Pseudoxanthoma elasticum

Pseudoxanthoma elasticum (PXE) is a rare, hereditary disorder in which the skin, eyes, and vascular system can be affected. In PXE, there is accelerated calcification of the vascular wall, leading to the development of vascular disease, often at a young age.

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Symptoms uitklapper, klik om te openen

Skin

Skin abnormalities are sometimes the first indication that a person has PXE. Small bumps (pseudoxanthomas) appear in the neck region, and later also in other places where the skin moves a lot, such as the armpits, elbow creases, and groin. At a later stage, loose skin folds may develop.

Eyes

Most patients develop fracture lines in the retina of the eye. These usually do not yet affect vision, but sometimes patients experience wobbly lines in diamond patterns. Small blood vessels can grow through these fractures and may start to bleed. Especially if this occurs in the macula, the area where central vision is located, the patient loses part of their vision. PXE usually does not lead to total blindness, but often does lead to social blindness due to the major consequences for social life.

Blood vessels

Typical symptoms caused by vascular problems in PXE include intermittent claudication. With intermittent claudication, pain develops in the legs and/or buttocks when walking, which subsides after resting for a while. Additionally, nocturnal leg cramps may occur, which decrease after letting the legs hang down or walking around for a bit. Furthermore, cardiac complaints (chest pain), stomach bleeding, and TIAs and/or strokes may occur.

Causes uitklapper, klik om te openen

PXE is caused by a hereditary defect in the ABCC6 gene. Dozens of mutations in this gene are now known that can cause the disease. PXE is a recessive disease, which means that two defects must be present in the genetic material to develop the disease. Children of PXE patients are usually only carriers and can only have the disease if their father or mother, who does not have PXE, is also a carrier. The chance of this happening is very small.

Because the ABCC6 gene does not function properly, the substance pyrophosphate is produced in insufficient quantities. Pyrophosphate is a natural inhibitor of (vascular) calcification, which under normal circumstances prevents us from developing severe calcifications of various tissues at a young age. In particular, elastic fibers of the skin, Bruch's membrane in the retina of the eye, and the muscle layer of the vascular wall (media) are susceptible to these calcifications. The result is typical skin abnormalities (pseudoxanthomas: ‘plucked chicken skin’), progressive decline in vision, and vascular abnormalities primarily in the legs, but also in the heart and brain.

There is a striking difference in the manifestation of PXE between patients, even with the same genetic abnormalities. Sometimes patients have pronounced eye abnormalities but hardly any skin or vascular abnormalities, and sometimes there are pronounced vascular abnormalities but hardly any eye or skin abnormalities. It is strongly suspected that environmental factors (diet?) play a role in the different manifestations of PXE. Currently, there is no treatment for PXE, but research is underway to determine whether so-called bisphosphonates are an effective treatment to slow down the disease.

Examination and diagnosis uitklapper, klik om te openen

At the National Expertise Center for PXE (LEP), patients undergo all necessary examinations in a single day to obtain the best possible picture of the (potential) involvement of the eyes, blood vessels, and skin. Patients are routinely seen by a combined internist-vascular physician and ophthalmologist. The specialist reviews your medical history, asks about specific symptoms and medication use, and performs a thorough physical examination. 

The additional examinations being performed are:

• Skin photos
• Blood tests, including possible genetic testing
• Running test
• Vascular stiffness measurements
• Vessel thickness measurements
• Fundoscopy and photography of the eye
• Autofluorescence examination of the eye
• Optical coherence tomography (OCT) of the eye

Treatment uitklapper, klik om te openen

Currently, there is no treatment for PXE. Until an effective treatment is found, close monitoring of the eyes and blood vessels in particular is crucial. Impending hemorrhages in the eye can be treated with eye injections of VEGF inhibitors. In this procedure, the ophthalmologist will inject a medication at the site of the (impending) bleeding that inhibits neovascularization. The aim is to preserve vision for as long as possible.

Furthermore, risk factors for cardiovascular disease (blood pressure, cholesterol, glucose, weight, smoking) will be assessed and treated where necessary to prevent further deterioration of vascular abnormalities.

Scientific research

TEMP-PREVENT: Inhibition of systemic calcifications in young patients with pseudoxanthoma elasticum (PXE)

At the UMC Utrecht uitklapper, klik om te openen

UMC Utrecht houses the National Expertise Center for PXE (LEP). Within this center, a multidisciplinary team of internist-vascular physicians, ophthalmologists, radiologists, a vascular surgeon, a clinical geneticist, and a dermatologist collaborates. Thanks to this unique collaboration, patients can access all necessary experts regarding this rare disease within a single center. Patients undergo all necessary examinations in a single day to obtain the best possible picture of the (potential) damage to the eyes, blood vessels, and skin. Depending on the findings, patients will receive tailored (preventive) treatments.

In addition, the LEP further aims to initiate scientific research to improve the diagnosis and treatment of PXE patients.

More information

What you can do yourself

It is important to live and eat as healthily as possible to prevent (extra) strain on the blood vessels.

On the website of the Heart Foundation There are many tips. For example, there is information on how to eat less salt, how to maintain a healthy weight, how to ensure a good balance between exercise and rest, and how to eat healthier. Your healthcare provider can also help you adopt a healthy lifestyle.

Emotional consequences

The support of a partner, a friend, or another loved one is important in daily life. Ask them to accompany you to your visits with the specialists. Together, you hear more than on your own. 

Receiving a PXE diagnosis often has a major impact, especially on young people (and their parents). The specialists at the National Expertise Centre for PXE have experience with this and will address this in detail where necessary.

Relevant links

• For patients with PXE, there is the patient association PXE NetherlandsYou can find more background information about the disease on the website. 
• More information about the TEMP StudyThe largest clinical study among PXE patients.

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What is associated with this clinical picture

• Vascular Medicine Outpatient Clinic

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