|
By Kenneth H. Neldner, MD
WHAT IS
PXE?
Pseudoxanthoma elasticum (PXE) is an inherited disorder in
which the elastic fibers, which are normally present in the
skin, the retina of the eyes, and the cardiovascular system,
become slowly calcified, producing characteristic changes in
these three sites.
PXE was first described about 100 years ago. Initially it
was believed to involve only the skin. The skin changes
were thought to be cholesterol deposits called xanthomas
that can occur in the skin of individuals with high blood
cholesterol levels. When it was later learned that the skin
changes were not xanthomas but were due to calcified elastic
fibers, the skin changes were called pseudo (false)
xanthomas. It took another 20 to 30 years of study to link
the eye (retinal) and the cardiovascular changes together
with the skin lesions, as we now know.
PXE occurs in about one in every 50,000 to 75,000 people,
although most physicians who have studied PXE feel that it
is more common. No doubt there are many individuals with
PXE who are never diagnosed because few physicians are
familiar with PXE.
HOW IS
PXE DIAGNOSED?
The first
manifestation of PXE, and the one that almost always makes
the diagnosis possible, is the appearance of highly
characteristic skin lesions. They resemble cobblestone
plaques of skin and most commonly appear first on the sides
of the neck at an average age of 13 years (range of 2 to 25+
years). Soon after, they appear in the folds of the arms,
axillae (under arms), groins and behind the knees. A small
(3 mm) skin biopsy and special stains for calcified elastic
tissue will always be positive and confirm the diagnosis if
there is a question.
Eye (retinal)
involvement usually follows the skin lesions by several
years. By age 20 to 25 years, most individuals will have
angioid streaks (thin cracks in the retina due to calcified
elastic fibers). The streaks cause no trouble on their own
and most patients are unaware that they have angioid
streaks. They are easily diagnosed by a routine retinal
exam with an ophthalmoscope or a retinal photo. The angioid
streaks are important, however, because they are the sites
of future retinal hemorrhages that become common past the
age of 40 to 45 years. The hemorrhages most commonly
involve the central part of the retina called the macula and
result in loss of central sharp vision. The hemorrhages
leave peripheral vision intact and therefore never cause
total blindness.
Cardiovascular problems usually involve the peripheral
arteries and rarely the central vasculature (heart and major
vessels). Aching in the thighs and legs after vigorous
walking is the most common early symptom. This is called
intermittent claudication and is due to calcification of the
elastic fibers in the arteries going to the legs.
Bleeding from the stomach occurs in about 10 to 15% of
people with PXE. It usually begins suddenly with little or
no warning and may be severe enough to require
hospitalization and blood transfusions. In the most severe
cases, surgical intervention may be required to stop the
bleeding.
It is important to emphasize that there is a great deal of
individual variation from one person with PXE to the next.
One may have more extensive skin lesions and mild eye or
cardiovascular involvement, while the next will be the
opposite. Essentially 100% of individuals with PXE will
sooner or later have some involvement of all three sites
(skin, eye, and vessels). It is believed that total life
expectancy is affected little, if any, by PXE.
HOW IS
PXE INHERITED?
The abnormal gene for PXE is passed from generation to
generation usually without the knowledge of the individuals
who pass and receive it. The abnormal PXE gene is most
always passed from one generation to the next by so-called
autosomal recessive (AR) inheritance. In recessive
inheritance, parents who do not have PXE themselves must be
carriers of the PXE gene in order to produce a child
affected with PXE. The children of two parents who are
carriers of the gene have a 25% chance of developing PXE.
Those children who do not develop PXE are likely to be
carriers but will not pass PXE to their children unless they
marry another carrier – in which case the cycle will begin
again.
The children of a parent affected with PXE mated to a parent
who does not carry the gene will all be carriers of the PXE
gene, but none will get PXE. Only if a parent with PXE
inadvertently marries a carrier of PXE will the child have
the possibility of developing PXE.
It is more common to see PXE, or any inherited disorder, in
families where there are cousin marriages because it is more
likely that cousins will carry the same bad genes.
There is a puzzling increased incidence of PXE in women
(about twice as many women as men) which cannot be explained
by ordinary inheritance patterns.
DOES PXE
AFFECT PREGNANCY?
Complications during pregnancy and delivery are always
possible but are essentially no different than in those who
do not have PXE. There are also no specific adverse effects
in the newborn infant. Studies have shown, however, that
women who have had multiple pregnancies do have more adverse
effects from their PXE later in life, compared to those who
have had fewer or no full-term pregnancies.
THE
GENETICS OF PXE
A search for the gene causing PXE was started in 1993 with
the help of many NAPE members who donated blood samples and
family histories. The gene mapping was performed in the
laboratory at Harvard University
by Drs. K. Lindpaintner and B. Struk with Dr. K. Neldner
providing the DNA. This group reported the chromosome
(16p13.1) that carries the abnormal gene in 1997 and the
gene itself (ABC-C6) in 2000. These are major steps in
finding the cause for PXE but finding the gene does not
automatically answer the question. The next step is to find
what this abnormal gene does (or does not do) that allows
the elastic fibers to become calcified. Research is now
being carried on to answer these questions. If and when a
substance is found that causes PXE, the next step will be to
find (or synthesize) a specific antidote that would prevent
the abnormal calcification and cure the disease.
THE MANAGEMENT OF PXE
It is important to keep in mind that with virtually every
hereditary disorder that affects humans, there are both
genetic and environmental factors which influence the
natural course of the condition. We obviously cannot change
our parents or our genes, but we can change our life styles
and reduce the environmental risk factors, thereby improving
our chances for fewer complications and a longer and
healthier life. PXE is no exception. There are many things
that can be done, from childhood on, that will reduce the
long-term risk factors for anyone with PXE. The
recommendations include the following:
- Do not ingest excessive calcium, especially
during childhood and adolescence. For those without PXE,
the recommended amount is 800 to 1000 mg per day. Children
and adolescents with PXE should try to stay in the 600 to
800 mg per day range. Most of our dietary calcium comes
from dairy products. We all need calcium for life, but not
in excessive amounts which may be harmful in PXE.
- Avoid sports at all ages with potential head
trauma or that require very heavy lifting and straining,
such as boxing, soccer, football, rugby, and weight
lifting. Sports with little or no potential head contact,
such as track, swimming, volleyball, bicycling, etc. should
be encouraged. Head trauma and very heavy lifting can
precipitate retinal hemorrhages.
- Maintain a normal weight for your age.
- Develop a regular exercise program and stick
to it!
- Never, never, never start smoking. If you do
use tobacco in any form – stop immediately.
- Check your lipid profile annually, including
cholesterol, triglycerides, HDL-C, LDL-C, and homocysteine.
If any are elevated, try reducing them with diet. If that
doesn’t work, see your doctor for cholesterol-lowering
medications.
- Use aspirin and any of the so-called
non-steroidal anti-inflammatory drugs sparingly, such as
Advilâ,
Motrinâ,
and Ibuprofenâ,
especially if there has been any retinal or stomach
bleeding. These medications thin the blood and make
bleeding easier. Occasional use is acceptable. Tylenolâ
has no such effect on the blood and may be used as needed.
- Any slight vomiting of blood or appearance of
black tarry stools is a medical emergency. See your doctor
immediately.
- Check your blood pressure from time to time.
If elevated, try to control it with diet and exercise. If
this isn’t enough, see your doctor for antihypertension
medications.
- Anyone with mitral valve prolapse (MVP) and a
heart murmur over the mitral valve should take antibiotics
before surgery or dental procedures.
- Get to know a good retinal specialist,
preferably someone with experience in treating PXE. Most
retinal specialists feel that vitamin/mineral supplements of
vitamins A, C, and E plus copper, zinc and selenium (Ocuviteâ)
are helpful in preventing retinal hemorrhages. Get an
Amsler grid from your retinal specialist and use it
regularly. Laser therapy is no longer considered of value
in the treatment of fresh retinal hemorrhages involving the
macula. Several new methods are being studied.
- Avoid vigorous rubbing of your eyes. When
outside in the bright sun for prolonged periods of time,
wear good ultraviolet-protective sunglasses.
- Trental is a
prescription medication that may be helpful for intermittent
claudication (pains in legs after walking). It should also
be stopped if there are signs of bleeding anywhere.
- And, finally, develop a healthy mental
attitude towards your PXE. Try to strike a balance between
excessive concern on one hand and denial or disregard for
preventive measures on the other hand. Learning to cope
with PXE may take many years for young individuals. Don’t
hesitate to ask for help. Join the National Association for
PXE (NAPE) and receive the newsletters that contain
up-to-date information on PXE and provide an opportunity to
ask questions through the mail.
FOR MORE INFORMATION
For more information, contact the National Association for
PXE (NAPE), which is now headquartered in St. Louis,
MO. Those with PXE, family members, and
anyone else interested in PXE are encouraged to join NAPE
and receive our quarterly newsletter. The newsletter
contains your best source of up-to-date information on all
aspects of PXE, plus a question and answer section devoted
to specific questions and problems posed by our members.
There is no charge for the newsletter for members of NAPE;
however, your annual voluntary contributions to NAPE are
more than welcome. Publication of the newsletter represents
a major expense for NAPE. Contributions given in
recognition of members, their families, or anyone else that
you would like to honor will be published in the newsletter.
NATIONAL
ASSOCIATION FOR PXE
(NAPE, Inc.)
Web
site: www.pxenape.org
8760
Manchester Road
St.
Louis, MO
63144, USA
Telephone
1-314-962-0100
Fax: 1-314-962-0100
E-mail:
NAPEStLouis@sbcglobal.net
NAPE, Inc.
is a nonprofit organization.
Contributions are tax deductible
in the
United States.
|
