Background/Purpose: Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis affecting medium-sized vessels. It is a life-threatening disease without appropriate treatment. In 2024, approximately one quarter of PAN will be secondary to another cause, particularly solid tumors or hematologic malignancies. VEXAS syndrome and chronic myelomonocytic leukemia (CMML) have been described to be associated with PAN, but no study has focused on the characteristics of PAN in these settings. We aimed to evaluate the presentation, management, and prognosis of patients with these secondary forms compared with primary forms.

Methods: We conducted a multicenter retrospective study including patients with PAN in the setting of VEXAS syndrome (VEXAS-PAN) or CMML (CMML-PAN). Data were collected for each patient using a standardized form. VEXAS-PAN and CMML-PAN were compared with a matched group of patients with primary PAN. Relapse-free survival and overall survival were compared by underlying cause using univariate Cox models and adjusted for known risk factors for relapse and survival in primary PAN.

Results: Twenty-three patients with secondary PAN were included (19 males and 4 females, median age at PAN diagnosis 72 [IQR 65-77] years), including 12 cases associated with VEXAS syndrome and 11 cases with CMML. VEXAS-PAN and CMML-PAN were older (73 [63-80] years and 70 [65-72] years, respectively) compared to primary PAN (54 [40-66] years; p < 0.01).

VEXAS-PAN was associated with constitutional symptoms in 100%, cutaneous nodules in 100%, livedo in 17% and purpura in 25%, orchitis in 67% and ocular symptoms in 58%, and a median C-reactive protein level of 110 (IQR 85-226) mg/L, with no eosinophilia or monocytosis.

Compared to primary PAN, VEXAS-PAN was more frequently associated with cutaneous (100% vs 44%, p < 0.001), testicular (67% vs 25%, p =0.015) and ocular (58% vs 11%, p =0.002) manifestations. Six VEXAS-PAN patients (50%) presented with myelodysplastic syndrome.

CMML-PAN was associated with constitutional symptoms in 91%, livedo in 36%, purpura in 45%, and arthralgia in 73%. No difference was observed between primary PAN and CMML-PAN.

During follow-up, vasculitis relapse occurred in 83% of VEXAS-PAN (adjusted HR 3.24; 95% CI 1.04-10.09; p = 0.043) and 82% of CMML-PAN (adjusted HR 2.23; 95% CI 0.76-6.54; p = 0.145) compared to 25% for primary PAN.

Death occurred in 50% of VEXAS-PAN (adjusted HR 2.17; 95% CI 0.67-7.08) and 15% of CMML-PAN (adjusted HR 2.23; 95% CI 0.76-6.54) compared to 17% for primary PAN.

Conclusion: VEXAS and CMML are possible secondary forms of PAN with a presentation and prognosis that may differ from primary PAN. VEXAS PAN and CMML PAN affect older patients, and VEXAS PAN more frequently presents with cutaneous, testicular, and ocular manifestations. Secondary PAN has a high risk of relapse and increased mortality, which supports different therapeutic approaches than the primary forms.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/polyarteritis-nodosa-associated-with-vexas-syndrome-and-chronic-myelomonocytic-leukemia-compared-with-primary-forms-a-case-control-study/