Case Repor t ByDr . 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 wasreferred to PORT_FOUAD General Hospital . She was born after 38-40 weeks ofgestation to a gravida I para 0, following anormal pregnancy Parents were relatives , mother was 25years old and the father was 30 years old.
Physical examination revealed to•An infant weighing 3000 g.•The patient’s temperature was 36 C, pulserate 120/min, and respiratory rate 49/min.• The clinical appearance of the baby wasstriking. The skin was hard, thickened, waxyand yellowish in colour. It was split irregularlyto reveal erythematous moist fissures.•The ears were underdeveloped andrudimentary.
There was severe ectropion and eclabium.The baby’s cry was normal, but he was unable tosuck effectively. The nose was deformed and flattened. Thenostrils were only being visible after skinremoval. A female genetalia were present, and thelimbs were in a semi flexed position and hadlimited mobility with marked edema . She had 60 degree flexion contractures atelbows and knees and no limitation in movementat the wrist. Restricted abduction in the hip joint.
The hands and feet were edematous withclaw-like fingers and toes were clenched in aflexed position. The fingers and toes were hypoplastic and ischemic. The nails were absent.
Laboratory findings included hemoglobin 14g/dl, white blood cell count 9700/mm3, plateletcount 182000/mm3, creatinine 0.6 mg/dl, Na 130mEq/L, K 3mEq/L, AST 10 U/L, ALT 11 U/L. Immediately after transfer to our neonatalintensive care unit, the baby was nursed in ahumidified incubator maintained at 34 C. Asperipheral venous access was difficult, anumbilical venous line was set up. An extra 25%allowance was provided for fluid and calorierequirements from the first day.
Antibiotics were commenced in order toprevent infection. Vaseline containing fivepercent lactic acid and local antiseptics wereapplied topically. Ectropion was covered with eyepads soaked in saline. Initially progress was slow. The plate likescales split and peeled off revealing glazed anderythematous skin underneath. There werenecrotic areas on the tips of the fingers. She didnot tolerate oral or N/G feeding.. She wasinvestigated for possible sites of sepsis. In day 11she was died.
HARLEQUIN ICHTHYOSIS SYNONYMS: Ichthyosis congenita,keratosis diffusa fetalis, harlequin fetus . It was described by OLIVER HART inhis diary 1750 ,published in 1896. It was invariably associated withstillbirth or early neonatal death until Lawlorreported a case that survived in 1985.
The term harlequin derives from thenewborns facial expression and thetriangular and diamond-shaped pattern ofhyperkeratosis .Race: No racial predilection is known.Sex: No increased risk based on sex isknown.
Frequency: Harlequin fetus is a rare disorder with anincidence of 1 in 300.000 births . Internationally: More than 100 cases havebeen reported. Mortality/Morbidity: The mortality rate is high.With neonatal intensive care and the advent ofretinoid therapy, some babies have survived thenewborn period. They are still at risk of systemicinfection, which is the most common cause of death.
Genetics: This disorder occurs in consanguineousrelationships; multiple siblings within a family can beaffected. This has led to the supposition of autosomalrecessive inheritance. A new mutation inherited as an autosomaldominant trait has also been suggested
History: This condition presents at birth. It may or maynot have been diagnosed prenatally in a high-riskfamily. The history should carefully explore thefollowing questions:1.Is the couple consanguineous?2.Does the couple have another child withichthyosis?3.Is there a family history of severe skin disorders?4.Is there a history of intrauterine or neonataldeaths 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 FEATURESSkin: Severely thickened skin with large, shinyplates of hyperkeratotic scale is present at birth.Deep erythematous fissures separate the scales.Eyes: Severe ectropion is present. The free edgesof the upper and lower eyelids are everted, leavingthe conjunctivae at risk of trauma.Ears: Pinnae may be small and rudimentary orabsent..
Lips: Severe traction on the lips causes eclabium and afixed, 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 thedigits. Limb motility is poor to absent. Circumferentialconstriction of a limb can occur, leading to distal swelling oreven gangrene. Hypoplasia of the fingers, the toes, and the fingernailshas been reported. Polydactyly has been described.
Temperature dysregulation Thickened skin prevents normal sweat glandfunction and heat loss. The infants are heat intolerant and canbecome hyperthermic.Respiratory status: Restriction of chest-wall expansion can resultin respiratory distress, hypoventilation, andrespiratory failure.Hydration status: Dehydration from excess water loss can causetachycardia and poor urine output.
Histologic, ultrastructural, and biochemicalstudies have identified several characteristicabnormalities in the skin of patients. The 2 mainabnormalities involve lamellar granules and thestructural proteins of the cell cytoskeleton. The interrelationship between these 2abnormalities and the mechanism by which theyalter desquamation of the skin is poorly understood
Abnormal lamellar granule structure and function Lamellar granules are intracellular granules thatoriginate from the Golgi apparatus of keratinocytes inthe stratum corneum. These granules are responsible for secretinglipids that maintain the skin barrier at the interfacebetween the granular cell layer and the cornified layer. The extruded lipids are arranged into lamellae inthe intercellular space with the help of concomitantlyreleased hydrolytic enzymes. The lamellae form theskin’s hydrophobic sphingolipid seal..
All patients with harlequin ichthyosis haveabsent or defective lamellar granules and nointercellular lipid lamellae. The lipid abnormality is believed to allowexcessive transepidermal water loss; lack of releasedhydrolases prevents desquamation, resulting in asevere retention hyperkeratosis
Some patients with harlequin ichthyosis haveshown persistence of profilaggrin and absence offilaggrin in the stratum corneum. A defect in protein phosphatase activity andsubsequent lack of conversion of profilaggrin tofilaggrin has been implicated in the disorderspathogenesis. Abnormal expression of keratin Abnormal keratohyalin granules
Abnormal conversion of profilaggrinto filaggrin Profilaggrin is a phosphorylated polyproteinresiding in keratohyalin granules in granular cell layerkeratinocytes. During the evolution to the corneal layer,profilaggrin converts to filaggrin viadephosphorylation. Filaggrin allows dense packing of keratinfilaments. Its subsequent breakdown into amino acidsoccurs prior to desquamation of the stratum corneum.
Prenatal diagnosis Amniotic fluid samples obtained as early as 17weeks’ gestation have demonstrated hyperkeratosisand abnormal lipid droplets within the cornified cells. Fetal skin biopsy can detect harlequinichthyosis as early as 20 weeks’ gestation; thisinformation is valuable to parents who may beconsidering aborting the pregnancy because thefetus is affected.
Biopsy samples from a number of sites in thefetus reveal the presence of characteristic changeson all skin surfaces, except the mucous membranes. Prenatal ultrasonography can be used toidentify characteristic physical features of harlequinichthyosis but not until late in the second trimesterwhen enough keratin buildup is present to besonographically detectable.
Termination is contraindicated late ingestation; however, prenatal identification of aneonate who is affected may allow parents andphysicians to better prepare for the infantsdelivery.
TREATMENT Ensure airway, breathing, and circulation arestable after delivery. Babies require intravenous access. Peripheralaccess may be difficult. Umbilical cannulation maybe necessary. Place infants in a humidified incubator. Monitortemperature, respiratory rate, heart rate, and oxygensaturation. Avoid hyperthermia.
Once stabilized, transfer newborns withharlequin ichthyosis to neonatal intensive carenursery. Apply ophthalmic lubricants to protect theconjunctivae. Bathe infants twice daily. Use frequentapplications of wet sodium chloride compressesfollowed by bland lubricants to soften hard skin andto facilitate desquamation
Intravenous fluids are almost always required;neonates initially do not feed well. Consider excess cutaneous water losses indaily fluid requirement calculations. Monitor serum electrolyte levels. A risk ofhypernatremic dehydration exists. Maintain a sterile environment to avoidinfection
Retinoids:- These agents decrease thecohesiveness of abnormal hyperproliferativekeratinocytes. They modulate keratinocytedifferentiation.Isotretinoin 0.5 mg/kg/d PO
:Complications Gram-positive and gram-negative sepsis hasbeen reported outside the newborn period. Children who survive have symptoms thatresemble nonbullous congenital ichthyosiformerythroderma, with chronic erythroderma and a finescale over the whole body. Relapses of severe ichthyosis with eclabiumand ectropion occur. Contractures and painfulfissuring of the hands and the feet may occur withoutadequate topical or systemic therapy.
PROGNOSIS Fulminant sepsis remains the most commoncause of death in these infants. Life expectancy is unknown. A report ofsurvival to 9 years of age has been published. Both normal intellect and developmental delayhave been described. In general, intellectualdevelopment is thought to be normal.