Pseudoxanthoma Elasticum (PXE)

What happens in PXE

The ABCC6 gene, active mainly in the liver, helps maintain substances in the blood (especially pyrophosphate) that prevent minerals depositing in soft tissues. When both copies are faulty, pyrophosphate levels fall and calcium gradually builds up in elastic fibers, making them brittle and fragmented. Tissues rich in elastic fibers are most affected.

Symptoms and signs

Skin

Usually the first sign, appearing in childhood or the teens:

• small, yellowish, raised bumps (papules) that merge into plaques, giving a "cobblestone" or "plucked chicken skin" appearance
• most often on the sides of the neck, then armpits, elbow creases, groin, back of the knees and around the navel
• skin may become loose and wrinkled in these areas
• similar changes inside the lower lip

Eyes

• angioid streaks: cracks in Bruch's membrane, a layer beneath the retina, seen by eye doctors in most adults with PXE
• peau d'orange: a mottled appearance of the retina, often an early sign
• choroidal neovascularization: abnormal blood vessels grow through the cracks, leak and bleed, causing central vision distortion and loss, often between ages 30 and 50
• the eye is fragile, and minor trauma can cause bleeding

Peripheral vision is preserved.

Blood vessels and heart

• peripheral artery disease: narrowed leg arteries cause calf pain on walking (claudication)
• gastrointestinal bleeding from fragile stomach vessels, uncommon
• high blood pressure, including from kidney artery narrowing
• angina and heart attack in a minority
• stroke, rarely

Diagnosis

• skin biopsy of an affected area, showing fragmented, calcified elastic fibers with special stains
• eye examination for angioid streaks and peau d'orange, with OCT scans
• genetic testing for ABCC6 variants, which confirms the diagnosis and allows family testing
• vascular assessment: ankle-brachial index, blood pressure and, as indicated, imaging
• heart assessment if symptoms or risk factors are present

PXE-like changes can occur with some other conditions, such as beta-thalassemia and sickle cell disease, and GGCX gene variants, which are considered in diagnosis.

Management

There is no treatment that reverses mineral deposits. Care focuses on prevention and early treatment of complications:

Eyes

• daily self-monitoring with an Amsler grid
• regular retinal exams, usually at least every 6 to 12 months
• anti-VEGF injections promptly for choroidal neovascularization, which can preserve vision
• protective eyewear for sports and avoiding contact sports or activities with head impact risk
• low-vision aids when needed

Arteries and heart

• no smoking
• control of blood pressure, cholesterol and blood sugar
• regular walking for claudication, and supervised exercise therapy
• avoid NSAIDs and aspirin unless clearly needed, because of gut bleeding risk, and discuss with your doctor

Skin

Changes are mainly cosmetic. Plastic surgery can remove excess loose skin in some cases.

Other

• some evidence suggests oral pyrophosphate or etidronate may slow mineral buildup. These remain under study
• a normal diet is recommended. Very high calcium supplementation is usually avoided
• pregnancy is generally safe, with monitoring
• genetic counseling for families

Outlook

Most people with PXE have a normal life expectancy. The main impact is loss of central vision in middle age for many, which can be reduced with regular monitoring and early anti-VEGF treatment, and leg artery disease. Severity varies widely, even within families.

Frequently asked questions

What is pseudoxanthoma elasticum?

Pseudoxanthoma elasticum (PXE) is a rare inherited disorder in which calcium and other minerals build up in elastic tissue. It mainly affects the skin, causing yellowish bumps and loose skin, the retina, causing angioid streaks and vision loss, and arteries, causing narrowing.

What causes PXE?

PXE is caused by changes in both copies of the ABCC6 gene, inherited from each parent in an autosomal recessive pattern. This lowers pyrophosphate in the blood, a substance that normally prevents minerals depositing in soft tissues.

How does PXE affect the eyes?

PXE causes angioid streaks, cracks in a layer beneath the retina. Abnormal blood vessels can grow through these cracks, leak and bleed, causing distorted or lost central vision, often in middle age. Anti-VEGF injections can protect vision if started early.

What does PXE skin look like?

The skin has small yellowish bumps that merge into plaques, often described as "plucked chicken skin" or cobblestone-like, most commonly on the sides of the neck, armpits, elbow creases and groin. Over time the skin in these areas may become loose and wrinkled.

Is there a cure for PXE?

There is no cure. Management focuses on regular eye exams and anti-VEGF treatment for vision complications, controlling cardiovascular risk factors, exercise for leg artery disease, and avoiding eye trauma. Research into treatments that restore pyrophosphate is ongoing.