Ichthyosis, Erythrokeratodermia Variabilis

National Organization for Rare Disorders, Inc.

Skip to the navigation


It is possible that the main title of the report Ichthyosis, Erythrokeratodermia Variabilis is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


  • EKV
  • Keratosis Rubra Figurata
  • Mendes Da Costa Syndrome

Disorder Subdivisions

  • None

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.


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.


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.

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:




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.


Foundation for Ichthyosis & Related Skin Types

2616 N Broad Street

Colmar, PA 18915

Tel: (215)997-9400

Fax: (215)997-9403

Tel: (800)545-3286

Email: info@firstskinfoundation.org

Internet: http://www.firstskinfoundation.org

NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

Information Clearinghouse

One AMS Circle

Bethesda, MD 20892-3675


Tel: (301)495-4484

Fax: (301)718-6366

Tel: (877)226-4267

TDD: (301)565-2966

Email: NIAMSinfo@mail.nih.gov

Internet: http://www.niams.nih.gov/

Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/

For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.