Aldara
Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals.

Harwood CA, Perrett CM, Brown VL, Leigh IM, McGregor JM, Proby CM.

Centre for Cutaneous Research, Barts and the London School of Medicine and Dentistry, Queen Mary College, University of London, 2 Newark Street, London, E1 2AT, UK. caharwood doctors.org.uk

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.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15656812&dopt=Abstract imiquimod Aldara



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Role of imiquimod in skin cancer treatment.

Urosevic M, Dummer R.

Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.

Cancer of the skin is by far the most common form of all cancers. Given the increasing incidence of skin cancer worldwide, it seems feasible to reconsider the treatment options available for dealing with this growing problem. Despite the lower costs associated with classical methods such as surgery and radiotherapy, immune response modifiers such as imiquimod appear to be good candidates for the future given their good cosmetic effects, the possibility of treating large areas, and the simpleness of patient-applied treatment with a cream formulation. This article reviews current literature on the use of imiquimod in the treatment of nonmelanoma and melanoma skin cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15663342&dopt=Abstract imiquimod Aldara



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Imiquimod is a strong inhibitor of tumor cell-induced angiogenesis.

Majewski S, Marczak M, Mlynarczyk B, Benninghoff B, Jablonska S.

Department of Dermatology and Venereology, Warsaw School of Medicine, Warsaw, Poland. majewski56 o2.pl

BACKGROUND: Imiquimod, a potent immunomodulator, not having a direct antiproliferative activity, was found to be effective in genital and cutaneous premalignancies and malignancies. As tumor development depends on blood vessel supply, the inhibition of angiogenesis could be responsible for the antitumor activity. OBJECTIVE: To find in a murine model whether imiquimod has antiangiogenic activity and whether this activity is mediated by locally induced cytokines. METHODS: The study was performed in two cell lines: Skv human keratinocytes containing multiple integrated copies of HPV16 derived from bowenoid papulosis, and murine L1 lung sarcoma cells of Balb/c mice. The murine model of cutaneous angiogenesis was used to assess and count the new blood vessel formation. The mice were immunosuppressed by a total body X-ray irradiation and treated with 5% or 2.5% imiquimod cream before or after induction of angiogenesis with intradermally injected tumor cell suspension. In some experiments the mice were, in addition, treated intraperitoneally with monoclonal antibodies against murine IFNalpha, TNFgamma or IL-18. RESULTS: Topical application of imiquimod on the murine skin resulted in reduction of angiogenesis (P < 0.001) induced by intradermal injection of both human and mouse tumor cells, more pronounced when 5% cream was applied on three consecutive days. Antibodies against murine IFNgamma, TNFalpha and IL-18 completely abolished the inhibitory effect of imiquimod on angiogenesis induced by murine L1 sacroma cells. When human Skv cells were used in angiogenesis assay, the effect of imiquimod was abolished by antibodies against IL-18 but not against TNFalpha, which may be due to overproduction of TNFalpha by Skv cells. CONCLUSIONS: Antiangiogenic effect of imiquimod was found to be mediated by IL-18, probably through promoting production of INFgamma, the most important inhibitor of angiogenesis.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15663652&dopt=Abstract imiquimod Aldara



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Treatment of patch and plaque stage mycosis fungoides with imiquimod 5% cream.

Deeths MJ, Chapman JT, Dellavalle RP, Zeng C, Aeling JL.

Department of Dermatology, University of Colorado Health Sciences Center, Denver, Colorado 80045-0510, USA.

BACKGROUND: Systemic interferon is effective in the treatment of mycosis fungoides (MF). Imiquimod is effective in the treatment of some epidermal neoplasms and induces localized interferon production. OBJECTIVE: To evaluate the safety and efficacy of topical imiquimod 5% cream for the treatment of patch and plaque stage MF. METHODS: Six patients with stage IA to IIB MF were treated with topical imiquimod 5% cream 3 times per week for 12 weeks in this open label pilot study. Index lesions were biopsied pre- and post- treatment, and up to 4 additional treated lesions were monitored for 16 weeks. RESULTS: Three of 6 patients had histologic clearance of disease in index lesions, and also demonstrated significant improvement in the clinical scores for all treated lesions. A fourth patient had 2 of 4 lesions respond clinically. Application site reactions were limited to those patients responding to treatment. CONCLUSION: In this preliminary open label study topical imiquimod 5% cream was well tolerated and associated with a histologic and clinical response rate of 50%.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15692473&dopt=Abstract imiquimod Aldara



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Aphthous ulcers associated with imiquimod and the treatment of actinic cheilitis.

Chakrabarty AK, Mraz S, Geisse JK, Anderson NJ.

Solano Clinical Research, Davis, California, USA. chakak3 yahoo.com

Our case series report is the first documented depiction of the appearance of aphthous ulcers secondary to imiquimod application. This case series presentation discusses the underlying pathophysiology of aphthous ulcer development and imiquimod therapy in terms of the stimulation of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha). The literature review suggests more than just a mere coincidence for the development of aphthous ulcers subsequent to the treatment of actinic cheilitis with imiquimod application.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15692510&dopt=Abstract imiquimod Aldara



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Imiquimod in the treatment of extensive recurrent lentigo maligna.

Kamin A, Eigentler TK, Radny P, Bauer J, Weide B, Garbe C.

Department of Dermatology, Skin Cancer Program, Eberhard Karls University, Tuebingen, Germany.

We report the case of a 70-year-old white male with an extensive recurrence of lentigo maligna in a skin-transplanted region. He was treated with imiquimod 5% cream topically applied 5 times a week for a total duration of 9 months. Clinically and histologically, a complete clearing of the lesion was observed after treatment. Topical treatment with imiquimod seems to be effective and safe in lentigo maligna.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15692515&dopt=Abstract imiquimod Aldara