Anal fissure is one of the most common lesions to consider in the differential diagnosis of anal pain. This is an ulcer in the squamous epithelium of the anus located just distal to the mucocutaneous junction and usually in the posterior midline. It typically causes episodic pain that occurs during defecation and for one to two hours afterwards.¹ This feature uniquely distinguishes anal fissure from other causes of anal pain such as thrombosed haemorrhoids, abscess, viral ulcers, and others. Atypical fissures may be multiple or off the midline, or be large and irregular. These may be caused by inflammatory bowel disease, local or systemic malignancy, venereal infection, trauma, tuberculosis, or chemotherapy. The cause of the typical or benign fissure is not clear nor are there accepted methods for the prevention of fissures—both fertile areas for research.

The most consistent finding in typical fissures is spasm of the internal anal sphincter, which is so severe that the pain caused by the fissure is thought to be due to ischaemia of the sphincter.² Relief of the spasm has been associated with relief of pain and healing of the fissure without recurrence. Historically the most common approach for relieving the pain associated with spasm of chronic adult anal fissure is surgical, though no placebo controlled surgical trials have been undertaken. Morbidity from operative procedures, mainly incontinence, was once thought to be extremely rare³ but has been substantial in some recent reports.⁴ So by the late 1990s when alternatives to surgery were sought because of cost, time for recovery, and risk of incontinence, rather than turn back to older treatments, such as lubricants and numbing agents, newer medications were investigated—in each case a medication that was known to relax muscle spasm. These have included nitroglycerin ointment, injection of botulinum toxin, and calcium channel blockers either given as tablets or applied topically.

The choice of treatment remains difficult for the following reasons. Although surgery is highly efficacious and succeeds in curing the fissure in more than 90% of patients, in a systematic review of randomised surgical trials the overall risk of incontinence was about 10%.⁵ This was mostly incontinence to flatus, and there are no reports delineating the duration of this problem (is it permanent or transitory?) Publications describing treatment for incontinence after sphincterotomy for fissure are strikingly absent, implying a lack of need compared with other incontinent populations.

Regarding medical treatment, in a similar systematic review combining all analyses in which a placebo was used as the comparison group,⁶ the healing rate in the placebo group was found to be 35%. This was a level of response that was fairly uniform across studies (standard deviation 12%). The medications being tested in the meta-analysis (nitroglycerin ointment, botulinum toxin injection, and calcium channel blockers) must have their efficacy viewed in the context of this placebo effect and also in the context of a cure rate for surgery that often exceeds 95%.⁵ In the combined analyses, nitroglycerin ointment was found to have a healing rate of about 55%. In comparisons of nitroglycerin ointment to botulinum toxin injection or calcium channel blockers, no significant difference in efficacy was found between the three. Overall nitroglycerin ointment was more effective than placebo, but in sensitivity analyses that excluded studies with placebo cure rates below 10%—more than two standard deviations below the mean—statistical evidence of efficacy disappeared. In addition, with nitroglycerin ointment, the most investigated medical treatment, headache was common, occurring in almost 40% of subjects in the combined analyses and severe enough often to stop treatment.⁶

So it would be advantageous if the risk of incontinence could be reduced after surgery or the success rate of medical treatments increased to that found in surgery, but with less risk of headache. The Cochrane reviews provide some direction here but not a quick fix. Anal stretch was found to have a significantly higher risk of incontinence than controlled sphincterotomy in surgical trials and a higher risk of treatment failure. Stretch should probably be abandoned in favour of partial internal sphincterotomy until a better operation is described. Among the medical treatments, calcium channel blockers applied topically caused fewer headaches and may be as efficacious as nitroglycerin ointment.

Medical treatment for chronic anal fissure, acute fissure, and fissure in children may therefore be applied with a chance of cure that is only marginally better than placebo. The risk of using such treatments is not great: mainly headache during the use of nitroglycerin ointment, without apparent adverse effect in the long term. Medical treatments can therefore be used in individuals wanting to avoid surgical treatment, and surgery can be reserved for treatment failures in adults with chronic typical fissure. Topical application of calcium channel blockers may be as effective as nitroglycerin ointment in the treatment of anal fissure, without the risk of headache, which many patients find unacceptably painful. Too few studies exist to establish this efficacy.