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Review
. 2012 Sep 12;2012(9):CD001781.
doi: 10.1002/14651858.CD001781.pub3.

Topical treatments for cutaneous warts

Chun Shing Kwok  1 , Sam Gibbs, Cathy Bennett, Richard Holland, Rachel Abbott
Affiliations
Review

Topical treatments for cutaneous warts

Chun Shing Kwok et al. Cochrane Database Syst Rev. .

Abstract

Background: Viral warts are a common skin condition, which can range in severity from a minor nuisance that resolve spontaneously to a troublesome, chronic condition. Many different topical treatments are available.

Objectives: To evaluate the efficacy of local treatments for cutaneous non-genital warts in healthy, immunocompetent adults and children.

Search methods: We updated our searches of the following databases to May 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), LILACS (from 1982), and CINAHL (from 1981). We searched reference lists of articles and online trials registries for ongoing trials.

Selection criteria: Randomised controlled trials (RCTs) of topical treatments for cutaneous non-genital warts.

Data collection and analysis: Two authors independently selected trials and extracted data; a third author resolved any disagreements.

Main results: We included 85 trials involving a total of 8815 randomised participants (26 new studies were included in this update). There was a wide range of different treatments and a variety of trial designs. Many of the studies were judged to be at high risk of bias in one or more areas of trial design.Trials of salicylic acid (SA) versus placebo showed that the former significantly increased the chance of clearance of warts at all sites (RR (risk ratio) 1.56, 95% CI (confidence interval) 1.20 to 2.03). Subgroup analysis for different sites, hands (RR 2.67, 95% CI 1.43 to 5.01) and feet (RR 1.29, 95% CI 1.07 to 1.55), suggested it might be more effective for hands than feet.A meta-analysis of cryotherapy versus placebo for warts at all sites favoured neither intervention nor control (RR 1.45, 95% CI 0.65 to 3.23). Subgroup analysis for different sites, hands (RR 2.63, 95% CI 0.43 to 15.94) and feet (RR 0.90, 95% CI 0.26 to 3.07), again suggested better outcomes for hands than feet. One trial showed cryotherapy to be better than both placebo and SA, but only for hand warts.There was no significant difference in cure rates between cryotherapy at 2-, 3-, and 4-weekly intervals.Aggressive cryotherapy appeared more effective than gentle cryotherapy (RR 1.90, 95% CI 1.15 to 3.15), but with increased adverse effects.Meta-analysis did not demonstrate a significant difference in effectiveness between cryotherapy and SA at all sites (RR 1.23, 95% CI 0.88 to 1.71) or in subgroup analyses for hands and feet.Two trials with 328 participants showed that SA and cryotherapy combined appeared more effective than SA alone (RR 1.24, 95% CI 1.07 to 1.43).The benefit of intralesional bleomycin remains uncertain as the evidence was inconsistent. The most informative trial with 31 participants showed no significant difference in cure rate between bleomycin and saline injections (RR 1.28, 95% CI 0.92 to 1.78).Dinitrochlorobenzene was more than twice as effective as placebo in 2 trials with 80 participants (RR 2.12, 95% CI 1.38 to 3.26).Two trials of clear duct tape with 193 participants demonstrated no advantage over placebo (RR 1.43, 95% CI 0.51 to 4.05).We could not combine data from trials of the following treatments: intralesional 5-fluorouracil, topical zinc, silver nitrate (which demonstrated possible beneficial effects), topical 5-fluorouracil, pulsed dye laser, photodynamic therapy, 80% phenol, 5% imiquimod cream, intralesional antigen, and topical alpha-lactalbumin-oleic acid (which showed no advantage over placebo).We did not identify any RCTs that evaluated surgery (curettage, excision), formaldehyde, podophyllotoxin, cantharidin, diphencyprone, or squaric acid dibutylester.

Authors' conclusions: Data from two new trials comparing SA and cryotherapy have allowed a better appraisal of their effectiveness. The evidence remains more consistent for SA, but only shows a modest therapeutic effect. Overall, trials comparing cryotherapy with placebo showed no significant difference in effectiveness, but the same was also true for trials comparing cryotherapy with SA. Only one trial showed cryotherapy to be better than both SA and placebo, and this was only for hand warts. Adverse effects, such as pain, blistering, and scarring, were not consistently reported but are probably more common with cryotherapy.None of the other reviewed treatments appeared safer or more effective than SA and cryotherapy. Two trials of clear duct tape demonstrated no advantage over placebo. Dinitrochlorobenzene (and possibly other similar contact sensitisers) may be useful for the treatment of refractory warts.

PubMed Disclaimer

Conflict of interest statement

None declared.

Figures

1
1
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies
1.1
1.1. Analysis
Comparison 1: Topical salicylic acid (SA/LA) vs placebo/no treatment, Outcome 1: Cure rate all studies all sites
1.2
1.2. Analysis
Comparison 1: Topical salicylic acid (SA/LA) vs placebo/no treatment, Outcome 2: Cure rate hands and feet
2.1
2.1. Analysis
Comparison 2: Cryotherapy vs placebo/no treatment, Outcome 1: Cure rate all studies all sites
2.2
2.2. Analysis
Comparison 2: Cryotherapy vs placebo/no treatment, Outcome 2: Cure rate hands and feet
3.1
3.1. Analysis
Comparison 3: Cryotherapy vs salicylic acid (SA/LA) acid, Outcome 1: Cure rate all sites
3.2
3.2. Analysis
Comparison 3: Cryotherapy vs salicylic acid (SA/LA) acid, Outcome 2: Cure rate hands and feet
4.1
4.1. Analysis
Comparison 4: Cryotherapy treatment intervals, Outcome 1: Cryotherapy at 2‐ vs 3‐week intervals
4.2
4.2. Analysis
Comparison 4: Cryotherapy treatment intervals, Outcome 2: Cryotherapy at 3‐ vs 4‐week intervals
4.3
4.3. Analysis
Comparison 4: Cryotherapy treatment intervals, Outcome 3: Cryotherapy at 2‐ vs 4‐week intervals
5.1
5.1. Analysis
Comparison 5: Aggressive vs gentle cryotherapy, Outcome 1: Cure rate
5.2
5.2. Analysis
Comparison 5: Aggressive vs gentle cryotherapy, Outcome 2: Adverse events
6.1
6.1. Analysis
Comparison 6: Cryotherapy + salicylic acid (SA/LA) vs salicylic acid (SA/LA) alone, Outcome 1: Cure rate
7.1
7.1. Analysis
Comparison 7: Cryotherapy + salicylic acid (SA/LA) vs cryotherapy alone, Outcome 1: Cure rate
8.1
8.1. Analysis
Comparison 8: Intralesional interferon vs placebo, Outcome 1: Cure rate
9.1
9.1. Analysis
Comparison 9: Topical DNCB vs placebo, Outcome 1: Cure rate
10.1
10.1. Analysis
Comparison 10: Duct tape vs placebo, Outcome 1: Cure rate
11.1
11.1. Analysis
Comparison 11: Duct tape vs cryotherapy, Outcome 1: Cure rate
12.1
12.1. Analysis
Comparison 12: Intralesional bleomycin vs placebo, Outcome 1: Cure rate
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References

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    1. Wenner R, Askari SK, Cham PMH, Kedrowski DA, Liu A, Warshaw EM. Duct Tape for the Treatment of Common Warts in Adults A Double-blind Randomized Controlled Trial. Archives of Dermatology 2007;143(3):309-13. - PubMed
Wilson 1983 {published data only}
    1. Wilson P. Immunotherapy v cryotherapy for hand warts; a controlled trial (abstract). Scottish Medical Journal 1983;28:191.
Wolff 1980 {published data only}
    1. Wolff K. Result of a clinical trial of Verrumal (Hermal-Chemie) versus placebo; double-blind and randomised left/right study [Ergebnis einer klinischen Untersuchung von Verrumal gegen Placebo; doppelblind und randomisiert im Halbseitenversuch]. Hermal internal report - Gutachten 1980 1-3.
Wu 2005 {published data only}
    1. Wu J, Wang J, Huang Y, Zhou J. Clinical observation on the therapeutic effects of Qu You Ding on flat wart. Journal of Traditional Chinese Medicine 2005;25(3):206-8. - PubMed
Yazar 1994 {published data only}
    1. Yazar S, Basaran E. Efficacy of silvery nitrate pencils in treatment of common wart. Journal of Dermatology 1994;21(5):329-33. - PubMed
Yazdanfar 2008 {published data only}
    1. Yazdanfar A, Farshchian M, Fereydoonnejad M, Farshchian M. Treatment of Common Warts with an Intralesional Mixture of 5-Fluorouracil, Lidocaine, and Epinephrine: A Prospective Placebo-Controlled, Double-Blind Randomized Trial. Dermatologic Surgery 2008;34(5):656-9. - PubMed
Zhang 1999 {published data only}
    1. Zhang X. Soakage with Chinese traditional medical liquid in the treatment of 89 plentiful plantar warts. Chinese Journal of Dermatology & Venereology 1999;13(5):296.

References to studies excluded from this review

Ahmed 2001 {published data only}
    1. Ahmed I, Agarwal S, Ilchyshyn A, Charles-Holmes S, Berth-Jones J. Liquid nitrogen cryotherapy of common warts: cryo-spray versus cotton wool bud. British Journal of Dermatology 2001;144(5):1006-9. - PubMed
Amer 1988 {published data only}
    1. Amer M, Diab N, Ramadan A, Galal A, Salem A. Therapeutic evaluation for intralesional injection of bleomycin sulfate in 143 resistant warts. Journal of the American Academy of Dermatology 1988;18(6):1313-6. - PubMed
Anderson 1963 {published data only}
    1. Anderson I, Shireffs E. Treatment of plantar warts. British Journal of Dermatology 1963;75:29-32. - PubMed
Androphy 1984 {published data only}
    1. Androphy EJ, Doveretzky I, Maluish AE, Wallace HJ, Lowy DR. Response of warts in epidermodysplasia verriformis to treatment with systemic and intralesion alpha interferon. Journal of the American Academy of Dermatology 1984;11 (2 Pt 1):197-202. - PubMed
Baggish 1985 {published data only}
    1. Baggish MS. Improved laser techniques for elimination of genital and extragenital warts. American Journal of Obstetrics and Gynaecology 1985;153(5):545-50. - PubMed
Benton 1991 {published data only}
    1. Benton EC, Nolan MW, Kemmett D, Cubie HA. Trial of inosine pranobex in the management of cutaneous viral warts. Journal of Dermatology Treatments 1991;1(6):295-7. - PubMed
Blancas 2002 {published data only}
    1. Blancas F, Leon G, Lugo L. Homeopathoic Thuja Occidentalis vs placebo in common warts [Abstract P1647]. 20th World Congress of Dermatology, 1st to 5th July 2002, Paris, France. Annales de Dermatologie et de Venereologie 2002;129(1S607-1S842):1S693.
Bleiker 1997 {published data only}
    1. Bleiker TO, Bourke J, Lear J, Eason L, Harling J, Hutchinson PE. A comparison of cryogun versus cotton buds for the treatment of warts (abstract and unpublished data). British Journal of Dermatology 1997;137(Suppl S50):26.
Braatz 1974 {published data only}
    1. Braatz JH, McAlistar BR, Broaddus MD. Ultrasound and plantar warts: a double blind study. Military Medicine 1974;139(3):199-201. - PubMed
Breitbart 1979 {published data only}
    1. Breibart EW. Controlled clinical trial with a new anti-wart preparation based on fluorouracil [Kontrollierte klinische Untersuchungen mit einem neuen Warzentherapeutikum auf Basis Fluorouracil]. Zeitshrift Hautkrankheiten 1979;57(19):853-5. - PubMed
Canpolat 2008 {published data only}
    1. Canpolat F, Cemil BC, Eskioglu F. Liquid nitrogen cryotherapy of plantar verrucae: Cryoblast is more effective than the cryo-spray. European Journal of Dermatology 2008;18(3):341-66. - PubMed
Ebrahimi 2007 {published data only}
    1. Ebrahimi S, Dabiri N, Jamshidnejad E, Sarkari B. Efficacy of 10% silver nitrate solution in the treatment of common warts: a placebo-controlled, randomized, clinical trial. International Journal of Dermatology 2007;46(2):215-7. - PubMed
El‐Tonsy 1999 {published data only}
    1. El-Tonsy MH, Anbar TA, El-Domyati M, Barakat M. Density of viral particles in pre and post Nd:YAG laser hyperthermia therapy and cryotherapy in plantar warts. International Journal of Dermatology 1999;38(5):393-8. - PubMed
Erbagci 2005 {published data only}
    1. Erbagci Z, Tuncel A. Therapeutic efficacy of topical imiquimod in recalcitrant cutaneous warts. [Abstract P08.68]. The 14th Congress of the European Academy of Dermatology and Venereology, 12-15th October 2005, London, UK. Journal of the European Academy of Dermatology & Venereology 2005;19(Suppl 2):236.
Fabbrocini 2001 {published data only}
    1. Fabbrocini G, Di Costanzo MP, Riccardo AM, Quarto M, Colasanti A, Roberti G, et al. Photodynamic therapy with topical delta-aminolaevulinic acid for the treatment of plantar warts. Journal of Photochemistry and Photobiology 2001;61(1-2):30-4. - PubMed
Gach 2005 {published data only}
    1. Gach JE, Humphreys F, Berth-Jones J. Randomized, double-blind, placebo-controlled pilot study to assess the value of free radical scavengers in reducing inflammation induced by cryotherapy. Clinical dermatology 2005;30(1):14-6. - PubMed
Goihman‐Yahr 1978 {published data only}
    1. Goihman-Yahr M, Fernandez J, Boatswain A, Convit J. Unilateral dinitrochlorobenzene immunopathy of recalcitrant warts (letter). Lancet 1978;1(8061):447-8. - PubMed
Gupta 2006 {published data only}
    1. Gupta A. Efficacy and safety of intense pulsed light therapies for treatment of resistant warts. [Abstract P2618]. American Academy of Dermatology 64th Annual Meeting, March 3-7 2006. Journal of the American Academy of Dermatology 2006;54(3):AB 190.
Johnson 2001 {published data only}
    1. Johnson SM, Robertson PK, Horn TD. Intralesional injection of mumps or candida skin test antigens: a novel immunotherapy for warts. Archives of Dermatology 2001;137(4):451-5. - PubMed
Jung 1971 {published data only}
    1. Jung EG, Grafe A. Virostatic treatment of eruptive warts. Preliminary report [Virustatische Behandlung eruptiver Warzen. Vorlaufige Mitteilung]. Deutsche Medizinishsce Wochenschrift 1971;96(48):1863-6. - PubMed
Kainz 1996 {published data only}
    1. Kainz JT, Kozel G, Haidovogel M, Smolle J. Morphometric assessment of common warts during homeopathic therapy: no difference to pure placebo. Journal of Investigative Dermatology 1996;105(3):503.
    1. Kainz JT, Kozel G, Haidvogl M, Smolle J. Homeopathic versus placebo therapy of children with warts on the hands: a randomized double-blind clinical trial. Dermatology 1996;193(4):318-20. - PubMed
    1. Smolle J, Prause G, Kerl H. A double-blind, controlled clinical trial of homeopathy and an analysis of lunar phases and postoperative outcome. A double-blind controlled clinical trial of homeopathy. Archives of Dermatology 1998;134(11):1368-70. - PubMed
Kang 1999 {published data only}
    1. Kang M, Liu J, Wang S. Comparative observation of immunoribonucleic acid and polyinosine for the treatment of verruca plana. Chinese Journal of Dermatology and Venereology 1999;13:318-20.
Kassis 1989 {published data only}
    1. Kassis V, Knudsen EA, Thomsen HK, Wilkinson W. Ultrasound in the treatment of hand and plantar warts. Journal of Dermatological Treatments 1989;1(2):69-70.
Khan 1998 {published data only}
    1. Khan MT, Cerio R, Watt R, Khan MT. The efficacy of Thuja Occidentalis on verruca pedis in children and adults. Journal of European Academy of Dermatology and Venereology 1998;11(Suppl 2):S150 (FC13-6).
Kim 2010 {published data only}
    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. Archives of Dermatology 2010;146(12):1431-3. - PubMed
Kubeyinje 1996 {published data only}
    1. Kubeinje EP. Evaluation of the efficacy and safety of 0.05% tretinoin cream in the treatment of plane warts in Arab children. Journal of Dermatological Treatments 1996;7(1):21-2.
Labecque 1992 {published data only}
    1. Labrecque M, Aduet D, Latulippe LG, Drouin J. Homeopathic treatment of plantar warts. Canadian Medical Association Journal 1992;146(10):1749-53. - PMC - PubMed
Lahti 1982 {published data only}
    1. Lanti A, Hannuksela M. Topical immunotherapy with tuberculin jelly for common warts. Archives of Dermatological Research 1982;273(1-2):153-4. - PubMed
Locke 1970 {published data only}
    1. Locke RK, Zang K. Controlled intralesional deposition of a sclerotic agent in verruca therapy. International Journal of Dermatology 1970;9(4):278-82. - PubMed
Lyell 1951 {published data only}
    1. Lyell A, Miles JAR. The myrmecia study: a study of inclusion bodies in warts. British Medical Journal 1951;1(4712):912-5. - PMC - PubMed
Ma 2000 {published data only}
    1. Ma HM, Gao WH, Zhang GQ. Clinical observation of 108 cases of verruca plana treated with Zhinyoutang made by us (Chinese). Chinese Journal of Leprosy & Skin Disease 2000;16(1):65.
Manchanda 1997 {published data only}
    1. Manchanda RK, Mehan N, Bahl R, Atey R. Double blind placebo controlled clinical trials of homeopathic medicines in warts and molluscum contagiosum. Central Council of Research in Homeopathy (CCRH) Quarterly Bulletin 1997;19:25-9.
Marchant 1974 {published data only}
    1. Marchant RE. Plantar warts. Chiropodist 1974;29:214-5.
Peng 2001 {published data only}
    1. Peng F, Li B, Huang N. A randomised controlled trial of polysaccharide nucleic acid fraction of BCG versus lecamsole in the treatment of verruca [Treatment of 46 cases of verruca plana with Sijikang injection liquid (Chinese)]. Journal of Clinical Dermatology 2001;30(3):185.
Penny 2005 {published data only}
    1. Penny L, Newcombe L. The effectiveness of low level laser therapy in the treatment of verrucae pedis. Australasian Journal of Podiatric Medicine 2005;39(1):7-10.
Pueyo 1990 {published data only}
    1. Pueyo S, Criscuolo M, Davidovich C, Zorzopulos J, Pesce A, Diaz A. Treatment of recurrent common warts with one low dose intralesional natural human leukocyte interferon alpha. Journal of Biological Regulator and Homeostatic Agents 1990;4(2):47-50. - PubMed
Schreiner 1995 {published data only}
    1. Schreiner T, Brzoska J, Fierlbeck G. Topical application of tretinoin, interferon beta and their combination in the treatment of flat warts. Journal of Dermatological Treatments 1995;6(1):17-9.
Shumer 1983 {published data only}
    1. Shumer SM, O'Keefe EJ. Bleomycin in the treatment of recalcitrant warts. Journal of the American Academy of Dermatology 1983;9(1):91-6. - PubMed
Stender 2006 {published data only}
    1. Stender IM, Borgbjerg FM, Villumsen J, Lock-Andersen J, Wulf HC. Pain induced by photodynamic therapy of warts. Photodermatology, Photoimmunology and Photomedicine 2006;22(6):304-9. - PubMed
Stern 1992 {published data only}
    1. Stern P, Levine N. Controlled localized heat therapy in cutaneous warts. Archies of Dermatology 1992;128(7):945-8. - PubMed
Stevens 1975 {published data only}
    1. Stevens DA, Ferrington RA, Merigan TC, Marinkovich VA. Randomised trial of transfer factor treatment of human warts. Clinical and Experimental Immunology 1975;21(3):520-4. - PMC - PubMed
Takigawa 1985 {published data only}
    1. Takigawa M, Oku T, Ginoza M, Yamada M, Yamamoto T, Kobayashi. Treatment of viral warts with pressure sensitive adhesive tape containing bleomycin sulphate. Archives of Dermatology 1985;121(9):1108. - PubMed
Xhao 2000 {published data only}
    1. Xhao XQ, Zhang YL, Shi P. Clinical observation of 58 cases of verruca plana treated by combination of Western medicine and traditional Chinese medicine [Chinese]. Chinese Journal of Leprosy and Skin Disease 2000;16(1):63.
Xia 2001 {published data only}
    1. Xia Q. Effectiveness observation of cimetidine combined with two external drugs in treating verruca plana (Chinese). Chinese Journal of Leprosy and Skin Disease 2001;17(1):69.
Yaghoobi 2009 {published data only}
    1. Yaghoobi R, Sadighha A, Baktash D. Evaluation of oral zinc sulfate effect on recalcitrant multiple viral warts: A randomized placebo-controlled clinical trial. Journal of the American Academy of Dermatology 2009;60(4):706-8. - PubMed
Yu 2000 {published data only}
    1. Yu KM, Hu P, Gong JF. Clinical observation of 180 cases of verruca plana treated by combination of Western medicine and traditional Chinese medicine. Chinese Journal of Leprosy and Skin Disease 2000;16(2):93.
Zedan 2009 {published data only}
    1. Zedan H, Hofny ER, Ismail SA. Propolis as an alternative treatment for cutaneous warts. International Journal of Dermatology 2009;48(11):1246-9. - PubMed

References to studies awaiting assessment

Bastuji‐Garin 2001 {published data only}
    1. Bastuji-Garin S, Laurent R, Basset-Seguin N, Bédane C, Combemale P, Dubertret L. [Photodynamic therapy with 5-aminolevulinic acid or placebo for recalcitrant foot and hand warts: randomised double-blind trial]. [French]. Annales de Dermatologie et de Vénéréologie 2001;128(10 Pt 1):1110-3. - PubMed
Dall'oglio 2012 {published data only}
    1. Dall'oglio F, D'Amico V, Nasca MR, Micali G. Treatment of cutaneous warts: an evidence-based review. [Review]. American Journal of Clinical Dermatology 2012;13(2):73-96. - PubMed

References to ongoing studies

ISRCTN78267267 {published data only}
    1. ISRCTN78267267. Cryotherapy versus Salicylic Acid with Monochloracetic Acid for the Treatment of Verrucae: A Randomised Controlled Trial. http://www.controlled-trials.com/ISRCTN78267267/.
NCT00155584 {published data only}
    1. NCT00155584. Topical 5-Aminolevulinic Acid Photodynamic Therapy for the Treatment of Verruca Vulgaris: Comparison of Red and Green Light-Emitting Diode Array. http://clinicaltrials.gov/ct2/show/NCT00155584.
NCT00254280 {published data only}
    1. NCT00254280. Treatment of Recalcitrant Hand and Foot Warts With Intense Pulsed Light and Paring Versus Paring Alone - a Randomized Controlled Trial With Blinded Response Evaluation. http://clinicaltrials.gov/ct2/show/NCT00254280.
NCT00973856 {published data only}
    1. NCT00973856. Evaluation of the Effectiveness of an Alcohol Based Hand Gel for the Reduction of Warts on the Hands. http://clinicaltrials.gov/ct2/show/NCT00973856.
NCT01059110 {published data only}
    1. NCT01059110. Comparison of Occlusive Dressings, Salicylate Ointment, Cryotherapy, Topical 5-fluoro-uracil and Imiquimod in Immunocompetent Patients Presenting Plantar Warts in Office-based Settings: a Randomized Clinical Trial. http://clinicaltrials.gov/ct2/show/NCT01059110.
NCT01084824 {published data only}
    1. NCT01084824. A Randomized Clinical Trial Examining the Efficacy of Treatment of Cutaneous Verruca Vulgaris in Adult Patients With Combined Liquid Nitrogen Cryotherapy and Topically Applied Cantharidin. http://clinicaltrials.gov/ct2/show/NCT01084824.
NCT01286441 {published data only}
    1. NCT01286441. A Randomized, Double-blind, Parallel-group, Multicenter, Vehicle-controlled Phase 2 Dose-Ranging Trial of the Safety and Efficacy of East Indian Sandalwood Oil in the Treatment of Common Warts (Verruca Vulgaris). http://clinicaltrials.gov/ct2/show/NCT01286441.

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