title: International periodic fever, aphthous stomatitis,  pharyngitis, cervical adenitis syndrome cohort:  description of distinct phenotypes in 301 patients.
abstract: OBJECTIVE
  The aims of this study were to describe the clinical features of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and identify distinct phenotypes in a large cohort of patients from different countries.
  
  
  METHODS
  We established a web-based multicentre cohort through an international collaboration within the periodic fevers working party of the Pediatric Rheumatology European Society (PReS). The inclusion criterion was a diagnosis of PFAPA given by an experienced paediatric rheumatologist participating in an international working group on periodic fever syndromes.
  
  
  RESULTS
  Of the 301 patients included from the 15 centres, 271 had pharyngitis, 236 cervical adenitis, 171 oral aphthosis and 132 with all three clinical features. A total of 228 patients presented with additional symptoms (131 gastrointestinal symptoms, 86 arthralgias and/or myalgias, 36 skin rashes, 8 neurological symptoms). Thirty-one patients had disease onset after 5 years and they reported more additional symptoms. A positive family history for recurrent fever or recurrent tonsillitis was found in 81 patients (26.9%). Genetic testing for monogenic periodic fever syndromes was performed on 111 patients, who reported fewer occurrences of oral aphthosis or additional symptoms. Twenty-four patients reported symptoms (oral aphthosis and malaise) outside the flares. The CRP was >50 mg/l in the majority (131/190) of the patients tested during the fever.
  
  
  CONCLUSIONS
  We describe the largest cohort of PFAPA patients presented so far. We confirm that PFAPA may present with varied clinical manifestations and we show the limitations of the commonly used diagnostic criteria. Based on detailed analysis of this cohort, a consensus definition of PFAPA with better-defined criteria should be proposed.
authors: Michaël
authors: M
authors: Hofer
authors: Pascal
authors: P
authors: Pillet
authors: Marie-Madeleine
authors: MM
authors: Cochard
authors: Stefan
authors: S
authors: Berg
authors: Petra
authors: P
authors: Krol
authors: Isabelle
authors: I
authors: Kone-Paut
authors: Donato
authors: D
authors: Rigante
authors: Véronique
authors: V
authors: Hentgen
authors: Jordi
authors: J
authors: Anton
authors: Riva
authors: R
authors: Brik
authors: Bénédicte
authors: B
authors: Neven
authors: Isabelle
authors: I
authors: Touitou
authors: Daniela
authors: D
authors: Kaiser
authors: Agnès
authors: A
authors: Duquesne
authors: Carine
authors: C
authors: Wouters
authors: Marco
authors: M
authors: Gattorno
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005060:Europe / Q000453:epidemiology; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D007391:International Cooperation; D008199:Lymphadenitis / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D009333:Neck; D010612:Pharyngitis / Q000175:diagnosis* / Q000453:epidemiology; D010641:Phenotype; D012008:Recurrence; D013281:Stomatitis, Aphthous / Q000175:diagnosis* / Q000453:epidemiology; D013577:Syndrome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein