In silico validation of the Autoinflammatory Disease Damage Index.
Ter Haar NMLaboratory for Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
van Delft ALJDepartment of Paediatrics, Universitair Medisch Centrum Utrecht-Locatie Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
Annink KVDepartment of Paediatrics, Universitair Medisch Centrum Utrecht-Locatie Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
van Stel HDepartment of Paediatrics, Universitair Medisch Centrum Utrecht-Locatie Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
Al-Mayouf SMDepartment of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Amaryan GNational Paediatric Centre for Familial Mediterranean Fever and Gastroenterology Service, Arabkir Medical Centre-Institute of Child and Adolescent Health, Yerevan, Armenia.
Anton JPaediatric Rheumatology Unit, Hospital Sant Joan de Déu, Barcelona, Spain.
Barron KSDivision of Intramural Research and National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Benseler SDepartments of Paediatrics and Rheumatology, Alberta Children's Hospital, Calgary, Alberta, Canada.
Brogan PADepartment of Infection, Inflammation and Rheumatology, University College London Institute of Child Health, London, UK.
Cantarini LRheumatology Unit, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy.
Cattalini MPaediatric Clinic, University of Brescia and Spedali Civili di Brescia, Brescia, Italy.
Cochino AVDepartment of Paediatrics, National Institute for Mother and Child Health Alessandrescu-Rusescu, Bucharest, Romania.
de Benedetti FDivision of Rheumatology, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Dedeoglu FRheumatology Program, Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
de Jesus AATranslational Autoinflammatory Disease Section, NIAMS/NIH, Bethesda, Maryland, USA.
Demirkaya EWestern University Children's Hospital, London Health Sciences Centre, London, UK.
Dolezalova PDepartment of Paediatrics and Adolescent Medicine, Charles University, General University Hospital, Praha, Czech Republic.
Durrant KLAutoinflammatory Alliance, San Francisco, California, USA.
Fabio GDepartment of Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.
Gallizzi RDepartment of Paediatric Rheumatology, AOUG Martino, Messina, Italy.
Goldbach-Mansky RTranslational Autoinflammatory Disease Section, NIAMS/NIH, Bethesda, Maryland, USA.
Hachulla EDépartement de Médecine Interne et Immunologie Clinique, Université de Lille, Lille, France.
Hentgen VReference Centre for Autoinflammatory Diseases (CEREMAI), Versailles Hospital, Le Chesnay, France.
Herlin TDepartmentof Paediatrics, Aarhus University Hospital, Aarhus, Denmark.
Hofer MDepartment of Paediatric Rheumatology, University of Lausanne, Lausanne, Switzerland.
Hoffman HMDepartment of Paediatrics, University of California, San Diego, California, USA.
Jansson AFPaediatric Pneumology and Immunology and Interdisciplinary Centre for Social Paediatrics, Charite University Medicine Berlin, Berlin, Germany.
Kallinich TPaediatric Pneumology and Immunology and Interdisciplinary Centre for Social Paediatrics, Charite University Medicine Berlin, Berlin, Germany.
Kone-Paut IDepartment of Paediatric Rheumatology and CEREMAI, Bicêtre Hospital, APHP, University of Paris Sud, Paris, France.
Kozlova ADepartment of Immunology, Federal Research and Clinical Centre for Paediatric Haematology, Oncology and Immunology, Moscow, Russian Federation.
Kuemmerle-Deschner JBDivision of Pediatric Rheumatology, Department of Pediatrics, University Hospital Tübingen, Tübingen, Germany.
Lachmann HJDivision of Medicine, University College London, London, UK.
Laxer RMDepartment of Paediatrics and Medicine, University of Toronto and the Hospital for Sick Children, Toronto, Ontario, Canada.
Martini ADirezione Scientifica, Istituto Giannina Gaslini, Genova, Liguria, Italy.
Nielsen SPaediatric Rheumatology Unit 4272, Rigshospitalet, Copenhagen, Denmark.
Nikishina IDepartment of Paediatric Rheumatic Diseases, VA Nasonova Research Institute of Rheumatology, Moscow, Russian Federation.
Ombrello AKInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA.
Özen SPediatric Rheumatology, Hacettepe University, Ankara, Turkey.
Papadopoulou-Alataki EFourth Department of Pediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Quartier PDepartment of Paediatric Immunology-Hematology and Rheumatology Unit and IMAGINE Institute, Institution Necker-Enfants Malades Hospital and Paris Descartes University, Paris, Île-de-France, France.
Rigante DInstitute of Paediatrics, Fondazione Policlinico Universitario A Gemelli, Università Cattolica Sacro Cuore, Rome, Italy.
Russo RServicio de Inmunología/Reumatología, Hospital de Pediatria Juan P Garrahan, Buenos Aires, Argentina.
Simon ADepartment of General Internal Medicine, Radboud Expertise Centre for Immunodeficiency and Autoinflammation, Radboud University Medical Centre, Nijmegen, The Netherlands.
Trachana MPaediatric Immunology and Rheumatology Referral Centre, First Paediatric Clinic, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Uziel YDepartment of Paediatrics, Meir Medical Centre, Kfar Saba, Israel.
Ravelli AInstitution Università degli Studi di Genova and G Gaslini Institute, Genova, Italy.
Schulert GDivision of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Gattorno MInstitution Università degli Studi di Genova and G Gaslini Institute, Genova, Italy.
Frenkel JDepartment of Paediatrics, Universitair Medisch Centrum Utrecht-Locatie Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
English
INTRODUCTION Autoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting.
METHODS The ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an 'observer-nested-within-subject' design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach's alpha.
RESULTS The ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items.
CONCLUSION The ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies.