Background/Purpose: VEXAS syndrome is a monogenic somatic autoinflammatory syndrome associated with UBA1 mutations.

Objective. To describe clinical characteristics, laboratory findings, main treatments and outcomes of VEXAS syndrome. 

Methods: Design. Case-series.

Setting. Patients referred to a French multicenter registry between November 2020 and January may 2024

Patients. 299 patients with VEXAS syndrome.

Measurements. Frequency and median of parameters and vital status, from diagnosis to the end of the follow-up.

Results: Results.

Among 299 patients, 291 (96%) were males with median age at diagnosis of 73 years old ranging from 49.9 to 96. The main clinical features were skin lesions (84,6%), mainly sweet syndrome and erythematous lesions, followed by alteration of general status with weight loss (66,7%), fever (58,6%) lung involvement (51,8%), mostly pulmonary infiltrates; thrombosis (48,8%) was frequent, almost always veinous. Ocular inflammatory involvement was present in 39,5%, mainly conjonctivitis (n=18), orbital mass (n=16) uveitis (n=15) episcleritis (n=14) and scleritis (n=10). The other main features were respectively relapsing chondritis in 38,5%; arthralgia (35,8%), adenopathies in 25%; nervous system (24,4%) with mainly aseptic meningitidis (n=45); splenomegaly in 14%, gastrointestinal involvement was not very frequent (10%) followed by hepatomegaly in 7,7%, kidney involvment in 7,7%, heart involvement in 4,3%. AA amyloidosis was present in only 2 cases.

Median hemoglobin rate was 9,9 g/dL [6-10,5] and median globular volume (MGV) 101,2 [82-122]; median platelets were 189000 [5-196000]. Median CRP levels were at 60 [0,5-335] mg/l; median ferritin was 860 [1-977]. UBA1sequencing was mostly performed by NGS panel (51,6%) and sanger (45,2%) and showed as most frequent mutations: p.M41T (40,7%), p.M41V (27,1%), p.M41L (20,3%), and other (11%).  Other myeloid somatic mutations were detected by panel in 70 cases (34,8%) mostly DNMTA3 and TET2.

Hematological disease was present myelodysplastic syndrome (MDS, n= 120; 40%), mostly MDS with single lineage dysplasia; monoclonal gammapathy of unknown significance was detected in (n=43, 23,2%). Karyotype had been performed in 135 cases and normal in 76,3%.

When researched, vacuoles were present in 70,8%.

Most patients received steroids (88,3%); JAK inhibitors were used in 53 patients (24,4%),, IL-6 inhibitors in 51 cases (23,4%) , mostly tocilizumab; azacytidine and IL1 blockers: each  in 37 patients (17,1%). Previous immunosuppressive therapies were TNF blockers (13%), cyclophosphamide (6%), MMF (5%).  Only 3 patients underwent stem cell allograft

Fourty patients died (13,4%) at a median age of 76 years old, mostly from infections (n=14); No patients progressed to acute leukemia

Conclusion: To date this is the largest cohort of VEXAS syndrome patients showing the heterogeneity of clinical presentation with mainly biological inflammation and systemic features such as alteration of general status and predominance of cutaneous features. Vacuoles are not always present; Recurrent chondritis and myelodysplastic syndrome are not mandatory.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/heterogeneity-of-vexas-syndrome-a-multicenter-case-series-of-299-cases-from-the-french-vexas-study-group-frenvex/