Definition
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New autoinflammatory disease discovered at the end of 2020.
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Rare disease.
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Genetic disease by somatic mutation (acquired) during life
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The acronym VEXAS stands for: Vacuoles, Enzyme E1, X-linked, Autoinflammatory, Somatic.
Epidemiology
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It is currently estimated that this syndrome affects one in 4,000 men over the age of 50.
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The disease is cosmopolitan.
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There are at least 220 cases in France to date and probably double in
the World.
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Men are mostly affected (95%) because the mutation is on a gene carried by the X chromosome.
Genetic
VEXAS syndrome is associated with somatic mutations in the UBA1 gene (located on the X chromosome). UBA1 is the main E1 enzyme that has a fundamental role in the functioning of cellular proteins.
Clinical
The patients, mostly men over 45 years old, present with a deterioration in their general condition (fatigue, weight loss) with fevers, an eruption of the 4 limbs and of the trunk of the neutrophilic dermatosis type. All present on the blood test anemia with large red blood cells (macrocytosis) and inflammation in the blood (raised C-reactive protein).
Among the clinical symptoms mens frequent, there are lung abnormalities, inflammation of the cartilages of the ears and nose (chondritis), ophthalmological abnormalities (swelling, redness), thrombosis of the limbs (phlebitis), pain in the joints and more rarely digestive abnormalities and kidneys.
On the blood test, one can see decreases in white blood cells and platelets and a hematological disease called myelodysplasia.
If you do a bone marrow puncture (myelogram), you can look under a microscope at the bone marrow cells that usually have the vacuoles that gave the disease its name.
Diagnostic
The diagnosis is genetic, it is based on a blood test highlighting the mutation of the UBA1 gene, most often in exon 3.
Evolution
It is not completely known because the disease is of recent description. It depends on the presence or absence of an associated severe hematological disease and whether the patient has severe infections.
Treatment
It is not codified to date. Most patients respond to corticosteroids, but may become resistant or dependent on this treatment. Other treatments are being tested, such as haematological drugs (azacytidine) and biotherapies (anti-interleukin 1, 6, anti JAK). For young patients with a severe prognosis related to blood disease, a bone marrow transplant can be offered.
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NEW article on VEXAS for the general public!
June 2023
Vexas syndrome
The challenge of a new, elusive disease
Identified in 2020, this pathology particularly affects
men over the age of 50. Once the first symptoms appear, the median life expectancy is around ten years.
For the moment, medicine is groping its way forward.
Frequently asked questions VEXAS Syndrome
1. What is VEXAS syndrome ?
VEXAS syndrome is a disease caused by a mutation in the UBA1 gene, discovered in 2020. This mutation is acquired during life (known as a somatic mutation) and affects bone marrow cells. It leads to a wide range of inflammatory manifestations that may involve the skin, joints, and lungs, and is often associated with blood abnormalities.
2. Can VEXAS syndrome be passed on to my children?
No. This is an acquired, non-hereditary mutation. It is not present at birth and is not transmitted to children. No pediatric cases have been described to date.
3. Why does this disease appear in adulthood?
The mutation is gradually acquired in bone marrow cells. Inflammation develops progressively, and it takes time for a threshold to be reached before clinical manifestations become visible. This is why the disease usually appears between the ages of 60 and 70, although a few younger cases (as young as 23) have been reported.
4. What warning signs should raise suspicion?
The most common signs are: • Significant fatigue and weight loss • Fever • Thick, infiltrated skin rashes on the arms, legs, and trunk • Redness of the ears (chondritis) or the nasal bridge • Joint and muscle pain • Shortness of breath • Blood abnormalities: anemia with enlarged red blood cells (macrocytosis) and high inflammatory markers (elevated CRP)
5. How is VEXAS syndrome diagnosed?
Diagnosis mainly relies on a blood test to detect the UBA1 gene mutation. If suspicion is high but the mutation is not detected, more sensitive techniques (next-generation sequencing) can be used. In some cases, a bone marrow biopsy may be necessary to confirm the diagnosis and to look for an associated myelodysplastic syndrome.
6. What is clonal hematopoiesis?
Clonal hematopoiesis refers to the presence of genetic abnormalities in bone marrow cells at low levels (usually less than 5%), without obvious blood dysfunction. These abnormalities may be associated with an increased risk of developing hematologic diseases or VEXAS syndrome. In VEXAS, this clonal hematopoiesis tends to expand and progressively replace normal hematopoiesis.
7. What is the difference between VEXAS and a blood cancer?
VEXAS is not a cancer. It is an inflammatory disease caused by a mutation that gives certain cells a growth advantage, but without the uncontrolled proliferation seen in cancers. VEXAS may be associated with “pre-cancerous” conditions such as myelodysplastic syndromes, but progression to cancer is rare. The main issue remains the inflammatory consequences of the disease.
8. What treatments are available?
Several therapeutic options exist: Corticosteroids (cortisone): effective anti-inflammatory treatment, but with significant side effects requiring dietary precautions and sometimes supplements (vitamins, calcium). JAK inhibitors – Ruxolitinib (Jakavi): oral treatment that may be effective for several years. Side effects include weight gain, reduced hemoglobin levels, and the need for long-term skin monitoring (risk of benign skin tumors). Tocilizumab: a biologic therapy targeting inflammation, currently being evaluated in clinical trials for VEXAS. Azacitidine (Vidaza): a key treatment, effective in 50–66% of cases. It may take 6–12 months to become effective. When it works, relapses are uncommon and the mutation often disappears. Stem cell transplantation: the only potentially curative treatment, with a 100% success rate when it works, but reserved for younger patients or those who have failed other treatments due to its toxicity. Treatments in development: ongoing clinical trials, notably with momelotinib (less toxic to red blood cells than Jakavi) and pacritinib.
9. How long should Vidaza be taken?
It is not yet known whether treatment can be stopped after several years. Experience shows that the disease usually relapses after discontinuation, even if this may take time. Given its good long-term tolerance and effectiveness, treatment is generally continued when it works well. This question is the subject of ongoing research.
10. Do frequent blood tests worsen my anemia?
No. Frequent blood tests do not worsen anemia. They are necessary for monitoring and help adjust treatment at the right time.
11. Which doctor should manage my follow-up?
Follow-up is usually coordinated by a hospital physician (internist or hematologist) experienced in biologic therapies and blood disorders. Close collaboration exists between specialists (internists, hematologists, dermatologists, rheumatologists). In France, a national multidisciplinary consultation meeting is held every two weeks to discuss complex cases.
12. How can one tell the difference between a disease flare and an infection?
This requires assessment by an expert physician, who can distinguish between an intercurrent infection and a disease flare requiring treatment adjustment based on clinical examination and laboratory tests. This cannot be determined without a medical consultation.
13. Are there triggers for inflammatory flares?
Apart from treatment-related factors (reduction in corticosteroid dose, end of chemotherapy cycles), no clear environmental or dietary triggers have been identified so far. Infections may sometimes act as triggers, but not consistently.
14. Can VEXAS cause neurological involvement?
Yes, neurological manifestations have been described, but they are very rare. There is no specific neurological presentation that strongly points toward a diagnosis of VEXAS.
15. Are there dietary or physical activity recommendations?
No natural treatment has proven effective for VEXAS. However, it is recommended to: • Follow an anti-inflammatory diet, avoiding ultra-processed foods • Maintain a healthy weight (fat tissue is inflammatory and may worsen the disease) • Engage in regular physical activity (daily walking, gentle exercise) • Avoid taking natural products or supplements without consulting your doctor
16. How can infections be prevented?
VEXAS increases susceptibility to infections, including opportunistic infections. It is recommended to: Be vaccinated against influenza, COVID-19, pneumococcus, and shingles Wear a mask in enclosed spaces and public transportation Carry hand sanitizer Keep all vaccinations up to date according to a personalized schedule established with your doctor
17. What is the life expectancy with VEXAS?
Although the mutation was identified in 2020, some patients have been followed for 15–30 years with symptoms consistent with VEXAS. Disease progression varies greatly between individuals. Early management since the disease’s identification should improve survival. Only stem cell transplantation offers a definitive cure; other treatments control the disease without curing it.
18. Are there ongoing clinical trials?
Yes. Research is very active, both in understanding the disease and developing treatments. Academic clinical trials are ongoing in 2026, notably with momelotinib (less toxic to red blood cells than Jakavi). A trial with pacritinib is expected to resume soon. More targeted and effective treatments are anticipated within the next 5 to 10 years.
19. How many patients are affected in France?
France has one of the largest cohorts worldwide, with approximately 300–400 diagnosed cases, thanks to a highly effective network organization between internists, hematologists, and biologists. Diagnosis is very rapid in France.
20. Are there any officially approved drugs for VEXAS?
No. All current treatments are used off-label. This is why clinical research and therapeutic trials are essential to define treatment standards and obtain official approvals.
21. Why do medications have two different names?
Medications have a generic name (the active substance) and a brand name. For example, paracetamol is the generic name, while Doliprane or Dafalgan are brand names. The same applies to all medications used in VEXAS.
22. Are there studies on possible causes of this mutation (chemical exposure, radiation, etc.)?
No. Unlike some blood diseases, no proven link has been established between VEXAS and exposure to toxins, smoking, or radiation. The main known factor is age, which induces bone marrow stress and chronic inflammation that favor the emergence of mutations. The disease has been observed on all continents, regardless of country, diet, or lifestyle, supporting the absence of identified environmental causes.
23. Why can platelet counts increase and decrease in VEXAS?
Low platelet counts are part of VEXAS symptoms. Fluctuations are common and natural, especially in moderate thrombocytopenia (for example, moving from 80,000 to 65,000 and back to 80,000). These variations often worry patients but are typical in blood disorders. The course is difficult to predict: platelet counts may stabilize, require specific treatment, or remain fluctuating over time.
24. Can VEXAS increase hypersensitivity reactions to other medications?
This has not been proven. There is no data showing that VEXAS treatments increase inflammatory hypersensitivity reactions to other drugs.
25. Can stem cell transplantation be performed at any age?
No. Transplantation is limited by physiological age and the body’s ability to tolerate this highly toxic procedure. It is reserved for younger patients or those for whom other treatments have failed, based on strict eligibility criteria evaluated by physicians.
26. White blood cells decrease after each Vidaza injection. Is this normal? Are there nutritional measures that can help?
Vidaza may take several months to become effective, and early hematologic toxicity is possible. There are no specific dietary measures proven to improve white blood cell recovery. Time and/or dose adjustment (dose reduction or spacing of cycles) improve tolerance. Symptoms such as headaches, palpitations, or faintness may be related to the disease itself rather than the treatment and should be reported to the physician.