Introduction Demographics Causes Clinical features Complications Diagnosis Differential diagnoses Treatment Outcome
Harlequin ichthyosis is a severe inherited form of ichthyosis that presents at birth as hard, thickened armour-like plates of skin covering the entire body. Harlequin ichthyosis is also called harlequin-type ichthyosis, and harlequin fetus [1].
Note that harlequin syndrome refers to a different condition characterised by asymmetrical, progressive, and segmental sweat loss (also known as progressive isolated segmental anhidrosis), and to unilateral sweating and flushing on the chest, neck, and face.
Harlequin change is another unrelated condition describing rapidly fluctuating unilateral erythema in neonates.
Harlequin ichthyosis is rare, and both sexes are affected in equal numbers. It affects approximately one in 300,000 newborns [2].
There is no racial predilection known for harlequin ichthyosis. Higher incidence may be encountered in cultures where parental consanguinity is common [3].
The inheritance of harlequin ichthyosis is autosomal recessive. It is due to mutations in the ABCA 12 (ATP-binding cassette sub-family A member 12) gene. The ABCA12 gene is believed to encode a transporter protein involved in the transport of epidermal lipids across cell membranes and is essential for normal skin development.
Some mutations in the ABCA12 gene prevent the cell from making any ABCA12 protein. Other mutations lead to the production of an abnormally small version of the protein that cannot transport lipids properly. A loss of functional ABCA12 protein disrupts the normal development of the epidermis, resulting in the hard, thick scales characteristic of harlequin ichthyosis [4].
The diagnosis of harlequin ichthyosis relies on a physical examination of the patient and genetic laboratory investigations.
Genetic testing for a loss of function mutation in the ABCA12 gene is the most specific diagnostic test for harlequin ichthyosis.
Skin biopsy shows a very thickened stratum corneum, parakeratosis, and hypergranulosis on histology.
Gaucher disease is an autosomal recessive inborn error in glucosylceramidase, which may present as a collodion baby with developmental and neurological problems.
Trichothiodystrophy is characterised by photosensitivity, ichthyosis, brittle hair, developmental delay, and/or short stature.
There is no cure for harlequin ichthyosis, and treatment is centred around protecting the skin and preventing infection.
After birth, the thick plate-like outer layer of skin eventually splits and peels, leaving the vulnerable inner layers of the dermis exposed. Most harlequin infants will need one-on-one nursing care for the first several weeks of life. Antibiotic treatment may also be necessary to prevent or treat infection during this time.
Softening emollients, especially those containing urea, salicylic acid or alpha hydroxy acids, are particularly effective when applied after bathing while the skin is still moist. These products work to keep the skin moisturised and pliable while preventing the cracking and fissuring that can lead to secondary bacterial infection.
Early systemic treatment with oral retinoids (eg, acitretin or isotretinoin) has also been shown to heal skin fissures, soften or resolve plate-like scales, and improve overall survival [6].
In the past, harlequin ichthyosis infants rarely survived beyond the first few days of life. With advancements in neonatal care, the survival rate has improved, with worldwide figures approaching 50% [3].
Children who survive the neonatal period usually evolve to a less severe phenotype of ichthyosis but continue to develop fish-like scales, and have retention of waxy, yellowing material in seborrhoeic areas, generalised poor hair growth and scarring alopecia. Harlequin ichthyosis survivors may continue to suffer from temperature dysregulation, have contractures of the digits, arthralgias, failure to thrive, hypothyroidism, and short stature.
