Harlequin Ichthyosis

Harlequin ichthyosis (HI) is the most severe form of autosomal recessive congenital ichthyosis, caused by loss-of-function mutations in ABCA12, with massive hyperkeratosis at birth.

• Incidence is about 1 in 300,000 births.
• ABCA12 encodes a lipid transporter needed for lamellar granule lipid secretion and stratum corneum barrier formation.
• Historically mortality was over 50% in the neonatal period; early retinoid use and neonatal intensive care have increased survival into adulthood.
• Prenatal diagnosis is possible by fetal DNA analysis or skin biopsy.

• Thick, hard, armour like plates of keratin separated by deep fissures over the entire body.
• Severe ectropion and eclabium (everted eyelids and lips), flattened ears, and hypoplastic nose.
• Restricted chest wall and limb movement leading to respiratory compromise; contractures; hands and feet bound by keratin, risk of ischaemia.
• Complications: hypothermia or hyperthermia, dehydration and hypernatraemia, infection and sepsis, feeding difficulties, and corneal exposure.

• Clinical diagnosis at birth with molecular confirmation of biallelic ABCA12 variants.
• Histology (if done): thick compact orthokeratosis with follicular plugging.
• Neonatal workup: blood cultures, electrolytes, renal function, glucose, and temperature monitoring.
• Exclude collodion baby (self-healing or lamellar ichthyosis), other ichthyoses, and congenital infections.
• Genetic counselling and prenatal testing for subsequent pregnancies.

• Neonatal intensive care: humidified incubator at 35 to 37 degrees Celsius and about 70 to 90% humidity, thermoregulation, and strict aseptic handling.
• Emollients: liberal petrolatum or paraffin based ointments every 2 to 4 hours, warm baths with careful peeling of loosened scale (avoid forced removal).
• Hydration and nutrition: increased fluid and calorie needs (up to 150 to 200 kcal/kg/day), early enteral feeding, and monitoring of sodium, creatinine, and weight.
• Ophthalmological care: lubricating ointments, eyelid taping or tarsorrhaphy for severe ectropion.
• Chest and limb care: physiotherapy, and treatment of digital ischaemia by releasing constricting bands.
• Systemic retinoids: acitretin 0.5 to 1 mg/kg/day (started within days to weeks, after stabilisation) markedly improves scale shedding and survival; monitor lipids, liver tests, bone growth, and skeletal changes.
• Antibiotics for suspected sepsis, analgesia, multidisciplinary follow up (dermatology, ophthalmology, ENT, nutrition, orthopaedics), and psychosocial support.