Polyarteritis nodosa and deficiency of adenosine deaminase 2 – Shared genealogy, generations apart

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that predominantly affects medium-sized arteries. With the establishment and refinement of vasculitis nomenclature and diagnostic criteria, clinical findings of PAN and distinguishing features from other vasculitides are now well characterized. Although PAN typically manifests in adulthood, cohort studies in paediatric patients have shaped our understanding of childhood-onset PAN. The paradigm of childhood-onset PAN changed considerably with the landmark discovery of deficiency of ADA2 (DADA2), a monogenic cause of vasculitis that is often indistinguishable from PAN. Testing for DADA2 has provided an explanation to numerous challenging cases of familial PAN and early-onset PAN around the world. The ability to distinguish DADA2 from classic PAN have important therapeutic implications as tumor necrosis factor inhibitors have demonstrated remarkable efficacy in the treatment of DADA2. In this review, we will discuss our current understanding of PAN and DADA2 and highlight similarities and differences between these vasculitides. •PAN and DADA2 are systemic vasculitis that primarily affect medium-sized arteries.•PAN is diagnosed by established criteria in adults and children while DADA2 is determined by genetic studies and/or enzymatic testing•DADA2 should be ruled out for familial and early-onset cases of PAN•PAN and DADA2 are often clinically indistinguishable but presence of hematologic and immunologic defects favors DADA2