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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

S Georgin-Lavialle  1 , B Terrier  2 , A F Guedon  3 , M Heiblig  4 , T Comont  5 , E Lazaro  6 , V Lacombe  7 , L Terriou  8 , S Ardois  9 , J-D Bouaziz  10 , A Mathian  11 , G Le Guenno  12   13 , A Aouba  14 , R Outh  15 , A Meyer  16 , M Roux-Sauvat  17 , M Ebbo  18 , L P Zhao  19 , A Bigot  20 , Y Jamilloux  21 , V Guillotin  12   13 , E Flamarion  22 , P Henneton  23 , G Vial  12   13 , V Jachiet  24 , J Rossignol  25 , S Vinzio  26 , T Weitten  27 , J Vinit  28 , C Deligny  29 , S Humbert  30 , M Samson  31 , N Magy-Bertrand  30 , T Moulinet  32 , R Bourguiba  1 , T Hanslik  33 , C Bachmeyer  1 , M Sebert  19 , M Kostine  34 , B Bienvenu  35 , P Biscay  36 , E Liozon  37 , L Sailler  38 , F Chasset  39 , A Audemard-Verger  20 , E Duroyon  40 , G Sarrabay  41 , F Borlot  42 , C Dieval  43 , T Cluzeau  44 , P Marianetti  45 , H Lobbes  12   13 , G Boursier  41 , M Gerfaud-Valentin  4 , J Jeannel  22 , A Servettaz  45 , S Audia  31 , M Larue  46 , B Henriot  47 , B Faucher  18 , J Graveleau  48 , B de Sainte Marie  12   13 , J Galland  49 , L Bouillet  26 , C Arnaud  38 , L Ades  19 , F Carrat  3 , P Hirsch  50 , P Fenaux  19 , O Fain  24 , P Sujobert  30 , O Kosmider  40 , A Mekinian  24 ; French VEXAS group; GFEV, GFM, CEREMAIA, MINHEMON
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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.

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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.
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    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.

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