BACKGROUND: Diagnosis of Periodic Fever, Aphthous stomatitis, Pharyngitis and Cervical Adenitis (PFAPA) syndrome is currently based on the modified Marshall's criteria, but no validated evidence based classification criteria for PFAPA has been established so far. METHODS: A multistep process, based on the Delphi and Nominal Group Technique was conducted. After 2 rounds of e-mail Delphi survey involving 21 experts in autoinflammation we obtained a list of variables that were discussed in an International Consensus Conference. Variables reaching the 80% of consensus between participants were included in the new classification criteria. In the second phase the new classification criteria and the modified Marshall's criteria were applied on a cohort of 80 pediatric PFAPA patients to compare their performance. RESULTS: The Delphi Survey was sent to 22 participants, 21 accepted to participate. Thirty variables were obtained from the survey and have been discussed at the Consensus Conference. Through the Nominal Group Technique we obtained a new set of classification criteria. These criteria were more restrictive in respect to the modified Marshall's criteria when applied on our cohort of patients. CONCLUSION: Our work led us to identify a new set of classification criteria for PFAPA syndrome, but they resulted to be too restrictive to be applied in daily clinical practice for the diagnosis of PFAPA.

Department of Infectious Diseases and Immunology Children's Hospital University of Munich Munich Germany

Department of Microbiology and Immunology Laboratory Paediatric Immunology UZ Leuven Hospital Leuven Belgium

Department of Paediatrics and Adolescent Medicine Paediatric Rheumatology Unit General University Hospital and 1st Faculty of Medicine Charles University Prague Praha Czech Republic

Department of Pediatric Rheumatology Hacettepe University Ankara Turkey

Department of Pediatrics and Pediatric Rheumatology Service Ruth Rappaport Children's Hospital Rambam Medical Center Haifa Israel

Department of Pediatrics The Queen Silvia Children's Hospital Goteborg Sweden

Istituto Giannina Gaslini Clinica Pediatrica e Reumatologia PRINTO Genoa Italy

Istituto Pediatrico della Svizzera Italiana Ospedale San Giovanni 6500 Bellinzona Switzerland

Pediatric Rheumatology Hospital Sant Joan de Déu Universitat de Barcelona Esplugues de Llobregat Barcelona Spain

Rhumatologie pédiatrique CHU Le Kremlin Bicêtre APHP University of Paris Sud CEREMAIA Paris France

Service de pédiatrie médicale CHRU de Bordeaux Bordeaux France

Unité d'Immunologie Hématologie et Rhumatologie Pédiatriques CHU Paris Hôpital Necker Enfants Malades Paris France

Unité Romande d'Immuno rhumatologie Pédiatrique CHUV University of Lausanne Lausanne and HUG Geneva Switzerland

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Marshall GS, Edwards KM, Butler J, Lawton AR. Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr. 1987;110(1):43–46. doi: 10.1016/S0022-3476(87)80285-8. PubMed DOI

Thomas KT, Feder HM, Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr. 1999;135(1):15–21. doi: 10.1016/S0022-3476(99)70321-5. PubMed DOI

Gattorno M, Caorsi R, Meini A, Cattalini M, Federici S, Zulian F, Cortis E, Calcagno G, Tommasini A, Consolini R, Simonini G, Pelagatti MA, Baldi M, Ceccherini I, Plebani A, Frenkel J, Sormani MP, Martini A. Differentiating PFAPA syndrome from monogenic periodic fevers. Pediatrics. 2009;124(4):e721–e728. doi: 10.1542/peds.2009-0088. PubMed DOI

Delbecq AL, Van de Ven AH, Gustafson DH. Group techniques for program planning. A guide to nominal group and Delphi processes. 1 ed. Glenview, ill, Scott, Foresman and company; 1975. Ruperto N, Meiorin S, Iusan SM, Ravelli a, Pistorio a, for the Paediatric rheumatology international trials organisation (PRINTO). Consensus procedures and their role in pediatric rheumatology. Curr Rheumatol Rep 2008; 10(2):142–146. PubMed

Hofer M, Pillet P, Cochard M-M, Berg S, Krol P, Kone-Paut I, Rigante D, Hentgen V, Anton J, Brik R, Neven B, Touitou I, Kaiser D, Duquesne A, Wouters C, Gattorno M. International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients. Rheumatology (Oxford) 2014;53(6):1125–1129. doi: 10.1093/rheumatology/ket460. PubMed DOI

Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation