The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Kader Cetin Gedik^#¹, Lovro Lamot^#², Micol Romano^#³, Erkan Demirkaya³, David Piskin^{4

5}, Sofia Torreggiani^{1

6}, Laura A Adang⁷, Thais Armangue⁸, Kathe Barchus⁹, Devon R Cordova¹⁰, Yanick J Crow^{11

12}, Russell C Dale¹³, Karen L Durrant^{9

14}, Despina Eleftheriou¹⁵, Elisa M Fazzi¹⁶, Marco Gattorno¹⁷, Francesco Gavazzi^{7

18}, Eric P Hanson¹⁹, Min Ae Lee-Kirsch²⁰, Gina A Montealegre Sanchez²¹, Bénédicte Neven²², Simona Orcesi^{23

24}, Seza Ozen²⁵, M Cecilia Poli²⁶, Elliot Schumacher⁹, Davide Tonduti²⁷, Katsiaryna Uss¹, Daniel Aletaha²⁸, Brian M Feldman^{29

30}, Adeline Vanderver^{7

31}, Paul A Brogan¹⁵, Raphaela Goldbach-Mansky³²

Affiliations

¹ Translational Autoinflammatory Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
² Department of Pediatrics, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
³ Division of Paediatric Rheumatology, Department of Paediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
⁴ Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.
⁵ London Health Sciences Center, Lawson Health Research Institute, London, Ontario, Canada.
⁶ UOC Pediatria a Media Intensità di Cura, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Lombardia, Italy.
⁷ Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁸ Pediatric Neuroimmunology Unit, Neurology Service, Sant Joan de Deu Children's Hospital, and IDIBAPS-Hospital Clinic, University of Barcelona, Barcelona, Spain.
⁹ Autoinflammatory Alliance, San Francisco, California, USA.
¹⁰ Aicardi-Goutieres Syndrome Americas Association, Manhattan Beach, California, USA.
¹¹ Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburg, Edinburg, UK.
¹² Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, Université de Paris, Paris, Île-de-France, France.
¹³ Kids Neuroscience Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
¹⁴ Kaiser San Francisco Hospital, San Francisco, California, USA.
¹⁵ Great Ormond Street Institute of Child Health, University College London, London, UK.
¹⁶ Child Neurology and Psychiatry Unit, Department of Clinical and Experimental Sciences ASST Civil Hospital, University of Brescia, Brescia, Italy.
¹⁷ Center for Autoinflammatory diseases and Immunodeficiencies, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
¹⁸ Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
¹⁹ Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA.
²⁰ Department of Pediatrics, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
²¹ Intramural Clinical Management and Operations Branch (ICMOB), Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
²² Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, Institut Imagine Institut des Maladies Genetiques, Paris, Île-de-France, France.
²³ Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy, Italy.
²⁴ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Lombardia, Italy.
²⁵ Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.
²⁶ Department of Pediatrics, Facultad de Medicina Clinica Alemana Universidad del Desarrollo, Santiago, Chile.
²⁷ Child Neurology Unit, COALA (Center for Diagnosis and Treatment of Leukodystrophies), V. Buzzi Children's Hospital, Milano, Italy.
²⁸ Department of Rheumatology, Medical University of Vienna, Vienna, Austria.
²⁹ Division of Rheumatology, Hospital for Sick Children, Toronto, Ontario, Canada.
³⁰ Department of Pediatrics, Faculty of Medicine, University of Toronto Institute of Health Policy Management and Evaluation, Toronto, Ontario, Canada.
³¹ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³² Translational Autoinflammatory Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA goldbacr@mail.nih.gov.

^# Contributed equally.

PMID: 35086813
PMCID: PMC9036471
DOI: 10.1136/annrheumdis-2021-221814

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Kader Cetin Gedik et al. Ann Rheum Dis. 2022 May.

. 2022 May;81(5):601-613.

doi: 10.1136/annrheumdis-2021-221814. Epub 2022 Jan 27.

Authors

Affiliations

¹ Translational Autoinflammatory Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
² Department of Pediatrics, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, Croatia.
³ Division of Paediatric Rheumatology, Department of Paediatrics, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
⁴ Department of Epidemiology and Biostatistics, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada.
⁵ London Health Sciences Center, Lawson Health Research Institute, London, Ontario, Canada.
⁶ UOC Pediatria a Media Intensità di Cura, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Lombardia, Italy.
⁷ Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
⁸ Pediatric Neuroimmunology Unit, Neurology Service, Sant Joan de Deu Children's Hospital, and IDIBAPS-Hospital Clinic, University of Barcelona, Barcelona, Spain.
⁹ Autoinflammatory Alliance, San Francisco, California, USA.
¹⁰ Aicardi-Goutieres Syndrome Americas Association, Manhattan Beach, California, USA.
¹¹ Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburg, Edinburg, UK.
¹² Laboratory of Neurogenetics and Neuroinflammation, Institut Imagine, Université de Paris, Paris, Île-de-France, France.
¹³ Kids Neuroscience Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
¹⁴ Kaiser San Francisco Hospital, San Francisco, California, USA.
¹⁵ Great Ormond Street Institute of Child Health, University College London, London, UK.
¹⁶ Child Neurology and Psychiatry Unit, Department of Clinical and Experimental Sciences ASST Civil Hospital, University of Brescia, Brescia, Italy.
¹⁷ Center for Autoinflammatory diseases and Immunodeficiencies, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
¹⁸ Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
¹⁹ Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana, USA.
²⁰ Department of Pediatrics, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
²¹ Intramural Clinical Management and Operations Branch (ICMOB), Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
²² Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, Institut Imagine Institut des Maladies Genetiques, Paris, Île-de-France, France.
²³ Child Neurology and Psychiatry Unit, IRCCS Mondino Foundation, Pavia, Italy, Italy.
²⁴ Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Lombardia, Italy.
²⁵ Pediatric Rheumatology, Hacettepe University, Ankara, Turkey.
²⁶ Department of Pediatrics, Facultad de Medicina Clinica Alemana Universidad del Desarrollo, Santiago, Chile.
²⁷ Child Neurology Unit, COALA (Center for Diagnosis and Treatment of Leukodystrophies), V. Buzzi Children's Hospital, Milano, Italy.
²⁸ Department of Rheumatology, Medical University of Vienna, Vienna, Austria.
²⁹ Division of Rheumatology, Hospital for Sick Children, Toronto, Ontario, Canada.
³⁰ Department of Pediatrics, Faculty of Medicine, University of Toronto Institute of Health Policy Management and Evaluation, Toronto, Ontario, Canada.
³¹ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
³² Translational Autoinflammatory Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA goldbacr@mail.nih.gov.

^# Contributed equally.

PMID: 35086813
PMCID: PMC9036471
DOI: 10.1136/annrheumdis-2021-221814

Abstract

Objective: Autoinflammatory type I interferonopathies, chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature/proteasome-associated autoinflammatory syndrome (CANDLE/PRAAS), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutières syndrome (AGS) are rare and clinically complex immunodysregulatory diseases. With emerging knowledge of genetic causes and targeted treatments, a Task Force was charged with the development of 'points to consider' to improve diagnosis, treatment and long-term monitoring of patients with these rare diseases.

Methods: Members of a Task Force consisting of rheumatologists, neurologists, an immunologist, geneticists, patient advocates and an allied healthcare professional formulated research questions for a systematic literature review. Then, based on literature, Delphi questionnaires and consensus methodology, 'points to consider' to guide patient management were developed.

Results: The Task Force devised consensus and evidence-based guidance of 4 overarching principles and 17 points to consider regarding the diagnosis, treatment and long-term monitoring of patients with the autoinflammatory interferonopathies, CANDLE/PRAAS, SAVI and AGS.

Conclusion: These points to consider represent state-of-the-art knowledge to guide diagnostic evaluation, treatment and management of patients with CANDLE/PRAAS, SAVI and AGS and aim to standardise and improve care, quality of life and disease outcomes.

Keywords: genetic; immune system diseases; inflammation; polymorphism.

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Conflict of interest statement

Competing interests: EMF received NIH Grant “Clinical Outcomes in Aicardi Goutières Syndrome” (Grant number 5U01NS106845-02) and participated in an advisory board of Biogen. EPH: Spouse employed by Eli Lilly and received stock options in 2019 and 2020. SO1: NIH Grant “Clinical Outcomes in Aicardi Goutières Syndrome” (Grant number 5U01NS106845-02) and participated in advisory board of Biogen. CP received consulting and lecture fees from Novartis. BMF is associate editor of Arthritis and Rheumatology and member of the ACR guidance document committee. AV received grant support from Eli Lilly. PAB received grants from Roche and consulting and lecture fees and travel support from Roche, SOBI and Novartis. RG-M received study support under government CRADAs from Eli Lilly, IFM and SOBI. The consensus meetings were sponsored as EULAR/ACR projects.

References

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The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Affiliations

The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS

Authors

Affiliations

Abstract

Conflict of interest statement

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