Overview of New VEXAS Syndrome Save

Medscape offers up an informative overview of the newly described syndrome called VEXAS discovered by researchers at the National Institutes of Health. These patients were previously misdiagnosed with Sweets syndrome, relapsing polychondritis, myelodysplastic syndrome, MGUS, or polyarteritis nodosa – but were now unified by a somatic (UBA1) mutation.

The disorder was discovered in 2020 from 3 middle aged men presenting to the NIH iwth an adult-onset, severe autoinflammatory syndrome.

Further investigations revealed somatic mutations in UBA1 in all three who appeared to have a relapsing polychondritis (RP) like disorder.  UBA1 is found mostly in myeloid cells (not T & B cells).  Bone marrow aspirates showed vacuolar changes in cellular aspirates. Characterization of 25 male patients with this UBA1 mutation with found patients with fevers, Sweets-like  rash,  neutrophilic pulmonary involvement, chondritis, venous thromboembolic events,  macrocytic anemia and BM vacuoles.

Key features of VEXAS are:

• V acuoles
• E1 ubiquitin-activating enzyme
• X - Linked
• A utoinflammatory
• S omatic

VEXAS could have a prevalence of 1 per 20,000-30,000 individuals.

The diagnosis of VEXAS should be considered in middle-aged or older men with refractory relapsing polychondritis, giant cell arteritis, polyarteritis nodosa, or Sweet syndrome. They may present with periodic fevers, lung infiltrates, venous thromboembolic events, neutrophilic dermatoses, ear chondritis, and periorbital edema. or features suggestive of myelodysplastic syndrome, multiple myeloma, or monoclonal gammopathy of unknown origin. Labs usually show very high C-reactive protein or erythrocyte sedimentation rate levels.

Currently the only reliable therapy is high-dose corticosteroids, but other therapies, including tocilizumab are being considered.