Key Publications Plantar Warts

Plantar Warts Publications

Plantar Warts Background Information

  • Plantar Warts: Epidemiology, Pathophysiology, and Clinical Management. Witchey DJ, Witchey NB, Roth-Kauffman MM, Kauffman MK. The Journal of the American Osteopathic Association 2018; 118(2): 92-105.
  • Verrucae plantaris (plantar warts) are common cutaneous lesions of the plantar aspect of the foot that are caused by the human papillomavirus (HPV). Ubiquitous in our environment, asymptomatic infection with HPV occurs frequently, with most infections controlled or cleared by cellular and humoral immune responses. However, certain populations have been observed to manifest plantar warts at higher rates compared with the general population, placing them at increased risk for wart-induced pain and complications.
  • Plantar warts shed HPV, which can then infect other sites in the plantar region or spread to other people. Although controlling risk factors is useful in preventing infection, the pervasive nature of HPV makes these preventive measures frequently impractical. This literature review outlines the current knowledge regarding the relationship between plantar wart pathophysiology, HPV transmission, and epidemiologic characteristics.
  • Given the high propensity for treatment resistance of plantar warts and no established, practical, and reliable method of prevention, HPV prophylaxis for populations that demonstrate high rates of plantar warts may be of benefit in controlling the spread of lesions.
  • https://doi.org/10.7556/jaoa.2018.024
  • Warts Transmitted in Families and Schools: A Prospective Cohort. Bruggink SC, Eekhof JAH, Egberts PF, van Blijswijk SCE, Assendelft WJJ, Gussekloo J. Pediatrics. 2013; 131(5): 928-934.
  • Background and Objective: Cutaneous warts are common in primary schoolchildren; however, knowledge on the routes of transmission of human papillomavirus (HPV) causing warts is scarce. This study examines the association between the degree of HPV exposure and incidence of warts in primary schoolchildren to support evidence-based recommendations on wart prevention.
  • Methods: In this prospective cohort study, the hands and feet of all children in grades 1 to 7 (aged 4–12 years) of 3 Dutch primary schools were inspected for the presence of warts at baseline and after 11 to 18 months of follow-up. Data on the degree of HPV exposure included information obtained from parental questionnaires: preexistent warts, warts in family, prevalence of warts at baseline in the class, and use of public places (eg, swimming pools).
  • Results: Of the 1134 eligible children, 97% participated; the response rate from parental questionnaires was 77%, and loss to follow-up was 9%. The incidence for developing warts was 29 per 100 person-years at risk (95% confidence interval [CI] 26–32). Children with a white skin type had an increased risk of developing warts (hazard ratio [HR] 2.3, 95% CI 1.3–3.9). Having family members with warts (HR 2.08, 95% CI 1.52–2.86) and wart prevalence in the class (HR 1.20 per 10% increase, 95% CI 1.03–1.41) were independent environmental risk factors.
  • Conclusions: The degree of HPV exposure in the family and school class contributes to the development of warts in schoolchildren. Preventive recommendations should focus more on limiting HPV transmission in families and school classes, rather than in public places.
  • https://pediatrics.aappublications.org/content/131/5/928
    • Paid Access
  • Wart (Plantar, Verruca Vulgaris, Verrucae). Al Aboud AM, Nigam PK. StatPearls. 2020.
  • Warts are benign lesions that occur in the mucosa and skin. Warts are caused by the human papillomavirus (HPV), with over 100 types of HPV identified. HPV may occur at any site. The primary manifestations of HPV infection include common warts, genital warts, flat warts, deep palmoplantar warts (Myrmecia), focal epithelial hyperplasia, Epidermodysplasia verruciformis, and Plantar cysts. Warts may be transmitted by direct or indirect contact. Events that disrupt the normal epithelial barrier increase the likelihood of developing warts. Treatment may be difficult. Warts often resolve spontaneously within a few years. Some high-risk HPV subtypes are associated with malignancies, including types 6, 11, 16, 18, 31, and 35. Malignant transformation usually is seen in patients with genital warts and immunocompromised patients. HPV types 5, 8, 20, and 47 have oncogenic potential leading to epidermodysplasia verruciformis.
  • https://www.ncbi.nlm.nih.gov/books/NBK431047/

Current Management of Plantar Warts

Treatment Landscape of Plantar Warts

  • Topical Treatments for cutaneous warts. Kwok CS, Gibbs S, Bennett C, Holland R, Abbott R. Cochrane Database of Systematic Reviews. 2012; 9: 1-180
  • 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.
  • https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001781.pub3/full
    • Paid access
  • The Effectiveness of Cutaneous Wart Resolution with Current Treatment Modalities. Ringin SA. Journal of Cutaneous and Aesthetic Surgery. 2020; 13(1): 24–30.
  • Non-venereal warts are a frequent dermatological presentation with potential spontaneous regression in immunocompetent adults and children within 2 years. Evidence shows that conventional wart treatments are not a guaranteed treatment modality and can carry concerns regarding safety.
  • The aim of this literature review was to identify the most effective treatments for wart resolution to guide clinical practice while identifying areas for further research. A systematic literature review was performed to determine the current treatment modalities for non-anogenital cutaneous warts in immunocompetent individuals and their effectiveness. Articles were categorized into one of eight groups depending on anatomical location, population age, or recalcitrant status with ranked levels of evidence.
  • This literature review highlights a variety of treatments for non-venereal warts shown to be effective. In this instance where optimal evidence-based treatments are not available, clinical experience determines the most appropriate clinical practice. Further reproducible immunotherapy research on wart resolution is required to enable clear comparisons of these treatment modalities to conventional methods. Future clinical practice will require the human papillomavirus type to target the wart treatment accordingly; however, further research is required to determine these correlations
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335473/
  • Treatment of cutaneous viral warts in children: a review. Soenjoyo KR, Chua BWB, Wee LWY, Koh MJA, Ang SB. Dermatologic Therapy. 2020; e14034.
  • Viral warts or verruca are very common skin infections in children. Although benign, lesions can be extensive, painful, bleed, or lead to cosmetic disfigurement. Although spontaneous resolution can occur, parents often bring their children for treatment, especially when they are symptomatic.
  • Many publications have assessed the efficacy and safety of treatment of warts in adults. However, treatment in children can be challenging due to their immune responses and lower threshold for pain.
  • We review the current literature on the methods, efficacy, and side effect profile of common treatment modalities for cutaneous viral warts in children. There is evidence that salicylic acid and cryotherapy are effective, and although cryotherapy is more effective, there is a higher risk of side effects such as pain and blistering. Combination treatment with salicylic acid and cryotherapy may reduce these side effects.
  • Although there is limited data, other treatment options such as cantharidin, immunotherapy and other mechanical therapies, for example, carbon dioxide lasers, may also be considered, especially for recalcitrant lesions.
  • https://onlinelibrary.wiley.com/doi/abs/10.1111/dth.14034
    • Paid access

Cantharidin Use in Plantar Warts

  • Efficacy and Safety of Topical Cantharidin Treatment for Molluscum Contagiosum and Warts: A Systematic Review. Vakharia PP, Chopra R, Silverberg NB, Silverberg JI. American Journal of Clinical Dermatology. 2018;19(6):791-803.
  • Background and objective: Topical cantharidin is routinely used for the treatment of molluscum contagiosum and warts. The objective of this systematic review is to assess the efficacy and safety of topical cantharidin treatment for molluscum contagiosum and warts.
  • Methods: We performed a systematic review of studies assessing topical cantharidin treatment of molluscum contagiosum or warts. We searched the databases of Cochrane, EMBASE, GREAT, LILACS, MEDLINE, and Scopus. Two authors performed the study selection and data extraction.
  • Results: Twenty studies (1958-2018) met inclusion/exclusion criteria. Twelve studies assessed warts, and eight studies assessed molluscum contagiosum. Overall, 1752 patients were included (range 0.3-62 years; specified in 15 studies). Clearance rates with topical cantharidin for molluscum contagiosum were variable (range 15.4-100%). Significant clearance of warts with maintenance of clearance was demonstrated with topical cantharidin alone. Topical cantharidin in combination with podophyllotoxin and salicylic acid demonstrated efficacy for plantar warts (pediatric and adult; clearance rate range 81-100%; four studies had 100% clearance), with the majority clearing after a single treatment. Satisfaction with cantharidin therapy was high, especially in molluscum contagiosum. Pain (7-85.7%), blistering (10-100%), and hyper-/hypopigmentation (1.8-53.3%) were the most commonly occurring adverse effects with cantharidin treatment.
  • Conclusion: Topical cantharidin demonstrated clearance of warts, particularly in combination with podophyllotoxin and salicylic acid, and modest benefit for pediatric molluscum contagiosum with good tolerability and safety.
  • https://link.springer.com/article/10.1007%2Fs40257-018-0375-4
    • Paid access
  • Safety and effectiveness of cantharidin-podophyllotoxin-salicylic acid in the treatment of recalcitrant plantar warts. López López D, Vilar Fernandez JM, Losa Iglesias ME, Alvarez Castro C, Romero Morales C, Garcia Sanchez MM, et al. Dermatologic Therapy. 2016;29:269–73.
  • The aim of our study was to evaluate the efficacy and safety of topical cantharidin–podophyllotoxin–salicylic acid (CPS) treatment of recalcitrant plantar warts (RPW). This study was carried out in a health center in the city of A Coruña (Spain) between January and December 2013.
  • A total of 75 patients completed all the stages of the research process. Information related to treatment with CPS and adverse effects was abstracted from medical records. Of 93 potential patients identified, 75 had at least one follow‐up visit or telephone call after treatment and were included in this study.
  • Patients experienced an average of 5.4 visits until complete resolution of their plantar wart occurred, although CPS was not applied at every visit. Fifty‐four patients required one application to eliminate the wart and 21 patients required two applications/patient.
  • Seventy‐seven percent of patients experienced blistering – an expected therapeutic side effect. All patients experienced some form of an adverse event, the most common being pain (81.3%) and significant blistering (15%). Other side effects were rare (18.7%) and included pruritus, possible mild infection, significant irritation, and bleeding.
  • All patients reported treatment, supporting our results that CPS is a safe and efficacious treatment modality for RPW and should be considered when symptomatic infection necessitates treatment.
  • https://onlinelibrary.wiley.com/doi/abs/10.1111/dth.12356
    • Paid access
  • Application of Cantharidin and Podophyllotoxin for the Treatment of Plantar Warts. Becerro de Bengoa Vallejo R, Losa Iglesias ME, Gómez-Martín B, Sánchez Gómez R, Sáez Crespo A. Journal of the American Podiatric Medical Association. 2008; 98 (6): 445–450.
  • Background: A variety of treatment modalities have been described for cutaneous warts. We sought to determine the safety and efficacy of a topical formulation of cantharidin, podophyllotoxin, and salicylic acid in the treatment of plantar warts. This combination treatment is widely used in Europe and elsewhere but has not been described in the podiatric medical literature.
  • Methods: A retrospective study was conducted of 144 patients with simple or mosaic plantar warts who were treated with a topical, pharmacy-compounded solution of cantharidin, 1%; podophyllotoxin, 5%; and salicylic acid, 30%. All of the patients, aged 8 to 52 years (mean ± SD, 20.9 ± 11.0 years), were treated according to the authors standard protocol. Of the 144 patients, 92 were being treated for the first time. None of the 52 previously treated patients had received more than one other type of treatment in the past.
  • Results: After 6 months of follow-up, complete eradication of the plantar warts was noted in 138 of the 144 patients (95.8%). Of these patients, 125 (86.8%) required a single application of the solution, and 13 (9.0%) needed two or more applications. No significant adverse effects or complications were observed.
  • Conclusion: A topical solution of cantharidin, podophyllotoxin, and salicylic acid was found to be safe and effective in the treatment of simple and mosaic plantar warts. This formulation is a promising alternative treatment modality for plantar warts.
  • https://doi.org/10.7547/0980445
    • Paid access
  • Cantharidin–podophyllotoxin–salicylic acid versus cryotherapy in the treatment of plantar warts: a randomized prospective study. Kaçar N, Taşlı L, Korkmaz S, Ergin S, Erdoğan BŞ. Journal of the European Academy of Dermatology and Venerology. 2012;26(7):889-893.
  • Background: Plantar warts are refractory to any form of treatment. High cure rates have been reported with a topical proprietary formulation consisting of 1% cantharidin, 5% podophyllotoxin and 30% salicylic acid (CPS). However, no data exists comparing the efficacy of this formulation with another treatment. Cryotherapy is a method that is also widely used in the treatment of plantar warts. Likewise, there is no evidence that it is more effective than any topical treatment.
  • Objective: We aim to compare the efficacy of topical CPS and cryotherapy in the treatment of plantar warts.
  • Methods: Patients with plantar warts were consecutively treated with either cryotherapy or topical CPS. Both treatments were performed every 2 weeks for up to five sessions. In patients without complete clearance, the therapy was switched to the other treatment option.
  • Results: Twenty‐six patients with a total of 134 warts were included. Fourteen patients were completely cleared of their warts with topical CPS, whereas only in five of 12 patients (41.7%) warts were completely cleared with cryotherapy (P = 0.001). In seven patients without complete clearance, the therapy was switched to CPS. Four of these patients missed the follow‐ While the two of the remaining three patients were cleared of their warts, one patient’s warts still failed to clear.
  • Conclusion: Topical CPS is more effective than cryotherapy in the treatment of plantar warts.
  • https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1468-3083.2011.04186.x
    • Paid access

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