From the Guidelines
A comprehensive surveillance investigation for pediatric DADA2 should include regular clinical evaluations and treatment with tumor necrosis factor inhibitors, such as etanercept or adalimumab, to prevent strokes and control systemic inflammation, as strongly recommended by the 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of polyarteritis nodosa 1.
Key Components of Surveillance Investigation
- Regular clinical evaluations every 3-6 months, focusing on neurological, immunological, and vascular systems
- Initial workup including complete blood count with differential, inflammatory markers (ESR, CRP), immunoglobulin levels, and ADA2 enzyme activity testing
- Genetic confirmation through ADA2 gene sequencing
- Imaging studies including brain MRI with angiography to detect strokes or vascular abnormalities, and abdominal ultrasound to assess for hepatosplenomegaly
Treatment Approach
- Treatment with tumor necrosis factor inhibitors, such as etanercept or adalimumab, which have shown effectiveness in preventing strokes and controlling systemic inflammation 1
- Anti-platelet therapy with low-dose aspirin may be recommended for stroke prevention
- Hematopoietic stem cell transplantation may be considered for severe manifestations
Rationale
- DADA2 has a variable presentation, including strokes, systemic inflammation, immunodeficiency, and hematological abnormalities
- Early detection and treatment can prevent irreversible organ damage, particularly strokes, which are a major cause of morbidity in these children
- The use of tumor necrosis factor inhibitors is strongly recommended due to its potential benefit and minimal risk, as supported by the 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of polyarteritis nodosa 1
From the Research
Pediatric DADA2 Surveillance Investigation
- The diagnosis of DADA2 can be challenging, especially in pediatric patients, as it presents with similar symptoms to other conditions such as polyarteritis nodosa (PAN) 2.
- A systematic review of childhood-onset PAN and DADA2 found that DADA2 patients had a younger age at onset, parental consanguinity, livedo reticularis, neurologic involvement, lymphopenia, and hypogammaglobulinemia more frequently than PAN patients 2.
- The primary treatment for DADA2 is anti-tumor necrosis factor (anti-TNF) therapy, which has been shown to be effective in treating vasculitic symptoms and preventing stroke 2, 3.
- In addition to anti-TNF therapy, some patients with DADA2 may require other treatments such as hematopoietic cell transplantation, which has been shown to be effective in resolving DADA2-related symptoms in some cases 4.
Clinical Characteristics of DADA2
- DADA2 is characterized by a variable presentation of systemic vasculitis, bone marrow failure, and immunodeficiency 5, 6.
- Common clinical findings in DADA2 patients include cutaneous involvement, (hepato)splenomegaly, recurrent infections, and stroke 6, 4.
- Laboratory abnormalities in DADA2 patients may include hypogammaglobulinemia, cytopenias, and elevated inflammatory markers 2, 4.
Treatment and Outcome of DADA2
- TNF inhibitors have been shown to be effective in treating vasculopathy-associated symptoms and preventing stroke in DADA2 patients 3, 4.
- However, TNF inhibitors may not be effective in treating hematologic manifestations of DADA2, and other treatments such as hematopoietic cell transplantation may be necessary in some cases 4.
- The overall mortality in DADA2 patients is significant, with one study reporting a mortality rate of 17.2% 4.