Periodic Fever, Aphthous stomatitis, Pharyngitis, cervical Adenitis (PFAPA) Syndrome

The origin story of the Ped EM Morsels includes my selfish desire to have a “library” of topics I could refer to, since I clearly was not going to remember everything I have learned (or at least it would serve as record that I have tried to learn things in my life). What I did not anticipate was that there would continue to be new things to add for so many years. Proof of this came this week when I had to pretend to know what one of my chief residents, Dr. Matthew Cravens, was presenting to me – “Yup FPAPA. Sure. Sounds like classic PFAPA.” So let this be a quick reference for my future self (you may feel free to use it also) on the interesting condition of Periodic Fever, Aphthous stomatitis, Pharyngitis, cervical Adenitis (PFAPA) Syndrome:

PFAPA : Basics

  • PFAPA is the MOST common Periodic Fever Syndrome in children. [Amarilyo, 2020: 32293478; Gaggiano, 2019: 30488366]
    • Periodic Fever Syndromes are:
      • Rare
      • Often involve episodes of “autoinflammatory” processes
      • NOT due to infections
      • NOT due to an defined autoimmune disease (ex, JIA)
    • Examples of other Periodic Fever Syndromes include:
      • Familial Mediterranean Fever
      • Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
      • Hyperimmunoglobulin D Syndrome (HIDS)
  • PFAPA presents: [Amarilyo, 2020: 32293478; Gaggiano, 2019: 30488366; Rigante, 2017: 27251674]
    • Typically in young children (pre-school age), but is increasingly recognized in non-pediatric populations.
      • Fever are more difficult to control in adult-aged patients.
      • Adult-aged patients often have more organs/tissues involved.
    • With regularly recurring fevers in the ABSENCE of infections (even URIs).
  • Diagnostic Criteria for children include: [Amarilyo, 2020: 32293478; Gaggiano, 2019: 30488366]
    • 3-7 days of fever (high, spiking; >102.1 F for 3 days per episode)
    • >/= 6 episodes occurring with regularity
      • If the fever cycle is 2-4 weeks, 1 week of variability is ok.
      • If the fever cycle is 5-8 weeks, 2 weeks of variability is ok.
    • During febrile episodes, should have Pharyngitis.
      • In absence of Pharyngitis, must have BOTH aphthous stomatitis AND cervical adenopathy.
    • Having normal growth and development.
    • NOT having:
      • Known autoimmune / auto-inflammatory disorder
      • Immunodeficiency (ex, cyclic neutropenia)
      • Malignancy
      • Infection
    • Being responsive to Steroid therapy
      • (if administered)
      • Fever should resolve within 24 hours after appropriate dose of steroids is given.

PFAPA: Management

  • There is no current “standard” of care for PFAPA. [Amarilyo, 2020: 32293478; Gaggiano, 2019: 30488366]
  • While there is no standard approach, there are several typical strategies. [Amarilyo, 2020: 32293478; Gaggiano, 2019: 30488366]
  • Corticosteroids
    • Considered 1st line therapy by many.
    • Used for treatment of symptoms during episode.
    • Prednisolone or Prednisone (Single dose of 1-2 mg/kg within 24 hours of fever)
  • NSAIDs
    • Ibuprofen or Indomethacin
    • Antipyretic and symptom relief.
  • Colchicine
    • Has been used in other Periodic Fever Syndromes (Familial Mediterranean Fever).
    • Used by some for prophylaxis (preventative therapy).
    • Dose used 0.5-1.25 mg/Day
  • Cimetidine
    • Also used for prophylaxis (preventative therapy).
    • Doses used 10-20 mg/kg twice a day.
  • Surgery!
    • Tonsillectomy with/without adenoidectomy has been an effective treatment of PFAPA.
    • Some evidence that it can reduce recurrence of episodes and hospitalization.
    • It may be “too extreme” for a generally self-limited illness.

Moral of the Morsel

  • Not all Fever is Infectious! We have discussed this several times before (ex, FUO)… so add this to the Ddx List.
  • You never know what you are going to encounter in the ED. Stay vigilant. You may not make this diagnosis, but you may have to understand how to manage the patient with PFAPA.
  • You’re Never to Old to Learn Something New! I may be too old to grow new hair though. These are the rules of life. Thank you for joining me on this adventure.

References

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Sean M. Fox
I enjoy taking care of patients and I finding it endlessly rewarding to help train others to do the same. I trained at the Combined Emergency Medicine and Pediatrics residency program at University of Maryland, where I had the tremendous fortune of learning from world renowned educators and clinicians. Now I have the unbelievable honor of working with an unbelievably gifted group of practitioners at Carolinas Medical Center. I strive every day to inspire my residents as much as they inspire me.
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