Beyond the application site: A case of imiquimod-induced cytokine-mediated systemic symptoms

Topical imiquimod is widely used for the treatment of external anogenital warts due to its potent immunomodulatory effects. Although local skin reactions are common, systemic side effects are rare and under-recognized. We describe the case of a 23-year-old male who developed recurrent, cytokine-mediated systemic symptoms-including fever, myalgias, and malaise-within hours of each application of imiquimod 5% cream to condylomata acuminata on the glans penis and inner prepuce. The lesions were located on non-keratinized, highly vascular mucosal surfaces, likely facilitating enhanced percutaneous absorption and systemic immune activation through Toll-like receptor 7 pathways. Symptoms resolved promptly with discontinuation of therapy and did not recur with alternative treatment using podophyllin resin. This case underscores the importance of recognizing systemic adverse reactions to topical immunotherapies, particularly when applied to mucosal surfaces, and highlights the need for appropriate patient counseling and individualized treatment approaches.