From the Guidelines
Pediatric DADA2 management should prioritize treatment with tumor necrosis factor inhibitors, such as etanercept or adalimumab, over glucocorticoids alone, due to the strong signal of benefit in preventing strokes and other vascular complications. This recommendation is based on the 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of polyarteritis nodosa, which strongly recommends treatment with tumor necrosis factor inhibitors for patients with clinical manifestations of DADA2 1. The guideline suggests that tumor necrosis factor inhibitors, instead of conventional immunosuppressive agents, can prevent strokes and other complications associated with DADA2.
Key considerations for pediatric DADA2 management include:
- Initiating treatment promptly upon diagnosis to prevent stroke and other vascular complications, even in asymptomatic patients with confirmed genetic mutations
- Using anti-TNF therapy, such as etanercept (0.8 mg/kg weekly, maximum 50 mg) or adalimumab (20-40 mg every 2 weeks based on weight), as first-line treatment
- Adding anti-platelet therapy with low-dose aspirin (3-5 mg/kg/day, maximum 81 mg daily) to the regimen
- Regular monitoring, including complete blood counts every 3 months, inflammatory markers, and annual brain MRI/MRA
- Immunological assessments at diagnosis and periodically thereafter
The use of tumor necrosis factor inhibitors is supported by the strong signal of benefit in preventing strokes and other complications associated with DADA2, as reported in the guideline 1. Additionally, the guideline notes that physical therapy may be beneficial for patients with nerve and/or muscle involvement, although this is based on indirect evidence from studies in inflammatory myositis 1. Overall, the management of pediatric DADA2 should prioritize treatment with tumor necrosis factor inhibitors and regular monitoring to prevent complications and improve outcomes.
From the Research
Pediatric DADA2 Guidelines
- The diagnosis of DADA2 should be considered in children with a PAN-like phenotype, particularly in the presence of young age at disease onset, parental consanguinity, strokes, lymphopenia, and lack of thrombocytosis during active disease 2.
- The primary treatment for DADA2 is anti-tumor necrosis factor (anti-TNF) therapy, which is effective in controlling inflammation and preserving vascular integrity 2, 3, 4.
- Hematopoietic stem cell transplantation (HSCT) may be necessary to treat refractory cytopenias, vasculopathy, or immunodeficiency in DADA2 patients 5, 4.
- Early diagnosis and treatment of DADA2 are crucial to prevent fatal outcomes, and ADA2 enzyme activity measurement can be used as a screening tool for patients and siblings at risk 6.
- The clinical manifestations of DADA2 can vary widely, including cutaneous vasculitis, polyarteritis nodosa-like lesions, stroke, and hematologic manifestations such as hypogammaglobulinemia, lymphopenia, and pure red cell aplasia 2, 3, 5, 4.
Treatment Options
- Anti-TNF therapy is the first-line treatment for DADA2, and it has been shown to be effective in controlling inflammation and preserving vascular integrity 2, 3, 4.
- HSCT may be necessary to treat refractory cytopenias, vasculopathy, or immunodeficiency in DADA2 patients 5, 4.
- Corticosteroids and cyclophosphamide or mycophenolate mofetil (MMF) may be used to treat systemic PAN, but cyclophosphamide can be switched to MMF when remission is confirmed with PVAS in severe PAN 2.
Diagnostic Considerations
- DADA2 should be considered in patients with early-onset fevers, rashes, and strokes, even in the absence of a positive family history 4.
- ADA2 enzyme activity measurement can be used as a screening tool for patients and siblings at risk 6.
- Genetic testing can confirm the diagnosis of DADA2 by identifying biallelic mutations in the ADA2 gene 5, 4.