Therapy of Chronic Anal Fissure: Efficacy and Safety of Botulinum Toxin A Injection Compared to Topical Nitroglycerin Ointment

Aims: Chronic anal fissures (CAF) belong to the most common and painful diseases in proctology. Due to the risk of incontinence associated with surgery and side effects of nitroglycerin ointment, medical alternatives for relaxation of the anal smooth muscle have been sought. AIM: To evaluate the efficacy and safety of botulinum toxin injections compared to topical nitroglycerin ointment for the treatment of CAF. Methods: 50 outpatients with CAF, defined as evidence of a linear ulcer, a sentinel pile at the anal verge and exposure of horizontal fibres of the internal anal sphincter; and symptoms lasting for more than two months, were included into this randomised open study. Patients were randomised to receive either a single botulinum toxin A injection into the anal sphincter (30 IE Botox^®, lateral and dorsal of the fissure) or anocutaneous applications of nitroglycerin ointment 0.2% b.i.d. for two weeks. If initial therapy failed, patients were switched to the other treatment group for further 2 weeks. If CAF still showed no healing at week 4, patients received combination therapy of Botox^® and nitroglycerin ointment for at least 2 additional weeks. Persisting CAF at week 8 was treated according to the investigator’s decision. Healing rates, symptoms, and side effects of the therapy were recorded at week 2, 4, 8, 12 and 24 after randomisation. Results: The group initially treated with nitroglycerin showed a higher healing rate (13/25; 52%) as compared to the botulinum toxin group (6/25; 24%) after 2 weeks of therapy (p<0.05). At the end of week 4, healing was observed in 3 additional patients, all receiving nitroglycerin ointment after initial botulinum toxin injection. Time to complete pain relief was significantly shorter in patients receiving nitroglycerin (4.0±3.4 vs. 9.3±0.6 days). 26% of patients with healed CAF had a relapse after 6 months. Mild side effects occurred in 13/50 (26%) patients (pruritus ani, headache), of which 12 were on nitroglycerin ointment. SUMMARY: Nitroglycerin ointment was superior to the more expensive botulinum toxin injection for initial healing of chronic anal fissure and was associated with only mild side effects. Conclusions: Nitroglycerin ointment is the preferred drug for the treatment of chronic anal fissure.

Keywords: botulinum toxin A, chronic anal fissure, efficacy, nitroglycerin ointment, therapy