MEDLINE Abstracts: Topical Imiquimod
Mackenzie-Wood A, Kossard S, De Launey J, Wilkinson B, Owens ML
J Am Acad Dermatol. 2001;44:462-470

Background: Large-diameter lesions of Bowen's disease at sites such as the shin may be difficult to treat surgically and may require alternate treatment modalities.
Objective: We investigated whether imiquimod 5% cream, a topical immune response modifier that stimulates the production of interferon alfa and other cytokines, is an effective topical treatment for Bowen's disease.
Methods: This was a phase II, open-label study in 16 patients, treating a single biopsy-proven plaque of Bowen's disease that was 1 cm or larger in diameter, with once-daily self-application of imiquimod 5% cream for 16 weeks. A biopsy was performed on the treated area 6 weeks after the end of treatment, with patient follow-up at 3 and 6 months. Lymphocyte CD4/CD8 ratios were analyzed in pretreatment and posttreatment biopsy specimens by immunophenotyping the lymphocytic infiltrate.
Results: Sixteen patients with Bowen's disease lesions ranging from 1 to 5.4 cm in diameter (0.7-21.6 cm(2) in area) were treated. Fifteen of these lesions were on the legs, and one was on the shoulder. Fourteen of the 15 patients (93% per protocol analysis) had no residual tumor present in their 6-week posttreatment biopsy specimens. One patient died of unrelated intercurrent illness before a biopsy specimen could be obtained. The median CD4/CD8 lymphocyte ratio in pretreatment biopsy specimens was 2:1, and this was reversed to a median of 1:2.2 in the posttreatment specimens. Ten patients completed 16 weeks of treatment, but 6 patients ceased treatment early (between 4 and 8 weeks) because of local skin reactions.
Conclusion: Imiquimod 5% cream appears to be an effective treatment for Bowen's disease on the lower limbs. The 93% positive treatment response in biopsy-proven cases (excludes patient who died from an intercurrent illness who did not undergo a posttreatment biopsy) compares favorably with other current treatment modalities. The dosing schedule and length of treatment for Bowen's disease require further evaluation.









Smith KJ, Germain M, Skelton H
Dermatol Surg. 2001;27:143-146

Background: Patients with chronic lymphocytic leukemia (CLL) often have a protracted course. However, all these patients are immunosuppressed and may have a high incidence of cutaneous malignancies.
Objective: To determine if combination therapy using topical imiquimod cream 5% and the oral cyclooxygenase (COX) inhibitor are useful in the therapy of squamous cell carcinoma in situ (SCC in situ)/Bowen's disease in patients with long-standing CLL.
Methods: Five CLL patients with head and neck cutaneous SCC in situ, which met criteria for Bowen's disease, were treated with topical 5% topical imiquimod cream and an oral COX inhibitor, sulindac 200 mg twice a day.
Results: All patients showed clinical resolution and histologic clearing of the tumors after 16 weeks of therapy.
Conclusion: The local immune modulator, 5% imiquimod, in combination with a COX inhibitor, with its many potential antitumor effects may stimulate the innate and possibly the adaptive immune responses to clear these malignancies.









Liota E, Smith KJ, Buckley R, Menon P, Skelton H
J Cutan Med Surg. 2000;4:76-82

Background: Molluscum contagiosum virus (MCV) is a large double-stranded DNA virus that is a member of the family Poxviridae, and which has a worldwide distribution. As with other poxviruses, MCV does not appear to develop latency but evades the immune system through the production of viral specific proteins.
Objective: To evaluate the therapeutic efficacy of imiquimod 5% cream for MCV.
Methods: Thirteen children >5 and <10 years old, 19 immune-competent adults and four adults with advanced, but stable HIV-1 disease with >10 MCV lesions were treated with topical 5% imiquimod cream three times weekly for up to 16 weeks.
Results: Fourteen of 19 immune-competent adults, four of four adults with HIV-1 disease, and six of 13 children had resolution of their MCV lesions in <16 weeks of imiquimod therapy. Children tended to have more pruritus and inflammatory reactions with imiquimod, although most treated lesions appeared to respond. The development of new MCV lesions resulted in a lower overall resolution of the lesions in children. Imiquimod appeared to be the most efficacious in patients with HIV-1 disease and in the genital area in immune-competent adults.
Conclusion: Although topical imiquimod appears to have some efficacy in the therapy of MCV, in children the pruritus correlated relatively well with the development of new lesions. In adults, areas that would be expected to have better penetration appeared to respond more consistently. Although the HIV-1-positive patients had the largest clinical lesions at the onset of therapy, as a group they had the best overall response to therapy.









Hengge UR, Esser S, Schultewolter T, et al
Br J Dermatol. 2000;143:1026-1031

Background: Despite numerous therapeutic options the treatment of common warts and molluscum contagiosum remains unsatisfactory for both patients and physicians. Imiquimod, a novel topical immune response modifier, has been successfully used for the treatment of external anogenital warts.
Objectives: We aimed to evaluate the safety, tolerance and efficacy of imiquimod for the treatment of common cutaneous warts and mollusca that were resistant to previous therapeutic interventions.
Methods: Imiquimod 5% cream was self-applied by the patients to the warts or mollusca once daily for 5 days per week and left in place overnight. Assessment for response and the occurrence of side-effects was performed every 4 weeks until clinical cure or up to a maximum of 16 weeks.
Results: Twenty-eight of 50 (56%) patients with warts achieved a total clearance (n = 15; 30%) or a > 50% reduction in wart size (n = 13; 26%) after a mean treatment period of 9.2 weeks. Twelve of 15 (80%) patients with mollusca achieved a total clearance (n = 8; 53%) or a > 50% reduction in molluscum size (n = 4; 27%). There was no difference in response with regard to gender, human immunodeficiency virus serostatus or atopic predisposition.
Conclusions: Patient-applied 5% imiquimod cream holds promise as an effective treatment of common warts and mollusca in a difficult-to-treat patient population.









Stockfleth E, Rowert J, Arndt R, Christophers E, Meyer T
Br J Dermatol. 2000; 143:846-850

Stucco keratosis is a skin disorder with papular warty lesions that usually appear on the lower limbs in elderly people. The aetiology, pathogenesis and treatment is still a matter of debate. We report a 75-year-old non-immunosuppressed man with extensive lesions all over his body, which had not responded to curettage or electrodesiccation. To determine the possible role of human papillomavirus (HPV) in stucco keratosis, we used nested polymerase chain reaction (PCR) to identify HPV DNA in the lesions. To include a broad range of both cutaneous and mucosal HPV types, PCR was performed with two sets of degenerate primers. Using this approach we detected HPV types 9, 16, 23b, DL322 and a variant of HPV type 37 in multiple stucco keratoses. Imiquimod (5% cream), a new compound that modifies the immune response by stimulating production of cytokines, applied overnight, three times a week for 5 weeks, resulted in resolution of all treated lesions.









Ahmed I, Berth-Jones J
Br J Dermatol. 2000;143:843-845

Lentigo maligna is the in situ phase of lentigo maligna melanoma, and if left untreated it may progress to invasive melanoma. It most commonly occurs on the exposed sites of the face and neck of middle-aged or elderly patients. Conventional surgery using a 5-10 mm margin is the recommended treatment; however, lesions can be quite large and surgical removal may involve extensive plastic repair. We report an elderly patient with a large lentigo maligna on the scalp who was reluctant to have surgery. We tried topical imiquimod 5% cream (Aldara), a local immunomodulator, which has recently become available for the treatment of external genital and perianal warts. Initially used over a test area and then over the whole of the lesion, for a total of 7 months, the imiquimod cream resulted in complete clinical and histological cure. The patient has been followed up for 9 months without evidence of recurrence.









Davis G, Wentworth J, Richard J
J Reprod Med. 2000;45:619-623

Background: Vulvar intraepithelial neoplasia (VIN) generally can be classified into viral and nonviral etiologies. The histopathologic diagnosis is often separable into basaloid and warty types. A large percentage of VIN lesions have been shown to harbor human papillomavirus (HPV), principally type 16. Imiquimod, an immune response modifier, has been shown to be safe and effective for the treatment of external and perianal genital warts caused by HPV.
Cases: Four cases occurred of clinical and histopathologically diagnosed viral VIN 3. An imiquimod treatment protocol, previously used in a study of this drug for the treatment of external genital warts, was followed. Imiquimod 5% cream was patient applied three times per week until all lesions cleared, for a maximum of 16 weeks.
Conclusion: Imiquimod may be an effective treatment modality for viral VIN 3 in the future.









Brown CW, O'Donoghue M, Moore J, Tharp M
Cutis. 2000;65:363-366

Molluscum contagiosum is a common cutaneous infection complicating the course of patients afflicted with acquired immunodeficiency syndrome. We describe a human immunodeficiency virus-positive patient with a disfiguring molluscum contagiosum infection of the face. Conventional cytodestructive therapies failed in this patient, but imiquimod 5% cream, an immunomodulator, clinically cleared his cutaneous disease.









Cutler K, Kagen MH, Don PC, McAleer P, Weinberg JM
Acta Derm Venereol. 2000;80:134-135

Imiquimod is a recently developed imidazoquinolin heterocyclic amine that is an immune response modifier. Treatment with topical 5% imiquimod cream has shown promising results in the treatment of genital warts in immunocompetent individuals. We report here the first case of successful treatment with topical 5% imiquimod cream of facial verrucae in an individual with human immunodeficiency virus.









Edwards L
J Am Acad Dermatol. 2000; 43:S12-17

Numerous clinical trials have shown topical imiquimod (Aldara) to be effective and safe for the treatment of anogenital warts. In addition, the recurrence rate appears to be lower than those reported for many standard therapies of genital warts. Clinical experience with this medication since its availability 2 years ago has shown that it is important in the therapy of this disease. However, it is not the ideal treatment in all cases, and the advantages and disadvantages in individual patients must be considered. In addition, the antiviral and antiproliferative effects of imiquimod, as well as early reports, indicate that this medication may prove useful in the treatment of other skin diseases, including some nongenital warts and molluscum contagiosum.









Sauder DN
J Am Acad Dermatol. 2000;43:S6-11

Imiquimod, an imidazoquinoline amine, is an immune response modifier recently approved for the topical treatment of external genital and perianal warts. Although the majority of immunomodulatory agents available or in development inhibit pathways involved in immune activation, imiquimod is unique in that it activates immune function. The exact mechanism of imiquimod's antiviral activity is unknown; however, its effects are likely to be related to its immunomodulating properties. Although in vitro studies have shown that imiquimod has no direct antiviral effects, the drug does exhibit antiviral and antitumor effects in vivo through induction of cytokines and enhancement of cell-mediated cytolytic antiviral activity. Imiquimod stimulates the innate immune response through induction of cytokines, and the cellular arm of acquired immunity through induction of interferon-alpha (IFN-alpha), IFN-gamma, and interleukin-12. Results from animal studies have indicated a possible use for imiquimod in the prevention and treatment of herpes simplex virus infection. In addition, recent studies demonstrated that imiquimod activates Langerhans' cells and enhances allergic contact hypersensitivity.









Suzuki H, Wang B, Shivji GM, et al
J Invest Dermatol. 2000;114:135-141

Langerhans cells are bone marrow derived dendritic cells that represent the major antigen-presenting cells in the skin. Langerhans cells take up and process antigen within the epidermis and present processed antigen to T lymphocyte in the regional lymph nodes and thus form an integral part of the cutaneous immune response. The cutaneous immune response can be modified by a number of pharmacologic agents, including corticosteroids, cyclosporine, and retinoids as well as physical agents, such as ultraviolet light. For the most part these agents act by suppressing immune function. A topical immune response modifier, imiquimod has been shown to enhance the cutaneous immune response. Imiquimod has anti-viral and anti-tumor effects in animal models and has been approved for the topical treatment of external genital and perianal warts in humans. The biologic activity of imiquimod in part is due to its effect as a cytokine inducer. Preliminary data suggested that imiquimod could have an effect on Langerhans cells. In order to clarify this effect on Langerhans cells, we examined Langerhans cell morphology and migration in imiquimod-treated skin. The density of Ia + cells decreased 2 d after treatment, falling to approximately 43% by day 10. The Ia positive in cells remaining in the skin appeared larger and more dendritic suggesting an activated state. ATPase staining of epidermal sheet confirmed the decreased number of Langerhans cells. To clarify status of Langerhans cells, the activation of B7 was examined. Activation of B7-1 or B7-2 was not detected. Imiquimod, however, did enhance Langerhans cell migration from skin to draining lymph nodes. This enhanced Langerhans cell migration was also associated with an enhanced allergic contact hypersensitivity. These results suggest that the mechanism of modulation of immune response by imiquimod is in part due to effects on Langerhans cells.