Features Associated with Response to Tonsillectomy in Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome in Children

Kalpana Manthiram, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD. Electronic address: kalpana.manthiram@nih.gov.
Ana M. Ortega-Villa, Biostatistics Research Branch, Division of Clinical Research, NIAID, NIH, Bethesda, MD.
Sivia Lapidus, Joseph M. Sanzari Children's Hospital, Hackensack University Medical Center, Hackensack, NJ.
Mary Bowes, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD.
Tina Romeo, National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD.
Kathryn Garguilo, Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN.
Laura Failla, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD.
Hemalatha Srinivasalu, Division of Rheumatology, Department of Pediatrics, George Washington University School of Medicine, Children's National Hospital, Washington, DC.
Pamela Mudd, Division of Pediatric Otolaryngology, Children's National Hospital, Washington, DC; Division of Otolaryngology, Department of Surgery, George Washington University School of Medicine and Health Sciences, Washington, DC.
Amanda Ombrello, National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD.
Karyl Barron, NIAID, National Institutes of Health, Bethesda, MD.
Daniel L. Kastner, National Human Genome Research Institute (NHGRI), NIH, Bethesda, MD. Electronic address: dan.kastner@nih.gov.
Kathryn M. Edwards, Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN. Electronic address: kathryn.edwards@vumc.org.

Document Type

Journal Article

Publication Date

3-21-2025

Journal

The Journal of pediatrics

DOI

10.1016/j.jpeds.2025.114559

Abstract

OBJECTIVES: To identify clinical features of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome associated with response to tonsillectomy among children and to determine optimal management of children with continued febrile episodes after tonsillectomy. STUDY DESIGN: Patients with PFAPA seen at Vanderbilt University Children's Hospital and the National Institutes of Health (NIH) who underwent tonsillectomy were enrolled and queried regarding symptoms before and after surgery. RESULTS: Ninety-seven subjects with PFAPA (43 Vanderbilt, 54 NIH) were followed for a median of 49 months following tonsillectomy. Nearly half of participants reported complete resolution of PFAPA episodes (65% at Vanderbilt and 35% at NIH), while 25% had less severe or frequent episodes, 23% had a period of remission with recurrence, and 4% had no change in episodes. By logistic regression, factors associated with a full response to tonsillectomy were episode resolution with glucocorticoid treatment, presence of exudative pharyngitis, absence of rash, and absence of arthralgia/myalgia during pre-tonsillectomy PFAPA flares. Among those requiring treatment for persistent flares post-tonsillectomy, 15/19 (79%) reported improvement with cimetidine or famotidine prophylaxis. CONCLUSION: Tonsillectomy remains effective in improving PFAPA flares in most patients. However, unique episode features prior to tonsillectomy appear to be clinical predictors of response to tonsillectomy. Histamine receptor 2 (H2R) antagonists like cimetidine were effective prophylactic agents for refractory cases post-tonsillectomy. Patients with incomplete response to tonsillectomy may represent a subset of PFAPA with unique factors affecting their pathogenesis.

Department

Pediatrics

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