STING-associated vasculopathy with onset in infancy (SAVI) is a rare monogenic autoinflammatory disease characterised by activation of the type I interferon (IFN-I) signalling pathway. Emerging evidence suggests that direct inhibition of the type I interferon receptor (IFNAR1) may provide superior therapeutic response and less treatment-emergent infective side effects than conventional JAK inhibition. We describe the case of a 2-year-old female with a de novo pathogenic TMEM173 variant who was born extremely preterm at 24+6 weeks as a dichorionic diamniotic twin and with a maternal history of undifferentiated autoimmune disease. Her clinical course was complicated by gastrointestinal dysregulation, including severe vomiting, failure to thrive, and hepatitis, alongside cutaneous manifestations such as vasculitis.
The patient was initially managed with ruxolitinib (JAK inhibitor) and systemic corticosteroids. Attempts to taper prednisolone below 3 mg daily were associated with recurrence of vomiting and weight loss. Anifrolumab (anti-IFNAR1 antibody) was subsequently commenced under compassionate access, and close monitoring of clinical progress, growth parameters, inflammatory markers, and type I interferon signature was undertaken.
Initiation of anifrolumab led to gradual but sustained clinical improvement with resolution of rash, successful transition to full oral feeding, and improved weight gain. This enabled the tapering and eventual discontinuation of both ruxolitinib and corticosteroids. Concurrently, normalisation of the interferon gene signature was achieved. Mild elevations in C-reactive protein, erythrocyte sedimentation rate, IgG, and platelet count persist, suggesting residual low-grade systemic inflammation versus active disease.
This case underscores the potential of targeted IFNAR1 inhibition with anifrolumab as an effective steroid-sparing agent in paediatric SAVI. Direct interferon blockade may represent a preferred therapeutic pathway in IFN-I–driven monogenic autoinflammatory disorders.
