Pseudoxanthoma elasticum (PXE): skin, eye and blood vessel effects explained

PiXiE, the UK PXE support organisation, describes PXE as a hereditary disorder that can lead to the normal elastic fibres of the skin, eyes and cardiovascular system gradually becoming calcified, causing characteristic symptoms. The PCDS, a society of dermatologists writing for GPs, uses similar wording: a rare, inherited, multisystem disorder characterised by generalised fragmentation and progressive calcification of elastic tissue predominantly in the dermis, blood vessels and the Bruch membrane of the eye.

Elastic tissue gives skin and blood vessels their stretch and recoil. When it becomes calcified and brittle, the tissues cannot function normally, which explains why a condition that begins in the skin can also affect vision and circulation. The PCDS notes that PXE is associated with considerable morbidity and occasional mortality, which is why monitoring is important even when symptoms are mild.

The PCDS says causative mutations occur in the ABCC6 gene and that there are subtypes, with a slightly different presentation and pattern of inheritance: two inherited as autosomal dominant and three as autosomal recessive. PiXiE explains the more usual recessive pattern: each parent carries one altered copy and typically has no symptoms, and when two carriers have a child there is a one in four chance that the child will be affected.

PiXiE also says that PXE is always a genetic disease, although the pattern of inheritance cannot always be identified in every family. The PCDS recommends that patients and their families should receive genetic counselling, which can be arranged through a GP or specialist referral to clinical genetics.

According to PiXiE, the first manifestation, and the one that almost always makes the diagnosis possible, is the appearance of slightly thickened, cobblestone-like patches of skin, most commonly on the sides of the neck and later in flexural areas such as the underarms, folds of the arms, groins and behind the knees. It says skin changes first appear at an average age of 13 years, with a range from 2 years to about 20 years.

The PCDS describes the lesions as small, 1 to 3 mm, yellowish papules in a linear or reticular pattern that tend to join into larger plaques, and says the skin can become soft, lax and slightly wrinkled, hanging in folds especially in older people. Once the changes appear they usually persist. PiXiE says skin lesions cause no medical problems themselves but can be cosmetically distressing, and that plastic surgery can help in some cases; the PCDS agrees that the appearance of loose skin can be improved by plastic surgery.

A skin biopsy can confirm the diagnosis: the PCDS says the elastic fibres in the mid-dermis are clumped, degenerate, fragmented and swollen, and stain positively for calcium.

The PCDS says that angioid streaks, vascular lesions affecting the retina, are found in most patients with PXE, usually between 20 and 40 years of age, and may lead to progressive visual failure and occasionally blindness. PiXiE says approximately 60% of people with PXE develop eye problems and that many experience loss of some central vision.

The key practical point, according to PiXiE, is that PXE affects the macula, the part of the retina used for detailed central vision, rather than the peripheral vision. It says that anyone with PXE who notices distortion, missing text when reading, flashing lights or lots of floaters should go to eye casualty immediately, because early treatment matters, and that ideally everyone with PXE should be seen by an eye specialist at least annually depending on their sight. It describes tests such as optical coherence tomography (OCT) and fluorescein angiography being used to find the affected area.

It also recommends testing each eye separately with an Amsler grid regularly if you have a problem, and reporting any change from the previous time of checking. Treatment decisions are made by your eye specialist; ask whether they have experience with PXE.

The PCDS says arterial involvement does not usually become clinically apparent until adult life, can involve larger arteries or those of the limbs, and may cause intermittent claudication (leg pain on walking) or hypertension. Rarely, death may result from cerebral haemorrhage, coronary occlusion or massive haemorrhage into the gut.

PiXiE says that calcified arteries can narrow, that it is estimated that approximately one-third of patients with PXE experience intermittent claudication, and that the heart valves may be affected, with mitral valve prolapse the most common abnormality. It stresses that most people with PXE have a life span close to normal, and that heart-healthy living is recommended.

Gastrointestinal bleeding is the other recognised complication. The PCDS says the most common problem is upper gastrointestinal bleeding, particularly from the stomach, with approximately 10% developing bleeding complications. Black stools or vomiting blood need urgent medical assessment.

Diagnosis rests on the characteristic skin findings, a skin biopsy, eye examination for angioid streaks and, where available, genetic testing for ABCC6. The PCDS notes that in most cases serum calcium and phosphate are normal.

The PCDS states that there is no specific treatment. The main aspects of management are the prevention and reduction of complications, and annual ophthalmology and cardiovascular assessments are often recommended. PiXiE offers a lifelong management checklist covering weight control, exercise, avoiding tobacco, blood pressure and cholesterol checks and eye care. Some of the specific advice on its pages, such as dietary calcium targets and supplements, is not described in the PCDS guidance, so discuss any change in diet or supplements with your specialist team before acting on it.

The PCDS adds that PXE probably has no adverse effect on foetal outcome in pregnancy, although approximately 12% of pregnancies are associated with worsening of skin manifestations. Planning a pregnancy is a good moment to ask for genetic counselling and a review by your specialists.

Call 999 or go to A&E for chest pain that does not settle, sudden severe breathlessness, signs of stroke, vomiting blood or passing black stools. Go to an eye casualty or A&E straight away for sudden distortion or loss of vision, new flashing lights or many new floaters, as PiXiE advises.

See a GP for new leg pain on walking, unexplained tiredness with pallor, or changes in your skin that you have not had assessed, especially if there is a family history of PXE.