Harlequin Ichthyosis 

  • Author: Julie Prendiville, MBBCh; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jul 28, 2011
 

Background

Harlequin ichthyosis is the most severe form of congenital ichthyosis. 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. This armor limits movement and compromises the protective skin barrier, leaving the newborn susceptible to metabolic abnormalities and infection.

Ichthyosis fetalis. Courtesy of Dr Bernice KrafchiIchthyosis fetalis. Courtesy of Dr Bernice Krafchik. Ichthyosis fetalis. Courtesy of Jason K Rivers, MDIchthyosis fetalis. Courtesy of Jason K Rivers, MD, FRCPC, and Dr Lawler.

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

The underlying genetic abnormality in harlequin ichthyosis has been identified as a mutation in the lipid-transporter gene ABCA12 on chromosome 2. The presence of homozygous mutations in affected individuals supports an autosomal recessive pattern of inheritance.

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 other autosomal recessive ichthyoses, such as lamellar ichthyosis or nonbullous congenital ichthyosiform erythroderma.[1, 2]

Other eMedicine articles on ichthyosis include

Ichthyosis Vulgaris, Hereditary and Acquired; Ichthyosis, Lamellar; Ichthyosis, X-Linked; and Ichthyosis (ophthalmology focus)

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Pathophysiology

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

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.

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Epidemiology

Frequency

International

More than 100 cases of harlequin ichthyosis have been reported.

Mortality/Morbidity

The mortality for harlequin ichthyosis rate is high. With neonatal intensive care and the advent of retinoid therapy, some babies have survived the newborn period. They are still at risk of dying from systemic infection, which is the most common cause of death. 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.[31]

Race

No racial predilection is known for harlequin ichthyosis.

Sex

No increased risk of harlequin ichthyosis based on sex is known.

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Contributor Information and Disclosures
Author

Julie Prendiville, MBBCh  Clinical Professor in Pediatrics, University of British Columbia; 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, and Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Abby S Van Voorhees, MD  Assistant Professor, Director of Psoriasis Services and Phototherapy Units, Department of Dermatology, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania

Abby S Van Voorhees, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, National Psoriasis Foundation, Phi Beta Kappa, Sigma Xi, and Women's Dermatologic Society

Disclosure: Amgen Honoraria Consulting; Abbott Honoraria Consulting; Merck Salary Management position; Abbott Honoraria Speaking and teaching; Amgen Honoraria Review panel membership; Centocor Honoraria Consulting; Leo Consulting; Merck None Other

Richard P Vinson, MD  Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Association of Military Dermatologists, Texas Dermatological Society, and Texas Medical Association

Disclosure: Nothing to disclose.

Van Perry, MD  Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery

Disclosure: Nothing to disclose.

Joel M Gelfand, MD, MSCE  Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania

Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology

Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds Investigator; Genentech Grant/research funds investigator; Centocor Consulting fee Consulting; Abbott Grant/research funds investigator; Abbott Consulting fee Consulting; Novartis investigator; Pfizer Grant/research funds investigator; Celgene Consulting fee DMC Chair; NIAMS and NHLBI Grant/research funds investigator

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

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

Disclosure: Nothing to disclose.

Acknowledgments

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

References

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  3. 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. [Medline]. [Full Text].

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  28. Hovnanian A. Harlequin ichthyosis unmasked: a defect of lipid transport. J Clin Invest. Jul 2005;115(7):1708-10. [Medline]. [Full Text].

  29. Prasad RS, Pejaver RK, Hassa A, al Dusari S, Wooldridge MA. Management and follow-up of harlequin siblings. Br J Dermatol. 1994;130 (5):650-653.

  30. Roberts LJ. Long-term survival of a harlequin fetus. J Am Acad Dermatol. Aug 1989;21(2 Pt 2):335-9. [Medline].

  31. 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. [Medline].

 
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Ichthyosis fetalis. Courtesy of Dr Bernice Krafchik.
Ichthyosis fetalis. Courtesy of Jason K Rivers, MD, FRCPC, and Dr Lawler.
 
 
 
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