CASE REPORT
MODERATOR
Asst Professor
Dr ASHA BENAKAPPA

NAME: B\o Laksmamma
 SEX : Male
 AGE :NB(6hrs)
 IP NO :234620
 DOA :27-1-05 at 9.30pm
 DOB :27-1-05 at 3.30pm
 DOE :28-1-05 at 8.30am
OBSTETRIC HISTORY

MA-27yrs
 ML-9yrs
2 degree consanguineous
marriage
 LMP ? EDD ?
 EDDs—23-2-05
 Hb:9gms%

G5 P4L1D3
 1— Hospital delivery male NVx died 1day, 9yrs
(resp difficulty)
 2– Home delivery female 7yrs FTND A & H
 3—home delivery male N Vx died 1day ,4yrs
(resp difficulty)
 4—Hospital delivery male LSCS extracted with
similar abnormal skin lesion ,died 2days(resp
difficulty)
 5 present one

1 ANC tumkur Pvt hospital
2ANC VVCH
71\2 mon amennorhea
T1 –N\o fever ,Rash
T2-N\o PIH ,quickening 5month
T3-H\o leaking P\V
DOA to VVCH 25-1-05at 11.35am because of
leaking P\v
2 doses inj Betnesol given
H\o Labour pains 27-1-05 at 6am
2USG scan done
USG 11/11/04:Single live fetus 25+/-7 days moderately
reduced liqour .Fetus shows narrow thorax & protruberant
abdomen ? Asphyxiated thoracic dystrophy.
USG 14/12/04 :Single live fetus 27+/-1week with breech in
lower pole.
Delivered live male baby 27-1-05 at 3.30pm breech
BCIAB
shifted NICU
2
7yrs

Wt-2kg
 HC-32cms
 CC-28cms
 Length –45cms
 RR-60 /min HR-130/min Temp-N
 CFT <2sec
.P.I—2.19 DS-6 SS-5

Head :hair loss
hyperkeratotic scale
 Eyes: Severe ectropion is present. The free
edges of the upper and lower eyelids are
everted. (ectropion)
Conjuctival congestion

Ears: Pinna --small and rudimentary.
 Nose:Flattened
 Lips: Severe traction on the lips ---eclabium and a fixed, open mouth.

o
o
o
o
Extremities
Limbs are encased in the thick hyperkeratosis,
resulting in flexion contractures of the arms, the
legs, and the digits.
Limb motility is poor .
Circumferential constriction of a limb, leading to
distal swelling .
Hypoplasia of the fingers, the toes, and the
fingernails

Skin: Severely thickened skin with large,
shiny plates of hyperkeratotic scale.
 Deep erythematous fissures separate the
scales .
 TESTES:Undescended

Weak cry.
 Activity :minimal
 NBR reflexes-Sucking-weak
Moro—absent
Grasp –absent
Rooting-absent

RS:Grunt
tachypneoa
SCR+ ICR +
B\l air entry+
CVS:S1 S2+
PA: no organomegaly
PHOTOS
VIDEO

PRETERM (32+\-2)WEEKS AGA LBW
RDS HARLEQUIN ICHTHYOSIS
Skin Biopsy

Marked Hyperkeratosis with follicular
plugging evident at places.Dermis is
thinned out with minimal inflamation.
 RESTRICTIVE DERMOPATHY
HARLEQUIN ICHTHYOSIS


SYNONYMS:Ichthyosis congenita, keratosis
diffusa fetalis, harlequin fetus .
It was described by OLIVER HART in his
diary 1750 ,published in 1896.
 It was invariably associated with stillbirth or
early neonatal death until Lawlor reported a
case that survived in 1985.

The term harlequin derives from the
newborn's facial expression and the
triangular and diamond-shaped pattern
of hyperkeratosis .

Frequency:
 Internationally: More than 100 cases have
been reported.
 Mortality/Morbidity: The mortality rate is
high. With neonatal intensive care and the
advent of retinoid therapy, some babies have
survived the newborn period. They are still at
risk of succumbing to systemic infection,
which is the most common cause of death.
Race: No racial predilection is known.
 Sex: No increased risk based on sex is
known.



Genetics: This disorder occurs in
consanguineous relationships; multiple
siblings within a family can be affected.
This has led to the supposition of autosomal
recessive inheritance.
 A new mutation inherited as an autosomal
dominant trait has also been suggested

History: This condition presents at birth. It
may or may not have been diagnosed
prenatally in a high-risk family. The history
should carefully explore the following
questions:
 Is the couple consanguineous?
 Does the couple have another child with
ichthyosis?
 Is there a family history of severe skin
disorders?





Is there a history of intrauterine or neonatal
deaths in the couple or their families?
What was the expected date of delivery?
Were decreased fetal movements or
intrauterine growth retardation noted during
the pregnancy?
Did the mother have a prenatal ultrasound?
Were any prenatal procedures (eg,
amniocentesis, fetal skin biopsy) performed?
CLINICAL FEATURES

Skin: Severely thickened skin with large,
shiny plates of hyperkeratotic scale is present
at birth. Deep erythematous fissures separate
the scales.
 Eyes: Severe ectropion is present. The free
edges of the upper and lower eyelids are
everted, leaving the conjunctivae at risk for
desiccation and trauma.
 Ears: Pinnae may be small and rudimentary
or absent.

Lips: Severe traction on the lips causes
eclabium and a fixed, open mouth.
 Nose: Nasal hypoplasia and eroded nasal
alae may occur.
 Extremities
o Limbs are encased in the thick
hyperkeratosis, resulting in flexion
contractures of the arms, the legs, and the
digits.
Limb motility is poor to absent.
Circumferential constriction of a limb
can occur, leading to distal swelling or
even gangrene.
 Hypoplasia of the fingers, the toes, and
the fingernails has been reported.
Polydactyly has been described.
o

Temperature dysregulation
o Thickened skin prevents normal sweat gland
function and heat loss.
o The infants are heat intolerant and can
become hyperthermic.

Respiratory status: Restriction of chest-wall
expansion can result in respiratory distress,
hypoventilation, and respiratory failure.
 Hydration status: Dehydration from excess
water loss can cause tachycardia and poor
urine output.

Central nervous system
o Metabolic abnormalities can cause seizures.
CNS depression can be a sign of sepsis or
hypoxia.
o Spontaneous movements may be restricted
by hyperkeratosis, making neurologic
assessment difficult.

Histologic, ultrastructural, and biochemical
studies have identified several characteristic
abnormalities in the skin of patients. The 2
main abnormalities involve lamellar granules
and the structural proteins of the cell
cytoskeleton.
 The interrelationship between these 2
abnormalities and the mechanism by which
they alter desquamation of the skin is poorly
understood
Abnormal lamellar granule
structure and function
Lamellar granules are intracellular granules
that originate from the Golgi apparatus of
keratinocytes in the stratum corneum.
o These granules are responsible for secreting
lipids that maintain the skin barrier at the
interface between the granular cell layer and
the cornified layer.
o The extruded lipids are arranged into
lamellae in the intercellular space with the
help of concomitantly released hydrolytic
enzymes. The lamellae form the skin’s
hydrophobic sphingolipid seal.
o .
o

All patients with harlequin ichthyosis have
absent or defective lamellar granules and
no intercellular lipid lamellae.
 The lipid abnormality is believed to allow
excessive transepidermal water loss; lack of
released hydrolases prevents desquamation,
resulting in a severe retention hyperkeratosis
Abnormal conversion of
profilaggrin to filaggrin
Profilaggrin is a phosphorylated polyprotein
residing in keratohyalin granules in granular
cell layer keratinocytes.
o During the evolution to the corneal layer,
profilaggrin converts to filaggrin via
dephosphorylation.
o Filaggrin allows dense packing of keratin
filaments. Its subsequent breakdown into
amino acids occurs prior to desquamation of
the stratum corneum.
o
Some patients with harlequin ichthyosis have
shown persistence of profilaggrin and
absence of filaggrin in the stratum corneum.
o A defect in protein phosphatase activity and
subsequent lack of conversion of profilaggrin
to filaggrin has been implicated in the
disorder's pathogenesis.
o Abnormal expression of keratin
o Abnormal keratohyalin granules
o

Based on the immunohistocytochemical
features, harlequin ichthyosis has been
classified into 3 types.
o Type 1 has a normal expression of keratins.
Profilaggrin is present, but filaggrin is absent.
Large, stellate keratohyalin granules that look
almost normal are present.
o In type 2, the hyperproliferative keratins
(K6/K16) are present,. Profilaggrin is present,
but filaggrin is absent. Keratohyalin granules
are abnormally small and rounded.
o
Type 3 has normal expression of keratins.
Profilaggrin is expressed in intraepidermal
sweat ducts and is barely present in the
interfollicular epidermis. Filaggrin is absent.
No interfollicular keratohyalin granules are
present; but like profilaggrin, keratohyalin can
be seen in the keratinizing cells around the
sweat ducts.
SKIN BIOPSY

The stratum corneum is thick and compact.
 Hyperkeratosis may be more marked around
hair follicles compared with the interfollicular
epidermis.
 Cells within the stratum corneum are
abnormally keratinized.
 Granular, spinous, and basal cell layers
appear unremarkable. Inflammatory cells may
infiltrate the papillary dermis.

Electron microscopy reveals absent or
abnormal lamellar granules within the
granular layer keratinocytes.
 Lamellae are absent in the intercellular
spaces between the granular cell layer and
the cornified cell layer.
 Densely packed lipid droplets and vacuoles
are seen within the cytoplasm of the
aberrantly cornified cells of the stratum
corneum.
. Keratohyalin granules may be absent,
normal, or abnormally small and
globular.
 Keratin intermediate filaments within
granular cells may have reduced
density.


TREATMENT

Ensure airway, breathing, and circulation are
stable after delivery.
 Babies require intravenous access.
Peripheral access may be difficult. Umbilical
cannulation may be necessary.
 Place infants in a humidified incubator.
Monitor temperature, respiratory rate, heart
rate, and oxygen saturation. Avoid
hyperthermia.

Once stabilized, transfer newborns with
harlequin ichthyosis to a level 3 neonatal
nursery.
 Apply ophthalmic lubricants to protect the
conjunctivae. Bathe infants twice daily. Use
frequent applications of wet sodium chloride
compresses followed by bland lubricants to
soften hard skin and to facilitate
desquamation

Intravenous fluids are almost always
required; neonates initially do not feed well.
 Consider excess cutaneous water losses in
daily fluid requirement calculations.
 Monitor serum electrolyte levels. A risk of
hypernatremic dehydration exists.
 Maintain a sterile environment to avoid
infection
Retinoids -- These agents decrease
the cohesiveness of abnormal
hyperproliferative keratinocytes. They
modulate keratinocyte differentiation.
 Isotretinoin
 0.5 mg/kg/d PO

Complications:

Gram-positive and gram-negative sepsis has
been reported outside the newborn period.
 Children who survive have symptoms that
resemble nonbullous congenital ichthyosiform
erythroderma, with chronic erythroderma and
a fine scale over the whole body.
 Relapses of severe ichthyosis with eclabium
and ectropion occur. Contractures and painful
fissuring of the hands and the feet may occur
without adequate topical or systemic therapy.
PROGNOSIS

Fulminant sepsis remains the most common
cause of death in these infants.
 Life expectancy is unknown. A report of
survival to 9 years of age has been
published.
 Both normal intellect and developmental
delay have been described. In general,
intellectual development is thought to be
normal.
Prenatal diagnosis

Amniotic fluid samples obtained as early as
17 weeks’ gestation have demonstrated
hyperkeratosis and abnormal lipid droplets
within the cornified cells.
o Fetal skin biopsy can detect harlequin
ichthyosis as early as 20 weeks’ gestation;
this information is valuable to parents who
may be considering aborting the pregnancy
because the fetus is affected.
o
Biopsy samples from a number of sites in the
fetus reveal the presence of characteristic
changes on all skin surfaces, except the
mucous membranes.
o Prenatal ultrasonography can be used to
identify characteristic physical features of
harlequin ichthyosis but not until late in the
second trimester when enough keratin
buildup is present to be sonographically
detectable.
o
o
o
Termination is contraindicated late in
gestation; however, prenatal
identification of a neonate who is
affected may allow parents and
physicians to better prepare for the
infant's delivery.