Treatment of recalcitrant plantar warts with long-pulsed Nd:YAG laser versus cantharidin–podophylline resin–salicylic acid

Background: Treatment for recalcitrant plantar warts remains a continuing challenge as the options for treatment have differing levels of success. long-pulsed Nd:YAG laser is considered a good treatment modality in resistant plantar warts. On the other hand, high cure rates have been reported with a topical proprietary formulation consisting of 1% cantharidin, 5% podophyllotoxin, 30% salicylic acid. Aim: To compare the efficacy of 1% cantharidin, 20% podophylline resin and 30% salicylic acid (CPS) versus long-pulsed Nd:YAG laser in the treatment of recalcitrant plantar warts. Methods: This study included 30 patients with single or multiple recalcitrant plantar warts; patients were assigned to two groups: the first group included 15 patients with 71 recalcitrant plantar warts who were treated by long-pulsed Nd:YAG laser (group I) and the second group included 15 patients with 78 recalcitrant plantar warts who received CPS (group II). The diagnosis of plantar warts was made by clinical examination. Results: Fourteen patients (93%) were completely cleared of their warts with topical CPS, while 11 patients (73%) showed complete clearance with long-pulsed Nd:YAG laser with statistically significant difference between the two groups. Conclusion: Topical CPS is safe and efficacious and represents a promising therapeutic modality than long-pulsed Nd:YAG laser in the treatment of recalcitrant plantar warts.     

Safety and effectiveness of cantharidin–podophylotoxin–salicylic acid in the treatment of recalcitrant plantar warts

The aim of our study was to evaluate the efficacy and safety of topical cantharidin–podophylotoxin–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.     

Topical treatment for plantar warts: A systematic review

There are a wide variety of treatments for plantar warts, but none has been shown to be effective in all patients. We aimed to perform a systematic review of the efficacy of different topical treatments on plantar warts. Systematic electronic searches (Pubmed, Cochrane Library, Embase, and Web of Science) were conducted in April 2020. Meta‐analyses, systematic reviews, and retrospective or prospective clinical trials of the effects of topical and nonsurgical treatments of plantar warts were included. Two authors performed the study selection and data extraction. Any discrepancies between the two reviewers were discussed with a third reviewer. Forty‐four studies were included. The average cure rates of the most frequent treatments were variable across the studies: cryotherapy (45.61%), salicylic acid (13.6%), cantharidin‐podophyllin‐salicylic acid formulation (97.82%), laser (79.36%), topical antivirals (72.45%), intralesional bleomycin (83.37%), and intralesional immunotherapy (68.14%). Twenty‐two studies (50%) had a level of evidence 1b and grade of recommendation A, five studies (11.4%) had a level of evidence 2b and grade of recommendation B, two studies (4.5%) had a level of evidence 3b and grade of recommendation B, and 15 studies (34,1%) with a level of evidence 4 and grade of recommendation C. First‐choice treatments for common warts, such as cryotherapy and salicylic acid, have low‐cure rates for plantar warts. Other treatments, such as CPA formulation, immunotherapy, and intralesional bleomycin, which have compassionate use, have higher cure rates. This review should stimulate future high‐quality research to evaluate these specialized treatments.     

Plantar warts treated with an immune response modifier: a report of two cases

Summary Viral warts are the most common disease of the skin and are caused by human papillomavirus (HPV). Plantar warts, a manifestation of infection by HPV-1, -2 and -4, tend to be smoother and flatter than common warts and can also be painful when pressure is applied. A variety of local treatments, including topical salicyclic acid, cryotherapy, topical 5-fluorouracil, intralesional interferons and photodynamic therapy, are available to treat plantar warts. Here we report two cases of plantar warts, which had been previously treated without success. Total clearance of the warts was observed in both cases after treatment with imiquimod 5% cream over a period of 12 weeks. No evidence of local skin reactions was observed in either case during the treatment period. Recurrent lesions were not evident in the follow-up period for each patient.     

Intralesional injection of measles,mumps, and rubella vaccine versus cryotherapy in treatment of warts: A randomized controlled trial

Cutaneous warts are benign hyperkeratotic papillomas resulting from infection by human papillomavirus (HPV). Cryotherapy is a known method for warts treatment. Immunotherapy stimulates HPV recognition by the immune system; this helps resolution of warts. To determine the efficacy of intralesional immunotherapy with measles, mumps, and rubella (MMR) vaccine versus cryotherapy in the treatment of patients with multiple common and plantar warts. Forty‐eight patients with multiple common and plantar warts were divided into two groups: to undergo either intralesional injection of MMR vaccine (Group A), or cryotherapy (Group B). Forty patients completed the study. In the MMR group, 70% of the patients showed complete response, 5% partial response, and 25% showed no response to treatment. In the CRYO group, 45% of the patients showed complete response, 35% partial response, and 20% showed no response to treatment. The complete response was higher in the MMR group (70%) as compared to the CRYO group (45%), but the difference between the two groups was not statistically significant. Meanwhile, the partial response was significantly higher in the CRYO group. Intralesional MMR injection was a safe and effective treatment for multiple common and plantar warts as compared to cryotherapy.     

Interferon in the treatment of persistent viral warts

7 patients with a diagnosis of common and/or plantar warts present for at least 1 year and resistant to previous vigorous therapy were studied. All patients entered completed the study and during the trial period the warts of 4 patients receiving intralesional injections were completely cleared. 2 other patients demonstrated partial clearance of their warts.     

Er:YAG laser followed by topical podophyllotoxin for hard‐to‐treat palmoplantar warts

BACKGROUND AND OBJECTIVES: Palmoplantar warts are often hard to treat. They tend to relapse and the course of therapy is frustrating in many cases. The erbium:YAG laser (Er:YAG) with a wavelength of 2.94?μm is capable of achieving a rapid and precise ablation of warts, but about 14% of patients are non‐responders as shown in a previous study. Podophyllotoxin is an established antimitotic agent derived from podophyllum plant resin, approved for human papilloma virus (HPV)‐induced genital warts. The combination of both ablative Er:YAG laser and topical 0.5% podophyllotoxin solution in hard‐to‐treat palmoplantar HPV warts was investigated.

PATIENTS AND METHODS: Thirty‐five patients with hard‐to‐treat warts (palmar or plantar) with a mean age of (32.2±12.1) years, range 17–50 years, with various pretreatments that had failed, were treated once by Er:YAG laser ablation with a spot size of 3?mm, a frequency between 8?Hz and 10?Hz, and a fluence of 5.7–11.3?J/cm². After wound healing, topical podophyllotoxin 0.5% solution was applied for 3 days followed by a break of 4 days. Four to six treatment cycles with podophyllotoxin were performed.

RESULTS: After laser treatment followed by topical podophyllotoxin cream a complete response was observed in 31 patients (88.6%). Two patients with plantar warts and a complete response showed a relapse within 3 months after treatment (5.7%). None of the patients developed pigmentary changes, wound infections or scarring.

CONCLUSION: The therapy of hard‐to‐treat warts with a combination of Er:YAG laser and topical podophyllotoxin is safe and effective. Compared with laser alone, the CR percentage seems to be higher and the percentage of relapses reduced.     

The SILVER study. Efficacy of topical nitric‐zinc complex solution in the treatment of resistant warts: A postmarketing evaluation

The treatment of cutaneous viral warts caused by human papillomavirus (HPV) infection is often subject to local recurrence and a long clinical and treatment course. Our aim was to analyze real‐life data on the treatment of difficult‐to‐treat warts from a multicenter postmarketing surveillance assessment on the efficacy, tolerability, and safety of a commercially available nitric‐zinc complex solution (NZCS). Dermatologists from 14 Italian centers completed a questionnaire about their clinical experience on treatment of “difficult‐to‐treat” warts, which included warts in the plantar, periungual, anogenital and aesthetically sensitive areas. The questionnaire was designed to obtain detailed information on wart treatment and compare NZCS efficacy with previous treatments. Of 106 questionnaires returned, 83 reported NZCS use; 67 had previous treatments (23 cryotherapy, 2 electrocoagulation, 12 other topical application, and 30 combined treatment, such as laser, cryotherapy, and/or electrocoagulation). NZCS had superior efficacy to that of previous treatments (p < .0001), resulting in 84.1% with a full or partial clearance (vs. 44.8% for previous treatments), and had better local tolerability (p < .0001). NZCS showed better efficacy and tolerability than other previous wart treatments.     

光动力联合二氧化碳激光治疗顽固性跖疣的研究

目的观察外用5-氨基酮戊酸(5-ALA)光动力联合二氧化碳(CO2)激光治疗顽固性跖疣的临床疗效。方法收集顽固性跖疣患者30例,超脉冲CO2激光去除厚硬的角质层,20%5-ALA霜封包4～5 h,633 nm的红光照射20 min(126 J/cm2),用聚合酶链反应技术(polymerase chain reaction,PCR)技术进行人乳头瘤病毒(humanpapillomavirus,HPV)病毒分型,分析各型HPV对光动力治疗反应的差异。结果本组30例患者经3次光动力治疗,16例患者完全缓解(完全缓解率53.3%),4例(13.3%)患者部分缓解,10例(33.3%)患者无反应。各型HPV对光动力治疗的反应差异无统计学意义。结论外用5-ALA光动力联合二氧化碳激光治疗顽固性跖疣是一种新的、有效的、安全的治疗方案,可以作为跖疣的二线治疗方案。     

Silver duct tape occlusion in treatment of plantar warts in adults: Is it effective?

Duct tape occlusive therapy may represent a convenient alternative to the standard wart therapies. The objective of the current study is to assess the therapeutic effect of duct tape occlusion in comparison to cryotherapy in treatment of plantar warts in adults, in a prospective comparative randomized non‐inferiority design. A total of 100 patients presenting with plantar warts were divided into two equal groups. First group was treated with silver duct tape occlusion for up to 8 weeks or disappearance of warts, whichever occurred first. Second group was treated with cryotherapy every 2 to 3 weeks for a maximum of four sessions or disappearance of warts. There was a statistically significant lower rate of complete resolution in duct tape than cryotherapy group (20% vs 58%, P = .0001, respectively). Degree of response to treatment in the duct tape and cryotherapy groups was not correlated to patients' age (P = .361 and .334, respectively) or disease duration (P = .266 and .285, respectively), while there was a statistically significant inverse relationship between the number (P = .0032 and .001, respectively) and diameter of warts (P = .013 and .003, respectively) and the degree of response in the two studied groups. Cryotherapy has higher efficacy than duct tape in the treatment of plantar warts in adults; however, duct tape may represent a practical and convenient alternative to cryotherapy in certain circumstances.     

Real‐life treatment of cutaneous warts with cantharidin podophyllin salicylic acid solution

Patients often request treatment of their burdensome cutaneous warts. However, a safe and effective treatment for cutaneous warts is lacking. This study evaluates treatment outcome, side effects, and patient satisfaction after topical application of cantharidin 1% podophyllin 2% salicylic acid 30% (CPS1) solution in a large series of children and adults with cutaneous warts. Fifty‐two children and 83 adults with warts, treated with CPS1 solution between October 2012 and October 2014, were included. Complete clearance of warts occurred in 86.5% of children and 62.7% of adults treated with CPS1 solution (p < .01). Resolution of warts was partial in 3.9 and 24.1% and absent in 9.6 and 13.2% of children and adults respectively. Side effects were present in 41.2% of children and 46.3% of adults (p = .7). Most common side effects were blistering, pain, and burning sensation. No serious adverse events occurred. On a 10‐point scale, median patient satisfaction score was 9.0 (interquartile range 7.8–10.0) and 8.0 (interquartile range 5.1–9.7) for children and adults respectively (p < .01). CPS1 solution is a safe and promising treatment modality with a high clearance and high patient satisfaction rate for the management of cutaneous warts, particularly in children.     

Efficacy and tolerability of a new topical nitric‐zinc preparation for “difficult‐to‐treat” warts

Treating plantar, periungual, and external genital warts can be challenging. A prospective study from four centers in Italy evaluated 37 immunocompetent patients with single or multiple warts and treated each lesion with a nitric‐zinc topical solution composed of organic and inorganic acids meant to devitalize tissue and destroy HPV DNA in infected keratinocytes. Thirty of the 37 patients had external genital warts, two had plantar warts, two had palm and finger warts, and three had subungual warts for a total of 55 lesions treated. Nitric‐zinc aqueous solution was applied over each wart utilizing a 30 µL capillary tube until a whitening response was observed. Additional applications as needed were accomplished at 2‐week intervals until the wart was gone. In those with hand, plantar, and subungual warts, there was a 100% clearance after two to three sessions. Three with external genital warts had only a partial response and one no benefit after four applications. Thus, this approach was effective in external genital and other “difficult‐to‐treat” warts in 90% of patients after one to four applications. It also was easy to use with no adverse events noted.     

Kontrollierte schichtweise Abtragung anogenitaler Warzen mittels Argon‐Plasma‐Koagulation

Background: According to guidelines of the German STD Association, appropriate treatment of extensive anogenital warts with comparable recurrence rates includes cryotherapy, surgical excision, electrosurgery, CO₂‐ and Nd:YAG‐laser vaporisation. All these procedures are associated with varying degrees of risk for bleeding, release of potentially infectious aerosol, deep thermal destruction, slow wound healing, and scarring. Methods: Using argon‐plasma coagulation anogenital warts can be removed in layers in a controlled manner. High frequency current flows through the argon plasma to the tissue, allowing well‐controlled, superficial tissue destruction. Results: From January 2001 to March 2003, 54 patients with extensive genital, anal or anogenital warts were treated. After one treatment, 66 % of the patients remained disease‐free in the following 4 months. Thirteen patients (24 %) showed early recurrence after 4 weeks, five patients (9 %) at a later date. In these patients, further treatment, in 9 cases combined with topical imiquimod cream, were necessary for complete remission. Conclusion: Compared to other therapeutic procedures, argon‐plasma coagulation is a better controlled, quick and low‐risk option for the treatment of anogenital warts. Depending on the type of involvement and individual risk factors, postoperative treatment with topical imiquimod cream may be useful.     

Wirksamkeit und Nutzen eines 5‐FU‐/Salicylsäure‐haltigen Präparates in der Therapie vulgärer und plantarer Warzen – systematische Literaturübersicht und Metaanalyse

Background: 1) Salicylic acid (SA) and 5‐Fluorouracil (5‐FU) are effective drugs in wart therapy. 2) In Germany, increasing data on the benefit and the economic efficiency of drugs at Level I of evidence‐based medicine are needed. Methods: Evaluation of the effectiveness and benefits of a drug combination containing 0.5 % 5‐FU and 10 % SA in the therapy of a) common and b) plantar warts in form of a two‐step procedure – 1. Systematic literature analysis, 2. Meta‐analysis of the randomised‐controlled studies (RCTs). Results: 1. The efficacy of 5‐FU/SA therapy was tested in a total of 625 patients (n = 8 RCTs) with common warts and 101 patients (n = 4 RCTs) with plantar warts. The therapeutic effect across all studies in common warts was 63.4 % response (complete healing) for 5‐FU/SA vs. 23.1 % for the 5‐FU‐free controls, respectively. In plantar warts, the response was 63.0 % vs. 11.0 %. 2. A meta‐analysis of n = 7 RCTs on common warts (n = 325 patients) showed a mean risk difference of 0.42 (CI 0.34 – 0.50, p < 0.05), thus a significant superiority of 5‐FU/SA over SA. A comparable result was also found for plantar warts. Conclusion: The combination of 5‐FU and SA is an effective and beneficial therapy for common and plantar warts.     

Topical Cidofovir for Refractory Verrucae in Children

Abstract: Warts are common and are a challenge to treat in some children, especially immunocompromised children and those who fail or cannot tolerate salicylic acid preparations and cryotherapy. Cidofovir, a nucleotide analogue with antiviral activity, has demonstrated promising results when compounded into a topical form to treat refractory warts. We present a retrospective institutional review of 12 children with refractory verrucae treated with 1% to 3% topical cidofovir compounded in an unscented moisturizing cream, applied every other day to daily. In our institutional series, only three patients (25%) demonstrated complete clearance of their verrucae. An additional four patients (33%) demonstrated partial clearance. Our experience using topical cidofovir has been less successful than previous institutional reviews, possibly because we used a lower concentration and less‐frequent dosing. More studies are needed to better characterize the efficacy, safety, and dosing of topical cidofovir for the treatment of refractory warts.     

Topical 5-fluorouracil has no additional benefit in treating common warts with cryotherapy: a single-centre, double-blind, randomized, placebo-controlled trial

The role of topical 5-fluorouracil (5-FU) in treating common warts is not well defined. We tried to evaluate the efficacy and adverse effects of combination cryotherapy and topical 5% 5-FU ointment in the treatment of common warts. The study was a single-centre, double-blind randomized placebo-controlled trial. In the study, 80 patients with common warts were randomized into two groups and underwent two 10-second freeze/thaw cycles of cryotherapy with liquid nitrogen once every three weeks for a maximum of five treatments. Between treatments, patients applied either topical 5% 5-FU ointment (group A) or placebo aqueous cream (group B) twice daily. The mean +/- SD reduction in wart area was 58.57 +/- 0.06% in group A and 65.29 +/- 0.06% in group B. In total, 19 patients in group A and 24 patients in group B had wart size reduced by 75% or more (P = 0.50), while 12 patients in group A and 17 patients in group B had clearance of their warts (P = 0.245). Logistic regression with age, sex, smoking status, immune status, site, duration and number of warty lesions, history of previous treatment, and treatment group found that only a history of previous treatment and acral lesions were significant adverse predictors of improvement. There was no significant difference in the number of adverse events between the two groups, although there was a trend towards more pain and blistering associated with topical 5-FU. We concluded that topical 5-FU has no added benefit in treating common warts with cryotherapy.     

Recalcitrant hand and foot warts successfully treated with photodynamic therapy with topical 5-aminolaevulinic acid: a pilot study

The purpose of this pilot study was to determine if photodynamic therapy with topical application of 5-aminolaevulinic acid followed by irradiation with incoherent filtered and unfiltered light (ALA-PDT) is an effective therapy for recalcitrant hand and foot warts. In 30 patients with recalcitrant warts, 49 regions with a total of 250 warts were randomized to one of the following five treatments: (i) ALA-PDT with white light applied three times within 10 days (W3); (ii) ALA-PDT with white light applied once (W1); (iii) ALA-PDT with red light applied three times within 10 days (R3); (iv) ALA-PDT with blue light applied three times within 10 days (B3), and (v) cryotherapy applied up to four times within 2 months (CRYO). The ALA-PDT treatment modality was repeated in case of partially responding warts. Significantly more warts were completely healed after W3 and W1 than after R3, B3 and CRYO (P < 0.01): 73% of the warts treated with W3 were completely healed, 71% after W1, 42% after R3, 23% after B3 and 20% after CRYO. No scars were observed in the ALA-PDT treated areas and patients treated for foot warts were all able to walk after the treatment. No recurrences in completely responding ALA-PDT treated warts were observed after 12 months of follow-up. In conclusion, photodynamic therapy with topical 5-aminolaevulinic acid followed by irradiation with white light is a promising treatment for recalcitrant hand and foot warts.     

The status of treatment for plantar warts in 2021: No definitive advancements in decades for a common dermatology disease

Plantar warts are among the most common skin conditions and are classically resistant to treatment. To perform an evidence-based evaluation of the efficacy and safety of available treatment options for plantar warts, we conducted a systematic review of PubMed and Cochrane databases to identify large interventional and observational studies involving more than 100 patients who were treated for plantar warts from inception to October 2020. We identified only nine contributions meeting our inclusion criteria (N ≥ 100), representing 1,657 adult and pediatric patients with plantar warts. Treatments included in this review were topical keratolytic agents, cryotherapy, laser therapies, and intralesional and systemic treatments. Our evidence-based review of the larger studies suggests keratolytic agents and destructive treatments, in particular salicylic acid and cryotherapy, remain the primary treatments for plantar warts. Treatment with pulsed dye laser had the lowest rate of recurrence. Newer treatments and intralesional treatments were not represented owing to lack of large studies involving these modalities.     

A comparison of acyclovir cream versus placebo cream versus liquid nitrogen in the treatment of viral plantar warts

52 patients with a clinical diagnosis of verruca plantaris were entered into a randomised study of acyclovir cream versus placebo cream versus liquid nitrogen. 47 completed the initial 8-week assessment period. At first, liquid nitrogen was used as a positive control but after the entry of 33 patients it was discontinued as an initial therapy in order to obtain maximal numbers of patients on the cream treatments. At the end of the 8-week assessment period 5 of 18 (placebo cream), 7 of 18 (acyclovir cream) and 1 of 11 (liquid nitrogen) patients were completely cleared of their plantar warts. Patients who failed to clear on cream or liquid nitrogen treatments after the initial assessment period but who wished to continue therapy were subsequently treated with liquid nitrogen. Of a total of 27 patients treated vigorously with liquid nitrogen, for periods of time ranging from 2 to 34 weeks, only 11 were completely cleared of their warts at the end of the study. It is concluded that liquid nitrogen should not be considered as a routine treatment for plantar warts and that acyclovir cream is no better than placebo in the treatment of this condition.     

The treatment of resistant mosaic plantar warts with aggressive cryotherapy under general anaesthetic

Twelve patients with treatment-resistant mosaic plantar warts were treated with aggressive cryotherapy under a general anaesthetic. Seven patients (58%) had complete cure, two patients (16%) experienced substantial but incomplete clearing of their warts and the remaining three patients (25%) had no improvement. The procedure was well tolerated and post cryotherapy pain was acceptable to the patients.