Treatment-refractory actinic keratoses successfully treated using simultaneous combination topical 5-fluorouracil cream and imiquimod cream: A case-control study

Background: Most actinic keratoses (AKs) respond to standard treatments, but a subset persist and require further intervention. We report a series of 10 patients with AKs that failed to respond to conventional treatment with cryotherapy and topical monotherapy but responded completely to simultaneous therapy with topical 5-fluorouracil (5-FU) and imiquimod creams. Objective: To report the success of this combination therapy in refractory AKs and to determine whether any clinical or histologic features predict for treatment resistance. Methods: Case-control study with two control groups matched to each patient according to lesion location and sex. Results: Mean lesion diameter (p <.001), lesion diameter greater than 1 cm (p <.001), and the presence of pain (p =.01) were statistically associated with failure of cryotherapy and topical monotherapy. None of the histologic features evaluated were found to be statistically significant, although thicker epidermis was nearly so (p =.054). Conclusions: In patients who have failed standard therapy for AKs, combination treatment using topical 5-FU and imiquimod cream may be an effective alternative therapeutic strategy. Larger lesion diameter, specifically greater than 1 cm, and the presence of pain predict conventional treatment resistance.