Fifteen patients (median age, 36 years) with a chronic anal fissure were studied. Ten had been unsuccessfully treated by local application of isosorbide dinitrate, of whom 6 had experienced a severe headache during treatment. The patients applied 1 ml of a gel containing L-arginine (400 mg/ml) to the affected area five times a day for at least 12 weeks. If the fissure persisted, the treatment was continued for a total of 18 weeks. Thirteen patients completed the trial. After 12 weeks, complete healing was seen in three of 13 patients (23%) and after 18 weeks complete healing was seen in eight patients (62%). None of the 13 patients experienced typical nitric oxide-induced headache. Anal resting pressure decreased significantly, both after the first dose and after 12 weeks of treatment, compared with the baseline value (p < 0.005), and anodermal blood flow increased (p < 0.005) at each of these times. Seven patients experienced mild perianal skin irritation, which disappeared after they were given instructions regarding perianal hygiene and care.

Comment: Chronic anal fissure has a poor healing rate. It is associated with high anal resting pressure caused by overactivity of the internal anal sphincter. The increased tone of this muscle results in reduced anodermal blood blow, especially at the posterior midline. Local application of nitric oxide donors, such as isosorbide dinitrate and glyceryl trinitrate, promotes healing by reducing anal resting pressure and improving anodermal blood flow. However, these treatments cause headache in approximately 40% of patients. The results of the present study indicate that local application of L-arginine promotes healing of anal fissures, even in patients who have failed to respond to isosorbide dinitrate, without causing headache as a side effect.

Gosselink MP, et al. Treatment of chronic anal fissure by application of L-arginine gel: a phase II study in 15 patients. Dis Colon Rectum. 2005;48:832-837.