INTRODUCTION
Toll-like receptors (TLRs) are located on antigen presenting
cells of the innate immune system such as macrophages
and dendritic cells.1 TLRs are links between the innate immune
response and the adaptive immune response.2 The process
begins when recognition of microbial pathogen-associated molecular
patterns upregulates pro-inflammatory cytokines (e.g., interferon
alpha, tumor necrosis factor alpha, interleukins 1, 2, 6 and 8)
and co-stimulatory molecules.2,3 This maturation process enhances
the ability of the antigen presenting cell to prime naïve T cells.2 Due
to their immunomodulatory effects, TLRs have become an enticing
target for therapeutic intervention. There is significant ongoing
investigation of TLR agonists as vaccine adjuvants or immune response
modifiers in the treatment of infectious diseases, allergic
diseases, asthma, inflammatory disorders and neoplasms.4-8
Imiquimod (IQ) is a topical imidazoquinolone and primarily functions
as a Toll-like receptor 7 agonist. IQ is distributed as a 5%
cream. It is Food and Drug Administration (FDA) approved for
the treatment of actinic keratoses, superficial basal cell carcinoma,
and external genital warts. IQs efficacy in these conditions is
likely mediated by cytokine induction in the skin. Induction triggers
the host immune system to recognize the presence of viral
infection or tumor and subsequently eliminates the presenting
lesion.9 Within dermatology, the recognized immunomodulatory
effects of IQ and its application as a topical cream have lead to a
variety of off-label therapeutic attempts.
Approximately 21 percent of all prescribed medications are
written for off-label applications. Among off-label uses, only 27
percent are supported by strong clinical evidence; the remaining
73 percent lack clinical efficacy.10,11 Once a medication is FDA
approved for a specific use, physicians are free to prescribe it
for non-FDA approved applications and at non-FDA approved
doses based on their clinical judgment and experience. There
are no known studies describing the percentage of IQ prescriptions
used off-label. Informed consent is not required; however,
discussion of risks and benefits of IQ with the patient is encouraged.
Prior to prescribing IQ, it is imperative that the physician
is aware of how well-studied and how effective IQ has been for
this application.
Forty-six off-label applications of IQ were reported in the
PubMed database at the time of our initial search in 2009. We
summarize published clinical trials, case series, and case reports
pertaining to each application. The strongest form of
clinical evidence reported is presented in the text. If available,
the total length of studies and follow-up periods are noted. Serologic
and histopathologic studies are presented. Please keep
in mind that suggestions made in this review are derived from
our review of how IQ has been used in practice. While larger trials
are necessary to develop standardized protocols, we hope
this review will be a useful tool in guiding your clinical use of IQ
should you choose to use IQ off-label.
