Treatment of warts

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Permalink: https://bitbucket.org/snippets/jhult/6eGney/

Author: Jonathan Hult

Version: 1.0.1

License: Attribution 4.0 International (CC BY 4.0)

Data gathered from:

PMC® (PubMed Central®) PubMed

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Treatment methods

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1. Overview
2. Intralesional/Topical - Zinc
3. Topical - Tape Occlusion
4. Topical - Salicylic acid (30%) + podophyllin (5%) + cantharidin
5. Topical - Imiquimod
6. Topical - 2% Povidone–Iodine
7. Cryotherapy - Liquid Nitrogen
8. Laser - Long-Pulsed Nd:YAG
9. Intralesional - Vitamin D3
10. Intralesional - Bleomycin
11. Intralesional - Candida
12. Oral - Cimetidine
13. Other (limited research)

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Overview

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Immunomodulators in warts: Unexplored or ineffective?

Good overall read PMC4372902 Full-text

Systematic review - PMC119440

Study selection: Randomised controlled trials of any local treatment for uncomplicated cutaneous warts. All published and unpublished material was considered, with no restriction on date or language. Results: 50 included trials provided generally weak evidence because of poor methods and reporting. The best evidence was for topical treatments containing salicylic acid. Data pooled from six placebo controlled trials showed a cure rate of 75% (144 of 191) in cases compared with 48% (89 of 185) in controls (odds ratio 3.91, 95% confidence interval 2.40 to 6.36). Some evidence for the efficacy of contact immunotherapy was provided by two small trials comparing dinitrochlorobenzene with placebo. Evidence for the efficacy of cryotherapy was limited. No consistent evidence was found for the efficacy of intralesional bleomycin, and only limited evidence was found for the efficacy of topical fluorouracil, intralesional interferons, photodynamic therapy, and pulsed dye laser. Conclusion: Reviewed trials of local treatments for cutaneous warts were highly variable in methods and quality, and there was a paucity of evidence from randomised, placebo controlled trials on which to base the rational use of the treatments. There is good evidence that topical treatments containing salicylic acid have a therapeutic effect and some evidence for the efficacy of dinitrochlorobenzene. Less evidence was found for the efficacy of all the other treatments reviewed, including cryotherapy.

Review - PMC5154650

Conclusion: High-quality evidence shows warts have resolved with cryotherapy or salicylic acid (SA) more often than with no treatment at 13 weeks. Cryotherapy causes more pain and blistering but gives greater patient satisfaction. Evidence for duct tape is limited and inconsistent. Salicylic acid is cheap and over-the-counter concentrations vary from 17% to 40%. Cryotherapy is less convenient, more painful, and more costly. For cryotherapy, frequent treatment (eg, 1- to 2-week intervals) might result in earlier cure and less recurrence, but more blistering.

Systematic review - 22972052

Study Criteria: Randomised controlled trials (RCTs) of topical treatments for cutaneous non-genital warts. 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. Conclusion: 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.

Guidelines for the Management of Cutaneous Warts

Sponsoring Organization: British Association of Dermatologists

Despite frequent use, few wart treatments have received large randomized clinical efficacy trials. Based on the published literature, estimated cure rates of placebo administered for 3 to 4 months are 20% to 30%, which complicates interpretation of nonrandomized studies. These guidelines highlight the need for new, reliable wart treatments and help provide an evidence-based rationale for currently available treatments. - Meta-analysis shows preparations containing salicylic acid as the active ingredient (the most common destructive wart therapy) to be more effective than placebo but less effective than cryotherapy for warts of the hands. - Liquid nitrogen cryotherapy is the most common treatment used by physicians. Results for plantar warts, but not hand warts, can be improved by paring the wart prior to treatment. The median cure rate with cryotherapy is 49%. It is more effective on the hands than on the feet. After 6 weeks, cryotherapy every 4 weeks produced cure rates equal to treatment every 2 to 3 weeks. - No high-quality studies have evaluated curettage, cautery, or CO2 laser treatment. - A few studies show that photodynamic therapy with topical aminolevulinic acid and pulsed dye laser are more effective than placebo. These methods may be combined with other therapies. - Topical 5% 5-fluorouracil applied with occlusion for up to 4 weeks has been shown to cure up to 95% of warts. In addition, 0.5% 5-FU in combination with salicylic acid was significantly better than salicylic acid alone. Several open-label studies show response rates of 65% to 85% with intralesional bleomycin, albeit with possible pain at the injection site. - Topical retinoids are effective primarily for flat warts. - Diphencyprone and squaric acid dibutylester are immunomodulatory agents seen in retrospective studies to regress warts in >85% of patients. Similar results were noted with intralesional candida, mumps, and tuberculin antigens. H2-receptor antagonists are thought to augment cell-mediated immunity. Cimetidine, however, was ineffective in randomized, controlled trials. Ranitidine was found to cause complete wart regression in 49% of patients in an open-label study. Imiquimod, used primarily for condyloma acuminata, was reported in open-label trials to regress 50% to 76% of cutaneous warts. - Little evidence supports alternative therapies - acupuncture, homeopathy, hypnosis - as effective wart treatments.

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Zinc

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Intralesional injection - Zinc Sulphate (2%)

PMC4830730

Results: From 225 warts injected, 135 warts (60%) cured from the first session, 51 warts (22.67%) cured from the second session, and 12 warts (5.33%) cured from the third session. There is no significant relation between improvement and patient's ages, duration, or number of warts (P > 0.05). Side effects: All patients complained from pain during injection, and all treated lesions showed redness, tenderness, and swelling in the first 3 days after injection. Late complications were postinflammatory hyperpigmentation in 90 patients (75%), scaring in 9 patients (7.5%), and ulceration in 3 patients (2.5%). Recurrence: Occurred in 3 lesions (1.33%). Conclusion: The clinical data indicate that intralesional injection of 2% zinc sulfate is an effective maneuver in the treatment of common warts; however, its associated complications limit its use.

17259762

Results: The total clearance rate of the treated lesions were 98.2% within 6 weeks of follow-up (80.92% of lesions needed a single injection and showed total clearance within 2 weeks), while none of the control lesions showed any spontaneous clearance within the same period.

Topical - Zinc Sulfate (10%)

17768472

Conclusion [by Hult]: Effective for plane warts. Not effective for common warts.

Results In the pilot trial, the full response for plane warts was 80%, while the full response for patients with plane warts in double blinded trial was 85.7%, 42.8% and 10% for those using 10% and 5% zinc sulphate solutions and distilled water subsequently. The difference was statistically significant (p<0.008). The full response for patients with common warts were 11%, 5% and 0% for those who used 10% and 5% zinc sulphate solutions and distilled water respectively, the difference was statistically insignificant. Recurrence: No recurrence of warts occurred during follow up that ranged from 2-6 months after therapy.

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Topical - Tape Occlusion

17088514

Method: Duct tape applied to the wart or placebo, a corn pad (protection ring for clavi), applied around the wart for 1 night a week. Both treatments were applied for a period of 6 weeks. Patients were blinded to the hypothesis of the study. Results: After 6 weeks, the wart had disappeared in 16% of the children in the duct tape group compared with 6% in the placebo group (P = .12). The estimated effect of duct tape compared with placebo on diameter reduction of the treated wart was 1.0 mm (P = .02, 95% confidence interval, -1.7 to -0.1). After 6 weeks, in 7 children (21%) in the duct tape group, a surrounding wart had disappeared compared with 9 children (27%) in the placebo group (P = .79). Fifteen percent of the children in the duct tape group reported adverse effects such as erythema, eczema, and wounds compared with 0 in the placebo group (P = .14). Conclusion: In a 6-week trial, duct tape had a modest but nonsignificant effect on wart resolution and diameter reduction when compared with placebo in a cohort of primary school children.

PMC3662932

Conclusion: We found that imiquimod 5% cream and duct tape occlusion therapy was appreciably more effective than petrolatum and duct tape occlusion therapy. Limitations: Small samples size; no placebo

12361440

Results: Of the 51 patients completing the study, 26 (51%) were treated with duct tape, and 25 (49%) were treated with cryotherapy. Twenty-two patients (85%) in the duct tape arm vs 15 patients (60%) enrolled in the cryotherapy arm had complete resolution of their warts (P =.05 by chi(2) analysis). The majority of warts that responded to either therapy did so within the first month of treatment. Conclusion: Duct tape occlusion therapy was significantly more effective than cryotherapy for treatment of the common wart.

Interpreting Negative Results From an Underpowered Clinical Trial

Conclusions: In summary, this study tests an inexpensive treatment for a common condition, and the results contradict an earlier randomized, controlled trial that had flaws of its own.3 However, several methodological limitations in the study by de Haen and colleagues lead us to question the investigators’ conclusions that the effects of duct tape were not significant. Further studies that address the limitations of these extant studies are needed before such definitive conclusions can be drawn.

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Topical - salicylic acid (30%) + podophyllin (5%) + cantharidin

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6504780

One hundred and twenty-one children with plantar warts were treated with a topical preparation containing salicylic acid, 30%; podophyllin, 5%; and cantharidin, 1%. One hundred patients or their families were reached 6 months to 1 year later. This treatment was effective in 81 cases.

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Topical - Imiquimod (5%) - self-administered

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11069514

Method: Imiquimod 5% cream was self-applied by the patients to the warts or mollusca once daily for 5 days per week and left in place overnight. Assessment for response and the occurrence of side-effects was performed every 4 weeks until clinical cure or up to a maximum of 16 weeks. Results: Twenty-eight of 50 (56%) patients with warts achieved a total clearance (n = 15; 30%) or a > 50% reduction in wart size (n = 13; 26%) after a mean treatment period of 9.2 weeks. Twelve of 15 (80%) patients with mollusca achieved a total clearance (n = 8; 53%) or a > 50% reduction in molluscum size (n = 4; 27%). There was no difference in response with regard to gender, human immunodeficiency virus serostatus or atopic predisposition. Conclusion: Patient-applied 5% imiquimod cream holds promise as an effective treatment of common warts and mollusca in a difficult-to-treat patient population.

12095879

Method: We report 10 cases of recurrent warts treated with a potential new topical therapy, imiquimod 5% cream. Results: Nine of the 10 patients were successfully treated with imiquimod 5% cream applied, under occlusion, once daily for 4 weeks. Recurrence: No recurrences were reported during 3 months of follow up.

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Topical - 2% Povidone–Iodine

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PMC4674451

Method: Twenty-one patients aged 8 years and older were enrolled in this single-center, randomized, double-blind, vehicle-controlled Phase II clinical trial to assess the efficacy, safety and tolerability of twice-daily application of a novel 2% topical povidone–iodine solution in a dimethyl sulfoxide vehicle for 12 weeks duration. Patients were block randomized into two groups consisting of 14 patients in the active arm and 7 patients in the vehicle only arm. All patients were evaluated at baseline, week 4, 8 and 12 and the results compared for overall Global Aesthetic Improvement Scale (GAIS) improvement. Results: There were a total of 21 patients included in the study. Sustained improvement in the GAIS scale was observed at the final week 12 exam visit in 77% of subjects in the treatment arm and 33% of patients in the control arm. There were no serious safety or tolerability issues reported. Conclusion: Twice-daily topical povidone–iodine solution in the novel vehicle employed for this study is an effective, safe and easy-to-use treatment for common warts. Further study of this agent in expanded Phase II and Phase III clinical trials is warranted.

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Cryotherapy - Liquid Nitrogen

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PMC1520330 (full-text)

Conclusion: While these results leave much to be desired, they are sufficiently good to justify the use of this method at least in selected cases of warts until some more specific treatment becomes available.

7718461

Summary: We studied the efficacy, and time to clearance, of more frequent cryotherapy of viral warts, by randomizing 225 patients to receive treatment at 1-, 2- or 3-weekly intervals. The mean times to clearance of warts in each group were 5.5, 9.5 and 15 weeks in the weekly, 2-weekly and 3-weekly groups, respectively (P < 0.01). Cure rates after 3 months correlated with frequency of treatment (P < 0.05). After 3 months, 43% (66% of non-defaulters) had cleared in the group treated weekly, 37% (47%) of the group treated every 2 weeks, and 26% (30%) of those treated every 3 weeks. The mean numbers of treatments needed to achieve clearance were similar in each group (5.5, 4.75 and 5 treatments). After 12 treatments, cure rates were similar for all three groups: 43% for the weekly-treated group (3 months), 48% for the 2-weekly group (6 months), and 44% for the 3-weekly group (9 months). Percentage cure is related to the number of treatments received, and independent of the interval between treatments. A more rapid cure may, therefore, be achieved by more frequent treatment.

PMC3119999

Methods: A retrospective study was designed to compare a 2 week interval and a 3 week interval between cryotherapy sessions on hand-foot viral warts with respect to cure rate, recurrence rate, treatment number, duration of treatment, mean time to recurrence and adverse events. Results: A total of 560 patients were enrolled. The overall cure rate was 75.7% and the recurrence rate was 19.6%. The mean time to recurrence was 7.8 months (range 1~26 months). For the 2-week and 3-week groups, cure rates were, respectively, 76.6% (196) and 75.0% (228); recurrence rates were 13.3% (26) and 25.0% (57). The mean time to recurrence was 9.8 months and 6.9 months, respectively. Adverse events were not statistically different. Conclusion: We suggested that 2-week cryotherapy is optimal not only because of the rapid cure but also because of the lower recurrence rate and similar adverse events.

11703280

Method: Patients attending a dedicated wart clinic were randomized to receive either a traditional freeze or a 10-s sustained freeze with liquid nitrogen delivered by a spray gun. Two hundred patients were recruited, 100 in each group. Results: After five treatments, 49 patients in the 10-s freeze group were clear of warts (64% of non-defaulters) as compared with 31 (39%) of those in the traditional freeze group (chi2 = 6.7; P = 0.009). Seventy-four patients in the 10-s freeze group as compared with 59 in the traditional freeze group had either improved or cleared after five treatments (chi2 = 5.0; P = 0.02). Side effects: Morbidity was significantly greater in the 10-s freeze group. Sixty-four patients suffered pain or blistering as compared with 44 in the traditional freeze group (chi2 = 10.8; P = 0.0045). Five patients were withdrawn from the 10-s freeze group because of pain as compared with one patient in the traditional freeze group. Conlusions: A 10-s sustained freeze is more effective in the cryotherapy of viral warts but carries a significantly greater morbidity in terms of pain and blistering.

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Laser - Long-Pulsed Nd:YAG

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PMC2752774 (full-text)

Over the course of 1 yr, 369 patients with recalcitrant or untreated warts were exposed to a long-pulsed Nd:YAG laser. The following parameters were used: spot size, 5 mm; pulse duration, 20 msec; and fluence, 200 J/cm2. No concomitant topical treatment was used. In all, 21 patients were lost during follow up; hence, the data for 348 patients were evaluated. Results: The clearance rate was 96% (336 of the 348 treated warts were eradicated). The clearance rate of verruca vulgaris after the first treatment was very high (72.6%), whereas the clearance rate of deep palmopantar warts after the first treatment was low (44.1%). Recurrence: During a median follow-up period of 2.24 months (range, 2-10 months), 11 relapses were seen (recurrence rate, 3.27%). In conclusion, long-pulsed Nd:YAG laser is safe and effective for the removal or reduction of warts and is less dependent on patient compliance than are other treatment options.

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Intralesional - Vitamin D3

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PMC5561717

Results: In total, 33 of 42 patients (78.57%) showed complete response, 6 patients (14.28%) showed moderate response and three patients (7.14%) showed mild response. Recurrence: Observed in one patient with the palmoplantar wart. Side effects: No serious adverse effects were reported. Limitations: Lack of control group was the main drawback in our study.

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Intralesional - Bleomycin

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8977721

Method: We have used a new technique of bleomycin injection to treat intractable palmar, plantar and periungual warts. Following local anaesthesia with topical EMLA (lignocaine and prilocaine) cream, 1 mg/ml bleomycin solution was dropped on to the wart and 'pricked' into the wart using a Monolet needle. Results: We achieved 92% success rate which compares well with other authors whose success rates with intralesional bleomycin vary between 33 and 92%. We conclude that this technique of intralesional bleomycin therapy is an effective, safe and generally well tolerated treatment for recalcitrant warts.

19439878

Method: Patients were randomized using computer-generated codes to receive either cryotherapy (double freeze-thaw cycle) or IL bleomycin (0.1% solution with concurrent anesthesia) for a maximum of four treatments 3 weeks apart and a maximum of five warts treated in each visit for both groups. Patients had their warts measured at base-line and with each return visit including a post treatment follow-up that was 8 weeks apart from last treatment taken. Results: Of the 73 patients completing the study, 39 (53%) were treated with IL bleomycin and 34 (47%) were treated with cryotherapy. Out of 155 treated warts, 87 (56%) were treated with IL beomycin and 68 (44%) were treated with cryotherapy. The clearance rates in context of number of patients and number of warts were 94.9% and 97% for bleomycin and 76.5% and 82% for cryotherapy respectively (P < 0.05 by x(2) analysis and RR = 7.67). Conclusion: IL bleomycin injection was significantly more effective than cryotherapy for treatment of cutaneous wart.

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Intralesional - Candida

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PMC3778775

Results: In these 34 patients, 19 (56%) showed a complete resolution of warts at all places on the body.

15897380

Objectives: To determine rates of wart resolution in response to injection of antigen alone, antigen plus interferon alfa-2b, interferon alfa-2b alone, and normal saline; and to compare response according to viral type, major histocompatibility complex antigens, and peripheral blood mononuclear cell proliferation to autologous human papillomavirus antigen before and after injection. Results: Responders were observed in all treatment arms, but were significantly more likely to have received antigen (P<.001). Resolution of distant untreated warts was observed, and was significantly more likely in subjects receiving antigen (P<.001). Interferon did not significantly enhance the response rate (P = .20) and did not differ from normal saline (P = .65). No viral type or major histocompatibility complex antigen correlated with response or lack of response (P>.99 and P = .86, respectively). A positive peripheral blood mononuclear cell proliferation assay result (2 times pretreatment levels) was significantly more likely among responders (P = .002). While there was no significant difference in response based on sex (P = .56), older subjects (>40 years) were less likely to respond (P = .01).

DOI: 10.4103/0019-5154.117301 (full-text)

Results: Of the 40 patients enrolled in the study, 34 completed the total treatment protocol of three injections and 6 months of follow-up. In these 34 patients, 19 (56%) showed a complete resolution of warts at all places on the body. In addition, two patients (6%) showed a partial or complete resolution of the treated wart, but there was no effect on the untreated warts. Thirteenpatients (38%) failed to show any response to the treatment regimen. Recurrence: In all patients showing resolution of all the warts, there were no relapses at any site over the next 6 months of follow-up. Side effects: The most common adverse effect seen was pain during the intralesional injection. Conclusion: Intralesional Candida immunotherapy seems to be an effective treatment option in more than half of the patients who fail to show a positive response to destructive modes of treatment or in whom there are multiple recurrences. Limitations: The small sample size and lack of control group are the main limitations of the study.

15996350 - complications in 1 patient

Side effects: Within 24 hours, the patient reported pain, edema, and a purple hue to only the index finger. Incision of the finger demonstrated no hematoma or compartment syndrome.

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Oral - Cimetidine

10411426

Three open-label, uncontrolled studies have documented successful treatment of warts with cimetidine, whereas two placebo-controlled, double-blind studies and two open-label comparative trials have failed to demonstrate efficacy. This double-blind, placebo-controlled study was designed with stringent enrollment and outcome criteria to minimize the confounding issue of spontaneous remission. Efficacy was not statistically superior to that of placebo, but a trend toward efficacy was suggested for younger subjects.

10333620

Hypothesis: Given the different target activities of immunomodulation by levamisole and cimetidine, we questioned whether the combination might be more effective and conducted this double-blind comparative trial of a combination of cimetidine and levamisole versus cimetidine alone. Forty-eight patients with multiple recalcitrant warts were assigned to two treatment groups (A and B) in double-blind fashion. Of the 48 patients, 22 in group A and 21 in group B were able to be evaluated. Results: At the end of therapy, cure rates obtained were 45.5% (10/21) in cimetidine treated patients (group A) and 85.7% (18/21) in combination treated patients (group B). A statistically significant improvement was seen in patients treated with the combination of levamisole and cimetidine (P < 0.01). A similar statistically significant result was obtained on using intention to treat analysis (P < 0.02). The rate of regression was faster in group B (average regression period of 7 weeks compared with 10 weeks in group A). Conclusion: The present study demonstrated that the combination of cimetidine with levamisole is more effective than cimetidine alone and is a highly effective therapy for the treatment of recalcitrant warts.

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Other (limited research)

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Topical - Vitamin A

• PMC3274422
• Full-text

Topical - Sandalwood Album Oil

• PMC5749697

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