Pseudoxanthoma Elasticum Workup

Updated: Jun 20, 2022
  • Author: Sheila Z Jalalat, MD; Chief Editor: Dirk M Elston, MD  more...
  • Print

Laboratory Studies

Perform a CBC count to screen for iron deficiency anemia.

Perform a fecal occult blood test to evaluate for GI bleeding.

Perform a urinalysis to screen for urinary tract hemorrhage.

Obtain serum lipid levels. Pseudoxanthoma elasticum (PXE) is associated with precocious atherosclerosis and elevated lipid levels should be treated aggressively.

Obtain serum calcium and phosphate levels. These are usually in the reference range in PXE, but hypercalcemia and hyperphosphatemia have been reported.

In patients with biopsy-confirmed PXE who have no or only one ABCC6 mutation identified, screening for gamma-glutamyl carboxylase (GGCX) and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) mutations is recommended as there could be digenic inheritance. [46]

It has been described that the presence of one or two major eye findings (ie, peau d’orange and/or angioid streaks) in addition to one or two skin findings (ie, classic pseudoxanthomatous skin lesions with or without cutaneous laxity and/or a positive skin biopsy) is diagnostic of PXE. The disease may not be definitively diagnosed if either skin or eye findings are absent, unless two ABCC6 mutations are found with molecular genetic testing. [9]

Although finding two pathogenic ABCC6 mutations is the criterion standard for the diagnosis of classic PXE, approximately 10% of individuals who fulfill diagnostic criteria have no or only one detectable mutation in ABCC6. [9] This lack of sensitivity of genetic testing and potential lack heterogeneity makes the accompanying clinical criteria especially important for accurate diagnosis.


Imaging Studies

Echocardiography is indicated in pseudoxanthoma elasticum (PXE) patients who have a murmur of mitral valve insufficiency, anginal symptoms, or a personal or family history of coronary artery disease.

CT scanning of the head may be performed if the physical examination shows focal neurologic deficits or other signs of cerebral hemorrhage.

Radiography may show soft tissue or large artery calcification, which may be noted as incidental findings on imaging performed for unrelated purposes.



An ophthalmologic examination, including funduscopy, is essential to detect early signs of retinopathy, angioid streaks, and retinal hemorrhages.

It has been recommended that patient’s with pseudoxanthoma elasticum (PXE) self-monitor their visual acuity with the Amsler grid as the risk for macular choroidal neovascularization increases with age. Additionally, fundus examinations are recommended every 2 years for those younger than 40 years and twice a year for those older than 40 years. [47]

Upper and/or lower endoscopy is indicated if the patient has hematemesis, occult blood in the stools, melena, or frank GI bleeding. Endoscopy allows for treatment as well as diagnosis and is more sensitive than upper GI series and barium enema.

Ankle/brachial blood pressure using Doppler methods is useful in patients experiencing intermittent claudication or in patients with significantly diminished peripheral pulses to ensure adequate tissue perfusion.

Skin biopsy can confirm the diagnosis of PXE and is most accurate when obtained from an area of primary skin changes.


Histologic Findings

On cutaneous hematoxylin-eosin stains, elastic fibers appear basophilic as a result of calcium deposition. The fibers are fragmented, swollen, and clumped in the middle and deep reticular dermis. Collagen fibers are also split and are said to unwind or flower. Similar calcification is noted in the tunica media and intima of the blood vessels. [48] Special stains for calcium deposits (eg, von Kossa) and elastic fibers (eg, Verhoeff van Gieson, Orcein) can confirm the diagnosis. See the images below.

Calcification and clumping of elastic fibers in ps Calcification and clumping of elastic fibers in pseudoxanthoma elasticum.
Aggregates of irregular calcified elastic fibers i Aggregates of irregular calcified elastic fibers in the dermis.
Basophilic clusters in the mid and deep reticular Basophilic clusters in the mid and deep reticular dermis representing calcium deposition within elastic fibers in PXE.