Treatment and outcome in deficiency of adenosine deaminase 2: a literature review.

Objectives Deficiency of adenosine deaminase 2 (DADA2) is a rare disease with varying phenotypes and disease outcomes. We aimed to summarize the treatments of DADA2 and to explore the factors associated with disease outcome. Material and methods A systemic literature review of DADA2 was conducted. Cases were included if they had documented detailed genotypes, phenotypes, treatment protocols and outcomes. Patients were categorized into uncontrolled and controlled groups. Factors associated with disease outcome were analyzed with logistic regression models. Results A total of 242 DADA2 patients with treatment protocols and responses were included, 17 of whom required no treatment. The general effective rate of TNFi was 78.6% (103/131). Hematological abnormalities and increased acute phase reactants are independently associated with TNFi effectiveness, OR=0.21 (95%CI 0.07-0.661, p=0.007) and 9.62 (95%CI 2.31-40.00, p=0.002), respectively. Among those 225 patients requiring active treatment, 157 (69.8%) patients were in the controlled group, and 68(30.2%) in the uncontrolled group. Neither age of disease onset nor genotype was associated with disease outcome. Increased acute phase reactants (APRs), constitutional symptoms, neurological symptoms, and treatment with TNF inhibitors (TNFi) were independently associated with disease control, while recurrent infections and severe vascular events were the main causes of mortality (10/21 and 6/21, respectively). Conclusions In patients requiring treatment, symptoms of systemic inflammation and vasculitis and TNFi treatment are associated with disease control; while recurrent infections and severe vascular events should be treated intensively as they are the main causes of death. Hematological abnormalities should be monitored as it would decrease TNFi effectiveness.