Objectives Mutations affecting the TMEM173 gene cause STING-associated vasculopathy with onset in infancy (SAVI). No standard immunosuppressive treatment approach is able to control disease progression in patients with SAVI. We studied the efficacy and safety of targeting type I IFN signaling with the Janus kinase inhibitor, ruxolitinib. Methods We used DNA sequencing to identify mutations in TMEM173 in patients with peripheral blood type I IFN signature. The JAK1/2 inhibitor ruxolitinib was administered on an off-label basis. Results We identified three patients with SAVI presenting with skin involvement and progressive severe interstitial lung disease. Indirect echocardiographic signs of pulmonary hypertension were present in one case. Following treatment with ruxolitinib, we observed improvements of respiratory function including increased forced vital capacity in two patients, with discontinuation of oxygen therapy and resolution of echocardiographic abnormalities in one case. Efficacy was persistent in one patient and only transitory in the other two patients. Clinical control of skin complications was obtained, and one patient discontinued steroid Stefano Volpi and Antonella Insalaco contributed equally.Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-019-00645-0) contains supplementary material, which is available to authorized users. treatment. One patient, who presented with kidney involvement, showed resolution of hematuria. One patient experienced increased recurrence of severe viral respiratory infections. Monitoring of peripheral blood type I interferon signature during ruxolitinib treatment did not show a stable decrease. Conclusions We conclude that targeting type I IFN receptor signaling may represent a promising therapeutic option for a subset of patients with SAVI syndrome and severe lung involvement. However, the occurrence of viral respiratory infection might represent an important cautionary note for the application of such form of treatment.

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Macleod/Swyer-James syndrome is an uncommon and complex disease characterized by roentgenographic hyperlucency of one lung or lobe due to loss of the pulmonary vascular structure and to alveolar overdistension. This syndrome seems to be an acquired disease that follows viral bronchiolitis and pneumonitis in childhood. It must be differentiated from many other causes of unilateral lung "transradiancy" on the chest roentgenogram, such as those related to congenital bronchial and/or vascular abnormalities. We here describe an 11-year-old patient with Macleod/Swyer-James syndrome and bronchiectasis resulting in severe recurrent bronchopulmonary infections. Despite the severe impairment of pulmonary function, the patient underwent resection of the right lung with progressive improvement of clinical and physiologic parameters.

Mild TC induced by AIA can be detected in a sizeable proportion of children with recurrent/chronic dry cough. The identification of this anomaly, that may at least partially explain the origin of their symptom, may avoid further unnecessary diagnostic examinations and ineffective chronic treatments.

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