American College of Rheumatology Guidance Statement for Diagnosis and Management of VEXAS Developed by the International VEXAS Working Group Expert Panel

Journal: Arthritis & Rheumatology

First author: Arsène Mekinian

Country of study: international guidance — expert panel from 18 countries

CEREMAIA Tenon author: Sophie Georgin-Lavialle

Reference: Mekinian A, Georgin-Lavialle S, Ferrada MA, Savic S, Koster MJ, Kosmider O, Comont T, Heiblig M, et al. American College of Rheumatology Guidance Statement for Diagnosis and Management of VEXAS Developed by the International VEXAS Working Group Expert Panel. Arthritis & Rheumatology. 2026;78(3):509–522.

DOI: https://doi.org/10.1002/art.43287

PubMed link: https://pubmed.ncbi.nlm.nih.gov/?term=10.1002%2Fart.43287

5 key points

• VEXAS syndrome is a rare disease caused by an acquired mutation in the UBA1 gene, leading to chronic inflammation and blood abnormalities.

• It mainly affects men over the age of 50, but it can also occur in some women, particularly in the context of X chromosome abnormalities.

• Persistent inflammation associated with skin, eye, lung or cartilage involvement, or with low blood cell counts, should raise suspicion of VEXAS.

• Diagnosis is based on genetic testing for a somatic UBA1 mutation, most often using blood or bone marrow samples.

• Care should be multidisciplinary and may include corticosteroids, targeted anti-inflammatory treatments, haematological therapies or, in selected cases, stem cell transplantation.

Introduction

VEXAS syndrome is a rare disease that was recently identified. Its name stands for vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic. It is caused by an acquired mutation in the UBA1 gene in certain blood cells. This mutation is not inherited from parents and is not transmitted like a familial genetic disease. VEXAS often combines major inflammation with blood abnormalities.

Methods

This article presents the first international American College of Rheumatology guidance for the diagnosis and management of VEXAS. The guidance was developed by a multidisciplinary panel of 57 international experts, based on available evidence and a formal consensus process.

Results

The experts describe situations in which VEXAS should be suspected: unexplained fever, persistent inflammation, skin, eye, lung or cartilage involvement, blood clots, macrocytic anaemia, low platelet counts or other blood abnormalities. Diagnosis must be confirmed by testing for a UBA1 mutation, usually in blood or bone marrow. Bone marrow examination is recommended in patients with low blood cell counts to look for associated haematological diseases, such as myelodysplastic syndrome.

Discussion

The article emphasizes the need for coordinated care involving internal medicine specialists, rheumatologists, haematologists, dermatologists, pulmonologists, infectious disease specialists and expert centres. Corticosteroids are often effective but must be tapered slowly. Some treatments targeting inflammation, such as JAK inhibitors or interleukin-6 inhibitors, may be helpful. In some patients, treatments targeting the abnormal blood cell clone, such as azacitidine, or stem cell transplantation may be discussed.

Conclusion

These recommendations are an important step toward better diagnosis and more consistent management of VEXAS. Early diagnosis, haematological monitoring and a multidisciplinary approach are essential to reduce complications and improve quality of life.

PubMed link: https://pubmed.ncbi.nlm.nih.gov/?term=10.1002%2Fart.43287

VEXAS syndrome

Journal: Nature Reviews Disease Primers

First author: David B. Beck

Country of study: international article — United States, France, Japan and Italy

CEREMAIA Tenon author: Sophie Georgin-Lavialle

Reference: Beck DB, Georgin-Lavialle S, Kirino Y, Patel BA, Ferrari S. VEXAS syndrome. Nature Reviews Disease Primers. 2026;12:19.

DOI: https://doi.org/10.1038/s41572-026-00695-w

PubMed link: https://pubmed.ncbi.nlm.nih.gov/?term=10.1038%2Fs41572-026-00695-w

5 key points:

• VEXAS syndrome is a rare adult-onset inflammatory disease, discovered in 2020, caused by an acquired mutation in the UBA1 gene in blood cells.

• It mainly affects men over the age of 50, but it can also occur in women, especially in the context of X chromosome abnormalities.

• Common signs include corticosteroid-dependent inflammation, skin lesions, cartilage and lung involvement, blood abnormalities and sometimes myelodysplastic features.

• Diagnosis is based on the combination of symptoms, laboratory abnormalities — especially macrocytic anaemia and inflammation — and confirmation by genetic testing for a UBA1 mutation.

• Treatments aim to control inflammation and/or the abnormal blood cell clone, but management remains complex and must be tailored to each patient.

Introduction:

VEXAS syndrome is a recently identified autoinflammatory disease. Its name stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic. It is caused by an acquired mutation in the UBA1 gene in certain blood stem cells. This mutation disrupts immune cell function and leads to significant chronic inflammation.

Methods:

This article is a general review, called a Primer, that brings together recent knowledge about VEXAS syndrome, including its frequency, biological mechanisms, clinical signs, diagnosis, complications, treatments and impact on quality of life.

Results:

VEXAS mainly affects men over the age of 50. Symptoms may include fever, fatigue, weight loss, skin involvement, cartilage inflammation — for example of the ears — lung involvement, joint pain, blood abnormalities and an increased risk of blood clots. Many patients have anaemia with enlarged red blood cells, sometimes low platelet counts, and bone marrow abnormalities. Diagnosis is confirmed by genetic testing for a UBA1 mutation.

Discussion:

The disease is often difficult to recognize because it can resemble other inflammatory, dermatological, rheumatological or haematological diseases. Corticosteroids often improve symptoms rapidly, but long-term corticosteroid dependence is common. Other treatments may be used, including JAK inhibitors, therapies targeting specific cytokines, azacitidine or, in selected cases, stem cell transplantation.

Conclusion:

VEXAS has changed the understanding of some adult inflammatory diseases by showing the link between inflammation, acquired genetics and blood disorders. Earlier diagnosis and prospective studies are needed to improve patient care and quality of life.

PubMed link: https://pubmed.ncbi.nlm.nih.gov/?term=10.1038%2Fs41572-026-00695-w

Therapeutic Outcomes in VEXAS Syndrome: A Multicenter Comparative Cohort of Allogeneic Hematopoietic Stem Cell Transplantation and Hypomethylating Agents

First author: Saubia Fathima

Journal: American Journal of Hematology, 2026

Link to the article: https://pubmed.ncbi.nlm.nih.gov/42260942/

Authors of the abstract: Pr Sophie Georgin-Lavialle et Pr Olivier Kosmider

Key points

- In this multicenter cohort of 66 patients with VEXAS syndrome, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was associated with better overall survival than hypomethylating agents (HMAs).

- Allo-HSCT achieved molecular remission in all evaluable patients, compared with 22% under HMAs.

- Corticosteroid withdrawal was markedly more frequent after transplantation than with HMAs.

- HMAs -mainly azacitidine- remained active in some patients, but with a high rate of discontinuation due to toxicity or lack of efficacy.

- These findings support allo-HSCT as a potentially curative strategy in selected patients.

Summary

VEXAS syndrome is an acquired hematoinflammatory disease caused by somatic mutations in the UBA1 gene, affecting mainly men over 50 years of age. It combines systemic autoinflammatory manifestations, cytopenias, and sometimes an associated myelodysplastic syndrome. Management remains challenging, with frequent corticosteroid dependence and often limited effectiveness of steroid-sparing treatments. In this context, this retrospective multicenter U.S. study compared outcomes of two approaches targeting the pathological clone: hypomethylating agents and allogeneic hematopoietic stem cell transplantation.

Sixty-six patients with confirmed VEXAS were included between 2019 and 2025, including 31 treated with allo-HSCT and 35 with an HMA, mainly azacitidine. Indications for therapy were glucocorticoid-refractory inflammation, progressive bone marrow failure or associated myeloid neoplasia, or combinations of these manifestations. The two groups were broadly comparable clinically and biologically, except for older age in the HMA group.

After a median follow-up of 18 months, 14 deaths were observed 3 in the transplant group and 11 in the HMA group. Allo-HSCT was associated with a significant improvement in overall survival, with median survival not reached versus 29.6 months with HMAs, including after adjustment for age and comorbidities. This superiority persisted across several sensitivity analyses, strengthening the robustness of the signal despite methodological limitations inherent to the retrospective design.

Beyond survival, allo-HSCT was associated with major clinical and biological benefit. All evaluable patients achieved molecular remission, with no re-emergence of the UBA1 clone at last follow-up. Corticosteroid discontinuation was also far more frequent after transplantation, with steroid cessation in 58% of patients, versus only 6% with HMAs. By contrast, HMAs showed real but more modest activity, with molecular remission in 22% of evaluable patients and a high treatment discontinuation rate. Nearly one in two patients stopped treatment, mainly due to infections, prolonged cytopenias, toxicity, or lack of response.

Overall, this North American study suggests that allo-HSCT is currently, as expected, the most effective and potentially curative option for eligible patients with VEXAS, particularly in severe disease, steroid dependence, or bone marrow involvement. HMAs may still have a role in patients not immediately eligible for transplant, as bridging therapy or a step toward transplantation, but in this study their benefit appeared more modest and less durable.