Pseudoxanthoma elasticum

ICD-11

Q82.8

Synonyms

Grönblad-Strandberg syndrome.

Epidemiology

Prevalence: 0.25 to 1 per 100,000 of the general population; slight female predominance. Cutaneous alterations develop during childhood; ocular and cardiovascular complications manifest in the thirdand fourth decade of life.

Definition

Autosomal recessive disorder; elastic fibers of skin, eyes and cardiovascular system become progressively calcified leading to a spectrum of manifestations with a variable phenotype.

Aetiology & Pathogenesis

Various gene-mutations on the short arm of chromosome 16, resulting in impairment of the proper function of elastin and elastic fibers in the mid and deep dermis, the media and the intima of mid-sized arteries, and Bruch’s membrane in the eye, with the clinical and histological typical pathologic alterations.

Signs & Symptoms

Skin: small yellow papules (diameter up to 10 mm) on the nape and sides of the neck and in flexural areas, coalescing into reticulated plaques as the disease progresses, giving a cobblestone aspect. Skin becomes loose and wrinkled.

Mucosal involvement: yellow papules in the inner aspect of the lower lip.

Eyes: angioid streaks, prevalence of 100% after the age of 30 years, results from breaks in the calcified elastic lamina of Bruch’s membrane, which is derived from the retina and the choroid plexus.

Extracutaneous symptoms are associated with complications: loss of visual activity, claudication, hypertension, angina and myocardial infarction.

Localisation

PXE affects the elastic fibers of skin, eyes and cardiovascular system.

Skin: papules cobblestone-like plaques in flexural areas: lateral neck, antecubital and popliteal fossae, wrists, axillae and groin.

Classification

According to sites of involvement: skin, eyes, mucosal, cardiovascular.

Laboratory & other workups

There are no specific or generally laboratory or biochemical assays for PXE.
Clinical examinations, exploration of the vascular vessels with MR angiography and ultrasound, fundus examination of the posterior pole of both eyes. Molecular biology: screening for ABCC6 mutations.

Dermatopathology

The mid-dermal elastic fibers (Verhoeff-van Gieson stain) in PXE are short, fragmented, clumped and calcified (von Kossa stain).

Complications

Systemic involvement: ocular and cardiovascular (see above).

Diagnosis

Clinical and histologic features. Additional workup (see above).

Differential diagnosis

Actinic damage, late-onset focal dermal elastosis, elastoderma, white fibrous papulosis of the neck, perforating periumbilical calcific elastosis and fibroelastolytic diseases of the skin. Treatment with D-penicillamine, longstanding end-stage renal disease, L-tryptophan-induced eosinophilia myalgia syndrome, beta-thalassemia or sickle cell anemia.

Prevention & Therapy

No treatments available. Antioxidant therapy: daily doses of tocopherol acetate and ascorbic acid.

Ophthalmologic exams: biannual or annual fundoscopy, prevention of retinal haemorrhage through avoidance of head trauma, and smoking. Use of sunglasses. Bevacizumab to stop choroidal neovascularization.

Cardiovascular prevention to avoid calcification of blood vessels: regular exercise, weight control, avoidance of smoking and alcohol consumption, treatment of hypercholesterinemia and hypertension. Low-dose of 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 in families with known mutations.

6.1.7 Pseudoxanthoma elasticum