The Challenge of Diagnosing SAVI: Case Studies

Background: Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) was first described in 2014 as a type I interferonopathy resulting from heterozygous mutations in the transmembrane protein 173 (TMEM173) gene. SAVI is characterized by the neonatal onset of systemic inflammation, severe cutaneous vasculopathy, and interstitial lung disease. Janus kinase inhibitors are considered effective therapeutics. We sought to describe 2 patients who were diagnosed with SAVI only at postmortem to increase awareness of this disorder. Methods: Clinical data were collected, and Sanger sequencing of the TMEM173 gene was performed in 2 patients suspected of SAVI. This article reviews details of these cases and lessons learned from clinical review and postmortem studies. Results: Two male children shared similar manifestations, including recurrent skin abscesses in winter, skin lesions, and recurrent respiratory tract infections, since birth. Computed tomography of the chest revealed pulmonary fibrosis, but no mutations in relevant genes (including ABCA3 and SFTPC) were discovered in patient 1 (P1). Joint pain was significant in P2 and he was diagnosed with arthritis. Antibiotic treatment yielded little improvement and did not prevent progression. Finally, P1 and P2 died of respiratory and circulatory failure in 2016 and 2012, respectively. In 2018, mutations (P1: c.463G>A, p.V155M; and P2: c.461A>G, p.N154S) in exon 5 of the TMEM173 gene were discovered, confirming the diagnosis of SAVI. Conclusions: The experience with these 2 patients suggests that SAVI should be considered in children with systemic inflammation, chilblain skin lesions, and pulmonary fibrosis, and TMEM173 gene analysis can be beneficial in the diagnosis of SAVI.