Harlequin ichthyosis or Harlequin baby

A rare autosomal recessive disease of infants in which the baby is encased in a massive, horny shell of dense, plate-like scale (hyperkeratotic ‘cocoon’) with deep cracks (fissures), accompanied by contraction abnormalities of the eyes (ectropion), turning outwards of a lip (eclabium), and flattened ears.
Also known as; Harlequin-type ichthyosis, keratosis diffusa fetalis, Harlequin fetus

It is the most severe form of autosomal recessive congenital ichthyosis where the dermis to be around 10 times thicker than normal.

Harlequin Baby ( Picture credit; Parakovacs )

It was first Described in 1750 by Rev. Oliver Hart, a cleric from South Carolina. The term "harlequin" derives from the newborn's facial expression, the triangular and diamond-shaped pattern of hyperkeratosis.

It has an incidence rate of less than 1/1,000,000. It has no racial predilection and affects male and female equally.

Risk Factors

• Family History of Ichthyosis or other Severe Skin disorders
• Consanguineous Couples; Marrying a blood relation
• Having another child with ichthyosis ( 25% risk of recurrence)

Pathophysiology

In Harlequin ichthyosis there is Mutations of ABCA12; The gene which is responsible for fat(lipids) transport from lamellar granules to the apical surface of granular layer keratinocytes (spaces between the cells in the skin’s uppermost layer). Thus this mechanism becomes defective resulting in a severe dyskeratosis, caused by defective lipid metabolism; as the lipids are not transported, the stratum corneum is up to 30-fold thicker than the stratum malpighii & the stratum granulosa is decreased to a one-cell layer or absent.

Signs & Symptoms
History of previous intrauterine or neonatal death,
Decreased fetal movements or intrauterine growth retardation noted during the pregnancy,
Preterm delivery,
Bleeding at birth,
Severely thickened & hyperkeratotic skin which is scale-like and shiny with deep cracks/fissures.
Everted eyelids (Ectropion) with dryness of the cornea
The Nose and Ears may be poorly formed or absent
The Lips are retracted (Eclabium)
Sparse hair distribution, alopecias
Poor movement in the joints & contractures
Failure to thrive
Dehydration as a result of fluid loss from the cracked skin.
Hyperthermia due to thickened skin and absence of sweating
Respiratory distress and respiratory failure following poor chest wall expansion

Diagnosis
This is purely clinical, the risk factors, signs and symptoms should be noted.
Prenatal diagnosis, using amniotic fluid sample at 17weeks of gestation, especially for fetuses with positive family history
Prenatal 2D or 3D ultrasonography shows; a large and gaping mouth, aplasia of the nose, abnormal limbs, and bulging eyes; all features of Harlequin ichthyosis.
Genetic testing for mutations in the ABCA12 gene
Full Blood Count; may show decreased heamoglobin, increase White blood cells
Blood culture for infections
Serum Electrolytes Urea and Creatinine may be abnormal due to dehydration.
Chest X-Ray in respiratory distress.
Skin Biopsy for histological studies.

Differential Diagnosis

Self-healing lamellar ichthyosis of the newborn.
Congenital ichthyosiform erythroderma.
Collodion baby.
Lethal restrictive dermopathy.
Infantile systemic hyalinosis.
Neu-Laxova syndrome.

Treatment
The management of Harlequin Ichthyosis is multidisciplinary as well as supportive. It involves the; Neonatologist, Ophthalmologist, Dermatologist, Dietician, Plastic Surgeon, Psychologists etc.
Intravenous access may be difficult here, thus umbilical cannulation is recommended.
Supportive measures include; 

• Monitoring the patient in a Neonatal Intensive care unit,
• The use of Humidified incubator (to maintain body temperature and to prevent the skin from cracking).
• Rehydration
• Lubricating the Cornea with Ophthalmic lubricants
• Emollients can be applied liberally to the skin
• Antibiotics to help prevent infection & sepsis
• Retinoids; Oral(Isotretinoin or acitretin) and Topical Retinoids (Tazarotene) to accelerate shedding of the skin scales.

Complications
Impaired vision
Delayed developmental milestones
Fulminant Sepsis
Failure to thrive
Respiratory failure
Renal failure

Prognosis
The mortality rate for harlequin ichthyosis is high, close to 50%. However, following the discovery of Isotretinoids the prognosis is improving.
Presently, the Oldest surviving person with Harlequin ichthyosis is Nusrit "Nelly" Shaheen, 30years old, from West Midlands in Britain. She was born in 1984,

Harlequin Ichthyosis (Picture Credit; ObGyn)

NOTES

1) Akiyama M. ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts. Hum Mutat. Oct 2010;31(10):1090-6.

2) Chua CN, Ainsworth J. Ocular management of harlequin syndrome. Arch Ophthalmol. Mar 2001;119(3):454-5

3) First foundation for Ichthyosis and related skin types | Harlequin Ichthyosis

4) Ichthyosis Support Group | harlequin-ichthyosis

5) Kelsell DP, Norgett EE, Unsworth H, et al. Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Am J Hum Genet. May 2005;76(5):794-803

6) Koochek A, Choate KA, Milstone LM. Harlequin Ichthyosis: Neonatal Management and Identification of a New ABCA12 Mutation. Pediatr Dermatol. Mar 2014;31(2):e63-4.

7) Lefevre C, Audebert S, Jobard F, et al. Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2. Hum Mol Genet. Sep 15 2003;12(18):2369-78.

8) Medscape; Harlequin Ichthyosis

9) Liu RH, Becker B, Gunkel J, Teng J. Rapid improvement in digital ischemia and acral contracture in a collodion baby treated with topical tazarotene. J Drugs Dermatol. Jun 2010;9(6):713-6.

10) Orphanet; ORPHA457, Harlequin ichthyosis

11) Rajpopat S, Moss C, Mellerio J, et al. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Arch Dermatol. Jun 2011;147(6):681-6.

12) Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0

13) Wikipedia; Harlequin Ichthyosis