Related Disorders List

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

• Congenital syphilis
• Ectodermal dysplasias
• Ichthyosis

Symptoms

Epidermolysis bullosa is divided into three subdivisions, based upon the depth of the blisters. Each subdivision also has subtypes.

In EB Simplex (non-scarring), the blisters occur within the outer layers of the skin (epidermis). These blisters, which leave open sores when they rupture, are usually associated with pain and, sometimes, with itching. In the most common subtype of EB simplex, the Weber-Cockayne variant, blisters are usually confined to the palms of the hands and soles of the feet, although they may develop elsewhere on the skin following injury. Dowling-Meara, another subtype, is characterized by the presence of grouped collections of blisters, and much of the body may be affected. Elevated body temperature (fever) may also be present. About one-third of all EB simplex patients experience some blisters and sores within the oral cavity. These may lead to difficulty related to feeding and/or swallowing. Some growth retardation and anemia may be seen in more severe subtypes of EB simplex. Warm weather may aggravate the condition. Children with the simplex form usually have normal mental and physical development. .

In junctional epidermolysis bullosa (JEB), the blisters occur deeper within the layers of the skin (lamina lucida of the basement membrane zone). There are two major subtypes, Herlitz JEB and non-Herlitz JEB, and several minor subtypes. Patients with JEB usually have widespread, painful blisters and skin erosions. The skin is very fragile and may peel off in sheets. Wounds eventually heal but may leave scars. Nails may be damaged or fall off following mild trauma, and there may be either enhancement of, or reduction in, pigment following injury. Blister formation within the upper airway is a serious concern, especially with infants. This may first present as a subtle hoarseness in the infant’s cry, but can rapidly progress to blockage of the upper airway. Oral cavity involvement is common in both subtypes. Another feature of all forms of JEB is irregular pitting of the surfaces of the teeth.

Dystrophic epidermolysis bullosa (DEB) is characterized by blisters that develop beneath the lowest layer of the skin (basement membrane zone) and are present at, or shortly after, birth. Patients with DEB have widespread, painful blisters and sores. There are two major subtypes, dominant DEB (DDEB) and recessive DEB (RDEB), referring to the way in which they are inherited. The recessive dystrophic form (Hallopeau-Siemens RDEB) is the most severe. Blisters appear on the arms and legs, and are widespread, affecting mucous membranes and skin. Blisters leave scars and small "seed-like" cysts after healing.

The tongue, eyes and esophagus are often affected. Teeth may be malformed and nails may be lost. Scars may leave "mitten" deformities of the fingers and toes. In some cases, hair follicles may be destroyed and hair loss (alopecia) develops. Malnutrition, anemia, and growth retardation can result from chronic blood loss and poor food intake.

Children with severe RDEB may experience profound growth retardation and severe anemia. Also, patients with RDEB have an increased risk of developing one or more squamous cell carcinomas on the skin during or after the second decade of life. These carcinomas may spread (metastasize) to other parts of the body if not treated promptly. In a few cases, patients with RDEB have also developed malignant melanoma during early childhood. .

Causes

Most forms of epidermolysis bullosa are inherited and this report focuses on those, although there is some evidence that EB may on rare occasions be an acquired autoimmune disease. The inherited forms may be either autosomal dominant or recessive traits. The genetic defect may cause abnormalities of the substances that are necessary for skin growth, such as keratin and collagen, and the enzyme collagenase.

Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

In dominant disorders, a single copy of the disease gene (received from either the mother or the father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is fifty percent for each pregnancy, regardless of the sex of the resulting child.

In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If one 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 of transmitting the disease to the children of a couple, both of whom are carriers of the recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

Most forms of EB simplex have an autosomal dominant inheritance pattern. All forms of JEB are transmitted as autosomal recessive traits. As noted above, DEB has both autosomal dominant and recessive forms.

Some forms of EB have been linked to specific genetic locations. For instance, in non-scarring epidermolysis bullosa simplex, researchers have found that genes on chromosomes 12 and 17 are involved in causing the disorder. The exact way in which this occurs has yet to be fully explained. However, scientists believe they have found the genes responsible for the development of EB Simplex and are studying these genes to determine the underlying biochemical defect.

The gene for type VII collagen has been located on chromosome 3 in a family with DDEB. Scientists are hopeful that this information may lead to improved treatment of patients in the future.

The gene associated with Herlitz type epidermolysis has been mapped to chromosome 1 (1q25-q31).

The gene associated with Koebner-type EB and Weber Cockayne-type EB has been mapped to chromosome 17 (17q12-q21). .

Affected Populations

Based on data from the National EB Registry, the incidence and prevalence of EB simplex have been estimated at 10.75 per one million live births and 4.60 per million population. Of these cases, about two-thirds represent Weber-Cockayne disease.

The estimated incidence and prevalence of JEB have been estimated at approximately 2.0 per one million live births and 0.4 per million population. The corresponding numbers for DDEB are approximately 2.9 cases per one million live births and 1.0 per million population. For RDEB, they are 2.0 per one million live births and 0.9 per million population. .

Related Disorders

Symptoms of the following disorders can be similar to those of epidermolysis bullosa. Comparisons may be useful for differential diagnosis:

Congenital Syphilis is a chronic infectious disease given to a baby by an infected mother. It is caused by a bacterium known as Spirochete treponema pallidum. Symptoms include, but are not limited to, low birth weight, fever, rash, and the shedding of skin on the palms of the hands and the soles of the feet. The shedding or absence of skin during infancy may be confused with the diagnosis of epidermolysis bullosa. (Fro more information on this disorder, choose "Congenital Syphilis" as your search term in the Rare Disease Database.)

The ectodermal dysplasias (Eds) are a group of rare inherited multisystem disorders that typically affect the skin, hair, teeth, and/or nails. There are several disorders belonging to the Eds that may be characterized by skin, hair, dental, nail, craniofacial, and/or other physical abnormalities. A number of the ectodermal dysplasia disorders may be characterized by skin rashes, impaired healing of the skin, and/or other skin abnormalities; sparse or absent hair; dental defects; abnormally developed nails; craniofacial malformations; eye abnormalities; short stature; and/or other abnormalities similar to those associated with certain types of epidermolysis bullosa. (For more information on these disorders, choose "Ectodermal Dysplasia" or the exact disease name in question as your search term in the Rare Disease Database.)

Ichthyosis or peeling skin syndrome is a group of rare genetic disorders characterized by the periodic shedding of the outer layer of the skin (stratum corneum). Patients with Ichthyosis have skin that is thicker than normal. Redness (erythroderma) and itching (pruritus) may also be present. Some patients with Ichthyosis have short stature. (For more information on these disorders, choose "Ichthyosis" as your search term in the Rare Disease Database.) .

Standard Therapies

Therapy for epidermolysis bullosa is symptomatic and supportive. Antibiotics are useful to prevent or treat infection. Patients need good nursing and support care. A high protein diet is helpful in cases where malnutrition develops. A modified, cool environment is also more comfortable for patients with this disease. Care should be taken when removing bandages so as not to disturb the scabs.

For JEB patients with severe disease activity, chronic malnutrition may require special treatment. Iron supplements may be prescribed for patients with severe anemia and, when necessary, transfusions given. Good dental care is important.

Nutritional monitoring and support are also important for patients with DEB. Careful surveillance for possible skin cancers should begin on, or about, age 10 in every child with RDEB, and any clinically suspicious lesions should be biopsied. Any proven squamous cell carcinomas should be excised. Patients should then be monitored carefully for the possible appearance of new cancers, as well as for local recurrence or the spread of previously treated lesions. .

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, in the main, contact:
www.centerwatch.com.

References

TEXTBOOKS
Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:665.

Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:1261.

Kasper, DL, Fauci AS, Longo DL, et al., eds. Harrison’s Principles of Internal Medicine. 16th ed. McGraw-Hill Companies. New York, NY; 2005:182, 184.

RECENT REVIEW ARTICLES
Bennett M, Kertesz T, Yeung P. Hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss and tinnitus: a systematic review of randomized controlled trials. J Laryngo Otol. 2005;119:791-98.

Smith PF, Darlington CL. Drug treatment for subjective tinnitus: serendipitous discovery versus rational drug design. Curr Opin Investig Drugs. 2005;6:712-16.

Lockwood AH. Tinnitus. Neurol Clin. 2005;23:893-900.

Hannan SA, Sami F, Wareing MJ. BMJ. 2005;330:237.

Waddell A. Tinnitus. Clin Evid. 2004 Jun;(11):718-28. Update in: Clin Evid. 2004 Dec;(12):798-807.

FROM THE INTERNET
Tinnitus. MedlinePlus. Last updated and reviewed: 28 April 2006. 2pp.
www.nlm.nih.gov/medlineplus/tinnitus.html

Severe Chronic Neutropenia-Family factsheets-GOSH and ICH
www.ich.ucl.ac.uk/factsheets/families/F010206/index.html

What is Neutropenia? Neutropenia Support Association. nd. 5pp.
www.neutropenia.ca/about/index.html