Port- Fouad

Case Repor tBy

Dr . Osama Arafa Abd El Hameed

M.S.c. PHD. PEDIATRICIAN AND NEONATOLOGIST

Head of Pediatric Department

Port–fouad Hospital

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.

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.

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.

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.

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.

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.

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 .

Race: No racial predilection is known.

Sex: No increased risk based on sex is known.

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.

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: 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?

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?

CLINICAL FEATURES

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..

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.

Temperature dysregulationThickened 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.

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.

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..

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

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

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.

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.

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.

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.

TREATMENT

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 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

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.