A rare autoimmune disorder in which a genetic change (mutation) negatively affects the ability of the cells to heal themselves is called VEXAS syndrome. It is often diagnosed with genetic testing. Healthcare professionals usually prescribe corticosteroids, immunosuppressants, and bone marrow transplants (sometimes).
Generally, VEXAS syndrome causes inflammation in the body. An autoimmune disorder often occurs when the immune system produces antibodies that mistakenly attack healthy cells instead of foreign invaders, such as bacteria, viruses, and other germs. Furthermore, healthcare providers do not know what causes this syndrome.
Those who develop this condition may have problems with the following structures and organs in the body. For example:
While physicians have identified the abnormal gene that causes VEXAS syndrome, they do not fully understand why this gene mutates. This gene is known as UBA1, and it is required to produce enzymes called E1 ubiquitin-activating enzyme (E1 enzyme). It helps clean the body waste and heal damage inside the cells. In people with this syndrome, E1 enzymes do not work properly. Without treatment, this condition can be fatal.
This syndrome occurs very rarely and affects about 1 in every 13,000 people in the United States.
Name
In addition, the name of this disorder is an acronym for how doctors can identify and diagnose it. For example:
- Vacuoles – These are empty spaces that appear in the abnormal cells. People with VEXAS syndrome usually have these vacuoles in the bone marrow cells.
- E1 enzyme – If E1 enzymes do not work correctly, it may indicate a mutated UBA1 gene.
- X-linked – In normal circumstances, there are two chromosomes that determine biological sex. For instance, females have XX chromosomes and males have XY chromosomes. In most cases, VEXAS syndrome is located on the X chromosome.
- Autoinflammation – This is a medical term for the immune system that attacks healthy cells and causes inflammation.
- Somatic – Genetic changes that cause VEXAS syndrome are not passed from biological parents and occur randomly.
Symptoms
The primary symptom of this syndrome is inflammation. However, you may also experience other symptoms. For example:
- Skin rashes
- Hypoxemia (low oxygen level in the blood)
- Swelling
- Joint pain
- Fever
- Cough
- Dyspnea (shortness of breath)
- Eye redness
- Headaches
- Orchitis (swollen testes)
If you experience any of the previous symptoms, immediately visit a healthcare professional.
Causes
The main cause of VEXAS syndrome is a mutation in the UBA1 gene. In general, genetic mutations are specific changes in part of the DNA that normally contain instructions that tell cells when to grow, multiply, and die. When a part of the DNA is not in the right place, it may lead to an incomplete or damaged DNA. As a result, it causes symptoms of a genetic disorder.
In people with VEXAS syndrome, the UBA1 gene does not work properly, which causes reduced or a lack of E1 enzyme levels. This enzyme is responsible for cleaning damaged or old proteins in the cells. However, if the levels of this enzyme are reduced, it does not work properly. As a result, the immune system produces antibodies that attack waste as a threat, causing damage to healthy cells.
The only known risk factors are sex (men are more likely to develop VEXAS syndrome than women) and age (those who are older than 50 have an increased risk of developing this disorder).
What Are The Possible Complications of VEXAS Syndrome?
People with this condition may also experience some complications, especially if VEXAS syndrome affects the bone marrow. Check below some complications depending on where the inflammation happens:
- Leukemia
- Myocarditis
- Dermatitis
- Chondritis (swollen cartilage)
- Arthritis
- Vasculitis
- Colitis
- Deep vein thrombosis (DVT)
- Anemia
- An increased risk of myelodysplastic syndrome (MDS)
- Thrombocytopenia
- Bone marrow failure
- Permanent damage to organs
This article does not contain a complete list of VEXAS syndrome complications. Moreover, you can consult with your doctor about ways to reduce the risk or prevent previous complications. Unfortunately, there is no way to prevent this syndrome because healthcare providers do not fully understand why it happens.
Diagnosis
Physicians usually begin with a physical examination and questions about the symptoms and medical history. However, the only way to confirm this syndrome is with a genetic test. To perform this test, doctors will take a sample of blood, skin, hair, and other tissue for testing in the laboratory. During this test, physicians will check for the UBA1 mutation that causes VEXAS syndrome.
Treatment
Healthcare professionals usually prescribe different treatments for people with this syndrome. It depends on the severity of the condition, existing health problems, age, and preferences. Check below the most common treatments recommended for people with VEXAS syndrome:
- Immunosuppressants (these medications help reduce the immune system’s response)
- Corticosteroids (this group of medications is often used to lessen inflammation)
- Bone marrow transplants – This is a procedure in which surgeons will take healthy bone marrow from a donor and replace it with your damaged bone marrow. However, this treatment is not an option for everyone. For more details, discuss it with your healthcare professional.
Additionally, in some cases, people need to work with a rheumatologist (a specialist trained in treating autoimmune conditions).
Frequently Asked Questions
What is the life expectancy of someone with VEXAS syndrome?
The life expectancy is often different among people with this syndrome because each body is unique. However, without treatment, this genetic disorder can be fatal.
When should I go to the ER?
Immediately go to the nearest emergency room (ER) or call 911 if any of the following symptoms occur. Examples include:
- High fever (above 103°F or 39.5 °C) for more than 2 hours
- Shortness of breath
- Fatigue (extreme tiredness)
What is the cause of death of VEXAS syndrome?
The primary cause of death is disease progression, especially in people who do not get treatment. Corticosteroids, immunosuppressants, and bone marrow transplants are the most common treatments for people with this syndrome. Ask your healthcare provider if you have additional questions.
