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Perinatal and early childhood determinants of disease persistence in PFAPA

Elif Benderlioğlu1, Gülşah Efeoğlu Gülsoy2, Emine Özçelik3

  • 1Department of Pediatrics, Ankara Bilkent City Hospital, 06800, Bilkent, Ankara, Turkey. elifbenderlioglu@gmail.com.

Pediatric Research
|May 16, 2026
PubMed

Insights

Early life factors like preterm birth and pacifier use are linked to a milder course of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA). This helps predict disease persistence and personalize treatment for children with this autoinflammatory condition.

Area of Science:

  • Pediatric Rheumatology
  • Autoinflammatory Diseases
  • Immunology

Background:

  • Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) is a prevalent autoinflammatory condition in children.
  • Understanding factors influencing PFAPA disease course is crucial for effective management.

Purpose of the Study:

  • To investigate the impact of early-life factors on the frequency of attacks and treatment resistance in pediatric PFAPA patients.
  • To identify predictors of persistent versus self-limiting PFAPA phenotypes.

Main Methods:

  • Retrospective evaluation of 81 children diagnosed with PFAPA between April 2021 and 2024.
  • Classification of patients into persistent (less than 50% reduction in attack frequency, post-tonsillectomy, or ongoing attacks beyond age 7) and non-persistent groups.
  • Multivariate analysis to identify independent predictors of disease course.

Main Results:

  • Persistent PFAPA patients experienced more frequent attacks (median 6 vs. 1 per year) but of shorter duration (median 3 vs. 4 days).
  • Preterm birth and pacifier use were significantly less common in the persistent PFAPA group.
  • Abdominal pain, preterm birth, and pacifier use independently predicted a non-persistent (self-limiting) PFAPA course.

Conclusions:

  • Early-life factors, specifically preterm birth and pacifier use, are independently associated with a milder, self-limiting PFAPA phenotype.
  • These findings highlight the role of early immune maturation in PFAPA pathogenesis and offer insights for personalized management and parental counseling.
  • The study provides a novel perspective on autoinflammatory conditions by linking early exposures to disease trajectory.
Abstract

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