Introduction: The first observations of "giant buccal aphthosis" induced by nicorandil were published in 1996. Nicorandil is a potassium channel activator used in the treatment of angina pectoris, which seems to induce specific buccal ulcerations. The purpose of this study was to analyze the clinicopathologic data of patients with aphthosis induced by nicorandil and to study the prevalence of this side effect.
Patients and methods: We have seen 3 patients who spontaneously consulted, and 5 patients who were addressed to us after a telephone survey. We have then examined 100 consecutive patients treated by nicorandil for at least 1 month, who were hospitalized in 3 departments of cardiology in Strasbourg, and 100 age- and sex-matched controls who were treated by other antianginal drugs.
Results: Our 8 patients suffered from large, chronic and painful ulcerations of a 4-week duration, located on the tongue, the gingiva and the cheeks despite various symptomatic treatments. In one case, histopathologic data were consistent with an eosinophilic ulcer. Prospective study: among 100 patients treated by nicorandil, 5 had unusual chronic buccal ulcerations, whereas none of the 100 controls had aphthosis (p = 0.03). The confidence interval (99 p. 100) of this side effect prevalence was therefore 1 p. 100 to 14 p. 100.
Discussion: Nicorandil can induce large and painful buccal ulcerations with severe dysphagia, weight loss, and depression. Dermatologists should be aware of this particular side-effect, since our study showed a high prevalence, and because lesions heal rapidly after withdrawal of nicorandil. Why nicorandil may be associated with mouth ulcers remains unanswered. A past history of aphthae could be a cofactor of this side-effect.