• Matthew J Koster, Taxiarchis Kourelis, Kaaren K Reichard, Tanaz A Kermani, David B Beck, CardonaDaniela OspinaDONational Institutes of Health, National Human Genome Research Institute, Bethesda, MD., Matthew J Samec, Abhishek A Mangaonkar, Kebede H Begna, C Christopher Hook, Jennifer L Oliveira, Samih H Nasr, Benedict K Tiong, Mrinal M Patnaik, Michelle M Burke, Clement J Michet, and Kenneth J Warrington.
• Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN. Electronic address: koster.matthew@mayo.edu.
• Mayo Clin. Proc. 2021 Oct 1; 96 (10): 2653-2659.

AbstractThe objective of this study is to describe the clinical features and outcomes of patients with the newly defined vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Nine men with somatic mutations in the UBA1 gene were identified; the most frequent variant was p.Met41Thr (7 of 9, 78%). The median age at VEXAS diagnosis was 74 (67, 76.5) years, and patients had a median duration of symptoms for 4 years before diagnosis. Refractory constitutional symptoms (88%), ear and nose chondritis (55%), and inflammatory arthritis (55%) were common clinical features. Vasculitis was noted in 44%. All patients had significantly elevated inflammatory markers and macrocytic anemia. Thrombocytopenia was present in 66% at diagnosis of VEXAS. Eight patients had bone marrow biopsies performed. All bone marrows were hypercellular, and there was vacuolization of the erythroid (100%) or myeloid precursors (75%). Glucocorticoids attenuated symptoms at prednisone doses ≥20 mg per day, but no other immunosuppressive agent showed consistent long-term control of disease. One patient with coexisting plasma-cell myeloma received plasma-cell-directed therapy with improvement of the inflammatory response, which is a novel finding. In conclusion, VEXAS syndrome is a clinically heterogeneous, treatment-refractory inflammatory condition caused by somatic mutation of the UBA1 gene. Patients often present with overlapping rheumatologic manifestations and persistent hematologic abnormalities. As such, internists and subspecialists, including pathologists, should be aware of this condition to avert diagnostic delay, now that the etiology of this syndrome is known.Copyright © 2021 Mayo Foundation for Medical Education and Research. All rights reserved.

22 keywords...

hide…