abSTRaCT
Skin changes are common in
children. Common concerns
are birthmarks (e.g.,
hemangiomas and port wine
stains), atopic and contact
dermatitis, acne, and alopecia
areata. The authors review
advances in common and not
so common skin changes in
C frequently in children; up to 30 percent
pediatric patients.
J Clin Aesthet Dermatol.
2017;10(3 Suppl1):S8S15
S8 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY March 2017 Vol. 10 No. 3 Supplement 1
REviEw
Pediatric Dermatology
aLESLIE CASTELO-SOCCIO, MD, PhD, and aPATRICK MCMAHON, MD
a
The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine,
Philadelphia, Pennsylvania
CUTANEOUS PROBLEMS OCCUR
of pediatric primary care visits involve a
skin-related problem.14 Common
among these problems are atopic
dermatitis, seborrheic dermatitis, contact
dermatitis, and acne. Yet pediatric
dermatology, first recognized in 2000 as
a boarded subspecialty of dermatology,
is in its infancy.5 Despite the demand,
there is a national shortage of pediatric
dermatologists, which has made it
difficult to impart adequate dermatology
training for pediatricians. For this
reason, many dermatologists,
pediatricians, and primary care
physicians manage the pediatric
population when it comes to
dermatology issues. Education for
clinicians is imperative to meet the
burden of pediatric dermatology cases,
many of which can be highly complex.
The aim of this review is to discuss
emerging concerns in pediatric
dermatology.
Infantile hemangiomas (IH),
INFANTILE HEMANGIOMAS
common tumors in infants with a
prevalence around five percent, may be
treated in several ways.6 More than half
of IH present in the head and neck
region (60%).7 It is crucial first to
Disclosures: The authors have no conflicts of interest relevant to the content of this article.
Author correspondence: Dr. Leslie Castelo-Soccio; email: castelosocciol@email.chop.edu
differentiate between a superficial
hemangioma, which may respond to
topical therapy, and a deep
hemangioma, which is typically treated
with oral propranolol. Timolol 0.5%, a
gel-forming solution, is the first-line
topical treatment for superficial IH.8
Early treatment is highly recommended.
Propranolol, a beta-adrenergic-
blocker, has emerged as a preferred
treatment option for complicated IH
cases.9,10 As a beta-blocker, propranolol
may be associated with changes in the
heart rate or rhythm, including
symptomatic bradycardia.11 The use of
propranolol therapy for IH may vary
from institution to institution. In a multi-
institutional survey of treatment
practices for IH (n=18 respondents, 15
institutions), respondents at 67 percent
of institutions said they routinely
consulted with cardiology colleagues
before initiating propranolol therapy,
and the median dosage of propranolol
hydrochloride to start therapy was
2.00mg/kg/d1.65mg/kg/d (range 0.45
2.50mg/kg/d). Treatment duration
ranged from 4 to 8 months (33%) or 8 to
12 months (67%), and the decision to
discontinue therapy was based on
clinical response (50%) or patients age
(43%).12
While guidelines have been
 REviEw
established for the initiation,
treatment indications, and clinical
monitoring of propranolol therapy
for IH, the role of
electrocardiography (ECG) testing
remains unclear. There is no
consensus as to whether it is
required for pretreatment
evaluation. The use of routine ECG
testing was evaluated in a two-
center study of 162 patients who
were examined prior to the planned
commencement of propranolol
treatment for IH.13 In this study, 43
percent of patients who underwent
routine ECG monitoring obtained
abnormal results. This, in turn, led
to 28 formal consultations with
pediatric cardiologists, but none of
those abnormal results were
ultimately precluded from
propranolol therapy. Moreover, no
patient in this study experienced any
adverse effects from propranolol
therapy that could have been
predicted by an ECG. Thus, the role
of ECG monitoring in this context
remains unclear, but this evidence
suggests that ECG testing may not
be necessary.14 For patients with
bradycardia or a history of
arrhythmias, features of posterior
fossa brain malformations (PHACE
syndrome), familial history of early
cardiac death or congenital heart
disease, or maternal history of
connective tissue disease, an ECG
may still be helpful and appropriate.
Thus, the potential benefits of an
ECG should be weighed against its
cost and potential utility.
PORT WINE STAINS AND STURGE-
It has long been thought that the
WEBER SYNDROME
JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY March 2017 Vol. 10 No. 3 Supplement 1
distribution of port wine stains
(PWS) follows the trigeminal nerve,
but new evidence has found a
relation to genetic mosaicism.15
PWS on the face, which appear to
follow the embryonic vasculature
(rather than the trigeminal nerve),
may be an isolated finding or may
occur along with Sturge-Weber
Syndrome (SWS). Today, it is more
useful to consider embryologic
segments when discussing PWS
rather than the older V1, V2, V3
criteria.
SWS may be diagnosed when the
patient presents with malformations
of the cerebral and ocular vascular
systems along with facial PWS. In a
study of 192 children with facial
PWS, two predictors of adverse
outcomes emerged: a PWS
involving any part of the forehead
(defined by the line joining the outer
canthus of the eye to the top of the
ear, including the upper eyelid) and
an abnormal magnetic resonance
imaging (MRI) scan. Thus, it may be
important for pediatric patients
presenting with PWS on the
forehead to undergo an
ophthalmology review and a brain
MRI.16
PWS and SWS are thought to be
somatic mosaic mutations that
disrupt vascular development. It has
been theorized that the development
time at which these mutations occur
defines the severity and extent of
PWS and SWS. In a study of whole-
genome sequencing of DNA, a
nonsynonymous single-nucleotide
variant in GNAQ was identified in
affected tissue samples of 88 percent
of participants with SWS and 92
percent of patients with non-SWS
PWS, but not in any of the affected
tissue of others with unrelated
cerebrovascular malformations or
control patients. The mutant allele
was prevalent in affected tissue at
rates of 1.0 to 18.1 percent.17
In a study of 192 pediatric
patients with facial PWS, adverse
outcomes (defined as seizures,
abnormalities in neurodevelopment,
glaucoma, and abnormal MRI scans)
were calculated. Based on the
Fishers exact p-value, patients with
forehead plaques were significantly
more likely to have seizures,
abnormal neurodevelopment, and
glaucoma (p<0.001 for all) and an
abnormal MRI (p=0.002) than
patients with PWS without forehead
involvement.16 A flowchart based on
these experiences is presented in
Figure 1. Thus, PWS on the
forehead represent the highest risk
for SWS, and MRI scans are the test
of choice.
NOVEL TOPICAL THERAPY FOR PORT
The preferred treatment for PWS
WINE STAINS
remains pulsed dye laser (PDL),
although it is thought that as much
as 90 percent of PWS are refractory
to PDL. This therapeutic resistance
is attributed to revascularization
post-laser-therapy. Oral sirolimus
has been used with some success as
adjunctive therapy to help reduce the
possibility of revascularization, but it
is associated with considerable side
effects. A case report in the literature
described a 56-year-old man with
extensive PWS who was treated
with PDL and topical sirolimus
(rapamycin) 0.5% ointment.
Significant improvement occurred
S9
 REviEw
Figure 1. Great Ormond Street Hospital management guidelines for children with
facial port wine stains (PwS) on the forehead.16
MRi, magnetic resonance imaging
with the combination therapy.18 In a
phase II, randomized, double-blind,
intra-individual, placebo-controlled
trial (N=23) of patients with SWS
and facial PWS, patients were
randomized into four study arms:
placebo, PDL + placebo, sirolimus
(rapamycin), and PDL + sirolimus
(rapamycin). The best result, defined
as lowest digital photographic image
score and lowest percentage of
vessels in histologic analysis, was
significantly better for patients in the
PDL + sirolimus group.19
It is thought that topical sirolimus
(rapamycin) suppresses the
regeneration and revascularization of
photo-coagulated blood vessels
produced by PDL.20 Topical
sirolimus (rapamycin) has been used
to treat angiofibromas as well.2123 It
is available in 1% or 0.5% cream
S10 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY March 2017 Vol. 10 No. 3 Supplement 1
and represents a promising new
adjunctive treatment.
While acne is ubiquitous in the
ACNE AND DAIRY INTAKE
industrialized world, affecting 79 to
95 percent of American adolescents,
epidemiological studies suggest that
acne rates are very low or
nonexistent in some nonwestern
societies, such as the Kitavan
Islanders of Papua, New Guinea,
and the Ach hunter-gathering
society of Paraguay, where no cases
of acne have been observed.24 These
stark differences in the incidence of
acne cannot be entirely explained by
genetic differences; it is likely that
environmental factors, including
diet, play a role. Recent evidence
suggests that diet affects the
proliferation of basal keratinocytes
within the pilosebaceous duct,
androgen-mediated sebum
production, colonization of the
comedo by Propionibacterium
acnes, and inflammation in and near
the comedo.25 Some evidence has
suggested the relationship between
diet and acne involved the dietary
glycemic load.26,27 More recent
studies suggest that dairy products,
specifically low-fat dairy products,
may induce acne.28
In a case-control study (N=225),
young people between the ages of 14
and 19 years with moderate to no
acne (based on the Global Acne
Assessment Scale) were interviewed
three times for dietary recall using
the Nutrition Data System for
Research software.28 Participants
with acne consumed significantly
more low-fat milk and skim milk
than those without acne (p=0.01),
but the study found no difference in
total dietary intake, saturated fat or
trans-fat intake, or glycemic load.
The study did not find any
significant differences in total energy
intake or body mass index (BMI)
with respect to acne. Thus, in this
study, full-fat milk was not
associated with acne, but low-fat
milk and skim milk were. However,
in a case-control study of 88 patients
aged 18 to 30 years with and without
acne, interviews found that patients
with acne had a significantly greater
dietary glycemic load (17535 vs.
12228, p<0.001) and significantly
greater consumption of milk and ice
cream (p<0.01).29 The intake of
refined sugar products has also been
associated with acne.30
By contrast, a longitudinal
survey-based study of students
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between the ages of 15 and 19
conducted in Norway found that
severe acne had a prevalence rate of
about 13.9 percent in this
population, and consumption of two
or more glasses of full-fat dairy milk
per day was associated with
moderate-to-severe acne, but there
was no association between the
consumption of low-fat or skim
milk products and acne.31 Thus, the
evidence in the literature about
dietary links to acne remains
equivocal and warrants further
study.
ATOPIC DERMATITITS, ALLERGIES,
AND THE EARLY INTRODUCTION OF
Prior to 2008, experts
PEANUTS
recommended that peanut
introduction be delayed in infants at
high risk for allergies, although
observational studies have
suggested that complementary food
introduction of high-risk allergens
may offer a protective effect. The
Learning Early About Peanut
Allergy (LEAP) study consolidated
this evidence and found that early
introduction may indeed be
beneficial.3234 A recent study
randomized 640 infants with severe
eczema and/or egg allergy to either
consume or avoid peanuts until five
years of age. In the peanut-
avoidance group, the prevalence of
peanut allergy at 60 months was
13.7 percent, while in the peanut-
consumption group, the prevalence
was 1.9 percent at five years
(p<0.001).35 Thus, early introduction
of peanuts into the diet of high-risk
children was associated with
decreased frequency of peanut
JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY March 2017 Vol. 10 No. 3 Supplement 1
allergy development.
Thus, for infants with early-onset
atopic disease (allergies), early
peanut introduction may be
beneficial. Skin testing or in-clinic
observation of peanut ingestion is
recommended because of the
sometimes severe nature of such
allergic reactions. An initial
consultation with an allergist may be
appropriate. Peanut introduction
may then be carried on at home once
the clinician can determine that the
patient is not clinically reactive.
Disordered sleeping and sleep
deficits occur in children with atopic
dermatitis and may cause a lower
quality of life and negatively impact
the childs neurocognitive
development.36 While the discomfort
of dermatitis, itching, and scratching
in the night may contribute to poor
sleep in these children, it is likely
that the cause of their sleep problems
is more complex. In a randomized,
double-blind, placebo-controlled,
crossover study of 73 pediatric
patients (aged 118 years) with
atopic dermatitis over at least five
percent of the body surface area,
patients were treated with either
melatonin 3mg/day or placebo for
four weeks, followed by a two-week
washout period, and then a crossover
four-week study.37 Children were
evaluated using the Scoring Atopic
Dermatitis (SCORAD) index and
were also evaluated for sleep-onset
latency. SCORAD indices decreased
by 9.1 versus placebo from a mean
49.124.3 to 40.220.9. Sleep-onset
latency decreased 21.4 minutes after
melatonin treatment compared to
placebo (p=0.02). No adverse events
were reported during the course of
the study, and no patients withdrew
from the study because of adverse
events. Clinicians treating children
with atopic dermatitis should ask
them or their parents about their
sleep hygiene.
Looking ahead in atopic
dermatitis, a new topical PDE4-
inhibitor currently in Phase III trials,
crisaborole ointment, may be on the
horizon.38 Systemic agents in the
pipeline include dupilumab, a
human monoclonal antibody against
IL-4 (SQ),39,40 and apremilast, an oral
PDE4-inhibitor.41
JANUS-KINASE INHIBITORS FOR
Alopecia areata is an autoimmune
ALOPECIA AREATA
disease with strong associations to
the genetic loci near immune-
function genes. In murine studies
and early human studies, Janus-
kinase (JAK) inhibitors interrupted
these immune signaling pathways.42
Two new JAK inhibitors considered
for use in alopecia areata in adults
are tofacitinib and ruxolitinib.43,44
However, the safety of these drugs
for use in pediatric patients remains
undetermined. A case report showed
the successful treatment of alopecia
universalis with topical ruxolitinib (a
topical JAK inhibitor).44 In a
literature review, oral tofacitinib was
found to be effective in the treatment
of alopecia areata as well as other
conditions, including psoriasis and
vitiligo.43
This early evidence suggests that
JAK inhibitors may offer an
alternative therapeutic option for
alopecia areata, and though they
should be avoided as first-line
therapy, may be considered in
S11
 REviEw
limited cases. There is no data on the
long term safety of this medication
in children..45 Topical JAK inhibitors
may also be an appropriate
prescribing choice. There is
considerable interest at this time in
finding a safe, effective, and
convenient treatment for alopecia.
CONGENITAL LANGERHANS CELL
Congenital Langerhans cell
HISTIOCYTOSIS
histiocytosis (LCH) is a clonal
disorder of the histiocytes, which are
cells derived from the bone marrow.
Morphologically, LCH appears to be
a benign proliferation of
inflammatory cells that somehow
have evaded the bodys regulatory
mechanisms, but our current
understanding is that there is clonal
proliferation of immune-processing
cells (Langerhans cells), which
suggests a malignant pathology.46
LCH manifests itself most
commonly as a solitary lesion on the
orbital bone of the eye, and can be
treated with minimally invasive
procedures. Recent studies have
suggested that LCH may be a risk
marker for central nervous system
(CNS) disorders.46 While LCH may
be systemic, it often affects only the
skin. LCH most commonly presents
in pediatric patients who exhibit
infiltration of mast cells and
Langerhans cells.47
LCH has four known variants:
congenital self-healing
reticulohistiocytosis (CSHRH, also
called Hashimoto-Pritzker disease),
Letterer-Siwe disease, Hand-
Schller-Christian disease, and
eosinophilic granuloma.48 CSHRH
appears to be a misnomer, because
S12 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY March 2017 Vol. 10 No. 3 Supplement 1
not all cases resolve spontaneously.49
Infants with CSHRH have a
mortality risk of three percent and a
10-percent chance of relapse.49
Infantile LCH may occur in the skin
folds. Diagnosing CSHRH requires
that the physician first rule out
infection and then conduct a
physical examination and a biopsy
with a complete blood count, a
comprehensive metabolic panel,
urine assay, prothrombin time/partial
thromboplastin time test, a chest X-
ray, and skeletal history. Timely
diagnosis and prompt treatment with
systemic agents are important. An
oncology consultation may be of
value.
Kawasaki disease (KD) is a type
MEDIUM VESSEL VASCULITIS
of medium vessel vasculitis that
typically presents in pediatric
patients. Infantile KD may exhibit
incomplete or atypical forms.
Typical infant manifestations of KD
include mucosal changes (64%),
extremity changes (64%), rash
(53%), conjunctival injection (47%),
and cervical lymphadenopathy
(17%). KD is associated with
abnormalities in the coronary
arteries. KD typically presents
incompletely in infants younger than
six months of age; KD should be
suspected when a baby presents with
unexplained fever extending beyond
five days.50
Other types of pediatric vasculitis
can be challenging to diagnose
because their clinical manifestations,
particularly in young children, can
be highly variable. The size of the
vessels involved, the organs
involved, the extent of vascular
injury, and underlying pathology all
play a role in pediatric vasculitis.51
The signs of medium vessel
vasculitis include fixed livedo,
nodules, ulcers, and stellate purpura.
To arrive at a differential diagnosis,
the physician must consider
granulomatosis with polyangiitis
(previously Wegeners
granulomatosis), polyarteritis
nodosa, various vasculopathies (for
instance, antiphospholipid
antibodies), and calciphylaxis. A
blood panel should be ordered
(complete blood count, complete
metabolic panel, erythrocyte
sedimentation rate/C-reactive
protein, prothrombin time/partial
thromboplastin time test,
antiphospholipid antibodies,
cryoglobulins, and QuantiFERON-
Gold hepatitis panel).52 Imaging can
be of great value.51 A skin biopsy
and consultation with a
dermatologist or rheumatologist may
be warranted. These conditions carry
a high morbidity and mortality
burden and are characterized by
frequent relapse.52
PEDIATRIC DERMATOLOGY:
Dermatology frequently involves
MAINTENANCE AND HOME CARE
strategies aimed at maintaining
therapeutic results and thus relies to
a great extent on home care and
tips.Here the authors present
several of the latest tips for clinicians
and their patients.
Perioral irritant dermatitis is a
frequent cause for clinic visits. This
distressing condition may be
triggered by excessive drooling,
pacifiers, and the use of wet wipes.
Parents of children suffering from
 REviEw
perioral irritant dermatitis should
avoid putting socks on the hands of
these children during sleep and
discourage sucking on blankets or
other items. This encourages saliva
production and, in turn, irritation.
Before the child eats or goes to
sleep, a thick barrier-type ointment
should be applied to the cheeks and
chin.
While phototherapy and systemic
agents such as methotrexate,
azathioprine, and mycophenolate
may be helpful for children with
atopic dermatitis, families can
institute many practices at home to
reduce atopic dermatitis. A diagnosis
of atopic dermatitis should, in and of
itself, mandate the exclusion of
certain common household products:
scented detergents, most shampoos,
and many so-called baby products
such as soaps and lotions. Parents
should be advised that many
seemingly benign products with
labels promoting natural or
organic soaps, cleansers, and
lotions may be particularly irritating
to children with atopic dermatitis
due to botanical ingredients. While
atopic dermatitis may be treated with
topical steroids and calcineurin
inhibitors, parents may also find it
helpful to administer to their
children probiotics or synbiotics
every day, to apply coconut oil or
shea butter to the skin, and to
establish a routine for after-bath
moisturizing. Bleach baths can be
helpful to stop bacterial infections.
Diaper rash is a common
complaint and can be treated with a
paste, such as Triple Paste, with
every diaper change. Hydrocortisone
ointment 2.5% twice a day can
JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY March 2017 Vol. 10 No. 3 Supplement 1
further help treat this uncomfortable
condition. In some cases, diaper
dermatitis may actually be an
allergic reaction to blue dye (blue-
dye diaper dermatitis). In the event
that the response is to blue dye, the
parents should switch to dye-free
diapers (Huggies Natural, 7th
Generation, Earths Best) and treat
the rash with a mid-potency topical
steroid ointment. If that ointment is
not entirely effective, mupirocin
ointment can be added at signs of
infection.
Likewise, dermatologists may see
cases of car seat dermatitis. This
occurs when the child is irritated by
or allergic to the linings of certain
car seats. An easy way to manage
this condition is to add a cotton
cover or some other cover to the car
seat so that there is no direct contact
between the childs skin and the
liner.
Pediatric dermatology is a
CONCLUSION
relatively new subspecialty in
medicine, although cutaneous
complaints in pediatric patients are
extremely common. New
breakthroughs in the treatments of
hemangiomas, PWS, SWS, and
medium vessel vasculitis offer hope
for these conditions, which have not
responded well to conventional
therapies. Topical sirolimus ointment
may be a helpful adjunct to PDL
therapy for treating PWS. Better
understanding of congenital LCH
may improve its management
outcomes and follow-up. New drugs
such as JAK inhibitors may offer
broader therapeutic choices for
alopecia. Long-standing issues such
as the relationship of diet to acne and
the early introduction of allergens to
high-risk patients have re-emerged
with more data to help guide
treatment. Finally, pediatric
dermatology requires maintenance
efforts, and parents should be
counseled on things that they can do
at home to help these conditions in
their children.
1. Hurwitz S. The history of pediatric
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