Journal of Diagnostics Concepts & Practice >
Current status and prospects of diagnosis and treatment of VEXAS syndrome
Received date: 2025-11-03
Revised date: 2025-11-19
Accepted date: 2025-11-19
Online published: 2026-02-25
VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently recognized autoinflammatory disease involving multiple systems, caused by somatic mutations in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene. Since the disease was first reported in 2020, the number of cases has increased rapidly worldwide, and single case and case series have also been reported in China. VEXAS syndrome predominantly occurs in middle-aged and elderly males, with complex and diverse clinical manifestations that often involve multiple systems, including fever, skin lesions, chondritis, pulmonary infiltrates, vasculitis, and macrocytic anemia, making it prone to misdiagnosis as other rheumatic or hematologic diseases. Diagnosis of VEXAS syndrome highly relies on UBA1 gene sequencing, which should be performed in patients with characteristic clinical presentations mentioned above and vacuolization of myeloid and erythroid precursor cells observed in bone marrow biopsy. The treatment of VEXAS syndrome is highly challenging, and there is currently no comprehensive standardized treatment guideline. Glucocorticoids are the first-line treatment for controlling acute inflammation, but most patients exhibit steroid dependence. Traditional immunosuppressants are mostly ineffective or difficult to sustain, while Janus kinase (JAK) inhibitors, interleukin-6 (IL-6) inhibitors, and hypomethylating agents have shown good efficacy in some patients. Allogeneic hematopoietic stem cell transplantation is currently the only method that can cure VEXAS syndrome, but the benefits and risks for patients must be strictly evaluated. Targeted precision therapy against UBA1-mutant clones may become a future research direction.
QIAN Haozhou , CHANG Chunkang . Current status and prospects of diagnosis and treatment of VEXAS syndrome[J]. Journal of Diagnostics Concepts & Practice, 2026 , 25(01) : 21 -29 . DOI: 10.16150/j.1671-2870.2026.01.004
| [1] | BECK D B, FERRADA M A, SIKORA K A, et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease[J]. N Engl J Med, 2020, 383(27):2628-2638. |
| [2] | MOLTENI R, FIUMARA M, CAMPOCHIARO C, et al. Mechanisms of hematopoietic clonal dominance in VEXAS syndrome[J]. Nat Med, 2025, 31(6):1911-1924. |
| [3] | BECK D B, BODIAN D L, SHAH V, et al. Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population[J]. JAMA, 2023, 329(4):318-324. |
| [4] | MOUDRY P, LUKAS C, MACUREK L, et al. Ubiquitin-activating enzyme UBA1 is required for cellular response to DNA damage[J]. Cell Cycle, 2012, 11(8):1573-1582. |
| [5] | LV Z, WILLIAMS K M, YUAN L, et al. Crystal structure of a human ubiquitin E1-ubiquitin complex reveals conserved functional elements essential for activity[J]. J Biol Chem, 2018, 293(47):18337-18352. |
| [6] | POULTER J A, COLLINS J C, CARGO C, et al. Novel somatic mutations in UBA1 as a cause of VEXAS syndrome[J]. Blood, 2021, 137(26):3676-3681. |
| [7] | MEISEL M, HINTERLEITNER R, PACIS A, et al. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host[J]. Nature, 2018, 557(7706):580-584. |
| [8] | ZHANG C R C, NIX D, GREGORY M, et al. Inflammatory cytokines promote clonal hematopoiesis with specific mutations in ulcerative colitis patients[J]. Exp Hematol, 2019,80:36-41,e3. |
| [9] | ARENDS C M, WEISS M, CHRISTEN F, et al. Clonal hematopoiesis in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis[J]. Haematologica, 2020, 105(6):e264-e267. |
| [10] | KUNIMOTO H, MIURA A, MAEDA A, et al. Clinical and genetic features of Japanese cases of MDS associated with VEXAS syndrome[J]. Int J Hematol, 2023, 118(4):494-502. |
| [11] | GUTIERREZ-RODRIGUES F, KUSNE Y, FERNANDEZ J, et al. Spectrum of clonal hematopoiesis in VEXAS syndrome[J]. Blood, 2023, 142(3):244-259. |
| [12] | FERRADA M A, SAVIC S, CARDONA D O, et al. Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis[J]. Blood, 2022, 140(13):1496-1506. |
| [13] | KOSTER M J, KOURELIS T, REICHARD K K, et al. Clinical heterogeneity of the VEXAS syndrome: A case series[J]. Mayo Clin Proc, 2021, 96(10):2653-2659. |
| [14] | GEORGIN-LAVIALLE S, TERRIER B, GUEDON A F, et al. Further characterization of clinical and laboratory features in VEXAS syndrome: Large-scale analysis of a multicentre case series of 116 French patients[J]. Br J Dermatol, 2022, 186(3):564-574. |
| [15] | FERRADA M A, SIKORA K A, LUO Y, et al. Somatic mutations in UBA1 define a distinct subset of relapsing polychondritis patients with VEXAS[J]. Arthritis Rheumatol, 2021, 73(10):1886-1895. |
| [16] | VAN DER MADE C I, POTJEWIJD J, HOOGSTINS A, et al. Adult-onset autoinflammation caused by somatic mutations in UBA1: A Dutch case series of patients with VEXAS[J]. J Allergy Clin Immunol, 2022, 149(1):432-439,e4. |
| [17] | ZAKINE E, SCHELL B, BATTISTELLA M, et al. UBA1 variations in neutrophilic dermatosis skin lesions of patients with VEXAS syndrome[J]. JAMA Dermatol, 2021, 157(11):1349-1354. |
| [18] | SAAD A J, PATIL M K, CRUZ N, et al. VEXAS syndrome: A review of cutaneous findings and treatments in an emerging autoinflammatory disease[J]. Exp Dermatol, 2024, 33(3):e15050. |
| [19] | ZAKINE è, PAPAGEORGIOU L, BOURGUIBA R, et al. Clinical and pathological features of cutaneous manifestations in VEXAS syndrome: A multicenter retrospective study of 59 cases[J]. J Am Acad Dermatol, 2023, 88(4):917-920. |
| [20] | BORIE R, DEBRAY M P, GUEDON A F, et al. Pleuropulmonary manifestations of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome[J]. Chest, 2023, 163(3):575-585. |
| [21] | KOSTER M J, SAMEC M J, WARRINGTON K J. VEXAS syndrome-a review of pathophysiology, presentation, and prognosis[J]. J Clin Rheumatol, 2023, 29(6):298-306. |
| [22] | KOSTER M J, LASHO T L, OLTEANU H, et al. VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management[J]. Am J Hematol, 2024, 99(2):284-299. |
| [23] | KUSNE Y, GHORBANZADEH A, DULAU-FLOREA A, et al. Venous and arterial thrombosis in patients with VEXAS syndrome[J]. Blood, 2024, 143(21):2190-2200. |
| [24] | GROARKE E M, DULAU-FLOREA A E, KANTHI Y. Thrombotic manifestations of VEXAS syndrome[J]. Semin Hematol, 2021, 58(4):230-238. |
| [25] | OBIORAH I E, PATEL B A, GROARKE E M, et al. Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1[J]. Blood Adv, 2021, 5(16):3203-3215. |
| [26] | PATEL N, DULAU-FLOREA A, CALVO K R. Characte-ristic bone marrow findings in patients with UBA1 somatic mutations and VEXAS syndrome[J]. Semin Hematol, 2021, 58(4):204-211. |
| [27] | HEBBAR M, BROUILLARD M, WATTEL E, et al. Association of myelodysplastic syndrome and relapsing polychondritis: Further evidence[J]. Leukemia, 1995, 9(4):731-733. |
| [28] | MEKINIAN A, GRIGNANO E, BRAUN T, et al. Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: A French multicentre retrospective study[J]. Rheumatology, 2016, 55(2):291-300. |
| [29] | MEKINIAN A M, GEORGIN-LAVAILLE S, FERRADA M A, et al. American college of rheumatology guidance statement for diagnosis and management of VEXAS deve-loped by the international VEXAS working group expert panel[J]. Arthritis Rheumatol, 2025. |
| [30] | BOURBON E, HEIBLIG M, GERFAUD VALENTIN M, et al. Therapeutic options in VEXAS syndrome: Insights from a retrospective series[J]. Blood, 2021, 137(26):3682-3684. |
| [31] | BOYADZHIEVA Z, RUFFER N, K?TTER I, et al. How to treat VEXAS syndrome: A systematic review on effectiveness and safety of current treatment strategies[J]. Rheumatology, 2023, 62(11):3518-3525. |
| [32] | COLLANTES-RODRíGUEZ C, JIMéNEZ-GALLO D, DE LA VARGA-MARTíNEZ R, et al. Vexas syndrome successfully treated with canakinumab[J]. J Dtsch Dermatol Ges, 2023, 21(1):69-70. |
| [33] | KHITRI M Y, HADJADJ J, MEKINIAN A, et al. VEXAS syndrome: An update[J]. Jt Bone Spine, 2024, 91(4):105700. |
| [34] | STAELS F, BETRAINS A, WOEI-A-JIN F J S H, et al. Case report: VEXAS syndrome: From mild symptoms to life-threatening macrophage activation syndrome[J]. Front Immunol, 2021,12:678927. |
| [35] | HEIBLIG M, FERRADA M A, KOSTER M J, et al. Ruxo-litinib is more effective than other JAK inhibitors to treat VEXAS syndrome: A retrospective multicenter study[J]. Blood, 2022, 140(8):927-931. |
| [36] | MINA A, KOMROKJI R. How I treat higher-risk MDS[J]. Blood, 2025, 145(18):2002-2011. |
| [37] | HEIBLIG M, PATEL B A, GROARKE E M, et al. Toward a pathophysiology inspired treatment of VEXAS syndrome[J]. Semin Hematol, 2021, 58(4):239-246. |
| [38] | MEKINIAN A, ZHAO L P, CHEVRET S, et al. A Phase Ⅱ prospective trial of azacitidine in steroid-dependent or refractory systemic autoimmune/inflammatory disorders and VEXAS syndrome associated with MDS and CMML[J]. Leukemia, 2022, 36(11):2739-2742. |
| [39] | COMONT T, HEIBLIG M, RIVIèRE E, et al. Azacitidine for patients with Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) and myelodysplastic syndrome: Data from the French VEXAS registry[J]. Br J Haematol, 2022, 196(4):969-974. |
| [40] | JACHIET V, KOSMIDER O, BEYDON M, et al. Efficacy and safety of azacitidine for VEXAS syndrome: A large-scale retrospective study from FRENVEX[J]. Blood, 2025, 146(12):1450-1461. |
| [41] | VAN LEEUWEN-KERKHOFF N, DE WITTE M A, HEIJSTEK M W, et al. Case report: Up-front allogeneic stem cell transplantation in a patient with the VEXAS syndrome[J]. Br J Haematol, 2022, 199(3):e12-e15. |
| [42] | LOSCHI M, ROUX C, SUDAKA I, et al. Allogeneic stem cell transplantation as a curative therapeutic approach for VEXAS syndrome: A case report[J]. Bone Marrow Transplant, 2022, 57(2):315-318. |
| [43] | DIARRA A, DUPLOYEZ N, FOURNIER E, et al. Successful allogeneic hematopoietic stem cell transplantation in patients with VEXAS syndrome: A 2-center experience[J]. Blood Adv, 2022, 6(3):998-1003. |
| [44] | WOLFF L, CARATSCH L, L?TSCHER F, et al. VEXAS syndrome: A Swiss national retrospective cohort study[J]. Swiss Med Wkly, 2025, 155(3):3879. |
| [45] | MANGAONKAR A A, LANGER K J, LASHO T L, et al. Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation in VEXAS syndrome: Data from a prospective series of patients[J]. Am J Hematol, 2023, 98(2):E28-E31. |
| [46] | AL-HAKIM A, POULTER J A, MAHMOUD D, et al. Allogeneic haematopoietic stem cell transplantation for VEXAS syndrome: UK experience[J]. Br J Haematol, 2022, 199(5):777-781. |
| [47] | GURNARI C, KOSTER L, BAAIJ L, et al. Allogeneic hematopoietic cell transplantation for VEXAS syndrome: Results of a multicenter study of the EBMT[J]. Blood Adv, 2024, 8(6):1444-1448. |
| [48] | ALI S B, GURNARI C. Allogenic haematopoietic stem cell transplantation in VEXAS: A review of 33 patients[J]. Clin Rheumatol, 2024, 43(11):3565-3575. |
| [49] | MOHTY R, RELJIC T, ABDEL-RAZEQ N, et al. Asses-sing the efficacy of allogeneic hematopoietic cell transplantation in VEXAS syndrome: Results of a systematic review and meta-analysis[J]. Bone Marrow Transplant, 2024, 59(10):1423-1427. |
| [50] | PENACK O, PECZYNSKI C, MOHTY M, et al. How much has allogeneic stem cell transplant-related morta-lity improved since the 1980s? A retrospective analysis from the EBMT[J]. Blood Adv, 2020, 4(24):6283-6290. |
| [51] | LABERKO A, SULTANOVA E, GUTOVSKAYA E, et al. Mismatched related vs matched unrelated donors in TCRαβ/CD19-depleted HSCT for primary immunodeficiencies[J]. Blood, 2019, 134(20):1755-1763. |
| [52] | FOX T A, CHAKRAVERTY R, BURNS S, et al. Successful outcome following allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency[J]. Blood, 2018, 131(8):917-931. |
| [53] | FASSLRINNER F, SCHETELIG J, BURCHERT A, et al. Long-term efficacy of reduced-intensity versus myeloablative conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: Retrospective follow-up of an open-label, randomised phase 3 trial[J]. Lancet Haematol, 2018, 5(4):e161-e169. |
| [54] | AOUDJHANE M, LABOPIN M, GORIN N C, et al. Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: A retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT)[J]. Leukemia, 2005, 19(12):2304-2312. |
| [55] | BEELEN D W, STELLJES M, REMéNYI P, et al. Treosulfan compared with reduced-intensity busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: Final analysis of a prospective randomized trial[J]. Am J Hematol, 2022, 97(8):1023-1034. |
/
| 〈 |
|
〉 |
