Pathology of Pseudoxanthoma Elasticum - 10 important facts

Pseudoxanthoma elasticum is a rare inherited metabolic disorder. The inheritance pattern of Pseudoxanthoma elasticum is almost always autosomal recessive.

In less than 2% of the families, it may be inherited in an autosomal dominant fashion.

The first clinical description of the disease was done in 1881 by Rigal.

In 1896 Darier adopted the term pseudoxanthoma elasticum after observing typical dermal histopathological alterations of the process.

Pseudoxanthoma elasticum is characterised by pathologic mineralisation of connective tissues, with primary clinical manifestations in the skin, eyes and the cardiovascular system.

Diagnosis of Pseudoxanthoma elasticum is currently based on cutaneous and ocular signs, histopathologic findings, and a patient's family history.

The cause of the lesion lies on mutations in the ABCC6 gene, which lead to reduction or absence of the transmembrane transport ADP dependent protein (MRP6), causing an accumulation of extracellular material and subsequent deposition of calcium and other minerals in the elastic tissue.

The cutaneous lesions:

- These are characterized by yellowish asymptomatic papules of 1-3 mm in diameter.

- Symmetrically distributed in the neck and flexural areas, especially the axillae.

- Same type of mucosal lesions are noted in the oral, genital and gastrointestinal mucosae.

The main ocular changes:

- Presence of angioid streaks visualized by ophthalmoscopy. Angioid streaks represent the calcium deposits in the retina - Bruch's membrane.

- Rupture of vessels, with subsequent neovascularization that is associated with retinal hemorrhages may lead to progressive loss of visual acuity.

The cases of ocular involvement must be monitored by periodical fluorescein angiography and ophthalmoscopy.

The main cardiovascular system changes:

- The calcification of small and medium sized arteries. This results in early atheromatosis. It can present as hypertension, acute myocardial infarction, cerebrovascular accident and peripheral arterial occlusion.

- Involvement of abdominal arteries causes recurrent gastrointestinal hemorrhage.

- There can be brain infarction due to narrowing and occlusion of cerebral arteries and aneurysm formation.

- Intracranial hemorrhage can occur in the absence of aneurysm.

- Peripheral arterial vascular disease can lead to intermittent leg claudication.

The microscopic features are characteristic and reveals fragmented and distorted elastic fibers in the reticular and deep dermis.

- These changes are noted in the Verhoeff–Van Gieson stain (VVG) ,specific for the elastic tissue.

- The calcification of fibers can be clearly identified in stains for calcium, as the Von Kossa.

Pseudoxanthoma elasticum-like change may occur adjacent to a benign adnexal neoplasm. Example: Short, distorted elastic tissue fibers (positive for EVG and Von Kossa stains)-features reminiscent of Pseudoxanthoma elasticum has been reported in a case of hidradenoma.

Sudden death may occur due to coronary atherosclerosis with acute myocardial ischemia, systemic hypertension, mitral valve prolapse, restrictive cardiomyopathy, gastrointestinal hemorrhage, and cerebral ischemia or hemorrhage.