How to pronounce it:

VEXAS - vex-us

AiArthritis defines VEXAS syndrome as:

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a rare autoinflammatory disorder that was first identified in 2020. This syndrome is characterized by a combination of symptoms, including recurrent fevers, blood abnormalities, and inflammatory skin lesions. The term "VEXAS" reflects some of the key features of the syndrome.

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

1. Vacuoles: This refers to the presence of atypical vacuoles in the myeloid cells of affected individuals, as observed in laboratory analyses.
2. 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.
3. 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.
4. Autoinflammatory: VEXAS syndrome is classified as an autoinflammatory disorder, which means it involves the immune system mistakenly causing inflammation in the absence of infection.
5. 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 Often Associated with VEXAS:

The diagnosis of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome involves a combination of clinical evaluation, genetic testing, and laboratory assessments. Given the rarity and complexity of VEXAS syndrome, a multidisciplinary approach involving rheumatologists, geneticists, and other specialists is often necessary. Here are key components of the diagnostic process:

• Clinical Evaluation:
• Healthcare providers assess the individual's medical history, including details about recurrent fevers, blood abnormalities, inflammatory skin lesions, and other relevant symptoms. A thorough physical examination is conducted to identify clinical features associated with VEXAS syndrome.
• Genetic Testing:
• Genetic testing is a crucial component of the diagnostic process for VEXAS syndrome. The specific genetic mutation associated with VEXAS involves somatic mutations in the UBA1 gene, which encodes the E1 ubiquitin-activating enzyme. Testing involves analyzing the DNA to identify these mutations.
• Laboratory Assessments:
• Blood tests are performed to assess various parameters, including complete blood counts (CBC), inflammatory markers (such as C-reactive protein or erythrocyte sedimentation rate), and other blood components. Abnormalities in these tests may support the diagnosis.
• Imaging Studies:
• Imaging studies, such as X-rays or other imaging modalities, may be used to assess joint and organ involvement, especially if musculoskeletal or respiratory symptoms are present.
• Exclusion of Other Conditions:
• As the symptoms of VEXAS syndrome can overlap with those of other autoinflammatory disorders, infectious diseases, or rheumatic conditions, healthcare providers may conduct tests to rule out alternative diagnoses.

Given the recent discovery of VEXAS syndrome and its unique genetic basis, specialized testing for the UBA1 gene mutation is a critical step in confirming the diagnosis. This genetic testing is typically not part of routine genetic screening and may require consultation with geneticists or experts in rare genetic disorders.

It's essential for individuals suspected of having VEXAS syndrome to consult with healthcare professionals experienced in rheumatology and rare inflammatory disorders. Accurate diagnosis is crucial for appropriate management and treatment planning.