Download Scar Management in the Pediatric and Adolescent

Scar Management in the Pediatric
and Adolescent Populations
Andrew C. Krakowski, MD,a Christine R. Totri, MD,b Matthias B. Donelan, MD,c Peter R. Shumaker, MDd
For most children and adolescents who have developed symptomatic scars,
cosmetic concerns are only a portion of the motivation that drives them
and their caregivers to obtain treatment. In addition to the potential for
cosmetic disfigurement, scars may be associated with a number of physical
comorbidities including hypertrichosis, dyshidrosis, tenderness/pain,
pruritus, dysesthesias, and functional impairments such as contractures, all
of which may be compounded by psychosocial factors. Although a plethora
of options for treating scars exists, specific management guidelines for
the pediatric and adolescent populations do not, and evidence must be
extrapolated from adult studies. New modalities such as the scar team
approach, autologous fat transfer, and ablative fractional laser resurfacing
suggest a promising future for children who suffer symptomatically from
their scars. In this state-of-the-art review, we summarize cutting-edge
scar treatment strategies as they relate to the pediatric and adolescent
populations.
Any significant injury to the deep
dermis, such as burns and other
trauma, inflammation, or surgery,
may result in wound healing that
presents clinically with the formation
of a scar.1 Much time and energy has
been spent attempting to classify
scars on the basis of histopathology or
clinical morphology. Although doing
so is useful for documentation and
management decisions, it belies the
reality that a scar by itself is neither
“good” nor “bad.” Scars are simply
the clinical end point of a confluence
of genetic and environmental factors
affecting the wound-healing process
after a cutaneous insult. From the
perspective of human history, most
serious wounds have been traumatic
(eg, “tooth and claw,” falls, burns,
combat), involving widespread areas
of damage that needed to be contained
quickly and efficiently to control
bleeding and infection. It is only
relatively recently that iatrogenic (ie,
surgical) scars have begun to strongly
influence the discussion of what type
of scar is “acceptable.” Any scar can
be symptomatic, and even clinically
benign-appearing scars may cause
a patient physical, psychological,
and social comorbidities leading to
severe impairment of quality of life.2
To label 1 type of scar “pathologic”
and another “normal” by virtue of
morphology or histopathology alone
misses this point.
Each year ∼100 million individuals
acquire scars after an estimated 55
million elective operations and 25
million operations after trauma in
the developed world. Within this
larger group, there are an estimated
15 million keloids and hypertrophic
scars per year, an estimated 70%
of which occur in children.3 The
dramatic increase in the survival
rate of pediatric patients suffering
from severe burns in the past several
decades has translated into an
increasing number of children left to
PEDIATRICS Volume 137, number 2, February 2016:e20142065
abstract
aDivision
of Pediatric and Adolescent Dermatology, Rady
Children’s Hospital, San Diego, California; bDepartment of
Dermatology, SUNY Downstate Medical Center, Brooklyn,
New York; cDepartment of Plastic Surgery, Shriner’s
Hospital for Children, Boston, Massachusetts; and
dDepartment of Dermatology, Naval Medical Center, San
Diego, California
Dr Krakowski conceptualized and designed the
review, acquired data from primary sources, patient
interactions, and procedures, and reviewed and
revised the manuscript; Dr Totri conceptualized the
review, drafted the initial manuscript, and reviewed
and revised the manuscript; Drs Donelan and
Shumaker conceptualized the review and reviewed
and revised the manuscript; and all authors
approved the final manuscript as submitted.
The views expressed in this article are those of
the authors and do not reflect the official policy or
position of the Department of the Navy, Department
of Defense, or the US government. Dr Shumaker is
a military service member. This work was prepared
as part of his official duties. Title 17, USC, § 105
provides that “Copyright protection under this
To cite: Krakowski AC, Totri CR, Donelan MB, et al.
Scar Management in the Pediatric and Adolescent
Populations. Pediatrics. 2016;137(2):e20142065
STATE-OF-THE-ART REVIEW ARTICLE
TABLE 1 Clinical Classification of Scars
Atrophic Scars
Hypertrophic Scars
Keloids
Net loss of collagen
Appear as concave depressions, recesses, or divots
(“ice-pick scars”)
Less associated with skin type
Net gain of collagen
Remain confined to original borders of injury
Net gain of collagen
Extend beyond original borders of injury
Less associated with skin type; common with burn
scars or deep lacerations
May regress with time
More common on high tension anatomic areas (eg,
presternum, shoulder, knees, and ankles)
Collagen bundles are relatively thin (compared
with keloids) and well-organized in parallel to
epidermis
More common in dark-skinned individuals and those
with a personal and/or family history
Do not regress with time
More common on extensor surfaces but can occur
anywhere
Collagen bundles are thick (“bundles of rope”) and
organized randomly to epidermis
Do not improve with time
Can occur anywhere in association with underlying
condition (acne, striae, discoid lupus, etc)
Relatively thin zone of small collagen bundles
organized in parallel to epidermis
deal with disabling and disfiguring
scars.4
With the high scar prevalence in
the pediatric population and the
associated physical, psychological,
and social comorbidities, there is a
need to enhance understanding and
management of scars among health
care providers. Goals of therapy
for any scar should be established
in conjunction with the individual
patient and, at a minimum, should
focus on relieving symptoms,
reducing comorbidities, decreasing
scar volume, and maximizing
functional and cosmetic outcomes.
In this state-of-the-art review, we
summarize current cutting-edge
scar treatment strategies as they
relate to the pediatric and adolescent
populations.
SCAR MORPHOLOGY
Several clinical and histopathological
classifications may be useful in a
discussion of scar management
(Table 1). Atrophic scars appear as
concave recesses in the skin and
result from net tissue loss, including
collagen. Atrophic scarring may
be observed in association with a
variety of conditions such as acne,
striae distensae, discoid lupus,
varicella, molluscum contagiosum,
malignant atrophic pustulosis (Degos
disease), infections (especially
Staphylococcus), surgery, and trauma
(Fig 1). Matrix metalloproteinases
(MMPs) assist the remodeling
process by degrading a variety of
2
FIGURE 1
Atrophic “ice-pick” scarring of the cheek and temple areas secondary to severe inflammatory acne.
extracellular matrix proteins. A
simplistic concept of atrophic scar
formation is a relative shift in the
ratio of MMPs to tissue inhibitors of
MMPs, resulting in a lytic cascade
that favors an atrophic scar.5
In contrast, hypertrophic scars and
keloids result from a net excess of
collagen deposition. Hypertrophic
scars remain within the boundaries
of the precipitating insult and
typically develop relatively soon
after injury to the deep dermis.
Keloids, in contrast, extend beyond
the boundaries of the original injury
and often have a delayed onset of
development. Keloid formation
typically affects dark-skinned
individuals (Fitzpatrick IV–VI skin
type) to a greater extent than those
with lighter skin (Fitzpatrick I–III
skin type), with the majority of
keloids manifesting in persons 10 to
30 years of age.2,6,7 Younger children
are still susceptible, however, as
bilateral earlobe keloids have been
documented in a 9-month-old
African American girl 6 months after
piercing.8 In addition to differences
in clinical appearance, keloids often
differ histopathologically from
hypertrophic scars in a variety of
ways, with the most distinguishing
feature being the presence of
thickened hyalinized collagen
(keloidal collagen).9 Keloid formation
has also been associated with a
family history of keloids, hyperimmunoglobulin E syndrome, blood
type A, and hormone peaks during
puberty and pregnancy.10–13
PHYSICAL SIGNS AND SYMPTOMS
Objectively, scars may appear
erythematous, a likely function
of the scar’s newly formed
vascular network that may serve
as an indicator that the scar has
entered the active remodeling/
maturation phase.14 Likewise, a
scar may be dyspigmented as a
result of disparities in melanocyte
concentration and/or melanin
production within affected and
unaffected tissue. Clinically, this may
lead to hypo- or hyperpigmented
skin, or both (ie, “mottling”; Fig 2).
KRAKOWSKI et al
Scars may manifest pruritus,
tenderness and pain, and
dysesthesias, all of which may result
in sleep disturbances and disruption
of daily activities.15,16 These are likely
exacerbated by a variety of factors,
including local friction, inflammation,
stimulation of nerve endings in
and around the scar, and increased
local levels of B-endorphin17,18 (Fig
3). Hypertrichosis within scars has
also been reported in postoperative
patients with knee replacement
surgeries19 and in patients with
surgical scars requiring the use of
orthopedic casts and splints.20 It is
postulated that this phenomenon
may be secondary to increased
friction, vascularity, and local
growth factors. Likewise, certain
scars may contribute to local hyperor hypohidrosis, exacerbating
skin irritation and maceration
in the setting of scar fragility.
Cumulatively, these factors may
interfere significantly with physical/
occupational rehabilitation efforts.
Contractures are a potentially
disabling consequence of the scar
maturation process, especially after
extensive burns and other traumatic
injuries. Scar contractures across a
joint may lead to a significant loss
of strength and range of motion,
significantly affecting function and
overall quality of life. Contractures
along a free edge such as the eyelid
or lip may have both a functional and
profound cosmetic impact. Patients
with suspected function-limiting
contractures may be assessed for
deficits according to standardized
guidelines.21 This is especially
important in the pediatric population,
in whom deficits may affect normal
development.22
Key anatomic locations may be
divided into multiple topographical
“cosmetic units.” The face, for
example, is commonly demarcated
into cosmetic units that include the
forehead, eyes, nose, lips, chin, ears,
and neck, with each of these units
further classified into additional
PEDIATRICS Volume 137, number 2, February 2016
FIGURE 2
A, Two-year-old girl with a split-thickness skin graft placed roughly 6 months earlier after a focal
burn injury. The graft is contracted, “mottled,” irregularly textured, and clearly conspicuous. B,
Postoperative photo 10 months later showing the same split-thickness skin graft after a single full
field ablative and a single ablative fractional laser resurfacing treatment, performed serially in
separate sessions. Further improvements in texture and pigmentation could likely be achieved with
an additional course of ablative or nonablative fractional laser resurfacing.
FIGURE 3
A, Two-year-old boy with painful, hypertrophic scars in the first and second interdigital space that
developed after syndactyly surgery. Chronic friction from “scar-on-scar” rubbing led to inflammation,
and the resultant pain limited the patient’s ability to ambulate normally. B, Intraoperative photo
demonstrating use of laser ablation to remove redundant scar tissue within the interdigital space.
Ablative fractional resurfacing with LAD of corticosteroid was performed subsequently; in this
procedure, topical triamcinolone acetonide suspension (40 mg/mL) was applied to the entire scar
field immediately after laser treatment to facilitate delivery of corticosteroid through the ablative
columns. C, Patient’s foot at 3-month follow-up from second (and final) treatment session. The
interdigital hypertrophic scars did not recur. The patient’s pain had dramatically improved, and he
was ambulating near normally, while continuing to follow-up with physical and occupational therapy.
anatomic subunits. Aesthetic
theory teaches that scars that fall
in a single cosmetic unit or at the
junction between units tend to be
less conspicuous than those that
cross boundaries.23 Consequently,
scars that disrupt cosmetic units are
often more noticeable and may be
more likely to lead to both physical
and psychosocial comorbidities
3
TABLE 3: Psychosocial Scar Comorbidities to
Consider
Anxiety/stress?
Depression?
Posttraumatic stress disorder?
School, work, social performance affected?
Overall perceived reaction of others to scar?
FIGURE 4
A, Ten-year-old boy with an atrophic, hypervascular/erythematous scar on his left cheek from a dog
bite. The scar is conspicuous, violates the “cosmetic unit” principle, and is unfavorably oriented.
B, Postoperative photo 7 years later; his scar “rehabilitation” consisted of excision of the lateral
atrophic tissue and multiple z-plasty and pulsed dye laser surgeries.
TABLE 2 Physical Scar Signs and Symptoms to Consider
Conspicuous or subtle?
Disruption of local cosmetic unit?
Erythema/hypervascularity?
Skin contracture?
Range of motion/functional deficit?
Dyspigmentation (hyperpigmentation/hypopigmentation/mottling)?
Pruritus?
Pain/tenderness?
Dysesthesia?
Hypertrichosis, hypotrichosis, or alopecia?
Hyperhidrosis, hypohidrosis, or anhidrosis?
Presence or history of infection (folliculitis, cellulitis, abscess, fasciitis, etc) within scar area?
Presence or history of chronic wound/chronic ulceration within scar area?
Presence or history of lymphedema locally or regionally (suggestive of outflow obstruction)?
Presence or history of skin cancer (ie, Marjolin ulcer) within scar area?
(Fig 4). Issues may manifest as a
direct physical consequence, or as
an indirect consequence of others’
reactions to the scarred individual
(eg, bullying; Table 2).
PSYCHOSOCIAL SIGNS AND SYMPTOMS
When caring for pediatric patients
with scars, it is important to note that
the contribution of psychological and
social factors to overall quality of
life is frequently underreported and
underdiagnosed (Table 3). Clinicianrated scar severity and scar types
may not necessarily correlate with
the extent of a patient’s psychosocial
distress.24 Rather, scar location, a
patients’ own subjective rating of scar
severity, and the personality traits
(eg, extraversion, optimism, hopeful)
of the affected individual appear to
best predict the psychological impact
4
a scar may have.25,26 Indirectly, the
reaction of others to a scar may play
a crucial role in the stigmatization
or discrimination of the affected
individual. This may manifest
in others as a lack of courteous
behavior, staring, startled responses,
intrusive questions, avoidance, rude
comments, teasing, and bullying.27
Such behaviors can lead to a sense
of rejection, loneliness, isolation,
and “social death,” with important
implications for social interaction
and employment opportunities.26
The combination of traumatic
burn accidents, laborious and
repetitive treatments, and residual
disfigurement and dysfunction
has been demonstrated to lead
to psychopathological responses
in children such as depression,
separation anxiety disorder, and
posttraumatic stress disorder.28
As such, >50% of burn-injured
children may eventually develop
manifestations of posttraumatic
stress disorder.29 For these reasons, a
multidisciplinary specialty team may
be beneficial when managing patients
with disfiguring and debilitating
scars.
STATE-OF-THE-ART SCAR MANAGEMENT
A recent proliferation of research
in scar therapeutics parallels
the recognition of the impact
of treatment beyond cosmetic
appearance alone. This is particularly
relevant in pediatrics, in which
utility must often be extrapolated
from adult studies and the profound
physical and psychological
implications associated with
scarring (such as the seemingly
ubiquitous atrophic scarring
secondary to acne) mandate a
consideration of multimodal
treatment options.15,30–32 Although a
wide range of “conventional” options
(Supplemental Information) reflect
the inconsistent and frequently
disappointing efficacy of traditional
therapies, the cutting-edge modalities
reviewed herein offer the potential
to advance the field of pediatric scar
mitigation, revision, and perhaps
eventually prevention.
MULTIDISCIPLINARY MANAGEMENT
Like in so many areas of medicine,
scar prevention and mitigation
are preferable to treatment of an
existing symptomatic scar. Scar
mitigation begins with coordinating
and optimizing procedural technique
and other factors such as keeping
KRAKOWSKI et al
wounds moist, timely and judicious
wound debridement, minimizing the
tension of wound closure, prevention
of infections and hematoma
formation, avoidance of sun exposure
to minimize postinflammatory
hyperpigmentation, and maximizing
nutritional status.33
Furthermore, a health care provider’s
ability to identify a situation likely to
result in symptomatic scar formation
is imperative. Certain anatomic
locations with high tension such
as the shoulder, neck, presternum,
and ankle are predisposed to
hypertrophic scars.11 Dark-skinned
patients and any patient with a
personal/family history of pathologic
scar formation should incite humility
in any provider contemplating an
elective procedure, especially in highrisk locations.
Complex scars may require multiple
interventions performed either
concurrently or in a step-wise
fashion for optimal results.13,34
A single provider from a single
specialty may not possess the
experience or expertise necessary
to consider and implement all of
the various approaches that may
be required. Combining experts
from dermatology, plastic surgery,
wound healing, trauma/abuse
counseling, nutrition, behavioral
health, physical/occupational
therapy, radiology, and social work,
a multidisciplinary scar team may
provide more efficient, optimized
care to complicated scar patients.35
This “team” approach has previously
demonstrated utility in the
management of vascular lesions, cleft
lip and palate, and pediatric burns.36–
38 Larger, prospective studies will
shed light on the true effectiveness
of this model of scar care as an
intervention in and of itself.
with a response rate of ∼50% to
100% and a recurrence rate of 9%
to 50% for keloids in 1 review.39
One prospective pediatric study
involving 15 patients with earlobe
keloids included treatment with
an aggressive regimen including
preoperative, intraoperative,
and postoperative intralesional
triamcinolone acetonide suspension
as an adjunct to keloid excision. Of the
pediatric patients who adhered to the
regimen, none showed signs of keloid
recurrence at 6 months of follow-up,
with a single recurrence noted at 18
months of follow-up.40 The efficacy
of corticosteroids for these types
of scars is likely secondary to their
ability to suppress inflammation,
promote collagen degeneration,
inhibit collagen production, and limit
wound oxygenation and nutrition.41
The optimal number of treatments
has yet to be determined, and
dosing for intralesional scar
therapy varies depending on lesion
characteristics and anatomic
location. Local cutaneous atrophy
and hypopigmentation are the most
common side effects of therapy.42
Pain on injection may be a significant
obstacle to use in pediatrics, with
1 study showing an attrition rate
of nearly 1 in 3 despite significant
efficacy in the treatment of facial
keloids.43 Topical lidocaine cream
before injection may help minimize
discomfort.44,45 Triamcinolone
acetonide injectable suspension
contains benzyl alcohol, which has
been reported to cause toxicity
in neonates, particularly in small
preterm infants. Although exposure
is likely negligible in the setting
of intralesional use, the amount
of benzyl alcohol at which toxicity
occurs is not known, and use of this
medication is not recommended in
neonates.46
INTRALESIONAL CORTICOSTEROIDS
Intralesional corticosteroids remain
a mainstay in the treatment of
hypertrophic scars and keloids,
PEDIATRICS Volume 137, number 2, February 2016
INTRALESIONAL 5-FLUOROURACIL
Five-fluorouracil (5-FU) is
a pyrimidine analog with
antimetabolite activity that has been
shown to inhibit collagen synthesis
both in vitro and in vivo.47–49 When
delivered intralesionally into keloids
and hypertrophic scars, 5-FU has
demonstrated significant efficacy
in several adult studies.50–52 A
44-week, double-blind, randomized
trial compared intralesional
triamcinolone acetonide (40 mg/mL)
with 5-FU (50 mg/mL) tattooing
every 4 weeks for a total of 12 weeks
for the treatment of keloids.53 Both
groups demonstrated improvement
in all assessed parameters including
erythema, pruritus, height,
surface, and induration. However,
improvement was more significant in
the 5-FU group.
5-FU is considered “off-label” for
scars, and its safety and effectiveness
in children have not been established,
either alone or in combination
with intralesional corticosteroid.
Adverse effects include pain and
hyperpigmentation. It is Pregnancy
Category D and may cause fetal harm
when administered to a pregnant
woman.54
AUTOLOGOUS FAT TRANSFER
For scars associated with volume
loss, the techniques of autologous
fat transfer (AFT) and composite
grafting offer significant promise.55
In the pediatric population, AFT
has been used in the treatment
of facial malformations due to
Goldenhar syndrome, Treacher
Collins syndrome, and hemifacial
microsomia.56 AFT may offer benefits
beyond volume replacement, with
graft components mediating a
dynamic remodeling process that
may accelerate revascularization
and decrease fibrosis after thermal
injury.57,58 Combinations of AFT with
ablative and nonablative fractional
laser resurfacing and platelet-rich
plasma have also been demonstrated
to enhance scar treatment.59
5
SURGICAL EXCISION
Surgical excision may prove useful in
cases in which conservative therapies
alone have failed to yield significant
improvement. As monotherapy,
excision of keloids has a dismal
recurrence rate that may approach
100%.60–62 Consequently, excision is
typically performed in combination
with adjunctive perioperative
modalities, which may help reduce
the risk of recurrence.63,64 In 1
study that included patients ranging
from 11 to 79 years of age, excision
of pathologic scars followed by a
corticosteroid injection every 2
weeks (for a total of 5 injections)
along with self-administered steroid
ointment application twice daily
for 6 months, showed a recurrence
of keloids in 14.3% of cases and a
recurrence of hypertrophic scars in
16.7% of cases.65
SURGICAL REVISION
Surgical revision may be required
for debilitating scar contractures
refractory to physical/occupational
therapy and other more conservative
measures. Surgical techniques
include scar-lengthening flaps,
excision, and skin grafting, which
may be delayed for a year or more
to allow for spontaneous scar
maturation. This delay has been built
into most scar treatment paradigms
because surgical treatment itself is
associated with additional morbidity
and relatively high recurrence
rates.60,62 Traditional surgical
techniques for contractures include
Z- and W-plasties; the former is a
scar lengthening procedure that
relieves tension and decreases
contracture to help improve range of
motion, and the latter helps render
lengthy linear scars irregular and less
discernable66,67 (Fig 5).
LASER SURGERY
Lasers such as the vasculaturetargeting 595-nm pulsed dye laser
6
FIGURE 5
A, Four-year-old girl with a hypertrophic, hypervascularized, hyperpigmented scar circumscribed
within hypopigmented skin after a scald burn to the left leg 1 year earlier. The patient had been
wearing compression stockings over the area as evidenced by the horizontal “ridging” pattern seen
overlying the wound area. B, Intraoperative planning of multiple z-plasty surgeries to lengthen scar
and release scar tension within the contracture. C, Immediate postoperative photo demonstrating
sutured z-plasty sites with corresponding reorientation of scar tissue. D, Postoperative photo 4 years
later demonstrating “successful rehabilitation” of the scar after multiple z-plasties, pulsed dye laser,
and fractional ablative laser resurfacing with a CO2 laser. No excision of the scar was ever performed.
and the full-field ablative 10 600-nm
CO2 laser continue to be effectively
integrated into the treatment of
various scar types. These modalities
are, however, somewhat limited
in large traumatic scars because
of modest efficacy and excessive
thermal damage, respectively.30,68–70
Treatment with pulsed dye laser is
based on selective photothermolysis,
with hemoglobin serving as the
target chromophore. Moderate
damage to local blood vessels results
in a remodeling response that can
help reduce scar erythema, pain, itch,
and prominence71–76 (Fig 6).
Some of the most exciting recent
advances in scar treatment are
associated with the emergence of
fractional photothermolysis in 2004.77
This involves the generation of a
pixelated pattern of narrow columns
of thermal injury (vaporization or
coagulation of tissue) in the treatment
area, based on the heating of tissue
water. Fractional lasers are the
first to offer a selectable depth of
penetration, up to several millimeters.
The tissue response to laser-induced
thermal injury shares some common
features with wound repair. An early
inflammatory response is followed
by cell proliferation, MMP-guided
turnover of extracellular proteins,
and long-term neocollagenesis and
dermal remodeling.78–80 In the case
of fractional ablative laser treatment,
vigorous remodeling appears to
eventuate in scar tissue with a dermal
architecture and ratio of collagen
subtypes closer to that of normal
skin.81 The combination of treatment
depths unavailable to previous
devices with an adjacent undamaged
reservoir of viable tissue is likely
responsible for the observed safety
and efficacy of treatment, which has
established a new gold standard in
KRAKOWSKI et al
the treatment of acne, surgical, and
traumatic scars.74,82–85 The recent
observation that ablative fractional
laser resurfacing can objectively
improve function and enhance
rehabilitation in the pediatric and
adult populations has profound
implications for current paradigms
in traumatic scar management74,85–87
(Fig 7).
Relatively few safety reports
involving fractional laser scar
treatment in the pediatric population
exist in the literature, although
there is largely anecdotal evidence
that fractional laser therapy is
well tolerated with a low rate of
complications.74,87–92 Lasers can be
associated with significant discomfort
during treatment, which is an
important consideration for pediatric
patients. Topical anesthetics, local
intradermal injection, regional nerve
block, oral and intravenous sedation,
and general anesthesia have all been
successfully used in laser therapy for
this population.93,94
FIGURE 6
A, Twelve-year-old boy with a hypervascular/erythematous, pruritic, hypertrophic sternotomy scar
after several life-saving heart surgeries that occurred when he was an infant. B, Postoperative photo
showing the sternotomy scar after 2 sessions, ∼2 months apart, of pulsed dye laser. The patient
reported less erythema, less discomfort, and an overall “softening” of his scar.
LASER-ASSISTED DELIVERY OF
MEDICATIONS
The use of topical corticosteroids
has traditionally been discouraged
in scar management because of a
lack of efficacy and risk of epidermal
atrophy.70,95 Numerous strategies
have been attempted to enhance
topical drug delivery through
fibrotic scar tissue. The technique of
laser-assisted delivery (LAD) takes
advantage of temporary barrier
impairment induced by various
ablative and nonablative fractional
photothermolysis technologies; it
pairs topically applied medications
with laser therapy to increase
penetration and absorption of the
applied agents (Fig 8).
Although the number of published
articles on the use of this technique in
pediatrics is limited, several reports
demonstrate the potential utility of
PEDIATRICS Volume 137, number 2, February 2016
FIGURE 7
A, Three-year-old girl with symptomatic hypertrophic scars ∼3 months after surgical revision of a
scar contracture that developed after total parenteral nutrition infiltration in the NICU within the
first 2 weeks of life. In addition to symptoms such as pain and itch, scar contractures resulting from
hypertrophic scars may lead to functional issues that are exacerbated in the developing child. B,
Patient ∼11 months after a series of combination treatments with intralesional steroids, pulsed-dye
laser, and ablative fractional laser resurfacing. Intervention can be instituted relatively early after
surgery to mitigate development of hypertrophic scars and contractures. Although some gradual
spontaneous improvement is anticipated for hypertrophic scars over months and years, the rapidity
and extent of improvement with appropriate procedures exceeds that expected with spontaneous
improvement alone. C, Patient ∼2 years after initial presentation, asymptomatic and fully functional
after additional pulsed-dye laser treatments to residual erythematous scars.
7
such an innovation. One prospective
case series involving 15 subjects with
hypertrophic scars reported the use
of ablative fractional laser followed
by immediate topical application
of triamcinolone acetonide (10–20
mg/mL depending on location and
thickness of the scar). The subjects
underwent 3 to 5 treatment sessions
at 2- to 3-month intervals. At the
end of the study, scar texture
showed the most improvement,
whereas dyschromia showed the
least amount of improvement.96
A second prospective case series
treated 4 subjects with hypertrophic
scars by using ablative fractional
radiofrequency followed by topical
triamcinolone acetonide 20 mg/mL.
Acoustic pressure ultrasound helped
“push” triamcinolone molecules
through the ablated microchannels.
Complete resolution of the treated
scar was noted in as little as 1
session for lesions on the nose
and mandibular area, with
significant improvement in all
areas of the body after 4 treatment
sessions.
A potential disadvantage of LAD
is that many topical medications
have not been evaluated for this
route of application, and patients
may experience side effects seen in
either or both topical medication
administration and laser surgery.
Likewise, LAD may increase
penetration of not only the
desired medication but also any
excipients applied to the treated
field; sterility and unintended side
effects must be considered with this
fact in mind.97
ON THE HORIZON
Our understanding of the
pathophysiology of scar formation
and fetal wound healing continues
to accelerate. The recent elucidation
of the role in scarring that engrailedpositive fibroblasts, which express
CD26 on their surface, play is an
example of how far scar-related
8
FIGURE 8
A, Sixteen-year-old boy with a hypervascular, pruritic, painful scar in the presternal area after
surgery to excise a cyst; side-lighting reveals severely irregular contour and thickness (4 mm at point
of maximal contour irregularity). B, Postoperative photo demonstrating marked improvement in
erythema and texture with combination ablative fractional laser resurfacing and LAD of triamcinolone
acetonide suspension (40 mg/mL), and home use of silicone gel sheeting. At his 9-month follow-up
appointment, the patient reported total resolution of pruritus and pain within the scar.
basic science has progressed; the
possibility that medications such
as sitagliptin and vildagliptin,
oral antihyperglycemics used in
the treatment of type 2 diabetes
mellitus, may actually inhibit this
specific lineage of fibroblasts lays
the groundwork for a true paradigm
shift in the field.98 Such discoveries
allow for the exploration of more
specific therapeutic options for scars
and, perhaps, may lead to future
applications in scarless wound
healing.
REACTIVATION OF FETAL PATHWAYS
Before the end of the first trimester
of gestation, human fetuses do not
follow the traditional “inflammatory
cascade” model of wound healing.
Instead, early fetal wound healing is
characterized by a relative paucity
of inflammatory cell activity and
reactivation of developmental
pathways. The end result appears to
be true tissue regeneration without
scar formation.99 How humans
transition from reactivation/
regeneration to the traditional
inflammatory model of wound
healing has yet to be demonstrated.
However, not all mammals lose
this ability. The African spiny
mouse appears to regenerate hair
follicles, sebaceous glands, dermis,
adipose tissue, and cartilage from
deep cutaneous injuries even in
its adult life.100 Elucidating these
fundamental mechanisms of
wound repair promises to inform
future therapeutic modalities, and
perhaps even reintroduce scarless
healing.101,102
STEM CELLS
Stem cells are a promising source
for novel therapies in scar treatment
and tissue repair. The presence
of induced pluripotent stem cell–
conditioned medium appears
to reduce levels of type I (adult)
collagen and attenuates the local
inflammatory cell response in
vitro.103 Additionally, mesenchymal
stromal cells may have the ability to
be reprogrammed into sweat gland–
like cells, offering the potential to
restore injured adnexal structures
from deep burn injuries.104
AUTOLOGOUS FIBROBLASTS
In a randomized, multicenter, doubleblind, placebo-controlled trial,
KRAKOWSKI et al
subjects with bilateral, moderate
to severe acne cheek scarring
treated with a series of unilateral
autologous fibroblast injections
had a statistically significant
improvement on blinded
photographic evaluation compared
with placebo-treated controls 4
months after their final injection.105
Trials are currently underway to see
if similar interventions can improve
scar pliability, improve range of
motion, and restore function in
contracture scars.
INTERLEUKIN-10
Interleukin (IL)-10 is an
antiinflammatory cytokine highly
expressed in midgestation human
fetal skin but absent in postnatal
human skin.106 In fetal regenerative
wound healing, IL-10 is believed
to play a prominent role because
it has been shown to deactivate
macrophages and neutrophils while
also diminishing the production of
proinflammatory cytokines IL-6
and IL-8.107–109 Furthermore, IL-10
levels and fibrotic processes appear
inversely correlated in postnatal
tissue repair.110 Recently, 2 murine
studies and a phase II randomized
controlled trial in humans have
confirmed the importance of
IL-10 in reducing inflammation,
accelerating wound healing, and
reducing scarring with the use of
exogenous recombinant human IL-10
application to cutaneous incisions,
suggesting that rhIL-10 may be a new
class of therapeutic options for scar
minimization.111
TRANSFORMING GROWTH FACTOR-Β
Transforming growth factor-β
(TGF-β) is thought to be an important
growth factor in scar formation.
In general, TGF-β1 and TGF-β2
physiologically promote fibroblast
proliferation and collagen production
in the proliferative phase of normal
wound healing and have been found
PEDIATRICS Volume 137, number 2, February 2016
to be overproduced and unregulated
in keloidal tissue.112 In contrast,
TGF-β3 appears to function as a scar
inhibitor.113
Animal studies have demonstrated
promising results with topical
application of TGF-β1 and TGF-β2
antagonists resulting in expedited
reepithelialization and reduced scar
formation and wound contraction
in partial-thickness/full-thickness
porcine burns as well as in rabbit
skin excision models.114,115 In
addition, application of recombinant
TGF-β3 has been shown to reduce
scar size.116 Recombinant TGF-β3
appears to be useful for prophylaxis
against and treatment of surgical
scars.117
BASIC FIBROBLAST GROWTH FACTOR
Basic fibroblast growth factor
(bFGF) is an important cytokine
that activates macrophages and
plays a crucial role in early wound
healing.118,119 In 1 controlled adult
study, topical bFGF resulted in
better scar quality and accelerated
wound healing.120 The potential for
therapeutic use of bFGF has been
studied in the pediatric population.
One study showed that children with
second-degree burns who received
topical bFGF had a significantly
enhanced skin/scar color match
compared with the placebo group
that received only impregnated
gauze after 1 year. Furthermore,
hypertrophic scars developed in 0
of 10 wounds in the bFGF treatment
group compared with 3 of 10 wounds
in the control group. Parameters
such as effective contact coefficient,
transepidermal water loss, water
content, and scar thickness were
also significantly greater in the
control group (P < .01).121 Further
prospective, randomized, controlled
clinical studies are needed to
establish the safety and efficacy of
bFGF for its potential role in scar
therapy.
MMPS
MMPs play an important role in
tissue remodeling by degrading
extracellular matrix components,
growth factors, cytokines, and
additional proteases.122 Studies
have demonstrated increased
MMP-1 expression, through either
a therapeutic factor or direct
application of purified MMP-1,
may have a beneficial impact on
hypertrophic scars.123
CONCLUSIONS
Myriad management options for
symptomatic scars exist, with
no universal consensus on what
constitutes the safest and most
efficacious treatment modalities.
Even less is certain regarding
the pediatric and adolescent
populations because of a lack of
controlled trials within these age
groups. Symptomatic scars remain a
challenge for both the patients who
must live with them and the health
care providers who are asked to
manage them. Nevertheless, much
progress has been made in the past
several years, with combination
therapy yielding tremendous clinical
improvements. The emergence of
scar therapies that target specific
molecular and cellular pathways
represents a promising future in scar
management and, possibly, even scar
prevention.
ABBREVIATIONS
5-FU: five-fluorouracil
AFT: autologous fat transfer
bFGF: basic fibroblast growth
factor
IL-10: interleukin-10
LAD: laser-assisted delivery
MMP: matrix metalloproteinases
TGF-β: transforming growth
factor-β
9
title is not available for any work of the United States Government.” Title 17, USC, § 101 defines a US government work as a work prepared by a military service
member or employee of the US government as part of that person’s official duties.
Dr Krakowski's current affiliation is DermOne, LLC, West Conshohocken, Pennsylvania and Division of Pediatric and Adolescent Dermatology, Rady Children’s
Hospital, San Diego, California.
DOI: 10.1542/peds.2014-2065
Accepted for publication Jul 22, 2015
Address correspondence to Andrew C. Krakowski, MD, Kids’ Scar Treatment and Revision (S.T.A.R.) Program, Rady Children’s Hospital, 8010 Frost St, Suite 602, San
Diego, CA 92123. E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
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