VEXAS syndrome: a new discovered systemic rheumatic disorder

Abstract

VEXAS syndrome is an adult-onset autoinflammatory disease associated with hematologic symptoms. The disease affects primarily males, and leads to death of a significant proportion of the patients. VEXAS syndrome is caused by a somatic mutation of the <i>UBA1</i><i> gene</i> in hematopoietic progenitor cells. The clinical picture of the syndrome consists of a number of organ manifestations including those akin to rheumatic diseases, arthritis, myalgia, vasculitis and chondritis.

Fever, Rash, and Shortness of Breath in a 69-Year-Old

“…UBA1 gene variants reduce function of the UBA1 enzyme, which facilitates protein ubiquitination, a posttranslational modification process essential for cell signaling and protein degradation. Patients with VEXAS syndrome experience autoinflammation, characterized by recurrent episodes of inflammation in various organs …”

“…Approximately 40% to 60% of patients develop thromboembolism, and up to 77% have pulmonary infiltrates on computed tomography scans . Patients with VEXAS syndrome also have frequently been diagnosed with Sweet syndrome, giant cell arteritis, polyarteritis nodosa, relapsing polychondritis, myelodysplastic syndromes, and multiple myeloma . VEXAS syndrome should be considered in men with late-onset, undiagnosed inflammatory syndromes with associated hematologic abnormalities.…”

“…Clinical manifestations of VEXAS syndrome are variable and include skin lesions (eg, cutaneous vasculitis, neutrophilic dermatoses, erythema nodosum), recurrent fever, weight loss, orchitis, hepatosplenomegaly, ocular manifestations (eg, orbital inflammation, uveitis, scleritis, episcleritis), sensorineural hearing loss, and inflammatory arthritis . Approximately 40% to 60% of patients develop thromboembolism, and up to 77% have pulmonary infiltrates on computed tomography scans .…”

“…Elevated inflammatory markers (C-reactive protein level, erythrocyte sedimentation rate) and macrocytic anemia are typical laboratory findings. Lymphopenia occurs in approximately 80% and thrombocytopenia in 50% of patients with VEXAS syndrome . On bone marrow biopsy, more than 10% cytoplasmic vacuoles in myeloid and erythroid precursor cells is an indication for UB1A testing .…”

“…Lymphopenia occurs in approximately 80% and thrombocytopenia in 50% of patients with VEXAS syndrome . On bone marrow biopsy, more than 10% cytoplasmic vacuoles in myeloid and erythroid precursor cells is an indication for UB1A testing . The diagnosis of VEXAS syndrome is made by identifying UBA1 gene variants with polymerase chain reaction–based sequencing of DNA extracted from peripheral blood, bone marrow, or formalin-fixed paraffin-embedded tissue in a patient with symptoms characteristic of VEXAS syndrome …”