Stimulator of InterferoN Genes (STING)-Associated Vasculopathy with Onset in Infancy Syndrome (SAVI) Associated with Disseminated Molluscum Contagiosum Under Baricitinib Treatment
Background/objectives: Stimulator of Interferon Genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a rare autoinflammatory disorder caused by gain-of-function mutations in the <i>TMEM173</i> gene. These mutations result in chronic activation of the STING pathway and ex...
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2025-04-01
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| author | Thilo Gambichler Yusa Devrim Laura Susok |
| author_facet | Thilo Gambichler Yusa Devrim Laura Susok |
| author_sort | Thilo Gambichler |
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| description | Background/objectives: Stimulator of Interferon Genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a rare autoinflammatory disorder caused by gain-of-function mutations in the <i>TMEM173</i> gene. These mutations result in chronic activation of the STING pathway and excessive type I interferon production, leading to systemic inflammation, vascular abnormalities, interstitial lung disease, and skin ulcerations. Janus kinase (JAK) inhibitors, including baricitinib, have shown promise in mitigating systemic and organ-specific manifestations. However, these inhibitors broadly suppress immune pathways, potentially increasing vulnerability to infections. Case presentation: This case report describes a 21-year-old woman with SAVI (due to a heterozygous <i>TMEM173</i> mutation) who developed disseminated molluscum contagiosum (MC) while receiving baricitinib therapy. Laboratory results revealed lymphopenia, low CD4/CD8 ratio, and impaired immune cell activity, suggesting compromised antiviral immunity. Discussion: Despite SAVI’s association with excessive type I interferon signaling, this chronic hyperactivation may cause immune dysregulation, exhausting T cells and natural killer cells vital for viral defense. Furthermore, baricitinib suppresses interferon signaling via the JAK-STAT pathway, reducing inflammatory damage in SAVI but also impairing antiviral responses. Moreover, MC viruses evade host immune defenses by antagonizing STING and TANK-binding kinase 1-mediated interferon activation, further contributing to infection risk. This report is the first to document MC in a SAVI patient and highlights the rare complication of disseminated MC due to impaired type I interferon signaling and immune suppression from baricitinib therapy. This case underscores the need for vigilance regarding viral infections in SAVI patients treated with JAK inhibitors. |
| format | Article |
| id | doaj-art-134181bb3f8f48fc9bcb627151310d0c |
| institution | Kabale University |
| issn | 2673-6179 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-134181bb3f8f48fc9bcb627151310d0c2025-08-20T03:27:18ZengMDPI AGDermato2673-61792025-04-0152610.3390/dermato5020006Stimulator of InterferoN Genes (STING)-Associated Vasculopathy with Onset in Infancy Syndrome (SAVI) Associated with Disseminated Molluscum Contagiosum Under Baricitinib TreatmentThilo Gambichler0Yusa Devrim1Laura Susok2Dortmund Hospital gGmbH, University Witten/Herdecke, 44137 Dortmund, GermanyDortmund Hospital gGmbH, University Witten/Herdecke, 44137 Dortmund, GermanyDortmund Hospital gGmbH, University Witten/Herdecke, 44137 Dortmund, GermanyBackground/objectives: Stimulator of Interferon Genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a rare autoinflammatory disorder caused by gain-of-function mutations in the <i>TMEM173</i> gene. These mutations result in chronic activation of the STING pathway and excessive type I interferon production, leading to systemic inflammation, vascular abnormalities, interstitial lung disease, and skin ulcerations. Janus kinase (JAK) inhibitors, including baricitinib, have shown promise in mitigating systemic and organ-specific manifestations. However, these inhibitors broadly suppress immune pathways, potentially increasing vulnerability to infections. Case presentation: This case report describes a 21-year-old woman with SAVI (due to a heterozygous <i>TMEM173</i> mutation) who developed disseminated molluscum contagiosum (MC) while receiving baricitinib therapy. Laboratory results revealed lymphopenia, low CD4/CD8 ratio, and impaired immune cell activity, suggesting compromised antiviral immunity. Discussion: Despite SAVI’s association with excessive type I interferon signaling, this chronic hyperactivation may cause immune dysregulation, exhausting T cells and natural killer cells vital for viral defense. Furthermore, baricitinib suppresses interferon signaling via the JAK-STAT pathway, reducing inflammatory damage in SAVI but also impairing antiviral responses. Moreover, MC viruses evade host immune defenses by antagonizing STING and TANK-binding kinase 1-mediated interferon activation, further contributing to infection risk. This report is the first to document MC in a SAVI patient and highlights the rare complication of disseminated MC due to impaired type I interferon signaling and immune suppression from baricitinib therapy. This case underscores the need for vigilance regarding viral infections in SAVI patients treated with JAK inhibitors.https://www.mdpi.com/2673-6179/5/2/6interferonopathiesJAK inhibitorsvasculitisDNA virus |
| spellingShingle | Thilo Gambichler Yusa Devrim Laura Susok Stimulator of InterferoN Genes (STING)-Associated Vasculopathy with Onset in Infancy Syndrome (SAVI) Associated with Disseminated Molluscum Contagiosum Under Baricitinib Treatment Dermato interferonopathies JAK inhibitors vasculitis DNA virus |
| title | Stimulator of InterferoN Genes (STING)-Associated Vasculopathy with Onset in Infancy Syndrome (SAVI) Associated with Disseminated Molluscum Contagiosum Under Baricitinib Treatment |
| title_full | Stimulator of InterferoN Genes (STING)-Associated Vasculopathy with Onset in Infancy Syndrome (SAVI) Associated with Disseminated Molluscum Contagiosum Under Baricitinib Treatment |
| title_fullStr | Stimulator of InterferoN Genes (STING)-Associated Vasculopathy with Onset in Infancy Syndrome (SAVI) Associated with Disseminated Molluscum Contagiosum Under Baricitinib Treatment |
| title_full_unstemmed | Stimulator of InterferoN Genes (STING)-Associated Vasculopathy with Onset in Infancy Syndrome (SAVI) Associated with Disseminated Molluscum Contagiosum Under Baricitinib Treatment |
| title_short | Stimulator of InterferoN Genes (STING)-Associated Vasculopathy with Onset in Infancy Syndrome (SAVI) Associated with Disseminated Molluscum Contagiosum Under Baricitinib Treatment |
| title_sort | stimulator of interferon genes sting associated vasculopathy with onset in infancy syndrome savi associated with disseminated molluscum contagiosum under baricitinib treatment |
| topic | interferonopathies JAK inhibitors vasculitis DNA virus |
| url | https://www.mdpi.com/2673-6179/5/2/6 |
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