VEXAS syndrome as a mimicker of ANCA-associated vasculitis

Differentiating VEXAS syndrome from cases of canonical forms of primary vasculitis remains a significant clinical challenge, particularly for ANCA-associated vasculitis (AAV). We reviewed the clinical features of VEXAS as an AAV mimicker, while adding three new cases to the existing literature.

We identified three cases of VEXAS with an AAV phenotype in our institution. We performed a comprehensive literature search of available similar cases and summarized and compared the findings. Inclusion criterion was a positive UBA1 mutation analysis.

Patient 1 was referred for evaluation of eosinophilic granulomatosis with polyangiitis (GPA), but had no active respiratory symptoms, despite CT imaging showing widespread ground-glass opacities. Patient 2 had no history of sinus disease, despite being referred under the diagnostic construct of limited GPA. Patient 3 developed a novel inflammatory syndrome suspected to represent GPA. Six other cases were identified upon literature review. In all the cases, the most common findings were pulmonary infiltrates (67%), skin involvement (55%) and ocular manifestations (44%). Additionally, 44% of cases had renal involvement, with half of them displaying kidney lesions resembling the typical AAV pattern.

VEXAS can mimic different phenotypes of AAV and should be considered in atypical AAV presentations, especially when refractory to multiple treatments. Further studies are needed to explore the immunologic basis for an AAV phenotype within the spectrum of VEXAS.