Evolving role of immunotherapy in the treatment of refractory warts

Devinder M Thappa, Minu J Chiramel, Devinder M Thappa, Minu J Chiramel

Abstract

Cutaneous and genital warts are common dermatological conditions caused by the human papilloma virus (HPV). Although it is a benign condition, it causes disfigurement, has a tendency to koebnerize, and can be transmitted to others. This makes adequate and timely treatment important. There are several conventional treatments available with variable response. Topical and systemic immunotherapy has now found a significant place in the treatment of warts because of its nondestructive action, ease of use, and promising results. Through this review, we would like to present a brief overview of the various immunotherapeutic agents used. These include more established agents such as imiquimod, Mycobacterium w vaccine, bacillus Calmette-Guérin vaccine, measles, mumps, and rubella vaccine, Candida antigen, trichophyton antigen, tuberculin, zinc, cimetidine, levamisole, HPV vaccine, and autoimplantation therapy. Other agents such as contact immunotherapy which is sparsely used now than before and newer agents such as Corynebacterium parvum, sinecatechins, echinacea, propolis, glycyrrizinic acid, and Vitamin D have also been discussed. The mechanism of action of these agents, along with their dosage, mode of administration, duration of use, expected outcomes and comparative efficacy, evidence for their use, and expected side effects, if any, are reviewed.

Keywords: Cutaneous; genital; immunotherapy; verruca; wart.

References

    1. Santos-López G, Márquez-Domínguez L, Reyes-Leyva J, Vallejo-Ruiz V. General aspects of structure, classification and replication of human papillomavirus. Rev Médica Inst Mex Seguro Soc. 2015;53(Suppl 2):S166–71.
    1. Singh S, Chouhan K, Gupta S. Intralesional immunotherapy with killed Mycobacterium indicus pranii vaccine for the treatment of extensive cutaneous warts. Indian J Dermatol Venereol Leprol. 2014;80:509–14.
    1. Sterling JC, Gibbs S, Haque Hussain SS, Mohd Mustapa MF, Handfield-Jones SE. British Association of Dermatologists’ guidelines for the management of cutaneous warts 2014. Br J Dermatol. 2014;171:696–712.
    1. Beutner KR, Tyring SK, Trofatter KF, Douglas JM, Spruance S, Owens ML, et al. Imiquimod, a patient-applied immune-response modifier for treatment of external genital warts. Antimicrob Agents Chemother. 1998;42:789–94.
    1. Arany I, Tyring SK, Brysk MM, Stanley MA, Tomai MA, Miller RL, et al. Correlation between pretreatment levels of interferon response genes and clinical responses to an immune response modifier (imiquimod) in genital warts. Antimicrob Agents Chemother. 2000;44:1869–73.
    1. Perry CM, Lamb HM. Topical imiquimod: Areview of its use in genital warts. Drugs. 1999;58:375–90.
    1. Moore RA, Edwards JE, Hopwood J, Hicks D. Imiquimod for the treatment of genital warts: Aquantitative systematic review. BMC Infect Dis. 2001;1:3.
    1. Ahn CS, Huang WW. Imiquimod in the treatment of cutaneous warts: An evidence-based review. Am J Clin Dermatol. 2014;15:387–99.
    1. Stefanaki C, Lagogiani I, Kouris A, Kontochristopoulos G, Antoniou C, Katsarou A. Cryotherapy versus imiquimod 5% cream combined with a keratolytic lotion in cutaneous warts in children: A randomized study. J Dermatol Treat. 2016;27:80–2.
    1. Ciavattini A, Tsiroglou D, Vichi M, Di Giuseppe J, Cecchi S, Tranquilli AL. Topical Imiquimod 5% cream therapy for external anogenital warts in pregnant women: Report of four cases and review of the literature. J Matern-Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet. 2012;25:873–6.
    1. Grillo-Ardila CF, Angel-Müller E, Salazar-Díaz LC, Gaitán HG, Ruiz-Parra AI, Lethaby A. Imiquimod for anogenital warts in non-immunocompromised adults. Cochrane Database Syst Rev. 2014;11:CD010389.
    1. Garg S, Baveja S. Intralesional immunotherapy for difficult to treat warts with Mycobacterium w vaccine. J Cutan Aesthetic Surg. 2014;7:203–8.
    1. Gupta S, Malhotra AK, Verma KK, Sharma VK. Intralesional immunotherapy with killed Mycobacterium w vaccine for the treatment of ano-genital warts: An open label pilot study. J Eur Acad Dermatol Venereol JEADV. 2008;22:1089–93.
    1. Meena JK, Malhotra AK, Mathur DK, Mathur DC. Intralesional immunotherapy with mycobacteriumw vaccine in patients with multiple cutaneous warts: Uncontrolled open study. JAMA Dermatol. 2013;149:237–9.
    1. Dhakar AK, Dogra S, Vinay K, Sarangal R, Kanwar AJ, Singh MP. Intralesional Mycobacterium w vaccine versus cryotherapy in treatment of refractory extragenital warts: A randomized, open-label, comparative Study. J Cutan Med Surg. 2016;20:123–9.
    1. Kumar P, Dar L, Saldiwal S, Varma S, Datt Upadhyay A, Talwar D, et al. Intralesional injection of Mycobacterium w vaccine vs imiquimod, 5%, cream in patients with anogenital warts: Arandomized clinical trial. JAMA Dermatol. 2014;150:1072–8.
    1. Singh S, Chouhan K, Gupta S. Intralesional immunotherapy with killed Mycobacterium indicus pranii vaccine for the treatment of extensive cutaneous warts. Indian J Dermatol Venereol Leprol. 2014;80:509–14.
    1. Zuo C, Huang J, Liao Z, Lu J, Chen J. Effects of BCG-PSN on serum levels of IL-4 and IL-12 in patients with condyloma acuminatum. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004;29:690–2.
    1. Sharquie KE, Al-Rawi JR, Al-Nuaimy AA, Radhy SH. Bacille Calmette-Guerin immunotherapy of viral warts. Saudi Med J. 2008;29:589–93.
    1. Salem A, Nofal A, Hosny D. Treatment of common and plane warts in children with topical viable Bacillus Calmette-Guerin. Pediatr Dermatol. 2013;30:60–3.
    1. Daulatabad D, Pandhi D, Singal A. BCG vaccine for immunotherapy in warts: Is it really safe in a tuberculosis endemic area? Dermatol Ther. 2016;29:168–72.
    1. Zamanian A, Mobasher P, Jazi GA. Efficacy of intralesional injection of mumps-measles-rubella vaccine in patients with wart. Adv Biomed Res. 2014;3:107.
    1. Nofal A, Nofal E, Yosef A, Nofal H. Treatment of recalcitrant warts with intralesional measles, mumps, and rubella vaccine: Apromising approach. Int J Dermatol. 2015;54:667–71.
    1. Na CH, Choi H, Song SH, Kim MS, Shin BS. Two-year experience of using the measles, mumps and rubella vaccine as intralesional immunotherapy for warts. Clin Exp Dermatol. 2014;39:583–9.
    1. Gamil H, Elgharib I, Nofal A, Abd-Elaziz T. Intralesional immunotherapy of plantar warts: Report of a new antigen combination. J Am Acad Dermatol. 2010;63:40–3.
    1. Shaheen MA, Salem SAM, Fouad DA, El-Fatah AAA. Intralesional tuberculin (PPD) versus measles, mumps, rubella (MMR) vaccine in treatment of multiple warts: Acomparative clinical and immunological study. Dermatol Ther. 2015;28:194–200.
    1. Kim KH, Horn TD, Pharis J, Kincannon J, Jones R, O’Bryan K, et al. Phase 1 clinical trial of intralesional injection of candida antigen for the treatment of warts. Arch Dermatol. 2010;146:1431–3.
    1. Muñoz Garza FZ, Roé Crespo E, Torres Pradilla M, Aguilera Peirò P, Baltà Cruz S, Hernández Ruiz ME, et al. Intralesional Candida antigen immunotherapy for the treatment of recalcitrant and multiple warts in children. Pediatr Dermatol. 2015;32:797–801.
    1. Alikhan A, Griffin JR, Newman CC. Use of Candida antigen injections for the treatment of verruca vulgaris: A two-year mayo clinic experience. J Dermatol Treat. 2015:1–4.
    1. Maronn M, Salm C, Lyon V, Galbraith S. One-year experience with candida antigen immunotherapy for warts and molluscum. Pediatr Dermatol. 2008;25:189–92.
    1. Majid I, Imran S. Immunotherapy with intralesional Candida albicans antigen in resistant or recurrent warts: Astudy. Indian J Dermatol. 2013;58:360–5.
    1. Wong A, Crawford RI. Intralesional Candida antigen for common warts in people with HIV. J Cutan Med Surg. 2013;17:313–5.
    1. Perman M, Sterling JB, Gaspari A. The painful purple digit: An alarming complication of Candida albicans antigen treatment of recalcitrant warts. Dermat Contact Atopic Occup Drug. 2005;16:38–40.
    1. Horn TD, Johnson SM, Helm RM, Roberson PK. Intralesional immunotherapy of warts with mumps, Candida, and Trichophyton skin test antigens: Asingle-blinded, randomized, and controlled trial. Arch Dermatol. 2005;141:589–94.
    1. Johnson SM, Horn TD. Intralesional immunotherapy for warts using a combination of skin test antigens: Asafe and effective therapy. J Drugs Dermatol JDD. 2004;3:263–5.
    1. Aldahan AS, Mlacker S, Shah VV, Kamath P, Alsaidan M, Samarkandy S, et al. Efficacy of intralesional immunotherapy for the treatment of warts: A review of the literature. Dermatol Ther. 2016;29:197–207.
    1. Abd-Elazeim FMA, Mohammed GFA, Fathy A, Mohamed RW. Evaluation of IL-12 serum level in patients with recalcitrant multiple common warts, treated by intralesional tuberculin antigen. J Dermatol Treat. 2014;25:264–7.
    1. Saoji V, Lade NR, Gadegone R, Bhat A. Immunotherapy using purified protein derivative in the treatment of warts: An open uncontrolled trial. Indian J Dermatol Venereol Leprol. 2016;82:42–6.
    1. Yang J, Pu Y, Zeng Z, Yu Z, Huang N, Deng Q. Interferon for the treatment of genital warts: Asystematic review. BMC Infect Dis. 2009;9:156.
    1. Raza N, Khan DA. Zinc deficiency in patients with persistent viral warts. J Coll Physicians Surg--Pak JCPSP. 2010;20:83–6.
    1. López-García DR, Gómez-Flores M, Arce-Mendoza AY, de la Fuente-García A, Ocampo-Candiani J. Oral zinc sulfate for unresponsive cutaneous viral warts: Too good to be true? A double-blind, randomized, placebo-controlled trial. Clin Exp Dermatol. 2009;34:e984–5.
    1. Al-Gurairi FT, Al-Waiz M, Sharquie KE. Oral zinc sulphate in the treatment of recalcitrant viral warts: Randomized placebo-controlled clinical trial. Br J Dermatol. 2002;146:423–31.
    1. Mun JH, Kim SH, Jung DS, Ko HC, Kim BS, Kwon KS, et al. Oral zinc sulfate treatment for viral warts: An open-label study. J Dermatol. 2011;38:541–5.
    1. Akhavan S, Mohammadi SR, Modarres Gillani M, Mousavi AS, Shirazi M. Efficacy of combination therapy of oral zinc sulfate with imiquimod, podophyllin or cryotherapy in the treatment of vulvar warts. J Obstet Gynaecol Res. 2014;40:2110–3.
    1. Stefani M, Bottino G, Fontenelle E, Azulay DR. Efficacy comparison between cimetidine and zinc sulphate in the treatment of multiple and recalcitrant warts. An Bras Dermatol. 2009;84:23–9.
    1. Sharquie KE, Khorsheed AA, Al-Nuaimy AA. Topical zinc sulphate solution for treatment of viral warts. Saudi Med J. 2007;28:1418–21.
    1. Khattar JA, Musharrafieh UM, Tamim H, Hamadeh GN. Topical zinc oxide vs. salicylic acid-lactic acid combination in the treatment of warts. Int J Dermatol. 2007;46:427–30.
    1. Paller AS. Cimetidine for the treatment of warts. West J Med. 1996;164:520–1.
    1. Mitsuishi T, Iida K, Kawana S. Cimetidine treatment for viral warts enhances IL-2 and IFN-gamma expression but not IL-18 expression in lesional skin. Eur J Dermatol. 2003;13:445–8.
    1. Gooptu C, Higgins CR, James MP. Treatment of viral warts with cimetidine: An open-label study. Clin Exp Dermatol. 2000;25:183–5.
    1. Yilmaz E, Alpsoy E, Basaran E. Cimetidine therapy for warts: Aplacebo-controlled, double-blind study. J Am Acad Dermatol. 1996;34:1005–7.
    1. Karaman G, Sendur N, Sevk E. Ranitidine therapy for recalcitrant warts in adults: Apreliminary study. J Eur Acad Dermatol Venereol. 2001;15:495–6.
    1. Sáenz-Santamaría MC, Gilaberte Y. Cimetidine and warts. Arch Dermatol. 1997;133:530–1.
    1. Lee SH, Rose B, Thompson CH, Cossart Y. Plantar warts of defined aetiology in adults and unresponsiveness to low dose cimetidine. Australas J Dermatol. 2001;42:220–1.
    1. Rogers CJ, Gibney MD, Siegfried EC, Harrison BR, Glaser DA. Cimetidine therapy for recalcitrant warts in adults: Is it any better than placebo? J Am Acad Dermatol. 1999;41:123–7.
    1. Parsad D, Pandhi R, Juneja A, Negi KS. Cimetidine and levamisole versus cimetidine alone for recalcitrant warts in children. Pediatr Dermatol. 2001;18:349–52.
    1. Fit KE, Williams PC. Use of histamine2-antagonists for the treatment of verruca vulgaris. Ann Pharmacother. 2007;41:1222–6.
    1. Amer M, Tosson Z, Soliman A, Selim AG, Salem A, al-Gendy AA. Verrucae treated by levamisole. Int J Dermatol. 1991;30:738–40.
    1. Moncada B, Rodriguez ML. Levamisole therapy for multiple warts. Br J Dermatol. 1979;101:327–30.
    1. Saúl A, Sanz R, Gomez M. Treatment of multiple viral warts with levamisole. Int J Dermatol. 1980;19:342–3.
    1. Schou M, Helin P. Levamisole in a double-blind study: No effect on warts. Acta Derm Venereol. 1977;57:449–54.
    1. Scheinfeld N, Rosenberg JD, Weinberg JM. Levamisole in dermatology: Areview. Am J Clin Dermatol. 2004;5:97–104.
    1. Blomberg M, Dehlendorff C, Sand C, Kjaer SK. Dose-related differences in effectiveness of human papillomavirus vaccination against genital warts: A nationwide study of 550,000 young girls. Clin Infect Dis. 2015;61:676–82.
    1. Clarke E, Board C, Patel N, Atkinson L, Tulloch H, Patel R. Why are anogenital warts diagnoses decreasing in the U.K.: Bivalent human papillomavirus (HPV) vaccine cross-protection or failure to examine? Sex Transm Infect. 2014;90:587.
    1. Chow EP, Read TR, Wigan R, Donovan B, Chen MY, Bradshaw CS, et al. Ongoing decline in genital warts among young heterosexuals 7 years after the Australian human papillomavirus (HPV) vaccination programme. Sex Transm Infect. 2015;91:214–9.
    1. Venugopal SS, Murrell DF. Recalcitrant cutaneous warts treated with recombinant quadrivalent human papillomavirus vaccine (types 6, 11, 16, and 18) in a developmentally delayed, 31-year-old white man. Arch Dermatol. 2010;146:475–7.
    1. Silling S, Wieland U, Werner M, Pfister H, Potthoff A, Kreuter A. Resolution of novel human papillomavirus–induced warts after HPV vaccination. Emerg Infect Dis. 2014;20:142–5.
    1. Riethmuller D, Jacquard AC, Lacau St Guily J, Aubin F, Carcopino X, Pradat P, et al. Potential impact of a nonavalent HPV vaccine on the occurrence of HPV-related diseases in France. BMC Public Health [Internet] 2015 [cited 2016 Mar 1];15. Available from: .
    1. Shivakumar V, Okade R, Rajkumar V. Autoimplantation therapy for multiple warts. Indian J Dermatol Venereol Leprol. 2009;75:593–5.
    1. Nischal KC, Sowmya CS, Swaroop MR, Agrawal DP, Basavaraj HB, Sathyanarayana BD. A novel modification of the autoimplantation therapy for the treatment of multiple, recurrent and palmoplantar warts. J Cutan Aesthetic Surg. 2012;5:26–9.
    1. Word AP, Nezafati KA, Cruz PD., Jr Treatment of warts with contact allergens. Dermatitis. 2015;26:32–7.
    1. Sljivić VS, Watson SR. The adjuvant effect of Corynebacterium parvum: T-cell dependence of macrophage activation. J Exp Med. 1977;145:45–57.
    1. Nasser N. Treatment of common warts with the immune stimulant Propionium bacterium parvum. An Bras Dermatol. 2012;87:585–9.
    1. Zedan H, Hofny ERM, Ismail SA. Propolis as an alternative treatment for cutaneous warts. Int J Dermatol. 2009;48:1246–9.
    1. Gupta AK, Daigle D. Sinecatechins 10% ointment: Agreen tea extract for the treatment of external genital warts. Skin Ther Lett. 2015;20:6–8.
    1. Domínguez Gómez J, Simón RD, Abreu Daniel A, Zelenkova H. Effectiveness of Glycyrrhizinic Acid (Glizigen) and an Immunostimulant (Viusid) to Treat Anogenital Warts. ISRN Dermatol [Internet] 2012. 2012. [cited 2016 Mar 2]. Available from: .
    1. Aktaş H, Ergin C, Demir B, Ekiz Ö. Intralesional Vitamin D injection may be an effective treatment option for warts. J Cutan Med Surg. 2016;20:118–22.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel