Epidermolytic Ichthyosis

Epidermolytic Ichthyosis

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Epidermolytic Ichthyosis 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.

Synonyms

  • BCIE
  • EHK
  • epidermolytic hyperkeratosis
  • bullous congenital CIE
  • bullous congenital ichthyosiform erythroderma (of Brocq)
  • EI

Disorder Subdivisions

  • None

General Discussion

Summary

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.



Introduction

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.

Symptoms

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 keratodermia 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).

Causes

EI is caused by a mutation in the genes coding for the proteins keratin 1 or 10 (KRT1/KRT10). These are cytoskeletal proteins that are normally expressed in the outer nucleated cell layer (the spinous 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. There are indications that cell growth may also be affected by the mutations. The severity of the disease depends on the location of the mutation in the protein. If keratin 1 is affected, the patient has a palmoplantar keratoderma. Keratin 10 is not expressed in the palmoplantar skin.



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 (inear 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.

Affected Populations

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

Standard Therapies

Diagnosis

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.



Treatment

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.

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



Contact for additional information about epidermolytic ichthyosis:



Prof. Maurice A.M. van Steensel, MD, PhD

Professor of Genetic Dermatology

Department of Dermatology

Maastricht University Medical Center

PO Box 5800

6202 AZ Maastricht

The Netherlands

Tel: 0031433875290

Fax: 0031433877293

References

JOURNAL ARTICLES

Oji V, Tadini G, Akiyama M, et al. Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009. J Am Acad Dermatol. 2010;63(4):607-41. http://www.ncbi.nlm.nih.gov/pubmed/20643494



Williams ML, Elias PM. Enlightened therapy of the disorders of cornification. Clin Dermatol. 2003;21(4):269-73.



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



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.



INTERNET

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Epidermolytic Hyperkeratosis; EHK. Entry No: 113800. Last Edited April 27, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed July 31, 2012.

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



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

USA

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/



Northwestern University Feinberg School of Medicine

Department of Surgery

233 East Erie Street

Suite 100

Chicago, IL 60611

Tel: (312)926-5427

Fax: (312)926-7404

Email: jrandolp@nmh.org

Internet: http://www.surgery.northwestern.edu/



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/



European Network for Ichthyosis (ENI)

In den Dellen 21

D-51515 Kürten

Germany

Tel: +49 2207849869

Email: e-n-i@gmx.net

Internet: http://www.ichthyosis.eu



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.

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