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Meta-Analysis
. 2025 Jul-Aug;101(4):494-500.
doi: 10.1016/j.jped.2025.03.006. Epub 2025 Apr 16.

Surgical management for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome: a systematic review and meta-analysis

Luís Fernando Ferreira Cavalcante  1 , Giovanna Costa  1 , Sophia Massafelli Battistuta  1 , Pedro Faria Makabe  1 , Isadora Silva Fanucci Bueno  1 , Bruno Yuamoto  1 , Felipe Endrigo Gonçalves Vilela  1 , Marco Aurélio Palazzi Sáfadi  2
Affiliations
Meta-Analysis

Surgical management for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome: a systematic review and meta-analysis

Luís Fernando Ferreira Cavalcante et al. J Pediatr (Rio J). 2025 Jul-Aug.

Abstract

Objective: This systematic review and meta-analysis aimed to evaluate the efficacy of surgical management, specifically total and partial tonsillectomy, for Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) syndrome, focusing on symptom resolution and recurrence reduction.

Data sources: A systematic search of MEDLINE, Scopus, and Cochrane databases identified randomized controlled trials (RCTs) comparing surgical to non-surgical management in children with PFAPA. Data extraction and quality assessment adhered to Cochrane guidelines and PRISMA protocols. Risk ratios (RR) and confidence intervals (CI) were calculated using random-effects models.

Summary of findings: After the removal of duplicates, 31 studies were screened and 3 studies were included. Pooled analysis revealed a 72% reduction in persistent symptoms following surgical interventions compared to non-surgical management (RR: 0.28, 95% CI: 0.12-0.68, I² = 22%, p = 0.005).

Conclusion: The findings confirm that surgical management, including total and partial tonsillectomy, is an effective therapeutic option for PFAPA, with substantial benefits in symptom resolution and quality of life improvement. While surgery offers long-term benefits, its risks, and broader immunological implications require careful consideration. The study underscores the necessity for larger, multicenter trials to validate these findings across diverse populations and optimize treatment strategies.

Keywords: Aphthous stomatitis, pharyngitis, and cervical adenitis; Meta-analysis; Randomized controlled trial; Syndrome of periodic fever; Tonsillectomy; Tonsillotomy.

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Conflict of interest statement

Conflicts of interest The authors declare no conflicts of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Figures

Figure 1
Figure 1
PRISMA flow diagram of study screening and selection.
Figure 2
Figure 2
Pooled analysis of the proportion of patients without symptoms of PFAPA after surgery or randomization compared to non-surgical management.
Figure 3
Figure 3
Risk of bias assessment.
See this image and copyright information in PMC

References

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Supplementary concepts