Abstract
Perianal Crohn’s Disease (CD) is a significant cause of morbidity in CD patients. Accurate identification of perianal involvement requires advanced imaging techniques in addition to physical exam. Treatment of the disease is aimed at improving both the perianal and intestinal manifestations. Proper treatment depends upon the severity of the disease and combines current medical and surgical therapies to maximize response. The ability to improve perianal disease has grown significantly since the introduction of anti-TNF agents which are now a mainstay of treatment along with antibiotics and immunomodulators. New experimental therapies are limited by lack of research to support their use.
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Rankin GB, Watts HD, Melnyk CS, Kelley Jr ML. National Cooperative Crohn’s Disease Study: extraintestinal manifestations and perianal complications. Gastroenterology. 1979;77:914–20.
Harper PH, Fazio VW, Lavery IC, et al. The long-term outcome in Crohn’s disease. Dis Colon Rectum. 1987;30:174–9.
Schwartz DA, Loftus Jr EV, Tremaine WJ, et al. The natural history of fistulizing Crohn’s disease in Olmsted County, Minnesota. Gastroenterology. 2002;122:875–80.
Hellers G, Bergstrand O, Ewerth S, Holmstrom B. Occurrence and outcome after primary treatment of anal fistulae in Crohn’s disease. Gut. 1980;21:525–7.
Schwartz DA, Wiersema MJ, Dudiak KM, et al. A comparison of endoscopic ultrasound, magnetic resonance imaging, and exam under anesthesia for evaluation of Crohn’s perianal fistulas. Gastroenterology. 2001;121:1064–72.
Sandborn WJ, Fazio VW, Feagan BG, Hanauer SB. AGA technical review on perianal Crohn’s disease. Gastroenterology. 2003;125:1508–30.
Haggett PJ, Moore NR, Shearman JD, Travis SP, Jewell DP, Mortensen NJ. Pelvic and perineal complications of Crohn’s disease: assessment using magnetic resonance imaging. Gut. 1995;36:407–10.
Lunniss PJ, Armstrong P, Barker PG, Reznek RH, Phillips RK. Magnetic resonance imaging of anal fistulae. Lancet. 1992;340:394–6.
Hori M, Oto A, Orrin S, Suzuki K, Baron RL. Diffusion-weighted MRI, a new tool for the diagnosis of fistula in ano. J Magn Reson Imaging. 2009;30:1021–6.
Beets-Tan RG, Beets GL, van der Hoop AG, et al. Preoperative MR imaging of anal fistulas: Does it really help the surgeon? Radiology. 2001;218:75–84.
• Buchanan G, Halligan S, Williams A, et al. Effect of MRI on clinical outcome of recurrent fistula-in-ano. Lancet. 2002;360:1661–2. This study showed use of MRI for fistula definition prior to surgery could reduce the recurrence rate of complex fistulas.
Karmiris K, Bielen D, Vanbeckevoort D, et al. Long-term monitoring of infliximab therapy for perianal fistulizing Crohn’s disease using magnetic resonance imaging. Clin Gastroenterol Hepatol. 2010.
Ng SC, Plamondon S, Gupta A, et al. Prospective evaluation of anti-tumor necrosis factor therapy guided by magnetic resonance imaging for Crohn’s perineal fistulas. Am J Gastroenterol. 2009;104:2973–86.
Poen AC, Felt-Bersma RJ, Eijsbouts QA, Cuesta MA, Meuwissen SG. Hydrogen peroxide-enhanced transanal ultrasound in the assessment of fistula-in-ano. Dis Colon Rectum. 1998;41:1147–52.
Navarro-Luna A, García-Domingo MI, Rius-Macías J, Marco-Molina C. Ultrasound study of anal fistulas with hydrogen peroxide enhancement. Dis Colon Rectum. 2004;47:108–14.
Schwartz DA, White CM, Wise PE, Herline AJ. Use of endoscopic ultrasound to guide combination medical and surgical therapy for patients with Crohn’s perianal fistulas. Inflamm Bowel Dis. 2005;11:727–32.
• Spradlin NM, Wise PE, Herline AJ, Muldoon RL, Rosen M, Schwartz DA. A randomized prospective trial of endoscopic ultrasound to guide combination medical and surgical treatment for Crohn’s perianal fistulas. Am J Gastroenterol. 2008;103:2527–35. Although a small study, this is the first trial comparing EUS guided management verses routine care.
Rosen MJ, Moulton DE, Koyama T, et al. Endoscopic ultrasound to guide the combined medical and surgical management of pediatric perianal Crohn’s disease. Inflamm Bowel Dis. 2010;16:461–8.
West RL, Van der Woude CJ, Endtz HP, et al. Perianal fistulas in Crohn’s disease are predominantly colonized by skin flora: implications for antibiotic treatment? Dig Dis Sci. 2005;50:1260–3.
Solomon MJ, McLeod RS, Oconnor BI, Steinhart AH, Greenberg GR, Cohen Z. Combination Ciprofloxacin and Metronidazole in Severe Perianal Crohns-Disease. 1993;7:571–3.
Blichfeldt P, Blomhoff JP, Myhre E, Gjone E. Metronidazole in Crohn’s disease. A double blind cross-over clinical trial. Scand J Gastroenterol. 1978;13:123–7.
Sutherland L, Singleton J, Sessions J, et al. Double blind, placebo controlled trial of metronidazole in Crohn’s disease. Gut. 1991;32:1071–5.
Jakobovits J, Schuster MM. Metronidazole therapy for Crohn’s disease and associated fistulae. Am J Gastroenterol. 1984;79:533–40.
Bernstein LH, Frank MS, Brandt LJ, Boley SJ. Healing of perineal Crohn’s disease with metronidazole. Gastroenterology. 1980;79:599.
Brandt LJ, Bernstein LH, Boley SJ, Frank MS. Metronidazole therapy for perineal Crohn’s disease: a follow-up study. Gastroenterology. 1982;83:383–7.
Turunen U, Farkkila M, Valtonen V. Long-term outcome of ciprofloxacin treatment in severe perianal or fistulous Crohn’s disease. Gastroenterology. 1993;104:A793.
West RL, van der Woude CJ, Hansen BE, et al. Clinical and endosonographic effect of ciprofloxacin on the treatment of perianal fistulae in Crohn’s disease with infliximab: a double-blind placebo-controlled study. Aliment Pharmacol Ther. 2004;20:1329–36.
• Dejaco C, Harrer M, Waldhoer T, Miehsler W, Vogelsang H, Reinisch W. Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn’s disease. Aliment Pharmacol Ther. 2003;18:1113–20. The only trial of azathioprine use in fistulizing disease that had a comparison group that did not receive azathioprine.
Thia KT, Mahadevan U, Feagan BG, et al. Ciprofloxacin or metronidazole for the treatment of perianal fistulas in patients with Crohn’s disease: a randomized, double-blind, placebo-controlled pilot study. Inflamm Bowel Dis. 2009;15:17–24.
Stringer EE, Nicholson TJ, Armstrong D. Efficacy of topical metronidazole (10 percent) in the treatment of anorectal Crohn’s disease. Dis Colon Rectum. 2005;48:970–4.
Maeda Y, Ng SC, Durdey P, et al. Randomized clinical trial of metronidazole ointment versus placebo in perianal Crohn’s disease. Br J Surg. 2010;97:1340–7.
Present DH, Korelitz BI, Wisch N, Glass JL, Sachar DB, Pasternack BS. Treatment of Crohn’s disease with 6-mercaptopurine. A long-term, randomized, double-blind study. N Eng J Med. 1980;302:981–7.
Klein M, Binder HJ, Mitchell M, Aaronson R, Spiro H. Treatment of Crohn’s disease with azathioprine: a controlled evaluation. Gastroenterology. 1974;66:916–22.
Pearson D, May G, Fick G, Sutherland L. Azathioprine and 6-mercaptopurine in Crohn disease: a meta analysis. Ann Intern Med. 1995;123:132–42.
Lecomte T, Contou JF, Beaugerie L, et al. Predictive factors of response of perianal Crohn’s disease to azathioprine or 6-mercaptopurine. Dis Colon Rectum. 2003;46:1469–75.
Jeshion WC, Larsen KL, Jawad AF, et al. Azathioprine and 6-mercaptopurine for the treatment of perianal Crohn’s disease in children. J Clin Gastroenterol. 2000;30:294–8.
Egan LJ, Sandborn WJ, Tremaine WJ. Clinical outcome following treatment of refractory inflammatory and fistulizing Crohn’s disease with intravenous cyclosporine. Am J Gastroenterol. 1998;93:442–8.
Hanauer SB, Smith MB. Rapid closure of Crohn’s disease fistulas with continuous intravenous cyclosporin A [see comments]. Am J Gastroenterol. 1993;88:646–9.
• Sandborn WJ, Present DH, Isaacs KL, et al. Tacrolimus for the treatment of fistulas in patients with Crohn’s disease: a randomized, placebo-controlled trial. Gastroenterology. 2003;125:380–8. One of the few randomized controlled trials investigating immunomodulator use in fistulizing CD. This study showed improvement in draining fistulas but no improvement in remission rates Tacrolimus is one of the last line agents to use failed fistula treatment.
Hart AL, Plamondon S, Kamm MA. Topical tacrolimus in the treatment of perianal Crohn’s disease: exploratory randomized controlled trial. Inflamm Bowel Dis. 2007;13:245–53.
Wenzl HH, Hinterleitner TA, Aichbichler BW, Fickert P, Petritsch W. Mycophenolate mofetil for Crohn’s disease: short-term efficacy and long-term outcome. Aliment Pharmacol Ther. 2004;19:427–34.
• Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Eng J Med. 1999;340:1398–405. This is the first major randomized trial to show that anti-TNF agents could significantly improve perianal disease.
Ricart E, Panaccione R, Loftus EV, Tremaine WJ, Sandborn WJ. Infliximab for Crohn’s disease in clinical practice at the Mayo Clinic: the first 100 patients. Am J Gastroenterol. 2001;96:722–9.
Orlando A, Colombo E, Kohn A, et al. Infliximab in the treatment of Crohn’s disease: predictors of response in an Italian multicentric open study. Dig Liver Dis. 2005;37:577–83.
Domenech E, Hinojosa J, Nos P, et al. Clinical evolution of luminal and perianal Crohn’s disease after inducing remission with infliximab: how long should patients be treated? Aliment Pharmacol Ther. 2005;22:1107–13.
Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–9.
• Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876–85. The first RCT that showed maintenance therapy with infliximab resulted in longer remission rates of fistulizing disease.
Lichtenstein GR, Yan S, Bala M, Blank M, Sands BE. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn’s disease. Gastroenterology. 2005;128:862–9.
Ng SC, Plamondon S, Gupta A, Burling D, Kamm MA. Prospective assessment of the effect on quality of life of anti-tumour necrosis factor therapy for perineal Crohn’s fistulas. Aliment Pharmacol Ther. 2009;30:757–66.
Colombel JF, Schwartz DA, Sandborn WJ, et al. Adalimumab for the treatment of fistulas in patients with Crohn’s disease. Gut. 2009;58:940–8.
• Lichtiger S, Binion DG, Wolf DC, et al. The CHOICE trial: adalimumab demonstrates safety, fistula healing, improved quality of life and increased work productivity in patients with Crohn’s disease who failed prior infliximab therapy. Aliment Pharmacol Ther. 2010;32:1228–39. This trial provided a treatment option for patients with fistulizing disease who had failed infliximab with the use of the newer anti-TNF antibody, adalimumab.
Schreiber S, Lawrance IC, Thomsen OO, Hanauer SB, Bloomfield R, Sandborn WJ. Randomised clinical trial: certolizumab pegol for fistulas in Crohn’s disease—subgroup results from a placebo-controlled study. Aliment Pharmacol Ther. 2010.
van Bodegraven AA, Sloots CE, Felt-Bersma RJ, Meuwissen SG. Endosonographic evidence of persistence of Crohn’s disease-associated fistulas after infliximab treatment, irrespective of clinical response. Dis Colon Rectum. 2002;45:39–45. discussion -6.
Ardizzone S, Maconi G, Colombo E, Manzionna G, Bollani S, Bianchi Porro G. Perianal fistulae following infliximab treatment: clinical and endosonographic outcome. Inflamm Bowel Dis. 2004;10:91–6.
Bell SJ, Halligan S, Windsor AC, Williams AB, Wiesel P, Kamm MA. Response of fistulating Crohn’s disease to infliximab treatment assessed by magnetic resonance imaging. Aliment Pharmacol Ther. 2003;17:387–93.
Takazoe M, Matsui T, Motoya S, Matsumoto T, Hibi T, Watanabe M. Sargramostim in patients with Crohn’s disease: results of a phase 1–2 study. J Gastroenterol. 2009;44:535–43.
Korzenik JR, Dieckgraefe BK, Valentine JF, Hausman DF, Gilbert MJ. Group SiCsDS. Sargramostim for active Crohn’s disease. N Engl J Med. 2005;352:2193–201.
Calam J, Crooks PE, Walker RJ. Elemental diets in the management of Crohn’s perianal fistulae. JPEN J Parenter Enteral Nutr. 1980;4:4–8.
Colombel JF, Mathieu D, Bouault JM, et al. Hyperbaric oxygenation in severe perineal Crohn’s disease. Dis Colon Rectum. 1995;38:609–14.
Lavy A, Weisz G, Adir Y, Ramon Y, Melamed Y, Eidelman S. Hyperbaric oxygen for perianal Crohn’s disease. J Clin Gastroenterol. 1994;19:202–5.
Asteria CR, Ficari F, Bagnoli S, Milla M, Tonelli F. Treatment of perianal fistulas in Crohn’s disease by local injection of antibody to TNF-alpha accounts for a favourable clinical response in selected cases: a pilot study. Scand J Gastroenterol. 2006;41:1064–72.
Poggioli G, Laureti S, Pierangeli F, et al. Local injection of Infliximab for the treatment of perianal Crohn’s disease. Dis Colon Rectum. 2005;48:768–74.
Loungnarath R, Dietz DW, Mutch MG, Birnbaum EH, Kodner IJ, Fleshman JW. Fibrin glue treatment of complex anal fistulas has low success rate. Dis Colon Rectum. 2004;47:432–6.
Cintron JR, Park JJ, Orsay CP, Pearl RK, Nelson RL, Abcarian H. Repair of fistulas-in-ano using autologous fibrin tissue adhesive. Dis Colon Rectum. 1999;42:607–13.
Vitton V, Gasmi M, Barthet M, Desjeux A, Orsoni P, Grimaud JC. Long-term healing of Crohn’s anal fistulas with fibrin glue injection. Aliment Pharmacol Ther. 2005;21:1453–7.
Lindsey I, Smilgin-Humphreys MM, Cunningham C, Mortensen NJ, George BD. A randomized, controlled trial of fibrin glue vs. conventional treatment for anal fistula. Dis Colon Rectum. 2002;45:1608–15.
• Grimaud JC, Munoz-Bongrand N, Siproudhis L, et al. Fibrin glue is effective healing perianal fistulas in patients with Crohn’s disease. Gastroenterology. 2010;138:2275–81. The largest prospective RCT investigating the use of fibrin glue for fistulae. This study shows a clinical improvement in drainage but did not use advanced imaging techniques to further assess fistula presence and followed patients for a short period of time.
Cintron JR, Park JJ, Orsay CP, et al. Repair of fistulas-in-ano using fibrin adhesive: long-term follow-up. Dis Colon Rectum. 2000;43:944–9. discussion 9–50.
Yeung JM, Simpson JA, Tang SW, Armitage NC, Maxwell-Armstrong C. Fibrin glue for the treatment of fistulae in ano—a method worth sticking to? Colorectal Dis. 2010;12:363–6.
de la Portilla F, Rada R, Vega J, Cisneros N, Maldonado VH, Sánchez-Gil JM. Long-term results change conclusions on BioGlue in the treatment of high transsphincteric anal fistulas. Dis Colon Rectum. 2010;53:1220–1.
Johnson EK, Gaw JU, Armstrong DN. Efficacy of anal fistula plug vs. fibrin glue in closure of anorectal fistulas. Dis Colon Rectum. 2006;49:371–6.
Schwandner O, Stadler F, Dietl O, Wirsching RP, Fuerst A. Initial experience on efficacy in closure of cryptoglandular and Crohn’s transsphincteric fistulas by the use of the anal fistula plug. Int J Colorectal Dis. 2008;23:319–24.
O’Connor L, Champagne BJ, Ferguson MA, Orangio GR, Schertzer ME, Armstrong DN. Efficacy of anal fistula plug in closure of Crohn’s anorectal fistulas. Dis Colon Rectum. 2006;49:1569–73.
Ky AJ, Sylla P, Steinhagen R, Steinhagen E, Khaitov S, Ly EK. Collagen fistula plug for the treatment of anal fistulas. Dis Colon Rectum. 2008;51:838–43.
Schwandner O, Fuerst A. Preliminary results on efficacy in closure of transsphincteric and rectovaginal fistulas associated with Crohn’s disease using new biomaterials. Surg Innov. 2009;16:162–8.
McGee MF, Champagne BJ, Stulberg JJ, Reynolds H, Marderstein E, Delaney CP. Tract length predicts successful closure with anal fistula plug in cryptoglandular fistulas. Dis Colon Rectum. 2010;53:1116–20.
García-Olmo D, García-Arranz M, Herreros D, Pascual I, Peiro C, Rodríguez-Montes JA. A phase I clinical trial of the treatment of Crohn’s fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum. 2005;48:1416–23.
• Garcia-Olmo D, Herreros D, Pascual I, et al. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum. 2009;52:79–86. The first RCT of stem cell injections for fistulizing diseae found a non-significant increase in healing rates of fistulizing disease. There have been no future RCT to show any significant improved with stem cell injections.
Ciccocioppo R, Bernardo ME, Sgarella A, et al. Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn’s disease. Gut. 2011.
Heuman R, Bolin T, Sjodahl R, Tagesson C. The incidence and course of perianal complications and arthralgia after intestinal resection with restoration of continuity for Crohn’s disease. Br J Surg. 1981;68:528–30.
Pescatori M, Interisano A, Basso L, et al. Management of perianal Crohn’s disease. Results of a multicenter study in Italy. Dis Colon Rectum. 1995;38:121–4.
Löffler T, Welsch T, Mühl S, Hinz U, Schmidt J, Kienle P. Long-term success rate after surgical treatment of anorectal and rectovaginal fistulas in Crohn’s disease. Int J Colorectal Dis. 2009;24:521–6.
Michelassi F, Melis M, Rubin M, Hurst RD. Surgical treatment of anorectal complications in Crohn’s disease. Surgery. 2000;128:597–603.
Pritchard TJ, Schoetz DJ, Roberts PL, Murray JJ, Coller JA, Veidenheimer MC. Perirectal abscess in Crohn’s disease. Drainage and outcome. Dis Colon Rectum. 1990;33:933–7.
Thornton M, Solomon MJ. Long-term indwelling seton for complex anal fistulas in Crohn’s disease. Dis Colon Rectum. 2005;48:459–63.
Takesue Y, Ohge H, Yokoyama T, Murakami Y, Imamura Y, Sueda T. Long-term results of seton drainage on complex anal fistulae in patients with Crohn’s disease. J Gastroenterol. 2002;37:912–5.
Galis-Rozen E, Tulchinsky H, Rosen A, et al. Long-term outcome of loose seton for complex anal fistula: a two-centre study of patients with and without Crohn’s disease. Colorectal Dis. 2010;12:358–62.
Buchanan GN, Owen HA, Torkington J, Lunniss PJ, Nicholls RJ, Cohen CR. Long-term outcome following loose-seton technique for external sphincter preservation in complex anal fistula. Br J Surg. 2004;91:476–80.
Whiteford MH, Kilkenny J, Hyman N, et al. Practice parameters for the treatment of perianal abscess and fistula-in-ano (revised). Dis Colon Rectum. 2005;48:1337–42.
Mizrahi N, Wexner SD, Zmora O, et al. Endorectal advancement flap: are there predictors of failure? Dis Colon Rectum. 2002;45:1616–21.
Yamamoto T, Allan RN, Keighley MR. Effect of fecal diversion alone on perianal Crohn’s disease. World J Surg. 2000;24:1258–62. discussion 62-3.
Mueller MH, Geis M, Glatzle J, et al. Risk of fecal diversion in complicated perianal Crohn’s disease. J Gastrointest Surg. 2007;11:529–37.
Kasparek MS, Glatzle J, Temeltcheva T, Mueller MH, Koenigsrainer A, Kreis ME. Long-term quality of life in patients with Crohn’s disease and perianal fistulas: influence of fecal diversion. Dis Colon Rectum. 2007;50:2067–74.
Williamson PR, Hellinger MD, Larach SW, Ferrara A. Twenty-year review of the surgical management of perianal Crohn’s disease. Dis Colon Rectum. 1995;38:389–92.
Figg RE, Church JM. Perineal Crohn’s disease: an indicator of poor prognosis and potential proctectomy. Dis Colon Rectum. 2009;52:646–50.
Fry RD, Shemesh EI, Kodner IJ, Timmcke A. Techniques and results in the management of anal and perianal Crohn’s disease. Surg Gynecol Obstet. 1989;168:42–8.
Tanaka S, Matsuo K, Sasaki T, et al. Clinical advantages of combined seton placement and infliximab maintenance therapy for perianal fistulizing Crohn’s disease: when and how were the seton drains removed? Hepatogastroenterology. 2010;57:3–7.
Sciaudone G, Di Stazio C, Limongelli P, et al. Treatment of complex perianal fistulas in Crohn disease: infliximab, surgery or combined approach. Can J Surg. 2010;53:299–304.
• Regueiro M, Mardini H. Treatment of perianal fistulizing Crohn’s disease with infliximab alone or as an adjunct to exam under anesthesia with seton placement. Inflamm Bowel Dis. 2003;9:98–103. A controlled study which showed that seton placement with infliximab was superior to infliximab treatment alone supporting the use of setons as an adjunt to medical therapy in complex fisutas.
Gaertner WB, Decanini A, Mellgren A, et al. Does infliximab infusion impact results of operative treatment for Crohn’s perianal fistulas? Dis Colon Rectum. 2007;50:1754–60.
Disclosure
Dr. D. A. Schwartz has worked as a consultant for Abbott, UCB, and Braintree Labs, and has received grant support from Abbott and UCB; Dr. D. M. Weise reported no potential conflicts of interest relevant to this article.
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Wiese, D.M., Schwartz, D.A. Managing Perianal Crohn’s Disease. Curr Gastroenterol Rep 14, 153–161 (2012). https://doi.org/10.1007/s11894-012-0243-y
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DOI: https://doi.org/10.1007/s11894-012-0243-y