Information on the following diseases can be found in the Related Disorders section of this report:

• Ichthyosis
• Ichthyosis Congenita
• X-Linked Ichthyosis

Erythrokeratolysis hiemalis is characterized by periodic attacks of red skin plaques. A thick layer of skin can be peeled off these plaques from the center outward. As new skin forms, the plaques are pushed outward. Symptoms may start during infancy or adolescence, and the disorder usually improves with age. Only the palms of the hands and the soles of the feet are involved in most cases. However, the disorder may spread to the skin of the back or elsewhere on the body surface. Appearance of new plaques may be precipitated by fever or surgery.

Erythrokeratolysis hiemalis is a hereditary disorder transmitted as an autosomal dominant trait. The mutated gene has been tracked to gene map locus 8p23-p22.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 8p23-p22" refers to the region on the short arm of chromosome 8 between bands 23 and 22. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

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.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Erythrokeratolysis hiemalis primarily affects descendants of farmers from the Oudtshoorn district in South Africa. This disorder starts during infancy or adolescence and usually improves after age 30. It is thought to affect males and females equally. One estimate is that 37 babies are born with this disorder annually.

Symptoms of the following disorders may be similar to those of erythrokeratolysis hiemalis. Comparisons can be useful for a differential diagnosis:

"Ichthyosis" 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 skin cells known as "corneocytes" or of the fat-rich matrix around these cells. The cells can be thought of as bricks, while the matrix would be the mortar holding these cells together. (For more information, choose "Ichthyosis" as your search term in the Rare Disease Database.)

Ichthyosis congenita (collodion baby; congenital ichthyosiform erythroderma; xeroderma; desquamation of newborn) is an inherited skin disorder. It is characterized by generalized, abnormally red, dry and rough skin, with large, coarse scales. Itchiness (pruritus) usually also develops. Skin on the palms of the hands and soles of the feet is abnormally thick. (For more information, choose "Ichthyosis Congenita" as your search term in the Rare Disease Database.)

X-linked ichthyosis is an inherited skin disorder affecting males. It is caused by a deficiency of the enzyme steroid sulfatase. This enzyme deficiency leads to biochemical alterations in steroid hormone metabolism. Cholesterol sulfate may accumulate in the blood and skin. (For more information, choose "X-Linked Ichthyosis" as your search term in the Rare Disease Database.)

Other forms of ichthyosis include Sjogren-Larsson syndrome, Netherton syndrome, ichthyosis hystrix, lamellar ichthyosis, Refsum syndrome, Darier disease, Conradi-Hunermann syndrome, Chanarin-Dorfman syndrome, and epidermolytic hyperkeratosis. (Choose the appropriate name as your search term for more information on that disorder in the Rare Disease Database.)

Diagnosis
In most instances, the appearance of the skin determines the diagnosis, but a family history and physical examination are often required to rule out other possible causes of scaly, dry skin. Some physicians may examine skin tissue under a light microscope or even under an electron microscope.

Treatment
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 effective for only as long as one takes the medication. After treatment is stopped, the skin build-ups 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.

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.

Drugs derived from vitamin A (retinoids) such as tretinoin, motretinide, and etretinate may be effective against symptoms of erythrokeratolysis hiemalis, but can cause toxic effects on the bones in some cases. A synthetic derivative of vitamin A, isotretinoin, when taken by pregnant women, can cause severe birth defects to the fetus. These vitamin A compounds have not yet been approved by the Food and Drug Administration (FDA) for treatment of ichthyosis.

The National Institute of Arthritis, Musculoskeletal and Skin Diseases is looking for patients with various kinds of ichthyosis willing to participate in research aimed at mapping the genes responsible for their disorder. Interested persons may contact:

Dr. Sherri Bale
National Institute of Arthritis, Musculoskeletal and Skin Diseases
9000 Rockville Pike
Bethesda, MD 20892
(301) 402-2679

The orphan product monolaurin (Glylorin), a topical cream, is being tested for treatment of Ichthyosis. More studies are needed to determine the long-term safety and effectiveness of this drug for the treatment of ichthyosis. For more information, contact:

Cellegy Pharmaceuticals, Inc.
371 Bel Marin Keys, Suite 210
Novato, CA 94949
(415) 382-6770

McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Keratolytic Winter Erythema. Entry Number; 148370: Last Edit Date; 3/18/2004.


TEXTBOOK
Champion RH, Burton JL, Ebling FJG., eds. Textbook of Dermatology. 5th ed. Blackwell Scientific Publications. London, UK; 1992:1352.

JOURNAL ARTICLES
Appel S, Filter M, Reis A, et al. Physical and transcriptional map of the critical regionfor keratolytic winter erythema (KWE) on chromosome 8p22-p23 between D8S550 and D8S1759. Eur J Hum Genet. 2002;10:17-25.

Danielsen AG, Weismann K, Thomsen HK. Erythrokeratolysis hiemalis (keratolytic winter erythema): a case report from Denmark. J Eur Acad Dermatol Venereol. 2001;15:255.

Brusasco A, Veraldi S, Tadini G, et al. Localized peeling skin syndrome: case report with ultrastructural study. Br J Dermatol. 1998;139:492-95.