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Collodion baby: An update with a focus on


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Collodion baby: An update with a focus on practical


management
Renata Prado, MD,a Lixia Z. Ellis, MD, PhD,a Ryan Gamble, MD,a Tracy Funk, MD,a
Harvey Alan Arbuckle, MD,c and Anna L. Bruckner, MDa,b
Aurora and Denver, Colorado
Collodion baby is an uncommon clinical presentation of several genetic conditions, primarily disorders of
cornification. The severely compromised epidermal barrier presents the greatest challenge during the
newborn period and advances in neonatal care have significantly improved the prognosis. This review
summarizes the clinical characteristics, complications, outcomes, and differential diagnosis of the collodion
baby. A practical approach to management based on the literature and clinical experience is presented.
( J Am Acad Dermatol 2012;67:1362-74.)
Key words: collodion baby; collodion membrane; congenital ichthyosiform erythroderma; congenital
ichthyosis; epidermolytic ichthyosis; lamellar ichthyosis.

he term collodion baby (CB), first introduced in 1884,1 describes the phenotype of a
newborn with a parchmentlike membrane
covering its body surface.2 Although most patients
will ultimately be given a diagnosis of lamellar
ichthyosis or congenital ichthyosiform erythroderma, a range of outcomes with varying clinical
severity is seen. In the neonatal period, management
is focused on minimizing transepidermal water loss
(TEWL), supporting caloric needs, monitoring and
treating complications, and performing diagnostic
studies. This review summarizes recent advances in
the understanding of CB with emphasis on a practical
approach to management.

CLINICAL CHARACTERISTICS
CB presents at birth with erythroderma and shiny,
tight skin resembling parchment (the so-called collodion membrane) covering the entire body (Fig 1).
In rare instances, a localized collodion membrane
occurs.3 The tautness of the skin may distort features
From the Departments of Dermatologya and Pediatrics,b University of Colorado School of Medicine, Aurora; and Dermatology,
Kaiser Permanente, Denver.c
Funding sources: None.
Conflicts of interest: None declared.
Reprint requests: Renata Prado, MD, Department of Dermatology,
University of Colorado School of Medicine, 1665 Aurora Ct, Mail
Stop F703, Aurora, CO 80045-2517. E-mail: renata.prado@
ucdenver.edu.
Published online August 2, 2012.
0190-9622/$36.00
2012 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2012.05.036

1362

Abbreviations used:
CB:
EM:
HI:
NICU:
NS:
TEWL:
TGM:

collodion baby
electron microscopy
harlequin ichthyosis
neonatal intensive care unit
Netherton syndrome
transepidermal water loss
transglutaminase

of the face and extremities and result in ectropion,


eclabium, pseudocontractures, absence of eyebrows, sparse hair, and hypoplasia of nasal and
auricular cartilage.2,4,5 Distal limb ischemia as a result
of mechanical compression from thigh membranes
has been observed.4,6 Hypohidrosis is often associated. Less common features include poor sucking,
restricted pulmonary ventilation, digital vascular
constriction, and edema of the extremities.5 After
birth, the expansion of the chest with breathing
causes tears in the inelastic membrane, which begins
to peel. The membrane is shed within 3 to 4 weeks,2,5
usually revealing an ichthyosis phenotype. CB is
rare, estimated to occur in 1 in 50,000 to 100,000
deliveries. Most CB are born at term and are not small
for gestational age. A slight male predominance of
unclear significance has been found in the literature.2,7 Cases have been reported in twins, and
consanguinity of parents has been noted.4

ASSOCIATED DIAGNOSES
It is important to remember that CB is an initial
presentation of several genetic conditions, and the
eventual phenotype depends on the underlying

J AM ACAD DERMATOL

Prado et al 1363

VOLUME 67, NUMBER 6

disease (Table I). Most CB have autosomal recessive


patients is never completely normal appearing, and
congenital ichthyosis as a result of mutations in
mild ichthyosis often persists.17 Missense mutations
TGM1, ALOXE3, or ALOX12B (Fig 2). Autosomal
in TGM1 have been identified in self-healing CB,
recessive congenital ichthyosis is an umbrella
leading to hydrostatic pressure-sensitive transglutaterm encompassing the clinical spectrum of classic
minase function as a potential pathogenic model.18
In addition, ALOX12B and ALOXE3 gene mutations
lamellar ichthyosis (large, dark platelike scales
have been found.5,17-19
without erythroderma) to congenital ichthyosiform
The final diagnostic outerythroderma (pronounced
come for an individual CB is
erythroderma
with
fine
CAPSULE SUMMARY
difficult to predict without
white scale), including overlaboratory analysis. Some aulapping phenotypes. Less
Collodion baby is an uncommon clinical
thors believe that the initial
commonly described outpresentation of several genetic disorders,
severity and time to memcomes for CB include
mainly disorders of cornification.
brane shedding may indicate
Conradi-H
unermann-Happle
Mutations in the genes TGM1, ALOXE3, or
future severity of the undersyndrome, trichothiodystroALOX12B are implicated in most cases of
lying ichthyosis.6 However, 2
phy with ichthyosis, neutral
collodion baby, although a range of
studies evaluating prognostic
lipid storage disease with ichphenotypic outcomesefrom nearly
indicators did not observe
thyosis, ichthyosis vulgaris,
normal-appearing skin to severe
clinical features that served
recessive X-linked ichthyosis,
ichthyosiseis seen.
as clues in predicting the
epidermolytic ichthyosis, and
final diagnosis.2,5,20 When
hypohidrotic ectodermal dysMinimizing transepidermal water loss,
2,4,5,8
Arbuckle and
counseling parents about
plasia.
ensuring adequate growth by optimizing
Morelli9 reported a case of
the prognosis of CB, it is
caloric intake, close observation, and
holocarboxylase synthetase
important to describe the
facilitating family bonding with the
deficiency presenting with
range of outcomes and disinfant form the foundation of
a collodion membrane.
cuss the possibility of a famanagement.
Gaucher disease type 2 is a
vorable eventual phenotype,
rare cause of collodion memas seen in patients with
brane,2,10 in which histopathologic and ultrastructural
self-healing CB.21
studies reveal extracellular lamellar bilayer abnormalities of the epidermis. This may help distinguish
DIFFERENTIAL DIAGNOSIS OF CB
patients with type 2 from type 1 or 3 disease before
Other congenital ichthyoses, such as ichthyosis
the development of severe neurologic signs.10
prematurity syndrome, Netherton syndrome (NS),
Although mutations in TGM1, ALOXE3, and
Sj
ogren-Larsson syndrome, and harlequin ichthyosis
ALOX12B are associated with generalized and per(HI), present with skin findings at birth that must be
sistent disease, more limited and mild phenotypes
distinguished from CB (Table II).
are possible. Jacyk11 reported 10 South African black
Ichthyosis prematurity syndrome is characterized
infants born as CB who evolved to have ichthyosis in
by erythematous swollen skin, covered by a greasy,
a bathing suit distribution, hence termed bathing
thick, vernix caseosaelike scale in a premature
suit ichthyosis. Bathing suit ichthyosis has been
infant, and is often associated with neonatal asreported in other races and ethnicities and is a result
phyxia.22 The skin rapidly improves to a mild,
of missense mutations in TGM1, which encodes the
chronic ichthyosis accompanied by severe pruritus,
enzyme transglutaminase 1, important in the formaeosinophilia, and atopy.23 Ichthyosis prematurity
12,13
Functional
tion of the cornified cell envelope.
syndrome is caused by mutations in the SLC27A4
studies of epidermal transglutaminase in bathing suit
gene, leading to decreased incorporation of very
ichthyosis skin have revealed a marked decrease of
long chain fatty acids into cellular lipids and defecenzyme activity when the temperature increased
tive skin barrier function.24-26
from 258C to 378C, resulting in a temperatureAlthough NS has been described as a rare outsensitive phenotype.14-16
come of CB, NS typically presents with generalized
In approximately 10% of CB, the ichthyosis pheerythroderma, scaling, and peeling of the skin (but
notype spontaneously improves, leaving nearly
not a true collodion membrane), beginning at birth
normal-appearing skin. This has been described as
or shortly thereafter. Because of profound skin
self-healing CB or lamellar exfoliation of the
barrier dysfunction, affected neonates are at high
newborn. The term self-improving collodion ichrisk for hypernatremic dehydration and can develop
thyosis has been proposed, as the skin of most
severe failure to thrive. Some patients retain the
d

1364 Prado et al

J AM ACAD DERMATOL

DECEMBER 2012

sepsis,5 and percutaneous toxicity from topical medications.33 Pneumonia secondary to aspiration of
squamous debris in the amniotic fluid has also been
observed.4,6 Mortality in CB was as high as 50% in
1960, decreased to 11% in 1986, and today is about
5%.2,20 The overall prognosis has improved thanks to
advances in neonatal care and the development of
neonatal intensive care units (NICU).6
Practical recommendations regarding the management of CB (Table IV) are as follows:

Fig 1. Collodion baby: collodion membrane in 1-day-old


newborn.

erythrodermic phenotype with age, whereas others


develop the classic changes of ichthyosis linearis
circumflexa. Atopy and the characteristic hair shaft
abnormality (trichorrhexis invaginata or bamboo
hair) can present in infancy or during early
childhood.27
HI, a severe and potentially fatal congenital ichthyosis, is a rare autosomal recessive condition
caused by mutations in ABCA12, a keratinocyte lipid
transporter.28 Neonates with HI present with massive
hyperkeratosis and deep fissures in the skin, along
with ectropion, eclabium, shortened and/or tapered
fingers and toes, and flattened nose and ears.29 A
recent review of 45 cases found a 56% overall survival,
with survivors ranging in age from 10 months to 25
years.29 Most deaths occurred in the first 2 months of
life as a result of sepsis and respiratory failure.

NEONATAL MANAGEMENT OF CB
The potential complications of CB are listed in
Table III. Of utmost concern is the epidermal
barrier, which is equivalent to that of a very
premature baby. The major consequence in the
neonatal period is increased TEWL, up to 7 times
more than normal-appearing skin,30 Buyse et al30
found that TEWL in CB was initially very high, and a
decrease in TEWL during the first month of life
paralleled the skin improvement. Exaggerated
TEWL is associated with heat loss, temperature
instability, and hypernatremic dehydration.4-6 The
heat loss of evaporation also causes significant
caloric drain, which, in association with caloric
expenditures from cutaneous hyperplasia and
chronic inflammation, can be sufficient to account
for the growth failure observed in patients with
moderate to severe barrier abnormalities.31,32
Because of the defective barrier function, these
newborn infants are at increased risk for bacterial
and Candida albicans cutaneous infections,4

Admission to NICU
The CB should ideally be transferred to NICU, or
to an institution with experience in caring for premature babies if NICU is not available.6
Placement in a high-humidity incubator and
close monitoring of body temperature
There is an inverse linear relationship between
ambient relative humidity and TEWL.34,35 Incubators
able to create high ambient humidity decrease TEWL
regardless of epidermal barrier function.34,36
Placement in a humidified incubator soon after birth
prevents hypernatremic dehydration and hypothermia as a result of excessive TEWL,2,4 and is considered the most important measure when treating
these infants.6 Hypohidrosis and overheating can
occur in CB, and incubator temperatures should be
adjusted to avoid overheating these patients.8,37,38
Although the optimal amount of humidification is
not clearly defined, some advocate a minimum of
40% to 60% humidity,33 whereas others suggest 90%
to 100%.6 At our institution, we follow protocols for
premature infants, using a minimum of 60% humidity, with adjustments as needed.
The literature provides no specific criteria for
transitioning the CB from incubator to open crib.39
At our institution, the decision for incubator weaning
is individualized. Typically, the infant is transferred
to an open crib when there is adequate caloric
intake, appropriate weight gain, and absence of
complications associated with the impaired skin
barrier. Transition should not be delayed unnecessarily as, although there is no information on CB, a
study in premature infants showed that delay in
transfer from incubator to open crib may result in
increased time to achieve full oral feedings, decreased growth velocity, and increased length of
hospital stay.40
Monitoring of water and electrolyte balance,
and energy expenditure
Buyse et al30 found that TEWL in a CB at day 4 was
112 g/m2/h, compared with 18 g/m2/h in healthy
babies. Because of increased TEWL, dehydration and

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VOLUME 67, NUMBER 6

Table I. Possible outcomes of collodion baby


Category

Nonsyndromic
ichthyoses

Disease

Lamellar ichthyosis

Congenital
ichthyosiform
erythroderma

Ichthyosis vulgaris

Recessive x-linked
ichthyosis

Epidermolytic
ichthyosis

Bathing suit ichthyosis

SHCB

Syndromic
ichthyoses

Neutral lipid storage


disease with
ichthyosis

Pertinent physical
findings37

Ancillary laboratory/
radiologic testing

Collodion membrane
with ectropion and
eclabium, congenital
ichthyosiform
erythroderma,
platelike scaling,
hypohidrosis
Collodion membrane
with ectropion and
eclabium, congenital
ichthyosiform
erythroderma, fine
scaling, hypohidrosis
Xerosis, generalized
scaling sparing
flexural areas, atopic
dermatitis, pruritus,
accentuated
palmoplantar
markings
Generalized scaling
sparing body folds,
neck usually more
severely involved,
corneal clouding,
cryptorchidism
Large erosions, mild
scaling, and
erythroderma at
birth, followed by
hyperkeratosis in first
few months
Collodion membrane at
birth, followed by
brownish scaling
restricted to bathing
suit areas
Nearly complete
resolution of
collodion membrane
and scaling within
first 3 mo
Generalized
ichthyosiform
erythroderma,
hepatosplenomegaly, mild
myopathy, cataract,
short stature, mild
intellectual disability

In situ
transglutaminase-1
assay in cryostat-cut
sections

TGM1, ABCA12,
ALOX12B, NIPAL4

In situ
transglutaminase-1
assay in cryostat-cut
sections

ALOX12B, ALOXE3,
TGM1, ABCA12,
CYP4F22, NIPAL4

H&E: reduced or absent


stratum granulosum

FLG

Absent steroid sulfatase


activity in leukocytes
and fibroblasts,
elevated blood
cholesterol sulfate
levels
H&E: epidermolytic
hyperkeratosis; EM:
aggregations and
clumping of keratin
filaments in
suprabasal cells
In situ
transglutaminase-1
assay in cryostat-cut
sections

STS

Gene(s)

KRT1, KRT10

TGM1

In situ
transglutaminase-1
assay in cryostat-cut
sections

TGM1, ALOX12B,
ALOXE3

Lipid vacuoles within


leukocytes,
monocytes, and
keratinocytes,
abnormal LFT results
and fasting lipids,
increased CPK

ABHD5

Continued

J AM ACAD DERMATOL

1366 Prado et al

DECEMBER 2012

Table I. Contd
Category

Disease

TTD with ichthyosis

Conradi-H
unermannHapple syndrome

KID syndrome

Loricrin keratoderma

ARC syndrome

KLICK syndrome

Metabolic
diseases

Holocarboxylase
synthetase deficiency

Pertinent physical
findings37

Ancillary laboratory/
radiologic testing

Generalized
ichthyosiform
erythroderma, brittle
hair, impaired
intelligence, short
stature, with or
without
photosensitivity
Congenital
ichthyosiform
erythroderma in lines
of Blaschko followed
by hyperkeratosis,
follicular
atrophoderma,
stippled epiphyses,
cataracts, asymmetric
facial appearance
Severe generalized or
localized
erythrokeratoderma
with spiky
hyperkeratosis, PPK,
keratitis, hearing loss
Congenital
ichthyosiform
erythroderma, diffuse
PPK with honeycomb
pattern, pseudoainhum, knuckle
pads
Generalized scaling
with sparing of skin
folds, arthrogryposis,
renal tubular
degeneration,
intrahepatic bile duct
hypoplasia with
cholestasis,
metabolic acidosis,
abnormal platelet
function, cerebral
malformation
Congenital ichthyosis,
linear keratosis in
skin folds, sclerosing
PPK
Metabolic acidosis,
hyperammonemia,
organic aciduria,
metabolic
encephalopathy,
poor feeding,
lethargy, respiratory
distress, and
hypotonia

Polarizing microscopy
of hair shaft:
alternating light and
dark bands, other
hair abnormalities,
eg, trichoschisis or
trichorrhexis nodosa

ERCC2/XPD, ERCC3/
XPB, GTF2H5/TTDA,
C7Orf11/TTDN1
(nonphotosensitive)

H&E: calcification in
follicular keratosis in
neonates, bone x-ray

EBP

MRI: absence of corpus


callosum

GJB2 (GJB6)

H&E: parakeratosis and


hypergranulosis; EM:
electron dense
intranuclear granules
in granular cells

LOR

Liver and renal biopsy

VPS33B

EM: hypergranulosis
and abnormally big
keratohyaline
granules
Carboxylases assay in
leukocytes or
cultured skin
fibroblasts

POMP

Gene(s)

HLCS

Continued

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VOLUME 67, NUMBER 6

Table I. Contd
Category

Disease

Gaucher disease type 2

Others

Hypohidrotic
ectodermal dysplasia

Congenital
hypothyroidism59-62

Pertinent physical
findings37

Ancillary laboratory/
radiologic testing

Congenital
ichthyosiform
erythroderma,
hepatosplenomegaly,
opisthotonus,
hypotonia, facial
anomalies,
arthrogryposis,
respiratory distress,
and progressive
neurologic
deterioration
Hypohidrosis or
anhidrosis with
hyperpyrexia, atopic
dermatitis, sparse
hair, frontal bossing,
saddle nose,
supraorbital ridging,
hypoplastic mid face,
thick everted lips,
hypodontia or
anodontia, pegshaped/conical
incisors and canines,
hypoplastic or absent
breast and nippleareolar complex
Clavicular pad;
puffiness of
periorbital tissues
and tongue, lips,
hands, and genitals;
dry, cold, and pale
skin; dry and brittle
nails and hair; patchy
alopecia; dwarfism;
mental retardation;
somnolence;
constipation; feeding
problems; poor
muscle tone;
persistence of
jaundice; and
respiratory problems

Deficiency of
b-glucosidase in
leukocytes or
cultured skin
fibroblasts, LFTs,
increased serum acid
phosphatase,
Gaucher cells in bone
marrow

GBA

Hair with longitudinal


groove on EM

EDA, EDAR, EDARADD

Serum total or free T4,


TSH, thyroid-binding
globulin

DUOX2, PAX8, SLC5A5,


TG, TPO, TSHB, TSHR

Gene(s)

Continued

hypernatremia are of concern; therefore, during the


first weeks of life, accurate calculation of intake and
output is essential.33 Body weight is one of the best
clinical indicators for the adaptation of nutrients and
fluid intake, and this should be checked daily.6
Electrolytes should be monitored and adjustments
of fluid intake made accordingly. Clinical evaluation

should dictate the need for intravenous lines and


blood sampling, which may induce further skin
damage and increase the risk of systemic infections.6
Nutrition
Because transcutaneous evaporation is accompanied by loss of heat (2.42 kJ/mL), excessive rates of

J AM ACAD DERMATOL

1368 Prado et al

DECEMBER 2012

Table I. Contd
Category

Disease

Koraxitrachitic
syndrome63

PPK with anogenital


leukokeratosis64

Pertinent physical
findings37

Ancillary laboratory/
radiologic testing

A syndromic form of
SHCB: collodion baby
at birth, with patchy
erythema,
progressive thinning
of hyperkeratotic
membrane,
generalized irregular
dermal atrophy,
alopecia, absent
eyelashes and
eyebrows, and
conjunctival pannus,
hypertelorism,
prominent nasal root,
large mouth,
micrognathia,
brachydactyly,
syndactyly involving
all interdigital spaces,
and camptodactyly
of fingers III-V
Diffuse, nonprogressive
PPK in combination
with intermittently
pruritic, slowly
progressive
anogenital
leukokeratosis

H&E:
orthohyperkeratosis
and marked atrophy
of dermis, immature
dermal extracellular
matrix, factor XIII-a
positive dendrocytes
are rare and globular
rather than dendritic

Unknown

Keratin immunocytochemistry shows


marked expression of
suprabasal K17 and
absence of K6 and
K16

Unknown

Gene(s)

ARC, Arthrogryposis-renal dysfunction-cholestasis; CPK, creatine phosphokinase; EM, electron microscopy; H&E, hematoxylin and eosin; KID,
keratitis-ichthyosis-deafness; KLICK syndrome, keratosis linearis with ichthyosis congenita and sclerosing keratoderma; LFT, liver function test;
MRI, magnetic resonance imaging; NAD, nicotinamide adenine dinucleotide; PPK, palmoplantar keratoderma; SHCB, self-healing collodion
baby; T4, thyroxine; TSH, thyroid-stimulating hormone; TTD, trichothiodystrophy.

Nutrition with intermittent gavage or through a


nasogastric tube4 should be initiated if the infant has
difficulty feeding and poor weight gain, as may be
seen when a very tight membrane causes significant
eclabium.4

Fig 2. Collodion baby: lamellar scales in 3-month-old girl


with lamellar ichthyosis.

TEWL constitute a significant caloric drain, and the


severity of the barrier defect correlates with increased metabolic demands.32 Infants with severe
CB should be treated with early caloric supplements
to maximize their growth potential.31

Monitoring for signs of cutaneous or systemic


infection
Prophylactic antibiotics are not recommended.
However, as there is an increased risk for developing
infections, surveillance is important and clinical
suspicion of infection should prompt appropriate
evaluation and treatment.6 Skin infections may further exacerbate the underlying permeability barrier
abnormality, and timely treatment will help to reduce cutaneous water and caloric losses.31
Emollients
Nopper et al41 evaluated the use of a water-in-oil
emollient (Aquaphor, Beiersdorf, Inc, Hamburg,

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VOLUME 67, NUMBER 6

Table II. Collodion baby differential diagnosis


Disease

Harlequin ichthyosis

Ichthyosis prematurity
syndrome

Netherton syndrome

gren-Larsson
Sjo
syndrome

Pertinent physical examination findings

Ancillary laboratory/radiologic testing

Large, diamond-shaped plates separated


by deep cracks, extreme ectropion and
eclabium, contractures, high mortality
Respiratory distress and generalized
hyperkeratosis with focal accentuation
on scalp and eyebrows at birth with
spontaneous improvement, followed
by atopic dermatitis and asthma
Congenital ichthyosiform erythroderma,
ichthyosis linearis circumflexa, atopic
dermatitis, frequent skin infections,
anaphylaxis from food allergy
Congenital ichthyosis with focal
accentuation on scalp and neck,
pruritus, spastic paraplegia, mental
retardation, glistening dot retinal
pigmentation, dental enamel dysplasia

Gene(s)

EM: reduced or absent lamellar


bodies in stratum corneum

ABCA12

Eosinophilia, lamellar deposits in


swollen corneocytes and
edematous granular cells

SLC27A4

Hair: trichorrhexis invaginata

SPINK5

Eye examination, increased fatty


alcohols in blood, reduced
aldehyde dehydrogenase or fatty
alcohol NAD oxidoreductase in
leukocytes

ALDH3A2

EM, Electron microscopy.

Table III. Complications in collodion baby


d
d
d
d
d
d
d

d
d

Temperature instability and hypothermia


Hypohidrosis and overheating
Hypernatremic dehydration
Poor feeding and failure to thrive
Infection (cutaneous or systemic)
Percutaneous toxicity
Pneumonia secondary to aspiration of squamous material in amniotic fluid
Mechanical compression leading to distal limb ischemia
Ectropion, keratitis, and other ophthalmologic
complications
Obstruction of external ear canal

Table IV. Management of collodion baby in


neonatal period
d
d
d

d
d
d

d
d

Germany) in preterm infants of estimated 30 and 36


weeks gestational age. Twice-daily application of
water-in-oil emollient decreased TEWL by 80% in the
first 30 minutes and by 37% in the next 4 to 6 hours.
Because CB has defective skin barrier function with
increased TEWL, there is a theoretical benefit from
the application of a bland emollient, but the literature
shows controversial results. In a study of 17 patients,
Van Gysel et al2 found that 72% of patients treated
with emollients (petrolatum, lanolin, and cetomacrogol cream) had cutaneous infections, in contrast
with 16% of patients who were not. A recent
Cochrane systematic review42 on the use of topical
ointment in preterm infants included 4 studies and
1304 preterm infants, and found that routine application of ointment increased the risk of coagulasenegative staphylococcal (relative risk 1.31, 95%
confidence interval 1.02-1.70) and nosocomial

d
d

d
d
d

Admission to NICU
Placement of newborn in highly humidified incubator
Monitoring of body temperature and avoidance of
hypothermia because of increased transepidermal water
loss and overheating caused by hypohidrosis
Monitoring of water and electrolyte balance
Caloric supplementation if necessary
Monitoring for signs of cutaneous or systemic infection,
and standard NICU precautions for infection control
when handling child
Use of petrolatum-based topical emollient several times
a day
Avoidance of medicated ointments
Ophthalmologic evaluation of ectropion
Otorhinolaryngologic evaluation if external ear canal is
obstructed
Pain management if necessary
Nasogastric tube placement if difficulty sucking prevents
adequate feeding
Use of oral retinoid when necessary
Encouragement of parental involvement in care of baby
Diagnosis of underlying condition

NICU, Neonatal intensive care unit.

(relative risk 1.20, 95% confidence interval 1.001.43) infections compared with standard care.36
There was heterogeneity in the results of the studies
included in this meta-analysis. For example, in the
study by Nopper et al, the water-in-oil emolliente
treated group had a 3.3% rate of sepsis versus 26% in
the control group.41 Taieb and Labreze6 reported

1370 Prado et al

that application of sterile petrolatum along with


proper hand washing of health care workers decreased the risk of infection. Shareef et al33 presented
a single case of CB who was treated with water-in-oil
emollient daily with close attention given to hand
washing by the medical staff. In this report the
infants electrolytes were normal, indicating that
TEWL was minimal and there were no episodes of
infection in the hospital or at home. In our institution, we recommend application of petroleum jelly
or water-in-oil emollient 4 to 6 times daily, and
encourage involvement of the parents in the skin
care of their newborn.
Avoid use of medicated ointments
Because of the disrupted epidermal barrier, application of topical medications carries a risk of
percutaneous absorption and systemic intoxication.43,44 Beverley and Wheeler45 described 2 patients with CB treated with 10% urea and 5% lactic
acid who were found to have elevated plasma urea
levels.45 The levels returned to normal after the
preparation was discontinued. Salicylic acid toxicity
requiring dialysis and ventilatory assistance has been
reported in a CB treated with 20% salicylic acid.46
Therefore, it is of the utmost importance to use
caution with the application of any topical medicated
product.
Ophthalmologic and otorhinolaryngologic
care
We recommend consultation with an ophthalmologist for ectropion in CB. It is crucial to protect the
exposed eyes with a bland lubricating ointment to
prevent development of conjunctivitis and keratitis.6
If the newborn fails a hearing screen or if the external
ear canal is obstructed, otorhinolaryngologic consultation to debride the ear canal is indicated.
Pain management
The baby should be assessed routinely for signs of
pain. If noted, soft bedding or a water bed may be
useful and analgesics before bathing and skin care
may be appropriate.6 In our experience with infants
with epidermolysis bullosa, cleansing the skin with
normal saline (which can be approximated at home
by using a dilution of 1 teaspoon or 5 g of pool salt in
1 L of water) is more comfortable than plain water.
This approach has also been used in patients with
HI46 and can be tried in CB when bathing appears to
be painful.
Oral retinoids
Systemic retinoid therapy is often recommended soon after delivery of an HI baby to promote

J AM ACAD DERMATOL

DECEMBER 2012

accelerated shedding of the hyperkeratotic plates


and improvement of ectropion and eclabium.47
Acitretin is available in liquid form for infants.
Oral isotretinoin has also been used with
success.48
In the neonatal period, however, oral retinoids are
rarely used for CB, because there is usually spontaneous improvement. In selected CB cases, when
shedding of the membrane is delayed, or in patients
with severe underlying ichthyosis, administration of
an oral retinoid may be considered. The dose of
acitretin may be 0.5 to 0.75 mg/kg/d,6 or for isotretinoin, 2 mg/kg/d.48 Systemic retinoid therapy should
be tapered or withdrawn once an improvement is
seen. Common side effects include cheilitis, fragile
skin, dry eyes, and abnormalities in the lipid profile
and liver enzymes.49 Monitoring of complete blood
cell count, liver function, serum creatinine, cholesterol, and triglyceride levels is necessary. Long-term
use of systemic retinoids in children is associated
with musculoskeletal side effects and premature
epiphyseal closure, although studies so far have
shown safety with the lower doses typically used,
even for periods greater than 10 years.47,49-52
Nevertheless, we limit the duration of retinoid therapy in neonates to resolution of severe findings and
we reserve long-term use of retinoids for adolescent
and adult patients.
Parental involvement
Bonding is stimulated by allowing the parents to
be at the bedside as much as possible during the
stabilization period. Parents should actively participate in the infants care. When possible, we encourage kangaroo mother care, in which the infant is
placed skin to skin with the mother for many hours
each day, with close monitoring. This treatment
modality has been compared with the use of incubators in preterm infants with birth weight less
than 2000 g, and shown to have benefits including
reduced pain and infections, shorter hospitalization,
and better cognitive and motor development.53,54
There are no studies comparing the use of incubator
to kangaroo mother care in CB.
Caregivers must anticipate the discharge needs of
the infant and family. One of the most challenging
problems is to communicate with the family regarding the actual diagnosis. The long-term prognosis is
difficult to assess at birth and the compromised skin
status can be difficult for the family to comprehend.6
Diagnosis of the underlying condition
During the neonatal period, the following diagnostic procedures may be considered:

J AM ACAD DERMATOL
VOLUME 67, NUMBER 6

Prado et al 1371

Detailed family history, including questions about


consanguinity of the parents and other affected
family members, with pattern of inheritance.
Microscopic examination of scalp and eyebrow
hairs with regular and polarized light, looking for
the tiger tail hair of trichothiodystrophy and
trichorrhexis invaginata of NS.
The value of skin biopsy specimen depends on
the availability of studies such as routine histopathology, immunohistochemistry, and electron microscopy (EM).

intermediate filaments in the stratum spinosum. It must be cautioned that the use of EM
for differentiating the ichthyoses depends on
the experience of the user and the methods
used. Elias et al57 have advocated processing
EM specimens using both osmium tetroxide
and ruthenium tetroxide postfixation to visualize lipid-containing structures in addition to
ultrastructural morphology. Although these
studies have been of tremendous use on the
research front, clinical availability is limited.

1. Routine histopathology of the collodion


membrane will show diffuse orthohyperkeratosis in most cases. After the membrane has
been shed and the resultant phenotype
emerges, routine skin biopsy specimen may
show disease-specific findings.55,56 For instance, the histopathologic features of bullous
and normal-appearing skin in patients with
epidermolytic ichthyosis are characteristic with
a thick stratum corneum and epidermolytic
hyperkeratosis in the suprabasilar malpighian
layer (vacuolar degeneration of keratinocytes,
with clear spaces surrounding keratinocyte
nuclei and indistinct cell boundaries, along
with hypergranulosis with irregularly sized and
shaped granules). In other conditions, the biopsy specimen may be suggestive but not
diagnostic, and clinicopathologic correlation
is necessary. For instance, the cutaneous histopathology of ichthyosis vulgaris shows lack
of the granular cell layer. Congenital ichthyosiform erythroderma and lamellar ichthyosis are
indistinguishable on histopathologic examination, with compact orthohyperkeratosis, follicular keratosis, and a prominent granular cell
layer. Neutral lipid storage disease with ichthyosis shows vacuolation of basal keratinocytes,
and sweat glands are foamy, vacuolated, and
may contain lipids.

The optimal time to obtain skin biopsy specimens


is controversial. Depending on the available studies,
a biopsy specimen in the first few days of life may
assist in establishing the diagnosis, help parents to
understand the condition, and provide prognostic
information. In the unfortunate case of a neonate at
risk for early demise, early biopsy might be the only
opportunity to obtain a skin specimen that could
provide information to guide genetic counseling and
planning for future pregnancy. However, if the baby
is stable and specialized testing is not available,
waiting for the collodion membrane to shed before
considering a skin biopsy is reasonable. The phenotype of the underlying diagnosis will often become
evident with time and in some cases it may be better
to wait until this is established and can help guide
further evaluation workup.
d Genetic testing for the known mutations associated with CB is available, and obtaining a blood
sample for DNA extraction is advised. Laboratories in Europe and the United States that perform
genetic testing for ichthyoses on a commercial
basis include: (1) Center for Human Genetics
Freiburg, Kohlhase Laboratory, Freiburg, Germany; (2) Centogene GmbH, Rare Disease Company, Rostock, Germany; (3) GeneDx,
Gaithersburg, MD; (4) Instituto de Medicina
Gen
omica, Innovagenomics, Salamanca, Spain;
(5) Instituto de Medicina Gen
omica, IMEGEN,
Paterna, Spain; and (6) University Clinic Freiburg,
Institute for Human Genetics, Freiburg, Germany.
Testing is often done on a gene-by-gene basis,
rather than in parallel, meaning the clinician must
request testing based on the suspected clinical
phenotype. The clinician should liaise with the
laboratory regarding the cost and variety of genes
tested. Up-to-date information on the clinical
laboratories offering genetic tests can be found
at the National Institutes of Health Genetics Home
Reference World Wide Web site (http://ghr.nlm.
nih.gov/conditionCategory/skin-hair-and-nails).
d Biochemical and metabolic assays may be warranted in selected cases. In patients with a clinical

2. Cellular expression of proteins involved in the


pathogenesis of the different ichthyoses may
be examined by immunohistochemistry. Before obtaining a skin biopsy specimen for
immunohistochemistry, the clinician should
identify a laboratory able to perform this
testing, as availability may be limited.
Transglutaminase-1 is often the first protein
to be tested as it is the most likely to be absent
in CB.
3. EM assists the diagnosis of several congenital
ichthyoses. In epidermolytic ichthyosis, for
example, EM reveals clumped keratin

J AM ACAD DERMATOL

1372 Prado et al

presentation suggestive of Sj
ogreneLarsson syndrome, fatty alcohol oxidoreductase activity can
be measured in fibroblasts, and mutation analysis
to identify fatty aldehyde dehydrogenase gene
mutations can confirm the diagnosis.55,58 Blood
samples may be examined for lipid inclusions in
leukocytes, which are found in neutral lipid storage disease with ichthyosis and Gaucher disease.

DECEMBER 2012

4.

5.

6.

POSTDISCHARGE FOLLOW-UP
We follow up patients every 3 months during the
first year of life in the dermatology clinic after their
discharge from the NICU. More frequent visits may
be necessary in patients with severe disease or who
require treatment with oral acitretin. Genetic counseling should be offered to affected families after an
exact diagnosis has been established.
For management of the ichthyoses after the newborn period readers are encouraged to read an
excellent review published by Oji and Traupe.38

RESOURCES FOR PHYSICIANS AND


FAMILIES
Because of the rarity of CB, not all physicians are
familiar with the diagnostic procedures and treatment recommendations. Therefore, it is important to
contact experts in this field and to refer families and
affected patients to support organizations, especially
when the underlying condition requires long-term
management. In the United States, FIRST
(Foundation for Ichthyosis and Related Skin Types)
is an active foundation that provides information,
education, and support to families and patients with
ichthyosis (http://firstskinfoundation.org). There is a
list of other foundations, organizations, and Internet
links in the report from the First Ichthyosis
Consensus Conference in Sor
eze, France, in 2009.37

CONCLUSIONS
CB is not a diagnosis but a neonatal phenotype
that can evolve into many distinct conditions, primarily disorders of cornification. The severely compromised epidermal barrier represents the greatest
challenge during the newborn period, and advances
in neonatal care have significantly improved the
prognosis of these babies.

7.

8.

9.
10.

11.

12.
13.

14.

15.

16.

17.

18.

19.
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