Combination therapy for the treatment of cutaneous and genital warts

Authors

  • Maryam Khalili Assistant Professor, Assistant professor of dermatology, Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran
  • Rezvan Amiri Department of Dermatology, Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran
  • Behzad Iranmanesh Department of Dermatology, Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran
  • Fatemeh Gheisoori Kerman University of Medical Sciences, Shiraz, Iran
  • Mahin Aflatoonian Associate professor of Dermatology, Clinical Research Development Unit, Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran

Keywords:

Cutaneous warts, Genital warts, Condyloma acuminate, Adjuvant therapy, Combination therapy

Abstract

Evidence-based studies demonstrated that combination therapy can optimize treatment efficacy along with faster response rates and lower recurrence rates which are essential factors in increasing patients' adherence to treatment. In this review, we discuss effectiveness, safety and recurrence rates of various combination therapies in the treatment of cutaneous and genital warts in detail. We searched literature with related keywords. Inclusion criteria were randomized clinical trials (RCTs) that investigated efficacy of combination of two or more treatments on various types of cutaneous and genital warts since January 2000 up to August 2023. Thirty articles were enrolled to final investigation. Adjuvant of destructive methods to other therapeutic options was the most common combination therapy in the treatment of warts. Cryo-immuno-therapy is an effective therapeutic method in the treatment of wart that can boost immune system response against human papilloma virus (HPV). This combination therapy demonstrated rapid remission of the both treated and distant untreated lesions, and reduces risk of recurrence. Application of topical destructive methods prior to laser leads to rapid remission and reduces treatment cost as well. Combination of laser with immunologic therapies can be especially effective in recalcitrant warts (i.e. periungual lesions). Combination therapy can particularly be recommended in immunocompromised patients and those with refractory warts that demonstrated poor response to other treatment options.

References

Iranmanesh B, Khalili M, Zartab H, Amiri R, Aflatoonian M. Laser therapy in cutaneous and genital warts: A review article. Dermatol Ther. 2021;34(1):e14671.

Işik S, Koca R, Sarici G, Altinyazar HC. A comparison of a 5% potassium hydroxide solution with a 5‐fluorouracil and salicylic acid combination in the treatment of patients with anogenital warts: a randomized, open-label clinical trial. Int J Dermatol. 2014;53(9):1145-50.

Parsad D, Pandhi R, Juneja A, Negi KS. Cimetidine and levamisole versus cimetidine alone for recalcitrant warts in children. Pediatr Dermatol. 2001;18(4):349-52.

Attwa E, Elawady R, Salah E. ‘Cryo-immuno-therapy’ is superior to intralesional Candida antigen monotherapy in the treatment of multiple common warts. J Dermatol Treat. 2021;32(8):1018-25.

Awad SM, Gomaa AS, Hassan HA, Tawfik YM. Efficacy of cryotherapy combined with intralesional purified protein derivative (PPD) versus intralesional PPD monotherapy in the treatment of multiple common warts. J Cutan Med Surg. 2023;27(2):117-25.

Moubasher AA, Kolta M. Tuberculin purified protein derivative and cryotherapy in the treatment of genital warts: A randomized controlled trial. Human Androl. 2021;11(11):1-6.

Ibrahim H, El Taieb M, Nada E, Kamal E, Hegazy E. Combined intralesional injection of tuberculin purified protein derivative plus cryotherapy versus each alone in the treatment of multiple common warts. Dermatol Ther. 2022;35(4):e15350.

Khalili M, Mehrabadi R, Mohammadi S, Pardakhty A, Amiri R, Aflatonian M. The Efficacy of Immunocryosurgery with Combined 2% Niosomal Zinc Sulfate Suspension and Cryotherapy in the Treatment of Verruca vulgaris. J Kerman Uni Med Sci. 2022;29(2):139-45.

Farajzadeh S, Pardakhti A, Mohammadi S, Fadaei F, Khalili M, Mohebbi A, Aflatonian M. A randomized clinical trial of using niosomal zinc sulfate plus cryotherapy in comparison with placebo along with cryotherapy in treatment of common wart. J Kerman Uni Med Sci. 2018;25(1):1-8.

Mahmoudi H, Ghodsi SZ, Tavakolpour S, Daneshpazhooh M. Cryotherapy plus oral zinc sulfate versus cryotherapy plus placebo to treat common warts: A double blind, randomized, placebo-controlled trial. Int J Women's Dermatol. 2018;4(2):87-90.

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(10):2110-3.

Sherrard J, Riddell L. Comparison of the effectiveness of commonly used clinic-based treatments for external genital warts. Int J STD AIDS. 2007;18(6):365-8.

Mahajan BB, Tilak Raj RB, Kumar R. A comparative evaluation of therapeutic efficacy and safety of the cryotherapy (liquid nitrogen) with topical 20% podophyllin vs. intralesional bleomycin with topical 5% placentrex gel in the treatment of condyloma acuminata. Asian J Pharm Clin Res. 2014;7(1):36-42.

Gilson RJ, Ross J, Maw R, Rowen D, Sonnex C, Lacey CJ. A multicentre, randomised, double-blind, placebo controlled study of cryotherapy versus cryotherapy and podophyllotoxin cream as treatment for external anogenital warts. Sex Transm Infect. 2009;85(7):514-9.

Reyna-Rodríguez IL, Chavez-Alvarez S, Garza-Rodríguez V, Franco-Marquez R, Gonzalez-Martinez G, Ocampo-Candiani J, Villarreal-Martinez A. Cryotherapy plus low-dose oral isotretinoin vs cryotherapy only for the treatment of anogenital warts: a randomized clinical trial. Arch Dermatol Res. 2021:1-3.

Luk NM, Tang WY, Tang NL, Chan SW, Wong JK, Hon KL, Lo KK. Topical 5‐fluorouracil has no additional benefit in treating common warts with cryotherapy: a single-centre, double-blind, randomized, placebo‐controlled trial. Clin Exp Dermatol. 2006;31(3):394-7.

Meymandi SS, Vaseli MB, Aflatoonian M, Abroud F. Efficacy of cryotherapy combined with topical cantharidin application versus cryotherapy and placebo in the treatment of verruca vulgaris: A randomized, controlled clinical trial. J Pak Assoc Dermatol. 2017;27(1):42-7.

Shi L, Luo M, Zhang F, Zhang L, Wang B, Liu P, Zhang Y, Zhang H, Yang D, Zhang G, Zhou F. Photothermal therapy enhanced the effectiveness of imiquimod against refractory cutaneous warts through boosting immune responses. J Biophotonics. 2019;12(2):e201800149.

Akarsu SE, Ilknur TU, Demirtaşoǧlu M, Özkan Ş. Verruca vulgaris: pulsed dye laser therapy compared with salicylic acid+ pulsed dye laser therapy. J Eur Acad Dermatol Venereol. 2006;20(8):936-40.

Khattab FM, Khashaba SA. Evaluation of combined treatment with long-pulsed neodymium-doped yttrium aluminum garnet laser and potassium hydroxide for the treatment of recalcitrant wart: a prospective comparative study. J Dermatol Treat. 2020;31(1):56-60.

Jiryis B, Avitan‐Hersh E, Mirmovich O, Nevet MJ, Khamaysi Z. Evaluation of combined treatment with Er: YAG laser and long‐pulsed Nd: YAG laser for the treatment of recalcitrant warts: a prospective randomized controlled trial. J Eur Acad Dermatol Venereol. 2023;37(12):2569-74.

Choi GS, Park JH, Kim YK, Choi GS. Combination therapy with Intralesional interferon α-2b and pulsed dye laser for the treatment of periungual warts. Ann Dermatol. 2002;14(2):82-7.

Xu H, Shen Q, Fan B, Xi C, Wang L. Effectiveness of a combination therapy of traditional Chinese medicine and CO2 laser treatment for condyloma acuminatum. J Med Virol. 2020;92(12):3889-94.

Ghonemy S, Ibrahim Ali M, Ebrahim HM. The efficacy of microneedling alone vs its combination with 5‐fluorouracil solution vs 5‐fluorouracil intralesional injection in the treatment of plantar warts. Dermatol Therapy. 2020;33(6):e14179.

Di Chiacchio NG, Di Chiacchio N, Criado PR, Brunner CH, Suaréz MV, Belda Junior W. Ungual warts: comparison of treatment with intralesional bleomycin and electroporation in terms of efficacy and safety. J Eur Acad Dermatol Venereol. 2019;33(12):2349-54.

Horn TD, Johnson SM, Helm RM, Roberson PK. Intralesional immunotherapy of warts with mumps, Candida, and Trichophyton skin test antigens: a single-blinded, randomized, and controlled trial. Arch Dermatol. 2005;141(5):589-94.

Nofal AA, Elkholy BM, Abd-Elmonsef ER, Nofal HO. Triple Intralesional antigen immunotherapy versus Monoantigen in the treatment of multiple recalcitrant warts. Dermatol Ther. 2022;12(5):1225-37.

Fawzy M, Nofal E, Abdelkhalek N, Ehab R. Intralesional bivalent and quadrivalent human papillomavirus vaccines didn’t significantly enhance the response of multiple anogenital warts when co-administered with intralesional Candida antigen immunotherapy. A randomized controlled trial. Arch Dermatol Res. 2023;315(10):2813-23.

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(1):80-2.

Fathy G, Abo-Elmagd WM, Afify AA. Intralesional combined digoxin and furosemide in plantar warts: Does it work? J Cosmet Dermatol. 2021;20(8):2606-11.

Lofty AR, Elbakry AM, Omar GA, Hamdino M. Intralesional combined furosemide and digoxin in cutaneous warts treatment: A randomized controlled clinical trial. Dermatol Ther. 2022;35(12):e15935.

Rijsbergen M, Niemeyer‐van der Kolk T, Hogendoorn G, Kouwenhoven S, Lemoine C, Klaassen ES, de Koning M, Beck S, Bouwes Bavinck JN, Feiss G, Burggraaf J. A randomized controlled proof-of-concept trial of digoxin and furosemide in adults with cutaneous warts. Br J Dermatol. 2019;180(5):1058-68.

Soenjoyo KR, Chua BW, Wee LW, Koh MJ, Ang SB. Treatment of cutaneous viral warts in children: A review. Dermatol Ther. 2020;33(6):e14034.

Gheisari M, Iranmanesh B, Nobari NN, Amani M. Comparison of long-pulsed Nd: YAG laser with cryotherapy in treatment of acral warts. Lasers Med Sci. 2019;34:397-403.

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Published

2024-10-11

How to Cite

1.
Khalili M, Amiri R, Iranmanesh B, Gheisoori F, Aflatoonian M. Combination therapy for the treatment of cutaneous and genital warts. J Pak Assoc Dermatol [Internet]. 2024Oct.11 [cited 2025Feb.7];34(4):1048-61. Available from: http://www.jpad.com.pk/index.php/jpad/article/view/2766

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