Imiquimod Cream - Recalcitrant Warts & Immunosuppression
Background: Viral warts may cause significant morbidity in individuals unable to mount an adequate T-helper 1 cell-mediated immune response to human papillomavirus. Imiquimod is a potent inducer of antiviral cytokine activity which has shown significant efficacy in the treatment of genital warts. Similar efficacy in cutaneous warts is not yet established.
Objectives: To assess the response of persistent cutaneous warts to 5% imiquimod cream in immunosuppressed individuals.
Methods: Fifteen immunosuppressed patients with warts on the hands and/or feet present for more than 18 months, which had failed to respond to a minimum of 12 weeks of topical salicylic acid and four cycles of cryotherapy, were recruited. Imiquimod 5% cream was applied in an open label, right vs. left comparison study for 24 weeks (three times weekly for 8 weeks, daily for 8 weeks, then daily with occlusion for 8 weeks).
Results: Twelve (80%) patients completed the study protocol. Benefit was seen in five patients [36% in the intent-to-treat analysis (14 patients)], including more than 30% clearance of warts in three patients and reduction in overall size of warts in two further cases. Local skin reactions occurred in four (29%) patients and were usually mild. A transient rise in creatinine (11–29% above baseline) was measured in three renal transplant recipients, but we did not consider that this was related to imiquimod exposure.
Conclusions: This is the first controlled study to assess therapeutic efficacy of topical 5% imiquimod cream in persistent warts associated with immunosuppression. It provides preliminary evidence that topical imiquimod may benefit a subgroup of immunosuppressed patients with recalcitrant cutaneous warts.
Immunocompromised individuals unable to mount an adequate T-helper 1 (Th1) cell-mediated immune (CMI) response are susceptible to human papillomavirus (HPV) infection and may develop extensive viral warts. These are often multiple, recalcitrant and painful and spontaneous regression is rare. Organ transplant recipients (OTRs) constitute one of the largest groups of CMI-deficient individuals and warts become more prevalent as the duration of immunosuppression increases. For example, up to 50% of renal transplant recipients have cutaneous warts at 1 year and 77–95% have warts at 5 years' post-transplant. Progression of these warts to dysplastic lesions and squamous cell carcinoma has also been documented, and a possible cofactor role of HPV in immunosuppression-associated skin cancer has been an area of intense research interest in recent years.
A variety of therapeutic modalities have been used in immunosuppression-associated warts. These are mainly directed towards tissue destruction and include surgery, cryotherapy, salicylic acid, retinoids, 5-fluorouracil and intralesional bleomycin. However, they are generally of limited efficacy and side-effects, including pain, are common. Specific stimulation of a local antiviral immune response represents an alternative approach which may be a more appropriate strategy for immunosuppressed individuals. Imiquimod, an imidazoquinoline derivative (1-[2-methylpropyl]-1H-imidazo[4,5-c]quinolin-4 amine), and the prototype of a family of topical immune response modifiers, appears to have such an effect. The clinical effect of imiquimod stems from activation of both innate and cell-mediated acquired immune responses, via induction, synthesis and release of specific cytokines from monocytes/macrophages (interferon-α, interleukin-1, -6 and -12 and tumour necrosis factor-α). This results in a Th1-dominant immune response, mediated through the activation of Toll-like receptors (TLR), specifically TLR-7. Induction of transcription factor NF-κB and secretion of regulatory and proinflammatory cytokines occurs through a TLR7 MyD88-dependent signalling pathway.
Imiquimod 5% cream has shown significant efficacy compared with placebo in double-blind, randomized controlled trials of genital warts for which it is a licensed treatment, with about 50% of patients experiencing complete clearance when warts are treated three times per week for up to 16 weeks. Similar efficacy in cutaneous warts is not yet established, and there are few published data of its use in immunosuppressed patients.
In this open-label, nonrandomized, prospective, right/left comparison study, we assess the safety and therapeutic efficacy of self-administered 5% imiquimod cream for recalcitrant cutaneous warts in immunosuppressed individuals.