Successful management of viral infections and other dermatoses with imiquimod 5% cream.

Abstract

) is a safe, effective and established treatmentfor external genital and perianal warts. It is the firstmember of the family of immune response modifiers,which stimulates innate and cell-mediated immunepathways, inducing potent antitumor, antiviral andimmunoregulatory effects (1, 2). Imiquimod stimulatesthe immune response through induction, synthesis andrelease of cytokines such as interferon (IFN) a, tumornecrosis factor (TNF) a and interleukin 12 (IL 12) (3, 4).In addition, imiquimod acts to stimulate other com-ponents of innate immunity such as natural killer cellactivity, secretion of nitric oxide from macrophages andproliferation and differentiation of B-lymphocytes (1).Imiquimod also stimulates the T-helper (Th)-1 cyto-kine, IFNc and enhances the migration of Langerhans’cells to the lymph nodes; these cells are importantantigen-presenting cells within the epidermis (5). Imi-quimod is not only a recommended treatment foranogenital warts (6–8), but has also been shown to beeffective in the treatment of other viral infections (9, 10)and epithelial neoplasms (11–13).IMIQUIMOD FOR THE TREATMENT OFEXTERNAL GENITAL WARTSHuman papillomavirus (HPV) is the most commonsexually transmitted infection in many countries. Figuresfrom the World Health Organization (WHO) and Com-municable Disease Surveillance Center (CDSC) showthat approximately 5.5 million new cases of HPV arereported every year, with 40 million cases in the UnitedStates of America (USA). In addition, 1% of sexuallyactive adults in the USA aged between 15 and 49 yearsdevelop genital warts. With a steady increase in world-wide incidence, genital warts are the most frequentlydiagnosed infection in sexually transmitted disease (STD)clinics in both the northern and southern hemispheres(14). Within the UK, HPV-associated anogenital wartsaccount for approximately 25% of total diagnoses atgenitourinary medicine (GUM) clinics (15). This increasein the epidemiology of anogenital warts is having asubstantial effect on the cost of healthcare services indeveloped countries, for instance in the UK in 2002 theestimated cost of external anogenital warts was threebillion dollars.HPV is prevalent in many different subtypes with theclinical manifestation being either anogenital or non-genital. Anogenital warts or condylomata acuminataare clinical conditions of HPV types 6 or 11. High-oncogenic risk anogenital lesions tend to arise fromHPV infections of subtypes 16, 18, 31, 33 and 35. HPVtypes 1, 2 and 3 have clinical manifestations that typifyverruca plantaris, verruca vulgaris and verruca planar,respectively (16, 17). In addition to being implicatedin many carcinomas of the skin (18), epidemiologicalstudieshaveunderlinedthatHPVsarethemainetiologicalfactor of anogenital cancer (19). Current recommendedtreatment options for genital warts are patient-appliedtherapies, which include imiquimod, or podophyllotoxin,an antimitotic agent. Alternative treatment optionsencompass physician-administered therapies, which mayeither be ablative, such as surgical excision, cryotherapy,laser therapy, and electrocautery or cytodestructive e.g.trichloroaceticacid(TCA).GuidelinesfromtheCentersforDisease Control and Prevention (USA), Australia andEurope for the management of genital warts stronglyrecommend patient-applied therapies as a first linetreatment option, with physician-administered therapiessuggested as alternative strategies (6–8).Imiquimod is available as a single-use sachet that isapplied directly to the lesion three times per week atnight and on the following morning, and the area washedwith mild soap and water. Treatment duration is recom-mended until wart clearance is achieved or for a maxi-mum of 16 weeks (20). The importance of ensuring athree times weekly application is highlighted by Gollnicket al. (21) who compared the safety and efficacy of threetimes weekly and once daily applications of imiquimod5% cream for the treatment of penile genital warts inuncircumcised men. Both groups showed similar levelsof efficacy and the only differences were in the sideeffects experienced. The most frequently reported localside effects were burning, pruritus, irritation or pain;however, the three times a week dosing regimen waswell-tolerated, with a lower incidence of local skin reac-tions than in the once daily group. The results indicatedthat the appropriate treatment regimen is three timesweekly, which demonstrated higher efficacy with toler-ability (21). Additional open-label studies have furtherestablished the successful and well tolerated use of imi-quimod for treating genital warts in both women andmen with low rates of recurrence (22, 23). With anytreatment modality, there are possible associated sideeffects, therefore it is important to highlight these to the