Plantar warts account for 30% of all cutaneous warts. These lesions could be very painful, especially if the lesion is located over pressure sites such as the metatarsal head. Plantar wart treatment remains a challenging therapeutic problem. A 67-year-old immunocompetent nonsmoking man presented with a large mosaic plantar wart on his right foot. The lesion had been present for 5 years. Several cryotherapy sessions (a total of 6 procedures) had been performed with no success. The lesion was therefore treated with a 5-fluorouracil (5-FU) regimen and then with a topical combination of 5-FU and salicylic acid, but also these approaches failed. At the initial visit, a large (16 cm2) mosaic wart lesion was present. Treatment with topical Polyphenon E, 10%, twice daily was prescribed and started. After 3 months of treatment, the lesion completely disappeared. Interestingly, no curettage or mechanical pickling of the hyperkeratotic parts of the lesion were performed before the start of the treatment. Local tolerability was evaluated as very good by the patient.

Plantar warts are a common viral skin disease caused by human papillomavirus (HPV) infection [1]. HPV has a specific tropism for squamous stratified epithelium [2] and this infection leads to proliferation of keratinocytes. HPV infection is characterized 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 and plantar warts and myrmecia [4]. On the other hand, genotypes 6 and 11 are the most common HPV involved in genital wart [5] development. Curettage, topical salicylic acid, and cryotherapy are often used in plantar warts [6]. Liquid nitrogen is the most frequently used treatment for this type of warts; however, this procedure is in general very painful [7]. Excision is not a good option owing to frequent recurrences or scarring [8]. In case of therapy-resistant lesions, laser and photodynamic therapy approaches could be used [9] but these methods are time- and cost-consuming. Therefore, in case of plantar warts, both first- and second-line treatments are in general still unsatisfactory due to their low efficacy, low local tolerability, and high recurrence rate [10]. Topical green tea extract containing catechins (Polyphenon E) is indicated as a first-line treatment for genital warts (condylomata acuminata) [11]. In subjects with genital warts, Polyphenon E, applied 3 times a day and up to 16 weeks, induced a complete clearance rate in more than 50% of patients [12]. In addition, the recurrence rate at 3 months after the conclusion of the therapy is as low as < 6% [9]. 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 [13]. EGCG has potent anti-inflammatory, antioxidant, and proapoptotic actions. These mechanisms could explain its antiviral properties [14]. Recent data have shown that EGCG is able to modulate the cellular genes involved in Toll-like receptor production and in the apoptosis mechanisms [15]. The product has shown a good safety and tolerability profile. Local skin reactions like erythema and edema, in general mild to moderate, have been reported in most treated subjects [16]. Polyphenon E has shown to be an effective and very well-tolerated treatment for common [17] and plane [18] warts. Data regarding the efficacy of Polyphenon E in plantar warts are lacking so far. We report the clinical efficacy and the tolerability of Polyphenon E 10% ointment (VeregenTM, Medigene, Germany) in a subject with a “difficult-to-treat”, treatment-resistant plantar wart.

A 67-year-old immunocompetent nonsmoking man presented with a large mosaic plantar wart on his right foot. The lesion had been present for 5 years. Several cryotherapy sessions (a total of 6 procedures) had been performed with no success. The lesion was therefore treated with a 5-fluorouracil regimen and then with a topical combination of 5-fluorouracil and salicylic acid, but also these approaches failed. At the initial visit, a large (16 cm2) mosaic wart lesion was present (Fig. 1). Treatment with topical Polyphenon E 10% twice daily was prescribed and started. After 3 months of treatment, the lesion completely disappeared (Fig. 2). Interestingly, no curettage or mechanical pickling of the hyperkeratotic parts of the lesion were performed before the start of the treatment. Local tolerability was evaluated as very good by the patient.

Fig. 1.

Plantar mosaic wart lesion on the right foot before treatment with green tea extract.

Fig. 1.

Plantar mosaic wart lesion on the right foot before treatment with green tea extract.

Close modal
Fig. 2.

Plantar region after a 3-month treatment with green tea extract.

Fig. 2.

Plantar region after a 3-month treatment with green tea extract.

Close modal

Plantar warts account for 30% of all cutaneous warts [19]. Large lesions are in general plaques with rough hyperkeratotic surface with some brown-black dots representing thrombosed capillaries [20]. These lesions could be very painful, especially if the lesion is located over pressure sites such as the metatarsal head [21]. Plantar wart treatment remains a challenging therapeutic problem [22]. Some procedures could be very painful with a long downtime posttreatment period [23]. Polyphenon E ointment is considered an effective, well-tolerated, self-applicable topical treatment of genital warts [24]. Clinical efficacy and tolerability was evaluated in randomized vehicle-controlled phase III trials in more than 1,000 patients [25]. Complete clearance rate is observed in 51% of the treated subjects. Mean treatment duration for complete clearance was between 14 and 16 weeks [26]. Polyphenon E has an antiviral action trough pathway triggering cell growth arrest and increasing proapoptotic molecules like p53 and p16 [27]. In addition, this compound interferes with cellular activity of E6 and E7, two HPV virus proteins [28]. E6 and E7are involved in the process of apoptosis inhibition and in the immune evasion mechanisms [29]. Therefore, Polyphenon E could express anti-HPV action through multiple mechanisms. The gene modulation expressed by Polyphenon could be of help in fighting therapy-resistant HPV lesions. Polyphenon E has shown to be an effective treatment of plane warts of the face [30]. 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 [23]. In this case report, we have shown a high clinical efficacy of Polyphenon E in the treatment of a therapy-resistant large mosaic plantar wart lesion. It is remarkable that complete clearance of the lesion was achieved with a 12-week treatment without any pretreatment curettage or pickling procedures and without a downtime period and without scar formation. This case report suggests that topical Polyphenon E 10% could be an effective therapeutic strategy in subjects with “difficult-to-treat” plantar wart lesions. Specific controlled trials in this specific population are warranted.

The authors have no ethical conflicts to disclose.

M.M. is an employee of Cantabria Labs Difa Cooper; Caronno P., Italy.

1.
Jenson
AB
,
Sommer
S
,
Payling-Wright
C
,
Pass
F
,
Link
CC
 Jr
,
Lancaster
WD
.
Human papillomavirus. Frequency and distribution in plantar and common warts
.
Lab Invest
.
1982
Nov
;
47
(
5
):
491
7
.
[PubMed]
0023-6837
2.
Majewski
S
,
Jablonska
S
.
Human papillomavirus-associated tumors of the skin and mucosa
.
J Am Acad Dermatol
.
1997
May
;
36
(
5 Pt 1
):
659
85
.
[PubMed]
0190-9622
3.
Tindle
RW
.
Immune evasion in human papillomavirus-associated cervical cancer
.
Nat Rev Cancer
.
2002
Jan
;
2
(
1
):
59
65
.
[PubMed]
1474-175X
4.
Pfister
H
,
zur Hausen
H
.
Seroepidemiological studies of human papilloma virus (HPV-1) infections
.
Int J Cancer
.
1978
Feb
;
21
(
2
):
161
5
.
[PubMed]
0020-7136
5.
Gissmann
L
,
Wolnik
L
,
Ikenberg
H
,
Koldovsky
U
,
Schnürch
HG
,
zur Hausen
H
.
Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers
.
Proc Natl Acad Sci USA
.
1983
Jan
;
80
(
2
):
560
3
.
[PubMed]
0027-8424
6.
Sterling
JC
,
Handfield-Jones
S
,
Hudson
PM
;
British Association of Dermatologists
.
Guidelines for the management of cutaneous warts
.
Br J Dermatol
.
2001
Jan
;
144
(
1
):
4
11
.
[PubMed]
0007-0963
7.
GIBBS
, Sam, et al. Local treatments for cutaneous warts: systematic review Commentary: Systematic reviewers face challenges from varied study designs. Bmj,
2002
, 325.7362: 461.
8.
Sterling
JC
,
Handfield-Jones
S
,
Hudson
PM
;
British Association of Dermatologists
.
Guidelines for the management of cutaneous warts
.
Br J Dermatol
.
2001
Jan
;
144
(
1
):
4
11
.
[PubMed]
0007-0963
9.
FUCHS
, Silke M., et al. Photodynamic therapy (PDT) and waterfiltered infrared A (wIRA) in patients with recalcitrant common hand and foot warts. German medical science: GMS e-journal,
2004
, 2.
10.
Kodner
CM
,
Nasraty
S
.
Management of genital warts
.
Am Fam Physician
.
2004
Dec
;
70
(
12
):
2335
42
.
[PubMed]
0002-838X
11.
WORKOWSKI
, Kimberly A.; BERMAN, Stuart M. Centers for Disease Control and Prevention sexually transmitted disease treatment guidelines. Clinical infectious diseases,
2011
, 53.suppl_3: S59-S63.
12.
Stockfleth
E
,
Beti
H
,
Orasan
R
,
Grigorian
F
,
Mescheder
A
,
Tawfik
H
, et al.
Topical Polyphenon E in the treatment of external genital and perianal warts: a randomized controlled trial
.
Br J Dermatol
.
2008
Jun
;
158
(
6
):
1329
38
.
[PubMed]
0007-0963
13.
Waltner-Law
ME
,
Wang
XL
,
Law
BK
,
Hall
RK
,
Nawano
M
,
Granner
DK
.
Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production
.
J Biol Chem
.
2002
Sep
;
277
(
38
):
34933
40
.
[PubMed]
0021-9258
14.
Valcic
S
,
Muders
A
,
Jacobsen
NE
,
Liebler
DC
,
Timmermann
BN
.
Antioxidant chemistry of green tea catechins. Identification of products of the reaction of (-)-epigallocatechin gallate with peroxyl radicals
.
Chem Res Toxicol
.
1999
Apr
;
12
(
4
):
382
6
.
[PubMed]
0893-228X
15.
Masuda
M
,
Suzui
M
,
Weinstein
IB
.
Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines
.
Clin Cancer Res
.
2001
Dec
;
7
(
12
):
4220
9
.
[PubMed]
1078-0432
16.
Tatti
S
,
Swinehart
JM
,
Thielert
C
,
Tawfik
H
,
Mescheder
A
,
Beutner
KR
.
Sinecatechins, a defined green tea extract, in the treatment of external anogenital warts: a randomized controlled trial
.
Obstet Gynecol
.
2008
Jun
;
111
(
6
):
1371
9
.
[PubMed]
0029-7844
17.
Gerlero
P
,
Hernández-Martín
Á
.
Treatment of Warts in Children: an Update
.
[English Edition]
.
Actas Dermosifiliogr
.
2016
Sep
;
107
(
7
):
551
8
.
[PubMed]
0001-7310
18.
Clouth
A
,
Schöfer
H
.
Treatment of recalcitrant facial verrucae vulgares with sinecatechins (greentea catechins) ointment
.
J Eur Acad Dermatol Venereol
.
2015
Jan
;
29
(
1
):
178
9
.
[PubMed]
0926-9959
19.
Kilkenny
M
,
Marks
R
.
The descriptive epidemiology of warts in the community
.
Australas J Dermatol
.
1996
May
;
37
(
2
):
80
6
.
[PubMed]
0004-8380
20.
Jabłońska
S
,
Majewski
S
,
Obalek
S
,
Orth
G
.
Cutaneous warts
.
Clin Dermatol
.
1997
May-Jun
;
15
(
3
):
309
19
.
[PubMed]
0738-081X
21.
Bacelieri
R
,
Johnson
SM
.
Cutaneous warts: an evidence-based approach to therapy
.
Am Fam Physician
.
2005
Aug
;
72
(
4
):
647
52
.
[PubMed]
0002-838X
22.
Stender
IM
,
Na
R
,
Fogh
H
,
Gluud
C
,
Wulf
HC
.
Photodynamic therapy with 5-aminolaevulinic acid or placebo for recalcitrant foot and hand warts: randomised double-blind trial
.
Lancet
.
2000
Mar
;
355
(
9208
):
963
6
.
[PubMed]
0140-6736
23.
Vlahovic
TC
,
Khan
MT
;
VLAHOVIC
.
Tracey C.; KHAN, M. Tariq. The Human Papillomavirus and Its Role in Plantar Warts
.
Clin Podiatr Med Surg
.
2016
;
33
(
3
):
337
53
.
[PubMed]
0891-8422
24.
Stockfleth
E
,
Meyer
T
.
The use of sinecatechins (polyphenon E) ointment for treatment of external genital warts
.
Expert Opin Biol Ther
.
2012
Jun
;
12
(
6
):
783
93
.
[PubMed]
1471-2598
25.
Gupta
AK
,
Daigle
D
.
Sinecatechins 10% ointment: a green tea extract for the treatment of external genital warts
.
Skin Therapy Lett
.
2015
Jan-Feb
;
20
(
1
):
6
8
.
[PubMed]
1201-5989
26.
Stockfleth
E
,
Meyer
T
.
The use of sinecatechins (polyphenon E) ointment for treatment of external genital warts
.
Expert Opin Biol Ther
.
2012
Jun
;
12
(
6
):
783
93
.
[PubMed]
1471-2598
27.
Thakur
VS
,
Ruhul Amin
AR
,
Paul
RK
,
Gupta
K
,
Hastak
K
,
Agarwal
MK
, et al.
p53-Dependent p21-mediated growth arrest pre-empts and protects HCT116 cells from PUMA-mediated apoptosis induced by EGCG
.
Cancer Lett
.
2010
Oct
;
296
(
2
):
225
32
.
[PubMed]
0304-3835
28.
Qiao
Y
,
Cao
J
,
Xie
L
,
Shi
X
.
Cell growth inhibition and gene expression regulation by (-)-epigallocatechin-3-gallate in human cervical cancer cells
.
Arch Pharm Res
.
2009
Sep
;
32
(
9
):
1309
15
.
[PubMed]
0253-6269
29.
Park
JS
,
Kim
EJ
,
Kwon
HJ
,
Hwang
ES
,
Namkoong
SE
,
Um
SJ
.
Inactivation of interferon regulatory factor-1 tumor suppressor protein by HPV E7 oncoprotein. Implication for the E7-mediated immune evasion mechanism in cervical carcinogenesis
.
J Biol Chem
.
2000
Mar
;
275
(
10
):
6764
9
.
[PubMed]
0021-9258
30.
Gerlero
P
,
Hernández-Martín
Á
.
Treatment of Warts in Children: an Update
.
[English Edition]
.
Actas Dermosifiliogr
.
2016
Sep
;
107
(
7
):
551
8
.
[PubMed]
0001-7310
Open Access License / Drug Dosage / Disclaimer
This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.