Related Experiment Video
Updated: Jun 14, 2025
Isolation of Tonsillar Mononuclear Cells to Study Ex Vivo Innate Immune Responses in a Human Mucosal Lymphoid Tissue
Published on: June 14, 2020
Features Associated with Response to Tonsillectomy in Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical
Kalpana Manthiram1, Ana M Ortega-Villa2, Sivia Lapidus3
1Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD.
Insights
Tonsillectomy effectively treats most children with Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) syndrome. Specific symptoms before surgery predict response, and histamine blockers help persistent cases.
Area of Science:
- Pediatric immunology
- Otolaryngology
- Genetics
Background:
- Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) syndrome is a common autoinflammatory disorder in children.
- Tonsillectomy is a recognized treatment, but predictors of response and management of refractory cases require further elucidation.
Purpose of the Study:
- To identify clinical features predicting tonsillectomy success in PFAPA patients.
- To determine optimal management for children with persistent PFAPA episodes post-tonsillectomy.
Main Methods:
- A retrospective study of 97 children with PFAPA who underwent tonsillectomy at two major hospitals.
- Data collected included pre- and post-operative symptoms, response to initial treatments, and outcomes after surgery.
Main Results:
- Nearly half of patients achieved complete PFAPA resolution post-tonsillectomy; 25% experienced less severe/frequent episodes.
- Pre-tonsillectomy factors associated with full response included glucocorticoid-responsive flares, exudative pharyngitis, and absence of rash/arthralgia/myalgia.
- Of those with persistent flares, 79% improved with cimetidine or famotidine prophylaxis.
Conclusions:
- Tonsillectomy is effective for most PFAPA cases, with specific clinical features predicting response.
- Histamine H2 receptor antagonists offer a viable prophylactic treatment for refractory PFAPA post-tonsillectomy.
- Incomplete responders may represent a distinct PFAPA subgroup requiring further investigation.
Objective:
To identify clinical features associated with response to tonsillectomy among children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome and to determine optimal management of children with continued 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 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.
Related Concept Videos
01:30Tonsillitis I: Introduction
Etiology
Three primary contributing factors have been identified.
01:23Chronic Pharyngitis
Etiology
It often arises from persistent viral or bacterial infections affecting sinuses and tonsils.
Additional contributing factors include inadequate dental hygiene, mouth breathing, recurring tonsillitis, allergic rhinitis, laryngopharyngeal reflux, and exposure to smoke, chemicals, and other environmental pollutants. Allergic reactions to pollen, mold, and pet dander, chronic cough, excessive voice usage,...
01:30Acute Pharyngitis
Acute pharyngitis is the inflammation of the back of the throat (pharynx), commonly resulting in a sore throat. It is a frequently encountered condition that prompts individuals to seek medical advice.
Classification
Acute pharyngitis can be categorized based on its underlying cause:
01:26Tonsillitis II: Management
01:26Patterns of Fever
01:30Inflammatory Response I: Vascular and Cellular