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Harlequin Ichthyosis

  • Author: Julie Prendiville, MBBCh; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jun 03, 2016
 

Background

Harlequin ichthyosis is the most severe form of autosomal recessive congenital ichthyosis.[1] Harlequin ichthyosis is characterized by a profound thickening of the keratin layer in fetal skin. The affected neonate is born with a massive, horny shell of dense, platelike scale and contraction abnormalities of the eyes, ears, mouth, and appendages, as is shown in the images below.

Harlequin ichthyosis. Courtesy of Dr Bernice Krafc Harlequin ichthyosis. Courtesy of Dr Bernice Krafchik.
Harlequin ichthyosis. Courtesy of Jason K Rivers, Harlequin ichthyosis. Courtesy of Jason K Rivers, MD, FRCPC, and Dr Lawler.

The term harlequin derives from the facial appearance and the triangular and diamond-shaped pattern of hyperkeratosis. The newborn's mouth is pulled wide open, mimicking a clown's smile.

Marked eclabium and ectropion are present secondary to the taut, unyielding skin. The ears may be absent or poorly developed. The arms, feet, and digits have flexion contractures and may be hypoplastic. The skin barrier is severely compromised, leading to excessive water loss, electrolyte abnormalities, temperature dysregulation, and an increased risk of life-threatening infection. The tight, armorlike scale can restrict respiration. Poor feeding and impaired intestinal absorption are common.

This disease primarily affects the skin. Other systems may be significantly compromised by the hyperkeratosis and concomitant deformities. Neonates are often born prematurely.

The underlying genetic abnormality in harlequin ichthyosis is a mutation in the lipid-transporter gene ABCA12 on chromosome 2.

Immunohistocytochemical examination of the skin reveals characteristic abnormalities in the structure of lamellar granules and in the expression of epidermal keratin.

In the past, harlequin ichthyosis was uniformly fatal. Improved survival has been achieved with intense supportive care and systemic retinoid therapy in the neonatal period. Patients who survive manifest a debilitating, persistent ichthyosis similar to severe congenital ichthyosiform erythroderma.[1, 2]

Other Medscape articles on ichthyosis include Hereditary and AcquiredIchthyosis Vulgaris, Lamellar Ichthyosis, X-Linked Ichthyosis, and Ichthyosis (ophthalmology focus).

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Epidemiology

Frequency

Approximately 200 cases of harlequin ichthyosis have been reported.[3] The incidence is calculated to be around 1 case in 300,000 births.[3]

Race

No racial predilection is known for harlequin ichthyosis. A higher incidence may be encountered in cultures where parental consanguinity is common.[4]

Sex

Sex distribution appears to be equal.

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Prognosis

The mortality for harlequin ichthyosis rate is high, with worldwide figures approaching 50%. A review of 45 cases by Rajpopat et al found 25 survivors (56%), ranging in age from 10 months to 25 years. Twenty deaths (44%) occurred from day 1 to day 52 and were as likely to be caused by respiratory failure as fulminant sepsis.[4] A Japanese survey of 16 patients reported survival of 81.3% (13 of 16 patients).[5] Respiratory failure, fulminant sepsis, or a combination of both are the most common causes of death in affected newborns.[4]

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Patient Education

Advise parents and caregivers that the baby’s appearance will improve after the neonatal period. Emphasize the need for attention to skin lubrication and for compliance with systemic therapy. Teach them to recognize signs of infection.

Congenital ichthyoses can have devastating medical and social consequences. Parents may wish to communicate with other families who have been similarly affected. Patient organizations (eg, The Foundation for Ichthyosis and Related Skin Types [FIRST]) are available in several countries to provide support to families.

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Contributor Information and Disclosures
Author

Julie Prendiville, MBBCh Clinical Professor in Pediatrics, University of British Columbia Faculty of Medicine; Head, Division of Pediatric Dermatology, British Columbia's Children's Hospital, Canada

Julie Prendiville, MBBCh is a member of the following medical societies: American Academy of Dermatology, Royal College of Physicians and Surgeons of Canada, Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Steven R Feldman, MD, PhD Professor, Departments of Dermatology, Pathology and Public Health Sciences, and Molecular Medicine and Translational Science, Wake Forest Baptist Health; Director, Center for Dermatology Research, Director of Industry Relations, Department of Dermatology, Wake Forest University School of Medicine

Steven R Feldman, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, North Carolina Medical Society, Society for Investigative Dermatology

Disclosure: Received honoraria from Amgen for consulting; Received honoraria from Abbvie for consulting; Received honoraria from Galderma for speaking and teaching; Received consulting fee from Lilly for consulting; Received ownership interest from www.DrScore.com for management position; Received ownership interest from Causa Reseasrch for management position; Received grant/research funds from Janssen for consulting; Received honoraria from Pfizer for speaking and teaching; Received consulting fee from No.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Arash Taheri, MD Research Fellow, Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine

Disclosure: Nothing to disclose.

Wen Lyn Ho, MBBCh, BAO(HON), MRCPI Clinical Fellow in Pediatric Dermatology, British Columbia Children’s Hospital, Canada

Wen Lyn Ho, MBBCh, BAO(HON), MRCPI is a member of the following medical societies: Royal College of Physicians of Ireland, British Association of Dermatologists, Irish Association of Dermatologists

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Sheila Au, MD, to the development and writing of this article.

References
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  2. Lawlor F. Progress of a harlequin fetus to nonbullous ichthyosiform erythroderma. Pediatrics. 1988 Dec. 82(6):870-3. [Medline].

  3. Ahmed H, O'Toole EA. Recent advances in the genetics and management of harlequin ichthyosis. Pediatr Dermatol. 2014 Sep-Oct. 31 (5):539-46. [Medline].

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

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Harlequin ichthyosis. Courtesy of Dr Bernice Krafchik.
Harlequin ichthyosis. Courtesy of Jason K Rivers, MD, FRCPC, and Dr Lawler.
 
 
 
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