Azathioprine (Imuran?, GlaxoSmithKline) at 50-150mg/day can reduce the frequency and extent of severe orogenital aphthosis in ABD, as demonstrated in placebo-controlled studies.18 It is contraindicated for women who are pregnant or breastfeeding, and it is not recommended for use in pediatric patients. During treatment, blood cell count and liver function should be monitored. Methotrexate (7.5-20mg/week) has been proven to be effective in severe orogenital aphthosis. While on therapy, folic acid should be administered intermittently. Cyclosporine A
Cyclosporine A, at a dosage of 3-6mg/kg, was shown to be effective in about 50% of ABD patients with respect to aphthosis.19 However, abrupt withdrawal of therapy may lead to a rebound phenomenon. Due to the potential for severe side-effects from therapy, clinical and serologic vigilance must be observed. Interferon-alpha (IFN-á)
Recombinant IFN-á preparations, IFN-á 2a and 2b, have not been tried for RAS; however, they have successfully treated ABD. A study evaluating the efficacy and safety of systemic IFN-á in patients with ABD reported complete or partial remission of mucocutaneous lesions.20 Intermediate or high doses of IFN-á 2a (6-9 x 106 units, 3 times/week) seemed to be more effective than the low dose (3 x 106 units 3 times/week). The low dose may be recommended for maintenance therapy if the treatment is shown to be effective within 1-4 months. Disease recurrences after stopping IFN therapy were common, but reinstatement of therapy also elicited a rapid response. Biologics
Infliximab (Remicade?, Centocor) at 5mg/kg IV can be administered at different time intervals. As early as several days following the first dose, rapid healing can occur, even in patients with refractory recurrent disease who exhibit both oral and genital ulcers. It is possible that relapses may not occur within the first 6 weeks of starting therapy. Etanercept (Enbrel?, Amgen-Wyeth) at 25mg, twice weekly, given subcutaneously) appears to be effective on oral, but not on genital aphthae.21 Alkylating Agents
Monotherapy with chlorambucil on orogenital ulcerations in ABD demonstrated a good response when administered at an initial dose of 0.1mg/kg, followed by a low maintenance dose of 2mg/day.22 Orogenital aphthae in ABD patients also improved when using pulse
therapy combined with cyclophosphamide. Treatment with alkylating agents should be limited exclusively to patients with severe forms of systemic aphthosis.22
Other Systemic Therapies In a study involving 13 patients, minocycline (100mg/day) was found to be effective in genital aphthosis, but it was ineffective against oral aphthosis.23 For the immunomodulator, levamisole, treatment at 150mg/day on 3 consecutive days/week during attacks has been occasionally reported to be effective against orogenital aphthae.24,25 Subcutaneous testosterone, administered once yearly, was shown to be effective in individual female patients who developed aphthae premenses.26 Also, oral contraceptives containing high levels of estrogen can be used successfully; improvement may be expected after 3-6 months.
Conclusion Localized topical regimens are considered to be the standard treatment in mild cases of RAS. In more severe cases, topical therapies are likewise very useful in reducing the healing time, but they are often ineffective at prolonging disease-free intervals. For most patients with RAS, monotherapy with colchicine, or in combination with either pentoxifylline or the short-term use of prednisolone, is satisfactory. Furthermore, highly efficacious drugs from a wide spectrum of immunomodulatory agents are available. However, they should not be utilized without first cautiously weighing the risks and the benefits for each patient.
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