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

• Ichthyosis
• Psoriasis

Infants born with epidermolytic hyperkeratosis are 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.

Epidermolytic hyperkeratosis is caused by a mutation in one of the proteins, or keratins, (K1, K10 or K2e) that are normally expressed in the outer nucleated cell layer of the skin. The mutant keratin pairs with a normal keratin, which interferes with the normal function of the keratin network in the cell. Normally, these keratins form protein filaments (cables) that loop between the cell membrane and nucleus. Disruption of these cables produces a cell that is poorly resistant to mechanical trauma and therefore susceptible to trauma or blistering.

Epidermolytic hyperkeratosis is a hereditary disorder transmitted by autosomal dominant genes. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting a dominant disorder from affected parent to offspring is fifty percent for each pregnancy. Some cases of epidermolytic hyperkeratosis are thought to be caused by a spontaneous mutation.

Epidermolytic hyperkeratosis occurs in approximately 1 in 100,000 individuals. It affects males and females in equal numbers.

Symptoms of the following disorders may be similar to those of epidermolytic hyperkeratosis. 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.)

Psoriasis is a common chronic and recurrent disorder characterized by dry, well-circumscribed silvery-gray scaling spots (papules) or plaques which usually appear on the scalp, elbows, or knees. (For more on this disorder, choose "Psoriasis" as your search term in the Rare Disease Database.)

Treating epidermolytic hyperkeratosis 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. 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 or urea) and oral retinoids.

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 website.

For information about clinical trials being conducted at the National Institutes of Health (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

Elias, PM, Williams, ML. Enlightened Therapy of the Disorders of Cornification. Clinics in Dermatology. 2003; 21: 269 – 273.

DiGiovanna, JJ, Robinson-Bostom, L. Ichthyosis: etiology, diagnosis, and management. Am J Clin Dermatol. 2003;4: 81-95.

Schmuth, M, Yosipovich, G, Williams, ML, Weber, F, Hintner, F, Ortiz-Urda, S, Rappersberger, K, Crumrine, D, Feingold, K, and Elias, PM. Pathogenesis of the Permeability Barrier Abnormality in Epidermolytic Hyperkeratosis. J Inves Derm, October 2001; 17(4): 837-847.

Buxman, M, et al. Therapeutic activity of lactate 12% lotion in the treatment of ichthyosis. Active versus vehicle and active versus a petroleum cream. J Am Acad Dermatol. December 1986; 15(6): 1253-1258.

Williams, ML, et al. Genetically Transmitted, Generalized Disorders of Cornification. The Ichthyoses. Dermatol Clin. January 1987; 5(1): 155-78.
Reviewed by Amy Paller, MD