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Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Warts are a common disease caused by infection with various strains of the human papillomavirus (HPV). They appear on different sites of the body and in various forms, including common, flat, filiform, periungual, plantar, mosaic, and genital warts. Children most commonly present with common or periungual warts on hands and feet, whereas adults often present with common warts on the back of hands or filiform warts on the face and neck. Genital warts are discussed in another chapter.
Management Strategy
Most warts resolve spontaneously with time. However, patients and children’s parents often ask for treatment because of pain, social stigma, or concern over infectivity. In some cases warts cause ridicule, distorted self-image, impaired dexterity, worry over loss of employment, or a health and safety issue. Immunosuppressed patients may have extensive and resistant warts.
Most patients will treat themselves with over-the-counter preparations containing keratolytics before presenting to the dermatologist. Salicylic acid has the best evidence base and is the most commonly used therapy. It can be applied in various concentrations, with or without occlusion, and is suitable for any cutaneous site except the face. However, it requires frequent application, and it may cause irritation of the surrounding skin. Cryotherapy with dimethyl ether and propane applicator, silver nitrate pencils, and occlusive ‘duct tape’ are also available over the counter.
When a dermatologist sees patients with warts, the diagnosis and the possibility of spontaneous resolution and watchful waiting should be explained. The patient should be educated on how to apply topical preparations accurately. Keeping the warts well pared down with the use of a file or pumice stone after soaking is especially important for plantar warts. Young and healthy individuals with short duration of infection have the highest clearance rate. Cryotherapy with liquid nitrogen is one of the most common treatments used by the dermatologist. Liquid nitrogen is applied with a cryospray or a cotton bud. The wart should be frozen outward from the center to include a 2-mm rim of normal skin and the freeze maintained for 5 seconds. Cryotherapy is best repeated at 2- to 3-week intervals. Hyperkeratotic warts should be pared before cryotherapy and plantar warts treated with two freeze–thaw cycles. This treatment is painful and not always well tolerated by young children. The treated warts are sore and may blister. In pigmented skin, posttreatment hypopigmentation and hyperpigmentation can be a problem. Cryotherapy with liquid nitrogen can be combined with other topical preparations such as salicylic acid. Cryotherapy with carbon dioxide snow or dimethyl ether applicators does not produce temperatures as low as liquid nitrogen and is less effective.
If cryotherapy is not successful, then various other options are available, including immunotherapy with diphencyprone (DCP) or squaric acid, or intralesional therapy with Mycobacterium w vaccine, Bacillus Calmette–Guérin (BCG), purified protein derivative (PPD) of tuberculin antigen, or mumps or Candida antigen. Intralesional bleomycin may be injected into the wart or the solution applied to the wart and then repeatedly pricked through with a lancet. Laser ablation, hyperthermia, curettage and cautery, or even surgical excision of troublesome and resistant warts can be attempted, but the risk of scarring and recurrence of the warts in the scar can be a problem. The pulsed dye laser (PDL), thought to target the rich capillary network in warts, can be effective. Photodynamic therapy (PDT) is another option; however, pain during and after ALA (aminolevulinic acid)-PDT is well recognized. Other treatments used occasionally include 5-fluorouracil, zinc, levamisole, cimetidine, topical and oral retinoids, and imiquimod. Novel treatments included in this chapter include intralesional vitamin D 3 , microwave therapy, topical hydrogen peroxide, digoxin and furosemide gel, topical sandalwood oil, and green tea sinecatechins.
First - Line Therapies
Topical treatments for cutaneous warts
Kwok CS, Gibbs S, Bennett C, et al. Syst Rev 2013; 9: CD001781.
This updated review contained 26 new studies. According to 85 trials meeting the criteria for inclusion, the best evidenced therapy for cutaneous warts is for salicylic acid. Data pooled from six placebo-controlled trials showed a statistically significant result favoring the topical application of salicylic acid for warts at all sites (response rate [RR] 1.56, 95% confidence interval, 1.20–2.03). On the contrary, no benefit was found between cryotherapy and placebo in three studies.
Efficacy of 10% silver nitrate solution in the treatment of common warts: a placebo-controlled, randomized, clinical trial
Ebrahimi S, Dabiri N, Jamshidnejad E, et al. Int J Dermatol 2007; 46: 215–7.
A topical solution of 10% silver nitrate applied to the warts on alternate days for 3 weeks in 30 patients resulted in complete clearance in 63% of patients after 6 weeks in the treatment group versus no healing in the placebo group.
Cryosurgical treatment of warts: dimethyl ether and propane versus liquid nitrogen: case report and review of the literature
Nguyen NV, Burkhart CG. J Drugs Dermatol 2011; 10: 1174–6.
Other coolants are probably less effective than liquid nitrogen.
Cryotherapy versus salicylic acid for the treatment of plantar warts: a randomised controlled trial
Cockayne S, Hewitt C, Hicks K, et al. BMJ 2011; 342: d3271.
A study of 240 patients treated by healthcare professionals with liquid nitrogen, for up to four treatments, 2–3 weeks apart, was compared with patient self-treatment with 50% salicylic acid daily, for up to 8 weeks. Overall, 14% had complete clearance at 12 weeks, with no significant difference between the two groups.
A two-week interval is better than a three-week interval for reducing the recurrence rate of hand–foot viral warts after cryotherapy: a retrospective review of 560 hand–foot viral warts patients
Youn SH, Kwon IH, Park EJ, et al. Ann Dermatol 2011; 23: 53–60.
In a retrospective study with 560 patients, a 2-week interval was compared with a 3-week interval between cryotherapy with liquid nitrogen. For the 2- and 3-week groups, cure rates were 77% and 75%, respectively. Recurrence rates were 13% and 25%, and mean time to recurrence was 9.8 months and 6.9 months, respectively.
Two-week cryotherapy is optimal not only because of the rapid cure but also because of the lower recurrence rate.
Value of a second freeze–thaw cycle in cryotherapy of common warts
Berth-Jones J, Bourke J, Eglitis H, et al. Br J Dermatol 1994; 131: 883–6.
In a randomized trial 300 patients received cryotherapy with either one or two freeze–thaw cycles at a 3-week interval. In addition, all subjects used keratolytic wart paints, and plantar warts were pared before freezing. At 3 months, the cure rate was 57% from the single freeze technique versus 62% from the double freeze technique. In plantar warts, the cure rate was 41% from single freezing and 65% for double freezing, whereas in the hand warts there was no additional benefit from the second freeze.
Liquid nitrogen and salicylic/lactic acid paint in the treatment of cutaneous warts in general practice
Steele K, Irwim WG. J R Coll Gen Pract 1988; 38: 256–8.
In this randomized study, 207 patients with common hand warts and simple plantar warts were assigned to one of three treatment groups: cotton wool bud cryotherapy applied weekly, daily application of wart paint (lactic acid one part, salicylic acid one part, collodion four parts), or a combination of the two. Combination therapy cured 87% of common hand warts over a 6-week period and was significantly more effective than either agent used separately ( p <0.05). The results for simple plantar warts were disappointing, and no treatment regimen proved to be significantly better than any other.
Third-Line Therapies
| Immunologic therapy | |
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| Complementary and alternative therapies | |
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Immunologic Therapy
Topical 5% imiquimod long-term treatment of cutaneous warts resistant to standard therapy modalities
Grussendorf-Conen EI, Jacobs S, Rübben A, et al. Dermatology 2002; 205: 139–45.
In this study, 10 of 37 (27%) patients cleared with imiquimod self-applied twice daily with mean duration of 19 weeks.
Investigations of the efficacy of diphenylcyclopropenone immunotherapy for the treatment of warts
Suh DW, Lew BL, Sim WY. Int J Dermatol 2014; 53: e567–71.
Patients were sensitized with 0.1% diphenylcyclopropenone (DPCP), and 2 weeks after sensitization, DPCP was applied to warts weekly. High clearance rates of 141/170 patients (82.9%) were achieved in 434/511 lesions (84.9%). Immunotherapy proved more effective in patients <20 years of age and for hand warts. The mean ± standard deviation number of applications was 9.02 ± 2.59. Side effects occurred in 36 patients, with blistering at the sensitized site being the most common. No serious adverse events occurred.
Does immunotherapy of viral warts provide beneficial effects when it is combined with conventional therapy?
Choi JW, Cho S, Lee JH. Ann Dermatol 2011; 23: 282–7.
This study assessed the efficacy of DCP as an adjunctive to cryotherapy. Retrospective chart review of 124 patients with warts showed that DCP may be a successful adjuvant to cryotherapy in reducing the number of cryotherapy sessions.
Clinical efficacy of diphenylcyclopropenone immunotherapy as monotherapy for multiple viral warts
Park JY, Park BW, Cho EB, et al. J Cutan Med Surg 2018; 22(3): 285–9.
The records of 250 patients with multiple viral warts was analyzed retrospectively, evaluating clinical efficacy of DPCP monotherapy compared with cryotherapy and PDL therapy. The DPCP-only group ( n = 43) showed a lower clinical response (75.6%) than the cryotherapy-only group ( n = 171, 89.8%, p <0.01) and PDL-only group ( n = 36, 90.3%, p <0.01).
Squaric acid immunotherapy for warts in children
Silverberg NB, Lim JK, Paller AS, et al. J Am Acad Dermatol 2000; 42: 803–8.
In this retrospective study, 61 children had their warts treated with home application of 0.2% squaric acid, 3–7 nights per week, for at least 3 months, after initial sensitization with 2% squaric acid on the forearm. Complete clearance after 7 weeks of this treatment occurred in 58% of patients, partial clearance occurred in 18%, and no response occurred in 24%.
Treatment of common and plane warts in children with topical viable bacillus Calmette–Guerin
Salem A, Nofal A, Hosny D. Pediatr Dermatol 2013; 30: 60–3.
Topical BCG paste (containing 3 mg of salicylic acid, dissolved in 3 mL of glycerin) was applied to all warts in 40 children weekly for a maximum of 12 weeks. A control group of 40 children were treated with saline once weekly for same duration. Complete response occurred in 65% of children with common warts and 45% of plane warts with no response in the control group. A statistically significant difference was found between the active and control groups.
Immunotherapy in viral warts with intradermal Bacillus Calmette–Guerin vaccine versus intradermal tuberculin purified protein derivative: a double-blind, randomized controlled trial comparing effectiveness and safety in a tertiary care center in Eastern India
Podder I, Bhattacharya S, Mishra V, et al. Indian J Dermatol Venereol Leprol 2017; 83(3): 411.
Sixty patients received three doses of 0.1 mL of Bacillus Calmette–Guerin vaccine or tuberculin purified protein derivative (PPD) intradermally in the deltoid region at 4-weekly intervals. They were followed up for another month. Complete clearance was noted in 48.5% and in 18.5% of the tuberculin PPD group. The number of lesions reduced significantly from baseline in both the groups from the first follow-up visit onward.
Intralesional Candida antigen immunotherapy for the treatment of recalcitrant and multiple warts in children
Muñoz Garza FZ, Roé Crespo E, Torres Pradilla M, et al. Pediatr Dermatol 2015; 32: 797–801.
In this retrospective review, 220 children with refractory warts received three intralesional injections of 0.2 mL of Candida albicans antigen, one per visit, at 3-week intervals. Results showed that 156 (70.9%) had a complete response, 37 (16.8%) had a partial response, and 27 (12.2%) had no response. An average of 2.7 injections were required.
Two-year experience of using the measles, mumps and rubella vaccine as intralesional immunotherapy for warts
Na CH, Choi H, Song SH, et al. Clin Exp Dermatol 2014; 39: 583–9.
A retrospective study of 136 patients with various types of warts who were treated for a total of six times at 2-week intervals. Thirty-six patients (26.5%) experienced complete resolution with an average of five treatments; 51.5% experienced >50% reduction in size and number of warts. Common warts showed statistically higher treatment response than other types of warts.
Intralesional Mycobacterium w vaccine versus cryotherapy in treatment of refractory extragenital warts: a randomized, open-label, comparative study
Dhakar AK, Dogra S, Vinay K, et al. J Cutan Med Surg 2016; 20(2): 123–9.
In this prospective, comparative study of 66 patients, 33 patients were randomized to receive 0.1 mL Mycobacterium w (Mw) vaccine weekly and the other 33 received cryotherapy every 2 weeks. Both groups were treated until resolution of lesions or for a maximum of 12 doses. Complete clearance of treated warts was seen in 66.7% and 65.5% of patients in the Mw and cryotherapy groups, respectively. Mw vaccine and cryotherapy were found to be equally efficacious.
A double-blind, randomized controlled trial to compare the effectiveness and safety of purified protein derivative of tuberculin antigen with Mycobacterium w vaccine in the treatment of multiple viral warts
Chandra S, Sil A, Datta A, et al. Indian J Dermatol Venereol Leprol 2019; 85(4): 355–66.
Sixty-four patients with multiple warts were randomized (1:1) to receive either PPD or Mw vaccine, via intradermal injections of 0.1 mL of either drug administered fortnightly over the deltoid region, until complete resolution or a maximum of six doses. Patients were followed up for another 3 months for recurrence. The number of warts reduced significantly with treatment in both groups. Complete remission was seen in 68.8% of the Mw group and 50% of the PPD group. Adverse events were significantly more with Mw compared to PPD of tuberculin antigen in patients with warts.
Cimetidine therapy for recalcitrant warts in adults: is it any better than placebo?
Rogers CJ, Gibney MD, Siegfried EC, et al. J Am Acad Dermatol 1999; 41: 123–7.
In this double-blind, placebo-controlled study, 70 patients with multiple viral warts were randomized to cimetidine 25–40 mg/kg daily or placebo for 3 months. Cimetidine was found to be no more effective than placebo.
Cimetidine therapy for recalcitrant warts in adults
Glass AT, Solomon BA. Arch Dermatol 1996; 132: 680–2.
In this prospective study, 20 patients received cimetidine 30–40 mg/kg/day. Complete resolution or a dramatic improvement was achieved in 84% of the 18 patients after 3 months.
Topical zinc oxide vs. salicylic acid–lactic acid combination in the treatment of warts
Khattar JA, Musharrafieh UM, Tamim H, et al. Int J Dermatol 2007; 46: 427–30.
In this double-blind trial, 44 patients were treated with either 20% zinc oxide ointment or 15% salicylic acid ointment + 15% lactic acid ointment combination, twice daily for 3 months. In the zinc oxide group, 50% patients were cured versus 42% with salicylic acid–lactic acid.
Topical zinc sulfate solution for treatment of viral warts
Sharqie KE, Khorhseed AA, Al-Nuaimy AA. Saudi Med J 2007; 28: 1418–21.
Topical zinc sulfate solution used three times daily for 4 weeks led to a higher cure rate than water placebo in a double-blind trial of 40 patients with plane warts and 50 patients with common warts. The cure rate appeared to be dependent on the concentration of zinc solution used and was better for plane than common warts. For plane warts, cure rates were 85.7% for 10% zinc sulfate (6/7 patients), 42.8% for 5% zinc sulfate (3/7 patients), and 10% for placebo 10% (1/10 patients). For common warts, cure rates were 11%, 5%, and 0%, respectively.
Treatment of viral warts by intralesional injection of zinc sulphate
Sharquie KA, Al-Nuaimy AA. Ann Saudi Med 2002; 22: 26–8.
One hundred patients with 623 warts were divided into two groups. In the treatment group, 53 patients had 173 warts treated with 2% zinc sulfate intralesionally, whereas 176 warts were left untreated as control. Within 6 weeks in the treatment group 98% of the warts cleared versus none in the control group.
Evaluation of oral zinc sulfate effect on recalcitrant multiple viral warts: a randomized placebo-controlled clinical trial
Yeghoobi R, Sadighha A, Baktash D. J Am Acad Dermatol 2009; 60: 706–8.
After 2 months of treatment with oral zinc sulfate (10 mg/kg to a maximum of 600 mg daily), 78% of patients cleared their warts (25/32) compared with 13% in the placebo group (3/23). The baseline serum zinc levels did not differ significantly between the two groups, but mean levels in both groups were low pretreatment.
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