Effect of Allium Cepa-Allantoin-Pentaglycan Gel on Skin

Hypertrophic Scars: Clinical and Video-Capillaroscopic Results

of an Open-Label, Controlled, Nonrandomized Clinical Trial
ANNA CAMPANATI, MD, ANDREA SAVELLI, MD, LUCIA SANDRONI, PHD,y BARBARA MARCONI, MD,
ANGELA GIULIANO, MD, KATIA GIULIODORI, MD, GIULIA GANZETTI, MD, AND
ANNAMARIA OFFIDANI, MD

BACKGROUND Hypertrophic scar formation is a process in which prolonged angiogenesis sustained by

vascular endothelial growth factor cutaneous expression plays an important role.
OBJECTIVE This in vivo study was conducted to evaluate the clinical effect of a topical gel containing
onion extract, allantoin, and pentaglycan on hypertrophic scars and keloids.
MATERIALS AND METHODS Thirty people with hypertrophic scars or keloids were examined. Fifteen
patients received a topical application of a gel containing allium cepa, allantoin, and pentaglycan twice a
day for 24 weeks, the remaining 15 patients received no topical treatments. A clinical evaluation and an
intravital videocapillaroscopy were performed on every patient at baseline (T0) and 24 weeks (T24) after
the treatment.
RESULTS Only the patients who received the topical treatment showed a significant reduction in
neoangiogenetic features, demonstrated through an improvement of erythema and all video-
capillaroscopic markers of neoangiogenesis. These changes induced by therapy led to a general improve-
ment of the lesions.
CONCLUSION Topical applications of a gel containing allium cepa, pentaglycan, and allantoin twice a
day for 24 weeks seems to be useful in reducing neoangiogenesis in hypertrophic scars and keloids,
resulting in clinical improvement of skin lesions.
The authors have indicated no significant interest with commercial supporters.

W ound healing is a multiphase process that

develops through three phases: inflamma-
tion, proliferation, and maturation.
that, of the above-mentioned molecules, VEGF plays
the most important role.2,4,5

The therapeutic management of keloids and HTSs is

During the whole process, several chemokines
and growth factors interact to regulate the wound
healing phases: interleukin-6 (IL-6), insulin-like
growth factor 1 (IGF-1), platelet-derived growth
factor (PDGF), transforming growth factor beta
(TGF-b), and vascular endothelial growth factor
(VEGF).1–5
an interesting clinical challenge because keloids and
HTSs show a poor response to the therapy. One of
the most used topical treatments for keloids and
HTSs is allium-cepa, also known as onion extract,
which is a natural ingredient with anti-angiogenetic,
anti-inflammatory, bacteriostatic, and collagen
down-regulatory properties.2

Prolonged angiogenesis is one of the major contrib- Data from the literature regarding the therapeutic
uting factors to hypertrophic scar (HTS) formation5–7 effect of allium-cepa in keloids and HTSs are still
and in vitro and in vivo studies have recently found controversial,8 mainly because the therapeutic effects

Dermatology Clinic, Department of Clinical Medicine and Biotechnology; yExternal Faculty Member, Universitá
Politecnica delle Marche, Ancona, Italy

& 2010 by the American Society for Dermatologic Surgery, Inc.  Published by Wiley Periodicals, Inc. 
ISSN: 1076-0512  Dermatol Surg 2010;36:1439–1444  DOI: 10.1111/j.1524-4725.2010.01654.x

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of this substance have never been evaluated in a A physician external to the study performed a clin-
reproducible way. ical evaluation and an intravital videocapillaroscopy
on every patient at baseline (T0) and 24 weeks (T24)
The purpose of this open-label, controlled, non- after the treatment.
randomized clinical trial was to study the clinical
and videocapillaroscopic profiles of skin lesions in Clinical evaluation of the patients included age, sex,
patients with keloids or HTSs receiving topical phototype, type of lesion (keloids or HTSs), number
application of an allium cepa-allantoin-pentaglycan of cutaneous lesions (single vs multiple), age of
gel twice a day for 24 weeks. This study had two cutaneous lesions, and body area involved (upper
purposes: reporting neoangiogenetic changes at the part vs lower part of the body).
lesional level and introducing a reproducible method
to indicate changes in skin lesions during treatment. Assessed clinical features were erythema, tension,
height, itching, and burning. Lesions were graded
according to the following scale: 0 (absent), 1 (mild),
Materials and Methods
2 (moderate), and 3 (severe).
Patients
Every lesion was investigated using intravital
Thirty-five Caucasian patients, with single or mul-
videocapillaroscopic (IVCP) analysis. IVCP examin-
tiple keloids or HTSs, were examined.
ation is a technique to obtain, store, and compare
over time the photographic images of skin lesions
All of the lesions were less than 1 year old and were
and skin capillaries using an optic contact probe
located in different parts of the body (neck, trunk,
microscope attached to a computerized video
arms, and legs). None of the patients had received a
microscope (Fotofinder at magnification  60,
scar treatment before the examination.
 100,  200).

Exclusion criteria were pregnancy, breastfeeding,

IVCP analysis was performed to investigate
involvement of cutaneous sun-exposed areas, low
general improvement of skin lesions and three
adherence to the treatment, skin phototype greater
angiogenetic markers (enlarged or tortuous loops,
than III, and a declared allergy or intolerance to one
architectural derangement, and quantitative changes
or more gel components.
of capillary lesions), according to the following
scale: 0 (absent), 1 (mild), 2 (moderate), and 3
Informed consent was obtained from all subjects,
(severe).
and the study protocol met the guidelines of the
1975 Declaration of Helsinki and was approved by
A physician external to the study compared clinical
our institutional review board.
images of skin lesions.

Study Design
In this open-label, controlled, non-randomized
clinical trial, participants were divided into two
groups; 20 received a topical application of an allium
cepa-allantoin-pentaglycan gel (Kaloidon gel,
Laboratori Farmacologici Milanesi, Milan, Italy)
(components: allium-cepa, allantoin, pentaglycan)
twice a day for 24 weeks (study group), and 15
received no topical treatments at all (control group).
At the end of the study, we asked the patients to
fill out a form about treatment efficacy. It addressed
the appearance of skin lesions and was scored
as follows: 0 = no improvement, 1 = mild improve-
ment, 2 = moderate improvement, 3 = severe
improvement.
In the case of more than one lesion, only the lesion
with the highest score was considered.

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Statistical Analysis TABLE 1. Demographic, Clinical, and Video-

capillaroscopic Data at Baseline
A parametric analysis of variance for repeated mea-
surements (Student t-test) was used to evaluate ery- Study Control
thema, tension, height, itching, burning sensation, Group Group P-
Variable n = 15 n = 15 Value
general appearance, and IVCP score in each
participant. Age, 37.5 7 14.3 37.7 7 14.5 .18
mean 7 SD
Female, n 9 10 .67
Comparisons of baseline and T24 measurements Phototype III, n 14 13 .58
were made to determine any significant change. Type of lesion, n
Keloid 2 3 .33
Hypertrophic 13 12
Results scar
Number of
Twenty participants with single or multiple keloids
lesions, n
or HTSs were examined; 15 completed the study Single 12 13 .33
(Table 1) (9 women, 6 men, mean age 37.5 7 14.3), Multiple 3 2
13 with HTSs and two with keloids. They had skin Age of lesion, 7.3 7 3.1 7.0 7 3.0 .77
months,
phototype III, except for one patient with phototype mean 7 SD
II. In 14 patients, the cutaneous lesions were located Site
in the upper part of the body. Three patients had Upper body 14 15 .33
Lower body 1 0
multiple lesions, the rest one. The mean age of the
Clinical score
lesions was 7.3 7 3.1 months. Erythema 1.4 7 0.6 1.5 7 0.6 .33
Tension 1.8 7 1.1 2.0 7 1.1 .53
In the control group, 15 patients (10 women, 5 men, Burning or 1.3 7 0.8 1.5 7 0.8 .16
itching
mean age 37.7 7 14.5) with single or multiple ke-
Height 2.3 7 0.7 2.2 7 0.8 .58
loids or HTSs were selected: 12 with HTSs and three Videocapillaro-
with keloids. All participants had lesions in the up- scopic score
per part of the body; two had multiple lesions. The Enlarged 2.7 7 1.0 2.5 7 0.9 .33
loops
mean age of the lesions in the control group was Architectural 2.3 7 0.9 2.5 7 0.8 .50
7 7 3.02 months. derangement
Increased 3.2 7 0.6 3.1 7 0.7 .33
capillaries
At baseline (T0), no significant differences were
found between the two groups in terms of demo- SD = standard deviation.
graphic features (age, sex, phototype) (p4.05),
clinical criteria (type, number, age, location of the
lesions, related symptoms: erythema, tension, height, A comparison of the study and control groups after
and burning and itching) (p4.05), and IVCP scores 24 weeks demonstrated that an important reduction
(p4.05) (Table 1). Thus the two groups were in erythema and in all videocapillaroscopic markers
considered homogeneous. of neoangiogenesis was clear only in the study group
(Table 3).
The mean clinical scores (erythema, tension, itching
or burning, height) and IVCP scores decreased after Participants and physicians agreed that the general
24 weeks in all participants, but the reduction was appearance of skin lesions was much better in
statistically significant (po.005) only for erythema patients treated with onion extract than in the
and IVCP score in the group of patients receiving untreated ones (Table 3). None developed moderate
topical treatment (Table 2, Figure 1). or severe side effects.

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TABLE 2. Treatment Results in Study and Control

other clinical investigated parametersFtension,
Groups itching and burning, heightFimproved without
reaching a statistically significant level. Participants
P-
Variable T0 T24 Value
in the study group reported more evident improve-
ment in the general appearance of skin lesions than
Study group
untreated participants.
Clinical score
Erythema 1.4 7 0.6 1.1 7 0.5 o.05
Tension 1.8 7 1.1 1.5 7 0.7 .10 Controversial data about the efficacy of topical
Burning or 1.3 7 0.8 1.2 7 0.6 .16 treatment containing onion extract for keloids and
itching
Height 2.3 7 0.7 2.1 7 0.6 .16
HTSs have been reported in the literature.
Videocapillaro-
scopic score Several studies have demonstrated the potential
Enlarged 2.7 7 1.0 1.9 7 0.7 o.05 therapeutic properties of individual components
loops
Architectural 2.3 7 0.9 1.5 7 0.7 o.05 contained in such topical preparation: allium-cepa
derangement produces an in vitro antiproliferative effect on
Increased 3.2 7 0.6 2.5 7 0.5 o.05 fibroblasts and connective-tissue components,
capillaries
such as collagen, and reduces inflammation and
Control group
Clinical score physiologic scar development.7,8 Flavonoids
Erythema 1.5 7 0.6 1.4 7 0.5 .33 (quercetin and kaempferol) in onion extract cause
Tension 1.5 7 0.8 1.4 7 0.6 .58 fibroblast inhibition and other antiproliferative
Burning or 2.0 7 1.1 1.9 7 0.8 .16
itching
effects.3 Allantoin has emollient and soothing
Height 2.2 7 0.8 2.1 7 0.7 .16 properties and can reduce inflammation.3
Videocapillaro- Pentaglycan, a mix of hyaluronic acid, chondroitin
scopic score sulfate, and glycosaminoglycans, plays an important
Enlarged 2.5 7 0.9 2.4 7 0.8 .33
loops role in tissue recovery, skin hydration, and elasticity.
Architectural 2.5 7 0.8 2.1 7 0.8 .08
derangement A previous prospective, randomized, controlled trial
Increased 3.1 7 0.7 2.9 7 0.8 .33
had demonstrated that a topical preparation of on-
capillaries
ion extract, heparin, and allantoin can be effective in
scar prevention after laser removal of tattoos.3 Re-
Discussion
cent studies have demonstrated that a combination
Management of keloids and HTSs is often a thera- of onion extract and silicon sheet gel is more effec-
peutic challenge for physicians; successful treatment tive than occlusive silicon dressing in decreasing scar
should bring physiological functional recovery, relief height9 and that a combination of intralesional
from symptoms, and aesthetic improvement of skin triamcinolone acetonide (TAC) and topical onion
lesions. extract gel increases the therapeutic effect of TAC.10

Our study focused on the efficacy of a topical gel
preparation containing allium cepa, allantoin, and
pentaglycan through clinical and intravital video-
capillaroscopic assessment.
In our study, participants treated with gel had a
significant reduction in erythema and video-
capillaroscopic signs of neoangiogenesis, although
On the other hand, two reported controlled clinical
trials were unable to demonstrate a real, in vivo,
therapeutic effect of onion extract on HTSs, but the
treatment period was short (4–8 weeks), and this
may represent a critical limitation.11,12
Another randomized, double-blind, split-scar
study of patients with new surgical wounds also

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Figure 1. Clinical and videocapillaroscopic profile of hypertrophic scars before (A) and after (B) therapy.

demonstrated that onion extract gel did not improve
scar appearance, erythema, and hypertrophy more
than a petrolatum-based ointment,13 but a bias of
this study is the high mean age of the patients, who
are at lower risk for hypertrophic scarring.
It has already been demonstrated that VEGF
production is strongly expressed in the keratinocytes
overlying keloids.4 Furthermore, in vitro studies
have shown that it is expressed at higher levels in
keloid-derived fibroblasts than in normal skin.4 It

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TABLE 3. Comparison Between Study and Con-

mation in vivo, even if further trials with a larger
trol Group after 24 Weeks number of patients are needed.

Study Control P-
Variable Group Group Value
References
Clinical score 1. Wolfram D, Tzankov A, Pülzl P, Piza-Katzer H. Hypertrophic
Erythema 1.1 7 0.5 1.4 7 0.5 .04 scars and keloids–a review of their pathophysiology, risk factors,
Burning or 1.2 7 0.6 1.4 7 0.6 .20 and therapeutic management. Dermatol Surg 2009;35:171–81.
itching
2. Wu W-S, Wang F-S, Yang KD, et al. Dexamethasone induction of
Tension 1.5 7 0.7 1.9 7 0.9 .08 keloid regression through effective suppression of VEGF expres-
Height 2.1 7 0.6 2.1 7 0.7 .67 sion and keloid fibroblast proliferation. J Inves Dermatol
Videocapillaro- 2006;126:1264–71.
scopic score
3. Ho WS, Ying SY, Chan PC, Chan HH. Use of onion extract,
Enlarged loops 1.9 7 0.7 2.4 7 0.8 .02 heparin, allantoin gel in prevention of scarring in Chinese patients
Architectural 1.5 7 0.7 2.1 7 0.8 .002 having laser removal of tattoos: a prospective randomized con-
derangement trolled trial. Dermatol Surg 2006;32:891–6.
Increased 2.5 7 0.5 2.9 7 0.8 .02
4. Gira AK, Brown LF, Washington CV, et al. Keloids demonstrate
capillaries high-level epidermal expression of vascular endothelial growth
Improvement of factor. J Am Acad Dermatol 2004;50:850–3.
general appearance
5. Pikula M, Źebrowska ME, Trzonkowski P, et al. Effects of
Physician 2.0 7 0.5 1.7 7 0.6 .04
enoxaparin and onion extract on cytokine production in skin
Patients 1.8 7 0.4 2.1 7 0.5 .01 fibroblasts. Centr Eur J Immunol 2009;34:68–71.

6. Amadeu T, Braune A, Mandarim-de-Lacerda C, et al. Vascular-

ization pattern in hypertrophic scars and keloids: a stereological
analysis. Pathol Res Pract 2003;199:469–73.
has also been postulated that it is directly implicated 7. Fitzpatrick RE. Treatment of inflamed hypertrophic scars using
in the pathogenesis of keloids2,5 and that a decrease intralesional 5-FU. Dermatol Surg 1999;25:224–32.

in skin expression of VEGF may affect development
and extension of HTSs and keloids.2,5
Moreover, a recent in vitro study has stated that
onion compounds may reduce cytokine levels in
human fibroblast cell lines through a modulation
of intracellular signalling pathway. The authors
demonstrated that onion substances may
inhibit nuclear factor kappaB activity and have
the ability to bind different growth factors, such
as VEGF.5
Our results agree with data from the literature; the
8. Zurada JM, Kriegel D, Davis IC. Topical treatments for hyper-
trophic scars. JAAD 2006;55:1024–31.
9. Hosnuter M, Payasli C, Isikdemir A, Tekerekoglu B. The effects of
onion extract on hypertrophic and keloid scars. J Wound Care
2007;16:251–4.
10. Koc E, Arca E, Surucu B, Kurumlu Z. An open, randomized,
controlled, comparative study of the combined effect of intrales-
ional triamcinolone acetonide and onion extract gel and
intralesional triamcinolone acetonide alone in the treatment of
hypertrophic scars and keloids. Dermatol Surg 2008;34:1507–14.
11. Jackson BA, Shelton AJ. Pilot study evaluating topical onion ex-
tract as treatment for postsurgical scars. Dermatol Surg
1999;25:267–9.
12. Clarke L, Baker B, Trahan C, et al. A prospective double-blinded
study of Mederma skin care vs placebo for post-traumatic scar
reduction. Cosm Dermatol 1999;12:19–26.

density of the capillary vessels in HTSs and keloids is
greater than in normal skin, and vessels are often
expanded, suggesting ongoing neovascularization.6
A topical treatment containing allium cepa, pent-
aglycan, and allantoin twice a day for 24 weeks
could be useful in reducing neoangiogenesis in HTSs
and keloids. All of these factors seem to bring clin-
ical improvement of skin lesions. These reported
data show the benefits of onion extract on scar for-
13. Chung V, Kelley L, Marra D, Jiang SB. Onion extract gel versus
petrolatum emollient on new surgical scars: prospective double-
blinded study. Dermatol Surg 2006;32:193–8.
Address correspondence and reprint requests to: Anna
Campanati, MD, Dermatology Clinic, Department of
Clinical Medicine and Biotechnology, Universitá Polite-
cnica delle Marche, Ancona, Italy, or e-mail: a.campa-
nati@univpm.it

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