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Surgical versus medical management of PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis): a

Mohammed Alsabri1,2, Shree Rath3, Mohamed Amr Elkarargy4

  • 1Emergency Department, Al-Thawra Modern General Hospital, Sana'a, Yemen. alsabri5000@gmail.com.

Pediatric Rheumatology Online Journal
|July 14, 2026
PubMed

Insights

Current evidence is insufficient to compare treatments for Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) syndrome. More high-quality studies are needed to determine the best approach for PFAPA management.

Area of Science:

  • Pediatrics
  • Rheumatology
  • Otolaryngology

Background:

  • Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) syndrome is the most common autoinflammatory disorder in children.
  • Optimal treatment strategies for PFAPA remain unclear, necessitating a comparative analysis of available interventions.

Purpose of the Study:

  • To systematically review and perform a network meta-analysis (NMA) comparing the effectiveness and safety of surgical versus medical treatments for PFAPA.
  • To evaluate clinical remission and symptom resolution as primary outcomes, alongside age and disease duration as secondary factors.

Main Methods:

  • Comprehensive literature search of Medline, Embase, and CENTRAL databases up to November 2025.
  • Inclusion of randomized and non-randomized comparative studies on surgical (tonsillectomy, adenotonsillectomy, tonsillotomy) and medical (corticosteroids, cimetidine, colchicine) PFAPA treatments.
  • Application of random-effects models for pairwise and network meta-analyses, with risk of bias and certainty of evidence assessed using RoB 2, ROBINS-I, and GRADE.

Main Results:

  • Sixteen studies involving 2,048 patients were analyzed.
  • The primary NMA revealed no statistically significant difference between pooled surgical and medical management (OR 1.10, 95% CI 0.21-5.69) with very high heterogeneity (I² 97.4%).
  • Exploratory analyses suggested potential trends favoring certain medical therapies, but wide confidence intervals and very low certainty of evidence precluded definitive conclusions.

Conclusions:

  • Existing evidence is inadequate for reliable comparative conclusions on surgical versus medical management of PFAPA.
  • Significant clinical and methodological heterogeneity, limited comparative data, and very low-certainty evidence hinder interpretation.
  • Well-designed prospective comparative studies with standardized outcomes are essential for guiding PFAPA treatment decisions.
Abstract

Keywords:
Inflammatory syndromeMedical managementPFAPAPeriodic feverSurgery

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