Deborah Brauser

March 18, 2009 — Treatment with colchicine or dapsone — 2 corticosteroid-sparing anti-inflammatory agents — alone or together is effective for most patients with complex aphthosis, according to the results of a retrospective review reported in the March issue of the Archives of Dermatology.
"Recurrent aphthous stomatitis...is the most common inflammatory ulcerative condition of the oral mucosa...characterized by intermittent episodes of painful oral aphthae of any morphologic origin," write Carrie B. Lynde, HBSc, LLB, from the Faculty of Medicine at the University of Toronto, Ontario, Canada, and colleagues. "Complex aphthosis refers to an almost constant presence of ≥3 oral ulcers, recurrent oral and genital aphthae, and exclusion of Behcet syndrome."
The researchers evaluated the medical records of 55 patients with complex aphthosis who had experienced multiple therapy failure. The patients were then treated with colchicine, dapsone, or both at the Mayo Clinic between January 1998 and July 2007. The mean age of the participants was 41 years, 69% were women, and the median duration of disease before presentation to the Mayo Clinic was 13 years. A total of 82% had oral aphthae only, and 18% having oral and genital aphthae. The main study endpoint was a substantial response to therapy with colchicine alone, dapsone alone, or both.
Patients received treatment according to a therapeutic ladder beginning with colchicine. Dapsone was then added for patients who did not have a substantial response to colchicine within 12 weeks or who discontinued use because of adverse events.
Patients started with a 0.6-mg dose of colchicine each evening for 1 week. If they had no significant gastrointestinal tract upset during this therapy, the dose was increased to 1.2 mg daily, receiving either 1 tablet in the morning and 1 in the evening or both tablets in the evening. If this dose was tolerable, it was increased to 1.8 mg daily. Dapsone was given in a stepwise manner at 25 mg daily for 3 days, followed by 50 mg daily for 3 days, 75 mg daily for 3 days, and 100 mg daily for 1 week. If the patient had a low hemoglobin level, the dose was held at 100 mg daily. However, if the patient's hemoglobin level was within the reference range, the dose was increased to 125 mg daily.
Monitoring during colchicine therapy included a complete blood cell count and liver function tests at baseline and once or twice a year thereafter. During dapsone treatment, a complete blood cell count, a reticulocyte count, liver and renal function tests, and urinalysis were performed weekly for the first 4 weeks, then monthly for the next 4 months, and once every 3 months after that. The response to treatment was evaluated by both physician and patient according to the frequency, intensity, and severity of aphthosis attacks.
Results showed that overall, 80% of the patients had a substantial response to therapy, with benefits noted within 4 to 8 weeks. In addition, no serious adverse events were reported.
Because of the severity of their disease, 2 patients began treatment with colchicine and dapsone simultaneously, with both having treatment success.
Fifty patients began treatment with colchicine only, with 30 (60%) reaching treatment success with this agent alone.
A total of 14 patients went on to receive combination therapy with colchicine and dapsone, and 10 of these patients (71%) achieved treatment success. Five patients went on to receive dapsone alone because of adverse events resulting from the colchicine or because of gastrointestinal tract intolerance. Four (80%) of these 5 patients had treatment success.
While there were no serious adverse events reported with either treatment, 21 of 52 patients experienced adverse events while taking colchicine, necessitating its discontinuation in 7 of the patients. The most common adverse event was diarrhea (31%). Other adverse events, reported once each, were a burning sensation in the feet, transient thrombocytopenia, rash with elevated liver enzyme levels, easy bruising, and vomiting.
Eleven of 19 patients had adverse events while taking dapsone, necessitating its discontinuation in 3 patients. The most common adverse event with dapsone was hemolytic anemia (37%). Other adverse events reported were transient leucopenia, paresthesia of the face, and asymptomatic dermatitis.
Limitations of this study included its retrospective nature, as well as the lack of standardized patient evaluation and the small number of patients treated with dapsone.
"This study demonstrates that colchicine is an effective first-line corticosteroid-sparing therapy for complex aphthosis," the study authors conclude. "The present study also demonstrates that dapsone is an effective second-line systemic treatment."
They continue, "In practice, we tend to follow the therapeutic ladder for additive therapies rather than abandoning one therapy in favor of another. Thus, we suggest that patients whose complex aphthosis does not respond to colchicine in their initial therapeutic trial continue taking colchicine when dapsone is added to the regimen."
Further prospective, double-blind, randomized, placebo-controlled studies are needed to assess the optimal overall treatment of this disease, the authors add.