Performance of Different Diagnostic Criteria for Familial Mediterranean Fever in Children with Periodic Fevers: Results from a Multicenter International Registry

J Rheumatol. 2016 Jan;43(1):154-60. doi: 10.3899/jrheum.141249. Epub 2015 Nov 15.


Objective: Our aims were to validate the pediatric diagnostic criteria in a large international registry and to compare them with the performance of previous criteria for the diagnosis of familial Mediterranean fever (FMF).

Methods: Pediatric patients with FMF from the Eurofever registry were used for the validation of the existing criteria. The other periodic fevers served as controls: mevalonate kinase deficiency (MKD), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS), aphthous stomatitis, pharyngitis, adenitis syndrome (PFAPA), and undefined periodic fever from the same registry. The performances of Tel Hashomer, Livneh, and the Yalcinkaya-Ozen criteria were assessed.

Results: The FMF group included 339 patients. The control group consisted of 377 patients (53 TRAPS, 45 MKD, 32 CAPS, 160 PFAPA, 87 undefined periodic fevers). Patients with FMF were correctly diagnosed using the Yalcinkaya-Ozen criteria with a sensitivity rate of 87.4% and a specificity rate of 40.7%. On the other hand, Tel Hashomer and Livneh criteria displayed a sensitivity of 45.0 and 77.3%, respectively. Both of the latter criteria displayed a better specificity than the Yalcinkaya-Ozen criteria: 97.2 and 41.1% for the Tel Hashomer and Livneh criteria, respectively. The overall accuracy for the Yalcinkaya-Ozen criteria was 65 and 69.6% (using 2 and 3 criteria), respectively. Ethnicity and residence had no effect on the performance of the Yalcinkaya-Ozen criteria.

Conclusion: The Yalcinkaya-Ozen criteria yielded a better sensitivity than the other criteria in this international cohort of patients and thus can be used as a tool for FMF diagnosis in pediatric patients from either the European or eastern Mediterranean region. However, the specificity was lower than the previously suggested adult criteria.


Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Chi-Square Distribution
  • Child
  • Child, Preschool
  • Cohort Studies
  • Diagnosis, Differential
  • Diagnostic Tests, Routine / methods*
  • Europe
  • Familial Mediterranean Fever / classification
  • Familial Mediterranean Fever / diagnosis*
  • Familial Mediterranean Fever / epidemiology
  • Female
  • Fever / classification
  • Fever / diagnosis*
  • Fever / epidemiology
  • Hereditary Autoinflammatory Diseases / classification
  • Hereditary Autoinflammatory Diseases / diagnosis*
  • Hereditary Autoinflammatory Diseases / epidemiology
  • Humans
  • Internationality
  • Male
  • Registries*
  • Retrospective Studies
  • Severity of Illness Index
  • Statistics, Nonparametric

Supplementary concepts

  • Periodic fever, familial, autosomal dominant