From the Guidelines
Pediatric DADA2 management should prioritize treatment with tumor necrosis factor inhibitors over glucocorticoids alone to prevent strokes and control vasculitis, as recommended by the 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of polyarteritis nodosa 1.
Key Considerations
- DADA2 is characterized by recurrent strokes and skin changes, and is diagnosed using ADA2 sequencing or ADA2 functional assays.
- Tumor necrosis factor inhibitors, such as adalimumab or etanercept, are the primary treatment recommendation for children with DADA2, as they effectively control the vasculitis and prevent strokes.
- Tertiary centers with multidisciplinary expertise, including rheumatology, neurology, hematology, and immunology specialists, are essential for providing comprehensive care and monitoring disease activity.
Treatment and Monitoring
- Anti-TNF therapy should be initiated promptly to prevent irreversible organ damage, particularly stroke.
- Regular monitoring should include complete blood counts, inflammatory markers (ESR, CRP), and periodic neuroimaging to detect silent cerebrovascular events.
- Genetic counseling is also important for families with a history of DADA2.
Additional Considerations
- Hematopoietic stem cell transplantation may be considered in severe cases with significant hematological manifestations.
- Physical therapy may be beneficial for patients with nerve and/or muscle involvement, as it has potential benefits and minimal risks 1.
From the Research
Pediatric DADA2 Tertiary Center Experience
- The study 2 analyzed the charts of pediatric PAN and DADA2 patients followed at the Pediatric Rheumatology Unit of Hacettepe University between 2010-2020 and conducted a systematic literature review for articles regarding pediatric PAN or DADA2.
- The results showed that 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, and for induction treatment, all systemic PAN patients received corticosteroids, and cyclophosphamide or mycophenolate mofetil (MMF) were used.
Clinical Characteristics and Treatment Response
- The study 3 described the clinical phenotypes and treatment response both in adults and in children with DADA2 in India, and found that nearly one-half of the confirmed cases presented during adulthood.
- All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients, and treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients, leading to marked improvement in all identified disease manifestations.
- The study 4 explored the pathophysiology and the underlying mechanisms of TNF-inhibitor response in patients with DADA2, and demonstrated increased inflammatory signals and overproduction of cytokines mediated by IFN and nuclear factor kappa B pathways in patients' primary cells.
Diagnosis and Treatment
- The study 5 retrospectively analyzed nine cases of DADA2-related pure red cell aplasia (PRCA) diagnosed over 5 years at a tertiary care hospital, and emphasized the need for comprehensive genetic analysis in PRCA to distinguish DADA2 from Diamond Blackfan anemia (DBA) for appropriate treatment.
- The study 6 provided updates on the phenotype, genetics, pathogenesis, and treatment of DADA2, and suggested that DADA2 should be primarily considered in patients with early-onset fevers, rashes, and strokes even in the absence of positive family history, and that the first-line treatment consists of TNF-inhibitors and is effective in controlling inflammation and in preserving vascular integrity.