Pearls of Wisdom: Anal Fissures

Marco is a 32-year-old who has complained of anal fissure, confirmed by anoscopy, for over 3 years. He has used stool softeners, emollients, and topical agents (eg, anal steroids and hemorrhoid treatment). He maintains a consistent bowel pattern of daily stool—moderately formed and able to be expelled with a minimum of straining.

Despite his adherence to the recommended treatment, he still evidences an anal fissure which produces burning at stool and blood spotting. The amount of blood loss is not sufficient to cause anemia, but he is still distressed that he has been unable to heal the fissure despite his best efforts.  

Is there anything short of surgery that might help?

A. Topical nitroglycerin ointment
B. Topical aloe vera cream
C. A low-glycemic index diet
D. Topical lidocaine jelly

What is the correct answer?
(Answer and discussion on next page)

Louis Kuritzky, MD, has been involved in medical education since the 1970s. Drawing upon years of clinical experience, he has crafted each year for almost 3 decades a collection of items that are often underappreciated by clinicians, yet important for patients. These “Pearls of Wisdom” often highlight studies that may not have gotten traction within the clinical community and/or may have been overlooked since their time of publishing, but warrant a second look.

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Answer: Topical nitroglycerin ointment

Our thought process about anal fissure (or rectal fissure) likely requires some revision due to recent recognition of previously unrecognized underlying pathology. We used to think fairly simplistically that anal fissure was a result of over-vigorous passage of hard, large caliber stool through the anus with sufficient intensity that a small tear occurred. Based upon this model, it was surmised that remedying the culprit issues (ie, large caliber stool, hard stool, and over-vigorous straining) would resolve the issue after sufficient time for healing elapsed.

Unfortunately, even though these well-intended interventions are often successful, they do not always work. Patients who maintain a consistent bowel habit of frequent, softly formed stools and avoid straining at stool still sometimes persist with anal fissure and its attendant pain and bleeding. Why?
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Anorectal Complaints: Office Diagnosis and Treatment, Part 1
Anorectal Complaints: Office Diagnosis and Treatment, Part 2
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Research

It has been clarified over the last 10 to 15 years that persistent anal fissure is often accompanied by what might properly be termed “anal hypertonus.” That is, anal manometry shows increased tonicity of the internal anal sphincter, which appears to impede healing of anal fissure.¹ Corroborating that this interpretation of pathophysiology is correct are the results of clinical trials with agents that reduce anal tone (eg, nitroglycerin, calcium channel blockers, botulinum toxin)—demonstrating remarkable success in otherwise refractory anal fissure, for which the next step would have been surgical intervention. 

An example of this success is demonstrated in the placebo-controlled trial by Lund and Scholefield¹ in which patients with refractory anal fissure (that is, having failed traditional stool modulation methods and topical agents) were randomized to placebo or topical nitroglycerin in a double-blind clinical trial.

Note: The nitroglycerin utilized was not traditional 2% paste as employed in persons with angina.

Application of 2% nitroglycerin applied cutaneously is associated with headaches and hypotension. As might be intuitive, nitroglycerin 2% applied to mucosal surfaces (eg, mouth or rectum) is even better absorbed than other cutaneous surfaces and would be anticipated to have an even greater adverse effect profile.

Hence, a diluted version of nitroglycerin—0.2% nitroglycerin ointment—was applied twice daily to the anus in 89 patients. The outcomes of the study were mean anal resting pressure, pain, and percent healed.

NTG Ointment for Rectal Fissure¹

At 8 weeks time, 68% of the previously refractory fissures were healed on nitroglycerin versus 8% on placebo. Pain reduction, as well as reduced mean anal pressure, on nitroglycerin was prompt and effective. Had these patients not been successfully treated, the next step treatment would be surgical.

What’s the “Take Home”?  

We have to re-think the mechanism of generation and propagation of anal fissure. Although it may be correct that direct rectal tissue trauma from hard caliber, forcibly expressed stool could induce a rectal fissure, it appears that increased mean anal resting pressure is associated with persistence of anal fissure. Agents that reduce anal tone, such as nitroglycerin ointment 0.2%, may offer rescue treatment for otherwise refractory anal fissure.

Reference:

1. Lund JN, Scholefield JH. A randomised, prospective, double-blind, placebo-controlled trial of glyceryl trinitrate ointment in the treatment of anal fissure. Lancet. 1997;349(4):11-14.