Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2022 Mar;186(3):564-574.
doi: 10.1111/bjd.20805. Epub 2021 Nov 28.

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients

Affiliations
Free article
Multicenter Study

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients

S Georgin-Lavialle et al. Br J Dermatol. 2022 Mar.
Free article

Abstract

Background: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome').

Objectives: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome.

Methods: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded.

Results: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis.

Conclusions: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

PubMed Disclaimer

Comment in

References

    1. Beck DB, Ferrada MA, Sikora KA et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med 2020; 383:2628-38.
    1. van der Made CI, Potjewijd J, Hoogstins A et al. Adult-onset autoinflammation caused by somatic mutations in UBA1: a Dutch case series of VEXAS patients. J Allergy Clin Immunol. https://doi.org/10.1016/j.jaci.2021.05.014.
    1. Ferrada MA, Sikora KA, Luo Y et al. Somatic mutations in UBA1 define a distinct subset of relapsing polychondritis patients with VEXAS syndrome. Arthritis Rheumatol 2021; 73:1886-95.
    1. Tsuchida N, Kunishita Y, Uchiyama Y et al. Pathogenic UBA1 variants associated with VEXAS syndrome in Japanese patients with relapsing polychondritis. Ann Rheum Dis. https://doi.org/10.1136/annrheumdis-2021-220090.
    1. Bourbon E, Heiblig M, Gerfaud-Valentin M et al. Therapeutic options in VEXAS syndrome: insights from a retrospective series. Blood 2021; 137:3682-4.

Publication types

MeSH terms

Substances