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.
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.
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.
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.
EI occurs in approximately 1 in 200,000 individuals, affecting males and females equally.
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.
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.
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: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
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
INTERNET
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.
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
View report
Your donation will help more than 30 million Americans with a rare disease navigate their diagnosis, receive financial assistance, and access the care and support they deserve. Make your tax-deductible gift today!