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Pseudoxanthoma elasticum
Evidence Levels: A Double-blind study B Clinical trial ≥ 20 subjects C Clinical trial < 20 subjects D Series ≥ 5 subjects E Anecdotal case reports
Pseudoxanthoma elasticum (PXE) is a rare, autosomal recessive disorder causing abnormal fragmentation and calcification of the elastic fibers in the skin, retina, and cardiovascular system. The prevalence of PXE in the population is approximately 1:50,000. The primary lesions are small, asymptomatic, yellow papules on the flexural surfaces of the skin. The papules gradually coalesce into plaques, and the skin begins to appear slightly thickened, inelastic, and leather-like. Ophthalmologic complications include retinal angioid streaks, choroidal neovascularization, and subretinal hemorrhages, with resultant scarring causing central vision loss. Cardiovascular complications include narrowing of the cerebral arteries, intracranial hemorrhage, intermittent leg claudication due to peripheral arterial disease, diminished peripheral pulses, hypertension, and angina pectoris. Gastrointestinal bleeding is reported in about 10% of patients, which may also be due to non-PXE–elated factors.
Most patients with PXE are found to harbor mutations in ATP-binding cassette sub-family C member 6 (ABCC6) gene on chromosome 16p13.1, which codes for an ATP-dependent transmembrane transporter. Hundreds of mutations have been identified, but approximately one-third are premature termination mutations. Certain mutations might be more commonly found in Caucasians compared with Asian patients. The differential diagnosis is PXE-like papillary dermal elastolysis (PXE-PDE), also known as white fibrous papulosis of the neck; the clinical history and histopathology can often help confirm the diagnosis of PXE. This distinction is important insofar as PXE can have systemic involvement as noted above.
Management Strategy
Establishing the diagnosis of PXE may be difficult during the early stages of the disorder. The initial clinical signs appear most commonly during the early teenage years in flexural skin sites on the neck, axillae, antecubital fossae, and groin as variably sized patches of slightly thickened, leathery-looking skin. The diagnosis is often missed during these early years. Larger patches gradually develop with age. Angioid streaks in the retina usually appear later, beginning in the late teens or early twenties. Frank retinal hemorrhages begin most commonly in the fifth decade, causing central vision loss. Cardiovascular changes are rarely noted in children, although rare cases have been reported.
A heart-healthy lifestyle, including a low-cholesterol diet, aerobic exercises, and avoidance of smoking, should be encouraged. Because of the bleeding diathesis, patients should be advised to avoid aspirin and other blood thinners unless essential, as well as contact sports and other activities that increase the risk of eye trauma. There is some evidence that increased dietary calcium results in more rapid progression of the disease, so patients should be encouraged to avoid calcium supplementation and excessive ingestion of milk products. In contrast, experiments with animal models suggest that diets high in magnesium can inhibit tissue mineralization. An interdisciplinary approach involving dermatologists, retina specialists, and cardiologists is essential. Because this is a rare disease, it is important to provide patients with resources; the following two organizations are good references for patients:
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Pseudoxanthoma Elasticum (PXE) International: https://www.pxe.org
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National Association for Pseudoxanthoma Elasticum (NAPE): https://www.napeusa.com
Specific Investigations
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First-Line Therapies
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The extent of pseudoxanthoma elasticum skin changes is related to cardiovascular complications and visual loss: a cross-sectional study
Navasiolava N, Gnanou M, Douillard M, et al. Br J Dermatol 2019, 180: 207–8.
A retrospective review of 125 patients with PXE illustrated that patients with a higher number of affected skin sites had more severe cardiovascular events (including heart attack or stroke) and/or ophthalmological complications (unilateral or bilateral blindness).
Long-term effectiveness of intravitreal bevacizumab for choroidal neovascularization secondary to angioid streaks in pseudoxanthoma elasticum
Finger RP, Charbel IP, Schmitz-Valckenberg S, et al. Retina 2011; 31: 1268–78.
Intravitreal bevacizumab improved visual acuity, stabilized leakage from active choroidal neovascularizations, and reduced central retinal thickness. There was improvement of visual acuity in early disease and preservation of function in advanced disease. Initiation of therapy as early as possible is important for preservation of vision.
The most severe ocular complication from PXE is choroidal neovascularization, which can lead to blindness if left untreated.
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