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Published in: International Journal of Colorectal Disease 1/2012

01-01-2012 | Review

Botulinum toxin and anal fissure: Efficacy and safety systematic review

Author: Eugenia Yiannakopoulou

Published in: International Journal of Colorectal Disease | Issue 1/2012

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Abstract

Purpose

The main purpose of this study was to investigate the efficacy and safety of botulinum toxin in the treatment of anal fissure. An answer was attempted to the following research questions: (i) what is the efficacy of botulinum toxin in healing of anal fissure compared to placebo, (ii) what is the efficacy of botulinum toxin in healing of anal fissure compared to other means of chemical sphincterotomy, (iii) what is the efficacy of botulinum toxin in healing of anal fissure compared to surgical sphincterotomy, (iv) what is the short term safety of botulinum toxin injections and (v) what is the long term safety of botulinum toxin injections.

Methods

Clinical trials investigating the effect of botulinum toxin in the treatment of anal fissure met inclusion criteria. Case reports and case series were also included for the estimation of safety. Meta-analysis was not performed due to clinical heterogeneity.

Results

The comparator could be placebo, nitroglycerin ointment, or lateral internal sphincterotomy, with dosage ranging from 20 IU to 50 IU of botulinum toxin. Fissure healing was the most commonly reported primary endpoint but the time period from botulinum toxin injection to fissure healing ranged from 2 weeks to 4 months. Accordingly, outcome data were also heterogenous.

Conclusions

Botulinum toxin injections should be considered a minimally invasive therapeutic option for the treatment of chronic anal fissure. However, well designed randomized trials are needed for the valid estimation of the efficacy and safety of botulinum toxin in this therapeutic indication.
Literature
1.
2.
go back to reference Shao WJ, Li GC, Zhang ZK (2009) Systematic review and meta-analysis of randomized controlled trials comparing botulinum toxin with injection with lateral internal sphincterotomy for chronic anal fissure. Int J Colorectal Dis 24:995–1000PubMedCrossRef Shao WJ, Li GC, Zhang ZK (2009) Systematic review and meta-analysis of randomized controlled trials comparing botulinum toxin with injection with lateral internal sphincterotomy for chronic anal fissure. Int J Colorectal Dis 24:995–1000PubMedCrossRef
3.
go back to reference Sajid MS, Vijaynagar B, Desai M, Cheek E, Baig MK (2008) Botulinum toxin vs. glyceryl trinitrate for the medical treatment of chronic anal fissure: a meta-analysis. Colorectal Dis 10:541–546PubMedCrossRef Sajid MS, Vijaynagar B, Desai M, Cheek E, Baig MK (2008) Botulinum toxin vs. glyceryl trinitrate for the medical treatment of chronic anal fissure: a meta-analysis. Colorectal Dis 10:541–546PubMedCrossRef
4.
go back to reference Sajid MS, Hunte S, Hippolyte S, Kiri VA, Maringe C, Baig MK (2008) Comparison of chemical vs. surgical sphincterotomy using botulinum toxin for the treatment of chronic anal fissure. A meta-analysis. Colorectal Dis 10:547–552PubMedCrossRef Sajid MS, Hunte S, Hippolyte S, Kiri VA, Maringe C, Baig MK (2008) Comparison of chemical vs. surgical sphincterotomy using botulinum toxin for the treatment of chronic anal fissure. A meta-analysis. Colorectal Dis 10:547–552PubMedCrossRef
5.
go back to reference Yiannakopoulou E, Damianou C, Bamia C, Papadopoulos J (2005) Adequacy of safety data reporting in randomized clinical trials comparing coxibs with non-selective NSAIDs. Epitheor Klin Farmakol Farmacokinet 23:42–43 Yiannakopoulou E, Damianou C, Bamia C, Papadopoulos J (2005) Adequacy of safety data reporting in randomized clinical trials comparing coxibs with non-selective NSAIDs. Epitheor Klin Farmakol Farmacokinet 23:42–43
6.
go back to reference Maria G, Cassetta E, Gui D, Brisinda G, Bentivoglio AR, Albanese A (1998) A comparison of botutinum toxin and saline for the treatment of chronic anal fissure. N Engl J Med 338:217–220PubMedCrossRef Maria G, Cassetta E, Gui D, Brisinda G, Bentivoglio AR, Albanese A (1998) A comparison of botutinum toxin and saline for the treatment of chronic anal fissure. N Engl J Med 338:217–220PubMedCrossRef
7.
go back to reference Siproudhis L, Sébille V, Pigot F, Hémery P, Juguet F, Bellissant E (2003) Lack of efficacy of botulinum toxin in chronic anal fissure. Aliment Pharmacol Ther 1:515–524CrossRef Siproudhis L, Sébille V, Pigot F, Hémery P, Juguet F, Bellissant E (2003) Lack of efficacy of botulinum toxin in chronic anal fissure. Aliment Pharmacol Ther 1:515–524CrossRef
8.
go back to reference Colak T, Ipek T, Kanik A, Aydin S (2002) A randomized trial of botulinum toxine vs. lidocaine pomade for chronic anal fissure. Acta Gastroenterol Belg 65:187–190PubMed Colak T, Ipek T, Kanik A, Aydin S (2002) A randomized trial of botulinum toxine vs. lidocaine pomade for chronic anal fissure. Acta Gastroenterol Belg 65:187–190PubMed
9.
go back to reference Brisinda G, Cadeddu F, Brandara F, Marniga G, Maria G (2007) Randomized clinical trial comparing botulinum toxin injections with 0.2% nitroglycerin ointment for chronic anal fissure. Br J Surg 94:162–167PubMedCrossRef Brisinda G, Cadeddu F, Brandara F, Marniga G, Maria G (2007) Randomized clinical trial comparing botulinum toxin injections with 0.2% nitroglycerin ointment for chronic anal fissure. Br J Surg 94:162–167PubMedCrossRef
10.
go back to reference Fruehauf H, Fried M, Wegmueller B, Bauerfeind P, Thumshirn M (2006) Efficacy and safety of botulinum toxin injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure. Am J Gastroenterol 101:2107–2112PubMedCrossRef Fruehauf H, Fried M, Wegmueller B, Bauerfeind P, Thumshirn M (2006) Efficacy and safety of botulinum toxin injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure. Am J Gastroenterol 101:2107–2112PubMedCrossRef
11.
go back to reference Festen S, Gisbetz SS, van Schaagen F, Gerhards MF (2009) Blinded randomised trial of botulinum toxin versus isosorbide dinitrate ointment for treatment of anal fissure. Br J Surg 96:1393–1399PubMedCrossRef Festen S, Gisbetz SS, van Schaagen F, Gerhards MF (2009) Blinded randomised trial of botulinum toxin versus isosorbide dinitrate ointment for treatment of anal fissure. Br J Surg 96:1393–1399PubMedCrossRef
12.
go back to reference De Nardi P, Ortolano E, Radaelli G, Staudacher C (2006) Comparison of glycerine trinitrate and botulinum toxin—a for the treatment of chronic anal fissure: long term results. Dis Colon Rectum 49:427–432PubMedCrossRef De Nardi P, Ortolano E, Radaelli G, Staudacher C (2006) Comparison of glycerine trinitrate and botulinum toxin—a for the treatment of chronic anal fissure: long term results. Dis Colon Rectum 49:427–432PubMedCrossRef
13.
go back to reference Brisinda G, Maria G, Bentivoglio AR, Cassetta E, Gui D, Albanese A (1999) A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure. N Engl J Med 341:65–69PubMedCrossRef Brisinda G, Maria G, Bentivoglio AR, Cassetta E, Gui D, Albanese A (1999) A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure. N Engl J Med 341:65–69PubMedCrossRef
14.
go back to reference Suknaic S, Patrlj L, SteresiniA M, Skopljanac Macina A, Erdelez L (2008) Surgical or biological sphincterotomy in the treatment of chronic anal fissure. Acta Med Croatica 62:73–80PubMed Suknaic S, Patrlj L, SteresiniA M, Skopljanac Macina A, Erdelez L (2008) Surgical or biological sphincterotomy in the treatment of chronic anal fissure. Acta Med Croatica 62:73–80PubMed
15.
go back to reference Massoud BW, Mehrdad V, Baharak T, Alireza Z (2005) Botulinum toxin injection versus internal anal sphincterotomy for the treatment of chronic anal fissure. Ann Saudi Med 25:140–142PubMed Massoud BW, Mehrdad V, Baharak T, Alireza Z (2005) Botulinum toxin injection versus internal anal sphincterotomy for the treatment of chronic anal fissure. Ann Saudi Med 25:140–142PubMed
16.
go back to reference Iswariah H, Stephens J, Rieger N, Rodda D, Hewett P (2005) Randomized prospective controlled trial of lateral internal sphincterotomy versus injection of botulinum toxin for the treatment of idiopathic fissure in ano. ANZ J Surg 75:553–555PubMedCrossRef Iswariah H, Stephens J, Rieger N, Rodda D, Hewett P (2005) Randomized prospective controlled trial of lateral internal sphincterotomy versus injection of botulinum toxin for the treatment of idiopathic fissure in ano. ANZ J Surg 75:553–555PubMedCrossRef
17.
go back to reference Arroyo A, Pérez F, Serrano P, Candela F, Lacueva J, Calpena R (2005) Surgical vs. chemical (botulinum toxin) sphinterotomy for chronic anal fissure: long term results of a prospective randomised clinical and manometric study. Am J Surg 189:429–434PubMedCrossRef Arroyo A, Pérez F, Serrano P, Candela F, Lacueva J, Calpena R (2005) Surgical vs. chemical (botulinum toxin) sphinterotomy for chronic anal fissure: long term results of a prospective randomised clinical and manometric study. Am J Surg 189:429–434PubMedCrossRef
18.
go back to reference Arroyo Sebastián A, Pérez Vicente F, Miranda Tauler E, Sánchez Romero A, Serrano Paz P, Calpena Rico R (2005) Surgical (close lateral internal sphincterotomy) versus chemical (botulinum toxin) sphincterotomy as treatment for chronic anal fissure. Med Clin (Barc) 23:573–575CrossRef Arroyo Sebastián A, Pérez Vicente F, Miranda Tauler E, Sánchez Romero A, Serrano Paz P, Calpena Rico R (2005) Surgical (close lateral internal sphincterotomy) versus chemical (botulinum toxin) sphincterotomy as treatment for chronic anal fissure. Med Clin (Barc) 23:573–575CrossRef
19.
go back to reference Giral A, Memisoglu K, Gültekin Y et al (2004) Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a non randomised controlled trial. BMC Gastroenterol 22:7CrossRef Giral A, Memisoglu K, Gültekin Y et al (2004) Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a non randomised controlled trial. BMC Gastroenterol 22:7CrossRef
20.
go back to reference Mentes BB, Irkörücü O, Akin M, Leventoğlu S, Tatlicioğlu E (2003) Comparison of botulinum toxin injection and lateral internal sphincterotomy for the treatment of chronic anal fissure. Dis Colon Rectum 46:232–237PubMedCrossRef Mentes BB, Irkörücü O, Akin M, Leventoğlu S, Tatlicioğlu E (2003) Comparison of botulinum toxin injection and lateral internal sphincterotomy for the treatment of chronic anal fissure. Dis Colon Rectum 46:232–237PubMedCrossRef
21.
go back to reference Algaithy JK (2008) Botulinum toxin versus surgical sphincterotomy in females with chronic anal fissure. Saudi Med J 29:1260–1263PubMed Algaithy JK (2008) Botulinum toxin versus surgical sphincterotomy in females with chronic anal fissure. Saudi Med J 29:1260–1263PubMed
22.
go back to reference Nasr M, Ezat H, Elsebae M (2010) Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a randomized controlled trial. World J Surg 34:2730–2734PubMedCrossRef Nasr M, Ezat H, Elsebae M (2010) Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a randomized controlled trial. World J Surg 34:2730–2734PubMedCrossRef
23.
go back to reference Sileri P, Mele A, Stolfi VM et al (2007) Medical and surgical treatment of anal fissure: a prospective study. J Gastrointest Surg 11:1541–1548PubMedCrossRef Sileri P, Mele A, Stolfi VM et al (2007) Medical and surgical treatment of anal fissure: a prospective study. J Gastrointest Surg 11:1541–1548PubMedCrossRef
24.
go back to reference Sileri P, Tolfi VM, Ranceschilli L, et al. Conservative and surgical treatment of chronic anal fissure: prospective long term study. J Gastrointest Surg 2010 (in press) Sileri P, Tolfi VM, Ranceschilli L, et al. Conservative and surgical treatment of chronic anal fissure: prospective long term study. J Gastrointest Surg 2010 (in press)
25.
go back to reference Arroyo A, Pérez-Vicente F, Miranda E, Serrano P, Pérez-Vázquez M, Calpena R (2005) Manometric factors associated with recurrence in botulinum toxin treatment for chronic anal fissure. Gastroenterol Hepatol 28:311–314PubMedCrossRef Arroyo A, Pérez-Vicente F, Miranda E, Serrano P, Pérez-Vázquez M, Calpena R (2005) Manometric factors associated with recurrence in botulinum toxin treatment for chronic anal fissure. Gastroenterol Hepatol 28:311–314PubMedCrossRef
26.
go back to reference Arroyo A, Perez F, Serrano P, Candela F, Calpena R (2005) Long term results of botulinum toxin for the treatment of anal fissure: prospective clinical and manometric study. Int J Colorectal Dis 20:267–271PubMedCrossRef Arroyo A, Perez F, Serrano P, Candela F, Calpena R (2005) Long term results of botulinum toxin for the treatment of anal fissure: prospective clinical and manometric study. Int J Colorectal Dis 20:267–271PubMedCrossRef
27.
go back to reference Jost WH (1997) One hundred cases of anal fissure treated with botulinum toxin. Early and long-term results. Dis Colon Rectum 40:1029–1103PubMedCrossRef Jost WH (1997) One hundred cases of anal fissure treated with botulinum toxin. Early and long-term results. Dis Colon Rectum 40:1029–1103PubMedCrossRef
28.
go back to reference Maria G, Brisinda G, Bentivoglio AR, Cassetta E, Gui D, Albanese A (1998) Botulinum toxin injections in the internal anal sphincter for the treatment of chronic anal fissure: long-term results after two different dosage regimens. Ann Surg 228:664–669PubMedCrossRef Maria G, Brisinda G, Bentivoglio AR, Cassetta E, Gui D, Albanese A (1998) Botulinum toxin injections in the internal anal sphincter for the treatment of chronic anal fissure: long-term results after two different dosage regimens. Ann Surg 228:664–669PubMedCrossRef
29.
go back to reference Minguez M, Herreros B, Espi A et al (2002) Long term follow up (42 months) of chronic anal fissure after healing with botulinum toxin. Gastroenterology 123:112–117PubMedCrossRef Minguez M, Herreros B, Espi A et al (2002) Long term follow up (42 months) of chronic anal fissure after healing with botulinum toxin. Gastroenterology 123:112–117PubMedCrossRef
30.
go back to reference Abd Elhady HM, Othman IH, Hablus MA, Ismail TA, Aboryia MH, Selim MF (2009) Long term prospective randomised clinical and manometric comparison between surgical and chemical sphincterotomy for treatment of chronic anal fissure. S Afr J Surg 47:112–114PubMed Abd Elhady HM, Othman IH, Hablus MA, Ismail TA, Aboryia MH, Selim MF (2009) Long term prospective randomised clinical and manometric comparison between surgical and chemical sphincterotomy for treatment of chronic anal fissure. S Afr J Surg 47:112–114PubMed
31.
go back to reference Brisinda G, Maria G, Sganga G, Bentivoglio AR, Albanese A, Castagneto M (2002) Effectiveness of higher doses of botulinum toxin to induce healing in patients with chronic anal fissures. Surgery 131:179–184PubMedCrossRef Brisinda G, Maria G, Sganga G, Bentivoglio AR, Albanese A, Castagneto M (2002) Effectiveness of higher doses of botulinum toxin to induce healing in patients with chronic anal fissures. Surgery 131:179–184PubMedCrossRef
32.
go back to reference Mínguez M, Melo F, Espí A et al (1999) Therapeutic effects of different doses of botulinum toxin in chronic anal fissure. Dis Colon Rectum 42:1016–1021PubMedCrossRef Mínguez M, Melo F, Espí A et al (1999) Therapeutic effects of different doses of botulinum toxin in chronic anal fissure. Dis Colon Rectum 42:1016–1021PubMedCrossRef
33.
go back to reference Brisinda G, Albanese A, Cadeddu F et al (2004) Botulinum neurotoxin to treat chronic anal fissure: results of a randomised “botox” vs. “dysport”controlled trial. Aliment Pharmacol Ther 15:695–701CrossRef Brisinda G, Albanese A, Cadeddu F et al (2004) Botulinum neurotoxin to treat chronic anal fissure: results of a randomised “botox” vs. “dysport”controlled trial. Aliment Pharmacol Ther 15:695–701CrossRef
34.
go back to reference Maria G, Brisinda G, Bentivoglio AR, Cassetta E, Gui D, Albanese A (2000) Influence of botulinum toxin site of injections on healing rate in patients with chronic anal fissure. Am J Surg 179:46–50PubMedCrossRef Maria G, Brisinda G, Bentivoglio AR, Cassetta E, Gui D, Albanese A (2000) Influence of botulinum toxin site of injections on healing rate in patients with chronic anal fissure. Am J Surg 179:46–50PubMedCrossRef
35.
go back to reference Godevenos D, Pikoulis E, Pavlakis E et al (2004) The treatment of chronic anal fissure with botulinum toxin. Acta Chir Belg 104:577–80PubMed Godevenos D, Pikoulis E, Pavlakis E et al (2004) The treatment of chronic anal fissure with botulinum toxin. Acta Chir Belg 104:577–80PubMed
36.
go back to reference Jones OM, Ramalingam T, Merrie A et al (2006) Randomized clinical trial of botulinum toxin plus glyceryl trinitrate vs. botulinum toxin alone for medically resistant chronic anal fissure: overall poor healing rates. Dis Colon Rectum 49:1574–1580PubMedCrossRef Jones OM, Ramalingam T, Merrie A et al (2006) Randomized clinical trial of botulinum toxin plus glyceryl trinitrate vs. botulinum toxin alone for medically resistant chronic anal fissure: overall poor healing rates. Dis Colon Rectum 49:1574–1580PubMedCrossRef
37.
go back to reference Charúa Guindic L, Fonseca Muñoz E, Guerra Melgar LR, Avendaño Espinosa O, García Pérez NJ, Charúa Levy E (2007) Treatment of chronic anal fissure with botulinum toxin type A. Rev Gastroenterol Mex 72:22–28PubMed Charúa Guindic L, Fonseca Muñoz E, Guerra Melgar LR, Avendaño Espinosa O, García Pérez NJ, Charúa Levy E (2007) Treatment of chronic anal fissure with botulinum toxin type A. Rev Gastroenterol Mex 72:22–28PubMed
38.
go back to reference Witte ME, Klaase JM (2006) Favourable results with local injections of botulinum—a toxin in patients with chronic isosorbide dinitrate ointment-resistant anal fissures. Ned Tijdschr Geneeskd 150:1513–1517PubMed Witte ME, Klaase JM (2006) Favourable results with local injections of botulinum—a toxin in patients with chronic isosorbide dinitrate ointment-resistant anal fissures. Ned Tijdschr Geneeskd 150:1513–1517PubMed
39.
go back to reference Radwan MM, Ramdan K, Abu-Azab I, Abu-Zidan FM (2007) Botulinum toxin treatment for anal fissure. Afr Health Sci 7:14–17PubMed Radwan MM, Ramdan K, Abu-Azab I, Abu-Zidan FM (2007) Botulinum toxin treatment for anal fissure. Afr Health Sci 7:14–17PubMed
40.
go back to reference Witte ME, Klaase JM (2007) Botulinum toxin A injection in ISDN-ointment resistant chronic anal fissures. Dig Surg 24:197–201PubMedCrossRef Witte ME, Klaase JM (2007) Botulinum toxin A injection in ISDN-ointment resistant chronic anal fissures. Dig Surg 24:197–201PubMedCrossRef
41.
go back to reference Jost WH, Schanne S, Mlitz H, Schimrigk K (1995) Perianal thrombosis following injection therapy into the external anal sphincter using botulin toxin [letter]. Dis Colon Rectum 38:781PubMedCrossRef Jost WH, Schanne S, Mlitz H, Schimrigk K (1995) Perianal thrombosis following injection therapy into the external anal sphincter using botulin toxin [letter]. Dis Colon Rectum 38:781PubMedCrossRef
42.
go back to reference Tilney HS, Heriot AG, Cripps NP (2001) Complication of botulinum toxin injections for anal fissure. Dis Colon Rectum 44:1721PubMedCrossRef Tilney HS, Heriot AG, Cripps NP (2001) Complication of botulinum toxin injections for anal fissure. Dis Colon Rectum 44:1721PubMedCrossRef
43.
go back to reference Brown SR, Matabudul Y, Shorthouse AJ (2006) A second case of long term incontinence following botulinum toxin injection for anal fissure. Colorectal Dis 8:452–453PubMedCrossRef Brown SR, Matabudul Y, Shorthouse AJ (2006) A second case of long term incontinence following botulinum toxin injection for anal fissure. Colorectal Dis 8:452–453PubMedCrossRef
44.
go back to reference Mallo-González N, López-Rodríguez R, Fentes DP, Campos-Franco J, Lado FL, Alende-Sixto MR (2008) Fourniere's gangrene after botulinum toxin injection. Scand J Nephrol Urol 42:301–303CrossRef Mallo-González N, López-Rodríguez R, Fentes DP, Campos-Franco J, Lado FL, Alende-Sixto MR (2008) Fourniere's gangrene after botulinum toxin injection. Scand J Nephrol Urol 42:301–303CrossRef
45.
go back to reference Yiannakopoulou Ε (2009) Βotulinum toxin safety issues: focus on serious and long term adverse events. Ann Plast Surg 62:E57–E59 Yiannakopoulou Ε (2009) Βotulinum toxin safety issues: focus on serious and long term adverse events. Ann Plast Surg 62:E57–E59
46.
47.
go back to reference Yiannakopoulou Ε (2009) Methodological issues regarding safety evaluation in randomized controlled trials of the effectiveness of antibiotic prophylaxis for the prevention of postoperative wound infection. J Antimicrob Chemother 63:843–845PubMedCrossRef Yiannakopoulou Ε (2009) Methodological issues regarding safety evaluation in randomized controlled trials of the effectiveness of antibiotic prophylaxis for the prevention of postoperative wound infection. J Antimicrob Chemother 63:843–845PubMedCrossRef
Metadata
Title
Botulinum toxin and anal fissure: Efficacy and safety systematic review
Author
Eugenia Yiannakopoulou
Publication date
01-01-2012
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 1/2012
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-011-1286-5

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