Farmacia italiana online: Comprare antibiotico Amoxicillina e Roma senza ricetta.
Topical treatments for hypertrophic scars
Joanna M. Zurada, AB,a David Kriegel, MD,b and Ira C. Davis, MDc
Hypertrophic scars represent an abnormal, exaggerated healing response after skin injury. In additionto cosmetic concern, scars may cause pain, pruritus, contractures, and other functional impairments.
Therapeutic modalities include topical medications, intralesional corticosteroids, laser therapy, andcryosurgery. Topical therapies, in particular, have become increasingly popular because of their easeof use, comfort, noninvasiveness, and relatively low cost. This review will discuss the properties andeffectiveness of these agents, including pressure therapy, silicone gel sheeting and ointment, polyurethanedressing, onion extract, imiquimod 5% cream, and vitamins A and E in the prevention and treatment ofhypertrophic scars. ( J Am Acad Dermatol 2006;55:1024-31.)
The wound healing process consists of 3 Clinically, hypertrophic scars are raised, red,
stages—inflammation, granulation, and ma-
nodular lesions that occur most commonly in areas
of thick skin. They frequently develop within 8
tion, produces exudate from damaged vessels that
weeks of a burn, wound closure with excess tension,
fills the wound. Neutrophils trigger an inflammatory
wound infection, hypoxia, or other traumatic skin
cell cascade and macrophages phagocytose cellular
and foreign debris. Subsequently, in the granulation
growth phase for up to 6 months that may be
phase, macrophages secrete cytokines that promote
followed by regression during the next 12 to 18
granulation tissue formation consisting of re-epithe-
lialization, recreation of an appropriate blood sup-
Early recognition of the potential development of
ply, and reinforcement of the injured tissue. In the
the hypertrophic scar is critical in its management.
final stage of wound healing, matrix remodeling,
Because hypertrophic scars are often painful and
fibroblasts proliferate and deposit new collagen and
difficult to treat, several treatments have been devel-
matrix materials at the wound site. The remodeling
oped in the past several years in an effort to minimize
process of collagen synthesis and lysis can last up to
tissue growth and wound contraction. This review
will focus on pressure therapy, silicone gel sheeting
Hypertrophic scars, by definition, represent an
and ointment, polyurethane dressing, onion extract,
exaggerated proliferative response to wound heal-
imiquimod 5% cream, and vitamins A and E in the
ing that stays within the boundaries of the original
management of hypertrophic scarring. A summary
wound, in contrast to keloids, which have a more
of these therapies and a selection of common com-
aggressive life cycle and extend beyond the original
borders. Because the collagen found is in a disor-
ganized, whorllike arrangement rather than inthe normal parallel orientation, hypertrophic scarsare indurated, elevated, and poorly ext
Hypertrophic scars are also characterized by hyper-
Pressure therapy has been the preferred conser-
vascularity, hence, their erythematous appearance.
vative management of scars since the 1970s, espe-cially in treating hypertrophic scarring after burninjury. Pressure therapy is influential primarily while
From the Columbia University College of Physicians and Sur-
the scar is active and, therefore, loses some efficacy
geons,a Mount Sinai Department of Dermatology,b and New
after 6 months of treatmeThe garments are typ-
York Medical College Department of Dermatology.c
ically custom-made from an elastic material with a
Funding sources: None.
Conflicts of interest: None identified.
high spandex content and are intended to be worn
Reprints not available from the authors.
for approximately 1 year until the scar matures.To
Correspondence to: Ira C. Davis, MD, 280 North Central Park Ave,
prevent a decrease in elasticity, garments should
Published online September 19, 2006.
of compression therapy include its limited use in
0190-9622/$32.00ª 2006 by the American Academy of Dermatology, Inc.
anatomic depressions, flexures, or areas of high
movement; patient discomfort; the need to be
sions, or high-motion but few studies have
subjective pressuremeasurements; sideeffects of local skinmaceration
hypertrophic scars andsome evidence thatimproves mature scars
Studies have shown: ÿ, no adequate benefit; ÿ/1, equivocal results; 1, some benefit; 11, marked benefit.
worn at all times; and occasional skin ulceration
a thinning of the dermis, decrease in edema, and a
from uneven pressure distribution. For these reasons,
reduction of blood flow and oxygen.The hypoxic
patient compliance can be a major problem, with re-
environment is hypothesized to decrease collagen
ports of noncompliance ranging from 8.5% to 59%
formation and increase collagen lysis and loosen the
Pressure treatment is believed to accelerate
collagen fibrils aligned to the skin surface, thereby
wound maturation by several mechanisms, namely
more closely approximating the elastic requirements
of the skin.This hypothesis remains controver-
(P = .072) that the proportion of patients developing
sial, however, as other studies have shown that
abnormal scars was lower in the topical silicone
qualitative improvements in scar tissue receiving
gel-sheeting group. However, of those patients at
pressure therapy correlate with increased blood
high risk who underwent scar revision there was a
significant statistical difference (P = .035) that topical
A fair body of evidence supports the use of
silicone sheets are effective in reducing the devel-
compression therapy but literature is generally lack-
opment of abnormal scars after surgical excision.
ing in reports on effectiveness and optimal pressures.
Katzsupported these findings in an examination
The consensus is that an applied pressure of 25 mm
of 14 patients with 14 hypertrophic scars less than
Hg may represent ideal loadingbut more recent
3 months old. Nine patients had long-standing hy-
studies suggest that good clinical results may be
pertrophic scars that were completely excised and
achieved at much lower compression levels.
treated with silicone sheeting soon after re-epitheli-
However, given that most often this measurement
alization. Five patients had a history of hypertrophic
is made clinically by the therapist together with
scar formation and were given silicone sheeting
feedback from the patient, pressure measurements
within 2 months of operation to prevent recurrence.
are subjective and not standardizOverall, there
In 11 of these cases (79%), hypertrophic scars did not
is some evidence to support that compression ther-
recur after at least 6 months of follow-up.
apy may be effective but more definitive research is
The mechanism of silicone gel sheeting remains
needed to evaluate the most optimum parameters.
unclear, although several hypotheses exist. Studieshave shown that silicone sheets do not change
pressure, temperature, or oxygen tension at the
Silicone, a soft, semiocclusive scar cover, is com-
posed of cross-linked polydimethylsiloxone poly-
rative water loss almost half that of skin and have
mer that has extensibility similar to that of skin. Since
been compared with the stratum corneum. Most
its introduction in 1982, topical silicone gel sheeting
researchers believe that silicone acts by creating
and ointment have been used widely to minimize
a hydrated, occluded environment that decreases
the size, induration, erythema, pruritus, and exten-
capillary activity, thereby reducing fibroblast-in-
sibility of pre-existing hypertrophic scars and to
duced collagen deposition and scar hypertro-
prevent the formation of new ones. Numerous for-
mulations exist, in addition to several gels and oint-
minimize fibroblast production of collagen and pro-
mote wound flatteningInterestingly, the use of
The therapeutic effect of topical silicone gel
silicone cream alone compared with silicone cream
sheeting on pre-existing hypertrophic scars is well
with occlusive dressing showed 22% and 82% scar
improvement, respectively, with respect to ery-
uncontrolled clinical reports stating that silicone
thema, tenderness, pruritus, and hardness.These
gel sheeting promotes resolution of hypertrophic
results supported that occlusion may be synergistic
in wound healing and suggested that silicone gel
alone may not be as effective as silicone sheeting.
trolled trial of 20 patients who had either evolving
Wounds treated with silicone gel sheeting have
hypertrophic scars or keloids, silicone gel sheeting
negligible amounts of silica in histologic sections.
stopped the development of and softened evolving
Therefore, the presence of silicone itself may not
hypertrophic lesions in 85% of caSilicone gel
sheeting has also been shown to significantly im-
showed that silicone gel dressings and nonsilicone
prove elasticity of old scars between 1 and 6 months
gel dressings were equally effective in improving
after treatment when compared with untreated
size, induration, and color of hypertrophic scar
In another study comparing a silicone-free cream
Silicone sheeting also helps minimize new hyper-
and occlusive dressing with petrolatum alone, scar
trophic scarring when applied about 2 weeks after
improvement was significantly greater in the cream-
occlusive dressing group with respect to pruritus,
in patients at high riskethose who had a significant
pain, hardness, elevation, and erythemfurther
history of hypertrophic scar or keloid formation after
a surgical proceduree29% developed hypertrophic
In summary, silicone gel sheeting is efficacious,
scars after silicone gel sheeting whereas 44% devel-
both in minimizing the severity of hypertrophic scars
oped hypertrophic scars after routine postoperative
in fresh wounds and in promoting the resolution
care. This finding provided only marginal evidence
of pre-existing hypertrophic scars. Silicone ointment
tacky sheets; varietyof configurations available(standard and large sheets,areola circles, mastopexy,strips, C-strips)
colorless, fast-dryingclear gel; once-dailyapplication; suitable undercosmetics
in conjunction withEpi-Derm sheetsand SilqueClenz scarand sheet cleanser
available in skin-tonedor clear formulations
pads; maintain a moistwound environment and helpprevent bacterial contamination
clear gel; new separatekid-friendly preparation
or gel, although more convenient and suitable for
healing environment that may promote re-epitheli-
exposed areas, is less effective than silicone sheeting.
alization and dermal extracellular matrix synthesisand, hence, decrease scarriDespite the the-
oretic risk that a moist environment is associated
Polyurethane dressing is a self-adherent, flexible,
with a higher risk of wound infection, studies have
hydroactive pad that should be worn 12 to 24 h/d for
shown that occlusive dressings do not increase the
a minimum of 8 consecutive weeks.Advantages
of this form of treatment are its availability as clear
Hydroactive dressings have been shown to pre-
pads for use on exposed areas such as the face or
vent the formation of hypertrophic scars.A pilot
hands and low incidence of skin maceration because
study of 60 patients noted significant improvements
of the pads’ evaporative properties. Polyurethane
in microcirculation and surface qualities in patients
occlusive dressings act by creating a moist wound-
who were treated with polyurethane dressing for
6 weeks after surgical incisions when compared
controlled clinical studies in the United States on the
with other patients who were randomized to receive
effect of onion extract on human wound healing.
either dry gauze dressing until removal of the sutures,
One clinical trial evaluating onion extract in the
hydroactive dressing until removal of the sutures, or
prophylactic treatment of 17 scars after Mohs micro-
dry gauze dressing until removal of sutures followed
graphic surgery showed no statistically significant
by hydroactive dressing for 6 weeks.In another
difference between pretreatment and posttreatment
study of 60 patients with acute facial lacerations, a 5-
evaluations of erythema and pruritus after 1 month
day course of polyurethane dressing after acute skin
of 3-times daily applications of onion extract gel
injuryedespite initially showing significantly im-
In fact, a significant reduction in scar erythema was
proved comfort, less erythema, and less potential for
demonstrated in control patients who used a petro-
scarring when compared with dry gauzeeshowed
latum-based ointment for 1 month, possibly because
negligible differences between the dry gauze control
of the effects of petrolatum on scar hydration.
group after 2 monthsThis suggested that the mag-
Another randomized, double-blinded trial evalu-
nitude of benefit from occlusive dressings may depend
ating 97 patients with new and old scars who were
assigned to a Mederma treatment group or placebo
Polyurethane dressing also reduces color, prom-
gel control group for 2 months showed similar
inence, and hardness of mature hypertrophic
results. Scar changes were measured using 6 cate-
scars.In a comparative study in which 12 pa-
gories of scar size, overall improvement, noticeable
tients were randomized to 4 groups (hydroactive
appearance, elevation, erythema, and softness. The
polyurethane dressing alone, polyurethane plus
only significant advantage in the treated group was
compression, silicone sheeting plus compression,
the patient-reported improvements of a softer, less
and compression alone for 24 h/d for 8 weeks), the
noticeable scar at 2 months.There were no notable
most pronounced effects were achieved with either
differences with respect to physician-measured
polyurethane dressing plus compression or silicone
appearance and size nor patient-measured erythema
and elevation. More patients in the placebo group
compression was slightly superior to silicone plus
than treated group reported improvement with a
compression in reduction of surface roughness.
less noticeable scar at 1 week and a less red scar
These effects lasted for at least 1 year after the
after 1 month. The study’s short follow-up time of
termination of therapy. Furthermore, polyurethane
2 months, however, was a limitation of this study.
dressing alone was found to provide functional
The most recent randomized, double-blinded,
and structural improvement in scar tissue that was
split-scar study of 24 patients with new surgical
slightly superior to that obtained from compression
wounds also demonstrated that onion extract gel
alone. It was speculated that scar dressings and
did not improve scar appearance, erythema, and
compression may promote dynamic shear forces
hypertrophy when compared with a petrolatum-
based ointment.Before enrollment, each patient
Currently, polyurethane dressing has unclear ef-
tested negatively for an allergic reaction to both
fects on the development of new hypertrophic scars
treatments by a 48-hour patch test on the forearm.
but has been shown to improve the prominence and
Each scar half then received either the onion extract
appearance of mature scars in a small randomized
or petrolatum ointment 3 times daily for 8 weeks.
trial. Further studies are necessary to elucidate its
The scars were evaluated by blinded investigators
role in hypertrophic scar treatment.
and patients at 2, 8, and 12 weeks after initiation oftreatment and by blinded patients at 11 monthspostoperatively. None of the scars became hyper-
trophic at 11 months, but it was uncertain whether
Allium cepa, or onion extract, is found in a num-
the patients would have developed abnormal scar-
ber of scar treatment products. Patients, in particular,
ring without treatments. One limitation of this study,
value this remedy because of its ease of use, relatively
however, was that all the patients were elderly
low cost, ‘‘botanical’’ ingredients, and widespread
Caucasians, a group inherently at lower risk for
availability. Onion extract exhibits anti-inflammatory,
hypertrophic scarring than patients who are younger
bacteriostatic, and collagen down-regulatory prop-
In summary, despite the wide use of onion extract
by patients, there is no evidence that it is beneficial
Documented clinical studies of onion extract have
in improving hypertrophic scars. In the few studies
shown that onion extract does not improve hyper-
conducted to date, more patients in the petrolatum
trophic scarring. To date, there have been 3 major
control group reported greater improvements in
wound healing when compared with those who
significant 20% reduction in scar size in the 0.05%
retinoic acid treatment group compared with the basecream control group. A more recent study of a
different form of vitamin A, 0.25% tocoretinate oint-
Imiquimod 5% cream, a topical immune response
ment, showed marked decreases in the size, stiffness,
modifier, is approved for treatment of genital warts,
erythema, and pruritus in all mature hypertrophic
basal cell carcinoma, and actinic keratoses.Imiqui-
scarsOnly 4 hypertrophic scars were examined,
mod stimulates proinflammatory cytokines, espe-
however, making these data preliminary.
cially interferon-a, which generate a cell-mediated
Vitamin A treatment has its downsides, however.
immune response. Interferon-a increases collagen
As topical retinoids may be absorbed systemically,
breakdown. In addition, imiquimod alters the ex-
hypervitaminosis and teratogenicity are potential
pression of genes associated with apoptosis.
complications of this form of therapy and, therefore,
Therefore, imiquimod has been used in an attempt
limit its use, especially in pregnant women and
people who take oral vitamin supplements.
Because of the success of imiquimod 5% cream in
In general, sufficient data are lacking on the
lowering keloid recurrences after operation, its role
efficacy of topical vitamin A on hypertrophic scarring
in the prevention of hypertrophic scars is currently
and its use may be associated with side effects.
under evaluation. A recent randomized, double-
Vitamin A should, therefore, not be recommended.
blinded study of 15 patients investigated the use ofimiquimod 5% cream in the prevention of hypertro-
phic scarring after breast operTreatment with
Vitamin E (tocopherol), a lipid-soluble antioxi-
imiquimod consisted of gently rubbing the cream
dant, has complex effects on wound healingIt has
over the scar for 3 to 5 minutes once every 3 to 4 days
been shown to penetrate into the reticular dermis
for a period of 8 weeks. At 24 weeks postsurgery,
and reduce the formation of oxygen radicals that
imiquimod treatment improved scar quality, espe-
impede healing and damage DNA, cellular mem-
cially color and elevation, when compared with two
branes, and lipids. Vitamin E also alters collagen
control groups (no treatment and treatment with
and glycosaminoglycan production and inhibits the
petrolatum.) There was an absence of hypertrophic
spread of peroxidation of lipids in cellular mem-
scars and keloids in the imiquimod group, although
branes, thereby acting as a membrane-stabilizing
this might have been related to the small sample size.
Of note, all patients in the treatment group experi-
Despite numerous anecdotal reports claiming
enced an inflammatory response characterized by
that vitamin E speeds wound healing and improves
erythema, local pain, and pinpoint bleeding. This
the cosmetic appearance of scars, little scientific
response allowed ‘‘blinded’’ physicians to distin-
evidence exists to support these claims. Jenkins
guish between treatment and control groups that
et al,in an attempt to reduce scarring after recon-
structive surgery in patients with burn, used topical
vitamin E in the postoperative period. No significant
improve hypertrophic scar quality after operation
differences were found in range of motion, scar
in a preliminary small, randomized, prospective
thickness, change in graft size, and overall cosmetic
clinical trial, but additional studies with a larger
appearance between the vitamin E treatment group
sample size and longer follow-up are necessary to
and base cream control group 1 year after surgery. In
determine the role of imiquimod 5% cream in
addition, 20% of patients reported local reactions
to the vitamin E cream. A subsequent double-blind,placebo-controlled clinical trial evaluating patients
who applied emollient with vitamin E and emollient
Vitamin A is required to maintain the integrity of
alone to each half of their scar from Mohs micro-
epithelial and mucosal surfaces. Based on the obser-
graphic surgery (twice daily for 4 weeks starting soon
vation that oral vitamin A improved the appearance
after surgery) also demonstrated similar results.
of keloid scait has been tested in the form of
Twelve weeks after surgery, vitamin E did not help
0.05% retinoic acid in wound healing. Daily appli-
in improving the cosmetic appearance of scars or
cation of retinoic acid to intractable hypertrophic and
keloid scars has been shown to reduce size
A high incidence (33%) of contact dermatitis was
and pruritusand cause scar softening, flattening,
noted. Limitations of the study included the use of
and fading of color.In a randomized, double-blind
the d-a-tocopheryl form of vitamin E, which has
study, Daly et demonstrated a statistically
been widely associated with contact dermatitis, and
the potentially diluted concentration of topical vita-
scars lack enough scientific data regarding their effect
min E (one crushed capsule of 320 IU in 1 g of
on this type of scar. Such topical therapies include
aloe vera, vitamin C, corticosteroids, and tacrolimus.
The use of vitamin E in scar management has
A new patent-pending product, a botanical QR340
other theoretic limitations. Because of its ability to
formula (Quigley Pharma, Doylestown, Pa), has
inhibit collagen synthesis, the use of vitamin E early
preliminarily demonstrated higher efficacy than
in scar therapy may reduce scar tensile strength and,
Mederma and placebo in hypertrophic scar improve-
hence, lead to the development of widened scars
ment. Further studies are necessary to determine
these products’ role in hypertrophic scarring.
When used in conjunction with silicone gel
In conclusion, there is no single, optimal modality
sheets, however, vitamin E has been shown to
that can eliminate or prevent hypertrophic scarring.
improve pre-existing hypertrophic scars. In all, 38
Currently, the most accepted treatment for old and
patients (95%) who received silicone gel sheets
new hypertrophic scars is silicone gel sheeting.
with added vitamin E improved by at least 50%
Silicone ointment or gel alone, however, is less
with respect to color, size, and cosmetic appearance,
effective than silicone sheeting. Pressure therapy
whereas only 30 patients (75%) using silicone gel
has demonstrated some efficacy but is cumbersome
sheets alone improved at least 50% after 2 months of
and not standardized. Polyurethane dressing has
treatment.This study led to the conclusion that the
equivocal effects on the development of new hyper-
combination of vitamin E and silicone gel sheeting is
trophic scars but may improve the appearance of
beneficial in hypertrophic scar treatment, possibly as
mature scars. Products in the United States contain-
ing onion extract do not improve scar cosmesis or
In conclusion, the evidence that topical vitamin E
symptomatology when compared with a petrolatum-
alone improves the cosmetic appearance of scars is
based ointment. Imiquimod 5% cream has been
poor. It is also associated with a high incidence of
shown to improve the quality of new hypertrophic
contact dermatitis. The use of vitamin E should,
scars after surgery in a preliminary clinical trial, but
further studies are necessary. Vitamin A lacks suffi-cient data and may be associated with side effects,
especially in pregnant women. Finally, vitamin E
Studies of scar treatments to date are limited for
alone may be detrimental to wound healing and
a number of reasons. A suitable animal model is
often leads to contact dermatitis; it should, therefore,
lacking. Many studies on scar treatments did not use
controused other confounding methodssuch as pressure or intermittent corticosteroid injec-
tions,or applied different methods of scar
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