Topical treatment of actinic keratosis with fluorouracil: is irritation associated with efficacy?

Actinic keratoses (AKs) are common dysplastic epidermal lesions that share clinical, histologic, and molecular features with squamous cell carcinoma. Therapeutic options include destructive modalities (i.e., cryosurgery, curettage) or topical fluorouracil treatment. The efficacy of topical fluorouracil for the treatment of widespread AK lesions has been demonstrated in multiple studies, but treatment is often associated with significant skin irritation. Various approaches to decrease irritation while maintaining efficacy have been attempted, including altered treatment regimens, combination therapies, and variations in vehicle formulations. Recently, a novel topical fluorouracil cream that contains 0.5% 5-fluorouracil in a microsphere vehicle has been approved for the treatment of AK. Data demonstrate that this low-dose formulation is effective in reducing AK lesions while maintaining a tolerable irritation profile.