VEXAS syndrome

VEXAS syndrome is a condition in which the immune system attacks the body by mistake. This is called an autoinflammatory condition. VEXAS syndrome causes swelling and irritation, called inflammation, throughout the body.

VEXAS syndrome is not common. A gene change causes the condition. But the gene change happens after birth, so parents don't pass the change to children. Diagnosis involves genetic testing to look for the changed gene.

VEXAS syndrome stands for the condition's features: vacuoles, E1 enzyme, X-linked, autoinflammation, somatic:

• Vacuoles are empty spaces that form in atypical cells. In VEXAS syndrome, vacuoles form in certain bone marrow cells.
• E1 enzyme is the enzyme affected in cells in people who have the changed gene. The enzyme doesn't work right.
• X-linked refers to the X chromosome, where the changed gene is found.
• Autoinflammation is what happens when the immune system attacks the body.
• Somatic means that the changed gene happens after birth and doesn't pass through families.

Treatment most often involves medicines. Sometimes it involves chemotherapy or a bone marrow transplant. Without treatment, the condition can lead to death.

Symptoms of VEXAS syndrome can affect organs throughout the body. Symptoms may differ from person to person and may include:

• Fever that keeps coming back.
• Tiredness.
• Painful skin rashes.
• Eye redness and irritation.
• Joint pain and swelling.
• Swelling and irritation of one or both testicles, also called orchitis.
• Swelling and irritation of the cartilage in the nose and ears, also called chondritis.
• Coughing and shortness of breath.
• Blood clots.

When to see a doctor

See your healthcare professional if you have any symptoms that trouble you.

The cause of VEXAS syndrome is a changed gene that happens after you're born. The changed gene is called a UBA1 mutation. Experts don't know the cause of this change. The gene doesn't pass through families, called hereditary. So people with the changed gene don't get it from their parents or pass it to their children.

Factors that raise the risk of getting VEXAS syndrome include:

• Sex assigned at birth. The changed gene that causes VEXAS syndrome happens on the X chromosome. People assigned male at birth have only one X chromosome. So a change in this gene affects more people assigned male at birth than it does people assigned female at birth, who have two X chromosomes.

  As a result, people assigned male at birth are more likely to have VEXAS syndrome than are people assigned female at birth.

• Older age. Most people diagnosed with VEXAS syndrome are older than 50.

Complications of VEXAS syndrome may include:

• Infections. These are common complications of VEXAS syndrome. Bacteria, viruses or parasites may cause them. They mainly affect the lungs, skin and urinary tract.

  Taking medicines to lessen the immune system response to treat VEXAS syndrome can raise the risk of infections. Serious infections may raise the risk of death.

• Blood clots. Blood clots can happen in the arms, legs or lungs. Once clots form, they can travel to other parts of the body and cause harm.
• Myelodysplastic syndromes. These are conditions that keep blood cells from forming as they should. The conditions are caused by issues with the spongy matter inside the bones where blood cells form, called bone marrow. Myelodysplastic syndromes can lower blood cell counts.
• Bone marrow failure. This can happen when bone marrow doesn't make enough red blood cells, white blood cells or platelets. Red blood cells carry oxygen through the body, white blood cells fight infection, and platelets help blood to clot. Bone marrow failure may be life-threatening.

VEXAS syndrome may be hard to diagnose because of the range of possible symptoms and because the symptoms can be like those of other conditions that cause swelling and irritation, called inflammation. The only way to confirm a diagnosis of VEXAS syndrome is through genetic testing.

To do genetic testing, a healthcare professional takes a sample of blood or bone marrow and sends it to a lab to look for the changed gene that causes the condition.

Treatment for VEXAS syndrome depends on the symptoms. Treatment most often involves medicines for swelling and irritation, called inflammation, and medicines that lessen the immune system response.

Medicines

• Corticosteroids. Corticosteroid medicines, such as prednisone, ease swelling and irritation, called inflammation, and pain. There can be serious side effects. The risk of side effects rises when taken at high doses over a long time. Side effects may include bone thinning, easy bruising from skin thinning, weight gain, high blood sugar, cataracts and glaucoma, among others.

• Medicines that suppress the immune system. These include medicines such as tocilizumab (Actemra, Tyenne, others). They also include a class of medicines called Janus kinase inhibitors (JAKi), such as ruxolitinib (Jakafi), tofacitinib (Xeljanz) and baricitinib (Olumiant).

  These medicines help keep the immune system from attacking healthy cells. This helps with swelling and irritation while lowering the need for steroid medicines.

• Chemotherapy medicines. For some people, treatment may involve chemotherapy, which uses strong medicines to kill cells.

Bone marrow transplant

Also called a stem cell transplant, this procedure replaces bone marrow that isn't working well with new stem cells to make healthy bone marrow. For VEXAS syndrome, the cells come from a donor. This is called an allogenic transplant.

Bone marrow transplant is a complex procedure. It involves lowering the immune system response with chemotherapy and radiation so that the body can accept the donor cells. Possible complications include infections and failure of the donated stem cells.

For some people who get stem cells from a donor, the donor cells attack the tissues of the people who get them. This is called graft-versus-host disease. Complications of bone marrow transplant can be life-threatening.

A bone marrow transplant isn't for everyone. Age and certain medical conditions may keep you from having one.

Potential future treatments

VEXAS syndrome is a newly identified condition. Researchers keep looking for the best ways to treat it.

You may start by seeing your main healthcare professional, who may send you to a specialist in arthritis and other inflammatory conditions, called a rheumatologist. Or you might see a specialist in blood conditions, called a hematologist.

Here's some information to help you get ready for your appointment.

What you can do

When you make the appointment, ask if there's anything you need to do before you go, such as fasting before certain tests. Make a list of:

• Your symptoms, including any that don't seem linked to the reason for your appointment, and when they began.
• Key personal information, including major stresses, recent life changes and family medical history.
• All medicines, vitamins and other supplements you take, including dosages.
• Questions to ask your healthcare professional.

Take a family member or friend along, if possible, to help you take in the information you get.

For VEXAS syndrome, some basic questions to ask include:

• What's likely causing my symptoms?
• What tests do I need?
• Is my condition likely to last or go away?
• What's the best course of action?
• I have other health conditions. How can I best manage them together?
• Are there restrictions I need to follow?
• Should I see a specialist?
• Are there brochures or fact sheets I can have? What websites do you suggest?

What to expect from your doctor

Your healthcare professional may ask you questions, such as:

• Have your symptoms stayed with you, or do they come and go?
• How bad are your symptoms?
• What, if anything, seems to make your symptoms better?
• What, if anything, seems to make your symptoms worse?