• Disease Overview
  • Synonyms
  • Subdivisions
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report
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Epidermolytic Ichthyosis


Last updated: December 01, 2022
Years published: 1987, 1988, 1990, 1992, 1993, 2003, 2004, 2008, 2012, 2015, 2022


NORD gratefully acknowledges Liana Arceri and Catherine Brennan, NORD Editorial Interns from the University of Notre Dame and Anders Vahlquist, MD, Emeritus Professor, Uppsala University, Sweden for assistance in the preparation of this report.

Disease Overview

Epidermolytic ichthyosis (EI) is a genetic skin disorder that is characterized by varying degrees of blistering and scaling of the skin. The symptoms of the disease are often noticed at birth or shortly after, and symptoms change as the patient ages. Symptoms may vary from mild blistering upon friction to severe erosions or widespread warty scaling. Hair and nail abnormalities, reduced sweating and the formation of calluses on the palms or soles (palmoplantar keratoderma) of the feet can also occur. Under a microscope, the skin may show mid-epidermal splitting and skin thickening (hyperkeratosis). Current treatments address the specific symptoms and can include topical treatments, medications and antiseptic washes for skin infections. The cosmetic issues and sometimes unpleasant odor associated with EI can lead to stress and psychological distress.

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  • bullous congenital ichthyosiform erythroderma (of Brocq)
  • epidermolytic hyperkeratosis (EHK)
  • congenital bullous ichthyosiform erythroderma (BCIE)
  • bullous ichthyosiform erythroderma congenita
  • bullous ichthyosiform erythroderma
  • bullous erythroderma ichthyosiformis congenita of Brocq
  • EI
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  • annular epidermolytic ichthyosis
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Signs & Symptoms

The symptoms of EI progress with the patient’s age. Infants more commonly show signs of red, blistering skin and will usually develop thickened skin (cornification) and scaling into adulthood. Infants may also show growths on the inner surface of the eyelid (conjunctival hamartoma). Scales tend to form in parallel rows of spines or ridges. Reddened skin (erythroderma), itchiness (pruritus) and abnormal dryness (xerosis) are common symptoms. Skin ulcers and other damage can lead to bacterial infections. Heat intolerance and sensitivity to sunlight may also occur. A palmoplantar keratoderma may be present and can be so severe as to limit movement and hand function. Milder cases usually show minimal blistering in areas subject to friction or have only a palmoplantar keratoderma.

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EI is caused by harmful changes (variants) in the KRT1 or KRT10 genes. These variants result in improper expression of keratin 1 and keratin 10, which are structural proteins specifically found in epithelial and epidermal cells. The malfunctioning proteins result in barrier abnormalities that can lead to epidermal inflammation, causing the various symptoms seen with the disease.

Some patients have some cells with the harmful gene variant and other cells without the harmful gene variant (somatic mosaicism). This can cause blistering and hyperkeratotic lesions specific to certain areas of the skin. The severity of the disease in these patients is directly correlated to the percentage of cells affected. In somatic mosaicism, the gene change is not inherited.

EI is an autosomal dominant genetic disorder. Dominant genetic disorders occur when only a single copy of a harmful gene variant is necessary to cause a particular disease. EI can be inherited or sporadic, meaning the gene variant can be the result of a new mutation (gene change) in the affected individual. About 50% of cases are caused by spontaneous changes in the KRT1 or KRT10 genes, and the variant can then be passed down to children. The risk of passing the harmful gene variant from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.

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Affected populations

EI occurs in approximately 1 in 200,000 individuals, affecting males and females equally.

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EI is diagnosed by clinical signs and symptoms. Histopathology tests and electron microscopy assessments may be used but are not the most definitive. Genetic testing for harmful variants in the KRT1 and KRT10 genes can confirm a diagnosis.

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Standard Therapies

The main goal of treating EI is to ease the presenting symptoms. This can be challenging as it may require a combination of treatments and therapies. The medications that help to remove the excess thickened skin (topical keratolytics or oral retinoids) can leave the very fragile epidermis (underlying living cell layers) exposed. Therefore, application of a barrier repair formula containing ceramides or cholesterol, or topical emollients, may be used in conjunction to relieve and protect the vulnerable skin. Since bacterial infections are a cause of concern, it is recommended that patients wash with antiseptic soap 2-3 times per week. Many patients find baths with salt or sodium bicarbonate, as well as bleach, beneficial as it helps to descale and prevent bacterial overgrowth. If symptoms are seen at birth, the newborn is recommended to be transferred to the neonatal ICU for proper monitoring and care.

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Clinical Trials and Studies

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

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

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Leclerc-Mercier S. How to deal with skin biopsy in an infant with blisters? Dermatopathology (Basel). 2021;8(2):159-175. doi: 10.3390/dermatopathology8020022 [doi].

Metze D, Traupe H, Süßmuth K. Ichthyoses-a clinical and pathological spectrum from heterogeneous cornification disorders to inflammation. Dermatopathology (Basel). 2021;8(2):107-123. Published 2021 May 7. doi:10.3390/dermatopathology8020017

Mikilita ES, Hernandez IP, Boff AL, Kiszewski AE. Annular epidermolytic ichthyosis: a case report and literature review. An Bras Dermatol. 2020;95(4):484-489. doi:10.1016/j.abd.2019.09.030

Sarkar T, Sarkar S, Gangopadhyay DN. Gene therapy and its application in dermatology. Indian J Dermatol. 2020;65(5):341-350. doi:10.4103/ijd.IJD_323-20.

Vahlquist A, Törmä H. Ichthyosis: a road model for skin research. Acta Derm Venereol. 2020;100(7):adv00097. Published 2020 Mar 25. doi:10.2340/00015555-3433

Rout DP, Nair A, Gupta A, Kumar P. Epidermolytic hyperkeratosis: clinical update. Clin Cosmet Investig Dermatol. 2019;12:333-344. Published 2019 May 8. doi:10.2147/CCID.S166849

Vahlquist A, Fischer J, Törmä H. Inherited nonsyndromic ichthyoses: An update on pathophysiology, diagnosis and treatment. American journal of clinical dermatology. 2018;19(1):51-66.

Eskin-Schwartz M, Drozhdina M, Sarig O, et al. Epidermolytic ichthyosis sine epidermolysis. Am J Dermatopathol. 2017;39(6):440-444. doi:10.1097/DAD.0000000000000674

Sethuraman G, Marwaha RK, Challa A, et al. Vitamin D: A new promising therapy for congenital ichthyosis. Pediatrics. 2016;137(1):e20151313.

Boehncke WH, Schön MP. Psoriasis. Lancet. 2015;386(9997):983-994. doi: S0140-6736(14)61909-7 [pii].

Knöbel M, O’Toole EA, Smith FJ. Keratins and skin disease. Cell Tissue Res. 2015;360(3):583-589. doi:10.1007/s00441-014-2105-4

Traupe H, Fischer J, Oji V. Nonsyndromic types of ichthyoses – an update. J Dtsch Dermatol Ges. 2014;12(2):109-121. doi:10.1111/ddg.12229

Hamada T, Tsuruta D, Fukuda S, et al. How do keratinizing disorders and blistering disorders overlap? Exp Dermatol. 2013;22(2):83-87. doi:10.1111/exd.12021

Epidermolytic ichthyosis. Genetic and Rare Diseases Information Center. Nov 8, 2021.https://rarediseases.info.nih.gov/diseases/1039/epidermolytic-ichthyosis Accessed Nov 15, 2022.

Rice AS, Crane JS. Epidermolytic Hyperkeratosis. In: StatPearls. August 9, 2021. https://www.ncbi.nlm.nih.gov/books/NBK544323/ Accessed Nov 15, 2022.

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