Childhood, Ministry of Health of the Moscow Regio
Russian Federation


E. A. Yablokova
Research Clinical Institute of Childhood, Ministry of Health of the Moscow Regio; Sechenov University
Russian Federation


M. A. Orlyuk
Moscow Financial and Industrial University «Synergy»
Russian Federation


References

1. Gaertner W.B., Burgess P.L., Davids J.S., Lightner A.L., Shogan B.D., Sun M.Y., Steele S.R., Paquette I.M., Feingold D.L.; Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Anorectal Abscess, Fistula-in-Ano, and Rectovaginal Fistula. Dis Colon Rectum. 2022 Aug 1;65(8):964-985. doi: 10.1097/DCR.0000000000002473.

2. Schwartz D.A., Peyrin-Biroulet L., Lasch K., Adsul S., Danese S. Efficacy and Safety of 2 Vedolizumab Intravenous Regimens for Perianal Fistulizing Crohn’s Disease: ENTERPRISE Study. Clin Gastroenterol Hepatol. 2022;20(5):1059-1067.e9. doi: 10.1016/j.cgh.2021.09.028.

3. Vuyyuru S.K., Solitano V., Narula N. et al. Pharmacological Therapies for the Management of Fistulizing Crohn’s Disease: A Systematic Review and Meta-Analysis. J Crohns Colitis. 2024;18(4):589-603. doi: 10.1093/ecco-jcc/jjad185.

4. Anosov I.S., Nanaeva B.A., Vardanyan A.V., Zakharov M.A. Perianal fistulas in Crohn’s disease (review). Koloproktologia. 2023;22(1):128-137. doi: 10.33878/2073-7556-2023-22-1-128-137.@@ Аносов И.С., Нанаева Б.А., Варданян А.В., Захаров М.А. Перианальные свищи при болезни Крона (обзор литературы). Колопроктология. 2023;22(1):128-137.

5. Shelygin Yu.A., Ivashkin V.T., Achkasov S.I. et al. Clinical guidelines. Crohn’s disease (К50), adults. Koloproktologia. 2023;22(3):10-49. doi: 10.33878/2073-7556-2023-22-3-10-49.@@ Шелыгин Ю.А., Ивашкин В.Т., Ачкасов С.И. и соавт. Клинические рекомендации. Болезнь Крона (К50), взрослые. Колопроктология. 2023;22(3):10-49. doi: 10.33878/2073-7556-2023-22-3-10-49.

6. Rizzo G., Rubbino F., Elangovan S. et al. Dysfunctional Extracellular Matrix Remodeling Supports Perianal Fistulizing Crohn’s Disease by a Mechanoregulated Activation of the Epithelial-to-Mesenchymal Transition. Cell Mol Gastroenterol Hepatol. 2023;15(3):741-764. doi: 10.1016/j.jcmgh.2022.12.006.

7. Sun X., Gao H., Lu L., Wang Q., Li Y., Gu Y. Tumor necrosis factor receptor-associated factor 5 enhances perianal fistulizing Crohn’s disease through epithelial-mesenchymal transition. Cytojournal. 2024;21:82. Published 2024 Dec 31. doi: 10.25259/Cytojournal_148_2024.

8. Bataille F., Rohrmeier C., Bates R. et al. Evidence for a role of epithelial mesenchymal transition during pathogenesis of fistulae in Crohn’s disease. Inflamm Bowel Dis. 2008;14(11):1514-1527. doi: 10.1002/ibd.20590.

9. Cheng F., Huang Z., Li Z. Mesenchymal stem-cell therapy for perianal fistulas in Crohn’s disease: a systematic review and meta-analysis. Tech Coloproctol. 2019;23(7):613-623. doi: 10.1007/s10151-019-02024-8.

10. Bislenghi G., Wolthuis A., Van Assche G., Vermeire S., Ferrante M., D’Hoore A. Cx601 (darvadstrocel) for the treatment of perianal fistulizing Crohn’s disease. Expert Opin Biol Ther. 2019;19(7):607-616. doi: 10.1080/14712598.2019.1623876.

11. Sun M., Ju J., Xu H., Wang Y.Intestinal fungi and antifungal secretory immunoglobulin A in Crohn’s disease. Front Immunol. 2023;14:1177504. Published 2023 Jun 8. doi: 10.3389/fimmu.2023.1177504.

12. Meima-van Praag E.M., van Rijn K.L., Monraats M.A., Buskens C.J., Stoker J. Magnetic resonance imaging after ligation of the intersphincteric fistula tract for high perianal fistulas in Crohn’s disease: a retrospective cohort study. Colorectal Dis. 2021;23(1):169-177. doi: 10.1111/codi.15296.

13. Kotenko K.V., Kovalev S.A., Bedzhanyan A.L. et al. Modern surgical technologies in the treatment of patients with chronic paraproctitis. Pirogov Russian Journal of Surgery. 2022;(4):80-85. (In Russ.) doi: 10.17116/hirurgia202204180.@@ Котенко К.В., Ковалев С.А., Беджанян А.Л. и др. Современные хирургические технологии в лечении больных хроническим парапроктитом. Хирургия. Журнал им. Н.И. Пирогова. 2022;(4):80-85. doi: 10.17116/hirurgia202204180.

14. Parian A.M., Obi M., Fleshner P., Schwartz D.A. Management of Perianal Crohn’s Disease. Am J Gastroenterol. 2023;118(8):1323-1331. doi: 10.14309/ajg. 0000000000002326.

15. Wang H., Jiang H.Y., Zhang Y.X., Jin H.Y., Fei B.Y., Jiang J.L. Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials [published correction appears in Stem Cell Res Ther. 2024 Feb 16;15(1):45. doi: 10.1186/s13287-024-03664-w.]. Stem Cell Res Ther. 2023;14(1):103. Published 2023 Apr 26. doi: 10.1186/s13287-023-03331-6.

16. Adamina M., Minozzi S., Warusavitarne J. et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Surgical Treatment. J Crohns Colitis. 2024;18(10):1556-1582. doi: 10.1093/ecco-jcc/jjae089.

17. Bemelman W.A., Warusavitarne J., Sampietro G.M. et al. ECCO-ESCP Consensus on Surgery for Crohn’s Disease. J Crohns Colitis. 2018;12(1):1-16. doi: 10.1093/ecco-jcc/jjx061.

18. García-Olmo D., Gómez-Barrera M., de la Portilla F. Surgical management of complex perianal fistula revisited in a systematic review: a critical view of available scientific evidence. BMC Surg. 2023;23(1):29. Published 2023 Feb 5. doi: 10.1186/s12893-023-01912-z.

19. Geldof J., Iqbal N., LeBlanc J.F. et al. Classifying perianal fistulising Crohn’s disease: an expert consensus to guide decision-making in daily practice and clinical trials. Lancet Gastroenterol Hepatol. 2022;7(6):576-584. doi: 10.1016/S2468-1253(22)00007-3.

20. Devi J., Ballard D.H., Aswani-Omprakash T., Parian A.M., Deepak P. Perianal fistulizing Crohn’s disease: Current perspectives on diagnosis, monitoring and management with a focus on emerging therapies. Indian J Gastroenterol. 2024;43(1):48-63. doi: 10.1007/s12664-024-01524-2.

21. Kim H., Lee D.I., Moon S.K., Park S.J., You M.W. Typical MR features and interpretation of perianal fistulas in patients with Crohn’s disease. Eur J Radiol. 2023;167:111046. doi: 10.1016/j.ejrad.2023.111046.

22. Lee E.H., Yang H.R., Kim J.Y.Comparison of Transperianal Ultrasound With Colonoscopy and Magnetic Resonance Imaging in Perianal Crohn Disease. J Pediatr Gastroenterol Nutr. 2018;66(4):614-619. doi: 10.1097/MPG.0000000000001752.

23. Sahni V.A., Ahmad R., Burling D. Which method is best for imaging of perianal fistula?. Abdom Imaging. 2008;33(1):26-30. doi: 10.1007/s00261-007-9309-y.

24. Raine T., Myrelid P., Gordon H., Adamina M. ECCO Crohn’s Disease Guidelines-A Personal View of the Journey from Questions to Recommendations. J Crohns Colitis. 2024;18(10):1527-1528. doi: 10.1093/ecco-jcc/jjae107.

25. Kaur M., Panikkath D., Yan X. et al. Perianal Crohn’s Disease is Associated with Distal Colonic Disease, Stricturing Disease Behavior, IBD-Associated Serologies and Genetic Variation in the JAK-STAT Pathway. Inflamm Bowel Dis. 2016;22(4):862-869. doi: 10.1097/MIB.0000000000000705.

26. Gionchetti P., Dignass A., Danese S. et al. 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn’s Disease 2016: Part 2: Surgical Management and Special Situations. Journal of Crohn’s and Colitis. 2017;11(2):135-149. doi: 10.1093/ecco-jcc/jjw169.

27. Shelygin Yu.A., Titov A. Yu., Anosov I.S., Kostarev I.V., Kozlov V.A. Results of using the LIFT technique in the treatment of rectal fistulas. Coloproctology. 2017;(3S):50-51. (in Russ.)@@ Шелыгин Ю.А., Титов А.Ю., Аносов И.С., Костарев И.В., Козлов В.А. Результаты применения LIFT методики при лечении прямокишечных свищей. Колопроктология. 2017;(3S):50-51.

28. van Praag E.M., Stellingwerf M.E., van der Bilt J.D.W., Bemelman W.A., Gecse K.B., Buskens C.J. Ligation of the Intersphincteric Fistula Tract and Endorectal Advancement Flap for High Perianal Fistulas in Crohn’s Disease: A Retrospective Cohort Study. J Crohns Colitis. 2020;14(6):757-763. doi: 10.1093/ecco-jcc/jjz181.

29. Garcia-Olmo D., Gilaberte I., Binek M. et al. Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel (Mesenchymal Stem Cell Treatment) in Patients With Perianal Fistulizing Crohn’s Disease: ADMIRE-CD Phase 3 Randomized Controlled Trial. Dis Colon Rectum. 2022;65(5):713-720. doi: 10.1097/DCR.0000000000002325.

30. Merten J., Eichelmann A.K., Mennigen R., Flammang I., Pascher A., Rijcken E. Minor Sphincter Sparing Surgery for Successful Closure of Perianal Fistulas in Patients with Crohn’s Disease. J Clin Med. 2021;10(20):4721. Published 2021 Oct 14. doi: 10.3390/jcm10204721.

31. Esposito C., Autorino.G, Cerulo M. et al. Video-assisted anal fistula treatment (VAAFT) combined with ozonide oil dressing: standardization of technique in pediatric patients. Surg Endosc. 2024;38(4):2273-2279. doi: 10.1007/s00464-024-10759-1.

32. Bemelman W.A., Warusavitarne J., Sampietro G.M. et al. ECCO-ESCP Consensus on Surgery for Crohn’s Disease. J Crohns Colitis. 2018;12(1):1-16. doi: 10.1093/ecco-jcc/jjx061.

33. Banasiewicz T., Eder P., Rydzewska G. et al. Statement of the polish expert group on the current practice and prospects for the treatment of complex perianal fistulas in Crohn’s disease. Update 2021. Pol Przegl Chir. 2021;93(4):70-79. doi: 10.5604/01.3001.0015.2335.

34. Vidon M., Munoz-Bongrand N., Lambert J. et al. Long-term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn’s disease. Colorectal Dis. 2021;23(4):894-900. doi: 10.1111/codi.15477.

35. Schaad M., Schoepfer A., Rossel J.B. et al. Long-Term Outcome of Surgery for Perianal Crohn’s Fistula. Medicina (Kaunas). 2024;60(7):1035. Published 2024 Jun 24. doi: 10.3390/medicina60071035.

36. Tsai L., McCurdy J.D., Ma C. et al. Epidemiology and natural history of perianal Crohn’s disease: A systematic review and meta-analysis of population-based Cohorts. Inflamm Bowel Dis. 2022;28(10):1477-84.

37. Vosough M., Nikfam S., Torabi S.H. et al. Mesenchymal Stromal Cell Therapy Improves Refractory Perianal Fistula in Crohn’s Disease: Case Series Clinical Interventional Study. Cell J. 2022;24(2):62-68. doi: 10.22074/cellj.2022.7981.

38. Ilkanich A. Ya., Darwin V.V., Krasnov E.A., Aliyev F. Sh., Zubailov K.Z. Surgical treatment of anal fistula. Siberian Scientific Medical Journal. 2023;43(5):74-84. (In Russ.) doi: 10.18699/SSMJ20230507.@@ Ильканич А.Я., Дарвин В.В., Краснов Е.А., Алиев Ф.Ш., Зубаилов К.З. Хирургическое лечение свищей заднего прохода. Сибирский научный медицинский журнал. 2023;43(5):74-84. doi: 10.18699/ SSMJ20230507.

39. Cheng F., Huang Z., Li Z. Efficacy and Safety of Mesenchymal Stem Cells in Treatment of Complex Perianal Fistulas: A Meta-Analysis. Stem Cells Int. 2020;2020:8816737. Published 2020 Nov 21. doi: 10.1155/2020/8816737.

40. Vitton V., Gasmi M., Barthet M., Desjeux A., Orsoni P., Grimaud J.C. Long-term healing of Crohn’s anal fistulas with fibrin glue injection. Aliment Pharmacol Ther. 2005;21(12):1453-1457. doi: 10.1111/j.1365-2036.2005.02456.x.

41. Arkenbosch J.H.C., van Ruler O., Dwarkasing R.S. et al. Stromal vascular fraction with platelet-rich plasma injection during surgery is feasible and safe in treatment-refractory perianal fistulising Crohn’s disease: A pilot study [published correction appears in Aliment Pharmacol Ther. 2025 Jan;61(2):414-415. doi: 10.1111/apt.18388.]. Aliment Pharmacol Ther. 2023;57(7):783-791. doi: 10.1111/apt.17347.

42. Dalby H.R., Perregaard H., Dige A., Hagen K.B., Nordholm-Carstensen A., Lundby L. [Treatment of perianal fistulas with mesenchymal stem cells]. Ugeskr Laeger. 2022;184(14): V05210392. Danish.

43. Ramachandran R., Gunasekharan V., Pillai A.V., Raja S., Nair A.S. Fibrin glue versus autologous platelet-rich fibrin - comparison of effectiveness on the cohort of patients with fistula-in-ano undergoing video-assisted anal fistula treatment. J Minim Access Surg. 2022;18(3):443-449. doi: 10.4103/jmas.jmas_297_21.

44. Knyazev O. V., Konoplyannikov A.G., Kagramanov A.V. et al.Combined use of mesenchymal stromal cells and infliximab in uncomplicated (luminal) Crohn’s disease. Coloproctology. 2016;(3):24-30. doi: 10.33878/2073-75562016-0-3-24-30.@@ Князев О.В., Коноплянников А.Г., Каграманов А.В. и др. Комбинированное применение мезенхимальных стромальных клеток и инфликсимаба при неосложненной (люминальной) форме болезни крона. Колопроктология. 2016;(3):24-30. doi: 10.33878/2073-75562016-0-3-24-30.

45. El-Nakeep S. Stem Cell Therapy for the Treatment of Crohn’s Disease; Current Obstacles and Future Hopes. Curr Stem Cell Res Ther. 2022;17(8):727-733. doi: 10.2174/1574888X16666210910112403.

46. Tutino R., Di Franco S., Massani M. et al. Autologous adipose-derived stromal vascular fraction and platelet concentrates for the treatment of complex perianal fistulas. Tech Coloproctol. 2023;27(2):135-143. doi: 10.1007/s10151-022-02675-0.

47. Mazzaro M.C., de Paula A.E.C., Pascoal L.B. et al. Optimizing Treatment Outcomes in Crohn’s Disease: A Comprehensive Systematic Review and Meta-Analysis of Regenerative Therapies with Emphasis on Platelet-Rich Plasma. Pharmaceuticals (Basel). 2024;17(11):1519. Published 2024 Nov 12. doi: 10.3390/ph17111519.

48. Yamaguchi T. [A new treatment option for complex perianal fistulas in Crohn’s disease patients; development of darvadstrocel (allogeneic expanded adipose-derived mesenchymal stem cells) in Japan]. Nihon Yakurigaku Zasshi. 2024;159(3):150-155. Japanese. doi: 10.1254/fpj.23046.

49. Teryushkova Zh.I., Vasiliev V.S., Vazhenin A.V., Kazachkov E.L., Vasiliev S.A., Dimov G.P., Baturina I.L. Treatment of post-radiation colovaginal fistula by microinjection autotransplantation of adipose tissue. Medical Bulletin of Bashkortostan. 2017;12 (6 (72)), 96-100. (in Russ.)@@ Терюшкова Ж.И., Васильев В.С., Важенин А.В., Казачков Е.Л., Васильев С.А., Димов Г.П., Батурина И.Л. Лечение постлучевого коловагинального свища методом микроинъекционной аутотрансплантации жировой ткани. Медицинский вестник Башкортостана. 2017;12 (6 (72)): 96-100.

50. Jeong I.S., Hwang S.H., Yu H.M., Jeong H. Cell-assisted lipotransfer in treating uncontrollable sepsis associated perianal fistula: a pilot study. Ann Coloproctol. 2024;40(2):169-175. doi: 10.3393/ac.2022.00486.0069.

51. Dozois E.J., Lightner A.L., Dietz A.B. et al. Durable Response in Patients With Refractory Fistulizing Perianal Crohn’s Disease Using Autologous Mesenchymal Stem Cells on a Dissolvable Matrix: Results from the Phase I Stem Cell on Matrix Plug Trial. Dis Colon Rectum. 2023;66(2):243-252. doi: 10.1097/DCR.0000000000002579.

52. Shcherbakova O.V., Razumovsky A. Yu., Shumilov P.V., Sytkov V.V. Surgical approaches to the treatment of children and adolescents with perianal Crohn’s disease. Bulletin of Surgical Gastroenterology. 2019;4:45-55. (In Russ.)@@ Щербакова О.В., Разумовский А.Ю., Шумилов П.В., Сытьков В.В. Хирургические подходы к лечению детей и подростков с перианальной болезнью Крона. Вестник хирургической гастроэнтерологии 2019 № 4. С. 45-55.

53. Shcherbakova O.V., Razumovskiy A. Yu., Shumilov P.V., Ionov A.L. The choice of the optimal strategy for treatment of children with Crohn’s disease and Crohn-like immunodeficiencies with perianal lesions. Vopr. det. dietol. (Pediatric Nutrition). 2019; 17(1): 7-16. (In Russ.) doi: 10.20953/1727-5784-2019-1-7-16.@@ Щербакова О.В., Разумовский А.Ю., Шумилов П.В., Ионов А.Л. Выбор оптимальной стратегии лечения детей с болезнью Крона и кроноподобными иммунодефицитами с перианальными поражениями. Вопросы детской диетологии. 2019; 17(1): 7-16. doi: 10.20953/1727-5784-2019-1-7-16.


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For citations:


Nikitina I.A., Leontyev A.V., Sytkov V.V., Danilov M.A., Khavkin A.I., Yablokova E.A., Orlyuk M.A. Treatment of perianal manifestations of Crohn's disease. Experimental and Clinical Gastroenterology. 2025;(2):187-193. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-234-2-187-193

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