PFAPA flares observed during COVID outbreak: can emotional stress trigger PFAPA attacks? A multicenter cohort study

Yoel Levinsky, Yonatan Butbul Aviel, Sabreen Abu Ahmad, Mor Broide, Yulia Gendler, Neta Dagan, Michal Gafner, Hadar Gavra, Shelly Kagan, Kfir Kedar, Hamada Mohammad Natour, Rotem Tal, Tamar Veres, Gil Amarilyo, Liora Harel

Research output: Contribution to journalArticlepeer-review


Objective: It is common knowledge among clinicians who treat PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis) patients that emotional stress can trigger PFAPA attacks similarly to other autoinflammatory diseases. However, it has never been proved scientifically. Our aim was to examine whether emotional stress serves as a trigger for PFAPA attacks. Methods: Patients aged 3-12 years, with active PFAPA, from two Israeli medical centers were enrolled to this study. Patient's parents were reached via phone calls in two occasions: a stressful period related to the COVID-19 pandemic restrictions and a less stressful period. In both times they were asked to report occurrence of PFAPA attacks in the preceding 2 weeks. The relative stress levels of the two periods were validated by an emotional distress scale questionnaire. The significance level was set at 0.05. Results: Mean age was 7.28 ± 2.7 for the 99 paediatric patients enrolled in the study. Scores for the mean emotional distress questionnaire were statistically significant higher in the stressful period compared to the less stressful period (35.6 ± 8.1 vs. 32.1 ±7.7, respectively, P = 0.047). In the stressful period, 41 (38.7%) reported at least one attack during the preceding 2 weeks, compared to 24 (22.6%) in the less stressful period (p = 0.017). Conclusion: PFAPA flares during COVID-19 outbreak are described. This study is the first to suggest that emotional stress is associated with PFAPA attacks.

Original languageEnglish
Article number46
Pages (from-to)46
JournalPediatric Rheumatology
Issue number1
StatePublished - Dec 2022


  • COVID-19/epidemiology
  • Child
  • Child, Preschool
  • Disease Outbreaks
  • Emotional stress
  • Emotions
  • Female
  • Fever/etiology
  • Flares
  • Humans
  • Israel
  • Male
  • Paediatric rheumatology
  • Stress, Physiological

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Rheumatology
  • Immunology and Allergy


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