Periodic Fever, Aphthosis, Pharyngitis, and Adenitis Syndrome: Analysis of Patients From Two Geographic Areas

Arthritis Care Res (Hoboken). 2016 Dec;68(12):1859-1865. doi: 10.1002/acr.22901.

Abstract

Objective: Periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome is a periodic fever syndrome of childhood with an unknown etiology. Our aim was to compare the features between PFAPA syndrome patients from Turkey and those from the US, and patients with and without MEFV variants, and to test the performance of the Eurofever criteria in excluding other autoinflammatory disorders.

Methods: Seventy-one children with PFAPA syndrome, followed in Hacettepe University, in Ankara, Turkey, and 60 patients at Boston Children's Hospital in the US were enrolled. MEFV gene-variant analysis was performed in 56 patients with Sanger sequencing.

Results: In patients from Turkey, symptom onset was at a younger age, fever attacks were of shorter duration, and pharyngitis was more frequent, whereas adenitis, headache, and nausea/vomiting were less frequent during attacks, when compared to patients from the US (P < 0.05). More patients from the Turkish cohort were classified in the familial Mediterranean fever (FMF) group according to the Eurofever criteria than patients from the US (66.2% versus 10%; P < 0.001). Two patients were diagnosed with FMF after MEFV analysis. Twenty-one patients (37.5%) had a single MEFV variant. No significant differences in phenotype were found between patients with and without MEFV variants.

Conclusion: The differences between patients from the Turkish and US cohorts may be due to epigenetic or environmental factors. In addition, the Eurofever FMF criteria may perform better in certain areas, if the weight of ethnic origin parameter or cutoff values were modified.

MeSH terms

  • Adolescent
  • Boston
  • Child
  • Child, Preschool
  • Familial Mediterranean Fever / complications
  • Familial Mediterranean Fever / diagnosis
  • Familial Mediterranean Fever / genetics
  • Female
  • Genetic Variation
  • Hereditary Autoinflammatory Diseases / complications
  • Hereditary Autoinflammatory Diseases / diagnosis*
  • Hereditary Autoinflammatory Diseases / genetics
  • Humans
  • Lymphadenitis / complications
  • Lymphadenitis / diagnosis*
  • Lymphadenitis / genetics
  • Male
  • Pharyngitis / complications
  • Pharyngitis / diagnosis*
  • Pharyngitis / genetics
  • Phenotype
  • Severity of Illness Index
  • Stomatitis, Aphthous / complications
  • Stomatitis, Aphthous / diagnosis*
  • Stomatitis, Aphthous / genetics
  • Syndrome
  • Turkey