Takashi Ishikawa1,2, Eiichiro Tamura1,2, Mureo Kasahara3, Hajime Uchida3, Masataka Higuchi4, Hisato Kobayashi4,5, Hirotaka Shimizu6, Eiki Ogawa7, Nobuyuki Yotani8, Rie Irie9, Rika Kosaki10, Kenjiro Kosaki11, Toru Uchiyama1, Masafumi Onodera1, Toshinao Kawai12,13. 1. Division of Immunology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. 2. Department of Pediatrics, The Jikei University School of Medicine, 3-19-18 Nishishinbashi, Minato-ku, Tokyo, 105-8471, Japan. 3. Center for Organ Transplantation, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. 4. Division of Pulmonology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. 5. Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. 6. Division of Gastroenterology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. 7. Division of Infectious Diseases, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. 8. Division of Palliative Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. 9. Department of Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. 10. Division of Medical Genetics, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. 11. Center for Medical Genetics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. 12. Division of Immunology, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. kawai-t@ncchd.go.jp. 13. Department of Pediatrics, The Jikei University School of Medicine, 3-19-18 Nishishinbashi, Minato-ku, Tokyo, 105-8471, Japan. kawai-t@ncchd.go.jp.
Abstract
PURPOSE: STING-associated vasculopathy with onset in infancy (SAVI) is a type-I interferonopathy, characterized by systemic inflammation, peripheral vascular inflammation, and pulmonary manifestations. There are three reports of SAVI patients developing liver disease, but no report of a SAVI patient requiring liver transplantation. Therefore, the relevance of liver inflammation is unclear in SAVI. We report a SAVI patient who developed severe liver disorder following liver transplantation. METHODS: SAVI was diagnosed in a 4-year-old girl based on genetic analysis by whole-exome sequencing. We demonstrated clinical features, laboratory findings, and pathological examination of her original and transplanted livers. RESULTS: At 2 months of age, she developed bronchitis showing resistance to bronchodilators and antibiotics. At 10 months of age, she developed liver dysfunction with atypical cholangitis, which required liver transplantation at 1 year of age. At 2 years of age, multiple biliary cysts developed in the transplanted liver. At 3.9 years of age, SAVI was diagnosed by whole-exome sequencing. Inflammatory cells from the liver invaded the stomach wall directly, leading to fatal gastrointestinal bleeding unexpectedly at 4.6 years of age. In pathological findings, there were no typical findings of liver abscess, vasculitis, or graft rejection, but biliary cysts and infiltration of inflammatory cells, including plasmacytes around the bile duct area, in the transplanted liver were noted, which were findings similar to those of her original liver. CONCLUSION: Although further studies to clarify the mechanisms of the various liver disorders described in SAVI patients are needed, inflammatory liver manifestations may be amplified in the context of SAVI.
PURPOSE: STING-associated vasculopathy with onset in infancy (SAVI) is a type-I interferonopathy, characterized by systemic inflammation, peripheral vascular inflammation, and pulmonary manifestations. There are three reports of SAVI patients developing liver disease, but no report of a SAVI patient requiring liver transplantation. Therefore, the relevance of liver inflammation is unclear in SAVI. We report a SAVI patient who developed severe liver disorder following liver transplantation. METHODS: SAVI was diagnosed in a 4-year-old girl based on genetic analysis by whole-exome sequencing. We demonstrated clinical features, laboratory findings, and pathological examination of her original and transplanted livers. RESULTS: At 2 months of age, she developed bronchitis showing resistance to bronchodilators and antibiotics. At 10 months of age, she developed liver dysfunction with atypical cholangitis, which required liver transplantation at 1 year of age. At 2 years of age, multiple biliary cysts developed in the transplanted liver. At 3.9 years of age, SAVI was diagnosed by whole-exome sequencing. Inflammatory cells from the liver invaded the stomach wall directly, leading to fatal gastrointestinal bleeding unexpectedly at 4.6 years of age. In pathological findings, there were no typical findings of liver abscess, vasculitis, or graft rejection, but biliary cysts and infiltration of inflammatory cells, including plasmacytes around the bile duct area, in the transplanted liver were noted, which were findings similar to those of her original liver. CONCLUSION: Although further studies to clarify the mechanisms of the various liver disorders described in SAVI patients are needed, inflammatory liver manifestations may be amplified in the context of SAVI.
Authors: Kader Cetin Gedik; Lovro Lamot; Micol Romano; Erkan Demirkaya; David Piskin; Sofia Torreggiani; Laura A Adang; Thais Armangue; Kathe Barchus; Devon R Cordova; Yanick J Crow; Russell C Dale; Karen L Durrant; Despina Eleftheriou; Elisa M Fazzi; Marco Gattorno; Francesco Gavazzi; Eric P Hanson; Min Ae Lee-Kirsch; Gina A Montealegre Sanchez; Bénédicte Neven; Simona Orcesi; Seza Ozen; M Cecilia Poli; Elliot Schumacher; Davide Tonduti; Katsiaryna Uss; Daniel Aletaha; Brian M Feldman; Adeline Vanderver; Paul A Brogan; Raphaela Goldbach-Mansky Journal: Ann Rheum Dis Date: 2022-01-27 Impact factor: 27.973