VEXAS syndrome is a rare inflammatory disease caused by mutations in the UBA1 gene. Responsible for a chronic inflammatory syndrome, the disease was first described in 2020 by an American team.
Definition: what is VEXAS syndrome?
VEXAS Syndrome is an acronym for Vacuoles, UBA1 Enzyme, X Chromosome, Autoinflammatory, Somatic. It’s about a rare disease linked to mutations in the UBA1 gene, located on the X chromosome, in the myeloid cells. “These mutations are called somatic, it is that they are not present at birth and appear during life.“, explains Pr. Sophie Georgin-Lavialle, internist at Tenon Hospital. Thus, the youngest patient described in the world with this disease is 46 years old. VEXAS syndrome was first described by a US team in October 2020.”Before this mutation was discovered, these patients were diagnosed polychondritis or inflammatory manifestation associated with probable blood disease“, develops the specialist. When the article came out in 2020, many patients could be diagnosed via DNA sequencing.
What is the cause of VEXAS syndrome?
“As we age we all develop mutations. People who develop mutations in that particular UBA1 gene will develop VEXAS syndrome because the mutation leads to excess inflammation in the body“, answers the doctor. However, it is currently impossible to know why one individual, rather than another, will develop this disease.
The disease mainly affects men over the age of 50.
What are the symptoms of VEXAS syndrome?
Patients present anemia, fever and rheumatological, dermatological symptoms and have inflammation in the blood:
- Fever
- Large joint pain
- Skin lesions
- great tiredness
- Anorexia
- Weightloss
Some patients suffer from chondritis, an inflammation of the cartilage ears and nose. One can also find on the imagery abnormalities in the lungs. “There is no acute phase. There are sometimes outbreaks but the inflammation is present permanently“, notes Sophie Georgin-Lavialle.
There C-reactive protein, marker of inflammation, is permanently very high in VEXAS syndrome. This inflammation is associated with a particular anemia in this syndrome, called “macrocytic” anemia, that is, the red blood cells are much larger than normal. “Usually the inflammation results in microcytic anemia. Thus, we think that mutations also affect progenitors of red blood cellswhich changes their size“, specifies our interlocutor. She adds: “poor general condition, fever, inflammation and macrocytic anemia should really put on the track of the VEXAS syndrome, especially if the patient presents cutaneous lesions”. If we make a bone marrow puncture, vacuoles can be observed in the myeloid progenitors which gave the letter V of the acronym VEXAS. The diagnosis is then confirmed by genetic analysis made by a simple blood test.
Who is most affected by VEXAS syndrome?
The disease affects very mostly men – who have only one X chromosome – over 50 years old. The average age of patients is around 65 years old. “In female carriers of the mutation, the second X chromosome takes over and the mutation is not expressed. On the 5% of women identified to date in France, all have monosomy X, they have only one X chromosome“, details the internist.
Are there cases in France?
Since the UBA1 gene mutation became known, “more than 250 patients have been diagnosed in France“. This disease is present in all countries of the world. “However, we have little data from black Africa, probably due to lack of access to genetic sequencing.“, she underlines.
Most patients respond well to corticosteroids. But these drugs have many side effects. “The goal is therefore to reduce corticosteroids to the minimum dose. We are therefore currently testing anti-cytokine treatments – anti-interleukin 1, anti-interleukin 6, JAK inhibitors“, enumerates Sophie Georgin-Lavialle. In rather young subjects, with heavy symptoms and severe mutations, a bone marrow transplant is also possibleand is the only curative treatment available to date.
Is it a fatal syndrome?
While the disease has only just been described, doctors do not have enough data to be specific on this issue. “Currently, according to our still partial data, we observed a mortality rate of 18% at 5 years with an average age of 70 years approximately. Life expectancy was not greatly altered. Our next results will be more revealing because they will be based on twice as many patients.”explains Sophie Georgin-Lavialle.
Thanks to Pr. Sophie Georgin-Lavialle, internist at Tenon Hospital and professor at the Sorbonne University Faculty of Medicine for her expertise.