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Ichthyosis, Erythrokeratodermia Variabilis

NORD is very grateful to the members of the Medical and Scientific Advisory Board of the Foundation for Ichthyosis & Related Skin Types for assistance in the preparation of this report.

Synonyms of Ichthyosis, Erythrokeratodermia Variabilis

  • EKV
  • Keratosis Rubra Figurata
  • Mendes Da Costa Syndrome

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Erythrokeratodermia variabilis is an inherited skin disorder characterized by two features: short-lasting red patches in various sizes and shapes that may involve any part of the body; and thickening of the skin (hyperkeratosis). The hyperkeratosis can either be generalized, or localized as fixed, sharply defined, thickened plaques. The hyperkeratosis may also involve the skin of the palms and soles. Skin lesions are made worse by sudden changes in temperature and friction. The red patches may be accompanied by a burning sensation.

Symptoms

Erythrokeratodermia variabilis is characterized by red skin areas with sharp borderlines, which tend to shift positions. Fixed plaques of hardened skin also develop independent from the red areas. The majority of patients present at birth or during infancy with short-lasting, circumscribed, red patches that may involve any part of the body surface. They are most prevalent during childhood and slowly subside later. The red spots persist for minutes to hours, although they may last for days. In about 35 % of patients, the red spots (erythema) may be preceded by or accompanied by a burning sensation, which may cause serious discomfort. The remarkable variability of the red patches in number, size, shape, location and duration is a typical feature of the disease.

In addition, progressive, yellow-brown, thickened, rough plaques (hyperkeratosis) develop slowly over time. The plaques can be distributed symmetrically over the extremities and trunk, or can be generalized. Most common are relatively fixed plaques over the knees, elbows, heels, back of the feet, and belt area. About half of all patients also have thickening of the palms and soles. The hyperkeratotic plaques are usually more stable, and last for months to years. After progression during infancy and childhood, the disorder seems to stabilize after puberty and slowly regresses in older age. Improvement and periodic clearing of the skin are not unusual. Hair, nails, teeth, and mucous membranes are normal.

Causes

Erythrokeratodermia variabilis is genetic and is inherited as an autosomal dominant trait. The risk of the disorder being transmitted from an affected parent to his or her offspring is 50% for each pregnancy.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the 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 regardless of the sex of the resulting child.

There are two different but related genes whose mutations are responsible for the disorder. Both genes are located at the short arm of chromosome 1. The genes are named GJB3 and GJB4 because they contain the genetic information for producing the gap junction proteins beta-3 and beta-4 (also known as connexin-31 and connexin-30.3). These proteins are found in the skin and inner ear. They are the building blocks for small channels that connect neighboring cells with each other, and are responsible for the transport of small molecules, ions, and nutrients between cells. It is assumed that disease-causing mutations alter the structure and/or function of these proteins, which in turn impairs normal communication between the skin cells.

Affected Populations

Erythrokeratodermia variabilis is a rare inherited disorder of the cornification of the skin, which often presents at birth. Males and females are affected in equal numbers. There seems to be no predilection by race or ethnicity.

Related Disorders

Symptoms of the following disorders may be similar to those of erythrokeratodermia variabilis. Comparisons can be useful for a differential diagnosis.

"Ichthyoses" or "disorders of cornification" are general terms describing a group of scaly skin disorders. They are characterized by an abnormal accumulation of large amounts of dead skin cells (squames) in the top layer of the skin. The conversion of an abnormally large number of epidermal cells into squamous cells is thought to be caused by a defect in the metabolism of the skin cells known as "corneocytes" or the fat-rich matrix around these cells. These cells can be thought of as bricks, while the matrix would be the mortar holding these cells together. (See "Ichthyosis" in the Rare Disease Database.)

EKV shares many overlapping features with progressive symmetric erythrokeratoderma and keratitis-ichthyosis-deafness (KID) syndrome. In the latter disorders, a person develops red, rough thickened plaques of skin on the extremities and face, which may progressively enlarge and spread over the body. Both disorders, however, lack the shifting erythematous patches characteristic for EKV. In addition to the skin involvement, KID syndrome is characterized by congenital sensorineural hearing loss and visual problems due to keratitis (inflammation of the cornea). (For more information choose "Progressive Symmetric Erythrokeratoderma" or "Keratitis-Ichthyosis-Deafness" as your search term in the Rare Disease Database.)

Standard Therapies

Therapy is symptomatic and focuses on diminishing the build-up of skin (hyperkeratosis). Systemic therapy with oral retinoids is very effective, but has to be carefully monitored because of side effects. Moreover, the treatment is only effective as long as one takes the medication. After stopping treatment, the skin changes reappear within a short period of time. Topical skin care may include emollients and keratolytics such as; urea, lactic acid, glycolic acid, propylene glycol, salicylic acid, and topical retinoids preparations. Avoiding mechanical irritation of the skin can be beneficial.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Organizations related to Ichthyosis, Erythrokeratodermia Variabilis

References

JOURNAL ARTICLES
Richard, G, Brown, N, Rouan, F, et al. Genetic heterogeneity in erythrokeratodermia variabilis: Novel mutations in the connexin gene GJB$ (Cx30.3) and genotype-phenotype correlations. J Invest Dermatol 2003; 120: 601-609.

Macari, F, Landau, M, Cousin, P, Mevorah, B, Brenner, S, Panizzon, R, Schorderet, DF, Hohl, D, Huber, M. Mutation in the gene for connexin 30.3 in a family with erythrokeratodermia variabilis. Am J Hum Genet 2000; 67: 1296-1301.

Richard, G, et al. Mutations in the human connexin gene GJB3 causes erythrokeratodermia variabilis. Nat Genet 1998; 20: 366-369.

Van der Kerhof, PC, Steijlen, PM, van Dooren-Greebe, RJ, Happle, R. Acitretin in the treatment of erythrokeratodermia variabilis. Dermatologica 1990; 181 (4): 330-3.

McFadden, N, Oppedal, BR, Ree, K & Brandtzaeg, P. Erythrokeratodermia variabilis: immunohistochemical and ultrastructure studies of the epidermis. Acta Derm Venereol 1987; 67:284-288.

Brown, J & Kierland, RR. Erythrokeratodermia variabilis. Report of three cases and review of the literature. Arch Dermatol 1966; 93: 194-201.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/05/30 00:00:00 GMT+0

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