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Case Report

Efficacy and Tolerability of Topical Green Tea Extract (Polyphenon E) application in “Therapy-Resistant” common and flat warts (verrucae planae): A report of two cases

*Correspondence to: Dr. Massimo Milani MD, Medical Department Cantabria Labs Difa Cooper Via Milano 160, Caronno P. (VA); Italy, 
E-mail: massimo.milani@difaccoper.com

Article Information

Article Type: Case Report

Received : 03/12/2018
Accepted : 10/12/2018 
Published : 20/12/2018

Abstract

Common and flat warts are frequent skin viral lesions.For both types of lesions treatment remains, at least in some cases, a challenging therapeutic problem. We reported here the efficacy of topical Polyphenon E 10% (green tea extract: sinetatechins) in the treatment of “difficult to treat” periungual common warts in a 6-years old girl and a case of flat warts of the hand and of the groin region in a 30-years old woman. Several cryotherapy sessions (a total of 3 procedures) had been performed with no success in both cases. Flat wart lesions were treated also with a cycle of topical tretinoin with no success. Treatment with topical Polyphenon E, 10%, twice daily was prescribed and started in both cases. After 1 month of treatment, all the warts lesions completely disappeared. No post-procedure perpigmentation was reported. Local tolerability was evaluated as very good by the two subjects. This two-case report suggests that topical Polyphenon E 10% could be an effective and very well tolerated therapeutic strategy in subjects with “difficult-to-treat” common and flat wart lesions.

Keywords: common warts; verruca planae; sinecaatechins

Article

Introduction

Common and flat warts are skin disease caused by human papillomavirus (HPV) infection [1] frequently seen in clinical practice. HPV has a specific tropism for squamous stratified epithelium [2] and this infection leads to proliferation of keratinocytes. HPV infection is haracterized by a relevant immune evasion mechanism that inhibits and delays the host immune response to the virus [3]. HPV genotypes types 2, 4, 27, 57, and 60 are responsible for common [4]. HPV genotypes 3 and 10 are involved in the pathogenesis of flat warts. Flat warts are common in children and young adults. Flat warts can spread through mildly traumatized skin such as an area of shaving (face in men or legs and groin region in women) [5]. Curettage, topical salicylic acid, and cryotherapy are often used in common and flat warts [6]. Liquid nitrogen is the most frequently used treatment for this type of warts; however, this procedure is in general very painful [7]. In addition, in case of flat warts the response to cryotherapy could be low. Excision is not a good option owing to frequent recurrences or scarring [8]. In case of therapy-resistant common warts lesions, laser and photodynamic therapy approaches could be used [9] but these methods are time- and cost-consuming. Therefore, in case of both common and flat warts, both first- and second-line treatments could be unsatisfactory due to their low efficacy, low local tolerability, risk of post procedure hyperpigmentation and high recurrence rate [10]. Imiquimod is a promising treatment of flat warts but its use is limited by the high cost and erythema and skin discomfort [11]. Topical green tea extract containing catechins (Polyphenon E or sinacatechins) is indicated as a first-line treatment for genital warts (condylomata acuminata) [12]. In subjects with genital warts, Polyphenon E/sinecatechins, applied 3 times a day and up to 16 weeks, induced a complete clearance rate in more than 50% of patients [13]. In addition, the recurrence rate at 3 months after the conclusion of the therapy is as low as <6% [14]. Polyphenon E is a quantified extract of green tea leaves (Camellia sinensis) where the main active substance is epigallocatechin gallate (EGCG), a polyphenol substance which represents the major component of the catechins fraction [15]. EGCG has potent anti-inflammatory, antioxidant, and proapoptotic actions. These mechanisms could explain its antiviral properties [16]. Recent data have shown that EGCG is able to modulate the cellular genes involved in Toll-like receptor production and in the apoptosis mechanisms [17]. The product has shown a good safety and tolerability profile. Local skin re-actions like erythema and edema, in general mild to moderate, have been reported in most treated subjects [18]. We report the clinical efficacy and the tolerability of Polyphenon E 10% ointment (VeregenTM, Medigene, Germany) in two subjects with a “difficult-to-treat,” treatment-resistant common and flat warts.

Cases Description

Case 1: Multiple common warts of the hands

This was a 6 years Albanese ancestor girl in a general wellness. No history of genetic or acquired immunodeficiencies. At the initial visit several common warts were detected in both hands (Figure 1) with a total lesion count of 13. A cycle of 3 cryotherapy procedures was done followed by a session of electrocauterization. These procedures were not successful. A treatment with topical Polyphenon E/sinecatechins 10% was stared with three application/daily for 25 days. The topical treatment induced a complete remission of all the lesions (Figure 2 and Figure 3, A and B). The product was very well tolerated.

Case 2: Multiple flat warts (verruca planae)

A 30-years old woman presented several flat warts lesions on the dorsal right hand and in the groin region (Figures 4 and 5; A). A previous ablative treatment with cryotherapy was attempted without success. A cycle of topical treatment with tretinoin was therefore performed. No clinical resolution was observed, also with this therapeutic approach. The subject was then treated with topical sinecatechins 10% twice daily for 30 days. A complete resolution of both hand and groin lesion was observed (Figures 4 and 5; B). No side effects were reported. No hyperpigmented lesions occurred.

Discussion

In some cases, both common and flat warts treatment could be a challenging therapeutic problem [19]. Some procedures could be very painful with a long down-time posttreatment period [20]. In the case of flat warts of the face postprocedural hyperpigmentation and scarring could be fearful complications [21]. Polyphenon E/sinecathechins ointment is considered an effective, well-tolerated, self-applicable topical treatment of genital warts [22]. Clinical efficacy and tolerability were evaluated in randomized vehicle-controlled phase III trials in more than 1,000 patients [23]. Complete clearance rate is observed in 51% of the treated subjects. Mean treatment du-ration for complete clearance was between 14 and 16 weeks [24]. Polyphenon E has an anti-viral action trough pathway triggering cell growth arrest and increasing proapoptotic molecules like p53 and p16 [25]. In addition, this compound interferes with cellular activity of E6 and E7, two HPV virus proteins [26]. E6 and E7are involved in the process of apoptosis inhibition and in the immune evasion mechanisms [27]. Therefore, Polyphenon E could express anti-HPV action through multiple mechanisms. The gene modulation expressed by Polyphenon E could be of help in fighting therapy-resistant HPV lesions. Polyphenon E has already shown to be an effective treatment of plane warts of the face [28]. An ideal wart therapy should be easy to apply (preferably home-based), painless, able to resolve all the treated lesions, not causing scarring, and with no or very short downtime period. In this two-case report, we have shown a high clinical efficacy of Polyphenon E in the treatment of multiple “therapy-resistant” common and flat wart lesions. It is remarkable that complete clearance of the lesions was achieved with a 4-week treatment. Conclusion This two-case report suggests that topical Polyphenon E 10% could be an effective and very well tolerated therapeutic strategy in subjects with “difficult-to-treat” common and flat wart lesions.

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