Along with disorders such as Aicardi-Goutières syndrome (AGS), familial chilblain lupus (FCL), and genetic variants of systemic lupus erythematosus (SLE), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is classified as a type I interferonopathy, a group of rare autoinflammatory diseases characterized by upregulation of type I interferon (IFN) signaling that disrupts normal immune function. SAVI is caused by gain-of-function mutations in the STING1 gene (also known as TMEM173), which encodes STING. Primarily expressed in vascular endothelial cells, alveolar type II pneumocytes, bronchial epithelium, and alveolar macrophages, STING is a transmembrane protein of the endoplasmic reticulum critical to the production of IFNs and expression of IFN-related genes. IFN overproduction in SAVI leads to excessive activation of Janus kinases (JAKs), causing a cytokine storm.

SAVI has been reported in fewer than 100 patients and occurs mostly de novo, with cases of autosomal dominant inheritance reported as well.

Due to its fairly new and rare occurrence in literature, prevalence is unknown and some infants may have been misdiagnosed. The median age of onset of SAVI is 3 months after birth, although atypical forms may present with adult onset and milder disease. Ages at time of reporting widely ranged from 1-86 years.

Although there is phenotypic heterogeneity, characteristic manifestations include early-onset systemic inflammation; severe cutaneous vasculopathy that causes chilblain-like lesions and may lead to nasal septum perforation, necrosis, and ulceration of distal extremities with subsequent tissue and nail loss; and interstitial lung disease (ILD). Additional reported manifestations may include growth retardation, failure to thrive, myositis, rheumatoid factor positive (RF+) polyarthritis, and recurrent bacterial infections of the skin, joints, and respiratory tract.

The leading cause of morbidity and mortality in SAVI is lung involvement, which may progress without treatment to end-stage respiratory failure by adolescence or early adulthood.