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      Uso de imiquimode tópico no tratamento da infecção anal pelo papilomavírus humano Translated title: The use of topic imiquimod in the treatment of the anal infection by human papillomavirus

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          Abstract

          Dos diversos tratamentos da infecção anal pelo papilomavírus humano, uma opção é o imunomodulador imiquimode. Derivado da família imidazoquinolina, o imiquimode é quimioterápico e imuno-estimulante com atividade antitumoral e antiviral. A medicação é aplicada em esquema domiciliar, três vezes por semana em noites alternadas, por oito a 16 semanas. Os efeitos adversos locais são comuns, mas bem tolerados. A droga atinge remissão de 74 a 84%, sendo completa entre 25 e 77% dos doentes, com menor taxa de remissão completa e maior índice de recidiva em imunodeprimidos. Aguardamos estudos com grandes casuísticas para avaliar melhor a eficácia dessa medicação, incluindo a incidência de recidivas e o tempo livre de novas lesões.

          Translated abstract

          Considering several kinds of treatments for human papillomavirus anal infection, the topical immune response modifier imiquimod is an option. An imidazoquinoline derivate, imiquimod is a chemotherapic drug and an immune stimulator with antitumoral and antiviral action. The medication is used at home, by patients, three times a week, in alternated nights, for eight to 16 weeks. Side-effects are common, but well tolerated. This drug reaches from 74 to 84% of remission, although from 25 to 77% are complete. There are lower complete remission and higher recurrence in immune compromised patients. Studies with more patients for better evaluation of this medication efficiency are needed, including those about recurrences and time free from new lesions.

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          Most cited references29

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          The role of toll-like receptors in the pathogenesis and treatment of dermatological disease.

          Toll-like receptors (TLR) are crucial players in the innate immune response to microbial invaders. These receptors are expressed on immune cells, such as monocytes, macrophages, dendritic cells, and granulocytes. Importantly, TLR are not only expressed by peripheral blood cells, but their expression has been demonstrated in airway epithelium and skin, important sites of host-pathogen interaction. Host cells expressing TLR are capable of recognizing conserved pathogen-associated molecular patterns, such as lipopolysaccharide and CpG DNA, and their activation triggers signaling pathways that result in the expression of immune response genes and cytokine production. As TLR are instrumental in both launching innate immune responses and influencing adaptive immunity, regulation of TLR expression at sites of disease such as in leprosy, acne, and psoriasis may be important in the pathophysiology of these diseases. Furthermore, since TLR are vital players in infectious and inflammatory diseases, they have been identified as potential therapeutic targets. Indeed, synthetic TLR agonists such as imiquimod have already established utility in treating viral pathogens and skin cancers. In the future, it seems possible there may also be drugs capable of blocking TLR activation and thus TLR-dependent inflammatory responses, providing new treatment options for inflammatory diseases.
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            Topical immunomodulators--progress towards treating inflammation, infection, and cancer.

            Immunomodulators include both immunostimulatory and immunosuppressive agents. Only recently have the basic mechanisms of topical immunotherapy been elucidated. Besides topical contact sensitisers (eg, diphencyprone or dinitrochlorobenzene), newer agents of the imidazoquinoline family such as imiquimod and resiquimod act by inducing cytokine secretion from monocytes or macrophages (interferon-alpha, interleukin-12, tumour-necrosis factor-alpha). The locally generated immune milieu leads to a Th1-dominance and cell-mediated immunity that have been used clinically to treat viral infections such as human papillomavirus (HPV), herpes simplex virus (HSV), mollusca, and cancerous lesions including initial squamous cell and basal cell carcinoma in immunocompetent and immunosuppressed patients. While these agents improve antigen-presentation by dendritic cells, they also act on B cells and lead to the synthesis of antibodies such as IgG2a much like the recently discovered immunostimulatory CpG-sequences that stimulate innate immunity. These sequences act as "danger signals" since they occur in bacterial and viral DNA, but are selectively methylated and inactivated in the mammalian genome. They share the induction of the same cytokines as imidazoquinolines but they show different magnitudes and kinetics of response. Topical immunotherapy with immunostimulatory agents shows potential for effective and patient-friendly treatment of inflammatory, infectious, and cancerous skin diseases. Immunoenhancers such as imdazoquinolines and CpG-sequences also have adjuvant properties that could improve conventional (protein) and DNA vaccination against cancer, atopy, and allergies.
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              High-resolution anoscopy targeted surgical destruction of anal high-grade squamous intraepithelial lesions: a ten-year experience.

              This study was designed to determine whether high-resolution anoscopy and targeted surgical destruction of anal high-grade squamous intraepithelial lesions is effective in controlling high-grade squamous intraepithelial lesions while preserving normal tissues. Retrospective review of 246 patients with high-grade squamous intraepithelial lesions treated with high-resolution anoscopy-targeted surgical destruction from 1996 to 2006, with at least one follow-up at a minimum two months with physical examination, high-resolution anoscopy, cytology, and biopsy when indicated. Lesions were extensive in 197 patients (81 percent); 207 (84 percent) were men, and 194 (79 percent) were immunocompromised (HIV or other). Persistent disease occurred in 46 patients (18.7 percent), requiring planned staged therapy; 10 required surgery. Recurrent high-grade squamous intraepithelial lesions occurred in 114 patients (57 percent) at an average 19 (range, 3-92) months; 26 of these required surgery. All other patients were retreated in-office with high-resolution anoscopy-directed therapies. Complications were seen in nine patients (4 percent). Despite treatment, three patients progressed to invasive cancer (1.2 percent). At their last visit, 192 patients (78 percent) had no evidence of high-grade squamous intraepithelial lesions. High-resolution anoscopy-targeted destruction combined with office-based surveillance and therapy is effective in controlling high-grade squamous intraepithelial lesions and is superior to reports of expectant management or traditional mapping procedures.
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                Author and article information

                Journal
                rbc
                Revista Brasileira de Coloproctologia
                Rev bras. colo-proctol.
                Cidade Editora Científica Ltda (Rio de Janeiro, RJ, Brazil )
                0101-9880
                March 2010
                : 30
                : 1
                : 92-94
                Article
                S0101-98802010000100014 S0101-9880(10)03000114
                88a29384-fdf2-40c2-b13a-192a74fa0cf3

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 02 December 2009
                : 22 October 2009
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 29, Pages: 3
                Product

                SciELO Brazil

                Categories
                Doenças Sexualmente Transmissíveis

                Immunotherapy,Immunomodulation,Condylomata Acuminata,Infecções por Papillomavirus,Imunoterapia,Condiloma acuminado,Imunomodulação,Papillomavirus infections

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