eMedicine Specialties > Ophthalmology > Connective Tissue Disorders

Pseudoxanthoma Elasticum

Author: Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute, The Institute for Family Health; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine
Coauthor(s): Diego Calonje, MD, Consulting Staff, Department of Ophthalmology, Private Practice; Sherif M El-Harazi, MD, MPH, Consulting Staff, Department of Ophthalmology, Sherif El-Harazi, MD
Contributor Information and Disclosures

Updated: Nov 18, 2008

Introduction

Background

Pseudoxanthoma elasticum (PXE) is an inherited systemic disease characterized by changes in the elastic tissue of the skin. Pseudoxanthoma elasticum mainly affects the skin, eyes, heart, and gastrointestinal (GI) system.

The cutaneous and ocular findings of pseudoxanthoma elasticum are referred to as Grönblad-Strandberg syndrome. The cutaneous changes in pseudoxanthoma elasticum are distributed in the intertriginous areas of the body, such as the flexural regions of the extremities, in the folds of the skin at the sides of the neck, the cubital and popliteal fossa, the axilla, in the creases of the groin, and periumbilical area. Typical lesions are described as yellow waxy papules associated with loose and thickened skin. Pseudoxanthoma elasticum may be autosomal dominant or autosomal recessive.

Other systemic findings in pseudoxanthoma elasticum include intracranial aneurysms, claudication, hypertension, cerebrovascular accidents, cerebral ischemia, myocardial infarction, and GI hemorrhage.

Pathophysiology

The lesions in pseudoxanthoma elasticum are characterized by increased amounts of elastic tissue that have the tendency to become calcified. The controversy has focused on the nature of the elastic tissue and whether the elastic tissue is abnormal from the time of synthesis or normal from the outset with subsequent degeneration.

The reason why elastic fibers become calcified in pseudoxanthoma elasticum remains unknown. Investigators have found polyanions within elastic fibers in both clinically affected and nonaffected dermis by using histochemical and electron microscopy techniques. This polyanionic material may explain the increased affinity of elastic fibers for calcium and may be a factor in the pathogenesis of the disease.

Frequency

United States

The reported prevalence of pseudoxanthoma elasticum is 1 in 160,000 births.

Mortality/Morbidity

Patients with pseudoxanthoma elasticum are at risk for loss of central vision, subarachnoid hemorrhage, severe GI hemorrhage, chronic peripheral occlusive disease, and cerebrovascular insufficiency. Subarachnoid hemorrhage has been a major cause of death.

Sex

Females are affected with pseudoxanthoma elasticum twice as often as males.

Age

Patients with pseudoxanthoma elasticum usually are diagnosed in the third to fourth decades of life.

Clinical

History

The syndrome of pseudoxanthoma elasticum is a disorder of connective tissue characterized by multisystem involvement. Clinically, involvement of the eyes, skin, central nervous system, heart, and GI system is present, as well as peripheral arterial disease. The stretchable skin, cardiac changes, and choroidal breaks are signs that pseudoxanthoma elasticum shares with variants of Ehlers-Danlos syndrome.

• Eye
  • It has been reported that 87% of patients with pseudoxanthoma elasticum have associated angioid streaks (AS). Angioid streaks appear as cracks deep to the retinal vascular architecture and originate in a ringlike fashion in the peripapillary area and radiate from the optic nerve head coursing in all directions. Angioid streaks are visible as dark red-to-brown bands and are variable in their pigmentation. These brown bands represent breaks in the thickened and calcified Bruch membrane. The Bruch membrane is a collagen- and elastin-containing membrane between the retina and the choroid.
  • Angioid streaks may progress slowly or remain stationary for years. Angioid streaks almost always occur bilaterally.
  • During fluorescein angiography, angioid streaks may show increased fluorescence in the early phase resulting from atrophy of the retinal pigment epithelium overlying an intact choriocapillaris.
  • Defects in the Bruch membrane may predispose to choroidal neovascular ingrowth, which can result in subretinal hemorrhage and ultimately disciform degeneration.
  • Macular involvement with loss of vision usually appears after age 40 years and may be due to retinal pigment epithelium atrophy or choroidal neovascular membrane. Some choroidal neovascular membranes are amenable to treatment with laser photocoagulation (however, visual results are disappointing). Visual field loss secondary to optic disk drusen has been reported in patients with pseudoxanthoma elasticum who have angioid streaks.
  • Peau d'orange has been described as diffuse mottling of the retinal pigment epithelium in an area temporal to the macula in patients with pseudoxanthoma elasticum. This may occur with or without the presence of angioid streaks.
  • Choroidal ruptures and retinal hemorrhages have been reported in patients with pseudoxanthoma elasticum who have minor ocular trauma.
  • Irregularly shaped lesions with variable depigmentation have been observed in the periphery of patients with pseudoxanthoma elasticum. This may represent isolated areas of peripheral dehiscences in the Bruch membrane.
• Skin
  • The characteristic skin changes in pseudoxanthoma elasticum consist of yellow plaques or xanthomalike papules in the flexural areas of the body. This change has been likened to plucked chicken skin. The skin lesions typically are distributed in the intertriginous areas of the body.
  • The most commonly affected areas of the body are as follows: the folds of the skin at the sides of the neck, the flexural regions of the extremities, the axilla, the popliteal and antecubital fossa, the creases of the groin, and the periumbilical region of the abdominal wall.
  • The skin changes usually are noted between the second and fourth decades of life. Late in the disease, the skin frequently becomes thickened and hangs in loose redundant folds.
• Central nervous system
  • Neurologic complications in patients with pseudoxanthoma elasticum have been reported in the literature. These include multiple lacunar infarcts, aneurysms, cerebrovascular insufficiency, subarachnoid and intracerebral hemorrhages, progressive intellectual deterioration, and psychic and mental disturbance.
  • Seizures occur more frequently than in the general population. Subarachnoid hemorrhage is a potential cause of death.
• Cardiovascular findings
  • Cardiovascular involvement in patients with pseudoxanthoma elasticum occurs at an early age, but it is rarely a presenting manifestation.
  • Angina pectoris is a common finding, but myocardial infarction is rare. Aneurysms may occur in any region of the cardiovascular system.
• GI system
  • Upper GI tract hemorrhage can be a serious complication of pseudoxanthoma elasticum. GI hemorrhage has been reported as early as age 6.5 years.
  • GI hemorrhage is a fairly common occurrence and usually occurs early in the course of the disease, when the cutaneous and ocular changes are minimal. It may be life threatening and can occur in as many as 15% of patients. The GI hemorrhage may be secondary to the degeneration of the elastic tissue of arteries of the gastric wall.
• Peripheral arterial system
  • Changes in the vascular system are characterized by premature calcification of the peripheral arteries of the extremities and can be detected by x-ray film.
  • Atherosclerotic changes cause peripheral vascular disease, which results in weak or absent peripheral pulses and claudication of the lower extremities.
  • Hypertension is 3 times more common in patients with this condition than in the general population and occurs at an early age.

Physical

• Yellow xanthomalike plaques are present in the flexural areas of the body. The sides of the neck are the most common sites.
• Angioid streaks are nearly always bilateral and usually appear in the second decade of life. Angioid streaks are brown streaks forming an incomplete ring around the optic nerve and radiating from the disk toward the equator of the eye. Angioid streaks may lead to macular degeneration, disciform scarring, and hemorrhagic maculopathy via the degenerative process of choroidal neovascularization (ie, abnormal choroidal vessels gaining access to the subretinal space through breaks in the Bruch membrane).
• Optic nerve drusen
• Diffuse mottling of the retinal pigment epithelium in the temporal periphery resembles the appearance of the skin of an orange (peau d'orange).
• Peripheral arterial pulsations are absent in both upper and lower extremities.
• Hypertension may result from the involvement of the renal arteries and may occur in the adolescent age group.

Causes

• Pseudoxanthoma elasticum is an inherited systemic disease characterized by abnormal amounts of elastic tissue that have an unusual propensity to become calcified.
• Genetics
  • Autosomal recessive is more common.
  • Autosomal dominant is less common.

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