Polyarteritis nodosa associated with VEXAS syndrome and chronic myelomonocytic leukemia: a case-control study

Abstract

Objectives: Polyarteritis nodosa (PAN) is a rare necrotizing vasculitis occurring alone or associated with other conditions, including VEXAS syndrome and chronic myelomonocytic leukemia (CMML). We aimed to compare the presentation and outcomes of VEXAS- or CMML-associated PAN (VEXAS-PAN and CMML-PAN) with those of primary PAN.

Methods: We conducted a retrospective, multicenter study of patients diagnosed with primary PAN, VEXAS-PAN, or CMML-PAN. Each VEXAS-PAN or CMML-PAN case was matched to three primary PAN cases by age and gender. We analyzed baseline and therapeutic characteristics, along with survival and relapse rates.

Results: Twenty-three patients were included (12 with VEXAS-PAN, 11 with CMML-PAN). Secondary PAN occurred at older ages: 73 years for VEXAS-PAN, 70 years for CMML-PAN, and 54 years for primary PAN; p <0.01. VEXAS-PAN was associated with a higher frequency of skin manifestations (100%), orchitis (67%), and ocular manifestations (58%) than primary PAN. By contrast, the clinical features of CMML-PAN closely resembled those of primary PAN. VEXAS-PAN was less likely than primary PAN to achieve (aOR: 0.15; 95% CI: 0.02-1.00) and more likely to experience relapses (aHR: 3.24; p = 0.043). Similar trends were observed for CMML-PAN regarding remission (aOR 0.12; 95% CI 0.02-0.73) and relapses (aHR: 2.23; p = 0.145). Mortality was higher in VEXAS-PAN (50%) than in CMML-PAN (15%) or primary PAN (17%).

Conclusion: VEXAS- and CMML-PAN are distinct clinical entities with poorer prognosis and unique therapeutic challenges. Recognizing these conditions early and providing individualized management are crucial to improving outcomes in these patients.

Keywords: Chronic myelomonocytic leukemia (CMML); Polyarteritis nodosa (PAN); VEXAS syndrome; Vasculitis.