Periumbilical Perforating Pseudoxanthoma Elasticum

Periumbilical perforating pseudoxanthoma elasticum (PXE) is a rare genetic disorder that affects the elastic tissue in various parts of the body. It is caused by mutations in the ABCC6 gene, which provides instructions for making a protein that is important for the transport of certain molecules in the body. When this protein is not functioning properly, it can lead to the accumulation of calcium and other minerals in the elastic fibers, causing them to become thickened, fragmented, and calcified.

Here are some key definitions and types of PXE:

1. Periumbilical perforating PXE: This type of PXE is characterized by the development of yellowish papules (small raised bumps) around the belly button. These papules can break down and form a central hole, which can then become infected or inflamed.
2. Ocular PXE: This type of PXE affects the eyes and can cause visual impairment or blindness. It can lead to the accumulation of calcium and other minerals in the Bruch’s membrane, which is a layer of the eye that separates the retina from the blood vessels.
3. Cardiovascular PXE: This type of PXE affects the blood vessels and can lead to cardiovascular problems such as high blood pressure, heart attacks, and strokes. It can cause the elastic fibers in the blood vessels to become stiff and calcified, leading to reduced blood flow and increased risk of cardiovascular events.
4. Cutaneous PXE: This type of PXE affects the skin and can cause yellowish papules to develop on various parts of the body, including the neck, armpits, and groin. These papules can also break down and form central holes.
5. Generalized PXE: This type of PXE affects multiple systems in the body and can cause a wide range of symptoms, including skin and eye problems, cardiovascular problems, and gastrointestinal problems.

Causes

Here are the top causes of PPXE, along with an explanation of each cause:

1. Genetic mutations: PPXE is primarily caused by mutations in the ABCC6 gene. This gene provides instructions for making a protein called multidrug resistance-associated protein 6 (MRP6), which plays a role in transporting certain molecules out of cells. Mutations in the ABCC6 gene can lead to a buildup of calcium and other minerals in the skin, eyes, and blood vessels.
2. Inheritance: PPXE is an autosomal recessive disorder, which means that an individual must inherit two copies of the mutated ABCC6 gene (one from each parent) to develop the condition.
3. Age: PPXE typically presents in early adulthood, with symptoms becoming more severe over time.
4. Gender: PPXE affects both males and females equally.
5. Race: PPXE is more common in individuals of European descent.
6. Family history: Having a family member with PPXE increases an individual’s risk of developing the condition.
7. Environmental factors: While the exact environmental factors that contribute to PPXE are unknown, some studies suggest that exposure to heavy metals or other toxins may play a role.
8. Vitamin K deficiency: Vitamin K is essential for the formation of healthy bones and blood vessels. Some studies have suggested that individuals with PPXE may have a deficiency in vitamin K, which could contribute to the development of the condition.
9. Calcium metabolism: PPXE is associated with abnormal calcium metabolism, which can lead to the buildup of calcium deposits in the skin, eyes, and blood vessels.
10. Liver disease: Some studies have suggested that liver disease may be a risk factor for PPXE, as the liver plays a role in regulating calcium metabolism.
11. Kidney disease: Kidney disease can disrupt calcium metabolism and contribute to the development of PPXE.
12. Obesity: Obesity is a risk factor for a number of health conditions, including PPXE.
13. Smoking: Smoking has been shown to increase the risk of a number of health conditions, including PPXE.
14. Diabetes: Diabetes is associated with abnormal calcium metabolism, which could contribute to the development of PPXE.
15. Hypertension: High blood pressure can contribute to the development of PPXE by damaging blood vessels and disrupting calcium metabolism.
16. Hyperlipidemia: High levels of lipids (such as cholesterol and triglycerides) in the blood can contribute to the development of PPXE.
17. Autoimmune disorders: Some autoimmune disorders (such as rheumatoid arthritis) have been associated with an increased risk of PPXE.
18. Chronic kidney disease: Chronic kidney disease can disrupt calcium metabolism and contribute to the development of PPXE.
19. Hemodialysis: Hemodialysis, a treatment for kidney failure, has been associated with an increased risk of PPXE.
20. Certain medications: Some medications (such as warfarin and phenytoin) have been associated with an increased risk of PPXE.

Symptoms

Symptoms associated with PPXE in detail.

1. Skin lesions: One of the most common symptoms of PPXE is the presence of skin lesions, which can be small, yellowish bumps or larger patches of thickened, discolored skin.
2. Thickened skin: PPXE can cause the skin to become thickened and leathery in texture, particularly in areas that are exposed to sunlight.
3. Yellowish discoloration: The skin affected by PPXE can take on a yellowish or brownish hue, due to the accumulation of calcium deposits.
4. Brittle nails: PPXE can cause the nails to become brittle and prone to splitting or cracking.
5. Eye problems: PPXE can affect the eyes, leading to a range of vision problems, including blurred vision, distorted vision, and loss of peripheral vision.
6. Angina: PPXE can cause chest pain or discomfort, known as angina, due to the buildup of calcium deposits in the coronary arteries.
7. Abnormal heart rhythms: PPXE can cause abnormal heart rhythms, known as arrhythmias, which can be life-threatening in some cases.
8. Hypertension: PPXE can cause high blood pressure, which can increase the risk of heart disease and stroke.
9. Varicose veins: PPXE can cause the veins in the legs to become enlarged and twisted, leading to discomfort and swelling.
10. Gastrointestinal problems: PPXE can cause a range of gastrointestinal problems, including abdominal pain, constipation, and diarrhea.
11. Joint pain: PPXE can cause joint pain, particularly in the fingers, wrists, and knees.
12. Easy bruising: PPXE can make the skin more fragile and prone to bruising, even with minor trauma.
13. Muscle weakness: PPXE can cause muscle weakness, particularly in the legs, which can affect mobility and quality of life.
14. Chronic wounds: PPXE can cause chronic wounds, particularly in areas where the skin is thickened and calcified.
15. Impaired wound healing: PPXE can impair the body’s ability to heal wounds, leading to delayed healing and an increased risk of infection.
16. Fatigue: PPXE can cause fatigue and weakness, particularly in individuals who experience angina or arrhythmias.
17. Sleep disturbances: PPXE can cause sleep disturbances, including insomnia and daytime sleepiness.
18. Mental health problems: PPXE can have a significant impact on mental health, leading to anxiety, depression, and social isolation.
19. Hearing loss: PPXE can cause hearing loss, particularly in individuals who experience hypertension or arrhythmias.
20. Diabetes: PPXE can increase the risk of developing diabetes, particularly in individuals who have a family history of the disease.

Diagnosis

Diagnosis of PPPE involves a combination of clinical evaluation, imaging studies, and genetic testing. Here are 20 common diagnostic tests and procedures used in the diagnosis of PPPE:

1. Physical examination: A doctor will examine the skin around the belly button for the presence of yellowish papules or nodules.
2. Medical history: A doctor will ask questions about the patient’s symptoms, medical history, and family history of PPPE.
3. Skin biopsy: A small piece of skin tissue will be removed and examined under a microscope to confirm the diagnosis of PPPE.
4. Blood tests: A doctor may order blood tests to check for abnormalities in liver function, calcium and phosphate levels, and other markers of bone metabolism.
5. X-ray: An X-ray of the abdomen may be taken to check for the presence of calcifications in the abdominal wall.
6. Ultrasound: An ultrasound of the abdomen may be done to check for the presence of calcifications in the liver, spleen, or other organs.
7. Computed tomography (CT) scan: A CT scan of the abdomen can provide detailed images of the calcifications in the organs and tissues.
8. Magnetic resonance imaging (MRI) scan: An MRI scan can provide detailed images of the calcifications in the organs and tissues.
9. Electrocardiogram (ECG): An ECG measures the electrical activity of the heart and can detect abnormalities in heart rhythm or structure.
10. Echocardiogram: An echocardiogram uses sound waves to create images of the heart and can detect abnormalities in heart structure and function.
11. Holter monitor: A Holter monitor is a portable device that records the heart’s electrical activity over a 24-hour period.
12. Cardiac stress test: A cardiac stress test measures the heart’s response to exercise and can detect abnormalities in heart function.
13. Genetic testing: Genetic testing can confirm the presence of mutations in the ABCC6 gene, which are responsible for PPPE.
14. Skin elastography: Skin elastography is a non-invasive imaging technique that can measure the stiffness of skin and detect abnormalities in elastic fibers.
15. Fluorescence in situ hybridization (FISH): FISH is a genetic test that can detect abnormalities in the number or structure of chromosomes.
16. Polymerase chain reaction (PCR): PCR is a technique that can amplify and detect specific DNA sequences and is used in genetic testing for PPPE.
17. Western blot: Western blot is a laboratory technique used to detect specific proteins in a sample of tissue or blood.
18. Enzyme-linked immunosorbent assay (ELISA): ELISA is a laboratory technique used to detect specific antibodies or proteins in a sample of blood or tissue.
19. Immunohistochemistry (IHC): IHC is a laboratory technique used to detect specific proteins in a sample of tissue.
20. Mass spectrometry: Mass spectrometry is a laboratory technique used to identify and quantify molecules in a sample of tissue or blood.

Treatment

While there is no cure for PPPXE, there are several treatments available to manage the symptoms and improve quality of life for those affected.

1. Topical corticosteroids: These creams or ointments can help reduce inflammation and itching associated with PPPXE lesions.
2. Topical retinoids: These medications can improve the appearance of skin lesions by promoting cell turnover and reducing hyperkeratosis (thickening of the skin).
3. Topical calcipotriene: This vitamin D analogue has been shown to improve skin lesions in PPPXE by regulating calcium metabolism and reducing inflammation.
4. Topical urea: This medication can soften and moisturize thickened skin, which can help reduce pain and itching.
5. Topical antibiotics: These medications can help treat secondary bacterial infections that may occur in PPPXE lesions.
6. Oral antibiotics: In more severe cases of PPPXE, oral antibiotics may be needed to treat bacterial infections.
7. Oral corticosteroids: In cases where PPPXE lesions are widespread and severely inflamed, oral corticosteroids may be prescribed to reduce inflammation and improve symptoms.
8. Systemic retinoids: These medications can improve skin lesions and reduce the risk of developing new lesions by promoting cell turnover and reducing hyperkeratosis.
9. Phototherapy: This treatment uses UV light to reduce inflammation and improve skin lesions in PPPXE.
10. Laser therapy: This treatment can help reduce the appearance of PPPXE lesions by targeting the abnormal elastic fibers in the skin.
11. Cryotherapy: This treatment uses extreme cold to destroy PPPXE lesions and promote healing.
12. Electrosurgery: This treatment uses an electrical current to remove PPPXE lesions and promote healing.
13. Excisional surgery: In severe cases of PPPXE, surgical removal of affected skin may be necessary to relieve pain and improve symptoms.
14. Skin grafting: This surgical procedure involves transplanting healthy skin to areas affected by PPPXE lesions.
15. Microdermabrasion: This treatment uses a special device to exfoliate the skin and improve the appearance of PPPXE lesions.
16. Chemical peels: These treatments use acids to exfoliate the skin and improve the appearance of PPPXE lesions.
17. Moisturizers: Regular use of moisturizers can help prevent dryness and cracking of PPPXE lesions, which can reduce pain and itching.
18. Sun protection: Because PPPXE skin is more susceptible to damage from UV radiation, it is important to protect affected areas from the sun by wearing protective clothing and sunscreen.
19. Diet and lifestyle changes: Some studies have suggested that a diet rich in antioxidants and low in calcium and vitamin D may help reduce the severity of PPPXE symptoms. Exercise and stress management techniques may also be beneficial.
20. Genetic counseling: Because PPPXE is a genetic disorder, individuals with a family history of the condition may benefit from genetic counseling to understand their risk of developing PPPXE or passing the condition on to their children.

While there is no cure for PPPXE, there are many treatments available to manage symptoms and improve quality of life for those affected. These treatments range from topical and oral medications to surgical procedures and lifestyle changes. By working closely with a healthcare provider, individuals with PPPXE can develop a personalized treatment plan that addresses their unique needs and goals.