Scar Management in the Pediatric and Adolescent Populations...comorbidities including...

Scar Management in the Pediatric and Adolescent PopulationsAndrew C. Krakowski, MD,a Christine R. Totri, MD,b Matthias B. Donelan, MD,c Peter R. Shumaker, MDd

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 fi nal manuscript as submitted.

The views expressed in this article are those of

the authors and do not refl ect the offi cial 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 offi cial duties. Title 17, USC, § 105

provides that “Copyright protection under this

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

abstractFor 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.

STATE-OF-THE-ART REVIEW ARTICLEPEDIATRICS Volume 137 , number 2 , February 2016 :e 20142065

To cite: Krakowski AC, Totri CR, Donelan MB, et al.

Scar Management in the Pediatric and Adolescent

Populations. Pediatrics. 2016;137(2):e20142065

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KRAKOWSKI et al

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

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, hyper-

immunoglobulin 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).

2

TABLE 1 Clinical Classifi cation of Scars

Atrophic Scars Hypertrophic Scars Keloids

Net loss of collagen Net gain of collagen Net gain of collagen

Appear as concave depressions, recesses, or divots

(“ice-pick scars”)

Remain confi ned to original borders of injury Extend beyond original borders of injury

Less associated with skin type Less associated with skin type; common with burn

scars or deep lacerations

More common in dark-skinned individuals and those

with a personal and/or family history

Do not improve with time May regress with time Do not regress with time

Can occur anywhere in association with underlying

condition (acne, striae, discoid lupus, etc)

More common on high tension anatomic areas (eg,

presternum, shoulder, knees, and ankles)

More common on extensor surfaces but can occur

anywhere

Relatively thin zone of small collagen bundles

organized in parallel to epidermis

Collagen bundles are relatively thin (compared

with keloids) and well-organized in parallel to

epidermis

Collagen bundles are thick (“bundles of rope”) and

organized randomly to epidermis

FIGURE 1Atrophic “ice-pick” scarring of the cheek and temple areas secondary to severe infl ammatory acne.


PEDIATRICS Volume 137 , number 2 , February 2016

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 hyper-

or 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

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

FIGURE 2A, 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 fi eld 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 3A, Two-year-old boy with painful, hypertrophic scars in the fi rst and second interdigital space that developed after syndactyly surgery. Chronic friction from “scar-on-scar” rubbing led to infl ammation, 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 fi eld 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 fi nal) 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.


KRAKOWSKI et al

(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). Clinician-

rated 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

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

4

FIGURE 4A, 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 defi cit?

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 outfl ow obstruction)?

Presence or history of skin cancer (ie, Marjolin ulcer) within scar area?

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?



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 high-

risk 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.

INTRALESIONAL CORTICOSTEROIDS

Intralesional corticosteroids remain

a mainstay in the treatment of

hypertrophic scars and keloids,

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 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

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KRAKOWSKI et al

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 vasculature-

targeting 595-nm pulsed dye laser

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

6

FIGURE 5A, 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.



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

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

7

FIGURE 6A, 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.

FIGURE 7A, Three-year-old girl with symptomatic hypertrophic scars ∼3 months after surgical revision of a scar contracture that developed after total parenteral nutrition infi ltration in the NICU within the fi rst 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.


KRAKOWSKI et al

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 engrailed-

positive fibroblasts, which express

CD26 on their surface, play is an

example of how far scar-related

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, double-

blind, placebo-controlled trial,

8

FIGURE 8A, 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.



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

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.

9

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


KRAKOWSKI et al

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10

title is not available for any work of the United States Government.” Title 17, USC, § 101 defi nes 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 offi cial duties.

Dr Krakowski's current affi liation 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 fi nancial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential confl icts of interest to disclose.



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