C3-01 Beyond BPD: A Novel Case of Sting-Associated Vasculopathy (SAVI) in a Preterm Infant

Introduction

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and their primary cause of hypoxemia, though severity varies widely. When clinical findings deviate from the expected course, alternative diagnoses should be considered. We report a novel case of STING-Associated vasculopathy with onset in infancy (SAVI) in a preterm infant with BPD.

Case Report

A male infant was born at 27 weeks 2 days gestation. He required resuscitation with positive-pressure ventilation, surfactant, and prolonged respiratory support. He was extubated to noninvasive ventilation on day of life (DOL) 54 and weaned to low-flow nasal cannula on DOL 145. Following discharge, he remained on 2 L/min nasal cannula and inhaled fluticasone. Daytime oxygen was discontinued at 16 months, but nocturnal oxygen persisted until after 3 years of age due to hypoxemia. Despite not requiring oxygen during the daytime, his normal daytime saturations were noted to be in the low 90s. He was hospitalized at 21 and 26 months with acute on chronic hypoxemic respiratory failure secondary to viral illnesses. Pulmonary consultation during the second hospitalization revealed digital clubbing. Chest CT demonstrated severe cystic parenchymal lung disease with patchy hyperinflation and ground glass opacities, including disproportionately large cystic lung disease (Figure 1). Given that lung disease seemed out of proportion for BPD, plus clubbing, and CT findings, an Invitae neonatal respiratory distress panel identified a pathogenic TMEM173 variant (c.842G>A, p.Arg281Gln) suggestive of SAVI. Bronchoscopy at 2 years 9 months showed normal anatomy without signs of airway inflammation. Bronchoalveolar lavage fluid was negative for PAS staining, with 93% macrophages, 6% lymphocytes, and 1% neutrophils. He was seen at the NIH, where gene expression profiling demonstrated an interferon gene signature in pre-treatment peripheral blood. Given the clinical, genetic, and immunologic testing results that were diagnostic of SAVI, he was started on baricitinib 2mg twice daily. Two years later, he has reduced digital clubbing, resolution of nocturnal oxygen dependence, and no further hospitalizations.

Discussion

SAVI is a rare autoinflammatory disorder caused by gain-of-function mutations in TMEM173, leading to activation of the type I interferon pathway that results in inflammation, vasculopathy, and interstitial lung disease. This case represents the first description of SAVI in a preterm infant with BPD. Targeted Janus kinase inhibitor therapy can alter disease trajectory. This case highlights the importance of considering alternate diagnoses in children with BPD whose course is atypical, develop digital clubbing, or is disproportionately severe.

This abstract is funded by: none