Very Severe — Requires specialist NICU care at birth and lifelong multidisciplinary team

Harlequin Ichthyosis

The most severe form of ichthyosis. Modern specialist care has transformed outcomes — many people with harlequin ichthyosis now live into adulthood and beyond.

ABCA12
Gene
1 in 500,000
Prevalence
Birth
Onset
Improving
Prognosis (with care)
Inheritance

Autosomal Recessive. Both parents carry a copy of the ABCA12 gene mutation. Each pregnancy has a 25% chance of being affected.

At birth

Born with extremely thick, cracked skin (fissures). Ectropion, eclabium (lips pulled back), restricted joints common. Immediate NICU admission required.

Ongoing challenges

Temperature regulation severely impaired. Infection risk high. Joint contractures. Feeding difficulties in infancy. Eye and ear involvement.

Modern prognosis

With acitretin started early, NICU expertise, and lifelong MDT care, survival and quality of life have dramatically improved since 2000.

Part of the ARCI family — the most severe subtype

Harlequin Ichthyosis (HI) is the most severe form of Autosomal Recessive Congenital Ichthyosis (ARCI). All ARCI subtypes share recessive inheritance and onset at birth, but differ in severity, gene cause, and appearance. Knowing the subtype guides treatment and prognosis.

Harlequin Ichthyosis (HI)
Most severe. ABCA12 gene. Armour-like plates at birth, NICU essential. With acitretin, survival rates have greatly improved.
Severe but survivable from birth without immediate NICU. Large plate-like scales, anhidrosis. Genes: TGM1, CYP4F22, others.
Congenital Ichthyosiform Erythroderma (CIE)
Fine white scales with whole-body redness (erythroderma). Less severe than HI. Overlaps genetically with LI.

Genetic testing confirms the specific ABCA12 variant and informs prognosis and family planning. See new EDD classification (2024–2025) for how the terminology is evolving.

Medical disclaimer: This page is for information only. Harlequin ichthyosis requires specialist medical care. All treatment decisions must be made with a multidisciplinary team including dermatology, ophthalmology, paediatrics, and other specialists.
If you have a newborn with suspected Harlequin Ichthyosis: This is a medical emergency. The baby should be in a specialist NICU with dermatology expertise. Do not try to remove the skin membrane. Maintain humidity, prevent infection, and start acitretin as soon as clinically appropriate under dermatologist guidance.

NICU Management Protocol (Birth–Discharge)

Immediate priorities at birth

  • Humidified incubator (85–90% humidity initially)
  • IV access — feeding support as oral feeding is difficult
  • Temperature management — overheating/hypothermia risk
  • Eye care: lubricant drops every 2 hours; temporary tarsorrhaphy if needed
  • Vaseline/white soft paraffin applied all over body 4–6x daily
  • Infection monitoring — skin barrier is severely compromised
  • Pain management — fissures are painful

First-week priorities

  • Start acitretin as soon as medically stable (0.5–1mg/kg/day)
  • Multidisciplinary team referrals: dermatology, ophthalmology, OT, physio
  • Gradual weaning of humidity as skin transforms
  • Begin gentle bathing with emollient once initial membrane softens
  • Physiotherapy for joint contractures
  • Speech therapy referral for feeding difficulties
  • Genetic counselling for parents

Ongoing Daily Routine (Child and Adult)

Daily routine for harlequin ichthyosis is intensive and non-negotiable. Plan 60–90 minutes each session.

  • 30–45 minute bath with bath oil (Oilatum Plus or similar)
  • Systematic, gentle scale removal with soft sponge — methodical, full body
  • Apply keratolytic: urea 40% or salicylic acid 6% to thickest areas
  • Apply thick emollient (50:50 paraffin mix, Epaderm ointment) to entire body
  • Eye lubricant drops, follow ophthalmologist protocol
  • Ear drops if required
  • Acitretin with food (fat helps absorption)
  • Temperature plan for the day: cooling vest, spray, air conditioning
  • Dress: loose, light, cotton-based clothing
  • Full bath 30–45 minutes with bath oil
  • Thorough scale removal — this is the primary therapeutic session
  • High-concentration emollient application to full body
  • Joint flexibility exercises with physiotherapist guidance
  • Eye ointment for overnight protection
  • Sleep in cool, humidified room if possible
  • Cotton or bamboo bedding — change frequently

Ectropion is nearly universal in harlequin ichthyosis. Corneal protection is essential to preserve vision:

  • Lubricant eye drops every 1–2 hours during waking hours
  • Overnight eye ointment (Lacrilube) and possible eye covering/tape
  • Annual or 6-monthly ophthalmology review
  • Surgical ectropion repair discussed with ophthalmologist — may be required
  • Avoid air conditioning directly on face — extremely drying for eyes
  • Sunglasses outdoors — UV protection and reducing glare
Temperature dysregulation in harlequin ichthyosis can be life-threatening. Overheating can occur rapidly, even in moderate temperatures.
  • Cooling vest: Prescribed by dermatologist. Worn during any physical activity or warm weather
  • Spray bottle: Carried at all times. Fine mist + air movement = evaporative cooling
  • Air conditioning: Bedroom and car. Apply on DLA/PIP and potentially for Disabled Facilities Grant
  • Activity timing: Exercise only in cool conditions, early morning or evening
  • School/work plan: Written heat management plan shared with school or employer — required by law
  • Emergency plan: Written protocol for heat crisis. School staff trained in recognition and response

Medications

DrugRoleEfficacyKey MonitoringNotes
Acitretin (Neotigason)First-line systemic — reduces scale production85–90%Liver, lipids, boneStart from birth/infancy. Life-changing.
50:50 Paraffin/White Soft ParaffinPrimary emollient75%Fire risk warningHuge quantities needed daily
Salicylic acid 6% in paraffinKeratolytic80%Salicylate levels in childrenAvoid in infants under 2
IsotretinoinAlternative retinoid70%Mental health, lipidsIf acitretin not tolerated
Prophylactic antibioticsInfection prevention in high-risk periodsVariableResistance monitoringShort-term only

Multidisciplinary Team — Who You Need

Dermatologist

Lead clinician. Manages acitretin, topical treatments, and overall skin management. Should have ichthyosis expertise.

Ophthalmologist

Ectropion management, corneal protection, surgical options. Annual review minimum.

Physiotherapist

Joint contracture management. Range of motion exercises. Functional independence.

Occupational Therapist

Adaptations for home and school. Equipment for daily routine. Grip aids, bathing equipment.

Dietitian

High protein and calorie needs due to skin turnover. Feeding support especially in infancy.

Psychologist / Counsellor

Appearance anxiety, social challenges, patient and family wellbeing. Essential component of care.

Community — You Are Not Alone

Real people with harlequin ichthyosis are living full lives. With modern care, acitretin, and a strong multidisciplinary team, survival rates and quality of life have transformed dramatically since the 1990s. Connect with others who understand.

Ichthyosis Support Group UK

Specific support for families with severe ichthyosis including harlequin. Annual family conference.

ichthyosis.org.uk →

FIRST Foundation (USA)

Global network. Camps, conferences, medical advisory board with harlequin expertise.

firstskinfoundation.org →

Red Flags

Call 999 / emergency services immediately for:
  • Heat stroke signs: confusion, very hot skin, no sweating, loss of consciousness
  • Widespread skin infection with high fever
  • Corneal injury or sudden vision loss
  • Severe breathing difficulty if skin restricts chest wall movement
  • Sepsis signs: cold clammy skin, rapid breathing, high or very low temperature, confusion

Your next step

Find a UK specialist centre with expertise in Harlequin Ichthyosis — including Great Ormond Street Hospital and St John's Institute of Dermatology.

→ Find Your Specialist