1. Port- Fouad

2. Case Repor t
By
Dr . Osama Arafa Abd El Hameed
M.S.c. PHD. PEDIATRICIAN AND NEONATOLOGIST
Head of Pediatric Department
Port–fouad Hospital

3. Case Report
A full term female in the first day of life was
referred to PORT_FOUAD General Hospital .
She was born after 38-40 weeks of
gestation to a gravida I para 0, following a
normal pregnancy
Parents were relatives , mother was 25
years old and the father was 30 years old.

4. Physical examination revealed to
•An infant weighing 3000 g.
•The patient’s temperature was 36 C, pulse
rate 120/min, and respiratory rate 49/min.
• The clinical appearance of the baby was
striking. The skin was hard, thickened, waxy
and yellowish in colour. It was split irregularly
to reveal erythematous moist fissures.
•The ears were underdeveloped and
rudimentary.

5. There was severe ectropion and eclabium.
The baby’s cry was normal, but he was unable to
suck effectively.
The nose was deformed and flattened. The
nostrils were only being visible after skin
removal.
A female genetalia were present, and the
limbs were in a semi flexed position and had
limited mobility with marked edema .
She had 60 degree flexion contractures at
elbows and knees and no limitation in movement
at the wrist. Restricted abduction in the hip joint.

6. The hands and feet were edematous with
claw-like fingers and toes were clenched in a
flexed position. The fingers and toes were hypo
plastic and ischemic. The nails were absent.

11. Laboratory findings included hemoglobin 14
g/dl, white blood cell count 9700/mm3, platelet
count 182000/mm3, creatinine 0.6 mg/dl, Na 130
mEq/L, K 3mEq/L, AST 10 U/L, ALT 11 U/L.
Immediately after transfer to our neonatal
intensive care unit, the baby was nursed in a
humidified incubator maintained at 34 C. As
peripheral venous access was difficult, an
umbilical venous line was set up. An extra 25%
allowance was provided for fluid and calorie
requirements from the first day.

12. Antibiotics were commenced in order to
prevent infection. Vaseline containing five
percent lactic acid and local antiseptics were
applied topically. Ectropion was covered with eye
pads soaked in saline.
Initially progress was slow. The plate like
scales split and peeled off revealing glazed and
erythematous skin underneath. There were
necrotic areas on the tips of the fingers. She did
not tolerate oral or N/G feeding.. She was
investigated for possible sites of sepsis. In day 11
she was died.

14. 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.

15. The term harlequin derives from the
newborn's facial expression and the
triangular and diamond-shaped pattern of
hyperkeratosis .
Race: No racial predilection is known.
Sex: No increased risk based on sex is
known.

16. Frequency:
Harlequin fetus is a rare disorder with an
incidence of 1 in 300.000 births .
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 systemic
infection, which is the most common cause of death.

17. 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

18. 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:
1.Is the couple consanguineous?
2.Does the couple have another child with
ichthyosis?
3.Is there a family history of severe skin disorders?
4.Is there a history of intrauterine or neonatal
deaths in the couple of their families?
5.What was the expected date of delivery?

19. 6) Were decreased fetal movements or intrauterine
growth retardation noted during the pregnancy?
7) Did the mother have a prenatal ultrasound?
8) Were any prenatal procedures (eg,
amniocentesis, fetal skin biopsy) performed?

20. CLINICAL FEATURES

21. 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 of trauma.
Ears: Pinnae may be small and rudimentary or
absent..

22. Lips: Severe traction on the lips causes eclabium and a
fixed, open mouth.
Nose: Nasal hypoplasia and eroded nasal alae may occur.
Extremities:
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.

23. Temperature dysregulation
Thickened skin prevents normal sweat gland
function and heat loss.
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.

25. 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

26. Abnormal lamellar granule
structure and function
Lamellar granules are intracellular granules that
originate from the Golgi apparatus of keratinocytes in
the stratum corneum.
These granules are responsible for secreting
lipids that maintain the skin barrier at the interface
between the granular cell layer and the cornified layer.
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..

27. 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

28. Some patients with harlequin ichthyosis have
shown persistence of profilaggrin and absence of
filaggrin in the stratum corneum.
A defect in protein phosphatase activity and
subsequent lack of conversion of profilaggrin to
filaggrin has been implicated in the disorder's
pathogenesis.
Abnormal expression of keratin
Abnormal keratohyalin granules

29. Abnormal conversion of profilaggrin
to filaggrin
Profilaggrin is a phosphorylated polyprotein
residing in keratohyalin granules in granular cell layer
keratinocytes.
During the evolution to the corneal layer,
profilaggrin converts to filaggrin via
dephosphorylation.
Filaggrin allows dense packing of keratin
filaments. Its subsequent breakdown into amino acids
occurs prior to desquamation of the stratum corneum.

30. Prenatal diagnosis
Amniotic fluid samples obtained as early as 17
weeks’ gestation have demonstrated hyperkeratosis
and abnormal lipid droplets within the cornified cells.
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.

31. Biopsy samples from a number of sites in the
fetus reveal the presence of characteristic changes
on all skin surfaces, except the mucous membranes.
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.

32. 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.

33. TREATMENT

34. 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.

35. Once stabilized, transfer newborns with
harlequin ichthyosis to neonatal intensive care
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

36. 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

37. Retinoids:- These agents decrease the
cohesiveness of abnormal hyperproliferative
keratinocytes. They modulate keratinocyte
differentiation.
Isotretinoin 0.5 mg/kg/d PO

38. :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.

39. 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.