VEXAS syndrome

Overview

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

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.

Causes

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.

Risk factors

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

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.