Pseudoxanthoma Elasticum: PXE Update

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By Kenneth H. Neldner, MD
(earlier version appeared in July 2002 PXE Awareness)

What is PXE?

Pseudoxanthoma elasticum (PXE) is an inherited disorder in which the elastic fibers normally present in the skin, 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 occur in the skin of individuals with high blood cholesterol levels. When it was 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 (retina) 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 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). Later they appear in the folds of the arms, axillae (under arms), groin and behind the knees. A small (3mm) skin biopsy and special stains for calcified elastic tissue will confirm the diagnosis.

Eye (retina) 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 retina exam by 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 do not 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 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 through autosomal recessive 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 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 abnormal genes.

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 also are no specific adverse affects 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 a 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 were major steps in finding the cause of PXE, but finding the gene does not automatically answer the question. Steps to find what this abnormal gene does (or does not do) that allows elastic fiber calcification is being conducted in labs around the globe. Recent reports indicate interference in vitamin K assimilation may be a primary cause. NAPE is involved in a study of vitamin K supplementation in PXE affected individuals.

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 environmental risk factors, thereby improving our chances for fewer complications and a longer and healthier life. There are many things that can be done from childhood on that will reduce the long-term risk factors for anyone with PXE. Recommendations include the following:

  • Eat a well-balanced diet rich in fruits, vegetables and grains, with less emphasis on red meats. Chicken, fish and dairy products, such as suggested in the often cited Mediterranean Diet, provide a good guide for an overall healthy life. Today doctors encourage consumption of the Daily Recommended Allowance of calcium according to age and gender. NAPE's quarterly newsletter, PXE Awareness, provides up-to-date articles on nutrition with food sources.

  • 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 (Advil®, Motrin® and ibuprofe), especially if there has been any retinal or stomach bleeding. These medications thin the blood and make bleeding easier. Occasional use is acceptable. Tylenol® has no such effect on the blood and may be used. Be sure to follow dosing instructions for all medications. Tell your doctor what medications you use each year at your annual checkup.

  • Any slight vomiting of blood or appearance of black tarry stool 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 retina specialist, preferably someone with experience in treating PXE. Most retina specialists feel that vitamin/mineral supplements of vitamins A, C and E plus copper, zinc and selenium (for example, Ocuvite®) are helpful in preventing retina hemorrhages involving the macula. Retina hemorrhages in PXE currently are treated with much success with injections of Avastin or Lucentis into the eye. Repeated injections are usually required with the result that vision is saved for many PXE patients.

  • Avoid vigorous rubbing of your eyes.

  • Trental® is a prescription medication that may be helpful for intermittent claudication (pain in legs after walking). It should be stopped if there are signs of bleeding anywhere.

  • And, finally, develop a healthy mental attitude towards your PXE. 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 years for some individuals. Don't hesitate to ask for help. Join the National Association for PXE (NAPE). Check our website (www.napxe.org) and receive newsletters which contain up-to-date information on PXE. Ask questions by email, telephone or regular mail service.

For more information

For more information, contact the National Association for PXE (NAPE), located in St. Louis, MO. Those with PXE, family members and anyone else interested in PXE are encouraged to join NAPE. Contributions to NAPE are welcome as they support our newsletter, website and telephone counseling service.

NATIONAL ASSOCIATION FOR PXE (NAPE, Inc)

Website: www.napxe.org

8760 Manchester Road

St. Louis, MO 63144-2724, USA

Telephone: 1-314-962-0100

Fax: 1-314-962-0100

Email: napestlouis@sbcglobal.net

NAPE, Inc., is a 501(c)3 nonprofit organization. Contributions are tax deductible in the United States.