From the Guidelines
Pediatric DADA2 management should begin with anti-TNF therapy as first-line treatment, specifically etanercept or adalimumab, due to its strong signal of benefit in preventing strokes and improving outcomes, as recommended by the 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of polyarteritis nodosa 1.
Key Considerations
- Treatment should be initiated promptly upon diagnosis to prevent irreversible organ damage and should be continued long-term as DADA2 is a chronic condition.
- For acute vasculitic crises, short courses of corticosteroids may be added temporarily.
- Anti-platelet therapy with low-dose aspirin is recommended for stroke prevention.
- Regular monitoring should include complete blood counts every 3-6 months to assess for cytopenia, inflammatory markers (ESR, CRP), and periodic neuroimaging to detect silent cerebrovascular events.
Rationale
- DADA2 causes excessive TNF-alpha production, leading to vasculitis and inflammation, making anti-TNF therapy particularly effective.
- Early intervention is crucial as the condition can cause strokes, peripheral neuropathy, and systemic vasculitis in children, with potentially devastating consequences if left untreated.
- The strong recommendation for anti-TNF therapy over glucocorticoids alone is based on the potential to prevent strokes and improve outcomes, as supported by the available evidence 1.
Additional Recommendations
- For patients with severe immunodeficiency or refractory disease, hematopoietic stem cell transplantation may be considered.
- Physical therapy may be beneficial for patients with nerve and/or muscle involvement, as conditionally recommended by the guideline 1.
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.
- Neurologic, gastrointestinal, and cardiac involvements are more frequent in DADA2, while constitutional symptoms and testis involvement are more common in PAN 2.
- Anti-TNF treatment is indicated for vasculitic DADA2, and cyclophosphamide could be switched to MMF when remission is confirmed with PVAS in severe PAN 2.
- TNF blockade is effective in controlling inflammation and preserving vascular integrity in DADA2 patients, and it may also be used for primary stroke prevention in genetically affected but clinically asymptomatic patients 3.
- Allogeneic hematopoietic cell transplantation (HCT) is curative for DADA2, reversing the hematological, immune, and vascular phenotype of the disease, but it requires careful consideration of disease-specific vulnerabilities and potential complications 4.
Treatment Approaches
- TNF inhibitors are the first-line treatment for DADA2, and they have been shown to be effective in controlling inflammation and preventing strokes 5, 3, 6.
- Hematopoietic stem cell transplantation (HSCT) may be considered for patients with hematological manifestations, such as pure red cell aplasia, immune thrombocytopenia, and neutropenia 6, 4.
- The choice of preparative regimen for HCT should take into account the specific vulnerabilities of DADA2 patients, including endothelial dysfunction and liver toxicity 4.
Clinical Features
- DADA2 is characterized by a variable phenotype, including systemic vasculitis, bone marrow failure, and immunodeficiency 5, 6.
- Clinical features may include livedo reticularis, polyarteritis nodosa, lacunar ischemic strokes, intracranial hemorrhages, end-organ vasculitis, recurrent fever, lymphoproliferation, immune cytopenias, and bone marrow failure 5, 6, 4.
- Neurologic involvement, including strokes, is a common feature of DADA2, and it may be prevented or treated with TNF blockade 2, 3.