Polyarteritis nodosa and deficiency of adenosine deaminase 2 - Shared genealogy, generations apart
Zhengping Huang1, Tianwang Li2, Peter A Nigrovic3
1Department of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, China; Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Abstract:
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.
Insights
Polyarteritis nodosa (PAN) is a vasculitis affecting medium arteries. Deficiency of ADA2 (DADA2) mimics PAN, especially in children, and requires distinct treatment with TNF inhibitors.
Area of Science:
- Rheumatology
- Immunology
- Genetics
Background:
- Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis primarily affecting medium-sized arteries.
- While typically seen in adults, childhood-onset PAN has been extensively studied.
- Advances in nomenclature and diagnostic criteria have refined understanding of PAN and its differentiation from other vasculitides.
Purpose of the Study:
- To review current understanding of PAN and deficiency of ADA2 (DADA2).
- To highlight similarities and differences between PAN and DADA2.
- To discuss the therapeutic implications of distinguishing DADA2 from classic PAN.
Main Methods:
- Review of established vasculitis nomenclature and diagnostic criteria.
- Analysis of cohort studies in pediatric patients.
- Discussion of genetic testing for DADA2.
- Evaluation of therapeutic responses to tumor necrosis factor inhibitors.
Main Results:
- Deficiency of ADA2 (DADA2) is a monogenic vasculitis often indistinguishable from PAN.
- DADA2 explains numerous cases of familial and early-onset PAN.
- Distinguishing DADA2 from classic PAN is crucial for effective treatment.
Conclusions:
- DADA2 represents a significant advance in understanding vasculitis, particularly in pediatric and familial cases.
- Tumor necrosis factor inhibitors show efficacy in DADA2 treatment, underscoring the importance of accurate diagnosis.
- Further research into the pathogenesis and management of both PAN and DADA2 is warranted.
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