VEXAS syndrome
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Based on current guidelines and the current state of research, there are various diagnostic recommendations for patients with VEXAS syndrome. We have summarized the most important information on classification and diagnostic methods at MLL. We also provide further links and literature on VEXAS syndrome.
VEXAS syndrome: Classification
VEXAS syndrome is a multisystemic disease that occurs predominantly in men (95.7-100% men) (Georgin-Lavialle et al. 2022). The clinical picture is autoinflammatory and was first described in 2020. The name is an acronym of the following words (Beck et al. 2020):
- V = vacuoles
- E = E1 Enzyme
- X = X-linked
- A = autoinflammatory
- S = somatic
The cause of VEXAS syndrome is a somatic mutation in the UBA1 gene, whereby various organ systems can be affected.
VEXAS syndrome is characterized by treatment-resistant or high-dose steroid-dependent inflammation, cytopenias and thrombotic events. Inflammatory symptoms, which can affect the ear, nose, skin and lungs, and fever are often the first symptoms (Patel et al. 2023). Various rheumatological diseases such as recurrent polychondritis and vasculitis are common diagnoses (Beck et al. 2020).
Hematological findings are also typical of VEXAS syndrome, with (macrocytic) anemia being the most common. As the disease progresses, lymphocytopenia (80%), monocytopenia (73%), thrombocytopenia (33%) and neutropenia (23%) may also occur (Obiorah et al. 2021, Olteanu et al. 2024). When these cytopenias are investigated, a diagnosis of myelodysplastic neoplasia (MDS) can be made (25-55%) (Gutierrez-Rodrigues et al. 2023), but most cases are classified as idiopathic cytopenias or ICUS. It is noteworthy that VEXAS syndrome can also occur together with MGUS, MBL and multiple myeloma (Beck et al. 2020, Obiorah et al. 2021, Beck et al. 2022) or can also develop during the course of an MPN (Djerbi et al. 2023).
VEXAS syndrome: Diagnostic methods and their relevance
VEXAS syndrome: Prognosis & Therapy
VEXAS syndrome typically occurs in men in the 5th to 6th decade of life (Gurnari & Visconte 2023). The 5-year survival rate is estimated at 50-80% (Baur et al. 2023). Risk factors associated with survival include the presence of ear perichondritis, the development of transfusion-dependent anemia and genotype (Ferrada et al. 2022).
VEXAS patients have a high risk of thrombotic events, most commonly venous thromboembolism (41%) (Kusne et al. 2024). However, sudden deep vein thrombosis in older men alone is not a sufficient criterion for the suspicion of VEXAS syndrome (Khider et al. 2022). Thromboprophylaxis is recommended if VEXAS syndrome is confirmed, provided it is not contraindicated.
A simple scoring system was developed and validated for the risk assessment of VEXAS syndrome, in which the parameters are age >50 years (1 point), cutaneous lesion (1 point), pulmonary involvement (1 point), chondritis (1 point) and macrocytic anemia (2 points). In patients with a score of more than 3, it is recommended to perform UBA1 sequencing (Maeda et al. 2023, Rogez et al. 2023).
The treatment of VEXAS syndrome can be divided into three approaches. The first is aimed at the UBA1-mutated clone, the second at the control of inflammatory symptoms and the third at the supportive treatment of cytopenias. Curative treatment to eradicate the UBA1-mutated clone is currently only possible through a blood stem cell transplantation (Al-Hakim et al. 2023). In patients who did not qualify for SCT, it was reported that therapy with azacitidine resulted in a reduction of the UBA1-mutatedclones, as well as clinical and hematologic remissions (Sockel et al. 2024). JAK inhibitors, in particular ruxolitinib (Heiblig et al. 2022) and the IL-6 inhibitor tocilizumab (Kirino et al. 2021) also appear to be an at least temporarily effective treatment option for patients with VEXAS syndrome. They lead to control of inflammatory symptoms, but often do not improve cytopenias. VEXAS patients also have an increased risk of infection and thrombosis, so individualized management is required. Further data needs to be collected in order to develop an optimal treatment concept (Conway 2022, Heiblig et al. 2022).
![](https://www.mll.com/media/pages/sonstige-maligne-und-benigne/vexas-syndrom/865d92c5c2-1715767426/fig-vexas-therapymanagement-1600x-q99.jpg)
ATG = anti-thyroglobulin, CR = complete remission, ESA = erythropoiesis stimulating agent, FB2 = fludarabine + bulsofan conditioning regimen, FluMel = fludarabine + melphalan conditioning regimen, HaploID = haplo-identical, BM = bone marrow, MDS = myelodysplastic neoplasia, MMF = mycophenolate mofetil, MSD = matched sibling donor, MUD = matched unrelated donor, PBMC = peripheral blood mononuclear cells, PTCY = post transplant cyclophosphamide, RIC = reduced intensity conditioning, Tacro = tacrolism
VEXAS syndrome: Recommendation
Currently, VEXAS syndrome is still a rarely diagnosed and poorly understood condition. The diagnosis therefore requires thorough evaluation by specialists. If possible, patients should be included in the VEXAS registry: https://vexas.net/.
Status: May 2024