Children and Adults with PFAPA Syndrome: Similarities and Divergences in a Real-Life Clinical Setting

Adv Ther. 2021 Feb;38(2):1078-1093. doi: 10.1007/s12325-020-01576-8. Epub 2020 Dec 14.


Introduction: Analogies or differences of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome in children and adults are barely known. The aim of our study was to compare the overall characteristics of a large cohort of patients, both children and adults, diagnosed with PFAPA syndrome.

Methods: In the last decade, we identified 120 children and 63 adults with periodically recurring fevers, who fulfilled the criteria for PFAPA diagnosis. The two subcohorts were analyzed according to demographic features, clinical manifestations, laboratory data, and responses to therapies.

Results: The mean age of onset was 2.4 ± 1.5 and 19.7 ± 10.3 years, respectively, in children and adults, while attacks occurred every 3.8 ± 0.8 and every 4.3 ± 2.3 weeks, respectively, in children and adults. A higher prevalence of exudative pharyngitis was observed in children (58.8%), and the majority of children had only two cardinal signs during flares. In adults, there was a higher interpersonal variability of the intercritical periods. Inflammatory markers measured during non-febrile periods were normal in children but altered in the totality of adults during febrile periods. A strong efficacy of corticosteroids in controlling the pediatric syndrome was observed, but response rates to steroids were less brilliant in adults. Colchicine and interleukin-1 inhibitors were used in the management of the steroid-resistant adult syndrome. Conversely, tonsillectomy was performed in a very low number of children, but was effective in 60.7% of adults when treated after 16 years. The mean age of disappearance of PFAPA symptoms has been 6.4 ± 2.4 years in children, while only 27% of adults have shown a complete drug-free symptom regression.

Conclusions: A linear conformity of the PFAPA syndrome has been observed between pediatric and adult patients. PFAPA symptoms tended to disappear with no sequelae in 94.1% of children, while the disease was still active in almost 3/4 of adults at the time of our assessment.

Keywords: Corticosteroid; Innovative biotechnologies; PFAPA syndrome; Periodic fever; Personalized medicine; Recurrent fever; auto-inflammation; auto-inflammatory disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • Fever / diagnosis
  • Fever / drug therapy
  • Fever / epidemiology
  • Humans
  • Infant
  • Lymphadenitis* / diagnosis
  • Lymphadenitis* / drug therapy
  • Lymphadenitis* / epidemiology
  • Pharyngitis* / diagnosis
  • Pharyngitis* / drug therapy
  • Pharyngitis* / epidemiology
  • Stomatitis, Aphthous* / diagnosis
  • Stomatitis, Aphthous* / drug therapy
  • Stomatitis, Aphthous* / epidemiology
  • Tonsillectomy*