Chapter Summary: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome

Karen Hovav, MD and Solomon Behar, MD

As a pediatrician, you know you’re going to see your fair share of children with fevers. But how often is too often? Sol sits down with pediatrician Karen Hovav to talk about one of the most common causes of recurrent fevers in children, Periodic Fever Aphthous Stomatitis Pharyngitis and Adenitis, or PFAPA syndrome. Learn to recognize the telltale signs and symptoms, along with the latest guidance for treatment.

Pearls:

• PFAPA is the most common recurrent periodic fever syndrome.
• The original criteria for PFAPA included the following features:
  • Onset of disease in early childhood
  • Regularly recurring intervals of episodes
  • Presence of at least one of these associated features during flares: aphthous stomatitis, pharyngitis, and/or cervical adenitis
  • Asymptomatic intervals between flares with normal growth
  • Absence of signs of respiratory tract infection during flares and exclusion of cyclic neutropenia
• Updated guidelines do not require an early age of onset and include responsiveness to steroids. 
  • They also recommend having six or more episodes to make a firm diagnosis. 
• PFAPA is considered an autoinflammatory disease with a genetic component. 
  • No clear geographic risk factor. 
• Unlike PFAPA, Familial Mediterranean Fever (FMF) occurs at random times and not in a periodic fashion. Individuals with FMF may also present with acute abdominal pain and/or arthritis. FMF is not responsive to steroids. 
• Cyclic neutropenia has a 21-day cycle of fevers that is at times accompanied by oral lesions. To distinguish it from PFAPA, serial CBCs should be performed.
• Obtaining blood work is advised by Dr. Hovav after the third episode of fevers. 
• Differential to include when evaluating a patient for possible PFAPA: 
  • Infectious disease
  • Inflammatory bowel disease 
  • Behcet’s Disease
  • Systemic lupus erythematosus
• Laboratory work at the time of illness is recommended; some will do lab work in between to ensure normalization of inflammation.
  • Invitae produces a Periodic Fever Syndromes panel that can help rule out other periodic fever syndromes (it does not test for PFAPA). 
• Treatment:
  • Symptomatic management with an nonsteroidal anti-inflammatory such as Ibuprofen.
    • There is not a role for antibiotics
      
  • Steroids are an effective abortive therapy when given at the onset (within the first few hours) of an episode. 
    • Typical dosing is 1 mg/kg of prednisone.
    • For some children (between 25-40% of PFAPA patients), steroid treatments, while working very well acutely, may result in shortening the intervals between attacks 
      
      • If this occurs, a higher dose of 2 mg/kg may be useful
  • Cimetidine dosed at 20-40 mg/kg/day divided BID (max dose 1200 mg/day) induces remission in about 25% of patients and is therefore a good option for families hoping to avoid steroids. 
  • There are a subset of patients in whom colchicine is used and is effective at decreasing the interval between episodes.
  • Vitamin D has been studied as a possible treatment; this is considered because their may be some seasonality of episodes with longer periods of time between illnesses in the summer
• Tonsillectomy can be curative in a large portion of patients with PFAPA.
• Most children outgrow PFAPA before adolescence.

Want to hear more from our experts? Listen to the full podcast episode here.

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