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

2025: A Year Rich in Autoinflammation, FMF, and VEXAS

In 2025, together with the team of the CEREMAIA Reference Center (Tenon Hospital, AP-HP / Sorbonne University), within the FAI2R network and the European Reference Network ERN RITA, we carried out extensive work focused on:

Familial Mediterranean Fever (FMF) and pyrin-associated diseases,

VEXAS syndrome, a prototype of hemato-inflammatory diseases,

AA amyloidosis and other rarer autoinflammatory diseases.

🔬 FMF and pyrin

We contributed to the update of the international EULAR/PReS recommendations for FMF, which incorporate recent advances regarding colchicine resistance and the use of biologic therapies (published in Annals of the Rheumatic Diseases, 2025).

Several studies based on the adult cohort of our reference center explored the following aspects: iron deficiency, liver involvement, FMF onset after the age of 65, the optimal daily dose of colchicine, and patients’ and prescribers’ perceptions of colchicine treatment.

We also conducted biological and genetic research on variants of the MEFV gene and pyrin-associated diseases, as well as on the role of IL-18 as a monitoring biomarker and as a specific signature of diseases involving the pyrin inflammasome.

🧬 VEXAS syndrome

In collaboration with the French VEXAS group and the MINHEMON club:

international reviews and recommendations were developed to structure the diagnosis and management of VEXAS syndrome, including a consensual definition of “flares,” infectious risks, and therapeutic strategies;

studies focused on specific organ involvement (kidney, nervous system, erythroblastopenia), as well as a multicenter study on VEXAS in women and across different ethnic backgrounds.

🧩 AA amyloidosis and other rare autoinflammatory diseases

We participated in a systematic review on AA amyloidosis in inflammatory rheumatic diseases, highlighting the importance of long-term strict control of inflammation.

We authored literature reviews on autoinflammatory actinopathies, A20 haploinsufficiency, and undifferentiated autoinflammatory diseases.

We also published work on diagnostic delay and the clinical presentation of cryopyrin-associated periodic syndromes (CAPS) in adulthood.

🧠 Therapeutic patient education programs

We continued the deployment of our three therapeutic education programs dedicated to AA amyloidosis, cryopyrinopathies (CAPS), and FMF. These programs aim to help patients and their relatives better understand the disease, treatments, monitoring, and warning signs.

In 2025, we notably led a session dedicated to CAPS during the weekend organized in July by the Muckle-Wells / CINCA association, in close collaboration with patient associations.

🎥 Patient webinars and online information

We launched a series of informational webinars for patients and their relatives on FMF, as well as educational videos on rare autoinflammatory diseases (AA amyloidosis, VEXAS syndrome, etc.), freely available on the CEREMAIA Tenon YouTube channel: CEREMAIA Tenon – Patient Webinars. These formats allow us to translate research findings and recommendations into practical messages for patients’ daily lives.

• All of this work shares a common goal:

• to better characterize these rare diseases,

• to refine diagnostic and monitoring strategies,

and ultimately, to provide more personalized and safer care for patients.

We warmly thank the patients, healthcare teams, colleagues from rare disease networks, and international partners for their commitment.

For those who would like to access specific articles in more detail, please feel free to contact us via private message or by email at:

ceremaia-medecine-int.tenon@aphp.fr

VEXAS syndrome and the risk of infections: what do we know and how can they be prevented?

Article title: Mapping the infectious burden in VEXAS syndrome:a systematic review and rationale for prevention

First author: Valentine Ribier

Journal: Lancet Rheumatology

Link to the article: https://doi.org/10.1016/S2665-9913(25)00225-5

Author of the abstract: Rim BOURGUIBA

Introduction:

VEXAS syndrome is an autoinflammatory disease associated with somatic mutations in the X‑linked UBA1 gene. Patients present with systemic inflammatory manifestations and an increased susceptibility to infections. In the French cohort, more than 50% of mortality was attributed to infections. Several factors have been identified as contributors to infection risk in these patients: long‑term corticosteroid therapy, combination and prolonged use of immunosuppressive treatments such as JAK inhibitors, and a likely functional immune deficiency of myeloid cells related to the disease itself. Multiple publications have reported opportunistic and invasive infections in VEXAS even in the absence of immunosuppressive or immunomodulatory therapy. Few recommendations existed regarding infection prophylaxis in VEXAS. The objectives of this review were: 1) to characterize the spectrum of infections in VEXAS, 2) to identify a high‑risk subgroup for infections, and 3) to propose a preventive strategy to reduce infection‑related complications.

Methods:

This systematic review followed PRISMA guidelines. The literature search included publications from October 2020 to October 31, 2024 without language restrictions on PubMed. The authors included case reports and case series. Eligibility criteria were the presence of infection, its frequency, and its nature among patients with VEXAS syndrome. Infection was confirmed when a pathogen was identified. A severe infection was defined as one requiring hospitalization with intravenous antibiotic therapy or resulting in death.

Results:

The authors identified 506 potentially eligible studies; after exclusions, 57 studies were retained, encompassing 813 patients.

Infection frequency was high: 37–60% of patients experienced at least one infection, with 12–15% dying from infections in large cohorts. Severe infections accounted for up to 60% of cases. The most frequent infection sites were respiratory (28–59%), skin and soft tissue (10–49%), and bloodstream (bacteremia 8–13%), with genitourinary and gastrointestinal infections less common. Main pathogens included bacteria (Gram‑negative bacilli and Gram‑positive cocci), and opportunistic infections such as Legionella, atypical mycobacteria, Pneumocystis jirovecii, VZV, CMV, HSV, Aspergillus, and Nocardia. (Figure 1)

Factors associated with infections included exposure to immunosuppressive treatments: azacitidine was associated with 44–62% infections, including deaths; IL‑6 inhibitors with 29–47%; and JAK inhibitors with 18–37%. IL‑1 inhibitors were associated with a lower rate (3%). Chronic corticosteroid therapy was associated with mycobacterial infections or pneumocystosis.

The authors proposed the following prevention strategy:

• Targeted anti‑infective prophylaxis, for example co‑trimoxazole to prevent Pneumocystis jirovecii pneumonia and valaciclovir to prevent VZV reactivation.

• Systematic vaccinations, including influenza, pneumococcus, VZV, and SARS‑CoV‑2, despite a potential for reduced vaccine responses.

• Comprehensive infectious disease screening before initiating immunosuppression, including serologies (HIV, HBV, HCV, TB) and chest CT.

Conclusion:

VEXAS syndrome is associated with a major predisposition to infections, resulting from both an intrinsic immune deficit linked to UBA1 mutation and the effects of immunosuppressive treatments. Infections are a leading cause of morbidity and mortality, particularly affecting the respiratory tract and skin. Prevention should be a central pillar of care, based on vaccination, targeted anti‑infective prophylaxis, and risk assessment prior to any immunosuppression. These data support an integrated, multidisciplinary, and proactive approach to improve survival and quality of life for people living with VEXAS.

Figure 1: Distribution of infection sites and pathogens across studies

Le syndrome VEXAS et le risque d’infections.pdf

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