VEXAS stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic.
VEXAS syndrome is an adult-onset severe inflammatory and/or hematologic disorder caused by a somatic mutation in the UBA1 gene located on the X chromosome. It was first identified in 2020 and is a rare genetic disorder that affects multiple systems of the body, including the blood vessels, nervous system, and bones.
VEXAS syndrome causes various blood disorders, pulmonary issues, and joint and skin disorders. It develops in adults who are in their 50s or older. People who develop VEXAS syndrome have a high mortality rate, and people with severe disease may not live beyond five years following the diagnosis.
- Somatic mutation in the UBA1 gene on the X chromosome affects hematopoietic progenitor cells, affects the process of ubiquitylation in the cells, and increases the activity of innate immunity pathways in myeloid cells. This leads to an overexpression of proinflammatory markers, causing systemic inflammation.
- VEXAS syndrome exhibits X-linked inheritance, which means that the disorder is caused by a gene located on the X chromosome. It usually affects men, whereas women act as carriers of defective gene.
- The exact cause of VEXAS syndrome is unknown, and there is no cure for the disorder.
- Treatment is primarily focused on managing the symptoms and complications of the disorder.
What are the symptoms of VEXAS syndrome?
VEXAS syndrome is a rare genetic disorder that affects multiple systems of the body, and it has multiple symptoms.
The most common symptoms of VEXAS syndrome can include
- Recurrent fevers
- Skin rashes
- Joint pain and swelling
- Chronic inflammation
- Muscle weakness
- Abnormal blood flow
- Inflammation of the blood vessels
- Skin and eye inflammation
- Deep vein clots
- Infections of the cartilage of the ear and nose
- Sensorineural hearing loss
- Pulmonary manifestations
- Pulmonary infiltrates
- Kidney issues
Individuals with the same genetic mutation causing VEXAS syndrome can have varied symptoms, including the severity of the symptoms.
What causes VEXAS syndrome?
VEXAS syndrome is caused by a mutation in the UBA1 gene that codes for the E1 enzyme located on the X chromosome. Specifically, the mutation results in a gain-of-function of the E1 enzyme, leading to the overactivity of this enzyme in certain cells in the body.
- The overactivity of the E1 enzyme is thought to lead to the formation of vacuoles (small pockets of fluid) in certain cells. This, in turn, causes chronic inflammation, leading to VEXAS syndrome symptoms.
- VEXAS is inherited in an X-linked manner. Women have two X chromosomes, so they are less likely to be affected by an X-linked disorder. Men have only one X chromosome, so they are more likely to be affected by an X-linked disorder.
- In VEXAS syndrome, mutations in the E1 enzyme gene are inherited from the mother who is usually a carrier of the disorder.
How is VEXAS syndrome diagnosed?
Your doctor will perform a physical examination and take a detailed medical history. They will look for signs and symptoms of VEXAS syndrome, such as enlarged lymph nodes, skin changes, breathing issues, joint pain, and others as most of the symptoms are caused due to inflammation and reduced immunity.
It is not easy to give a definitive diagnosis with a physical exam, so you may be subjected to various tests to confirm the diagnosis, which includes
- Genetic testing: Most important tool for diagnosing VEXAS syndrome. The test will look for mutations in the UBA1 gene associated with the disorder.
- Imaging studies: An MRI or a CT scan can be done to identify the abnormalities in the brain and blood vessels, which can help confirm the diagnosis.
- Biopsy: In a bone marrow biopsy, a small sample of bone marrow is collected and studied in the laboratory to detect possible tissue malformations, which can help confirm the diagnosis.
Is there a cure for VEXAS syndrome?
Currently, there is no known cure for VEXAS syndrome because it is a relatively new condition. Numerous studies are going on to determine the best treatment for this syndrome. However, several treatment options are available to manage the symptoms and complications of the disorder.
Some of the treatment options that may be considered for VEXAS syndrome include
- Anti-inflammatory drugs
- Physical therapy and occupational therapy
- May be recommended to help manage any muscle weakness or developmental delays.
- Allogenic bone marrow transplant
- Initially, the condition manifests as inflammation; however, as the disease progresses, the bone marrow (spongy tissue inside of your bones) becomes the target organ, resulting in bone marrow failure.
- For this condition, a donor bone marrow transplant may be helpful in rectifying blood disorders such as anemia.
- However, it is believed that the bone marrow may lose functionality in later years.
- Clinical trials
- The field of autoinflammatory diseases is ongoing, and new therapies are being developed. Some of these therapies may potentially be used to treat VEXAS syndrome in the future.
- According to the NIH, people with VEXAS syndrome showed clinical, genetic, and morphological remissions after being treated with the hypomethylating medication azacytidine. However, this approach is still under trial.
VEXAS syndrome manifests differently in each individual, so work closely with your doctor to determine the suitable treatment for your condition.
Can rheumatoid arthritis go into spontaneous remission?
Rheumatoid arthritis (RA) is a chronic autoimmune disorder that can cause inflammation and damage to the joints and other parts of the body. Although there is no cure for RA, treatment options can help manage the symptoms and slow the progression of the disease. In some cases, RA may go into a state of remission, which means that the symptoms of the disease improve or disappear completely.
- Spontaneous remission is used to describe a situation in which RA goes into remission without any specific treatment or intervention. This is considered rare, but it does occur in some cases. The severity of the disease at diagnosis, the presence of certain genetic markers, and the individual's overall health influence the spontaneous remission of RA.
- Going into remission does not mean that RA has been cured. You may have flare-ups again at any time. Therefore, continuous monitoring and managing of the disease even during remission.
- Spontaneous remission is less likely in people with more severe RA, those with a more aggressive disease course, and those with higher disease activity at the time of diagnosis.
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VEXAS syndrome: https://medlineplus.gov/genetics/condition/vexas-syndrome/#references
What is VEXAS syndrome? https://www.niams.nih.gov/labs/grayson-lab/vexas#:~:text=VEXAS%20syndrome%20is%20a%20disease,and%20acquired%20later%20in%20life.
Pulmonary Manifestations in VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) Syndrome: A Systematic Literature Review: https://acrabstracts.org/abstract/pulmonary-manifestations-in-vexas-vacuoles-e1-enzyme-x-linked-autoinflammatory-somatic-syndrome-a-systematic-literature-review/
Remission in Rheumatoid Arthritis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927687/
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