Pseudoxanthoma Elasticum

Pseudoxanthoma Elasticum (PXE) is a rare genetic disorder that affects the elastic fibers in some tissues of the body. This condition primarily impacts the skin, eyes, and cardiovascular system. Understanding PXE, its symptoms, causes, and treatment options is crucial for managing the condition effectively.

---

Symptoms of Pseudoxanthoma Elasticum

The manifestation of PXE can vary significantly among individuals, but there are common symptoms observed in those affected by this disorder.

Skin Symptoms

One of the earliest and most noticeable symptoms of PXE is the appearance of small, yellowish papules on the skin. These papules typically develop on areas of the body where the skin flexes, such as the neck, armpits, and groin. Over time, these papules may coalesce into larger plaques, causing the skin to take on a cobblestone appearance. The affected skin often becomes lax and redundant, leading to an aged or wrinkled appearance.

Ocular Symptoms

PXE can also have significant effects on the eyes. The hallmark ocular manifestation is the presence of angioid streaks, which are crack-like deformations in Bruch’s membrane of the retina. These streaks can lead to vision problems, including a loss of central vision if the macula is involved. Additionally, individuals with PXE may experience retinal hemorrhages, which can further compromise vision.

Cardiovascular Symptoms

The cardiovascular system is another primary area affected by PXE. The disorder can lead to calcification and fragmentation of elastic fibers in blood vessels. This can result in a variety of complications, including intermittent claudication (pain caused by too little blood flow), hypertension, and an increased risk of myocardial infarction and stroke.

---

Causes of Pseudoxanthoma Elasticum

PXE is caused by mutations in the ABCC6 gene, which provides instructions for making a protein that is thought to play a role in the transport of certain molecules across cell membranes. The exact function of the ABCC6 protein is not fully understood, but it is believed to be involved in the maintenance of elastic fibers.

Genetic Inheritance

PXE is inherited in an autosomal recessive pattern, which means that both copies of the ABCC6 gene in each cell must have mutations for the disorder to be expressed. Individuals with only one mutated copy of the gene are carriers and typically do not exhibit symptoms of the disorder. However, when two carriers have children, there is a 25% chance that their child will inherit both mutated genes and develop PXE.

---

Diagnosis of Pseudoxanthoma Elasticum

Diagnosing PXE involves a combination of clinical evaluation, histopathological examination, and genetic testing.

Clinical Evaluation

A thorough clinical evaluation is the first step in diagnosing PXE. This includes a detailed medical history and a physical examination to look for characteristic skin changes. An ophthalmologic examination is also essential to identify angioid streaks and other retinal abnormalities.

Histopathological Examination

A skin biopsy can provide definitive evidence of PXE. Under the microscope, the affected skin shows fragmented and calcified elastic fibers. Special stains, such as Verhoeff-Van Gieson stain, are used to highlight these changes.

Genetic Testing

Genetic testing can confirm a diagnosis of PXE by identifying mutations in the ABCC6 gene. This is particularly useful in cases where the clinical and histopathological findings are inconclusive. Genetic testing can also be used for carrier screening and prenatal diagnosis in families with a known history of PXE.

---

Pseudoxanthoma Elasticum vs. Other Skin Disorders

It is important to differentiate PXE from other skin disorders that may present with similar features.

Elastosis Perforans Serpiginosa (EPS)

EPS is another disorder involving abnormal elastic fibers, but it is characterized by transepidermal elimination of these fibers. Clinically, EPS presents with keratotic papules arranged in an annular or serpiginous pattern, typically on the neck, face, and arms. Unlike PXE, EPS does not involve systemic manifestations.

Cutis Laxa

Cutis laxa is a group of connective tissue disorders characterized by loose, sagging skin due to defective elastic fibers. Unlike PXE, cutis laxa can present at birth or develop later in life, and it often involves more widespread systemic symptoms, including pulmonary and gastrointestinal involvement.

---

Risk Factors for Pseudoxanthoma Elasticum

The primary risk factor for developing PXE is having a family history of the disorder, due to its genetic nature. However, there are other factors that can influence the severity and progression of the disease.

Genetic Mutations

As mentioned earlier, mutations in the ABCC6 gene are the primary cause of PXE. The specific type and location of these mutations can affect the severity of the disease. Some mutations may result in a milder form of the disorder, while others can lead to more severe manifestations.

Environmental Factors

While PXE is primarily a genetic disorder, certain environmental factors may influence its progression. For example, exposure to sunlight and other sources of ultraviolet radiation can exacerbate skin symptoms. Additionally, lifestyle factors such as smoking and poor diet can have negative effects on cardiovascular health, potentially worsening related complications in individuals with PXE.

---

Treatment Options for Pseudoxanthoma Elasticum

Currently, there is no cure for PXE, but various treatment options can help manage the symptoms and complications associated with the disorder.

Dermatological Treatments

For skin-related symptoms, dermatologists may recommend topical treatments, such as retinoids or other agents that can help improve skin texture. In some cases, surgical interventions may be considered to remove redundant skin or to improve cosmetic appearance.

Ophthalmological Treatments

For ocular symptoms, regular monitoring by an ophthalmologist is crucial. Laser therapy and anti-VEGF (vascular endothelial growth factor) injections can be used to treat retinal hemorrhages and other complications affecting vision.

Cardiovascular Treatments

Managing cardiovascular symptoms involves regular monitoring and treatment of related conditions, such as hypertension and intermittent claudication. Lifestyle modifications, such as a healthy diet and regular exercise, are essential for maintaining cardiovascular health. In some cases, medications or surgical interventions may be necessary to address specific complications.

Genetic Counseling

Genetic counseling is an important aspect of managing PXE. It can provide valuable information for affected individuals and their families regarding the inheritance pattern, risks of transmission to offspring, and options for prenatal diagnosis.