VEXAS Syndrome

What is VEXAS syndrome?

VEXAS syndrome is a rare autoimmune condition that causes inflammation throughout your body.

Autoimmune conditions are the result of your immune system accidentally attacking your body instead of protecting it. Experts don’t know why your immune system turns on you. It’s like it can no longer tell the difference between what’s healthy and what’s not — between what’s you and what’s an invader.

If you have VEXAS syndrome, your immune system attacks tissue throughout your body and causes inflammation and swelling. VEXAS syndrome can affect your:

• Blood.
• Bone marrow.
• Blood vessels.
• Skin.
• Cartilage (especially in your ears and nose).
• Joints.
• Lungs.
• Eyes.
• Testicles.

A genetic mutation causes VEXAS syndrome. Specifically, a mutation happens on the UBA1 gene. The UBA1 gene is supposed to make an enzyme called E1 ubiquitin-activating enzyme (E1 enzyme). E1 enzyme helps your body clean up waste proteins and heal damage inside your cells. If you have VEXAS syndrome, the UBA1 gene produces E1 enzymes that don’t work correctly.

VEXAS syndrome can be fatal if it’s not treated. Healthcare providers will suggest treatments to manage your symptoms.

What does VEXAS syndrome stand for?

The letters in VEXAS syndrome’s name are an acronym for how healthcare providers can identify and diagnose it:

• Vacuoles: Vacuoles are rounded, empty spaces that form in abnormal cells. People with VEXAS syndrome usually have vacuoles in their bone marrow cells.
• E1 enzyme: The ineffective E1 enzyme your cells make when you have a mutated UBA1 gene.
• X-linked: Two chromosomes determine your biological sex. People assigned female at birth have XX chromosomes and people assigned male at birth have XY chromosomes. The mutated UBA1 gene that causes VEXAS syndrome is located on the X chromosome.
• Autoinflammation: Autoinflammation is the medical term for the inflammation your immune system causes when it attacks your body.
• Somatic: The mutation that causes VEXAS syndrome is somatic. That means it happens randomly and isn’t passed from biological parents to their children (it’s not hereditary).

How common is VEXAS syndrome?

VEXAS syndrome is very rare. Experts estimate that it affects 1 in every 13,000 people in the U.S.

What are the symptoms of VEXAS syndrome?

The main symptom of VEXAS syndrome is inflammation. Where you experience inflammation causes other symptoms, including:

• Fever.
• Low blood oxygen levels (hypoxemia).
• Skin rashes.
• Swelling.
• Joint pain.
• Cough.
• Shortness of breath (dyspnea).
• Red eye.
• Headaches.
• Swollen testicles (orchitis).

What causes VEXAS syndrome?

A genetic mutation to the UBA1 gene causes VEXAS syndrome. Genetic mutations are changes to your DNA sequence that happen during cell division when your cells make copies of themselves. If part of your DNA sequence is in the wrong place, isn’t complete or is damaged, you might experience symptoms of a genetic condition.

If you have VEXAS syndrome, your UBA1 gene malfunctions and doesn’t produce E1 enzyme like it’s supposed to. E1 enzyme usually acts like a janitor that cleans up damaged or old proteins inside your cells. When you have VEXAS syndrome, the E1 enzyme cleaning crew is understaffed. Eventually, damaged proteins and waste build up inside your cells. This backup triggers your immune system, which sees the excess waste as a threat. But — because there isn’t actually an infection in that area — your immune system attacks and damages healthy tissue, which causes inflammation.

VEXAS syndrome risk factors

Studies have found that men or people assigned male at birth are much more likely to experience VEXAS syndrome. It’s also more common among people older than 50.

What are complications of VEXAS syndrome?

If the inflammation from VEXAS syndrome affects your bone marrow, you can experience bone marrow failure — which can be fatal.

Depending on where the inflammation occurs, having VEXAS syndrome might make you more likely to develop other health conditions, including:

• Leukemia.
• Myocarditis.
• Anemia.
• Dermatitis.
• Chondritis (swollen cartilage).
• Vasculitis.
• Arthritis.
• Deep vein thrombosis (DVT).
• Colitis.

How is VEXAS syndrome diagnosed?

A healthcare provider will diagnose VEXAS syndrome with a physical exam and genetic testing. They’ll examine your symptoms and ask you when you first noticed them.

The only way to confirm if you have VEXAS syndrome is with genetic testing. Your provider will take a sample of your blood, skin, hair or other tissue and send it to a lab. Technicians at the lab will look at your DNA for the UBA1 mutation that causes VEXAS syndrome.

How is VEXAS syndrome treated?

The most common treatments for VEXAS syndrome include:

• Corticosteroids to reduce inflammation.
• Immunosuppressants to slow down your immune system’s response.
• A bone marrow transplant if your bone marrow shows signs of failing. Bone marrow transplants can also help reduce the severity of some autoimmune conditions.

You might need to work with a rheumatologist, a healthcare provider who specializes in treating autoimmune conditions.

Can VEXAS syndrome be prevented?

There’s no way to prevent VEXAS syndrome. The genetic mutation to the UBA1 gene happens randomly without a known cause.

What is the life expectancy of someone with VEXAS syndrome?

Every person is different, and how VEXAS syndrome affects your body will be unique. But VEXAS syndrome can be fatal if it’s not treated. Talk to your healthcare provider about what you can expect and which treatment options will work best for you. Your provider will help you manage your symptoms and can recommend mental health professionals and other support resources.

When should I see my healthcare provider?

Visit a healthcare provider if you experience any symptoms of VEXAS syndrome like fevers, skin rashes or shortness of breath. It can be hard to diagnose VEXAS syndrome right away because it causes so many different symptoms that might not seem connected. But trust your body and talk to a healthcare provider if you’re experiencing symptoms you can’t explain or that aren’t connected to any of your other health conditions.

Visit your provider if you’ve been diagnosed with VEXAS syndrome and you feel like you’re experiencing new or more severe symptoms.

Go to the emergency room if you have a fever above 103°F (39.5°C) longer than two hours after home treatment. Go to the ER or call 911 (or your local emergency services number) if you can’t breathe.

What questions should I ask my healthcare provider?

• Do I have VEXAS syndrome or another condition?
• Will I need genetic testing?
• Which treatments will I need?
• Which symptoms or changes should I watch out for?
• Will VEXAS syndrome be fatal?

A note from Cleveland Clinic

VEXAS syndrome is a rare autoimmune condition that happens when you have a specific genetic mutation. It causes inflammation throughout your body and it can be fatal. Your healthcare provider will help you find treatments that manage your symptoms.

Visit a healthcare provider if you experience any symptoms of VEXAS syndrome. Trust yourself and trust your body. Don’t ignore symptoms like fevers, rashes or shortness of breath.