What is VEXAS syndrome?

VEXAS syndrome is a disease that causes inflammatory and hematologic (blood) manifestations. The syndrome is caused by mutations in the UBA1 gene of blood cells and acquired later in life. Patients do not pass the disease to their children.

What does VEXAS mean?

VEXAS is an acronym defined as follows:

V: - vacuoles are often seen in cells identified in bone marrow biopsies from patients with VEXAS syndrome.

E: - E1 ubiquitin activating enzyme, encoded by the UBA1 gene which is mutated in patients.

X: - the UBA1 gene is located on the X chromosome.

A: - patients have autoinflammation.

S: - the mutations are somatic, meaning they are acquired at some point in life and not inherited.

What are the symptoms of VEXAS syndrome?

Illustration of a male body, highlighting the locations of the many possible symptoms of VEXAS.

High Resolution Image

Patients with VEXAS can have a wide range of inflammatory symptoms affecting multiple organs including:

skin (rashes that can be painful).
cartilaginous structures (pain and swelling of the ear and nose).
lungs (cough and shortness of breath).
joints (swelling and pain).
vasculature (inflammation of vessels).

Patients often have fever and extreme fatigue. The hematologic features can include anemia, low platelets, and blood clots. On many occasions patients with VEXAS have associated clinical diagnoses, including relapsing polychondritis, polyarteritis nodosa, sweet syndrome and myelodysplastic syndrome.

How do you diagnose and treat VEXAS syndrome?

A VEXAS diagnosis uses genetic testing, which looks for mutations in the UBA1 gene located in the X chromosome.

There is no standardized treatment for VEXAS currently, however the inflammatory features can be treated with steroids and other immunosuppressants. Some patients may be candidates for bone marrow transplantation. Since VEXAS can affect multiple organs, patients will need a team of doctors—including a rheumatologist and hematologist—to manage their disease.

Who gets VEXAS syndrome?

Research studies indicate that VEXAS is primarily observed in biological males.

What research is being done in VEXAS syndrome?

Since the syndrome was first described in 2020, there has been a worldwide interest in understanding the disease. At the NIH, a clinical trial is currently underway to evaluate stem cell transplant as a possible treatment for patients with VEXAS. The David Beck Lab at New York University is also actively researching the condition.

For more information on research being conducted at the NIAMS please contact:

Nurse Wendy Goodspeed, Research Nurse Specialist
goodspew@mail.nih.gov
Dr. Peter Grayson, Principal Investigator
peter.grayson@nih.gov

Selected Publications

VEXAS syndrome: An inflammatory and hematologic disease.

Patel BA, Ferrada MA, Grayson PC, Beck DB

Semin Hematol.

2021 Oct;

58(4).

doi: 10.1053/j.seminhematol.2021.10.005

PMID: 34802540

VEXAS syndrome.

Grayson PC, Patel BA, Young NS

Blood.

2021 Jul 1;

137(26).

doi: 10.1182/blood.2021011455

PMID: 33971000

Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS.

Ferrada MA, Sikora KA, Luo Y, Wells KV, Patel B, Groarke EM, Ospina Cardona D, Rominger E, Hoffmann P, Le MT, Deng Z, Quinn KA, Rose E, Tsai WL, Wigerblad G, Goodspeed W, Jones A, Wilson L, Schnappauf O, Laird RS, Kim J, Allen C, Sirajuddin A, Chen M, Gadina M, Calvo KR, Kaplan MJ, Colbert RA, Aksentijevich I, Young NS, Savic S, Kastner DL, Ombrello AK, Beck DB, Grayson PC

Arthritis Rheumatol.

2021 Oct;

73(10).

doi: 10.1002/art.41743

PMID: 33779074

Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease.

Beck DB, Ferrada MA, Sikora KA, Ombrello AK, Collins JC, Pei W, Balanda N, Ross DL, Ospina Cardona D, Wu Z, Patel B, Manthiram K, Groarke EM, Gutierrez-Rodrigues F, Hoffmann P, Rosenzweig S, Nakabo S, Dillon LW, Hourigan CS, Tsai WL, Gupta S, Carmona-Rivera C, Asmar AJ, Xu L, Oda H, Goodspeed W, Barron KS, Nehrebecky M, Jones A, Laird RS, Deuitch N, Rowczenio D, Rominger E, Wells KV, Lee CR, Wang W, Trick M, Mullikin J, Wigerblad G, Brooks S, Dell'Orso S, Deng Z, Chae JJ, Dulau-Florea A, Malicdan MCV, Novacic D, Colbert RA, Kaplan MJ, Gadina M, Savic S, Lachmann HJ, Abu-Asab M, Solomon BD, Retterer K, Gahl WA, Burgess SM, Aksentijevich I, Young NS, Calvo KR, Werner A, Kastner DL, Grayson PC

N Engl J Med.

2020 Dec 31;

383(27).

doi: 10.1056/NEJMoa2026834

PMID: 33108101