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NORD is very grateful to Anne W. Lucky, MD, Children's Hospital of Cincinnati, Brett Koplen, Executive Director, DebRA of America, Inc., and Geraldine Kelly-Mancuso, RN, DEBRA Nurse Educator, Cincinnati Children's Hospital Medical Center, for assistance in the preparation of this report.
Epidermolysis bullosa (EB) is a genetic skin disorder characterized clinically by blister formation from mechanical trauma. There are four main types with additional sub-types identified. There is a spectrum of severity, and within each type, one may be either mildly or severely affected. EB ranges from being a minor inconvenience requiring modification of some activities, to being completely disabling and, in some cases, fatal.
Friction causes blister formation. Blisters can form anywhere on the surface of the skin, within the oral cavity and in more severe forms may also involve the external surface of the eye, as well as the respiratory, gastrointestinal and genitourinary tracts. In some forms of the disease, disfiguring scars and disabling musculoskeletal deformities occur.
Currently, there is no cure for EB. Supportive care includes daily wound care, bandaging, and pain management as needed.
Epidermolysis bullosa is divided into four subdivisions, and each subdivision has subtypes.
Epidermolysis bullosa simplex (EBS) is usually dominantly inherited, and involves disorders of the genes for Keratins 5 and 14 and plectin. Recently, several suprabasal types of EBS have been described as well. Blistering occurs within the uppermost layer of the skin, the epidermis. EBS may be localized to the hands and feet or there may be a generalized distribution, with relatively mild internal involvement. Those with EBS may have thickened calluses on the palms and soles, oral blistering during infancy and rough, thickened fingernails/toenails. EBS does not usually scar. There are rare recessive forms. EBS with plectin mutations may be associated with muscular dystrophy.
Junctional epidermolysis bullosa (JEB), is recessively inherited, and involves mutations in the genes for several components of the junction between the epidermis and dermis such as Laminin 332 (previously known as Laminin 5), plectin, and a6b4integrin. There are two major subtypes, Herlitz JEB and JEB- other (includes non-Herlitz JEB, and JEB with pyloric atresia and several other subtypes). Junctional Herlitz EB is due to mutations in any of the three Laminin 332 chains and can be a very severe form of EB. Death often occurs during infancy due to overwhelming infection (sepsis), malnutrition, dehydration, electrolyte imbalance or obstructive airway complications. There is a wide spectrum of JEB- O. Oral cavity involvement and irregular pitting of the surfaces of the teeth is common in all subtypes. Infants presenting with pyloric atresia will have trouble with feeding and abdominal distension as neonates and present as surgical emergencies in the newborn period.
Dystrophic epidermolysis bullosa (DEB) can be either dominantly or recessively inherited, and involves defects in Type VII collagen. Blisters occur within the lower layer of the skin, the dermis. There are two major subtypes, dominant DEB (DDEB) and recessive DEB (RDEB).
Dominant dystrophic EB (DDEB): DDEB is usually mild. Blistering may be localized to the hands, feet, elbows and knees or it may be generalized. Common findings include scarring, milia (tiny white bumps), mucous membrane involvement, and abnormal or absent nails. Some family members may only have nail dystrophy.
Recessive dystrophic EB (RDEB): RDEB is typically more generalized and severe than DDEB. In addition to scarring, milia, mucous membrane involvement and nail dystrophy, common manifestations include malnutrition, anemia, esophageal strictures, growth retardation, webbing or fusion of the fingers and toes causing mitten deformity (pseudosyndactyly) with loss of function, development of contractures, malformation of teeth, microstomia and corneal abrasions. Severe generalized RDEB (formerly Hallopeau-Siemens RDEB) tends to be the most severe form.
Kindler syndrome is very rare and involves all layers of the skin with extreme fragility.
Inherited epidermolysis bullosa is the focus of this report. The inherited forms follow either autosomal dominant or autosomal recessive inheritance. There is also a rare acquired autoimmune disorder called epidermolysis bullosa aquisita. A mutation in any of at least 18 genes encoding the proteins in the epidermis, basement membrane or dermis causes poor integrity of the skin leading to fragility.
Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one 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 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 at least 4-5 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.
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 type of EB occurs in an estimated 1 out of every 50,000 live births. The disorder occurs in every racial and ethnic group throughout the world and affects both sexes equally.
Any blistering disorder in the newborn period may mimic EB. These include herpes simplex virus, epidermolytic ichthyosis, bullous impetigo and incontinentia pigmenti.
Clinical diagnosis of the type of EB based on presentation in the neonatal period should be avoided as all types of EB may look alike in this age group. When EB is suspected, a skin biopsy should be obtained and sent to an appropriate laboratory to confirm the diagnosis with transmission electron microscopy (TEM) and/or immunofluorescent antibody/antigen mapping. Molecular genetic testing for mutations in most of the genes known to be associated with the various types of EB is clinically available.
By definition, inherited EB is a genetically transmitted disorder characterized by marked fragility of the skin. Any trauma, no matter how minimal it may seem, is likely to cause the skin of an EB child or adult to tear or blister. The following are recommended ways to avoid or minimize this problem:
1. Reducing friction: Extreme care should be employed in handling the skin of any patient with EB.
2. Non-adhesive bandages and dressings: Adhesive or semi-adhesive dressings, bandages, Band-aids, or tape should not be used on the surface of the skin. Instead, wounds should be covered with an appropriate non-adhesive dressing and then further wrapped loosely with rolled gauze. This can be secured by using a tubular dressing retainer.
3. Keeping the skin cool: Nothing hot should ever be applied to the skin of a patient with EB. In particular, bath water should be no warmer than body temperature. Patients should avoid prolonged exposure to ambient heat and humidity. If possible, air conditioned environments should be sought whenever possible.
4. Managing blisters: Because blisters in EB are not self-limiting, and can fill with fluid and grow quite large, they need to be drained.
5. Clothing: In younger children, diapers may require additional padding at the legs and waist. Whenever possible, loose-fitting garments should be worn. If blisters develop from the seams of clothing, garments may be worn inside-out and tags, cuffs and necklines may be removed. Loosely-fitted, padded shoes are generally better tolerated.
6. Nutritional deficiencies: Many children with EB become anemic due to a chronic loss of blood through wounds, poor nutritional intake, poor absorption of iron and bone marrow suppression from chronic inflammation. It is important to work with a nutritionist experienced in the care of special needs patients. Treatment for iron deficiency anemia is often necessary. Other patients have selenium and carnitine or vitamin D deficiencies which may predispose them to cardiomyopathy and osteoporosis. Many patients develop failure to thrive and require feeding gastrostomies.
7. Monitoring for cancer: Squamous cell carcinoma is the leading cause of death in EB usually occurring after the 2nd decade of life. Patients with RDEB and JEB are at increased risk of developing skin cancers during their lifetimes. It is very important that all EB patients have at least yearly examination of all skin areas.
Stem cell transplant therapy trials for recessive dystrophic epidermolysis bullosa are being conducted at at least two institutions. For further information contact the following :
University of Minnesota Center for Translational Medicine Tim Krepski, RN 612-273-2800 Toll-free: 1-888-601-0787
Cincinnati Children's Hospital
Epidermolysis Bullosa Center
Anne W. Lucky, MD or Richard G. Azizkhan, MD
(Severe Junctional EB) 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: firstname.lastname@example.org
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
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Marinkovich MP. Epidermolysis Bullosa Updated: Aug. 10, 2012. Medscape. Available at: http://emedicine.medscape.com/article/1062939-overview Accessed May 30, 2013.
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Report last updated: 2013/06/27 00:00:00 GMT+0