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Harlequin Ichthyosis

What Is It, Causes, Signs, Symptoms, and More

Author:Lily Guo

Editors:Alyssa Haag,Ian Mannarino, MD, MBA,Kelsey LaFayette, DNP, ARNP, FNP-C

Illustrator:Jessica Reynolds, MS

Copyeditor:Stacy L. Johnson, LMSW


What is harlequin ichthyosis?

Harlequin ichthyosis, also known as a harlequin fetus, ichthyosis fetalis, or harlequin baby syndrome, is a type of ichthyosis that typically covers newborns' entire face and body. Ichthyosis is a general term for a family of rare, genetic skin diseases characterized by dry, scaling, and thick skin. The thick layer of skin, or plates, seen in harlequin ichthyosis (particularly when on the face) can crack and split, leading to impaired breathing and eating. 

Harlequin ichthyosis is the most serious, potentially life-threatening form of congenital ichthyosis inherited in an autosomal recessive pattern. A newborn with harlequin ichthyosis typically requires care and treatment in a neonatal intensive care unit by a multidisciplinary team consisting of a dermatologist, clinical geneticist, nutritionist, physical therapist, occupational therapist, and social worker. 

Infant with dry, scaly, thick skin.

What causes harlequin ichthyosis?

Harlequin ichthyosis is a genetic disorder caused by mutations in the ABCA12 gene, which encodes an adenosine triphosphate-binding cassette (ABC) transporter. Lack of this protein transporter leads to defects in lipid transport to the epidermis and atypical skin barrier formation, thereby causing the characteristically thickened skin. 

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What are the signs and symptoms of harlequin ichthyosis?

Harlequin ichthyosis commonly occurs in newborns and results in plate-like scales covering the entire body. The plates can appear transparent, shiny, and taut; eventually, they may dry out to form diamond-shaped plaques separated by deep red fissures. The plates can stretch out the skin on the face, resulting in the inversion of the eyelids and lips. Typically, affected newborns have an associated flat nose and a missing nasal bridge. The entire outer ear may also be fused to the head by the thick skin, making the ears appear misshapen or missing. Diminished hearing may result. 

Infants with harlequin ichthyosis can have restrictions on the chest and abdomen due to the tightness of the skin. The hands and feet can be swollen and remain flexed at the joints, resulting in limited mobility. This is a leading cause of infant mortality for those with harlequin ichthyosis. Mortality typically occurs within two days of birth due to feeding and breathing complications and an increased risk of respiratory infections and respiratory distress. Harlequin ichthyosis further predisposes infants to bacterial skin infections (e.g., Staphylococcus aureus), low body temperature, dehydration, and hypernatremia (i.e., elevated sodium levels in the blood) due to a disrupted skin barrier, causing insensible loss of fluid. 

Harlequin ichthyosis affects all sexes equally and can occur in several ethnic groups. Currently, the condition affects approximately one in 500,000 births annually in the United States.

How is harlequin ichthyosis diagnosed?

Harlequin ichthyosis is diagnosed at birth on clinical presentation alone. Babies with harlequin ichthyosis are born prematurely. There are ways to diagnose harlequin ichthyosis before birth, including prenatal testing for genetic defects in the ABCA12 gene. In some cases, the associated features may be found on ultrasound during the second or third trimester. 

How is harlequin ichthyosis treated?

Harlequin ichthyosis is treated using a multidisciplinary approach focused on symptom management and prevention of infection. If the plates of skin are causing constriction and swelling of the mouth, thereby preventing the infant from sucking, the infant may require a feeding tube. If the eyelids are forced open by the tightness of the skin, lubrication of the corneas can help prevent damage if constrictive skin bands are found around the fingers.

Early treatment with oral retinoids (e.g., acitretin) can improve outcomes by expediting the shedding of the thick scales as well as reducing discomfort and disfigurement. If treatment is discontinued, ichthyotic skin may recur; therefore, long-term use is required. Retinoids are typically reserved for severe cases due to their side effects of cheilitis (i.e., lip inflammation), dry nose, eye irritation, elevation of fasting lipids levels, and skeletal system defects. Exfoliation of the skin plaques can also help expedite the shedding process. Long baths with at least 30 minutes of soaking, once or twice a day, can soften scales before exfoliation.

The thick, plate-like skin will usually gradually split and peel off on its own for several weeks. During this time, the skin’s barrier is compromised; therefore, antibiotics (e.g., erythromycin) may be administered to prevent infection. The infant is usually kept warm at this time in a humidified incubator to mitigate water loss and potential issues with thermoregulation. Additional supportive measures with fluid and electrolyte replacement may also be necessary. After the skin plates peel off, the underlying skin can become dry and red. Soft skin emollients, such as ointments and creams, are commonly used to hydrate the skin. Moisturizers containing ceramides, cholesterol, petrolatum, lanolin, alpha-hydroxy acids, and urea help maintain soft skin and prevent further cracking or fissuring. 

What are the most important facts to know about harlequin ichthyosis?

Harlequin ichthyosis is an autosomal recessive genetic condition caused by mutations in ABCA12 that causes thick, scaly plaques of skin that cover the infant’s entire face and body. These plaques can crack and create red fissures across the skin, predisposing to skin infections, contributing to difficulty breathing and feeding, and increasing infant mortality. Harlequin ichthyosis is typically diagnosed on clinical presentation at birth or through genetic testing. Management of harlequin ichthyosis requires a multidisciplinary team to address the various symptoms. Once the plaques are shed, moisturization is crucial to keep the skin soft and prevent further cracking and fissuring. The infant may be kept in a humidified incubator to regulate temperature and to avoid water loss. The infant may need a feeding tube if unable to suck with their mouth, and acitretin medication may be used to expedite skin shedding. 

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Related links

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Resources for research and reference

Digiovanna JJ, Mauro T, Milstone LM, Schmuth M, Toro JR. Systemic retinoids in the management of ichthyoses and related skin types. Dermatol Ther. 2013;26(1):26-38. doi:10.1111/j.1529-8019.2012.01527.x

Harlequin ichthyosis. NORD (National Organization for Rare Disorders). (2019, July 16). Retrieved from https://rarediseases.org/rare-diseases/ichthyosis-harlequin-type/ 

Kelsell, D. P., Norgett, E. E., Unsworth, H., Teh, M. T., Cullup, T., Mein, C. A., Dopping-Hepenstal, P. J., Dale, B. A., Tadini, G., Fleckman, P., Stephens, K. G., Sybert, V. P., Mallory, S. B., North, B. V., Witt, D. R., Sprecher, E., Taylor, A. E., Ilchyshyn, A., Kennedy, C. T., Goodyear, H., … O'Toole, E. A. (2005). Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. American journal of human genetics, 76(5), 794–803. https://doi.org/10.1086/429844

Skin Care Tips.  (2022). The Foundation for Ichthyosis and Related Skin Types. Retrieved from https://www.firstskinfoundation.org/skin-care-tips   

Thomas AC, Cullup T, Norgett EE, et al. (2006).  ABCA12 is the major harlequin ichthyosis gene. J Invest Dermatol.;126(11):2408-2413. doi:10.1038/sj.jid.5700455