VEXAS Syndrome

Here's a breakdown of the components of the term "VEXAS":

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• Vacuoles: This refers to the presence of atypical vacuoles in the myeloid cells of affected individuals, as observed in laboratory analyses.
• E1 enzyme: The syndrome is associated with somatic mutations in the UBA1 gene, which encodes the E1 ubiquitin-activating enzyme. These mutations are believed to contribute to the dysregulation of the immune system.
• X-linked: The UBA1 gene is located on the X chromosome. The X-linked nature indicates that the syndrome primarily affects males, as they have only one X chromosome. Females, who have two X chromosomes, might have one unaffected copy that can compensate for the mutation.
• Autoinflammatory: VEXAS syndrome is classified as an autoinflammatory disorder, which means it involves the immune system mistakenly causing inflammation in the absence of infection.
• Somatic: Somatic mutations are those that occur in the body's non-reproductive cells and are not passed on to offspring. In VEXAS syndrome, somatic mutations in the UBA1 gene are acquired during a person's lifetime.

Symptoms & Characteristics

Common in All AiArthritis Diseases

Flares: Periods of worsening symptoms are called flares. A flare can last for hours, days, weeks, or months.

Physical Activity: Condition improves with activity and exercise and worsens with rest.

Comorbidities: When inflammation is left uncontrolled due to lack of proper treatment, comorbidities can develop. 70% of patients with chronic, lifelong disease will develop comorbidities, including dual or triple diagnoses.

Family History: Autoimmune diseases often run in families, indicating a potential genetic predisposition where that gene can cause disease. Autoinflammatory diseases can occur multiple times in a family, but is based off of genetic mutation. It is not a gene that causes the disease— but a mutation on the gene that can cause the disease which can then be passed on to the next generation.

"Auto" Symptoms

Fatigue: Severe fatigue or exhaustion that may not be helped by caffeine/stimulants and can happen even after a long period of rest.

Cognitive Dysfunction: Brain fog  or periods of time where thinking gets clouded and it becomes difficult to concentrate.

Flu-like symptoms: Without having the flu- nausea, muscle weakness, and general malaise.

Fever: Typically low grade in autoimmune (with exception of juvenile idiopathic arthritis) and higher grade in autoinflammatory (% strongly varies per disease).

Reference: Early Symptoms of AiArthritis Study, AiArthritis, 2019.

Inflammatory Arthritis Symptoms

Stiffness: Severe stiffness in one or more joints, especially in the morning or after sitting for long periods of time. 

Joint Pain: Episodes of joint pain that may last for hours, days, or even weeks, that can appear and disappear suddenly. Often described as “jumping pain” into different locations.

Typically the joint pain will coincide with one or more “Auto” symptoms and start and stop suddenly - for no apparent reason (which is called a "flare"). Some people will experience all of the above symptoms, others only a few.

 If you have any of the arthritis features, and at least one of the “Auto” features, please consult your physician about a referral to a specialist.

Symptoms Often Associated with VEXAS Syndrome

• Inflammatory skin lesions
• Respiratory symptoms (cough, trouble breathing)
• Anemia
• Pain and swelling of the ears and nose
• Inflammation of blood vessels (vasculitis)
  

In an effort to ensure this page has the most accurate and up-to-date information, this page is currently awaiting medical review. Some information is subject to change.

Page Last Updated: 10/31/2024