The connective tissues are the structural portions of the body that essentially hold the body cells together. These tissues form a framework or matrix for the body, and are composed of two major structural molecules, collagen and elastin.
There are many different collagen protein types which vary in abundance depending on body area. Elastin is another protein which has the capability of stretching and returning to original length like a spring.
Pseudoxanthoma elasticum (PXE) is a rare disorder of degeneration of the elastic fibers with tiny areas of calcification in the skin, back of the eyes (retinae), and blood vessels.
Interestingly, while elastin is the major component of ligaments (tissues which attach bone to bone), the ligaments are not apparently affected by PXE.
How is pseudoxanthoma elasticum inherited?
PXE is inherited from the parents, either as an autosomal recessive or as an autosomal dominant trait. Identification of the gene responsible for PXE can facilitate the determination of the exact patterns of inheritance.
Pseudoxanthoma elasticum is an inherited disorder of elastin.
Signs & Symptoms
PXE results in a variety of signs and symptoms that vary in their number, type, and severity from person to person. Certain effects of PXE can cause serious medical problems, while others have less impact.
Effects may include: skin changes, changes in the retina of the eye that may result in significant loss of central vision, changes in the cardiovascular system that may involve calcification of arteries and decreased blood flow in the arms and legs, and/or changes in the gastrointestinal system that may lead to bleeding in the stomach or intestines.
At present, there is no way to predict the exact progression of the disorder for a particular individual. Some people have no skin lesions; others have no vision loss.
Many people do not experience gastrointestinal complications or cardiovascular difficulties.
A few have no manifestations of PXE except for a positive skin biopsy or angioid (resembling a blood vessel) streaks in the retina of the eye. The effects of PXE and its rate of progression seem to have no discernible pattern.
Skin: PXE often causes visible changes in the skin. These changes vary from person to person. The earliest changes tend to be in the skin on the sides of one’s neck.
Small lesions may develop. They may resemble a rash or have a “cobblestone” appearance. These lesions in the skin tend to progress slowly and unpredictably from the neck downward. Skin changes have often been reported in young children.
The areas of the body that are most affected are those that bend and flex. The neck, the underarms, the skin on the inside of the elbows, the groin, and the skin behind the knees may be progressively affected, leading to loose folds in these areas.
Lesions may appear on the inside of the lower lip or lining of the rectum or vagina. Some of these effects may be alleviated by reconstructive, or plastic, surgery.
It is possible to have PXE and not have any apparent skin lesions. In some individuals, careful examination of the skin by a dermatologist does not reveal any visible sign of lesions, but a positive biopsy indicates the diagnosis of PXE.
Since the identification of mutations in the ABCC6 transporter gene as the cause of PXE, analysis of blood can be performed in research centers to confirm the presence or absence of mutations.
Eyes: PXE affects the retina of the eye. The first changes, visible only during an ophthalmologic examination, are called “peau d’orange” because the retina begins to resemble the skin of an orange.
This does not affect vision and neither do characteristic irregular streaks, called angioid streaks that develop later.
These streaks occur when mineralization of the highly elastic membrane behind the retina, called Bruch’s membrane, leads to cracking.
Small blood vessels beneath this layer take advantage of these breaks in the membrane and grow through the membrane. This is called neovascularization. Sometimes, these blood vessels leak and bleed. This bleeding results in the loss of central vision.
While people with PXE may lose so much vision that they become legally blind, almost all people with PXE continue to have peripheral vision.
People who have PXE can use a tool called an Amsler grid to monitor their central vision. If there is swelling or bleeding in the center of the retina, this may cause the intersecting lines of the Amsler grid to appear distorted.
A retinal specialist can instruct a patient in the use of an Amsler grid.
Cardiovascular system: Because PXE can cause mineralization and narrowing of blood vessels, affected individuals may experience cramping in the legs when they are walking, due to decreased blood flow.
This decreased flow of blood is called intermittent claudication. Decreased flow of blood to the arms and legs may mean that one’s pulse can no longer be felt in the wrists or feet.
Some clinicians believe that hypertension (high blood pressure) and mitral valve prolapse may be more common among people with PXE than in the general population.
Individuals with PXE should make periodic visits to their physician for monitoring of blood pressure, cholesterol, and pulses in the arms and legs. A heart-healthy lifestyle is recommended, with low-fat foods and plenty of exercise.
Consistent exercise may decrease the effects of PXE on the blood vessels. Maintaining normal weight may also be beneficial. Smoking should be avoided.
Gastrointestinal system: Uncommonly, PXE may cause gastrointestinal bleeding. This is sometimes not recognized immediately and can be life-threatening.
Little is known about the gastrointestinal effects of PXE, except that the bleeding is usually widespread in the stomach and/or intestines. In a few cases, this bleeding is mistaken for ulcers.
A person with PXE experiencing any gastrointestinal difficulty should be sure to tell the attending physician that he or she has PXE.
Some physicians recommend that affected individuals avoid non-steroidal, anti-inflammatory medications, such as aspirin, ibuprofen, and naproxen.
Pregnancy: It is thought that most women with PXE have normal pregnancies and that the incidence of pregnancy-related complications is similar to that of the general population.
However, for some, gastric or intestinal complications have been reported. In general, complications affecting the fetus have not been reported. There are no prenatal tests to determine whether the fetus has PXE.
Estimates of the incidence of PXE range from 1 in 100,000 people to 1 in 25,000. However, the true incidence of PXE is not known in any population.
It is likely that many individuals with PXE have not been diagnosed, particularly people with mild signs of PXE or those whose signs are not typical.
Symptoms of the following disorders may be similar to those of Pseudoxanthoma Elasticum. Comparisons may be useful for a differential diagnosis:
Ehlers-Danlos syndrome is a rare inherited connective tissue disorder.
It is characterized by the ability of affected individuals to flex their bodies beyond the normal range (articular hypermobility), to abnormally stretch their skin (hyperelasticity of the skin), and widespread tissue fragility (i.e., skin, blood vessels, and other tissues can rupture from even minor trauma).
Many forms of Ehlers-Danlos Syndrome are inherited as an autosomal dominant genetic trait, but some forms of the disorder are inherited as either an autosomal recessive or a x-linked recessive genetic trait.
Marfan syndrome is an inherited disorder that affects the connective tissues of the heart and blood vessels (cardiovascular system).
The musculoskeletal system (ligaments and muscles) is also affected. Major symptoms also include unusual height, large hands and feet, and involvement of the lungs and the eyes.
In addition to peudoxanthoma elasticum, other disorders may be characterized by the development of angioid streaks (e.g., Ehlers-Danlos syndrome, sickle cell disease, hemochromatosis, etc.).
There are also additional disorders that may have skin changes similar to those associated with pseudoxanthoma elasticum (e.g., solar elastosis, etc.).
These disorders usually have other physical and microscopic features that may differentiate them from pseudoxanthoma elasticum.
Changes in the skin are usually the earliest sign of PXE and lead to the definitive diagnosis.
Although the signs of PXE and the age of onset vary considerably, many people first notice an unusual appearance of their skin, typically on the sides or back of the neck.
Small bumps, called lesions, may appear. Some individuals have described these as looking like a rash or an unwashed neck. Usually, a small biopsy of a lesion is done to confirm the diagnosis of PXE.
This biopsy requires that a very small piece of skin, the size of a pencil eraser, be taken from the neck, underarm, and/or inside the elbow.
The dermatologist sends this sample to a laboratory where a special stain, called a von Kossa stain, is used to detect calcium in the tissue.
Sometimes, changes in the eye are the first noticeable sign of PXE. Early changes in the eye are visible only during an ophthalmological examination.
Later symptoms can include loss of central vision. Some people are first diagnosed with PXE when they notice distortion of their vision.
What is the treatment for patients with pseudoxanthoma elasticum?
There is no cure for PXE. Treatment of patients with PXE involves monitoring organ function and consequences of the effects of the weakened elastin fibers in the body as well as measures to prevent injury and promote overall health.
For further information about Pseudoxanthoma Elasticum, please visit the following site: PXE International: Pseudoxanthoma Elasticum.