Aldara
Psoriasis induced by topical imiquimod.

Wu JK, Siller G, Strutton G.

Departments of Dermatology and Pathology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

We report the provocation of localized psoriasis at the sites of application of topical imiquimod, possibly evolving into a generalized flare. A patient with pre-existing psoriasis that had been stable for 14 years was treated with imiquimod 5% cream daily for 6 weeks to three superficial basal cell carcinomas. During treatment one of the lesions developed severe local skin reactions necessitating rest periods, and received only 18 applications in 6 weeks. The other two lesions were treated for all 42 days. Psoriasiform changes developed at all three application sites. Nine-and-a-half weeks after completing treatment the patient developed disseminated small psoriatic lesions. Other recognized triggers of psoriasis were not identified. The psoriasis resolved slowly with conventional treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14961909&dopt=Abstract imiquimod Aldara



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Imiquimod-induced interleukin-1 alpha stimulation improves barrier homeostasis in aged murine epidermis.

Barland CO, Zettersten E, Brown BS, Ye J, Elias PM, Ghadially R.

Department of Dermatology, University of California at San Francisco, and Veterans Affairs Medical Center, San Francisco, California 94121, USA.

In response to acute disruption of the permeability barrier of aged mammals there is a diminished capacity for barrier recovery, analogous to other aged organs when stressed. Acute barrier disruption increases levels of epidermal cytokines, and cytokines are known regulators of keratinocyte mitogenesis, as well as lipid synthesis in extracutaneous tissues. Underlying the sluggish barrier recovery in aged skin are diminished mRNA and protein levels for the interleukin-1 cytokine family, and its receptors. To further elucidate the role of the interleukin-1 family of cytokines in the barrier repair response, cytokine production was stimulated in aged murine skin with topical imiquimod application. Imiquimod accelerated barrier recovery after acute insults to aged and young skin. These functional results correlated temporally with increased interleukin-1 alpha production in the epidermis following topical imiquimod administration to murine skin. Furthermore, intracutaneous injections of interleukin-1 alpha accelerated barrier recovery in aged mice. Finally, we showed that interleukin-1 alpha added to cultured human keratinocytes stimulates epidermal lipid synthesis. These studies provide further evidence for the role of reduced interleukin-1 alpha signaling in the decline of permeability barrier function in aged skin, and point to the potential use of cytokine augmentation in barrier dysfunction of the aged.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15009713&dopt=Abstract imiquimod Aldara



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Combination topical treatment of molluscum contagiosum with cantharidin and imiquimod 5% in children: a case series of 16 patients.

Ross GL, Orchard DC.

Dermatology Department, Royal Children's Hospital, Flemington Road, Parkville, Melbourne, Victoria 5052, Australia.

The objective of this study was to assess the efficacy and tolerability of combination therapy for molluscum contagiosum (MC) with topical cantharidin and imiquimod 5%. A prospective case series of 16 paediatric patients with a mean age of 4.8 years had cantharidin applied to lesions by a dermatologist, followed by home treatment with imiquimod 5% cream nightly for an average of 5 weeks. This regimen resulted in >90% of lesions clearing in 12 patients, with half of these being totally clear. Two patients had 80-90% of lesions resolve. Two patients had 30-50% clearance of lesions at the end of the treatment period. One patient found the cantharidin reaction too strong. The mean number of imiquimod 250 mg sachets used was 4.25. In conclusion, this study suggests that combination therapy using cantharidin and imiquimod for treatment of MC in children is effective and well tolerated.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15068455&dopt=Abstract imiquimod Aldara



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Topical delivery of imiquimod to a mouse model as a novel adjuvant for human immunodeficiency virus (HIV) DNA.

Zuber AK, Brave A, Engstrom G, Zuber B, Ljungberg K, Fredriksson M, Benthin R, Isaguliants MG, Sandstrom E, Hinkula J, Wahren B.

Swedish Institute for Infectious Disease Control, SE-17182 Stockholm, Sweden.

We evaluated the compound imiquimod as a possible adjuvant for DNA immunization against human immunodeficiency virus (HIV). We found that gene-gun epidermal delivery of the DNA in combination with imiquimod resulted in the strongest HIV specific immune responses. The effect of imiquimod was further compared to that of recombinant granulocyte macrophage-colony stimulating factor (GM-CSF), a known DNA vaccine adjuvant. Both adjuvants were able to enhance the immune responses induced by the HIV-1 genes alone. The delivery of an adjuvant as a topical cream rather than through injections has a clear clinical benefit. We show for the first time that imiquimod can act as an adjuvant for DNA vaccination.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15068863&dopt=Abstract imiquimod Aldara



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Imiquimod and resiquimod in a mouse model: adjuvants for DNA vaccination by particle-mediated immunotherapeutic delivery.

Thomsen LL, Topley P, Daly MG, Brett SJ, Tite JP.

LindyDepartment of Immunotherapeutics, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. lindy.l.thomsen gsk.com

Imiquimod, an immune response modifier and inducer of cytokines in vitro and in vivo, has been shown to have potent antiviral and antitumour activity and to act as an adjuvant for protein vaccination. We have undertaken studies in mice to investigate the potential of imiquimod and resiquimod to adjuvant DNA vaccination. These imidazoquinolines were administered by subcutaneous injection at the vaccination site immediately after particle-mediated immunotherapeutic delivery of plasmid DNA using a gene gun. Imiquimod was found to increase the number and maturation status of dendritic cells in draining lymph nodes, and to enhance antigen-specific CD4(+) and CD8(+) T cell responses, as assessed by analyses of clonal expansion, and the quantity and kinetics of cytokine production from these cells in lymph nodes and spleens collected after vaccination. A more substantial increase in IFN-gamma-producing, compared with IL-4-producing CD4(+) T cells suggested that imiquimod biased the immune response towards a predominance of Th1 cells. The analogue resiquimod was found to be to produce a similar Th1 biased immune response with a 10-fold reduced dose compared with imiquimod. Collectively, these studies suggest that both imiquimod and resiquimod may be suitable adjuvants for therapeutic DNA vaccines requiring induction of potent cytotoxic T cell responses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15068864&dopt=Abstract imiquimod Aldara



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Closing the feedback loop: an audit of the use of imiquimod for the treatment of genital warts.

Brady S, Wilson JD.

Department of Genitourinary Medicine, The General Infirmary at Leeds, Great George Street, Leeds LS1 3EX, UK. sophie.brady leedsth.nhs.uk

A retrospective case-note audit of 74 patients with 81 treatment episodes of anogenital warts with imiquimod from April 1999 until July 2000 was performed. The majority of patients had failed to clear their warts with other treatments, had recurrences after other treatments, or had other medical problems complicating their genital wart treatment. The overall clinically confirmed complete clearance rate was 33%. This is lower than other published data, but may be so because it includes patients with immunosuppression and difficult-to-treat warts. The complete clearance rate in immunocompetent patients was 37%. In addition, in this audit of clinical practice 17% of the patients did not return for full response to be assessed. The complete clearance rate in those who were able to tolerate treatment and who returned for follow-up was 45%. Based on the results of the audit we have extended the indications for the use of imiquimod in the clinic treatment guidelines. Patients are now offered imiquimod if six or more episodes of other treatments fail to give a good response. Earlier treatment with imiquimod is also offered to those patients with recurrent anogenital warts, and it is recommended as a first-line therapy for patients with multiple keratinized warts.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15096142&dopt=Abstract imiquimod Aldara