Background/Purpose: VEXAS syndrome is an autoinflammatory disease associated with somatic mutations in the UBA1 gene, which is located on the X chromosome, which explains the male preponderance of the disease [1].  Several case reports of females  with VEXAS syndrome have been published.

Our aim was to describe a series of female VEXAS from the French VEXAS cohort and to compare the clinical, biological and genetic characteristics of the disease between men and women.

Methods: A French national multicenter retrospective study was conducted between November 2020 and September 2023. All cases of VEXAS syndrome confirmed by the presence of a UBA1 mutation were included.

Results: The French cohort included 263 patients with VEXAS syndrome, 9 of whom (3%) were women with a mean age of 72.6 (± 10.4) years, which was not significantly different from men (p=0.56).

Clinically, the VEXAS syndrome in these 9 women was characterized by the presence of fever (n=8), altered general condition (n=5), neutrophilic dermatosis (n=3), chondritis (n=4), pulmonary infiltrate (n=3) and thromboembolic events (n=1). Comparison with the cohort of 263 men showed no statistically significant difference except for diarrhea (8/263 men  vs 1/9 women, p=0.05) and aortitis (7/263 men vs 1/9 women, p=0.04), which were observed more common in women.

In the female group, the median CRP was 56 mg/l [22-128].  Myelograms were performed in 8 patients; myeloid vacuoles were reported in five patients. The main features of the myelogram were MDS with a single lineage dysplasia (n=2), MDS with ring siberoblast (n=2), MDS with isolated del(5q) (n=1). Bone marrow karyotype showed X monosomy in 7 patients. Anemia was more profound in females: the mean hemoglobin level at diagnosis was 8.96 g/dl (± 0.96) versus 11.18 g/dl (± 10.1) in males (p=0.02). There was no difference in median corpuscular volume (103.45 (± 8.6) fl in women versus 101.46 (± 8.1) fl in men, p=0.44). 

UBA1 mutations in women were: p.M14V (n=4), p.M41L (n=2), p.M41T (n=2), other mutation in UBA1 c.T122C (20% detected with new generation sequencing) in one patient. Two additional mutations were identified by next-generation sequencing: ASXL1 (n=2) and U2AF1 (n=1).
During follow-up period, only one patient died in the female group.

Conclusion: This is the largest series of women diagnosed with VEXAS syndrome and supports what has been reported previously that VEXAS syndrome can affect women, although less frequently. The main clinical and laboratory features were similar to those reported in the first French series of patients with VEXAS [1]. Anemia was more profound in women than in men. In the presence of a suggestive clinical picture associated with macrocytic anemia and a biological inflammatory syndrome, sequencing of the UBA1 gene should be considered in both females and males especially in those with known Turner syndrome or X monosomia.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-and-biological-features-of-vexas-syndrome-in-women-study-of-9-french-cases-compared-with-263-men/