An International Delphi Survey for the Definition of New Classification Criteria for Familial Mediterranean Fever, Mevalonate Kinase Deficiency, TNF Receptor-associated Periodic Fever Syndromes, and Cryopyrin-associated Periodic Syndrome

J Rheumatol. 2019 Apr;46(4):429-436. doi: 10.3899/jrheum.180056. Epub 2018 Nov 1.


Objective: Provisional evidence-based classification criteria for hereditary periodic fever (HPF) have been recently developed. However, no consensus on how to combine clinical criteria, laboratory tests, and results of molecular analysis has been reached. The objective of this study is to understand which variables physicians consider important for the classification of patients with HPF.

Methods: Two Delphi surveys were sent to health professionals in the field of autoinflammation. In the first open survey, 124 researchers could list all the variables they consider useful for the diagnosis of each monogenic periodic fever. The variables could be of any type and each researcher could complete the survey for 1 or more diseases. In the second survey, 162 researchers were asked to select, from a list of items coming from the first survey, the 10 top variables and to rank them by assigning a score from 10 to 1.

Results: The response rates to the Delphi surveys were 85% for the first session and 87% for the second. The variables selected for each disease (corresponding to the third quartile, considering the total score obtained by the variables after the second Delphi survey) were 21 for mevalonate kinase deficiency, 22 for cryopyrinopathies, 18 for familial Mediterranean fever, and 20 for tumor necrosis factor receptor-associated periodic fever syndrome. A positive genetic test reached the top rank in all the HPF.

Conclusion: Our process led to the identification of those features considered the most important as candidate variables to be included in a new set of evidence-based classification criteria for HPF.


Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Consensus*
  • Cryopyrin-Associated Periodic Syndromes / classification*
  • Cryopyrin-Associated Periodic Syndromes / genetics
  • Delphi Technique*
  • Familial Mediterranean Fever / classification*
  • Familial Mediterranean Fever / genetics
  • Fever / classification*
  • Fever / genetics
  • Genetic Testing
  • Hereditary Autoinflammatory Diseases / classification*
  • Hereditary Autoinflammatory Diseases / genetics
  • Humans
  • International Cooperation*
  • Mevalonate Kinase Deficiency / classification*
  • Mevalonate Kinase Deficiency / genetics
  • Physicians / psychology
  • Research Design
  • Surveys and Questionnaires

Supplementary concepts

  • Periodic fever, familial, autosomal dominant