Aldara
Determination of the area of skin capable of being covered by the application of 250 mg of 5% imiquimod cream.

Berman B, Ricotti CA Jr, Cazzaniga A, Davis SC.

Department of Dermatology and Cutaneous Surgery, University of Miami, School of Medicine, Miami, Florida 33136, USA. bberman med.miami.edu

BACKGROUND: Five percent imiquimod cream is FDA-approved for the treatment of genital and perianal warts and actinic Keratosis. The manufacturer recommends that a single sachet containing 250 mg of 5% imiquimod cream (12.5 mg of imiquimod) is adequate for a single use and is sufficient to cover a wart area of up to 20 cm(2). OBJECTIVE: To determine the maximal area of skin that can be evenly covered by 250 mg of 5% imiquimod cream that is contained in one single-use sachet. METHODS: The contents of one 250-mg single-use sachet of 5% imiquimod cream were mixed with less than 1 mg of fluorescein sodium. The cream was applied evenly onto the abdomen of two Yorkshire female pigs and onto the medial and lateral aspects of the upper left arm of a human subject. The area of application was then measured. RESULTS: The average area obtained on the pig skin was 196 cm(2). The area covered on the human subject was 386 cm(2). CONCLUSION: We have found that one sachet of 250 mg of 5% imiquimod cream can be applied to an area of skin up to 386 cm(2). In light of the increasing use of 5% imiquimod cream in the treatment of cutaneous diseases, such as actinic keratoses, which affect larger areas of skin than genital warts, a more efficient use of 5% imiquimod cream may make this medication a more cost-effective treatment modality.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15099325&dopt=Abstract imiquimod Aldara



Aldara
Treatment of experimental leishmaniasis with the immunomodulators imiquimod and S-28463: efficacy and mode of action.

Buates S, Matlashewski G.

Institute of Parasitology, McGill University, Ste. Anne de Bellevue, Quebec, Canada H9X 3V9. sureemas parasit.lan.mcgill.ca

There is a need for new, effective, and less toxic treatments for leishmaniasis, an infectious disease caused by Leishmania protozoa and is a major cause of suffering and morbidity in much of the developing world. Imiquimod, an immune-response modifier, has recently been approved by the Food and Drug Administration for the treatment of genital warts caused by human papillomaviruses. Imiquimod initiates a local immune reaction, including the stimulation of macrophages, resulting in resolution of human papillomavirus infection and regression of the viral lesion. Since imiquimod activates a number of immune cells, including macrophages, which are the only host cells of Leishmania species, an investigation was done to determine whether it induces leishmanicidal properties in infected macrophages in vitro and in vivo in a mouse model. Imiquimod and a related compound, S-28463, effectively stimulated leishmanicidal activity in macrophages; moreover, imiquimod stimulated signal transduction associated with inducing nitric oxide synthesis in macrophages.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10228071&dopt=Abstract imiquimod Aldara



Aldara
Immunomodulatory therapy in the management of viral infections in patients with HIV infection.

Conant MA.

University of California Medical Center, San Francisco, CA, USA.

Human immunodeficiency virus (HIV) causes disease by infecting lymphocytes and progressively destroying critical regulatory and effector cells of the immune system, leaving patients vulnerable to a number of bacterial, fungal, and viral infections. Facial herpes (herpes simplex virus-1 [HSV-1]), genital herpes (HSV-2), herpes zoster (varicella zoster virus), oral hairy leukoplakia (Epstein-Barr virus), Kaposi's sarcoma (HHV-8), molluscum contagiosum, condyloma acuminata (human papillomavirus [HPV-6, HPV-11]), plantar warts (HPV-1), and facial warts and flat warts (HPV-5) are some of the cutaneous viral diseases most commonly seen in HIV-infected patients. Two immunomodulatory agents, imiquimod (Aldara), shown to be safe and effective in the management of genital warts, and alitretinoin gel, shown to be safe and effective in the treatment of Kaposi's sarcoma, may offer a new therapeutic approach to treatment of cutaneous viral diseases. There is a strong scientific rationale to suggest that imiquimod and alitretinoin gel may be useful in the treatment of a variety of cutaneous viral diseases that have been shown to respond to immunomodulatory drugs. This represents a new approach in the therapeutic treatment paradigm for treatment of cutaneous viral diseases at their site of infection.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10861104&dopt=Abstract imiquimod Aldara



Aldara
Imiquimod treatment induces expression of opioid growth factor receptor: a novel tumor antigen induced by interferon-alpha?

Urosevic M, Oberholzer PA, Maier T, Hafner J, Laine E, Slade H, Benninghoff B, Burg G, Dummer R.

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

PURPOSE: Imiquimod represents a synthetic local immune response modifier that has demonstrated efficacy in clearing basal cell carcinoma. Via interaction with Toll-like receptor 7 on immune cells, imiquimod induces local production of cytokines, such as interferon (IFN)-alpha. EXPERIMENTAL DESIGN: To more closely define and elucidate mechanisms leading to basal cell carcinoma clearance in vivo, we examined gene expression profiles of skin basal cell carcinoma before and after treatment with 5% imiquimod cream (Aldara) by using high-density oligonucleotide arrays. RESULTS: We show that imiquimod predominantly induces genes involved in different aspects of immune response. In addition to effects on immunity, imiquimod treatment modulates the expression of genes involved in the control of apoptosis and oncogenesis. Array data indicated that imiquimod treatment induces expression of opioid growth factor receptor, a molecule recently reported to be a target for antitumor antibody responses. Immunohistochemistry revealed in vivo up-regulation of opioid growth factor receptor protein on tumor and on infiltrating cells after treatment. By using basal cell carcinoma cell lines treated with IFN-alpha or imiquimod, we show that opioid growth factor receptor up-regulation is IFN-alpha-mediated, rather then directly imiquimod-mediated. By using tissue microarray containing 52 basal cell carcinomas, we demonstrate opioid growth factor receptor expression in almost half of the cases. Expression of opioid growth factor receptor correlated with a longer recurrence-free period in basal cell carcinoma that recurred after radiotherapy (Kaplan-Meier analysis, P = 0.041). CONCLUSIONS: In addition to its immunomodulatory and antiproliferative activity, opioid growth factor receptor seems to have a prognostic significance in basal cell carcinoma patients. Our data add to the growing list of basal cell carcinoma-associated tumor antigens.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15297396&dopt=Abstract imiquimod Aldara



Aldara
Identification and characterization of pDC-like cells in normal mouse skin and melanomas treated with imiquimod.

Palamara F, Meindl S, Holcmann M, Luhrs P, Stingl G, Sibilia M.

Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Austria.

Among the different subsets of dendritic cells (DC) described in humans and mice, epidermal Langerhans cells and dermal DCs represent the only DC populations resident in normal skin. In this study we describe a population of CD4(+)CD3(-) plasmacytoid DC (pDC)-like cells that accumulate in the dermis and spleens of mice topically treated with imiquimod, a low m.w. immune response modifier with potent antiviral and antitumor activities. These CD4(+)CD3(-) cells coexpress GR-1, B220, MHC class II, and, to a lesser extent, CD11c and display the phenotypic features of pDCs described in lymphoid organs. The accumulation of pDC-like cells after imiquimod treatment was detected not only in normal skin, but also in intradermally induced melanomas. Imiquimod treatment leads either to complete regression or to a significant reduction of the tumors. The number of pDCs correlates well with the clinical response of the tumors to the drug, suggesting that the antitumor effects of imiquimod could be mediated at least in part by the recruitment of pDC-like cells to the skin. Therefore, strategies aimed at activating and directing these cells into neoplastic tissues may be a promising and novel approach for the immunotherapy of various types of cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15322165&dopt=Abstract imiquimod Aldara



Aldara
A pilot study of treatment of lentigo maligna with 5% imiquimod cream.

Fleming CJ, Bryden AM, Evans A, Dawe RS, Ibbotson SH.

Departments of Dermatology and Pathology, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK. colin.j.fleming tuht.scot.nhs.uk

BACKGROUND: Lentigo maligna (LM) is an in situ form of malignant melanoma, and surgical excision is often unsatisfactory. Imiquimod cream is an immune response modifier and induces a predominantly T-helper 1 type response. OBJECTIVES: Assessment of histological and clinical response of surgically resectable LM after treatment with 5% imiquimod cream. METHODS: Six patients with LM were treated with 5% imiquimod cream daily for 6 weeks. The whole site of the original lesion was then excised. Clinical and histological and appearances were measured using clinical response and histological grading scores. RESULTS: Complete or almost complete clearance of pigmentation with minimal residual histological evidence of LM was observed in four patients, one patient showed no clinical or histological improvement, and the remaining patient had almost no residual pigmentation clinically after treatment yet histopathological changes remained as severe as before treatment. CONCLUSIONS: Topical imiquimod cream merits further investigation as a new therapy for LM.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15327559&dopt=Abstract imiquimod Aldara