VEXAS syndrome is a hematologic inflammatory condition that primarily affects the bone marrow and blood. The disease, which researchers first identified in late 2020, typically causes symptoms like a painful rash and inflammation in the blood vessels, lungs, joints, and skin.

Research has found that VEXAS syndrome may be more common than previously thought, particularly among men over the age of 50. Although rare, VEXAS syndrome may affect as many as one in 4,269 men and one in 26,238 women, both older than 50, in the U.S. Read on to learn what VEXAS syndrome is, symptoms, treatments, and more.

Gendered Language Disclaimer

The verbiage in this article uses gendered language based on how researchers describe VEXAS syndrome in men in studies. Health recognizes that not everyone assigned male at birth identifies as a man, and not everyone assigned female at birth identifies as a woman. Likewise, not everyone identifies as any one gender. Therefore, anyone assigned male at birth may have a high risk of developing the following VEXAS syndrome symptoms. 

What Does VEXAS Stand For?

VEXAS is an acronym that describes key characteristics of the disease, such as:

• Vacuoles: These are small spaces in your cells that healthcare providers can see in a bone marrow biopsy.
• E1 enzyme: Your cells make this ineffective E1 enzyme if you have VEXAS syndrome.
• X-linked: The gene mutation that causes VEXAS syndrome is on the X chromosome.
• Autoinflammation: This inflammation occurs if your immune system mistakenly targets and attacks your healthy cells.
• Somatic: This is a gene mutation you acquire in your lifetime rather than inheriting.

How Common Is It?

A study published in 2023 found that about one in 13,591 people may have VEXAS syndrome, the disease mainly affecting men older than 50. The study analyzed genetic data from more than 163,000 people, looking for a gene mutation that links to VEXAS syndrome. The researchers identified 11 people with the gene mutation, including two women and nine men. Those people had reported symptoms consistent with VEXAS syndrome.

In 2020, when researchers first identified VEXAS syndrome, the disease was not considered prevalent. Researchers discovered a gene mutation in a group of people who could not get a clear diagnosis or effective treatment for various symptoms.

"At first pass, it wasn't totally clear that these patients [had] the same symptoms because with rheumatologic diseases, symptoms can change over time," David Beck, MD, PhD, lead author of the 2023 study, told Health. "When we found enough patients, [...] we were able to find a lot of similarities in their symptoms and clinical presentations."

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VEXAS Syndrome Symptoms 

VEXAS syndrome is difficult to diagnose because it has a wide range of non-specific symptoms that frequently mimic other diseases. Plus, its phenotype, or its observable characteristics and clinical traits, is still evolving. Inflammation of several organs results in symptoms like:

• Cough
• Fever
• Pain and swelling of the ear, nose, and joints
• Painful rashes
• Severe fatigue
• Shortness of breath

People may have previously sought the help of rheumatologists, hematologists, dermatologists, or other healthcare providers, which can lead to misdiagnosis. Research has brought attention to VEXAS syndrome. Healthcare providers are more aware of what to look for, Ifeyinwa Obiorah, MD, PhD, an assistant professor of pathology at the University of Virginia School of Medicine, told Health. 

Causes 

A somatic mutation in the UBA1 gene in the bone marrow causes VEXAS syndrome. People acquire somatic mutations over their lifetime instead of inheriting them. Genetic testing can identify a gene mutation, said Dr. Obiorah.

VEXAS syndrome primarily affects men, likely due to the UBA1 mutation being on the X chromosome. Men have one "X" and one "Y" chromosome, so they are more likely to have the disease, but it's still possible for women to develop it. 

Treatment Options 

Many unanswered questions about VEXAS syndrome exist, especially about how to treat it. Many people with VEXAS syndrome take glucocorticoids, an anti-inflammatory medication, to help manage symptoms. Glucocorticoids often have unwanted side effects, such as acne, gastrointestinal (GI) bleeding, insomnia, and mood changes.

A bone marrow transplant is a potentially promising treatment, said Dr. Beck: "This can be curative because you're replacing the mutation in the blood, but it comes with considerable risks associated with the procedure."

Risks of a bone marrow transplant include:

• An abnormal taste in your mouth
• Chest pain
• Fever and chills
• Headache
• Hives
• Low blood pressure
• Nausea
• Pain
• Shortness of breath

How Long Is Life Expectancy With VEXAS Syndrome?

Research has shown that the disease has high morbidity and mortality rates. About 47% of people die within five years of diagnosis. Life expectancy may be dependent on the type of mutation. For example, research found people with a valine variant had shorter life expectancies than people with other variants.

It's important to diagnose and treat VEXAS syndrome as early as possible. If untreated, the disease may cause anemia, blood clots, fatigue, and low platelets. Some people with VEXAS syndrome are likely to develop blood cancer.

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A Quick Review

VEXAS syndrome is a hematologic inflammatory condition caused by a gene mutation on the X chromosome. Researchers discovered the disease in 2020, and in 2023, they found that it primarily affects men older than 50. Some of the most common symptoms are painful rashes and inflammation of several organs. 

Researchers are learning about VEXAS syndrome, including how to treat it. Glucocorticoids and bone marrow transplants are possible treatments. Early diagnosis and treatment are essential since the disease has high morbidity and mortality rates.