Pediatric-Onset Polyarteritis Nodosa and Deficiency of Adenosine Deaminase 2: Clinical Overlap and Divergence.

Abstract

Background: To compare the clinical features and disease severity of classic polyarteritis nodosa (PAN) with its monogenic form, deficiency of adenosine deaminase 2 (DADA2), in pediatric patients, in order to distinguish overlapping vasculitic phenotypes.

Methods: This cross-sectional study included 36 pediatric patients with PAN-like vasculitis, comprising 22 with classic PAN (14 systemic, 8 cutaneous) and 14 with DADA2, followed up at our tertiary referral pediatric rheumatology department between August 2016 and February 2025. Demographic features, clinical manifestations, treatment choices, and outcomes were compared between the groups.

Results: DADA2 patients had significantly earlier symptom onset (median 4 vs. 11 years, p = 0.002) and higher rates of parental consanguinity (p < 0.001) compared with systemic PAN (sPAN) patients. The most common clinical features in sPAN were constitutional symptoms (100%), followed by cutaneous (78.6%), musculoskeletal (57.1%), and renal involvement (57.1%). Growth retardation (14.3% vs. 57.1%, p = 0.018) and livedo racemosa (7.1% vs. 50%, p = 0.012) were more common in DADA2, whereas fatigue (92.9% vs. 35.7%, p = 0.002), renal involvement (57.1% vs. 0%, p < 0.011), diastolic hypertension (78.6% vs. 7.1%, p < 0.001), and purpura (35.7% vs. 0%, p = 0.014) predominated in PAN. Neurological manifestations were observed in 4 PAN patients (2 peripheral, 2 central) and 1 DADA2 patient with ischemic stroke. Biologic therapy was required in 4 PAN patients, whereas 11 of 14 DADA2 patients were treated with anti-tumor necrosis factor agents.

Conclusion: Anti-TNF therapy remains the mainstay of treatment in DADA2 and is effective in preventing disease progression. In contrast, classic sPAN may require escalation to biologic agents in refractory cases or when neurologic or end-organ involvement is present.