# Case Report: Diagnostic challenges in VEXAS syndrome with novel ultrastructural lung findings: IgG4-RD and vasculitis as relevant differential diagnoses

## TL;DR

A 70-year-old man with symptoms resembling IgG4-related disease and vasculitis was diagnosed with VEXAS syndrome after genetic testing, highlighting diagnostic challenges and the need for considering this rare condition.

## Contribution

The paper presents novel ultrastructural lung findings in VEXAS syndrome using transmission electron microscopy of transbronchial lung cryobiopsy samples.

## Key findings

- VEXAS syndrome can mimic IgG4-related disease and vasculitis, leading to diagnostic challenges.
- Transmission electron microscopy of TBLC samples provided new insights into the pathophysiology of VEXAS syndrome.
- Ruxolitinib and steroids provided temporary stabilization but did not improve long-term prognosis in this case.

## Abstract

VEXAS syndrome is a rare, adult-onset autoinflammatory disorder caused by somatic mutations in the UBA1 gene. Patients may present with symptoms similar to IgG4-related disease (IgG4-RD) or systemic vasculitis. We report the case of a 70-year-old man who presented with periorbital swelling, fever, and elevated serum IgG4. However, a biopsy of the lacrimal gland did not show histological evidence of IgG4-RD. Consecutively, the patient developed progressive pulmonary infiltrations, bicytopenia and leukocytoclastic vasculitis. Chest-CT showed organizing pneumonia, which was histologically proven by transbronchial lung cryobiopsy (TBLC), again excluding IgG4-RD. PET/CT revealed hypermetabolic bone marrow and bone marrow aspiration biopsy showed vacuolization of granulocytic precursor cells. Finally, genetic testing for UBA1 mutation confirmed the diagnosis of VEXAS syndrome. Treatment with ruxolitinib in addition to steroids, led to temporary stabilization but long-term prognosis was unfavorable. This case highlights the importance of considering VEXAS syndrome a relevant differential diagnosis of vasculitis and IgG4-RD in men. Furthermore, we present valuable insights into the pathophysiology of VEXAS through transmission electron microscopy (TEM) of TBLC samples.