title: Clinical and genetic characterization of the autoinflammatory diseases diagnosed in an adult reference center.
abstract: BACKGROUND
  Autoinflammatory diseases (AID) are usually diagnosed during the pediatric age. However, adult-onset disease or diagnosis during adulthood has been occasionally described.
  
  
  OBJECTIVE
  To assess the clinical and genetic characteristics of adult patients diagnosed with an AID in an adult referral center for AID.
  
  
  METHODS
  We retrospectively evaluated clinical and genetic features of adult patients (≥16 years) diagnosed with an AID or referred after AID diagnosis to the Clinical Unit of AID, at the Department of Autoimmune Diseases, Hospital Clínic of Barcelona, from 2008 to 2014.
  
  
  RESULTS
  During the study period, a genetic study for suspected AID was requested to 90 patients at the Department of Autoimmune Diseases. A final diagnosis of monogenic AID was achieved in 17 patients (19% of patients tested). Five additional cases were diagnosed with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome and 10 patients with AID were referred from other adult departments. Finally, a total of 32 patients with AID were finally diagnosed or monitored in our Clinical Unit. These included 12 (37.5%) familial Mediterranean fever, 6 (18.8%) tumour necrosis factor-receptor associated periodic syndrome, 8 (25%) cryopirin-associated periodic syndromes (Muckle-Wells syndrome [MWS] or overlap familial cold-associated periodic syndrome/MWS), 1 (3.1%) mevalonate kinase deficiency, and 5 (15.6%) PFAPA. Clinical evidence of disease-onset during childhood and adulthood was observed in 15 (47%) and 17 (53%) patients, respectively. Overall, the final diagnosis was obtained after a delay of a mean of 12 years (range 0-47 years). Compared to children, adult patients with AID in our series presented more frequently with non-severe manifestations and none of them developed amyloidosis during follow-up. Adult patients also carried higher proportion of low-penetrance mutations or polymorphisms and all genetic variants were presented in heterozygosis or as heterozygous compounds.
  
  
  CONCLUSIONS
  Adult disease-onset or delayed diagnosis of AID during adulthood is associated with milder disease phenotypes, and seem to be driven by mild genotypes, with predominant presence of low-penetrance mutations or polymorphisms.
authors: Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Vasculitis Research Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain. Electronic address: jhernan@clinic.ub.es.
authors: José
authors: J
authors: Hernández-Rodríguez
authors: Autoinflammatory Diseases Laboratory Unit, Department of Immunology, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Estíbaliz
authors: E
authors: Ruíz-Ortiz
authors: Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Adrià
authors: A
authors: Tomé
authors: Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Gerard
authors: G
authors: Espinosa
authors: Autoinflammatory Diseases Laboratory Unit, Department of Immunology, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Eva
authors: E
authors: González-Roca
authors: Autoinflammatory Diseases Laboratory Unit, Department of Immunology, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Anna
authors: A
authors: Mensa-Vilaró
authors: Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Vasculitis Research Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Sergio
authors: S
authors: Prieto-González
authors: Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Vasculitis Research Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Georgina
authors: G
authors: Espígol-Frigolé
authors: Department of Infectious Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Josep
authors: J
authors: Mensa
authors: Muscle Research Unit, Department of Internal Medicine, Centro de Investigación Biomédica en Red (CIBER) on Rare Diseases, Centro de Investigación Biomédica en Red (CIBER) on Rare Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Francesc
authors: F
authors: Cardellach
authors: Muscle Research Unit, Department of Internal Medicine, Centro de Investigación Biomédica en Red (CIBER) on Rare Diseases, Centro de Investigación Biomédica en Red (CIBER) on Rare Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Josep M
authors: JM
authors: Grau
authors: Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain; Vasculitis Research Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Maria C
authors: MC
authors: Cid
authors: Autoinflammatory Diseases Laboratory Unit, Department of Immunology, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Jordi
authors: J
authors: Yagüe
authors: Autoinflammatory Diseases Laboratory Unit, Department of Immunology, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Juan I
authors: JI
authors: Aróstegui
authors: Autoinflammatory Diseases Clinical Unit, Department of Autoimmune Diseases, Working Group of Adult Rare Diseases, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain.
authors: Ricard
authors: R
authors: Cervera
mesh_terms: D000328:Adult; D001327:Autoimmune Diseases / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D009154:Mutation; D018579:Patient Selection; D010641:Phenotype
keywords: Adult-onset; Autoinflammatory diseases