6.1.7 Pseudoxanthoma elasticum

PXE typically affects the elastic fibers of three organ systems: the skin, eyes and cardiovascular system. Cutaneous features include discrete yellowish skin papules, localized in flexural areas, most commonly during the first or second decade of life. The lateral aspects of the neck is usually the first site. Over the time, the papules coalesce to form cobblestone-like plaques, with a ‘plucked chicken skin’ appearance. Other flexural areas affected are the antecubital and popliteal fossae, the wrists, axillae and groin. In the extensive cases, also the non-flexural areas are involved.

Ocular involvement may cause visual impairment, whereas cardiovascular disease may cause claudication, hypertension, renal failure, angina and myocardial infarction.

Cutaneous involvement is characterized by small yellow papules with diameter of up to 10 mm on the nape and sides of the neck and in flexural areas, with coalesce into reticulated plaques as the disease progresses, giving a cobblestone aspect of the skin. The skin subsequently becomes loose and wrinkled. A specific characteristic of PXE is the presence of horizontal and oblique chin creases before age of 30 years. In the advanced disease, significant calcium deposits may present as firm papules or plaques, and may occasionally extrude from the skin in ‘perforating PXE’. Mucosal involvement is most prominent in the inner aspect of the lower lip, manifesting as yellow papules.

The ophthalmologic complications are characterized by angioid streaks, with a prevalence of 100% after the age of 30 years. Angioid streaks results from breaks in the calcified elastic lamina of Bruch’s membrane, which is derived from the retina and the choroid plexus. These fractures can lead to neovascularization from choriocapillaris, and leakage of newly formed vessels may lead to haemorrhage and scarring. These pathologic alterations cause progressive loss of visual activity and, rarely, blindness.

The cardiovascular complications affect primarily mid-sized arteries, in particular the extremities, with a progressive calcification of the elastic media and intima that leads to the formation of atheromatous plaques. Clinical manifestations are intermittent claudication, loss of peripheral pulses, renovascular hypertension, angina pectoris, and myocardial rupture; moreover, cerebral ischemic attacks, mitral valve prolapse and, in the case of the blood vessels calcification of gastric and intestinal mucosa, the rupture and haemorrhage, with a gastrointestinal bleeding, particularly from the stomach.

Elastin is stained with Orcein or Verhoeff-van Gieson reagent, whereas calcium deposits are stained with Von Kossa. The mid-dermal elastic fibers in PXE are short, fragmented, clumped and calcified. In addition, in some PXE patients, splitting, thickening, coiling, calcification and flower-like deformation of cutaneous collagen fibers, are observed.

Differential diagnosis encounters actinic damage for older individuals, but this typically involves the neck, but not axillae or groin. In addition, late-onset focal dermal elastosis, elastoderma, white fibrous papulosis of the neck, perforating periumbilical calcific elastosis and fibroelastolytic diseases of the skin. PXE-like lesions in flexural sites and with similar histological findings have been observed in patients treated with D-penicillamine, in longstanding end-stage renal disease and in L-tryptophan-induced eosinophilia myalgia syndrome. In these cases, ophthalmologic and cardiovascular findings are absent. In addition, PXE-like phenotype is present in up to 20% of patients affected by beta-thalassemia or sickle cell anaemia.

No treatments are currently available. Antioxidant therapy with daily doses of tocopherol acetate and ascorbic acid is important to combat oxidative stress.

Ophthalmologic exams include biannual or annual fundoscopy, prevention of retinal haemorrhage through avoidance of head trauma, and avoidance of smoking. Use of sunglasses is recommended. Bevacizumab (anti-VEGF) is a treatment for stopping choroidal neovascularization.

Cardiovascular prevention is important to avoid the calcification of blood vessels, through regular exercise, weight control, avoidance of smoking and alcohol consumption and treatment of hypercholesterolemia and hypertension. Low-dose acetylsalicylic acid may be indicated to prevent myocardial infarction in some cases. Pentoxifylline, cilostazol and clopidogrel are used in patients with intermittent claudication.

Prenatal diagnosis is essential in families with known mutations.