Efficacy and risks of topical 5-fluorouracil in Darier's disease

Background. - Darier's disease, an autosomal dominant disorder, is often resistant to therapy. There have been few encouraging reports in recent years of treatment using topical 5-fluorouracil (5FU) in this indication. We describe three cases of Darier's disease treated with Efudix (R) : though it initially proved very effective, after several months this treatment became inefficacious. Patients and methods. - Case 1: a 16-year-old girl with Darier's disease refractory to conventional treatments. Treatment with topical 5FU was initiated. After 3 weeks, her cutaneous lesions had practically disappeared, leaving only pigmented scars. At 6 months, worsening of the disease was controlled by increasing 5FU. At 11 months, the disease worsened and 5FU, which proved inefficient, was stopped. Case 2: a 59-year-old woman presenting treatment-resistant Darier's disease was given 5FU. After 1 week, improvement began and was evident at 4 months. However, after 13 months of treatment, the disease progressed, and increased 5FU proved completely ineffective. Case 3: a 29-year-old woman was hospitalized for inflammatory Darier's disease. Topical 5FU was applied to the left half of the body and a short course of oral corticosteroids was prescribed. After 10 days of treatment, there was a clear improvement. After 6 weeks, the patient showed episodes of healthy skin. However after 3 months, the patient stopped taking her treatment due to inefficacy. Discussion. - While topical 5FU seems to be effective initially in treating Darier's disease, this efficacy subsides over time. Although no adverse effects were noted in our patients, use of 5FU can result in serious adverse reactions. Because of the loss of efficacy of this treatment following initial success, coupled with its poorly evaluated safety, caution must be exercised when prescribing it, particularly in patients with dihydropyriminidine dehydrogenase (DPD) deficiency or for use on damaged skin. (C) 2010 Elsevier Masson SAS. All rights reserved.