Clinical and laboratory markers to distinguish VEXAS from Schnitzler's syndrome: data from the AIDA network registries

Background A substantial overlap in demographic, clinical, and laboratory features can complicate the differential diagnosis between Schnitzler's syndrome and VEXAS syndrome. The present study was undertaken to identify clinical and laboratory parameters that should raise suspicion for VEXAS syndrome among patients previously diagnosed with, or under evaluation for, Schnitzler's syndrome. Methods Data from male-only patients with Schnitzler's syndrome or VEXAS syndrome were obtained from international AIDA Network registries. Subjects with Schnitzler's syndrome were compared to VEXAS patients with urticarial skin manifestations resembling cutaneous features typically observed in Schnitzler's syndrome. Results A total of 19 VEXAS patients and 18 patients with Schnitzler's syndrome were enrolled. At univariate binary logistic regression, the diagnosis of VEXAS syndrome was associated with the age at disease onset (OR = 1.08, 95% CI. 1.01–1.16, p = 0.02), hemoglobin levels (OR = 0.44, 95% CI. 0.26–0.77, p = 0.003), anemia (OR = 13.9, 95% CI. 3.4–5.7, p = 0.02), leucocytosis (OR = 0.04, 95% CI. 0.06–0.22, p < 0.001), lymphadenopathy (OR = 7.8, 95% CI. 1.41–45.4, p = 0.02), and thrombocytopenia (OR = 13.5, 95% CI. 1.47–123.7, p = 0.02). In the multivariable logistic regression analysis with the stepwise forward selection approach, the diagnosis of VEXAS syndrome was significantly associated with the age at disease onset (OR: 1.13, 95% CI: 1.02–1.30, p = 0.04) and the presence of lymphadenopathy (OR: 67.49, 95% CI: 5.36–3284.89, p = 0.007), while thrombocytopenia showed a trend toward statistical significance (OR: 12.02, 95% CI: 1.07–315.86, p = 0.06). Conclusions Patients with lymphadenopathy, thrombocytopenia, anemia, particularly in older age and in the absence of leucocytosis, are more likely to be affected by VEXAS syndrome rather than Schnitzler's syndrome.