Categories
Integumentary system Ocular System ORGAN SYSTEMS

Pseudoxanthoma elasticum (PXE)

Genetic metabolic disease (lack of functional ABCC6 protein) in which dystrophic calcification leads to cutaneous, ocular, cardiovascular and other manifestations

Genetic metabolic disease (lack of functional ABCC6 protein) in which dystrophic calcification leads to cutaneous, ocular, cardiovascular and other manifestations.

  • Autosomal recessive inheritance
(a) Characteristic skin lesions on the predilection site on the neck, with yellowish papules coalescing into a plaque of inelastic and leathery skin. (b) Presence of angioid streaks. (c) Mineralization of the aortic valve revealed by echocardiography in a 6-year old patient and with PXE-like skin findings and cardiovascular involvement due to mutations in the ABCC6 gene | Guo H, Li Q, Chou DW, et al. Atorvastatin counteracts aberrant soft tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6−/−) J Mol Med (Berl) 2013;91:1177–84.

History:

The term “pseudoxanthoma elasticum” was coined by the French dermatologist Ferdinand-Jean Darier in 1896, by reference to the yellowish tone of skin features (seen in true cases of xanthoma) and the lax aspect of the skin at flexural surfaces. Darier also observed abnormal histological features of the skin. However, skin plaques in what was probably PXE were first described by Rigal in 1881. The link between retinal angioid streaks and skin features in PXE was reported by Grönblad and by Strandberg in 1929, and PXE is occasionally referred to as Grönblad-Strandberg syndrome.

Clinical features

Cutaneous manifestations:

  • Characteristic skin changes:
    1. Small yellow papules ≤ 10 mm on nape and sides of neck and in flexural areas
    2. Coalesce into reticulated plaques, giving a cobblestone aspect
    3. Skin subsequently becomes loose and wrinkled

Ophthalmological manifestations:

M/serious, since they can lead to blindness in late-stage disease
  • Angioid streaks in retina (reflect lesions in Bruch’s membrane – the innermost, elastic layer of the choroid)
    • Calcification of Bruch’s membrane → Choroidal neovascularization (M/critical clinical change) → Hemorrhage, scarring, loss of central vision and thus blindness
  • Blue sclera
  • Optic nerve head drusen
  • Peau d’orange retina
Characteristic ophthalmological feature of PXE: angioid streaks on the fundus | Germain D. P. (2017). Pseudoxanthoma elasticum. Orphanet journal of rare diseases, 12(1), 85. https://doi.org/10.1186/s13023-017-0639-8

Vascular and systemic manifestations:

Usually become apparent years after the onset of skin and ocular changes
  • Intermittent claudication (in both lower and upper limbs)
  • Peripheral artery disease
  • Increased risk of:
    • Aneurysms
    • Stroke
    • Transient ischemic attack (TIA)
    • Stenosis of medium-sized arteries (eg. radial and carotid arteries)
    • Stenosis of the aorta

Management

Management of cutaneous manifestations:

  • Antioxidant therapy:
    • Tocopherol acetate
    • Ascorbic acid

Management of ophthalmologic manifestations:

  • Intravitreal treatment: Vascular endothelial growth factor (VEGF) inhibitors (such as bevacizumab) → Stop choroidal neovascularization

Management of vascular and systemic manifestations:

  • Reduction of cardiovascular risk factors through lifestyle changes (smoking cessation, weight loss, daily walking, moderate physical exercise, etc.)
  • Specific management

Leave a Reply

%d