Harlequin-type ichthyosis

Not to be confused with Harlequin syndrome.
Harlequin-type ichthyosis

Harlequin fetus (1886)
Classification and external resources
Specialty Dermatology
ICD-10 Q80.4
ICD-9-CM 757.1
OMIM 242500
DiseasesDB 30052
eMedicine derm/192
MeSH D017490
Orphanet 457

Harlequin-type ichthyosis (also known as harlequin baby,[1] harlequin ichthyosis,[1] hyosis fetalis, keratosis diffusa fetalis, harlequin fetus,[2]:562 and ichthyosis congenita gravior[1]), is a severe genetic skin disease, which causes thickening of the stratum corneum of the epidermis.[3] At birth, the child’s whole body is encased in an 'armour' of thick white plates of skin, separated with deep cracks. In addition, the eyes, ears, penis, and the appendages may be abnormally contracted. Because of resultant cracked skin in locations where normal skin would fold, it is easily pregnable by bacteria and other contaminants, which can result in serious risk of fatal infection. Constant care is required to moisturise and protect the skin.[4]

The harlequin-type designation comes from the diamond shape of the scales at birth (resembling the costume of Arlecchino), caused by severe hyperkeratosis. The disease can be diagnosed in the uterus by way of fetal skin biopsy or by morphologic analysis of amniotic fluid cells obtained by amniocentesis. Doctors can now usually recognize common features of the disease through ultrasound, and follow up with 3D ultrasound to diagnose the condition.

It is associated with a mutation in the gene for the protein ABCA12.[5]

Signs and symptoms

Sufferers feature severe cranial and facial deformities. The ears may be very poorly developed or absent entirely, as may the nose. The eyelids may be everted (ectropion), which leaves the eyes and the area around them very susceptible to infection. Babies with this condition often bleed during birth. The lips are pulled back by the dry skin (eclabium). Joints are sometimes lacking in movement, and may be below the normal size. Hypoplasia is sometimes found in the fingers. Polydactyly has also been found on occasion.

Patients with this condition are extremely sensitive to changes in temperature due to their hard cracked skin, which prevents normal heat loss. Respiration is also restricted by the skin, which impedes the chest wall from expanding and drawing in enough air. This can lead to hypoventilation and respiratory failure. Harlequins are often dehydrated, as their plated skin is not well suited to retaining water.

Diagnosis

The diagnosis of Harlequin-type Ichthyosis relies on both physical examination and certain laboratory tests. Physical assessment at birth is vital for the initial diagnosis of Harlequin ichthyosis. Physical examination reveals characteristic symptoms of the condition especially the abnormalities in the skin surface of newborns. Abnormal findings in physical assessments usually result in employing other diagnostic tests to ascertain the diagnosis. Genetic testing is the most specific diagnostic test for harlequin ichthyosis. This test reveals a mutation on the ABCA12 gene. This gene is important in the regulation of protein synthesis for the development of the skin layer. Mutations in the gene may cause impaired transport of lipids in the skin layer and may also lead to shrunken versions of the proteins responsible for skin development. Biopsy of skin may be done to assess the histologic characteristics of the cells. Histological findings usually reveal hyperkeratotic skin cells, which leads to a thick and hard skin layer.

Treatment and prognosis

Constant care is required to moisturise and protect the skin. The hard outer layer eventually peels off, leaving the vulnerable inner layers of the dermis exposed. In the past, the disorder was always fatal, whether due to dehydration, infection (sepsis), restricted breathing due to the plating, or other related causes. The most common cause of death was systemic infection and sufferers rarely survived for more than a few days.

However, there have been improvements in care, most notably retinoids such as the drug Isotretinoin (Isotrex). The oldest known survivor is Nusrit "Nelly" Shaheen, who was born in 1984 and is in relatively good health as of May 9, 2008.[6] Lifespan limitations have not yet been determined with the new treatments.

A study published in 2011 in the Archives of Dermatology concluded, "Harlequin ichthyosis should be regarded as a severe chronic disease that is not invariably fatal. With improved neonatal care and probably the early introduction of oral retinoids, the number of survivors is increasing."[7]

History

The disease has been known since 1750, and was first described in the diary of a cleric from Charleston, South Carolina, the Rev. Oliver Hart:

"On Thursday, April the 5th, 1750, I went to see a most deplorable object of a child, born the night before of one Mary Evans in 'Chas'town. It was surprising to all who beheld it, and I scarcely know how to describe it. The skin was dry and hard and seemed to be cracked in many places, somewhat resembling the scales of a fish. The mouth was large and round and open. It had no external nose, but two holes where the nose should have been. The eyes appeared to be lumps of coagulated blood, turned out, about the bigness of a plum, ghastly to behold. It had no external ears, but holes where the ears should be. The hands and feet appeared to be swollen, were cramped up and felt quite hard. The back part of the head was much open. It made a strange kind of noise, very low, which I cannot describe. It lived about forty-eight hours and was alive when I saw it."[8]

Notable cases

References

  1. 1 2 3 Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
  2. ↑ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
  3. ↑ Shibata, Akitaka; Akiyama, Masashi (2015). "Epidemiology, medical genetics, diagnosis and treatment of harlequin ichthyosis in Japan". Pediatrics International 57 (4): 516–22. doi:10.1111/ped.12638. PMID 25857373.
  4. ↑ "Harlequin Ichthyosis". http://www.shhirt.org.uk. Retrieved 18 February 2015. External link in |website= (help)
  5. ↑ David Kelsell, P.; Elizabeth Norgett, E.; Unsworth, Harriet; Teh, Muy-Teck; Cullup, Thomas; Mein, Charles A.; Patricia Dopping-Hepenstal, J.; Beverly Dale, A.; Tadini, Gianluca; Fleckman, Philip; Karen Stephens, G.; Virginia Sybert, P.; Susan Mallory, B.; Bernard North, V.; David Witt, R.; Sprecher, Eli; E. M. Taylor, Aileen; Ilchyshyn, Andrew; Cameron Kennedy, T.; Goodyear, Helen; Moss, Celia; Paige, David; John Harper, I.; Bryan Young, D.; Irene Leigh, M.; Robin Eady, A.J.; Edel O'Toole, A. (2005). "Mutations in ABCA12 Underlie the Severe Congenital Skin Disease Harlequin Ichthyosis". The American Journal of Human Genetics 76 (5): 794–803. doi:10.1086/429844. PMC 1199369. PMID 15756637.
  6. 1 2 Alison Jones (May 9, 2008). "Nelly is a real diamond girl". Birmingham Post. Retrieved 2008-11-10.
  7. ↑ Rajpopat, Shefali; Moss, Celia; Mellerio, Jemima; Vahlquist, Anders; Gånemo, Agneta; Hellstrom-Pigg, Maritta; Ilchyshyn, Andrew; Burrows, Nigel; Lestringant, Giles; Taylor, Aileen; Kennedy, Cameron; Paige, David; Harper, John; Glover, Mary; Fleckman, Philip; Everman, David; Fouani, Mohamad; Kayserili, Hulya; Purvis, Diana; Hobson, Emma; Chu, Carol; Mein, Charles; Kelsell, David; O'Toole, Edel (2011). "Harlequin Ichthyosis". Archives of Dermatology 147 (6): 681–6. doi:10.1001/archdermatol.2011.9. PMID 21339420.
  8. ↑ Waring, J. I. (1932). "Early mention of a harlequin fetus in America". Archives of Pediatrics & Adolescent Medicine 43 (2): 442. doi:10.1001/archpedi.1932.01950020174019.
  9. ↑ "Harlequin Ichthyosis". Archived from the original on October 14, 2008. Retrieved 2008-11-10.
  10. ↑ Sean D. Hamill (June 27, 2010). "City girl aims to educate about her skin disease". Pittsburgh Post-Gazette. Retrieved 2010-06-27.
  11. ↑ Man Survives Rare Skin-Shedding Disease: Harlequin Ichthyosis Usually Fatal At Birth, 10News.com San Diego; posted November 16, 2004; backup at WayBack Machine
  12. ↑ Mid-South woman with rare genetic condition defies odds, deliverers healthy baby, by Ursula Madden; at Fox19 Cincinnati; posted Aug 26, 2013; retrieved Aug 27, 2013
  13. ↑ 'People ask me if I've been in a fire', says mother, 23, with rare condition which causes her skin to grow seven times faster than normal, Daily Mail, 2 December 2015
  14. ↑ News24 (Dec 31, 2014). "21-month-old boy defies the odds, thrives living with Harlequin Ichthyosis". News24. Retrieved 2015-01-01.

Further reading

External links

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