| Patient Education |
|
Click here for patient education.
|
|
You are in: eMedicine Specialties >
Ophthalmology > CONNECTIVE TISSUE DISORDERS
Pseudoxanthoma Elasticum
Article Last Updated: Jun 18, 2006
AUTHOR AND EDITOR INFORMATION
Section 1 of 9  
Author: Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine
Andrew A Dahl is a member of the following medical societies: Alpha Omega Alpha, American Academy of Ophthalmology, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, and Wilderness Medical Society
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
Editors: Vytautas A Pakainis, MD, Chief of Ophthalmology, Dorn Veterans Administration Medical Center, Professor of Ophthalmology, Ophthalmology, University of South Carolina School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine; Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Author and Editor Disclosure
Synonyms and related keywords:
PXE, Grönblad-Strandberg syndrome
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 GI system. The cutaneous and ocular findings of PXE are referred to as Grönblad-Strandberg syndrome. The cutaneous changes in PXE 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 PXE include intracranial aneurysms, claudication, hypertension, cerebrovascular accidents, cerebral ischemia, myocardial infarction, and GI hemorrhage.
Pathophysiology
The lesions in PXE are characterized by increased amounts of elastic tissue that have the tendency to become calcified. The controversy has focused on both 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 PXE remains unknown. Recently, 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 PXE is 1 in 160,000 births.
Mortality/Morbidity
Patients with PXE 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 twice as often as males.
Age
Patients with PXE usually are diagnosed in the third to fourth decades of life.
History
The syndrome of PXE 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 PXE shares with variants of Ehlers-Danlos syndrome.
- Eye
- It has been reported that 87% of patients with PXE have associated angioid streaks (AS). AS 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. AS 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.
- AS may progress slowly or remain stationary for years. AS almost always occur bilaterally.
- During fluorescein angiography, AS 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 PXE who have AS.
- Peau d'orange has been described as diffuse mottling of the retinal pigment epithelium in an area temporal to the macula in patients with PXE. This may occur with or without the presence of AS.
- Choroidal ruptures and retinal hemorrhages have been reported in patients with PXE who have minor ocular trauma.
- Irregularly shaped lesions with variable depigmentation have been observed in the periphery of patients with PXE. This may represent isolated areas of peripheral dehiscences in the Bruch membrane.
- Skin
- The characteristic skin changes in PXE 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 PXE 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 PXE 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 PXE. 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 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. AS are brown streaks forming an incomplete ring around the optic nerve and radiating from the disk toward the equator of the eye. AS 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).
- Absent peripheral arterial pulsations in both upper and lower extremities.
- Hypertension may result from involvement of the renal arteries and may occur in the adolescent age group.
Causes
- Abnormal amounts of elastic tissue that have unusual propensity to become calcified
- Genetics
- Autosomal recessive is more common.
- Autosomal dominant is less common.
Angioid Streaks
Sickle Cell Disease
Other Problems to be Considered
Paget disease
Ehlers-Danlos syndrome
Lab Studies
- Complete blood count
- Serum electrolytes
- Calcium and phosphorus
- Blood glucose
Procedures
Histologic Findings
Histopathologic studies from skin biopsy show characteristic changes consisting of fragmented elastic fibers, which may be calcified in the deeper layers of the dermis.
Medical Care
Evaluation usually can be conducted on an outpatient basis.
Consultations
- Ophthalmologist
- Neurologist
- Pediatrician
- Internist
- Cardiologist
- Gastroenterologist
Diet
Dietary calcium and phosphorus restriction to minimum daily requirement levels has shown arrest in progression of the disease.
Activity
Eye protection for contact sports or physical activity is indicated. Patients with PXE that are exposed to ocular trauma are predisposed to the development of AS and subsequent visual loss.
Further Outpatient Care
- Monitor hypertension.
- Patients should receive regular eye examinations.
Deterrence/Prevention
- Pregnancy, oral contraceptives, and high calcium and phosphorus intake seem to aggravate all manifestations of PXE.
Complications
- Death
- Recurrent GI hemorrhage
- Blindness
- Myocardial infarction
- Subarachnoid hemorrhage
- Cerebrovascular accidents
Prognosis
- The greatest morbidity in patients affected with PXE and angioid streaks is the loss of central vision that occurs in a high percentage of patients in the fifth to sixth decade of life.
Patient Education
- Inform and educate patients about the multisystem potential complications of the disease.
Medical/Legal Pitfalls
- Failure to recognize associated conditions, such as subarachnoid hemorrhage, upper GI hemorrhage, and decrease in visual acuity, and failure to inform patient of the possibility of these conditions occurring.
Special Concerns
- Careful evaluation of the patient and a detailed dilated eye examination of the ocular fundus aids in the diagnosis because angioid streaks eventually are present in almost all the cases.
- Agarwal A, Patel P, Adkins T. Spectrum of pattern dystrophy in pseudoxanthoma elasticum. Arch Ophthalmol. Jul 2005;123(7):923-8. [Medline].
- Albert DM, et al. Pseudoxanthoma elasticum (PXE)-angioid streaks/systemic associations. In: Principles and Practice of Ophthalmology Clinical Practice. Philadelphia: WB Saunders;1994.
- Chung AK, Gauba V, Ghanchi FD. Photodynamic therapy (PDT) using verteporfin for juxtafoveal choroidal neovascularisation (CNV) in angioid streaks (AS) associated with pseudoxanthoma elasticum: 40 months results. Eye. May 2006;20(5):629-31. [Medline].
- Clarkson JG, Altman RD. Angioid streaks. Surv Ophthalmol. Mar-Apr 1982;26(5):235-46. [Medline].
- Coleman K, Ross MH, Mc Cabe M, et al. Disk drusen and angioid streaks in pseudoxanthoma elasticum. Am J Ophthalmol. Aug 15 1991;112(2):166-70. [Medline].
- Connor PJ Jr, et al. Pseudo-xanthoma elasticum and angioid streaks: a review of 106 cases. Am J Med. 1961;30:537-43.
- Engelman MW, Fliegelman MT. Pseudoxanthoma elasticum. Cutis. Jun 1978;21(6):837-40. [Medline].
- Goodman RM, et al. Pseudoxanthoma elasticum: A clinical and histopathological study. Medicine. 1963;42:297.
- Grand MG, Isserman MJ, Miller CW. Angioid streaks associated with pseudoxanthoma elasticum in a 13-year- old patient. Ophthalmology. Feb 1987;94(2):197-200. [Medline].
- Iqbal A, Alter M, Lee SH. Pseudoxanthoma elasticum: a review of neurological complications. Ann Neurol. Jul 1978;4(1):18-20. [Medline].
- Martinez-Hernandez A, Huffer WE. Pseudoxanthoma elasticum: dermal polyanions and the mineralization of elastic fibers. Lab Invest. Aug 1974;31(2):181-6. [Medline].
- Sawa M, Ober MD, Freund KB. Fundus autofluorescence in patients with pseudoxanthoma elasticum. Ophthalmology. May 2006;113(5):820.e1-2. [Medline].
Pseudoxanthoma Elasticum excerpt Article Last Updated: Jun 18, 2006
|
