Imiquimod in the Treatment of Cutaneous Warts: An Evidence-Based Review

American Journal of Clinical Dermatology - Tập 15 - Trang 387-399 - 2014
Christine S. Ahn1, William W. Huang1
1Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, USA

Tóm tắt

Cutaneous warts are highly prevalent lesions caused by the infection of keratinocytes by different types of human papillomaviruses. Although cutaneous warts are capable of resolving spontaneously, these infections can persist for long periods of time by evading the host immune system, and, as a result, many patients choose to seek treatment. Imiquimod is an immune response modifier that is approved as a topical cream for the treatment of anogenital warts by the US Food and Drug Administration. However, the efficacy of imiquimod in the treatment of cutaneous warts has not been well established. The purpose of this article is to systematically review the published literature regarding the efficacy of imiquimod in the treatment of cutaneous warts, and to evaluate the quality and outcomes of these studies. A literature search was performed through clinical queries PubMed (National Library of Medicine) database and the Cochrane database. All completed studies written in English and published through May 2014 were considered. Studies evaluating the use of imiquimod for anogenital warts were excluded. There were no other restrictions based on patient age, sex, ethnicity, or skin type. The studies were evaluated and assessed based on study design, patient population, treatment regimen, clinical outcome, and adverse events. A total of 393 records were identified in the initial search; 23 full-text articles were assessed for eligibility and included in the review. Of these studies, six publications reported on immunocompromised individuals only. The highest quality study identified was a grade B, level 3 case-control cohort study in which patients with multiple warts had certain warts treated with imiquimod and others left untreated to serve as a control. The remaining studies identified were level 4 non-controlled case series (grade C) and level 5 case reports (grade D). In immunocompetent patients enrolled in non-controlled studies, the combined rate of patients achieving complete response to therapy was 44 %, ranging from 27 to 89 %. However, there was variation in the dose frequency and application among these studies. In immunosuppressed patients, two studies and four case reports were identified. Clinical improvement was seen in 33–50 % of patients, with no patients experiencing complete clinical clearance. There have been several studies demonstrating the successful use of imiquimod to treat recalcitrant cutaneous warts, either alone or as combination therapy. However, these studies are limited in number, include small populations, and are non-controlled. Further studies are needed to determine the efficacy of imiquimod, dose frequency and application, and optimal combination with other therapeutic measures such as paring, salicylic acid, or other destructive procedures.

Tài liệu tham khảo

Bolognia JL, Jorizzo JL, Schaffer JV. Human papillomaviruses. Dermatology. 3rd ed. Philadelphia: Elsevier Saunders; 2012 (Print). Bruggink SC, de Koning MN, Gussekloo J, et al. Cutaneous wart-associated HPV types: prevalence and relation with patient characteristics. J Clin Virol. 2012;55(3):250–5. Kilkenny M, Merlin K, Yunng R, Marks R. The prevalence of common skin conditions in Australian school students: 1. Common, plane and plantar viral warts. Br J Dermatol. 1998;138:8411–5. Spira R, Mignard M, Doutre MS, et al. Prevalence of cutaneous disorders in a population of HIV-infected patients. Southwestern France, 1996. Groupe d’Epidémiologie Clinique du SIDA en Aquitaine. Arch Dermatol. 1998;134(10):1208–12. Wilmer EN, Gustafson CJ, Ahn CS, et al. Most common dermatologic problems identified by dermatologists and non-dermatologists, 2001–2010. Cutis (in press). Fox PA, Tung MY. Human papillomavirus: burden of illness and treatment cost considerations. Am J Clin Dermatol. 2005;6(6):365–81. Dall’oglio F, D’Amico V, Nasca MR, Micali G. Treatment of cutaneous warts: an evidence-based review. Am J Clin Dermatol. 2012;13(2):73–96. Fields K, Milikowski C, Jewell T, Fields J. Localized diffuse melanosis associated with melanoma successfully treated with imiquimod cream 5 %: a case report and review of the literature. Cutis. 2014;93(3):145–50. Luyten A, Sörgel P, Clad A, et al. Treatment of extramammary Paget disease of the vulva with imiquimod: a retrospective, multicenter study by the German Colposcopy Network. J Am Acad Dermatol. 2014;70(4):644–50. Salasche S, Shumack S. A review of imiquimod 5 % cream for the treatment of various dermatological conditions. Clin Exp Dermatol. 2003;28(Suppl 1):1–3. Edwards L, Ferenczy A, Eron L, et al. Self-administered topical 5 % imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus. Arch Dermatol. 1998;134(1):25–30. Reeder VJ, Gustafson CJ, Davis SA, et al. The treatment and demographics of warts: an analysis of national trends. J Drugs Dermatol. 2013;12(12):1411–5. Oxford Centre for Evidence-based Medicine—Levels of Evidence. University of Oxford, Medical Sciences Division. March 2009. http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/. Accessed 18 June 2014. Hengge UR, Esser S, Schultewolter T, et al. Self-administered topical 5 % imiquimod for the treatment of common warts and molluscum contagiosum. Br J Dermatol. 2000;143(5):1026–31. Grussendorf-Conen EI, Jacobs S. Efficacy of imiquimod 5 % cream in the treatment of recalcitrant warts in children. Pediatr Dermatol. 2002;19(3):263–6. Grussendorf-Conen EI, Jacobs S, Rübben A, Dethlefsen U. Topical 5 % imiquimod long-term treatment of cutaneous warts resistant to standard therapy modalities. Dermatology. 2002;205(2):139–45. Muzio G, Massone C, Rebora A. Treatment of non-genital warts with topical imiquimod 5 % cream. Eur J Dermatol. 2002;12(4):347–9. Housman TS, Jorizzo JL. Anecdotal reports of 3 cases illustrating a spectrum of resistant common warts treated with cryotherapy followed by topical imiquimod and salicylic acid. J Am Acad Dermatol. 2002;47(4 Suppl):S217–20. Atzori L, Pinna AL, Ferreli C. Extensive and recalcitrant verrucae vulgares of the great toe treated with imiquimod 5 % cream. J Eur Acad Dermatol Venereol. 2003;17(3):366–7. Kim MB, Ko HC, Jang HS, et al. Treatment of flat warts with 5 % imiquimod cream. J Eur Acad Dermatol Venereol. 2006;20(10):1349–50. Oster-Schmidt C. Imiquimod: a new possibility for treatment-resistant verrucae planae. Arch Dermatol. 2001;137(5):666–7. Schwab RA, Elston DM. Topical imiquimod for recalcitrant facial flat warts. Cutis. 2000;65(3):160–2. Khan Durani B, Jappe U. Successful treatment of facial plane warts with imiquimod. Br J Dermatol. 2002;147(5):1018. Leong CM, Tarbotton J, Hibma M. Self-applied treatment of persistent plantar wart with 5 % imiquimod cream. N Z Med J. 2007;120(1259):U2668. Sparling JD, Checketts SR, Chapman MS. Imiquimod for plantar and periungual warts. Cutis. 2001;68(6):397–9. Tucker SB, Ali A, Ransdell BL. Plantar wart treatment with combination imiquimod and salicylic acid pads. J Drugs Dermatol. 2003;2(2):124–6. Yesudian PD, Parslew RA. Treatment of recalcitrant plantar warts with imiquimod. J Dermatol Treat. 2002;13(1):31–3. Zamiri M, Gupta G. Plantar warts treated with an immune response modifier: a report of two cases. Clin Exp Dermatol. 2003;28(Suppl 1):45–7. Micali G, Dall’Oglio F, Nasca MR. An open label evaluation of the efficacy of imiquimod 5 % cream in the treatment of recalcitrant subungual and periungual cutaneous warts. J Dermatol Treat. 2003;14(4):233–6. Poochareon V, Berman B, Villa A. Successful treatment of butcher’s warts with imiquimod 5 % cream. Clin Exp Dermatol. 2003;28(Suppl 1):42–4. Harwood CA, Perrett CM, Brown VL, et al. Imiquimod cream 5 % for recalcitrant cutaneous warts in immunosuppressed individuals. Br J Dermatol. 2005;152(1):122–9. Ben M’barek L, Mebazaa A, Euvrard S, et al. 5 % topical imiquimod tolerance in transplant recipients. Dermatology. 2007;215(2):130–3. Weisshaar E, Gollnick H. Potentiating effect of imiquimod in the treatment of verrucae vulgares in immunocompromised patients. Acta Derm Venereol. 2000;80(4):306–7. Hagman JH, Bianchi L, Marulli GC, Soda R, Chimenti S. Successful treatment of multiple filiform facial warts with imiquimod 5 % cream in a patient infected by human immunodeficiency virus. Clin Exp Dermatol. 2003;28(3):260–1. Cutler K, Kagen MH, Don PC, et al. Treatment of facial verrucae with topical imiquimod cream in a patient with human immunodeficiency virus. Acta Derm Venereol. 2000;80(2):134–5. Juschka U, Hartmann M. Topical treatment of common warts in an HIV-positive patient with imiquimod 5 % cream. Clin Exp Dermatol. 2003;28(Suppl 1):48–50. Am Massing. Epstein WL. Natural history of warts. Arch Dermatol. 1963;87:306–10. Plasencia JM. Cutaneous warts: diagnosis and treatment. Prim Care. 2000;27:423–34. Bunney MH, Nolan MW, Williams DA. An assessment of methods of treating viral warts by comparative treatment trials based on a standard design. Br J Dermatol. 1976;94:667–79. Miller DM, Brodell RT. Human papillomavirus infection: treatment options for warts. Am Fam Physician. 1996;53:135–50. Bolton RA. Non-genital warts: classification and treatment options. Am Fam Physician. 1991;43:2049–56. Kenton-Smith J, Tan ST. Pulsed dye laser therapy for viral warts. Br J Plast Surg. 1999;52:554–8. Sloan K, Haberman H, Lynde CW. Carbon dioxide laser-treatment of resistant verrucae vulgaris: retrospective analysis. J Cutan Med Surg. 1998;2:142–5. Jacobsen E, McGraw R, McCagh S. Pulsed dye laser efficacy as initial therapy for warts and against recalcitrant verrucae. Cutis. 1997;59:206–8. Langley PC. A cost-effectiveness analysis of sinecatechins in the treatment of external genital warts. J Med Econ. 2010;13(1):1–7. Langley PC, Tyring SK, Smith MH. The cost effectiveness of patient-applied versus provider-administered intervention strategies for the treatment of external genital warts. Am J Manag Care. 1999;5(1):69–77.