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.

中文翻译：

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诊断SAVI的挑战：案例研究。

背景：2014年，婴儿期发作时与干扰素基因（STING）相关的血管病（SAVI）的刺激物首次被描述为由跨膜蛋白173（TMEM173）基因的杂合突变导致的I型干扰素。SAVI的特征是新生儿出现全身性炎症，严重的皮肤血管病变和间质性肺疾病。Janus激酶抑制剂被认为是有效的治疗剂。我们试图描述2名仅在死后才被诊断出患有SAVI的患者，以提高对该疾病的认识。方法：收集临床资料，对2例疑似SAVI患者进行TMEM173基因的Sanger测序。本文回顾了这些病例的详细信息以及从临床回顾和验尸研究中汲取的教训。结果：两个男孩有相似的表现，自出生以来，包括冬季反复出现的皮肤脓肿，皮肤病变和反复出现的呼吸道感染。计算机胸部断层扫描显示肺纤维化，但在患者1（P1）中未发现相关基因（包括ABCA3和SFTPC）的突变。关节痛在P2中很明显，他被诊断出患有关节炎。抗生素治疗几乎没有改善，也没有阻止进展。最后，P1和P2分别在2016年和2012年死于呼吸和循环衰竭。2018年，在TMEM173基因第5外显子中发现了突变（P1：c.463G> A，p.V155M; P2：c.461A> G，p.N154S），证实了SAVI的诊断。结论：这2例患者的经验表明，对于全身性炎症，冻疮皮肤病变和肺纤维化的儿童应考虑使用SAVI，