Anal Fissure Pharmacology

Mr Justin Davies, Consultant Colorectal Surgeon, Bradford Royal Infirmary

Powerpoint File

It is hypothesised that the aetiology of anal fissure is internal anal sphincter hypertonia, which results in ischaemia of the anal mucosa culminating in painful ulceration (1). Relief of the hypertonia has been associated with reduction of pain and healing of the fissure without recurrence.

Although lateral sphincterotomy is highly efficacious and achieves healing in over 90% of patients with a fissure, systematic review of randomised trials report an overall risk of incontinence of 10% (2). This is mainly incontinence to flatus, but sphincterotomy is associated with severe incontinence in a small number of patients (3).

In recent years the treatment for chronic anal fissures has shifted from surgical to medical management. There has been a radical reduction in the number of patients undergoing surgical sphincterotomy since the introduction of the chemical sphincterotomy. In the UK the number of patients undergoing lateral internal sphincterotomy has reduced from 10,000 procedures in 1996/1997 to 5,500 procedures in 1999/2000 (4).

Greater understanding of the physiology of regulation within the internal sphincter led to development of medical treatments, which reduce internal sphincter pressure. Initial studies looked at glyceryl trinitrate (GTN), a nitric oxide donor, known to cause internal sphincter relaxation. The first prospective randomised controlled trial comparing GTN versus placebo was performed by Lund and Scholefield (5). In this study healing rates were significantly higher in the GTN than the placebo group (68% versus 8%). Although early studies showed promise, initial enthusiasm has been tempered by concern over medium-term treatment failure and side effects, notably headaches and tachyphylaxis (6). Subsequently, prospective studies assessing various nitric oxide donors; GTN, isosorbide dinitrate, calcium channel blockers; nifedipine, diltiazem and Botulinum toxin have reported in the world literature. Whilst initial reports were often extremely encouraging (5,7), subsequent papers questioned the long-term efficacy of all medical treatments in healing fissures (8,9). More recently a systemic review of medical therapy for chronic fissures has called into question the efficiacy of both GTN and botulinum toxin in healing fissures when compared to placebo. Meta-analysis suggests that both GTN and botulinum toxin may be applied with a chance of cure that is only marginally superior to placebo and for chronic fissure far less effective that surgery (10).

In conclusion, medical therapy remains the first-line treatment for most patients with chronic fissure-in-ano using a 'safety-first' approach. Whilst of limited efficacy, medical treatment remains relatively cheap, convenient and not associated with a risk of permanent incontinence. Surgery should be reserved for those patients who have failed medical management (11).

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2. Nelson RL. Operative procedures for fissure in ano (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd.

3. Wiley M, day P, Rieger N, Stephens J, Moore J. Open vs. closed lateral internal sphincterotomy for idiopathic fissure-in-ano: A prospective, randomised, controlled trial. Dis Colon Rectum 2004; 47:847-852.

4. Christie A, Guest JF. Modelling the economic impact of managing a chronic anal fissure with a proprietary formulation of nitroglycerin (Rectogesic) compared to lateral internal sphincterotomy in the United Kingdom. Int J Colorectal Dis 2002; 17: 259-267.

5. Lund JN, Scholefield JH. A randomised prospective, double-blind placebo-contolled trial of glyceryl trininritate ointment in the treatment of anal fissure. Lancet 1997; 349: 11-14.

6. Carapeti EA, Kamm MA, MacDonald PJ, Chadwick SJ, Melville D, Phillips RK. Randomised controlled trial shows that glyceryl trinitrate heals anal fissures, higher doses are not effective, and there is a higher recurrence rate. Gut 1999; 44: 727-730.

7. 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.

8. Hyman Nh, Cataldo PA. Nitrogylcerin ointment for anal fissures: effective treatment or just a headache? Dis Colon Rectum 1999; 42: 383-385.

9. Siproudhis L, Sebille V, Pigot F, Hemery P, Juguet F, Bellissant E. Lack of efficacy of botulinum toxin in chronic anal fissure. Aliment Pharmacol Ther 2003; 18: 515-524.

10. Nelson R. A systematic review of medical therapy for anal fissure. Dis Colon Rectum 2004; 47: 422-431.

11. Lindsey I, Jones OM, Cunningham C, Mortensen NJ. Chronic anal fissure. British J Surg 2004; 91: 270-279.