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STING-associated vasculopathy with onset in infancy in Adult
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STING-associated vasculopathy with onset in infancy in Adult

Contributors: Jessica Duong, Susan Burgin MD
Other Resources UpToDate PubMed

Synopsis

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.

Codes

ICD10CM:
I77.89 – Other specified disorders of arteries and arterioles
M35.89 – Other specified systemic involvement of connective tissue

SNOMEDCT:
711164003 – STING-associated vasculopathy with onset in infancy

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

  • Granulomatosis with polyangiitis (GPA) – Cutaneous features that worsen during cold months differentiate SAVI from GPA, among other differences.
  • Childhood interstitial lung disease (chILD) – Frequent variants for chILD that cause congenital surfactant deficiency are SFTPC or ABCA3 mutations in alveolar type II pneumocytes, which are also present in SAVI. Gene sequencing for SFTPC or ABCA3 mutations may be performed; in contrast to insidious onset of ILD in SAVI, chILD has an earlier and more fulminant presentation in neonates.
  • RF-positive polyarticular juvenile idiopathic arthritis (JIA) – SAVI can have arthritic involvement and be RF positive.
  • Severe combined immunodeficiency
  • AGS – SAVI patients similarly present with severe skin vasculopathy and elevated IFNα protein in their blood, and 3 patients have demonstrated intracranial calcification of basal ganglia, shared characteristics of AGS. There are no neurological symptoms demonstrated in SAVI, unlike AGS.
  • Familial chilblain lupus
  • Familial pulmonary fibrosis
  • Chronic granulomatous disease – This may be suspected due to skin abscesses and recurrent respiratory tract infections. Can be ruled out if nitroblue tetrazolium (NBT) or DHR123 tests produce normal results.
  • Cystic fibrosis – Similarly causes early respiratory failure progressing to ILD; cystic fibrosis may additionally affect the pancreas, liver, sweat glands, and vas deferens. Screen with measurement of immunoreactive trypsinogen and the sweat chloride test.

Best Tests

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Management Pearls

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Therapy

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References

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Last Reviewed:09/02/2021
Last Updated:01/24/2022
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STING-associated vasculopathy with onset in infancy in Adult
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STING-associated vasculopathy with onset in infancy
Copyright © 2022 VisualDx®. All rights reserved.