OBJECTIVES: To describe the clinical characteristics, treatment response and genetic findings in a large cohort of patients with undefined systemic autoinflammatory diseases (SAIDs). METHODS: Clinical and genetic data from patients with undefined SAIDs were extracted from the Eurofever registry, an international web-based registry that retrospectively collects clinical information on patients with autoinflammatory diseases. RESULTS: This study included 187 patients. Seven patients had a chronic disease course, 180 patients had a recurrent disease course. The median age at disease onset was 4.3 years. Patients had a median of 12 episodes per year, with a median duration of 4 days. Most commonly reported symptoms were arthralgia (n=113), myalgia (n=86), abdominal pain (n=89), fatigue (n=111), malaise (n=104) and mucocutaneous manifestations (n=128). In 24 patients, relatives were affected as well. In 15 patients, genetic variants were found in autoinflammatory genes. Patients with genetic variants more often had affected relatives compared with patients without genetic variants (p=0.005). Most patients responded well to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine and anakinra. Complete remission was rarely achieved with NSAIDs alone. Notable patterns were found in patients with distinctive symptoms. Patients with pericarditis (n=11) were older at disease onset (33.8 years) and had fewer episodes per year (3.0/year) compared with other patients. Patients with an intellectual impairment (n=8) were younger at disease onset (2.2 years) and often had relatives affected (28.6%). CONCLUSION: This study describes the clinical characteristics of a large cohort of patients with undefined SAIDs. Among these, patients with pericarditis and intellectual impairment appear to comprise distinct subsets.

4th Department of Pediatrics Aristotle University of Thessaloniki Papageorgiou Hospital Thessaloniki Greece

Børnereumatologisk Juliane Marie Centret Rigshospitalet København Denmark

Center for Autoinflammatory Diseases and Immunodeficiency IRCCS Instituto Giannina Gaslini Genoa Italy

Clinica Pediatrica e Reumatologia Istituto Giannina Gaslini Genova Italy

Department of Clinical Sciences and Community Health University of Milan Milan Italy

Department of Medical Genetics University Medical Center Utrecht Utrecht Netherlands

Department of Paediatric Rheumatology and CEREMAI Hôpital de Bicêtre National Reference Centre for Auto Inflammatory Diseases le Kremlin Bicêtre Paris France

Department of Paediatric Rheumatology and Immunology University Hospital Centre Zagreb Zagreb Croatia

Department of Paediatrics University Medical Center Utrecht Utrecht Netherlands

Department of Pediatric Rheumatology Institute of Rheumatology BelgradeInstitute of Rheumatology Belgrade Serbia

Department of Pediatrics and Adolescent Medicine Charles University Prague and General University Hospital Praha Czech Republic

Department of Woman and Child and General and Specialistic Surgery University of the Study of Campania Luigi Vanvitelli Napoli Italy

Dipartimento di Scienze della Sanità Pubblica e Pediatrica Università degli Studi di Torino Torino Italy

Faculty of Medicine Utrecht University Utrecht Netherlands

Institute of Child Health University College London London UK

Laboratory of Translational Immunology and Department of Paediatric Rheumatology and Immunology University Medical Center Utrecht Utrecht Netherlands

Paediatric Department Riga Stradins University Children University Hospital Rīga Latvia

Pediatric Department 5 A Nasonova Research Institute of Rheumatology Moscow Russian Federation

Pediatric Rheumatology Hospital Universitario Vall d'Hebron Barcelona Spain

Pediatric Rheumatology Ospedale Pediatrico Bambin Gesù Roma Italy

Pediatric Rheumatology Unit Department of Pediatrics Meir Medical Centre Kfar Saba and Sackler School of Medicine Kfar Saba Israel

Pediatrie Institutul pentru Ocrotirea Mamei și Copilului București Romania

Rheumatology Unit Department of Medical Sciences Surgery and Neurosciences University of Siena Siena Italy

Unité Centre Multisite Romande d'Immuno e Rhumatologie Pediatrique Centre Hospitalier Universitaire Vaudois Lausanne Switzerland

Ann Rheum Dis. 2021 Jul;80(7):e117. doi: 10.1136/annrheumdis-2019-216158. PubMed

Ann Rheum Dis. 2021 Jul;80(7):e118. doi: 10.1136/annrheumdis-2019-216184. PubMed

Ann Rheum Dis. 2023 Jan;82(1):e26. doi: 10.1136/annrheumdis-2020-218422. PubMed

Ann Rheum Dis. 2023 Oct;82(10):e218. doi: 10.1136/annrheumdis-2020-219566. PubMed

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