NORD gratefully acknowledges Maurice A.M. van Steensel, MD, PhD, Professor of Dermatology, University of Dundee, College of Life Sciences and of Medicine, Dentistry and Nursing, Dundee, UK / Institute of Medical Biology, Singapore, for assistance in the preparation of this report.
Epidermolytic ichthyosis (EI) specifically refers to a hereditary skin disorder that is characterized by varying degrees of blistering and subsequent reactive scaling of the skin. The underlying histopathology shows mid-epidermal splitting and hyperkeratosis, together referred to as epidermolytic hyperkeratosis (EHK). Depending on the nature of the causative mutation, the symptoms may vary from mild blistering upon friction to severe erosions or widespread warty scaling (“porcupine man”). A palmoplantar keratoderma (excessive callus formation on palms and soles) and/or hair abnormalities may be present in some forms of the disorder.
The term epidermolytic ichthyosis was agreed upon by the International Ichthyosis Consensus Group in 2009 and replaces the older, confusing labels of bullous congenital ichthyosiform erythroderma (Brocq) and epidermolytic hyperkeratosis.
A number of disorders show epidermolytic hyperkeratosis, including EI, superficial epidermolytic ichthyosis bullosa and desmosomal disorders such as McGrath ectodermal dysplasia-skin fragility syndrome. Much confusion has resulted from use of the term EHK to refer to the disorder now known as epidermolytic ichthyosis.
Infants with EI may be born with red, blistering and denuded skin with visible areas of skin thickening. Over time, there is a gradual decrease in blistering, but an increase in the severity of the scaling and skin thickening. Scales tend to form in parallel rows of spines or ridges. A generalized erythroderma (redness of the skin) may be present in some individuals. Skin infections with common bacteria can be a problem. Heat intolerance is common. A palmoplantar keratoderma may be present and can be so severe as to limit ambulation and hand function. Surgical intervention may then be required. On the other end of the scale, there are individuals who have only minimal blistering in areas subject to friction, or have only a palmoplantar keratoderma. Rarely patients are covered in brown-grey hyperkeratotic spines. This is called ichthyosis hystrix (Curth-Macklin).
EI is an autosomal dominant genetic disorder. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females. Some cases of EI are caused by a spontaneous mutation.
Somatic mosaicism for KRT1 and KRT10 mutations causes epidermolytic epidermal nevi, which are blistering and hyperkeratotic lesions limited to certain areas of the skin, and often following Blaschko’s lines (linear epidermolytic hyperkeratotic nevus). In somatic mosaicism, the mutation of the gene occurs after fertilization and is not inherited. The mutation is found in some of the cells of the body, but not in others. The severity of the disease in these cases depends on the percentage of cells affected, and it is less severe than in individuals who have the mutation in all of their cells. When we see a mosaic disorder there is a slight risk of gonadal mosaicism (1-6%).
EI occurs in approximately 1 in 100,000 individuals. It affects males and females in equal numbers.
EI is diagnosed by physical signs and symptoms. Molecular genetic testing for mutations in the KRT1 and KRT10 genes is available to confirm the diagnosis.
Treating EI is a challenge. The medications that help to remove the excess thickened skin layers (topical keratolytics or oral retinoids) often remove too much scale, leaving a very fragile epidermis (underlying living cell layers) exposed. Severe palmoplantar keratoderma is very difficult to treat. A combination of therapies may help, including: application of a barrier repair formula containing ceramides or cholesterol; application of a barrier repair formula containing petrolatum or lanolin; topical or systemic anti-bacterial agents; and cautious use of keratolytics (lotions containing alpha-hydroxy acids, propylene glycol, lactic acid or urea). Since bacterial colonization is almost always present due to the scaling, it is recommended that patients wash with antiseptic soap 2-3 times per week. Many patients find baths with salt or sodium bicarbonate beneficial (helps to descale). Also, some bleach added to the bath may assist in combating bacterial overgrowth.
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Contact for additional information about epidermolytic ichthyosis:
Prof. Maurice A.M. van Steensel, MD, PhD
Professor of Dermatology
Colleges of Life Sciences and of Medicine, Dentistry and Nursing
University of Dundee
Institute of Medical Biology
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Schmuth M, Yosipovich G, Williams ML, et al. Pathogenesis of the Permeability Barrier Abnormality in Epidermolytic Hyperkeratosis. J Inves Derm. 2001;17(4):837-847.
Buxman M, Hickman J, Ragsdale W, Stretcher G, Krochmal L, Wehr RF. Therapeutic activity of lactate 12% lotion in the treatment of ichthyosis. Active versus vehicle and active versus a petroleum cream. J Am Acad Dermatol. 1986;15(6):1253-1258.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Epidermolytic Hyperkeratosis; EHK. Entry No: 113800. Last Edited 01/24/2013. Available at: http://omim.org/entry/113800 Accessed May 12, 2015.
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