Deficiency of adenosine deaminase 2: a challenging differential diagnosis of polyarteritis nodosa

Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive disorder that was first described in 2014. It is a monogenic disease that is caused by loss-of-function variants in the ADA2 gene. Deficiency of adenosine deaminase 2 involves small- and medium-sized vessels and its clinical presentations include polyarteritis nodosa (PAN)-like features such as livedoid rash, early-onset stroke, hypogammaglobulinemia, hematological abnormalities, and systemic inflammation. Early diagnosis and treatment of DADA2 are crucial as the clinical features could be potentially life-threatening but might be treatable. The first-line treatment of choice in DADA2 is tumor necrosis factor α inhibitors. We aimed to provide an overview of the known pathophysiology, clinical presentations, diagnosis, and treatment of DADA2. A clearer knowledge of DADA2 may help to better diagnose, manage, and improve the clinical outcome of DADA2 patients. However, further studies are required to investigate the genotype-phenotype associations and exact pathophysiology of DADA2.