Imiquimod is a novel synthetic molecule with potent immune-modifying activities. Formulated in a 5% vanishing cream as
Aldara, this self-applied
therapy has shown good efficacy and safety in the treatment of external genital and perianal
warts caused by human papillomavirus (HPV)
infection (Condyloma acuminata). The molecule does not demonstrate direct
antiviral activity, but through induction of
cytokines results in immune-based resolution of
wart tissue and reduction of viral burden. Phase III trials of
imiquimod have demonstrated that patients who experience complete clearance of either new or recalcitrant
warts tend to remain clear, possibly related to Th1 immune recognition and memory. Self-application, good tolerability and a unique mechanism of action combine to make
imiquimod a reasonable first-line
therapy for
genital warts. The effects of
imiquimod on immune function suggest several potential uses. Preclinical studies of
infection with herpes simplex virus (HSV),
cutaneous leishmaniasis, Rift Valley Fever virus and vesiculostomatitis virus have shown reduced viral persistence, reduced recurrence (HSV) and diminished pathology (Leishmania donovani). In a murine tumour model using the FCB
bladder cancer cell line,
imiquimod behaves as a potent adjuvant leading to immune-based tumour cell eradication and immunity against subsequent FCB cell challenge. The ability of
imiquimod to induce significant production of
interferon alpha (IFN-alpha) by monocytes/macrophages suggests that diseases responsive to recombinant
interferon therapy, such as
basal cell carcinoma, may be reasonable clinical targets. The induction of tumour
necrosis factor alpha (
TNF-alpha),
interferon gamma (IFN-gamma) and
interleukin-12 (IL-12) leads to inhibition of
IL-5, with animal models demonstrating immune deviation away from Th2 immune responses. The observation that several patients with
hepatitis C infection and
eosinophilia showed normalisation of elevated eosinophil counts in association with oral
imiquimod therapy encourages further exploration of the immune modifying properties of this novel molecule. This review is focused on the use of
imiquimod for the treatment of external genital and perianal
warts.