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

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Abstract

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.

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Acknowledgements

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.

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    Authors and Affiliations

    1. Vanderbilt University School of Medicine, Nashville, TN, USA

      Kalpana Manthiram & Kathryn Edwards

    2. Hackensack University Medical Center, Hackensack, NJ, USA

      Suzanne C. Li

    3. Boston Children’s Hospital, Boston, MA, USA

      Jonathan S. Hausmann & Fatma Dedeoglu

    4. Beth Israel Deaconess Medical Center, Boston, MA, USA

      Jonathan S. Hausmann

    5. Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

      Gil Amarilyo

    6. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

      Gil Amarilyo

    7. National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA

      Karyl Barron

    8. National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

      Hanna Kim

    9. Pediatric Rheumatology, Goryeb Children’s Hospital, Atlantic Health System, Morristown Medical Center/Overlook Hospital, Morristown, NJ, USA

      Simona Nativ & Sivia Lapidus

    10. University of California, San Francisco, San Francisco, CA, USA

      Geraldina Lionetti

    11. The Cleveland Clinic, Cleveland, OH, USA

      Andrew Zeft

    12. Drexel University College of Medicine, Philadelphia, PA, USA

      Donald Goldsmith

    13. Pediatric Infectious Diseases Society, Arlington, VA, USA

      David Kimberlin

    14. University of Alabama at Birmingham, Birmingham, AL, USA

      David Kimberlin

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    1. Kalpana Manthiram
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    For the Childhood Arthritis and Rheumatology Research Alliance (CARRA) PFAPA Subcommittee

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    Correspondence to Sivia Lapidus.

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    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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    Fatma Dedeoglu and Sivia Lapidus contributed equally as senior authors.

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    Manthiram, K., Li, S.C., Hausmann, J.S. et al. Physicians’ perspectives on the diagnosis and management of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Rheumatol Int 37, 883–889 (2017). https://doi.org/10.1007/s00296-017-3688-3

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    • DOI: https://doi.org/10.1007/s00296-017-3688-3

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