University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• In previously healthy children with clinically suspected Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome, what treatment when compared to follow-up alone would decrease recurrence of fever episodes?

Clinical Bottom Lines

1. PFAPA syndrome is generally a self-limited benign disease process that has a mean duration of 4.5 years. Several therapies are available including oral steroids, cimetidine and tonsillectomy.
2. This paper is the only randomized controlled clinical trial to evaluate one of the therapeutic modalities (tonsillectomy) and reports statistically significant data suggesting that tonsillectomy is effective for treating PFAPA syndrome.
3. While the paper does have statistically significant findings, tonsillectomy as first line preventive therapy for PFAPA syndrome should be advised with caution.

Summary of Key Evidence

1.Twenty-six consecutive children (mean age 4.1 years) with at least 5 PFAPA attacks were recruited from three tertiary care pediatric hospitals during 1999-2003 and randomly allocated to tonsillectomy or follow-up alone.

2. They were all followed with symptom diaries for twelve months.

3. Six months after randomization all 14 children in the tonsillectomy group and 6/12 children in the control group were free of fever episodes (difference 50%, 95% CI 23-75%, P<0.001).

4. Six months after tonsillectomy, 4/14 children in the tonsillectomy group had 1 fever episode compatible with periodic fever (0.05 episodes per person-month at risk) and the 12 children in the control group had altogether 34 such episodes in the same time interval (0.44 episodes per person-month at risk, difference 0.40, 95% CI 0.17-0.62, P=0.007).

5. Tonsillectomy was performed in 5/6 patients in the control group who still had symptoms after six months. Summarize the key evidence so that others can see it for themselves.

Additional Comments

• There is a high rate of spontaneous resolution/remission in the control population at six months from randomization (50%).
• There are multiple limitations to study design including small sample size, lack of concealment, subjective primary outcome and abbreviated use of outcome measures (symptom diaries).
• Not all patients included in the study meet the criteria proposed by Thomas et al (1999) for diagnosis of PFAPA syndrome.
• Tonsillectomy is an invasive therapeutic measure and PFAPA syndrome is not currently one of the defined indications for the procedure.2
• The study was performed in Finland where cimetidine and prednisolone are not used in the treatment of PFAPA syndrome.

Citation

1. Renko M et al. A Randomized, Controlled Trial of Tonsillectomy in Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome. J Pediatr 2007: 289-292.
2. Petcu, LG et al. Tonsillectomy and Adenoidectomy. AAP Textbook of Pediatric Care.

CAT Author: Rebecca Lombel, MD

CAT Appraisers: Beth Tarini,, MD

Date appraised: February 25, 2009