THU0528 Sting-associated vasculopathy with onset in infancy (SAVI): a differential diagnosis of inflammatory interstitial lung disease

Abstract

Background: STING-Associated Vasculopathy with onset in Infancy (SAVI) is an auto-inflammatory monogenic disease. SAVI is caused by an upregulation of type I interferon signaling due to sporadic or inherited gain-of-function mutations in the STimulator of INterferon Gene (STING)/Transmembrane Protein 173 (TMEM173). The first description of this phenotype, and the identification of the mutated gene, was in 2014. SAVI is characterized mainly by cutaneous vasculopathy leading to necrotic lesions, and progressive interstitial lung disease with secondary fibrosis. Objective(s): SAVI is a rare disease with unknown prevalence. To the best of our knowledge, 25 cases have been reported so-far. These patients variably manifest cutaneous lesions and inflammatory lung disease. Here we present a case of SAVI with onset of features at the age of 3 years. Method(s): A now 8 year old boy born to non-consanguineous parents was described to have experienced recurrent fevers, polyarthralgia and polyarthritis, livedo of the limbs, facial telangiectasia, necrotic lesions of auricles and digits and failure to thrive since the age of 3 years. He has normal cognitive development. His familial history is notable for epilepsy in 2 of his siblings and Behcet disease in a paternal cousin. Laboratory tests at age 6.5 years revealed increased ESR (60mm/h) while CRP varied from 3 to 14 mg/L. ANA titres were positive (1/640), with normal complement level and negative anti-DNA. c-ANCA and p-ANCA were negative. ECA and lysozymes were in the normal range. Although the child had no respiratory symptoms, chest X-ray revealed diffuse interstitial parenchymal infiltrates. Chest angio-CT showed ground-glass lesions with fibrotic bands and mediastinal and para-hilar adenopathies. FVC and DLCO were reduced on pulmonary functional testing. Lung biopsy was not performed. Empirical treatment with pulse and oral corticosteroids along with azathioprine was started. Over a period of one year, systemic inflammation and skin involvement regressed dramatically, but his lung disease showed no improvement. Result(s): Genetic testing identified a previously reported V155M mutation in TMEM173. Conclusion(s): SAVI is associated with significant morbidity and mortality. The diagnosis should be considered in children with interstitial lung disease after more common causes have been ruled out. Steroids and immunosuppressive therapies apparently show no efficacy in avoiding progression to irreversible lung damage. Promising results with treatment by Janus Kinase inhibitors as a means of blocking signaling downstream of the type I interferon receptor were recently published.