Imiquimod is an immune response modifier with the chemical structure 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amin. Since imiquimod was authorized on the US market in 1997 and on the Chinese market in 2003, it has been approved as a patient-applied topical treatment for condylomata acuminata in adults. We find it is a well-tolerated drug but with the frequent side effects of erythema, burning, blistering, and excoriation. We also noted its other adverse effect of inducing localized vitiligo, which occurred in the treated areas.
Vitiligo is a condition characterized by depigmentation of the skin and mucous membranes, with well-demarcated, depigmented macules and patches. The etiology of vitiligo is unknown, but research suggests that it may involve autoimmune, genetic, and other factors. Autoimmune disorders are often associated with thyroid abnormalities, pernicious anemia, systemic lupus erythematosus, and other diseases. Our patient denied any family history of vitiligo or autoimmune disorder, the possibility of which was excluded by laboratory analysis. He denied use of any other topical treatments in the areas treated with imiquimod 5% cream. The features of his depigmented patches and histopathology support the diagnosis of vitiligo. Therefore, we believe that the vitiligo patches of our patient were induced by the imiquimod. We were able to obtain a small amount of superficial skin from the dorsal surface of the genital lesions in the perineal region. All eight of the patients reported in the English literature refused biopsies of the depigmented areas, and one even refused to have the lesions photographed. Therefore, our patient is the first to undergo histopathological examination and whose diagnosis was based on clinical and histopathological findings.
The possible mechanism for the destruction of the human papilloma virus (HPV) by imiquimod is that it stimulates peripheral blood monocytes, macrophages, and dendritic cells to produce such cytokines as interferon alfa (IFN-α), interleukin-12 (IL-12), and tumor necrosis factor alfa (TNF-α), so imiquimod can enhance the host’s innate and cellular immune response and combat anogenital HPV infection [12, 13]. To study the safety and effectiveness of imiquimod 5% cream in the treatment of external anogenital warts, Edwards et al. applied it on 109 patients; 50% of the patients experienced eradication of all treated baseline warts . Other studies also indicated that imiquimod 5% cream was effective in treating condylomata acuminata. However, imiquimod not only kills the HPV but also destroys melanocytes. Similarly, the mechanism of imiquimod-induced vitiligo may be that the medication activates the Langerhans cells in the lesions via antigen presentation, leading to the destruction and apoptosis of the melanocytes. Imiquimod-induced apoptosis of melanocytes was confirmed by TUNEL assay, Hoechst 33258 staining, and measuring mitochondrial membrane potential in melanocytes . Moreover, imiquimod can induce cytokines such as IFN-α, TNF-α, IL-6, IL-8, and nitric oxide to cause vitiligo . Additionally, imiquimod binds to Toll-like receptor-7 and −8, increasing production of proinflammatory cytokines such as IFN-α, TNF-α, and LI-12 [17, 18], which play a role in the pathogenesis of vitiligo.
Accompanying the use of imiquimod on increasing numbers of patients with condylomata acuminata, dermatologists should keep this potential side effect in mind.