Imiquimod

Imiquimod is the first of the immune response modifiers to stimulate a localized immune response to treat infectious skin conditions. The reported TLR-7 activation to provoke an immune response suggests that imiquimod might mimic a microbial antigen. The immune response initiated by induced production of IFN-alpha and TFN-alpha is specifically aimed at an infectious antigen and appears mediated (in part) by enhanced migration of Langerhans' cells to regional lymph nodes. The approved indication for imiquimod is for treatment of genital warts. The drug has demonstrated a 50% to 60% clearance rate and a 12% to 20% recurrence rate for this indication (Table 1). This recurrence rate is the lowest reported among the currently recommended treatment modalities. The self-applied treatment avoids costly and painful office-based procedures. Case reports and open-label studies have demonstrated the efficacy of imiquimod in treating some cases of common, plantar, and flat warts, as well as molluscum contagiosum and leishmaniasis. Common and plantar warts respond better to imiquimod in combination with cryosurgery, occlusion, and keratolytics. Reports of successful imiquimod treatment of granuloma annulare, alopecia areata, and vitiligo might suggest an infectious etiology to those conditions, although this hypothesis is highly speculative.     

Imiquimod in mycosis fungoides

Imiquimod is a topically active imidazoquinoline immunomodulator agent. It works as an indirect antiviral and antitumoral and stimulates the production of INF-alpha and various other cytokines. We assayed topical imiquimod in treating early stages of mycosis fungoides. We applied imiquimod 5% cream in four patients with multi-treatment resistant plaques of MF (stages IA and IIB). We applied it on one patient in association with systemic INFalpha-2a. We observed a complete clinical clearance of the lesions in all four patients. In three cases we achieved a complete histopathological clearance and in one case a partial histopathological clearance. The patient treated with imiquimod and systemic INFalpha-2a showed the most spectacular improvement with a rapid total response. We ascribe this improvement to a synergic effect of imiquimod and systemic INFalpha-2a treatment. Before the introduction of imiquimod, this patient had been treated for 2 years with systemic INFalpha-2a alone, without any evidence of clinical response. Imiquimod could be an effective therapy for early-stage disease of CTCL, used alone or in combination with systemic immunomodulatory therapy.     

Imiquimod: a review

Background and Objective: Imiquimod (Aldara) is an immune response modifier used primarily to treat anogenital warts. Imiquimod induces cytokines and enhances cell-mediated cytolytic antiviral activity in vivo. It exhibits antiviral and antitumor effects; however, it does not exhibit direct antiviral effects in vitro. By inducing cytokines, such as interferon a, imiquimod stimulates both the innate immune response and the cellular arm of acquired immunity. Currently, imiquimod is approved for use in the treatment of external genital and perianal warts in adults. Conclusion: Beyond its established use, there are case reports and preliminary studies suggesting the effectiveness of imiquimod 5% cream in the treatment of nongenital human papillomavirus warts, molluscum contagiosum, actinic keratosis, basal cell carcinoma, squamous cell carcinoma, Bowen's disease, nongenital human papillomavirus infection, and vulvar intraepithelial neoplasia.     

Imiquimod reactivation of lichen planus

A 44-year-old man who was previously diagnosed with actinic cheilitis was prescribed imiquimod cream 5%, which resulted in thick hemorrhagic crusting of the lower lip after 4 applications. He subsequently noted the development of lichen planus lesions on his arms and legs for the first time in 15 years following imiquimod use. On follow-up he also was noted to have characteristic Wickham striae on his lower lip. Lichen planus is an autoimmune inflammatory condition in which autoreactive T lymphocytes attack keratinocytes. The mechanism of action for imiquimod is upregulation of IFN-alpha and IFN-beta. Treatment with clobetasol cream 0.05% led to resolution of his lichen planus lesions.     

Imiquimod therapy for molluscum contagiosum

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.     

咪喹莫特抗皮肤肿瘤的作用机制

咪喹莫特是一种新型的局部小分子免疫调节物，可以通过与免疫相关细胞表面的Toll样受体结合、促进干扰素-α、肿瘤坏死因子-α、白介素-12等多种前炎症细胞因子的分泌，进而激活天然与获得性免疫反应的方式，发挥抗肿瘤活性。通过上调Fas和／或下调bcl-2表达诱导肿瘤细胞凋亡，可能是咪喹莫特抗皮肤肿瘤的另一重要机制。     

Imiquimod induces apoptosis of human melanocytes

Development of vitiligo-like hypopigmentary lesions associated with topical imiquimod has been reported. We hypothesized that mode of action of imiquimod in melanocytes may include triggering of apoptosis resulted in loss of cells, which may be a possible mechanism of imiquimod-induced hypopigmentary lesions. Therefore, we investigated whether imiquimod induces apoptosis of human melanocytes and also whether it modulates expression of apoptosis-related molecules in human melanocytes. Imiquimod treatment induced apoptosis of melanocytes, which was observed by TUNEL assay and Hoechst 33258 staining. Imiquimod-induced apoptosis was further shown by measuring mitochondrial membrane potential in melanocytes. The apoptotic activity of imiquimod was associated with caspase-3, Bcl-2 and mitogen-activated protein kinase expression in melanocytes. These results indicated that imiquimod induces apoptosis of melanocytes. These findings may provide a clue to understand pathogenesis of imiquimod-induced vitiligo-like hypopigmentary lesions.     

Imiquimod in dermatology: an overview

Imiquimod is an immune response modifier commercially available as a 3.75 and 5% cream. Topical imiquimod stimulates the innate and adaptive immune responses and induces cytokine production. This allows its use for the treatment of a wide variety of benign and malignant skin conditions due to its potential antiviral, antitumor, and immunoregulatory effects. Currently, topical imiquimod is US Food and Drug Administration (FDA)‐approved for the treatment of anogenital warts, actinic keratosis, and superficial basal cell carcinomas. However, it has also shown a beneficial effect in the treatment of many other skin disorders. In this review, we describe existing evidence on the mechanism of action of topical imiquimod, its FDA‐approved indications, off‐label uses, and side effects.     

Imiquimod for the treatment of skin cancer

Imiquimod is a topically applied immunomodulator. Although initially approved for genital and perianal warts, dermatologists have prescribed this compound for many neoplastic and nonneoplastic skin conditions. The US Food and Drug Administration recently approved imiquimod for the treatment of actinic keratoses. This article reviews the literature on imiquimod in the treatment of cutaneous malignancies.     

Imiquimod: potential risk of an immunostimulant

A 19-year-old woman with severe HLA B27 spondyloarthropathy whose disease was controlled on cyclosporin, methotrexate and prednisolone had human papillomavirus infection and developed cervical dysplasia and a large number of cutaneous and vulval warts. These were not responsive to cryotherapy, salicylic acid or cimetidine, so she was treated with topical imiquimod 5% cream. Two weeks after starting this treatment she had a significant flare of her spondyloarthropathy. She was so ill that she stopped using the imiquimod cream. She had full resolution of her warts after 3 weeks' treatment with imiquimod cream, but her spondyloarthropathy took more than 3 months to improve, despite significant augmentation of her immunosuppression. This case highlights the potential risk of using imiquimod cream (an immunostimulant) in a patient who has a condition requiring immunosuppression, such as autoimmune disease or an organ transplant.     

Imiquimod in the treatment of lentigo maligna

BACKGROUND: Lentigo maligna (LM) is treated to prevent progression to lentigo maligna melanoma (LMM). Surgery remains the treatment of choice, although topical immunotherapy with imiquimod has recently become a popular alternative. OBJECTIVES: In this review, we have analysed the published literature relating to the use of imiquimod for LM, in order to understand better the utility of this treatment. METHODS: All English language studies relating to the use of imiquimod for LM were analysed up to January 2006. RESULTS: Eleven case reports and four open-label studies were identified, comprising a total of 67 patients who completed treatment with imiquimod for LM. There was significant variability in treatment schedules and regimens. Eight patients failed to respond, with LMM developing in two of these. In certain cases there were discrepancies between clinical and histological response with some patients clearing clinically but not histologically, and vice versa. Follow-up periods were short, exceeding 12 months in only five cases. CONCLUSIONS: Although imiquimod clearly has an effect on LM, this analysis of available studies has helped to identify concerns about its use. Without controlled evidence and prolonged follow up, the use of imiquimod for LM must still be considered experimental.