Rheumatology International

, Volume 37, Issue 6, pp 883–889 | Cite as

Physicians’ perspectives on the diagnosis and management of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome

  • Kalpana Manthiram
  • Suzanne C. Li
  • Jonathan S. Hausmann
  • Gil Amarilyo
  • Karyl Barron
  • Hanna Kim
  • Simona Nativ
  • Geraldina Lionetti
  • Andrew Zeft
  • Donald Goldsmith
  • David Kimberlin
  • Kathryn Edwards
  • Fatma Dedeoglu
  • Sivia LapidusEmail author
  • For the Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA Subcommittee
Health Services Research


To assess the practice patterns of pediatric rheumatology and infectious diseases subspecialists in the diagnosis and treatment of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. An online survey assessing diagnostic and treatment approaches was sent to 424 members of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and 980 members of the Pediatric Infectious Disease Society (PIDS). 277 physicians (123 from CARRA and 154 from PIDS representing 21% of the total membership) completed the survey. To diagnose PFAPA, most respondents agreed that patients must have the following features of the diagnostic criteria: stereotypical fever episodes (95%), asymptomatic intervals between episodes (93%), and normal growth and development (81%). However, 71% of the respondents did not require age of onset <5 years, 33% did not require regular intervals between episodes, and 79% did not require the concomitant signs of aphthous stomatitis, adenitis, or pharyngitis during episodes as long as episodes were regular. Over half (58%) considered episode resolution with steroids to be diagnostic of PFAPA. Corticosteroids, antipyretics, tonsillectomy, and cimetidine were the most commonly prescribed treatments, while steroids and tonsillectomy were most effective. Subspecialists in pediatric rheumatology and infectious diseases showed limited adherence to the complete published criteria for diagnosing PFAPA suggesting heterogeneity in the characteristics of patients diagnosed with the disorder. These findings emphasize the need to develop consensus diagnostic and treatment guidelines in well-characterized patient populations.


Autoinflammatory syndrome Periodic fever Physician practice patterns PFAPA 



We thank the members of CARRA and PIDS who participated in this survey and Sheffa Ariens (CARRA) and Christy Phillips (PIDS) for their help in distributing the survey. We are also grateful to Drs. Robert Sundel, Larry Zemel, Deborah Rothman, Lori Tucker, Debby McCurdy, Kelly Brown, and Annabelle de St. Maurice for their review of the survey. Dr. Tucker has received funding from Novartis to support research activities. No other conflicts of interest. CARRA is supported by Grants from National Institute of Arthritis and Musculoskeletal and Skin Diseases (RC2AR058934), Friends of CARRA, and the Arthritis Foundation, as well as by the Duke Clinical Research Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Arthritis and Musculoskeletal and Skin Diseases or the National Institutes of Health. Support for REDCap provided by Vanderbilt Institute for Clinical and Translational Research Grant support (UL1 TR000445 from NCATS/NIH). Kalpana Manthiram was supported by the Childhood Infection Research Program (1T32AI095202-01) and Conducting Child Health Care Research in Vulnerable Populations (1T32HD060554-05) training Grants from Vanderbilt University School of Medicine.

Compliance with ethical standards

Conflict of interest

Dr. Goldsmith is a member of the Novartis Advisory Speakers Board. Authors report no other conflicts of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Kalpana Manthiram
    • 1
  • Suzanne C. Li
    • 2
  • Jonathan S. Hausmann
    • 3
    • 4
  • Gil Amarilyo
    • 5
    • 6
  • Karyl Barron
    • 7
  • Hanna Kim
    • 8
  • Simona Nativ
    • 9
  • Geraldina Lionetti
    • 10
  • Andrew Zeft
    • 11
  • Donald Goldsmith
    • 12
  • David Kimberlin
    • 13
    • 14
  • Kathryn Edwards
    • 1
  • Fatma Dedeoglu
    • 3
  • Sivia Lapidus
    • 9
    Email author
  • For the Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA Subcommittee
  1. 1.Vanderbilt University School of MedicineNashvilleUSA
  2. 2.Hackensack University Medical CenterHackensackUSA
  3. 3.Boston Children’s HospitalBostonUSA
  4. 4.Beth Israel Deaconess Medical CenterBostonUSA
  5. 5.Schneider Children’s Medical Center of IsraelPetach TikvaIsrael
  6. 6.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  7. 7.National Institute of Allergy and Infectious DiseaseNational Institutes of HealthBethesdaUSA
  8. 8.National Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institutes of HealthBethesdaUSA
  9. 9.Pediatric Rheumatology, Goryeb Children’s Hospital, Atlantic Health SystemMorristown Medical Center/Overlook HospitalMorristownUSA
  10. 10.University of California, San FranciscoSan FranciscoUSA
  11. 11.The Cleveland ClinicClevelandUSA
  12. 12.Drexel University College of MedicinePhiladelphiaUSA
  13. 13.Pediatric Infectious Diseases SocietyArlingtonUSA
  14. 14.University of Alabama at BirminghamBirminghamUSA

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