Clinical Heterogeneity of the VEXAS Syndrome: A Case Series

Matthew J. Koster, Taxiarchis Kourelis, Kaaren K. Reichard, Tanaz A. Kermani, David B. Beck, Daniela Ospina Cardona, 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, Kenneth J. Warrington

Research output: Contribution to journalArticlepeer-review

Abstract

The 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.

Original languageEnglish (US)
Pages (from-to)2653-2659
Number of pages7
JournalMayo Clinic proceedings
Volume96
Issue number10
DOIs
StatePublished - Oct 2021

ASJC Scopus subject areas

  • Medicine(all)

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