VEXAS Syndrome—A Review of Pathophysiology, Presentation, and Prognosis

Abstract

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a newly identified disease caused by somatic mutations in the UBA1 gene resulting in refractory autoinflammatory features, frequently accompanied by cytopenias. Although the prevalence of this syndrome is yet unknown, understanding the clinical phenotype can assist clinicians in prompt recognition of cases among patients with glucocorticoid-responsive but immunosuppressive-resistant inflammatory symptoms. The pathophysiology, clinical presentation, diagnostic methods, treatment, and prognosis of VEXAS are herein reviewed.

Treatment-Resistant Edematous Annular Plaques and Mild Leukopenia in a Man in His 60s

“…3 Three amino acid substitutions have been described: threonine, valine, and leucine. 4 The amino acid substitution portends disease phenotype and prognosis. 2,5 VEXAS syndrome has predominantly been described in men aged 55 to 65 years, although women with monosomy X have also been reported.…”

“…2,5 VEXAS syndrome has predominantly been described in men aged 55 to 65 years, although women with monosomy X have also been reported. [4][5][6] A recent observational study suggests VEXAS syndrome prevalence is 1 in 13 591 individuals. 6 Patients typically present with fever, skin lesions (usually neutrophilic der- matosis), and hematologic abnormalities (eg, macrocytic anemia and thrombocytopenia).…”

“…4 Tocilizumab may have steroid-sparing effects. 4 Patients who develop high-risk MDS have been treated with azacitidine and stem cell transplant. 4 VEXAS syndrome is a highly morbid disease, with mortality of approximately 50% at 5 years.…”

“…4 Patients who develop high-risk MDS have been treated with azacitidine and stem cell transplant. 4 VEXAS syndrome is a highly morbid disease, with mortality of approximately 50% at 5 years. Drug-induced SCLE (DI-SCLE) presents as erythematous scaling and annular plaques on the chest, back, and upper outer arms.…”

“…Impaired cellular ubiquitination activates the unfolded protein response and ultimately upregulates type 1 interferons . Three amino acid substitutions have been described: threonine, valine, and leucine . The amino acid substitution portends disease phenotype and prognosis .…”