Atypical adult polyarteritis nodosa unmasking deficiency of adenosine deaminase 2: a case report about the importance of genetic testing in adults.
Antolini Sofia S, Cassandrini Denise D, Bindoli Sara S, Bronte Vincenzo V et al.
Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder caused by biallelic mutations in the ADA2 gene. It presents as a monogenic vasculitis with heterogeneous manifestations that often resemble small- and medium-vessel vasculitis, particularly polyarteritis nodosa (PAN)-like disease, leading to frequent misdiagnosis, especially in adults. Early recognition of DADA2 is crucial, as prompt treatment can control inflammation, preserve vascular integrity, and prevent irreversible organ damage. Rising awareness of the wide clinical spectrum of DADA2 is fundamental to improve recognition and facilitate timely diagnosis, ultimately enhancing prognosis. We herein describe the case of a middle-aged woman with skin lesions, central nervous system, peripheral nervous system, and gastrointestinal tract ischemic manifestations who was initially diagnosed with PAN. The patient was treated with glucocorticoids as well as several steroid-sparing immunosuppressive agents (methotrexate, azathioprine, rituximab, tocilizumab, and cyclophosphamide), which all proved to be ineffective. Meanwhile, the patient developed cytopenias and hypogammaglobulinemia. Subsequent genetic testing identified a homozygous missense mutation in the ADA2 gene (c.1358A>G, p.Tyr453Cys), supporting the diagnosis of DADA2 and enabling the initiation of effective therapy with the tumor necrosis factor-α inhibitor etanercept. This case underscores the importance of considering DADA2 in adult patients presenting with recurrent vasculitic manifestations refractory to conventional immunosuppressive therapy, as timely genetic testing can be pivotal in redirecting treatment toward targeted and effective therapy.