Artikel
STING-associated vasculopathy with onset in infancy (SAVI): Severe autoinflammatory disease with mutilating necrotizing dermatitis and relapsing pneumonias
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Autoren
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Kathrin Julia Siepermann
- Helios Klinikum Krefeld Abteilung: Padiatrie, Krefeld
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Gregor Dückers
- HELIOS Kliniken Krefeld, Krefeld
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Nina Brauer
- Helios Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin, Krefeld
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Ruy Perez-Becker
- Helios Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin, Krefeld
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Kumar Sinha
- HELIOS Kliniken Wuppertal, Zentrum für Kinder- und Jugendmedizin, Wuppertal
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Stefan Wirth
- Helios Klinikum Wuppertal, Zentrum für Kinder- und Jugendmedizin, Wuppertal
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Percy Lehmann
- Helios Klinikum Wuppertal, Klinik für Dermatologie, Wuppertal
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Gerd Horneff
- Asklepios Klinik Sankt Augustin, Zentrum für Allgemeine Pädiatrie und Neonatologie, St. Augustin
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Tim Niehues
- HELIOS Kliniken Krefeld, Krefeld
| Veröffentlicht: | 1. September 2015 |
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Gliederung
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Results: Our patient, second male of nonconsanguineous Italian parents, presented with failure to thrive due to a severe idiopathic, systemic inflammation with onset in the first weeks of life, continuous fever (39-40°C), recurrent ulcerative, erythematous pyoderma, ulcerative mucositis, mutilating vasculopathy affecting acral regions and bacterial superinfection, e. g. Pseudomonas aeruginosa. Histology of skin showed interface dermatitis with signs of dyskeratosis, strong signs of inflammatory cell infiltrates, suspected for SLE or neutrophilic dermatosis. The clinical course showed recurrent severe pneumonias, relapsing pancytopenias, perianal abscess, CMV and Adenovirus infection.
The disease course was refractive to corticosteroids (2-30 mg/kg/d), immunoglobulins, colchicine, cyclosporine A and administration of IL-1 and IL-6 inhibition therapies and the patient died at the age of 4,10 years from a septic shock with multiorgan failure.
Periodic fever syndromes and primary immunodeficiency had been excluded by genetic analyses (e.g. FMF, CAPS, DILRA, NALP12 etc.). Lab results showed weakly positive ANCA titre, elevated titre for C3d and C1q immune-complex, increased cytokines in serum (IL-6, TNFa and CD25, Univ. Ulm), hypergammaglobulinaemia, anaemia and decreasing numbers of CD3+/CD4+ cells, IgD 237 mg/l.
Postmortem genetic analyses revealed a pathgenic mutation (TMEM173NM_198282 c.461A>G, p.N154S heterozygous mutation) for STING Associated Vasculopathy with onset in Infancy (SAVI) (NEJM, Liu 2014).
Conclusion: STING-associated vasculopathy with onset in infancy is an aggresive, potential fatal autoinflammatory disease caused by gain-of-function mutations in TMEM173. The mutation leads to induction of type 1 interferon signaling, constitutive or dependent on endogenous or environmental stimuli.
Early detection of SAVI is important as there may be effective treatment available (JAK inhibitors) with blocking in vitro IFNB1 transcription and the induction of interferon-response.
