Dual mechanism of action of ingenol mebutate gel for topical treatment of actinic keratoses: Rapid lesion necrosis followed by lesion-specific immune response

Current topical agents for field therapy of actinic keratoses have single mechanisms of action and must be applied for weeks. Ingenol mebutate gel, a novel drug for field therapy of actinic keratoses, appears to have a dual mechanism of action: (1) rapid lesion necrosis and (2) specific neutrophil-mediated, antibody-dependent cellular cytotoxicity. Because of the rapid destruction of actinic keratosis lesions after application of ingenol mebutate gel, treatment is necessary for only 2 or 3 days. The subsequent immune-mediated response targets any residual dysplastic epidermal cells. This dual mechanism of action should provide efficacy equivalent to that of current topical agents with a substantially shorter treatment period. (J Am Acad Dermatol 2012;66:486-93.)