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

Polyarteritis nodosa (PAN) is a rare necrotizing vasculitis occurring alone or associated with other conditions, including VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome and chronic myelomonocytic leukaemia (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.

We conducted a retrospective, multicentre 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 analysed baseline and therapeutic characteristics, along with survival and relapse rates.

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 remission [adjusted odds ratio (aOR) 0.15; 95% CI 0.02-1.00] and more likely to experience relapses [adjusted hazard ratio (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%).

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.