Pseudoxanthoma elasticum (PXE) is a rare inherited disorder also known as Grönblad-Strandberg syndrome. It primarily affects the skin, eyes, and blood vessels.
What is pseudoxanthoma elasticum?
The condition pseudoxanthoma elasticum is also called elastorrhexis generalista or Grönblad-Strandberg syndrome. It is a hereditary disorder. The elastic fibers of the connective tissue are affected. Grönblad-Strandberg syndrome manifests in the tissues of the skin, blood vessels, cardiovascular system, and gastrointestinal tract. The eyes are also frequently involved. Nationwide, about 1000 people are affected by the disease. However, the course of the disease varies greatly and not every affected person shows all symptoms. In addition, diagnosis is often difficult, so scientists assume a high number of undiagnosed PXE cases.
Causes
Pseudoxanthoma elasticum is inherited in an autosomal recessive manner. Thus, the defective allele must be present on both homologous chromosomes for the disease to occur. The mutation is found on chromosome 16, where it affects a so-called transmembrane ATP-binding transporter. Due to this gene defect, calcium is increasingly deposited in the elastic fibers of the connective tissue. This causes the fibers to become brittle and break into short pieces. The resulting changes are usually first visible on the neck. However, the disease progresses slowly, so that later the entire body may be affected.
Symptoms, complaints, and signs
Initial symptoms of Grönblad-Strandberg syndrome usually appear on the neck, in the elbows, on the trunk, and in the region around the belly button. However, the armpits, flexor sides of large joints, groin, popliteal fossa, rectum, or vagina may also be affected. The skin lesions are usually symmetrically arranged and indistinctly demarcated. The skin surface is yellowish in color and nodular. Prominent skin folds develop. These are mainly visible when the skin is stretched. Yellowish skin lesions also develop on the oral mucosa. Since the elastic fibers of the connective tissue are affected in the disease, the manifestations are also found on the arteries of the elastic type. Especially the large arteries belong to this type. Arteriosclerosis appears in the patients at a very early stage. There is a risk of massive bleeding in the gastrointestinal tract, lungs, urogenital area, brain and heart. However, the calcifications do not only make the arteries porous, they also narrow them. Narrowing affects not only the large arteries, but all arterial blood vessels in the body. Narrowing of the leg arteries causes peripheral arterial occlusive disease with pain when walking or even pain at rest. Patients with pseudoxanthoma elasticum are also significantly more likely to suffer from hypertension than healthy individuals. Ocular funduscopy reveals dark stripes around the optic disc. These stripe-like changes are also called android streaks. They are probably the result of bleeding. As the disease progresses, retinal hemorrhages occur with increasing frequency. Between the ages of 30 and 40, the vision of those with the disease deteriorates significantly. This process may continue until blindness occurs.
Diagnosis and course of the disease
Because the disease is very rare, few physicians think of PXE when the first skin symptoms appear. However, if a suspicion exists, a skin biopsy is usually performed. On histopathology, the extracted elastic connective tissue appears scaly and fragmented. Calcium salts are found between the normal collagenous fibers. However, an unequivocal diagnosis is not always possible on the basis of the skin preparation. Differentially, changes in the area of scars and actinic elastosis must be excluded. Therefore, molecular diagnostics may be necessary. In this case, mutation analysis in the ABCC6 gene can detect the mutation in chromosome 16.
Complications
First and foremost, this disease causes various skin complaints and, most importantly, skin lesions. Those affected suffer from itching or a rash.Especially on the face or other visible parts of the body, these changes can be very unpleasant and lead to inferiority complexes or significantly lowered self-esteem. In many cases, this disease also causes discomfort in the region of the stomach and intestines, so that those affected suffer from bleeding in the stomach. High blood pressure or anemia may also develop as a result of this disease. Furthermore, patients also suffer from visual complaints, which can occur relatively suddenly and in most cases without any particular reason. In the worst case, this leads to complete blindness of the patient. Unfortunately, a causal treatment of the disease is not possible. In some cases, the symptoms can be limited. Likewise, those affected are dependent on regular examinations in order to avoid further complications. It is also possible that the patient’s life expectancy may be reduced by the disease.
When should you see a doctor?
In the case of pseudoxanthoma elasticum, a doctor must be consulted in any case. Only timely medical treatment can prevent further complications. Since pseudoxanthoma elasticum is a hereditary disease, this disease can only be treated purely symptomatically and not causally. In order to avoid further inheritance, the affected person can undergo genetic counseling if he/she wishes to have children. A doctor should be consulted if the patient suffers from various skin changes. In this case, the skin may turn yellow or brown and have a negative effect on the aesthetics of the affected person. Patients also often suffer from complaints of the lungs or digestive problems. High blood pressure can also be an indication of pseudoxanthoma elasticum and should be examined by a physician if it persists for a long time. Furthermore, reduced vision of the patient is also one of the symptoms of pseudoxanthoma elasticum. The diagnosis of the disease can be made by a general practitioner. However, further treatment requires a visit to a specialist.
Treatment and therapy
To date, there is no therapy that can cure the condition. The genetic cause of the calcium deposits cannot be corrected, so the elastic connective tissue fibers gradually harden more and more. Due to the increased risk of bleeding and blindness, the patient’s health must be checked regularly by a physician. Particular caution is required when medications that increase blood flow must be used. Although these relieve the discomfort caused by vasoconstriction, they can be life-threatening in the event of bleeding. Movements and activities that can cause bleeding should be strictly avoided. Surgery may be necessary for individual symptoms of Grönblad-Strandberg syndrome. Surgery is often the last resort to spare patients blindness. Hopes are pinned on new therapies, such as gene therapy or stem cell research. Many patients with pseudoxanthoma elasticum suffer from pain due to peripheral arterial occlusive disease. Here, a low-cholesterol diet combined with running training can provide relief. Blood circulation in the legs is stimulated and the progression of the disease is prevented or slowed down. Regular running causes the small vessels in the legs to dilate. So-called collaterals are formed. Collaterals are a kind of “bypass road”. Blood can flow through the collaterals, bypassing the narrowed arteries in the leg.
Prevention
Pseudoxanthoma elasticum is a hereditary disease. There are no known preventive measures. If the disease is suspected, a physician should be consulted as soon as possible. The disease is not curable, but with early therapy, the course of the disease can be slowed. Late consequences such as blindness or diabetes can possibly be prevented in this way.
Aftercare
Pseudoxanthoma elasticum requires specific follow-up care to avoid secondary diseases that may result from pseudoxanthoma elasticum. The prevention of blindness is crucial in this regard. For this purpose, regular examinations of the fundus of the eye by an ophthalmologist should be performed. The ophthalmologist can detect hemorrhages in the retina at an early stage and take countermeasures to prevent blindness.Furthermore, the use of blood-thinning medications (Macumar) should be avoided in any case, as this greatly increases the risk of bleeding throughout the body. Instead, especially if there is bleeding in the stool or hemorrhage in the retina, it may be more helpful to take medications that thicken the blood. Additionally, a diet rich in vitamin K (green vegetables) may be helpful in reducing the bleeding tendency that occurs as a result of pseudoxanthoma elasticum. In addition, regular examinations of the lungs, heart, and vessels, as well as the brain, must be performed to detect and treat any hemorrhage that occurs, any developing atherosclerosis, and any pulmonary embolism at an early stage. This takes place with imaging procedures (MRI, CT, X-ray, ultrasound). Existing high blood pressure must also be treated with medication, as this increases the risk of vascular disease. In addition, patients should refrain from smoking and alcohol consumption in order to keep the vascular burden as low as possible. In addition, exercise can prevent atherosclerosis.
Here’s what you can do yourself
Pseudoxanthoma elasticum is a very rare genetic connective tissue disease that cannot be cured. However, it is possible to slow down individual disease processes through self-help. The skin changes lead to cosmetic problems in particular. Thus, the development of the unsightly skin folds can be delayed by self-help measures. Above all, the patient should reduce the exposure of the skin to light by refraining from solarium visits, beach visits or the use of sun creams. Furthermore, smoking should be avoided and both severe overweight and extreme underweight should be avoided. Physical training and a balanced diet also counteract rapid skin changes. What cosmetic options are available for concealing skin wrinkles can be exchanged in self-help groups. Moderate exercise and a reduction in body weight also have a positive effect on the cardiovascular system. Eye functions should be examined regularly by a doctor to avoid possible sudden deterioration of vision or even blindness. Depending on the individual findings, the rules of conduct can be discussed with the doctor in each individual case. However, the basic rule is that patients should exercise moderately, eat a balanced diet and strictly refrain from smoking. It is also important for patients to visit their doctor regularly to have their blood pressure, blood lipid levels and eyes examined. Since the disease often also leads to psychological stress, psychological or psychiatric support may be useful.