Systematic review of childhood-onset polyarteritis nodosa and DADA2

Semin Arthritis Rheum. 2021 Jun;51(3):559-564. doi: 10.1016/j.semarthrit.2021.04.009. Epub 2021 Apr 19.


Background: Diagnosis of childhood polyarteritis nodosa (PAN) has become challenging after the definition of deficiency of adenosine deaminase 2 (DADA2). We aimed to define the differential features of pediatric PAN and DADA2 patients in our center and in the literature.

Methods: The charts of pediatric PAN and DADA2 patients followed at the Pediatric Rheumatology Unit of Hacettepe University between 2010-2020 were analyzed. A systematic literature review was conducted for articles regarding pediatric PAN or DADA2.

Results: Thirty-four pediatric PAN and 18 pediatric DADA2 patients were included. The age at onset was younger, parental consanguinity, livedo reticularis, neurologic involvement (especially strokes), lymphopenia, and hypogammaglobulinemia were more frequent, while thrombocytosis and panniculitis were less frequent in DADA2 patients. The primary treatment was anti-tumor necrosis factor (anti-TNF) in DADA2. For induction treatment, all systemic PAN patients received corticosteroids, and cyclophosphamide (n=11) or mycophenolate mofetil (MMF) (n = 3). Cyclophosphamide was replaced with MMF in nine once remission was confirmed with PVAS. In the literature, 28 articles describing 613 pediatric PAN patients and 26 articles describing 207 pediatric DADA2 patients were identified. Neurologic, gastrointestinal, and cardiac involvements were more frequent in DADA2, while constitutional symptoms and testis involvement were more common in PAN.

Conclusion: In a child with PAN-like phenotype, DADA2 should be considered in the presence of young age at disease onset, parental consanguinity, strokes, lymphopenia, and lack of thrombocytosis during active disease. Anti-TNF treatment is indicated for vasculitic DADA2. Cyclophosphamide could be switched to MMF when remission is confirmed with PVAS in severe PAN.

Keywords: Biological therapies; Child, immunosuppressants; Deficiency of adenosine deaminase 2; Outcome measures; Polyarteritis nodosa; Systematic review; Vasculitis.

Publication types

  • Systematic Review

MeSH terms

  • Adenosine Deaminase / genetics
  • Agammaglobulinemia*
  • Child
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Polyarteritis Nodosa* / diagnosis
  • Polyarteritis Nodosa* / drug therapy
  • Polyarteritis Nodosa* / epidemiology
  • Tumor Necrosis Factor Inhibitors


  • Intercellular Signaling Peptides and Proteins
  • Tumor Necrosis Factor Inhibitors
  • Adenosine Deaminase