Intralesional immunotherapy for pediatric warts: A review

Cutaneous warts are a common pediatric complaint with modest response to first-line treatments. Warts are a manifestation of human papillomavirus (HPV) infection and are cleared by cell-mediated immunity (CMI). Intralesional immunotherapy treatments have been studied as alternative therapies, particularly for recalcitrant or multiple warts, including Candida antigen, mumps antigen, the combined measles, mumps, and rubella (MMR) vaccine, tuberculin purified protein derivative (PPD), and bacille Calmette-Guerin (BCG) vaccine. These treatments are thought to increase HPV recognition by stimulating CMI. In this review, we evaluate and compare the efficacy and adverse effects of intralesional immunotherapy in the treatment of pediatric warts. Articles met inclusion criteria if they specifically evaluated the effects of intralesional immunotherapy (candida, MMR, tuberculin PPD, or BCG) as treatment for cutaneous warts in a pediatric population, and if they quantified treatment effect in a reproducible manner. Twenty-one studies met criteria. Many studies demonstrated complete clearance of injected common warts in pediatric patients with clearance rates ranging from 23.3% to 95.2%. Distant wart resolution was common. Intralesional immunotherapy is a promising treatment option for cutaneous warts in children.     

5% 5-Fluorouracil Cream for Treatment of Verruca Vulgaris in Children

Abstract:   Warts are a common pediatric skin disease. Most treatments show only modest benefit, and some are poorly tolerated because of pain. 5-fluorouracil interferes with deoxyribonucleic acid and ribonucleic acid synthesis, and is used to treat genital warts in adults. Efficacy, safety, and tolerability of topical 5% 5-fluorouracil for treatment of common warts were examined in an open-label pilot study with pediatric patients. Thirty-nine children who have at least two hand warts applied 5% 5-fluorouracil cream (Efudex, Valeant Pharmaceuticals International) once or twice daily, under occlusion for 6 weeks. Assessment of treatment response and side effects was performed at baseline, treatment completion, and 3- and 6-month follow-ups. Hematology measures, liver function tests, and medication blood levels were reassessed at treatment completion. Eighty-eight percent of treated warts improved after 6 weeks of treatment, and 41% of subjects had complete resolution of at least one wart. Treatment response did not differ between once or twice daily applications. Tolerability and patient satisfaction were excellent. No subject had clinically significant blood levels of 5-fluorouracil. At 6 month follow-up, 87% of complete responders had no wart recurrence. Topical 5% 5-fluorouracil is a safe, effective, and well-tolerated treatment for warts in children.     

Cold urticaria as a complication of cryotherapy in the treatment of viral warts

Cryotherapy with liquid nitrogen has been established as the first-line treatment for pediatric patients with viral warts. Cold-induced urticaria (CU) is a rare skin reaction triggered by cold stimuli. We present the case of a pediatric patient with viral warts who developed CU after receiving cryotherapy.     

Pulsed dye laser treatment for viral warts: a study of 120 patients

A prospective, non-blinded, non-randomized study on 120 wart patients treated with pulsed dye laser was performed to evaluate the efficacy and safety of pulsed dye laser treatment for viral warts and to demonstrate the proper application and effective technique of this method. The overall clearance rate was 49.5%. The clearance rates of flat warts, periungual warts, plantar warts and common warts were 67.6%, 51.1%, 47.6% and 44.3%, respectively. Overall, the response rates of pediatric warts, recalcitrant warts and old warts were superior to those of adult warts, simple warts and non-old warts, respectively; however, those trends were not statistically significant. We concluded that pulsed dye laser treatment is a safe, tolerable and relatively effective treatment method for viral warts. Pulsed dye laser treatment may be a more efficacious method for flat warts and recalcitrant periungual warts, and it can be an effective modality for newly-developed warts. The highest clearance rate was noted at a fluence of 9.5 J/cm2 (P < or = 0.05) and it is recommended that practitioners perform pulsed dye laser treatments for viral warts at the fluences of 9.0-9.5 J/cm2. A replacement of pulsed dye laser treatment should be considered unless prominent improvement is observed after three treatment sessions.     

Pulsed dye laser therapy for pediatric warts

Viral wart infections constitute one of the most common pediatric skin diseases, and various modalities have been used to manage them. Although pulsed dye laser therapy is known to be a safe and efficacious modality, the reported cure rates for this method have varied, and no studies have reported treatment of pediatric patients alone. This prospective, nonblinded, nonrandomized study was performed to evaluate the efficacy and safety of pulsed dye laser therapy for pediatric warts. We found that this method is safe, relatively effective, and worth considering as an additional therapeutic option for viral warts in children, although not as a first-line therapy.     

Clearance of recalcitrant warts in a pediatric patient following administration of the nine-valent human papillomavirus vaccine

Verruca vulgaris is a common, benign infection of the skin and mucous membranes caused by human papillomavirus (HPV). Although many therapeutic options for warts exist, they have limited efficacy and there is no definitive cure for warts. We report the case of a 10-year-old girl with recalcitrant cutaneous warts persisting more than two years which resolved completely following vaccination with the nine-valent HPV vaccine.     

Immunotherapy for recalcitrant warts in children using intralesional mumps or Candida antigens

Intralesional injection of mumps and Candida skin test antigens has been shown to be effective in the treatment of warts. Warts are generally difficult to treat in children. To determine the efficacy of intralesional skin test antigen injection for the treatment of resistant warts in children, we treated 47 pediatric patients with one or more warts with intralesional injection of mumps or Candida skin test antigen into one wart. Twenty-two patients (47%) with resistant warts experienced complete resolution of treated warts. An average of 3.78 treatments were necessary. An additional 34% of children had a greater than 25% improvement in their warts. Sixty-eight percent of subjects with more than one wart also noted at least partial resolution (greater than 25% resolution) of untreated warts at distant sites, with 34% experiencing complete resolution. We concluded that intralesional injection of skin test antigens is an effective therapy for children who have recalcitrant, nongenital, cutaneous warts.     

Intralesional measles,mumps, and rubella vaccine after failure of intralesional Candida antigen for the treatment of recalcitrant pediatric warts

Numerous studies have investigated the efficacy of intralesional immunotherapy for warts, but there are a lack of studies investigating the efficacy of alternative intralesional immunotherapies following failure of initial intralesional immunotherapy. In this retrospective study, we aimed to investigate the efficacy of intralesional measles, mumps, and rubella vaccine for the treatment of pediatric warts following failure of intralesional therapy with Candida antigen. Following intralesional measles, mumps, and rubella vaccine administration, 8/51 (15.5%) patients had complete resolution of their warts, 6/51 (12%) had near complete resolution, 19/51 (37%) had partial improvement, 12/51 (23.5%) had no change, and 6/51 (12%) had worsening. Although limited by retrospective nature and low sample size, our results demonstrate that intralesional immunotherapy with measles, mumps, and rubella vaccine provides an alternative therapeutic option for the treatment of recalcitrant pediatric warts in patients who fail to respond to intralesional Candida antigen.     

Selected applications of technology in the pediatric dermatology office

The pediatric dermatologist is equipped with several diagnostic and therapeutic tools that can be used in the office. The Wood's lamp, introduced nearly a century ago, continues to be a safe, noninvasive diagnostic tool used today for diagnosing cutaneous infections, pigmentary disorders, and porphyrias. The pulsed dye laser is the treatment of choice for vascular lesions and has an expanding list of other applications, such as warts, which are extremely common in the pediatric population. Dermoscopy has emerged as an effective adjunctive tool in the in vivo examination of pigmented skin lesions and early diagnosis of cutaneous malignant melanoma. Other uses are also being explored including diagnosis of scabies. Future directions of technology in the pediatric dermatology office include implementation of electronic medical record systems and treatment of conditions such as molluscum, warts, and acne vulgaris with photodynamic therapy.     

CO2 laser treatment for plantar warts in children: A case series

Several types of human papillomaviruses induce warts. Warts are one of the most common infections in childhood with a reported prevalence of up to 20%. Warts are divided clinically into genital and nongenital forms. Plantar warts are common nongenital warts. In this series, five pediatric cases treated with CO₂ laser for their plantar warts are presented. One patient was a known case of Hodgkin's lymphoma. Three of our patients had history of unsuccessful treatments with other modalities, while the other had received no previous treatment. CO₂ laser with continuous mode (focused and defocused) was used. In our cases, only one session was enough for clearance of the warts. All the patients were visited 1 week and 3 months after treatment to assess the efficacy and any possible recurrences. Follow‐up showed that all the patients remained in remission up to 3 months posttreatment with no adverse events.     

Examining the Efficacy and Safety of Squaric Acid Therapy for Treatment of Recalcitrant Warts in Children

The objective of the study was to determine the safety and efficacy of squaric acid dibutyl ester (SADBE) therapy on the treatment of recalcitrant warts in children. This retrospective chart review examined 72 patients treated using SADBE from July 2002 to December 2012. Patients were followed for 6 months to 11 years. Patients were treated at a pediatric dermatology outpatient clinic at the University of North Carolina at Chapel Hill. Seventy‐two children with verrucae who failed initial treatment for warts were selected for the study. Full long‐term follow‐up was obtained in 48 patients. Four patients discontinued the use of SADBE because of adverse effects. The primary study outcome was efficacy of SADBE treatment. Adverse effects, dosages administered, type of wart, other cutaneous disease present, and level of immunosuppression were measured. Forty of 48 (83%) patients in whom treatment outcomes could be obtained reported complete resolution of their warts. Seventy percent of patients used a maximum concentration of 0.4% SADBE and 60% of patients reported no adverse effects. The majority of patients treated with SADBE reported complete resolution of warts. Most patients reported no adverse effects even while receiving doses as high as 2% daily. This study shows that SADBE is a safe and effective treatment for recalcitrant warts in children.     

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.     

Successful treatment of florid cutaneous warts with intravenous cidofovir in an 11-year-old girl

Abstract:  Cutaneous warts, commonly seen in children and the immunosuppressed are socially distressing and are often resistant to traditional treatments. Here, we report an 11-year-old girl with bilateral florid verrucous lesions on her hands, feet and chin, which were refractory to a number of standard treatments including cryotherapy, cantharidin preparations, topical salicylic acid, surgical debulking techniques, oral Cimetidine, and topical and intralesional Cidofovir. As the disfiguring lesions had a marked adverse effect on her quality of life, a trial of IV Cidofovir was instituted. We administered five cycles of IV Cidofovir with a 1-week interval between the first and second treatment, followed by 2-week intervals thereafter. This regime was well tolerated and we report dramatic resolution of the lesions with persistent clearance 6 months after completion of the fifth infusion. Resolution of recalcitrant warts with IV Cidofovir has been reported in a limited number of cases. Our experience supports its efficacy in this setting, and to the best of our knowledge this is the first report of successful treatment of cutaneous warts with IV Cidofovir in a pediatric case.     

Efficacy and Safety of Topical Cantharidin Treatment for Molluscum Contagiosum and Warts: A Systematic Review

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 podophyllotixin and salicylic acid, and modest benefit for pediatric molluscum contagiosum with good tolerability and safety.

     

Closing the feedback loop: an audit of the use of imiquimod for the treatment of genital warts

A retrospective case-note audit of 74 patients with 81 treatment episodes of anogenital warts with imiquimod from April 1999 until July 2000 was performed. The majority of patients had failed to clear their warts with other treatments, had recurrences after other treatments, or had other medical problems complicating their genital wart treatment. The overall clinically confirmed complete clearance rate was 33%. This is lower than other published data, but may be so because it includes patients with immunosuppression and difficult-to-treat warts. The complete clearance rate in immunocompetent patients was 37%. In addition, in this audit of clinical practice 17% of the patients did not return for full response to be assessed. The complete clearance rate in those who were able to tolerate treatment and who returned for follow-up was 45%. Based on the results of the audit we have extended the indications for the use of imiquimod in the clinic treatment guidelines. Patients are now offered imiquimod if six or more episodes of other treatments fail to give a good response. Earlier treatment with imiquimod is also offered to those patients with recurrent anogenital warts, and it is recommended as a first-line therapy for patients with multiple keratinized warts.     

Anthralin stick (Anthraderm) in the treatment of mosaic warts

Thirty patients having mosaic warts of the soles for 2 years (range 3 months-6 years) were treated daily with a wax-based anthralin stick supplemented by weekly paring. Six patients dropped out, because they failed to appear for follow-up. Of the remaining patients 17/24 cleared, whereas the warts persisted in 7/24. Although the trial was an open study, this result can hardly be explained by placebo effect since mosaic warts are notoriously resistant to treatment.     

Photodynamic therapy for dermatologic conditions in the pediatric population: a literature review

Photodynamic therapy (PDT), using topical aminolevulinic acid (ALA), has been used for years to treat a variety of dermatologic conditions, including actinic keratosis, superficial basal cell carcinoma, and in situ squamous cell carcinoma. While there is a wide range of neoplastic and non‐neoplastic skin diseases for which ALA‐PDT is used in adults, there is a knowledge gap when it comes to its use in children. This review highlights what is currently known regarding the use and efficacy of this therapy in the pediatric population. A PubMed search was conducted to identify studies including pediatric patients undergoing monotherapy PDT with topical aminolevulinate (published 2005–2016). Twenty pediatric articles were identified. ALA‐PDT has been used successfully in children to reduce the number and size of basal cell tumors, inflammatory acne lesions, plantar warts, and linear porokeratoses. ALA ‐ PDT may be an attractive alternative to surgery for children with basal cell nevus syndrome, or to conventional destructive and/or topical methods used for plantar warts or linear porokeratoses. PDT can be considered for inflammatory acne when topical treatments have failed and systemic medications are not an option. Pain associated with treatment and insurance coverage may be a barrier to use.     

Density of viral particles in pre and post Nd:YAG laser hyperthermia therapy and cryotherapy in plantar warts

BACKGROUND: Warts often present a difficult treatment problem for clinicians because of the lack of specific antipapillomavirus agents. Plantar warts, in particular, represent a therapeutic challenge. METHODS: Twenty-five patients with plantar warts were treated with Nd:YAG hyperthermia and another 25 were treated with cryotherapy. Biopsies were taken before and after treatment in both groups and were examined for the presence of human papillomavirus deoxyribonucleic acid (HPV DNA) using in situ hybridization (ISH). RESULTS: HPV DNA was detected in 100% of untreated warts and in 96% of cryotreated warts, but was not detected in any of the hyperthermia-treated warts. CONCLUSIONS: HPV is more vulnerable to hyperthermia than to cryotherapy.     

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.     

A randomized controlled proof-of-concept trial of digoxin and furosemide in adults with cutaneous warts

This is a study of the effect of two topically-applied (i.e. applied to the skin) drugs, digoxin and furosemide, on the healing of viral warts on the skin. It was performed by a group from the Netherlands and Pennsylvania, USA. The investigation is known as a proof of concept study, which is a preliminary experiment to show whether there is likely to be a benefit of a particular course of treatment. These two medicines are believed to improve healing rates of viral warts because they block the passage of potassium into cells, a process that is necessary for the growth of wart viruses in human skin. The team used a topically applied preparation containing the two medications and measured the size of warts, the presence of visible features on their surface and their disappearance; in addition, samples were taken for testing for the presence of wart virus. All the patients had warts that had not responded to other treatments. The study followed different groups of 20 patients who received either both medications combined, each singly or a placebo. This showed that after 6 weeks of daily treatment and a follow up of 14 weeks, only those patients who had received the treatment with both digoxin and furosemide together showed improvements, with some achieving elimination of the warts. This is an encouraging result, but the work should now be carried out on a larger number of patients with warts that have not been treated before as, although the new treatment led to greater improvement, the numbers of patients whose warts disappeared completely was small. There were no side effects associated with the treatment.