VEXAS SYNDROME - INSIGHTS INTO THE NEWLY DISCOVERED AUTOIMMUNE DISEASE

VEXAS syndrome is an autoimmune disorder that primarily affects men over 50. It may cause blood-related issues, inflammation, and fever resulting in organ damage. It is a newly discovered disease by the National Institutes of Health in 2020.

If VEXAS syndrome is not treated, it might be fatal. While a standardized care protocol is not yet established, your doctor will recommend treatments to control your symptoms.

What Is VEXAS Syndrome?

VEXAS is an acronym for the features of the disorder; an abbreviation for how medical professionals can recognize and diagnose it. They include the following:

• Vacuoles: Circular, empty spaces called vacuoles emerge in abnormal cells. The bone marrow cells of people with VEXAS syndrome typically contain vacuoles.
• E1 enzyme: When the UBA1 gene is mutated, your cells produce the ineffective E1 enzyme.
• X-linked: Your biological sex is determined by two chromosomes. XX chromosomes are found in females, while XY chromosomes are found in males. The X chromosome houses the defective UBA1 gene that causes VEXAS syndrome.
• Autoinflammation: This is the medical term for inflammation your immune system causes when it attacks your body.
• Somatic: The VEXAS syndrome-causing mutation is somatic, i.e., relating to, or affecting the body. That indicates that it is acquired and not inherited from one's biological parents.

VEXAS syndrome is a rare autoimmune condition that produces inflammation all over your body.

Autoimmune diseases are brought on when your immune system accidentally attacks your body rather than defending it. Why your immune system turns against you is unclear to experts.

When you have VEXAS syndrome, your immune system attacks the tissue all over your body, resulting in swelling and inflammation. VEXAS syndrome can have an impact on:

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

What Causes VEXAS Syndrome?

A genetic mutation causes VEXAS syndrome—specifically, a UBA1 gene mutation. Genetic mutations are modifications to your DNA sequence as your cells divide and generate duplicates of themselves. You may exhibit signs of a genetic disorder if a piece of your DNA sequence is misplaced, incomplete, or damaged.

In people with VEXAS syndrome, the UBA1 gene malfunctions and fails to create the E1 enzyme as it should. The E1 enzyme cleans up broken or outdated proteins inside your cells, acting as a janitor.

The E1 enzyme cleaning crew is understaffed in VEXAS syndrome. As a result, your cells eventually become clogged with garbage and broken proteins. This backup triggers your immune system and perceives the extra waste as dangerous. However, your immune system attacks and damages healthy tissue, which results in inflammation even though there is no infection in that region.

VEXAS Syndrome Symptoms

Inflammation is the main symptom. The other symptoms of VEXAS syndrome include the following:

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

People with VEXAS may additionally have:

• Polyarteritis nodosa
• Relapsing polychondritis
• Sweet syndrome

How Common Is VEXAS Syndrome?

Very few people have VEXAS syndrome. However, a recent study indicates that the prevalence (while rare) may be higher than previously estimated. According to the study published in JAMA on January 24, 2023, the incidence is about 1 in 13,591 people in the United States. According to the surveyed data, it occurs more frequently than inflammatory diseases such as vasculitis and myeloid dysplasia syndrome.

Who Are At Risk?

Current research shows that while the condition affects both genders, males are far more likely to develop VEXAS syndrome. Furthermore, people over 50 are also more prone to the disease. In this age group, the study revealed a prevalence of 1 in 4,269 among men and 1 in 26,238 among women. It develops later in life because of a genetic mutation.

How Long Is Life Expectancy With VEXAS Syndrome?

In individuals with VEXAS, disease progression has been found to vary. However,, if left untreated, the condition can be lethal. VEXAS syndrome life expectancy, what to anticipate, and which treatment choices will work best for you should all be discussed with your healthcare professional. Your doctor will assist you in controlling your symptoms and can suggest referrals to mental health specialists and other kinds of support.

VEXAS Syndrome Diagnosis

A medical professional uses a physical examination and genetic tests to identify VEXAS syndrome. They will evaluate your symptoms and inquire when you first became aware of them.

Genetic testing (UBA1 mutation testing) is the only way to determine if you have VEXAS syndrome. First, a sample of your skin, blood, hair, or other tissue will be collected by your healthcare professional and sent to a lab. Then, technicians will examine your DNA for the UBA1 mutation that causes VEXAS syndrome.

Is There a Cure For VEXAS Syndrome?

There is no standard treatment yet. However, your doctor may use immunosuppressants and steroids to treat your inflammation.

Although biological treatments for autoimmune diseases have been tested, corticosteroids have shown to be the only ones that work for VEXAS thus far. Unfortunately, however, some people do not respond to steroids, which can result in potentially fatal complications.

VEXAS syndrome treatment includes the following:

1. Corticosteroids to decrease inflammation.
2. Immunosuppressant medications that reduce your immune system's response.
3. A bone marrow transplant, if your bone marrow shows signs of failure. Additionally, bone marrow transplants can decrease the severity of several autoimmune diseases.

Working with a rheumatologist, a medical professional who focuses on treating autoimmune diseases, may be necessary.

Other VEXAS treatments being investigated by researchers include stem cell therapy and drugs like IL-6 inhibitors and JAK inhibitors. In addition, they are attempting to comprehend multiple mutations in the UBA1 gene.

While some individuals may not have the gene mutation, they exhibit blood and inflammatory signs indicative of VEXAS. Therefore, doctors aim to identify people who may have VEXAS and determine when these people should be evaluated.

Complications of VEXAS Syndrome

Your bone marrow may fail if the VEXAS syndrome-related inflammation damages it; this condition can be lethal.

Depending on where the inflammation manifests, having VEXAS syndrome may increase your risk of developing other medical conditions, such as:

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

When To See A Doctor?

See a doctor if you have any symptoms of VEXAS syndrome, such as skin rashes, fevers, or shortness of breath. Because VEXAS syndrome causes many diverse symptoms that may not seem related, it might be challenging to diagnose the condition immediately. However, if you are suffering symptoms that you cannot explain or are unrelated to your previous medical conditions, listen to your body and get medical attention.

It is also essential to see your doctor immediately if you already have VEXAS syndrome and believe you are exhibiting new or more severe symptoms.

Outlook

Although the outlook seems poor right now, part of that is because scientists need to comprehend the disorder fully. However, more research will allow for more remarkable advancements and learning.

The Bottom Line

VEXAS syndrome is a rare autoimmune disorder brought on by a particular genetic abnormality. It can be fatal and produces inflammation all over your body. Your doctor will assist you in locating therapies that treat your problems.

If you have any VEXAS syndrome symptoms, get medical attention. Trust your body and yourself. Symptoms like rashes, fevers, or shortness of breath should not be disregarded.

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References

• Grayson, Peter C et al. “VEXAS syndrome.” Blood vol. 137,26 (2021): 3591-3594. doi:10.1182/blood.2021011455
• Koster, Matthew J et al. “VEXAS Syndrome-A Review of Pathophysiology, Presentation, and Prognosis.” Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 10.1097/RHU.0000000000001905. 14 Oct. 2022, doi:10.1097/RHU.0000000000001905
• Coattrenec, Yann et al. “Syndrome VEXAS : quand y penser ?” [VEXAS syndrome : when do we have to consider it ?]. Revue medicale suisse vol. 18,776 (2022): 652-659. doi:10.53738/REVMED.2022.18.776.652
• Beck DB, Bodian DL, Shah V, Mirshahi UL, Kim J, Ding Y, Magaziner SJ, Strande NT, Cantor A, Haley JS, Cook A, Hill W, Schwartz AL, Grayson PC, Ferrada MA, Kastner DL, Carey DJ, Stewart DR. Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated With VEXAS Syndrome in a Clinical Population. JAMA. 2023 Jan 24;329(4):318-324. doi: 10.1001/jama.2022.24836. PMID: 36692560.

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