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Is it VEXAS or is it vasculitis?

Megan M Sullivan1, Matthew J Koster2

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VEXAS syndrome, caused by UBA1 gene mutations, leads to refractory autoinflammatory disease with diverse vasculitis. Early consideration is key for patients with difficult-to-treat vasculitis.

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Area of Science:

  • Genetics and Immunology
  • Molecular Biology
  • Rheumatology

Background:

  • VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently identified autoinflammatory disorder.
  • It arises from somatic mutations in the UBA1 gene, crucial for the ubiquitin pathway.
  • This pathway dysfunction results in treatment-refractory systemic inflammation and hematologic issues.

Purpose of the Study:

  • To review the vasculitic manifestations of VEXAS syndrome.
  • To guide clinicians in identifying VEXAS syndrome in patients with atypical vasculitis.
  • To provide recommendations for considering VEXAS in refractory vasculitis cases.

Main Methods:

  • Literature review focusing on VEXAS syndrome and vasculitis.
  • Analysis of clinical features, genetic basis, and treatment responses.
  • Synthesis of current knowledge on vasculitic presentations.

Main Results:

  • VEXAS syndrome presents with a spectrum of vasculitis, affecting small, medium, and large vessels.
  • Clinical heterogeneity is a hallmark, often complicating diagnosis.
  • The condition is frequently resistant to standard treatments.

Conclusions:

  • Vasculitis is a significant, albeit heterogeneous, manifestation of VEXAS syndrome.
  • Increased awareness and consideration of VEXAS are crucial for patients with refractory vasculitis.
  • Timely diagnosis can potentially improve patient outcomes by guiding appropriate management strategies.