Correspondence

A Comparison of Botulinum Toxin and Nitroglycerin Ointment for Chronic Anal Fissure

N Engl J Med 1999; 341:1701November 25, 1999

Article

To the Editor:

Brisinda et al. (July 8 issue)1 report that healing of chronic anal fissure occurred in 22 of the 25 patients in the group receiving botulinum-toxin injections and in 10 of the 25 patients treated with topical nitroglycerin ointment. In addition, symptomatic improvement, defined by the authors as the absence of symptoms despite the persistence of the fissure, occurred in 2 of the 3 remaining patients in the botulinum-toxin group and 8 of the remaining 15 patients in the nitroglycerin group. These results indicate that healing of fissure and resolution of symptoms should not be equated. The authors did not report the rate of symptomatic improvement in the patients with healed fissures. Did only two thirds of the fissures healed with the use of botulinum toxin result in symptomatic improvement? If so, then perhaps a multimodal approach, aimed at both healing and symptomatic improvement, would be more efficacious therapy for patients with chronic anal fissure.

Jon D. Vogel, M.D.
Johns Hopkins Hospital, Baltimore, MD 21287

1 References

1. 1

   Brisinda G, Maria G, Bentivoglio AR, Cassetta E, Gui D, Albanese A. A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure. N Engl J Med 1999;341:65-69
   Full Text | Web of Science | Medline

To the Editor:

Although a six-week treatment with 0.2 percent nitroglycerin ointment will cost no more than 10 to 15 Swiss francs (equivalent to $6 to $10), a single injection of 20 U of botulinum toxin, taken from a vial containing 100 U, currently costs 357 Swiss francs ($238). Assuming that the lack of response to an initial treatment of topical nitroglycerin varies between a maximum of 40 percent (as reported by Brisinda et al.) and a minimum of 12 percent (as reported by others1,2) and that these patients would have to be offered an injection of botulinum toxin later, the resulting overall costs of the treatment of 100 patients would be considerably lower with an initial treatment of nitroglycerin ointment than with a single injection of botulinum toxin. Initial treatment with nitroglycerin should therefore be favored in patients with chronic anal fissures, and botulinum-toxin injections should be reserved for patients without an adequate response after six weeks.

Andreas M. Kaiser, M.D.
University Hospital, CH-8091 Zurich, Switzerland

2 References

1. 1

   Lund JN, Scholefield JH. A randomised, prospective, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in treatment of anal fissure. Lancet 1997;349:11-14[Erratum, Lancet 1997;349:656.]
   CrossRef | Web of Science | Medline

2. 2

   Schouten WR, Briel JW, Boerma MO, Auwerda JJ, Wilms EB, Graatsma BH. Pathophysiological aspects and clinical outcome of intra-anal application of isosorbide dinitrate in patients with chronic anal fissure. Gut 1996;39:465-469
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Symptomatic improvement, defined in our study as the persistence of fissure and the absence of post-defecatory pain, occurred in less than 10 percent of the patients in the botulinum-toxin group because of that group's higher rate of complete healing, which was defined as the healing of the fissure and the disappearance of symptoms. We believe that the combination of both treatments is less helpful; complete healing and symptomatic relief can be achieved with botulinum-toxin injections alone. Nitrates have a short duration of action; thus, frequent application is mandatory. Side effects, such as headaches and tachyphylaxis, limit their utility.1 Nitroglycerin ointment causes headaches more often than it treats symptoms of anal fissure.2 In addition, higher doses of nitroglycerin are not more effective than lower doses in inducing healing.3

In patients with posterior anal fissure, we found a healing rate of 96 percent when botulinum toxin was injected anteriorly into the internal sphincter. The different injection site induces a greater decrease in resting pressure and improves the clinical outcome. This effect should be related to the fibrosis of the internal sphincter, which is more prominent at the site of the fissure than at other sites in the smooth muscle.4 The fibrosis may reduce the compliance of the internal sphincter and limit the diffusion of the toxin. Moreover, botulinum toxin is more effective than nitroglycerin in alleviating sphincter hypertonia.5

Kaiser states that in order to reduce the costs of treatment, nitroglycerin ointment should be used initially in patients with chronic anal fissure and botulinum-toxin injections should be reserved for patients with unhealed fissures. Nevertheless, we found that botulinum toxin was more effective and safe in inducing healing than nitrate therapy; the efficacy is not related to the patient's willingness to complete treatment. Although treatment with botulinum toxin is more costly than treatment with nitroglycerin ointment, denying patients a more effective treatment for this reason makes little sense.

Giorgio Maria, M.D.
Giuseppe Brisinda, M.D.
Catholic University, 00168 Rome, Italy

5 References

1. 1

   Hasler WL. The expanding spectrum of clinical uses for botulinum toxin: healing of chronic anal fissures. Gastroenterology 1999;116:221-223
   CrossRef | Medline

2. 2

   Hyman NH, Cataldo PA. Nitroglycerin ointment for anal fissures: effective treatment or just a headache? Dis Colon Rectum 1999;42:383-385
   CrossRef | Web of Science | Medline

3. 3

   Carapeti EA, Kamm MA, McDonald PJ, Chadwick SJ, Melville D, Phillips RK. Randomised controlled trial shows that glyceryl trinitrate heals anal fissures, higher doses are not more effective, and there is a high recurrence rate. Gut 1999;44:727-730
   CrossRef | Web of Science | Medline

4. 4

   Brown AC, Sumfest JM, Rozwadowski JV. Histopathology of the internal anal sphincter in chronic anal fissure. Dis Colon Rectum 1989;32:680-683
   CrossRef | Web of Science | Medline

5. 5

   Brisinda G, Maria G, Bentivoglio AR, Cassetta E, Gui D, Albanese A. A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure. N Engl J Med 1999;341:65-69
   Full Text | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Harsha Vittal, Pankaj Jay Pasricha. (2006) Botulinum toxin for gastrointestinal disorders: Therapy and mechanisms. Neurotoxicity Research 9:2-3, 149-159
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2. 2

   Mariusz H. Madalinski, Jaroslaw Slawek. (2003) Safety of botulinum toxin therapies. Diseases of the Colon & Rectum 46:12, 1719-1720
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3. 3

   Michael G. Ross, Meredith Fresquez, Mostafa A. El-Haddad. (2000) Impact of FDA advisory on reported vacuum-assisted delivery and morbidity. The Journal of Maternal-Fetal Medicine 9:6, 321-326
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