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4.7 Disorders of Hair and Nails
childhood and include back pain or headache, muscle
atrophy, weakness/numbness, and bowel/bladder
dysfunction 2° to spinal compression
• MRI 5 imaging modality of choice
Bonnet–Dechaume–Blanc syndrome is the
similar association of a facial metameric AVM
extending to the brain/orbit.
Other vascular disorders
Cutis marmorata telangiectatica congenita
• Unknown etiology; may represent mosaicism
• Present at birth as reticulated erythematous-violaceous
vascular network (Fig. 4.17)
■
Usually on lower extremities and unilateral
■
Cold exposure may accentuate cutaneous features
■
Atrophy and ulceration can occur within the lesion →
scarring
■
Often fades somewhat over rst 2 to 3 years of life
• Ipsilateral limb atrophy may occur (girth and length)
• Neurologic abnormalities in some: seizures,
macrocephaly, developmental delay, and/or
ophthalmologic anomalies (e.g., glaucoma)
• Adams-Oliver syndrome: CMTC with scalp aplasia cutis
congenita and transverse limb defects
Angiokeratoma corporis diffusum (ACD)
• Finding seen in Fabry disease, fucosidosis, sialidosis,
GM1 gangliosidosis, galactosialidosis, aspartylglycosaminuria, and Kanzaki disease
• Histology: numerous thin-walled ectatic blood-lled
capillaries in the papillary dermis with a hyperkeratotic
epidermis
• Fabry disease:
■
XLR lysosomal storage disease 2° to deciency of
alpha-galactosidase (GLA gene mutation)
Glycosphingolipids accumulate in the vascular
endothelium and in epithelial, perithelial, and
smooth muscle cells of multiple organs (skin, eye,
heart, brain, kidney, and peripheral nervous system)
→ endothelial swelling and proliferation
■
Pubertal males develop thousands of angiokeratomas
in “bathing trunk” distribution between umbilicus
and knees, as well as oral mucosa/conjunctiva; a/w
hypohidrosis
■
“Whorl-like” corneal opacities, and posterior capsular
cataracts
■
Episodic and/or chronic paresthesias, often triggered by
stress/temperature/fatigue (“Fabry crisis”); often the
initial manifestation in early childhood; can develop
peripheral neuropathy
■
Cardiac rhythm/conduction abnormalities,
cardiomegaly, CHF, CVAs, angina/myocardial infarction
(MI), peripheral edema, and hypertension
■
Renal destruction → polyuria, hematuria, and renal
failure
Urinalysis typically reveals birefringent lipid
globules (“Maltese crosses”)
■
Female heterozygotes have much milder presentation
(30% w/ ACD; 70% w/ corneal opacities)
■
Recombinant enzyme therapy is the treatment of
choice, and can reverse/delay cardiac, renal, and
neurologic complications
Progressive neuropathy, renal failure, and cardiac
disease
Symptomatic strokes in fourth decade, w/ recurrence
In patients receiving enzyme replacement, cardiac
complications and cerebrovascular disease are the
main causes of mortality
■
Median age of death 5 50 years of age
• Fucosidosis:
■
AR lysosomal storage disease as a result of a mutation/
deciency in a-L fucosidase
■
ACD occurs earlier in life (around 5 years old) and is
more generalized
■
Hypo- or hyperhidrosis, coarse facies, progressive
neuromotor and cognitive deterioration/seizures,
growth failure, visceromegaly, recurrent infections, and
dysostosis multiplex
■
Ultimately fatal
Fig. 4.17 Cutis marmorata telangiectatica congenita. The reticulate mottling was
limited to the chest in this newborn male. (From Paller AS, Mancini AJ. Vascular
disorders of infancy and childhood. In: Hurwitz Clinical Pediatric Dermatology: A
Textbook of Skin Disorders of Childhood and Adolescence. 5th ed. Philadelphia:
Elsevier; 2016:279–316.)
Vascular disorders characterized by
telangiectasias
See Table 4.11
4.7 DISORDERS OF HAIR AND NAILS
Pachyonychia congenita
• AD mutations in KRT6A, KRT6B, KRT16, and KRT17
genes
• Three characteristic features: onychodystrophy, plantar
keratoderma, and plantar pain, which develop during
childhood
■
Onychodystrophy: discoloration and progressive
hyperkeratosis of the nail plate most pronounced at the
free edge with a pincer-like appearance (does not have
to affect all nails) (Fig. 4.18)
255
CHAPTER 4 • Pediatric Dermatology
Table 4.11 Vascular Disorders Characterized by Telangiectasias
Diagnosis Etiology
Spider angioma (nevus
araneus)
Unilateral nevoid
telangiectasia
Angioma serpiginosum Unclear if this represents a vascular
Generalized essential
telangiectasia
Hereditary benign
telangiectasia
Hereditary hemorrhagic
telangiectasia (HHT,
Osler-Weber-Rendu
syndrome)
Ataxia telangiectasia
(Louis-Bar syndrome)
Usually idiopathic in children and
not indicative of underlying systemic disorder
Associated with liver disease,
pregnancy, and estrogen therapy more in adults
Rarely congenital
When acquired may be idiopathic
or associated with puberty, pregnancy, estrogen therapy, or liver
disease
malformation or proliferation
Sporadic and idiopathic Macular, retiform, or linear
AD mutations in TELAB1 gene on
5q14
AD mutations in endoglin (HHT1),
activin receptor-like kinase 1
(ALK1) (HHT 2) or growth/differentiation factor-2 (GDF2) gene;
other genes may be involved
Juvenile polyposis with HHT (JPHT)
caused by mutations in SMAD4
gene
AR mutations in ataxia-telangiecta-
sia mutated (ATM) gene (regulates cell cycle control and the
cellular damage response to
double-strand DNA breaks and
confers radiosensitivity and chromosomal instability)—see ↑ chromosomal breakage in vitro w/
ionizing radiation
Of note, female carriers of the
ATM gene have ↑ risk of
breast cancer
Key Characteristics of
Telangiectasia(s)
Central erythematous papule
(arteriole) with radiating
linear macules
Blanches with diascopy
Usually macular, but may
have papular center
Pallor or vasoconstriction
around telangiectasias
represents “vascular steal”
Pinpoint red to violaceous
papules usually in a serpiginous pattern
May be purpuric
May coalesce to form large
patches
Variable morphology includ-
ing macular, punctate, or
plaque-like
Surrounding pallor rst ap-
pear between 2 and 12
years of age
Dark red and may be ele-
vated
May not appear until third or
fourth decade of life
Oculocutaneous telangi-
ectasias appear around
3–5 years of age
Ocular lesions often striking
Skin lesions may be subtle
and pinpoint
Not present in all patients
Distribution of
Telangiectasia(s) Other Clinical Features
Most commonly on
cheeks, nose, or
dorsal hands
Unilateral distribution
on upper extremity,
trunk, neck, or
face
May have dermato-
mal distribution
Most commonly on
lower extremities,
but may be more
extensive
Usually begins on
legs and spreads
proximally
Eventually wide-
spread, but usually
spares face
Predominantly on
face, arms, and
upper trunk
May be on lips and
palate
Predilection for lips,
tongue, palate,
nasal mucosa, ears,
palms, soles, and
nail beds
Typically rst ap-
pear on bulbar
conjunctivae at
3–5 years of age
Skin telangiectasias
tend to be symmetric and predilection for sunexposed areas
None when idiopathic, treat with
PDL if desired
None when idiopathic
More common in females (90%)
More common in females
Slowly progressive
May be asymptomatic or associ-
ated with paresthesias (numbness, tingling, or burning)
Slowly progressive
No associated systemic disease
Most common initial presenta-
tion is epistaxis (night time)
Can also get anemia from GI
bleeding
AVMs: pulmonary (HHT1 typi-
cally), cerebral, and hepatic
(HHT2 typically)
Truncal ataxia usually rst
manifestation, followed by
choreoathetosis, myoclonus,
and oculomotor signs
(progressive neurologic
deterioration)
Other dermatologic manifesta-
tions: noninfectious granu-
lomas, progeroid/sclerodermoid changes of skin,
hypo- or hyperpigmented
patches, and canities
Growth failure, thymus hypopla-
sia, developmental delay, and
endocrine anomalies (hypogonadism and diabetes)
↑ alpha-fetoprotein
Immunodeciency (↓ IgA/↓
IgG/↓ IgE/↑ IgM)
Chronic sinopulmonary infec-
tions w/ Streptococcus pneu-
moniae
Bronchiectasis → respiratory
failure 5 #1 cause of death
(average 20 years of age)
↑ Risk of malignancies (esp.
leukemia and lymphoma in
adolescence; also breast CA)
256
Fig. 4.18 Pachyonychia congenita. Nails show progressive discoloration, tenting,
and thickening, particularly owing to accumulation of a horny, yellowish-brown
material of the undersurface that causes the nail to project upward from the nail
bed at the free margin. Although unusual, this adolescent’s nail changes began
during the teenage years. (From Paller AS, Mancini AJ. Disorders of hair and nails.
In: Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Child-
hood and Adolescence. 5th ed. Philadelphia: Elsevier; 2016:136–174.)
4.7 Disorders of Hair and Nails
■
Female carriers may demonstrate features as a result of
random x-inactivation of ED1 (e.g., alopecia, dental
defects, and Blaschkoid linear patches of hypohidrosis)
• Clinical triad: ↓ sweating, hypotrichosis, and abnormal
dentition
■
Facial features: frontal bossing, at nasal bridge
(saddle nose), large nostrils, wide/at malar cheeks,
thick everted lips, and prominent chin (Fig. 4.19)
■
Hair: hypotrichosis with thin, light hair; eyelashes absent
■
Skin: soft/smooth, thin wrinkled skin; periorbital
hyperpigmentation; hypoplastic breast/areola, mild
onychodystrophy
■
Teeth: dentition delayed; may have peg-shaped,
conical or missing teeth
■
Eccrine glands: risk for hyperthermia (may present as
fever of unknown origin) as a result of ↓ perspiration;
↓ lacrimation may be seen
■
Notably: nails are NORMAL (unlike hidrotic ED)
■
May develop chronic sinus disease, pulmonary
infections, and asthma
■
Painful focal plantar keratoderma with hyperhidrosis
and secondary bullae and ssures develop during
childhood; palmar involvement is less severe
■
Other manifestations may include pilosebaceous cysts,
cheilitis, corneal dystrophy, and hoarseness
■
Type I: Jadassohn-Lewandowski
KRT6A and KRT16
Full expression usually not until late childhood or
adulthood
Recurrent paronychia
Benign oral leukoplakia of the tongue and buccal
mucosa (vs. premalignant in dyskeratosis congenita)
Follicular hyperkeratosis of knees, elbows, back,
and buttocks
■
Type II: Jackson-Lawler
KRT6B and KRT17
Natal teeth
Minimal oral leukokeratosis
Steatocystomas
Milder keratoderma
■
EGFR inhibitors (e.g. erlotinib) may be useful for the
painful plantar keratoderma
Ectodermal dysplasias
Heterogeneous group of genetic disorders w/ variable abnormalities of hair, teeth, nails, and eccrine glands
Hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome)
• XLR mutations in ectodysplasin (ED1) classically; AD/AR
mutations in ectodysplasin receptor (EDAR) and
ectodysplasin receptor-associated death domain (EDARDD)
Fig. 4.19 (A) and (B) Hypohidrotic ectodermal dysplasia with at nasal bridge,
depressed nasal tip, sparse hair (scalp, eyebrows, and eyelashes), and pegshaped teeth. (From James WD, Elston DM, McMahon PJ. Genodermatoses
and congenital anomalies. In: Andrews’ Diseases of the Skin Clinical Atlas
Philadelphia: Elsevier; 2018:379–404. A, Courtesy of Scott Bartlett, MD.)
257
CHAPTER 4 • Pediatric Dermatology
• Boards factoid: hypohidrotic ectodermal dysplasia with
immunodeciency is a result of mutations in IKBKG/
NEMO (XLR) or NFKBIA (AD); susceptible to recurrent
pyogenic or atypical mycobacterial infections
Hidrotic ectodermal dysplasia (Clouston syndrome)
• AD mutation in GJB6 (connexin 30)
• Clinical triad: marked onychodystrophy, PPK (with
stippling, a common feature in connexin PPKs), and
hair abnormalities
■
Onychodystrophy with variably hyperkeratotic/thin/
striated/discolored nails; hypotrichosis with thin/
brittle hair
■
Normal sweating, facial features, and teeth
■
Possible ophthalmologic (e.g., conjunctivitis,
strabismus, and cataracts) and musculoskeletal (tufted
distal phalanges) anomalies
Fig. 4.20 Congenital malalignment of the great toe. (From Paller AS, Mancini AJ.
Disorders of hair and nails. In: Hurwitz Clinical Pediatric Dermatology: A Textbook
of Skin Disorders of Childhood and Adolescence. 5th ed. Philadelphia: Elsevier;
2016:136–174.)
Ectodermal dysplasias due to p63 mutation
• AD mutation in p63 (critical transcription factor required
for ectodermal, orofacial, and limb development)
• Overlapping features of clinical disease from p63
mutations (thought to be a disease spectrum)
• Dened clinical syndromes include:
■
Rapp-Hodgkin syndrome: clefting of lip/palate/uvula,
hypoplasia of maxilla, small narrow nails, and small
conical teeth
■
Ankyloblepharon-ectodermal dysplasia-clefting
syndrome (AEC; Hay-Wells syndrome): congenital
fusion of eyelids (ankyloblepharon) a/w facial clefting
or mid-face hypoplasia; diffuse collodion-like peeling/
erythema seen at birth; scalp w/ chronic erosive
dermatitis → frequent Staphylococcus infections
■
Ectrodactyly ectodermal dysplasia-cleft lip/palate
syndrome (EEC): ectrodactyly (developmental anomaly
of median ray of feet . hands → “lobster claw”
deformity/missing digits), facial clefting, mild PPK,
conductive hearing loss, and genitourinary anomalies
■
p63 mutations also underlie acro-dermato-ungual-lacrimaltooth (ADULT) syndrome, limb-mammary syndrome
(LMS), and split hand/foot malformation (SHFM)
• All syndromes may have wiry/sparse hair, dystrophic nails,
↓ number of teeth/hypoplastic enamel, hypohidrosis,
↓ tearing, and short stature or poor weight gain
• CMs, short stature, severe developmental delay, cryptorchidism,
congenital heart defects, and typical facies (beaked nose,
downslanting palpebral ssures, low-set ears, epicanthal folds,
and grimacing smile), multiple pilomatricomas
Parakeratosis pustulosa
• Subacute paronychia, school-aged girls
• Fingers (thumb, rst nger most common; toes rare),
typically single digit
• Associated with underlying inammatory disease
(atopic dermatitis, psoriasis, contact dermatitis)
Congenital Malalignment of the great toenails
• Likely AD, with variable expression
• Lateral deviation of nailplate (due to lateral deviation of
nail matrix), rst toe, with nail ridging, thickening,
darkening, and triangular shape (Fig. 4.20)
• 50% spontaneously improve
Other nail changes are discussed in Chapter 3, General Dermatology. Menkes disease, Björnstad syndrome, Crandall syndrome,
argininosuccinic aciduria, and citrullinemia are also discussed in
Chapter 3, General Dermatology. See Table 4.12 and Figs. 4.21
and 4.22 for selected pediatric hair disorders.
Schöpf-Schulz-Passarge syndrome
• AR, WNT10A mutation
• Ectodermal dysplasia with multiple eyelid apocrine
hidrocystomas, increased risk of BCC, hypodontia,
hypotrichosis, PPK, and nail dystsrophy
Other disorders
Rubinstein-Taybi syndrome
• Sporadic mutation in CREBBP
• Broad thumbs/halluces w/ racquet nails (brachyonychia)
258
4.8 INHERITED METABOLIC AND NUTRITIONAL DISORDERS
Acrodermatitis enteropathica (genetic form)
• Primary form is AR—mutations in SLC39A4 (encodes
intestinal zinc-specic transporter ZIP4)
■
Acquired/secondary zinc deciency (acrodermatitis-like
syndrome): similar clinical ndings and histology, but
due to low zinc intake (alcoholics, anorexia) or
malabsorption (IBD); also may arise in infants who
are initially breastfed but switch to formula (lower
4.8 Inherited Metabolic and Nutritional Disorders
Table 4.12 Selected Pediatric Hair Disorders
Disorder Pathogenesis Clinical Features of Alopecia Additional Clinical Features Microscopy/Trichoscopy
Temporal triangular
alopecia
Atrichia with
papules
Wooly hair Nonsyndromic forms
Uncombable hair
(pili trianguli et
canaliculi)
Monilethrix Mutations in hair keratins
Pili torti Depending on
Trichorrhexis
nodosa (Fig. 4.21)
Trichorrhexis
invaginata
(“bamboo hair”)
(Fig. 4.22)
Marie Unna
hypotrichosis
Alopecia mucinosa
(follicular
mucinosis)
Unknown May be present at birth
Mutations in hairless
(HR) gene
may be AD or AR
Syndromic forms are
AR
Unknown Presents during infancy or early child-
(e.g., KRT81, KRT83,
and KRT86) and des-
moglein 4 (DSG4)
Mutations in hair kera-
tins are AD but mutation in DSG4 is AR
associated syndromes
Most commonly ac-
quired as a result of
trauma, such as from
chemical and thermal treatments
AD form also exists
AR mutation in SPINK5
(encodes LEKT1)
AD mutations in U2HR Absence of scalp hair, eyebrows, and
In children, usually an
idiopathic inammatory dermatosis
In children, rarely a
presentation of
cutaneous T-cell
lymphoma
Usually diagnosed between 2 and 9
years of age
Localized triangular patch of alopecia
involving the frontotemporal scalp
Often unilateral (left . right)
Hair is normal at birth, then is
quickly shed after birth
Follicular cysts and milia-like papules
appear later
Poor hair growth noted from birth
Hair is ne, dry, and curly with a corru-
gated appearance
hood
Hair is pale/blonde, dry, and unruly w/
shiny/“spun glass” appearance
Hair typically appears normal at birth
During infancy, hair becomes short
and brittle with a beaded appearance
Hair typically sparse or absent at birth
Poor hair growth
Hair appears spangled
Most common hair shaft anomaly
Variably dry, lusterless, sparse hair
Inherited form presents in infancy
Acquired form presents in adolescence
Dry, lusterless, sparse hair
Poor hair growth
eyelashes at birth
Hair grows in coarse and twisted
Beginning in adolescence, hair is pro-
gressively lost
Favors head, neck, and upper torso in
children; may involve scalp or eyebrows
Usually solitary
Presentation may include grouped fol-
licular papules, with or without erythema, and scaling, which may coalesce into a boggy plaque
Alopecia is a prominent feature
If large areas of involvement,
consider cerebellotrigeminal
dermal dysplasia
May be associated with vitamin
D–resistant rickets (earlyonset rickets, hypocalcemia,
2° hyperparathyroidism, and
↑ 1,25-OH vitamin D3)
Naxos syndrome: PPK, wooly
hair, and right ventricular
dysplasia/ cardiomyopathy
Carvajal syndrome: PPK, wooly
hair, and left-sided cardiomyopathy
Mild onychodystrophy
Various ectodermal dysplasias
Koilonychia
Keratosis pilaris (most com-
mon association)
Menkes kinky hair syndrome
Bazex-Dupre-Christol
syndrome
Rombo syndrome
Björnstad syndrome
Crandall syndrome
Argininosuccinic aciduria
Citrullinemia
Oculo-dental-digital dysplasia
Trichothiodystrophy
Netherton syndrome
Marker for Netherton
syndrome
Widely spaced central incisors Histology: mild-moderate inam-
NA Follicular degeneration
Trichoscopy and microscopy:
↓ terminal hairs and ↑ vellus
hairs
Disintegration of the lower two
third of the hair follicle
Multiple small cystic structures
NA
Light microscopy or scanning
EM of hair: in cross section,
hair shaft appears triangular
or reniform with a canalicular
longitudinal depression
Light microscopy/ trichoscopy
of hair: uniform elliptical
nodes along hair shaft
Light microscopy/ trichoscopy
of hair: flattened, twisted hair
shafts occurring at irregular
intervals
Light microscopy/trichoscopy
of hair: intermittent nodules
with the appearance of
broom bristles
Light microscopy/
trichoscopy of hair: hair shaft
intussuscepts into itself,
creating the appearance of
a “golf tee” or “ball in cup”
joint seen
mation, w/ ↓ # of hair follicles,
and without scarring or brosis
Scanning EM: longitudinal
grooves and peeling of the
cuticle
Light microscopy of hair:
hair shafts have variable
diameter and a twisted, bent
appearance
Accumulation of mucin within
hair follicles
Periappendageal, perivascular,
and/or interstitial lymphocytic/mixed inammatory cell
inltrate
If histologic features suggest
mycosis fungoides, check
T-cell receptor gene rearrangement assay from a
skin biopsy
Continued
259
CHAPTER 4 • Pediatric Dermatology
Table 4.12 Selected Pediatric Hair Disorders—cont'd
Disorder Pathogenesis Clinical Features of Alopecia Additional Clinical Features Microscopy/Trichoscopy
Loose anagen
syndrome
Short anagen
syndrome
Nevoid
hypertrichosis
Congenital
hypertrichosis,
generalized
Typically sporadic
AD inheritance may be
seen
Defective anchoring of
the hair shaft (defec-
tive inner root
sheath keratinization) to the follicle
resulting in easily
and painlessly
plucked hair
Shortened anagen
growth phase
Unknown Localized patches of terminal hair of
Unknown; XLD
inheritance has
been reported, with
both syndromic
and nonsyndromic
presentations
Common in young, fair-haired girls
2–6 years of age
Diffuse hair thinning
Hair may appear ne, limp, and matted
Girls typically grow out of this without
any intervention
Fine, short hair present at birth
Poor hair growth
abnormal length, color, and/or
diameter
Common sites include lumbosacral
area, anterior neck, and elbows
(hypertrichosis cubiti)
Universal overgrowth of terminal hair Ambras syndrome: excessive
Noonan-like syndrome cause
by SHOC2 mutations
NA Histology and trichogram:
Rare associations with
neurodevelopmental
abnormalities
vellus-like hairs on the face,
ears, and shoulders; associ-
ated with mutations in
tricho-rhino-phalangeal syn-
drome gene TRPS1
Hypertrichosis lanuginosa: per-
sistence of generalized la-
nugo hairs
Trichoscopy: multiple anagen
hairs with ruffled cuticles
and misshapen bulbs
(“hockey stick”)
↑ telogen hairs
NA
NA
Keratosis pilaris Abnormal keratinization
Keratosis pilaris
atrophicans,
atrophoderma
vermiculatum
subtype
of hair follicles
Usually sporadic; AD
inheritance reported
Affects 25%–60% of adolescents and
adults
Multiple small, scaling, and skin-col-
ored to pink follicular papules
Favor the cheeks, upper arms,
thighs, and buttocks
Treatments: keratolytics (e.g. salicyclic
acid, TCA, glycolic acid, ammonium
lactate), chlorine dioxide, lasers (e.g.
diode, Nd:YAG)
Erythematous papules with follicular
plugging, horn cysts, and atrophic
cribriform scarring
Cheeks and forehead; less commonly
neck and extremities
Typically presents between 5 and
12 yo
perplasia: diffuse overgrowth
of terminal hair, gingival hy-
perplasia
Cornelia de Lange syn-
drome: AD mutation in
NIPBL in some cases; hirsut-
ism, synophrys, tricho-
megaly, low hairline, devel-
opmental delay/psychomotor
retardation, cutis marmo-
rata, hypertonicity, short
stature, fth nger clinodac-
tyly, cryptorchidism, congeni-
tal heart defects, and recur-
rent lung infections/
aspiration → death or hear-
ing loss
Often associated w/ atopy,
xerosis, or ichthyosis vulgaris
Trisomy 21
Some ectodermal dysplasias
Trisomy 21
Rombo syndrome (atropho-
derma vermiculatum, basal
cell carcinoma, milia, telangi-
ectasias, acral erythema)
Histology: keratotic plugging
of the pilosebaceous follicles;
mild hypogranulosis and
hyperkeratosis
Histology: epidermal atrophy;
atrophic hair follicles with
keratotic follicular plugs
and dermal cysts; variable
perifollicular inflammation
260
4.8 Inherited Metabolic and Nutritional Disorders
Table 4.12 Selected Pediatric Hair Disorders—cont'd
Disorder Pathogenesis Clinical Features of Alopecia Additional Clinical Features Microscopy/Trichoscopy
Keratosis pilaris
atrophicans,
ulerythema
ophyrogenes
subtype
Keratosis pilaris
atrophicans,
keratosis
follicularis
spinulosa
decalvans
subtype
Eruptive vellus hair
Usually sporadic; AD
inheritance reported
XLR mutations in sper-
midine/ spermine
N(1)-acetyltransferase (SSAT)
Mutations in mem-
brane-bound transcription factor protease site 2 reported
(similar to IFAP)
AD inheritance also de-
scribed
Unknown, but may
mental anomaly of
vellus hair follicles
Often sporadic
AD reported
Erythematous papules with follicular
plugging and atrophic scarring
Scarring alopecia of eyebrows
Eyebrows, cheeks, and scalp; less
commonly extremities
Boys . girls; presents during infancy
Pink hyperkeratotic papules with follic-
ular plugging
Progressive scarring alopecia
Eyebrows, eyelashes, and scalp
Extensive keratosis pilaris begins in
early childhood
Scarring alopecia begins in adoles-
cence
1- to 3-mm skin-colored to hyperpig-
mented follicular papules
Seen in school-aged children and ado-
lescents
Favor the mid chest, but may also be
seen on the face, neck, extremities,
buttocks, back, and abdomen
Noonan syndrome
Cardio-facio-cutaneous syn-
drome
Cornelia de Lange syndrome
Rubenstein-Taybi syndrome
Wooly hair
Palmoplantar keratoderma
Corneal dystrophy with photo-
phobia
Atopic disease
Hidrotic ectodermal dysplasia
Hypohidrotic ectodermal dys-
plasia
Pachyonychia congenita
Histology: keratotic plugging of
pilosebaceous follicles and
mild perifollicular inammation (early)
Dermal brosis and atrophy of
the hair follicles and sebaceous glands (late)
Histology: concentric
perifollicular fibrosis w/ mixed
perifollicular inflammation and
follicular plugging
Histology: cystic dilation of the
infundibulum; cysts contain
vellus hairs and laminated
keratinaceous debris
Fig. 4.21 Trichorrhexis nodosa. Light microscopic appearance. (From Lam JM,
Wong LC. Hair disorders. In: Eicheneld LF, Frieden IJ, eds. Neonatal and Infant
Dermatology. 3rd ed. Philadelphia: Elsevier; 2015.)
bioavailability) or breastfeed from a mother who has a
low serum/breastmilk zinc level or premature infants
(have lower baseline zinc stores)
• Triad of erosive vesiculopustular eczematous lesions
involving the diaper area, face (perioricial), and acral
areas, along with diarrhea and alopecia (Fig. 4.23)
■
Severe irritability, failure to thrive, photophobia, stomatitis/
glossitis/perlèche, and nail dystrophy commonly seen
• On histology, cytoplasmic pallor of keratinocytes in
upper epidermis, with ballooning and reticular
degeneration; necrosis of keratinocytes in early lesions
• On laboratory, ↓ serum zinc (,70 mg/dL), ↓ serum
alkaline phosphatase (zinc-dependent enzyme); if zinc is
normal in a patient with suspected acrodermatitis
enteropathica, consider screening for biotin deciency and
cystic brosis as these can present similarly
Fig. 4.22 Trichorrhexis invaginata in Netherton syndrome. Light microscopic appearance. (From Lam JM, Wong LC. Hair disorders. In: Eicheneld LF, Frieden
IJ, eds. Neonatal and Infant Dermatology . 3rd ed. Philadelphia: Elsevier; 2015.)
• Treatment: life-long zinc sulfate supplementation → fast
resolution
Biotinidase (BTD) deciency and multiple
carboxylase deciency
• Biotin is required for the function of four carboxylase
enzymes (pyruvate carboxylase, propionyl-CoAcarboxylase, alpha-methylcrotonyl-CoA carboxylase,
and acetyl-CoA carboxylase); in BTD deciency and
multiple carboxylase deciency, loss of function of these
enzymes results in disruption of fatty acid oxidation and
accumulation of toxic metabolites
• BTD deciency: AR disorder caused by mutations
in BTD gene
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CHAPTER 4 • Pediatric Dermatology
Fig. 4.23 Zinc deciency. Erosions with a peripheral collarette of scale in the diaper area. (Personal collection, Dr. Jennifer Schoch.)
• Holocarboxylase synthetase (HLCS) deciency: AR
disorder caused by mutations in the HLCS gene (→ loss
of BTD function), more severe (fatal if untreated)
■
BTD deciency presents in childhood, whereas HLCS
deciency presents in early infancy
• Dermatologic manifestations: perioral/generalized
dermatitis and alopecia
• Extracutaneous manifestations: seizures, developmental
delay, hypotonia/ataxia, diarrhea, metabolic ketoacidosis,
hepatosplenomegaly, and optic atrophy (BTD
deciency)
• Treatment 5 IV biotin replacement (HLCS deciency
requires ↑ doses)
Hartnup disease
Phenylketonuria
• AR disorder 2° to loss-of-function mutation in
phenylalanine hydroxylase (PAH gene) → inability to
convert phenylalanine to tyrosine
• Cutaneous features: diffuse hypopigmentation with
blonde hair and blue eyes, eczematous dermatitis,
photosensitivity, and sclerodermatous changes of the
torso and thighs
■
Hypopigmentation of skin/hair 2° to inhibitory effect
of ↑ phenylalanine on tyrosinase
■
Mousy odor of urine, short stature, and microcephaly
• Developmental delay, seizures, irritability, limb posturing
and purposeless movements, psychosis, hyperactivity, and
autistic features may develop if untreated
• Neonatal screening for phenylketonuria is included in the
newborn screen in all states
• Treatment with low-phenylalanine diet/formula under
the guidance of a nutritionist → good prognosis; AVOID
aspartame
Homocystinuria
• AR disorder → deciency of cystathionine beta-
synthetase (CBS gene), which catalyzes the formation of
cystathionine from homocysteine and serine; thus
deciency → ↑ homocysteine
• Cutaneous manifestations: hypopigmentation of skin and
hair, brittle hair, malar erythema, livedo reticularis, and
leg ulcers
• Other ndings: myopia, ectopia lentis (downward
displacement of lens), glaucoma, seizures, developmental
delay, marfanoid habitus, mitral valve prolapse, pectus
excavatum, arachnodactyly, and cardiovascular and
cerebrovascular thromboembolic events (including
venous thrombosis)
• Amino acid chromatography of the serum and urine:
↑ urinary homocysteine and methionine; ↑ serum
homocysteine and methionine 1 ↓ cysteine
• 50% of patients respond to vitamin B6 (1 folic acid and
vitamin B12)
■
Otherwise, methionine-restricted, cysteinesupplemented diet
• AR disorder caused by mutations in SLC6A19 (encodes
B(0)AT1, the intestinal and renal neutral amino acid
transporter) resulting in low tryptophan
■
↓ Tryptophan → ↓ nicotinic acid and pellagra-like
symptoms (e.g., photosensitivity)
• Cutaneous eruption presents in childhood as an acute
photodermatitis with erythema, blistering, scaling,
crusting, and scarring occurring after sun exposure in
sun-exposed areas of the face, neck, arms, dorsal hands,
wrists, and lower legs
■
Atrophic glossitis, angular stomatitis, hair loss/fragility,
and longitudinal nail streaks
• Untreated patients may develop cerebellar ataxia, seizures,
intellectual disability, and emotional lability/psychosis
• Treatment: avoid sunlight; oral nicotinamide
supplementation
262
Lesch-Nyhan syndrome
• XLR disorder 2° to hypoxanthine-guanine
phosphoribosyl transferase mutation (HGPRT gene) →
↑ uric acid, ↓ dopamine
• Orange uric acid crystals in the diaper or hematuria may
be seen in the rst few months of life
• Neurodevelopmental delays, spastic cerebral palsy,
choreoathetosis, and intellectual impairment
• Signicant self-mutilation is characteristic
• Short stature/sstugrowth retardation, uric acid
nephropathy, gout, and megaloblastic anemia
• Treatment of choice 5 allopurinol (100–300 mg/day) in
divided doses; other hypouricemic agents may be
considered
• Renal failure → morbidity and mortality
4.9 Inherited Connective Tissue Disorders
Prolidase deciency
• AR disorder 2° to mutations in peptidase D (PEPD)
(encodes prolidase, a ubiquitous metalloenzyme involved
in the catabolism of proteins)
• Cutaneous manifestations: severe, progressive ulceration
of lower extremities, diffuse telangiectasias,
photosensitivity, and an eczematous dermatitis
■
Recurrent infections contribute to morbidity and mortality
• Other ndings: intellectual impairment, and abnormal
facies with hypertelorism/ptosis/beaked nose/frontal
bossing
Alagille syndrome
• AD mutation in Jagged 1 (JAG1) (encodes ligand for
Notch receptor; pathway plays role in determining cell
fates in early development)
• Typical triangular facies
• Tuberous xanthomas, hypercholesterolemia, and
hypertriglyceridemia
■
High serum cholesterol (.200 mg/dL) and
triglyceride (500–2000 mg/dL) levels
• Congenital intrahepatic biliary hypoplasia (cholestasis,
pruritus, and failure to thrive)
• Treatment: liver transplantation is treatment of choice;
pharmacologic management of hyperlipidemia →
resolution of cutaneous xanthomas
■
Without treatment, death before 5 years of age
Hunter syndrome
• XLR disorder 2° to mutation in IDS gene (encodes the
lysosomal enzyme iduronate 2-sulfatase → accumulation
of glycosaminoglycans in almost all organs and tissues)
• Cutaneous features: hypertrichosis, coarse facies (thick
nose, thick lips, and tongue), pebbled ivory-colored
plaques between scapulae on upper back, as well as the
upper arms/thighs
• Cardiomyopathy, hepatosplenomegaly, skeletal
deformities, progressive neurodegeneration
• ↑ Urinary heparin sulfate and dermatan sulfate
(chondroitin sulfate B)
• Part of a family of disorders termed mucopolysaccharidoses—
Hurler syndrome has dermal melanosis, developmental
delay and “gargoyle” appearance; all mucopolysaccharidoses
have hypertrichosis and coarse facies and may be
associated with extensive dermal melanosis (Mongolian
spots)
4.9 INHERITED CONNECTIVE TISSUE
DISORDERS
Cutis laxa/generalized elastolysis
• AD forms (less common): elastin gene (ELN) or bulin
5 (FBLN5) mutations → dysregulation of elastic ber
network in the skin mainly (internal involvement
uncommon); presents in early adulthood
• AR forms (most common): FBLN5, EFEMP2/FBLN4,
LTBP4, ATPase, ATP6V0A2, PYCR1, and ALDH18A1;
presents at birth to early childhood; skin 1 severe
internal involvement
• XLR form (occipital horn syndrome, previously Ehlers-
Danlos syndrome [EDS] type IX): mutations in ATPase,
Cu(21)-transporting, alpha polypeptide (ATP7A) (allelic
to Menkes disease)
• “Aged” facial appearance (hound-dog facies) with down-
slanting palpebral ssures and a long philtrum (Fig. 4.24)
• Loose, sagging skin with reduced elasticity and resilience;
deep voice 2° to vocal cord laxity
• Histology: sparse and/or fragmented elastic bers
• AD cutis laxa
■
Primarily generalized cutaneous ndings, cardiac valve
abnormalities, aortic dilatation (variable), emphysema
(uncommon), and hernias
• AR cutis laxa (ARCL)
■
ARCL type I
FBLN5, EFEMP2, or LTBP4 mutations
Potentially fatal involvement of lungs (hypoplastic
lungs and emphysema)
Cardiovascular abnormalities (aortic tortuosity and
aneurysms)
Inguinal/diaphragmatic/umbilical hernias
GI/GU diverticula
Joint laxity, arachnodactyly, and fractures (variable)
Alkaptonuria
• AR disorder 2° to mutation in homogentisic
1,2-dioxygenase (HGO) gene
• Blue-gray pigmentation (ochronosis) on face, nose, ears
(seen well on cartilage), and sclera
• Dark sweat, cerumen, and urine (pH . 7.0; adding NaOH
to urine → darkening)
• Mitral/aortic valvulitis w/ ↑ MI risk
• Intervertebral disc calcication; severe arthritis
Fig. 4.24 Cutis laxa. (Personal collection, Dr. Helen Shin.)
263
CHAPTER 4 • Pediatric Dermatology
■
ARCL type II
ATP6V0A2 (type IIA) or PYRC1 (type IIB)
mutations
Craniofacial anomalies
Cutaneous features may be primarily acral
Pachygyria (IIA) and absent corpus callosum (IIB)
Translucent skin (IIB)
■
ARCL type III (De Barsy syndrome)
ALDH18A1 (type IIIA) or PYRC1 (type IIIB)
mutations
Developmental delay/dystonia/neurologic
deterioration
Progeroid appearance
Athetosis
Corneal clouding/cataracts
• XLR cutis laxa (now termed occipital horn syndrome)
■
Easy bruising and coarse hair (variable)
■
Tortuous arteries
■
GU diverticula
■
Inguinal, diaphragmatic, and umbilical hernias
■
Long face w/ high forehead and hooked nose
■
Wedge-shaped occipital calcications (occipital
horns)
■
Hip dislocations (joint laxity)
• Acquired cutis laxa
■
Primarily adults w/ sagging of skin and little associated
internal involvement
■
Cutaneous involvement may be primarily acral;
generalized involvement typically begins on the face/
neck
■
May occur in association with drugs (penicillamine
and isoniazid), other cutaneous disorders (e.g.,
cutaneous lymphoma, Sweet’s syndrome-like eruption,
interstitial granulomatous dermatitis, and cutaneous
mastocytosis) or systemic disease (rheumatoid
arthritis, sarcoidosis, SLE, and infectious disorders)
Pseudoxanthoma elasticum
• AR disorder as a result of mutations in ABCC6 (ATP-
binding cassette, subfamily C, member 6) gene → 2°
calcication of the elastic tissue of the eyes, skin, and
arteries
• Presents during childhood or second/third decade of life
• Cutaneous manifestations
■
Thin, yellowish papules in exural areas arise during
the rst or second decade of life (Fig. 4.25)
Typically rst appear on the lateral aspects of the
neck
Papules coalesce to form cobblestone-like plaques
resembling “plucked chicken skin”
Antecubital and popliteal fossae, wrists, axillae,
groin, and periumbilical area (in multiparous
women) are involved; can also occur inside lips
Perforating pseudoxanthoma elasticum: in
advanced disease, ↑ dermal calcium deposition and
extrusion of this yellowish material through the
epidermis may occur
Loss of recoil and sagging skin in axillae and groin
Yellow papules may develop in oral/anogenital
mucosa
Fig. 4.25 Pseudoxanthoma elasticum. (From Neldner KH, Lebwohl MG. Pseudoxanthoma elasticum. In: Lebwohl MG, Heymann WR, Berth Jones J, Coulson
I, eds. Treatment of Skin Disease: Comprehensive Therapeutic Strategies .
4th ed. Philadelphia: Elsevier; 2013:638–639.)
• Ocular manifestations
■
Asymptomatic angioid streaks (Bruch’s membrane
rupture) usually in rst decade
“Owl’s eyes”: paired areas of hyperpigmented spots
straddling an angioid streak
Agioid streaks also seen in Paget’s disease of bone,
sickle cell anemia, thalassemia, EDS, lead
poisoning, and age-related degeneration
■
Macular degeneration, optic drusen, and retinal
hemorrhage (→ blindness)
■
Mottling of retinal pigment epithelium
Most prevalent ophthalmologic nding; may
precede development of angioid streaks
• Cardiovascular manifestations
■
Intermittent claudication, loss of peripheral pulses,
renovascular hypertension, mitral valve prolapse,
angina/MI, and stroke
■
Progressive calcication of elastic media and intima
→ atheromatous plaques involving predominantly
medium-sized arteries (esp. in extremities)
• GI manifestations
■
Gastric artery hemorrhage, hematemesis, epistaxis
• Obstetric complications
■
↑ Risk of rst trimester miscarriage and maternal
cardiovascular complications
• On histology, distorted, basophilic, and fragmented
calcied elastic bers in mid/deep reticular dermis
(Figs. 4.26 and 4.27)
• Morbidity and mortality 2° to GI hemorrhage, cerebral
hemorrhage, atherosclerotic disease, and MI
Osteogenesis imperfecta (OI)
• Mutations in type I collagen → fragile bones (poor
cortical modeling and less trabecular bone formation)
• There are at least eight well-dened types of OI, but types
I to IV account for 90%
■
Types I (most common form, accounts for 50% of OI;
generally mild; fractures in childhood and adolescence),
II (most severe form, fatal in perinatal period), III
(progressive and deforming—skull fractures [soft at
birth] and respiratory infection), and IV (milder form)
264