Stevens-Johnson Syndrome and Erythema Multiforme Induced by Imiquimod 5% Cream

Topical imiquimod is a safe and effective treatment for actinic keratoses, superficial basal cell carcinomas, and anogenital warts. The treatment is commonly associated with local inflammatory reactions, while systemic side effects are rare and generally mild. Only few cases of erythema multiforme and Stevens-Johnson syndrome have been described in association with topical imiquimod application.

We present a narrative review of the existing cases of erythema multiforme and Stevens- Johnson syndrome reported in the literature, analyzing the clinical appearance, the histology, and the treatment of the lesions.

Twenty-one articles were retrieved. All the sourced articles were full-text reviewed to ensure that the contents were relevant to the study, which resulted in the exclusion of 10 articles.

Nine case of erythema multiforme were reported, characterized by cutaneous rash, bullae, crusting, and erosive and targetoid lesions, mainly located at the extremities. Mucosal involvement and systemic symptoms were present in five and in three cases, respectively. Three cases of Stevens-Johnson syndrome were associated with topical imiquimod. In all cases, the authors reported targetoid lesions and areas of erosion affecting trunk and limbs, associated with systemic symptoms, and, in two cases, with mucosal erosions.

We hypothesize a possible role of interferon-γ, a cytokine involved in the pathogenesis of both herpes-associated erythema multiforme and Stevens-Johnson syndrome, which is released in response to the administration of imiquimod.