Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review

Koushan Kouranloo; Mrinalini Dey; Jude Almutawa; Nikki Myall; Arvind Nune

doi:10.1007/s00296-023-05513-0

Clinical characteristics, disease trajectories and management of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome: a systematic review

Rheumatol Int. 2023 Dec 21. doi: 10.1007/s00296-023-05513-0. Online ahead of print.

Authors

Koushan Kouranloo^{1

2}, Mrinalini Dey³, Jude Almutawa⁴, Nikki Myall⁵, Arvind Nune⁶

Affiliations

¹ Department of Rheumatology, East Surrey Hospital, Canada Avenue, Redhill, RH1 5RH, UK. k.kouranloo@doctors.net.uk.
² School of Medicine, Cedar House, University of Liverpool, Ashton Street, Liverpool, L69 3GE, UK. k.kouranloo@doctors.net.uk.
³ Centre for Rheumatic Diseases, Weston Education Centre, Cutcombe Road, London, SE5 9RJ, UK.
⁴ Liverpool University NHS Foundation Trust, Prescot Street, Liverpool, L7 8XP, UK.
⁵ British Medical Association Library, BMA House, Tavistock Square, London, WC1H 9JP, UK.
⁶ Department of Rheumatology, Southport & Ormskirk Hospital NHS Trust, Town Lane, Kew, Southport, PR8 6PN, UK.

PMID: 38129348
DOI: 10.1007/s00296-023-05513-0

Abstract

Background: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly discovered autoinflammatory condition characterised by somatic mutation of the UBA1 gene. The syndrome leads to multi-system inflammation affecting predominantly the skin, lungs and bone marrow.

Methods: We undertook a systematic review of the multisystem features and genotypes observed in VEXAS syndrome. Articles discussing VEXAS syndrome were included. Medline, Embase and Cochrane databases were searched. Information was extracted on: demographics, type and prevalence of clinical manifestations, genetic mutations and treatment. Meta-analysis using a random effects model was used to determine pooled estimates of serum markers.

Results: From 303 articles, 90 were included, comprising 394 patients with VEXAS. 99.2% were male, with a mean age of 67.1 years (SD 8.5) at disease onset. The most frequent diagnoses made prior to VEXAS were: relapsing polychondritis (n = 59); Sweet's syndrome (n = 24); polyarteritis nodosa (n = 11); and myelodysplastic syndrome (n = 10). Fever was reported in 270 cases (68.5%) and weight loss in 79 (20.1%). Most patients had haematological (n = 342; 86.8%), dermatological (n = 321; 81.5%), pulmonary (n = 297; 75.4%%) and musculoskeletal (n = 172; 43.7%) involvement, although other organ manifestations of varying prevalence were also recorded. The most commonly reported mutations were "c.122T > C pMET41Thr" (n = 124), "c.121A > G pMET41Val" (n = 62) and "c.121A > C pMet41Leu" (n = 52). Most patients received glucocorticoids (n = 240; 60.9%) followed by methotrexate (n = 82; 20.8%) and IL-6 inhibitors (n = 61, 15.4%). One patient underwent splenectomy; 24 received bone marrow transplants.

Conclusion: VEXAS syndrome is a rare disorder affecting predominantly middle-aged men. This is the first systematic review to capture clinical manifestations, genetics and treatment of reported cases. Further studies are needed to optimise treatment and subsequently reduce morbidity and mortality.

Keywords: Autoinflammation; Miscellaneous disorders; Systematic review; VEXAS.

Publication types

Systematic Review