title: Anakinra as a diagnostic challenge and treatment option for systemic autoinflammatory disorders of undefined etiology.
abstract: Some adult patients presenting with unexplained pyrexia, serositis, skin rashes, arthralgia, myalgia, and other symptoms commonly found in autoinflammatory disorders may not fit a specific diagnosis, either because their clinical phenotype is nondiagnostic or genetic tests are negative. We used the term undifferentiated systemic autoinflammatory disorder (uSAID) to describe such cases. Given that well-defined autoinflammatory diseases show responses to IL-1 blockade, we evaluated whether anakinra was useful for both diagnosing and treating uSAID patients.
  
  
  
  We performed a retrospective analysis of consecutive patients presenting with uSAID between 2012-2015 who were treated with the recombinant IL-1 receptor antagonist anakinra. uSAID was diagnosed after excluding malignancy, infection, and pathogenic mutations in known hereditary fever syndromes (HFS) genes and where clinical criteria for adult onset Still's disease (AOSD) were not met.
  
  
  
  A total of 11 patients presented with uSAID (5 males and 6 females), with a mean time to diagnosis of 3.5 years (1-8 years). Patients were unresponsive or only partially controlled on disease-modifying antirheumatic drug (DMARD)/steroid treatment. Anakinra controlled symptoms within 4-6 weeks of starting treatment in 9 of 11 cases. Two patients discontinued therapy - one due to incomplete response and another due to severe injection-site reactions.
  
  
  
  This retrospective case series demonstrates that the spectrum of poorly defined autoinflammatory disorders that show responsiveness to anakinra is considerable. Anakinra seems a viable treatment option for these patients, who are unresponsive to standard steroid/DMARD treatments. Moreover, given the mechanisms of action, response to anakinra implicates underlying IL-1 dysregulation in the disease pathogenesis of responding uSAIDs patients.
authors.affiliation: NIH Research-Leeds Musculoskeletal Biomedical Research Unit (NIHR-LMBRU) and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner Building, St. James's University Hospital, Beckett Street, Leeds, United Kingdom.
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Harrison
authors.affiliation: NIH Research-Leeds Musculoskeletal Biomedical Research Unit (NIHR-LMBRU) and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner Building, St. James's University Hospital, Beckett Street, Leeds, United Kingdom.
authors.forename: Dennis
authors.initials: D
authors.lastname: McGonagle
authors.affiliation: Department of Rheumatology, Pinderfields Hospital, Wakefield, United Kingdom.
authors.forename: Sharmin
authors.initials: S
authors.lastname: Nizam
authors.affiliation: Department of Rheumatology, Pinderfields Hospital, Wakefield, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Jarrett
authors.affiliation: Department of Infectious Diseases and Immunity, Jessa Hospital, Hasselt, Belgium.|BIOMED Research Institute, University of Hasselt, Hasselt, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Hilst
authors.affiliation: NIH Research-Leeds Musculoskeletal Biomedical Research Unit (NIHR-LMBRU) and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner Building, St. James's University Hospital, Beckett Street, Leeds, United Kingdom.
authors.forename: Michael F
authors.initials: MF
authors.lastname: McDermott
authors.affiliation: NIH Research-Leeds Musculoskeletal Biomedical Research Unit (NIHR-LMBRU) and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner Building, St. James's University Hospital, Beckett Street, Leeds, United Kingdom.|Department of Clinical Immunology and Allergy, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Sinisa
authors.initials: S
authors.lastname: Savic
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein