Vasculitis associated with VEXAS syndrome

Abstract

Objectives: To define the prevalence, distribution and characteristics of patients with VEXAS (vacuoles, E1-enzyme, X-linked, autoinflammation, somatic) syndrome who have confirmed vasculitis.

Methods: Patients with VEXAS syndrome, verified by positive UBA1 mutation, were included. Chart review was performed to identify patient characteristics and outcomes. Vasculitis diagnosis was based on either histopathology showing vascular inflammation or non-invasive angiography findings. Summary statistics were calculated.

Results: Eighty-nine patients met inclusion criteria. All were male with a median age of onset of 66.9 years (interquartile range 60.1, 72.7). Median (interquartile range) follow-up was 3.8 (2.2-5.5) years, during which 21 patients (23.6%) had evidence of vasculitis. Vasculitis subtypes included small vessel vasculitis (19.1%), cutaneous medium vessel vasculitis (2.2%) and large vessel vasculitis (2.2%). No patient had more than one vessel size involved. Histopathology in small vessel vasculitis patients was consistent with cutaneous leukocytoclastic vasculitis in the majority, though one patient had leukocytoclastic peritubular capillaritis on renal biopsy. Cranial symptoms (headache, vision changes or jaw pain) were noted in 18.0%. Two additional patients not experiencing cranial symptoms exhibited large vessel involvement with confirmed carotid thickening on non-invasive angiography; one of these had a positive temporal artery biopsy.

Conclusion: VEXAS syndrome manifests as a variable vessel vasculitis in a quarter of patients, with cutaneous small and medium vessel involvement being particularly common. Some patients may have positive ANCA serologies or even renal vasculitis leading to misdiagnosis. Cranial symptoms are common and may mimic GCA, though documented large vessel inflammation is rare.

Keywords: UBA1 mutation; VEXAS syndrome; autoinflammatory disease; giant cell arteritis; somatic mutation; vascular inflammation; vasculitis.

Graphical abstract

Figure 1.

Small and large vessel vasculitis in VEXAS syndrome. (A) Gross image of petechial rash in a patient with VEXAS syndrome. (B) Pathology from above patient with sparse neutrophilic inflammation surrounding superficial dermal blood vessel walls consistent with small vessel vasculitis, scale bar is 50 μm. (C) Left internal (solid arrow) and external (dashed arrow) carotid circumferential periarterial thickening on CT angiography in a patient with VEXAS syndrome. (D) Endothelialitis with mixed inflammation is present in the intima of a muscular temporal artery, scale bar 100 μm, haematoxylin and eosin stain. VEXAS: vacuoles, E1-enzyme, X-linked, autoinflammation, somatic.