VEXAS syndrome as a mimicker of ANCA-associated vasculitis

Objectives 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.Methods 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.Results 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.Conclusion 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. What does this mean for patients?The vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory disorder caused by a genetic mutation in immune cells that mainly affects elderly males and, much less frequently, females. The most common findings in VEXAS are persistent fever and abnormally large red blood cells; however, it can also present with a myriad of symptoms that resemble other autoimmune disorders, including vasculitis (autoimmune inflammation of blood vessels). We describe three cases that were initially diagnosed with certain forms of ANCA-associated vasculitis (AAV) but were later diagnosed with VEXAS. Additionally, we compared these cases with similar ones already published. We found that VEXAS can mimic certain types of AAV and, when it presents as such, the symptoms usually do not respond to multiple treatments and long-term use of steroids, such as prednisone, is required. Patients can also have poor kidney function. Further research is needed to better characterize VEXAS and clinicians should consider it in cases of difficult-to-treat or atypical AAV.