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Acknowledgements
Special thanks to Madeline Weiner and Kari McGrath for the preperation of this
matereal and to the following for their contributions to the manuscript " Living
With Epidermolysis Bullosa" from which much of this material was adapted for the
following text. National Institutes of Health, National Institute of Arthritis
Diabetes and Digestive and Kidney Diseases. Arlene Pessar, R.N., B.S.N.,
Founder, Dystrophic Epidermolysis Bullosa Research Association of America, Inc.,
and to Anne Brown, R.D., M.S., Director of Dietetics, Rockefeller University
Hospital and a group of communications students from Rider College,
Lawrenceville, New Jersey, for their thoughtful review of the manuscript and for
their contributions to the text.
We also acknowledge the help of members of the DebRA Scientific Advisory Board
for their kind revisions for the updated text, Dr. Amy Paller, Dr. Lawrence
Schachner, Dr. Susan B. Mallory, Dr. Jo-David Fine, Dr. Mary K. Spraker, Dr.
Daniel Siegel, Dr. Robert Meirowitz. In cooperation with Dr. Alan R. Shalita,
Dr. Sharon Glick. Special thanks to Dr. Ellen Pfendner Clinical Laboratory
Manager of the DebRA Molecular Diagnostics Laboratory and Dr Alan Moshell, Skin
Disease Program Director, EP, NIAMS for additional articles. Much gratitude to
DebRA UK for their informative booklets about the various types of EB and to
their EB Nurse Specialists for their kindness, care and broad knowledge base of
EB. In addition, we would like to express our appreciation to several EB
patients, family members and care givers for sharing with us their insights into
the special problems people with EB face.
The following information describes a group of genetic blistering diseases of
the skin that are collectively referred to as epidermolysis bullosa or EB. It
has been written for patients, their families and friends, and health
professionals to explain briefly what we know about these disorders. In addition
to outlining various approaches to treatment, this text reviews current research
in EB and related areas-research that ultimately will lead to control and
possibly prevention of these distressing afflictions.
EB Subtypes
Most forms of EB are inherited although it may also rarely arise as an acquired,
autoimmune, bullous disease known as EB Aquisita. Our focus is on the inherited
forms of EB, each of which range from mild to severe and can require major
adjustments in the lifestyle of both the EB patient and his or her family.
There are three main forms of inherited EB: EB Simplex, Junctional EB and
Dystrophic EB. These different subtypes are defined by the depth of blister
location within the skin layers.
Blister formation of EB simplex is within the epidermis. Sometimes EB simplex is
called epidermolytic. Blister formation in Junctional EB is seen at the level of
the lamina lucida within the basement membrane zone. Dystrophic EB or dermolytic
EB is a scarring form of EB which occurs in the deeper tissue at the level the
lamina densa or upper dermis.
In severe EB, blisters are not confined to the outer skin.
They may develop on the soft tissues (mucous membranes) inside the body such as
the linings of the mouth, esophagus, stomach, intestines, lungs, bladder and
genitals. The extent of tissue involvement experienced by an individual is
usually determined by the severity of the disease and the subtype present.
Testing for EB includes the following :
In order to appropriately identify the depth of blister location in the skin, a
skin biopsy must be taken by a dermatologist. This procedure includes numbing an
area and taking a small sample of skin (~4mm) for examination under a
microscope.
Immunofluorescence antigenic mapping and monoclonal antibody studies are
performed to detect the location of the split in the skin and the absence of
proteins (antigens) that are normally present in the basement membrane zone of
the skin. Monoclonal antibodies are used to bind to certain antigens (proteins)
that are normally present in the basement membrane zone of the skin. If specific
antigens or proteins are missing, there will be an absence of staining,
identifying the missing protein and supporting the diagnosis of subtype.
Transmission electron microscopy involves the use of a high powered microscope
to study the sample of skin to identify structural defects.
Upon identification of subtype, Molecular studies (DNA analysis) may be done to
identify the specific genetic mutation and to determine the mode of inheritance
(recessive vs dominant). This is helpful information in regard to future family
planning.
Once the genetic mutation is identified in a family, prenatal diagnosis of
subsequent pregnancies is possible. A sample of the chorionic villi (part of the
outer membrane surrounding the fetus) can be taken in the later part of the
first trimester, or some amniotic fluid can be collected during the second
trimester. The sample can then be sent to the genetic molecular lab, where it
can be matched against the previously identified mutation.
Unfortunately, knowledge of prognosis will depend on the diagnoses of the skin
biopsy and the results of DNA testing. Waiting for these results can be
difficult, so it is helpful to locate measures of support. Support systems such
as family, other parents with children affected by EB and organizations such as
DebRA can help alleviate the stress of certain situations by providing resources
and education to families of affected individuals and their caregivers.
How is Epidermolysis Bullosa Inherited?
Autosomal Dominant Inheritance: An autosomal dominant disorder is one in which
one gene for the condition expresses itself in an individual. A parent with an
autosomal dominant form of EB has a 50:50 chance with each pregnancy of
transmitting the abnormal gene. The chance is the same whether the child is a
boy or a girl, and birth order does not make a difference. A child who does not
inherit the gene for EB from an affected parent will not have the condition and
cannot pass it on. In some instances, neither parent has EB, but the couple has
a child with an autosomal dominant form of EB. In this situation, the condition
has usually been caused by a change, or mutation in the genetic material of the
egg or the sperm. When a new mutation occurs, the affected individual will have
a 50:50 risk of passing the gene on in his/her pregnancies, but his/her parents
will not. They have no increased risk of having a child with EB in subsequent
pregnancies.
Autosomal Recessive Inheritance: An autosomal recessive disorder is one in which
a recessive (unexpressed) gene for the disorder is passed from each parent and
the two genes are paired together, causing the disorder to be expressed in the
child. If a person has one recessive EB gene paired with a normal gene, the
person is “a carrier", but does not have the disorder. If parents are each
carriers of an autosomal recessive gene, there is a 25 percent chance with each
pregnancy that their children will have the disorder. Again, the sex of the
child and the birth order do not matter. An individual with a recessive form of
EB will be at risk of having an affected child only if he or she has a child
with a carrier or another person with recessive EB.
How is EB Treated?
Because EB involves many systems of the body, parents and health professionals
must take a team approach to the treatment of an EB patient. Intense and total
patient care often must be provided, particularly for young children. The severe
forms of EB require meticulous nursing care which is similar to that given to
burn patients. Much of this care is often provided by the parents; however, the
education of all people who have contact with the patient is essential,
including the primary care physician, the dermatologist, the nurse, the
pediatric dentist, the specialist in gastrointestinal (digestive) diseases, the
dietitian or nutritionist, the plastic surgeon, the psychologist or social
worker, and the genetic counselor, as well as teachers, relatives, baby sitters,
and others.
Although there is no cure for EB, many complications can be lessened or avoided
through early intervention. In all cases, treatment of EB is directed towards
the symptoms and is largely supportive. This care should focus on prevention of
infection, protection of the skin against trauma, attention to nutritional
deficiencies and dietary complications, minimization of deformities and
contractures, and the need for psychological support for the entire family. Many
persons with milder forms have minimal symptoms and may require little or no
treatment.
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