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

Abstract

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.

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Acknowledgements

We thank the generous support by Novartis for paying the publication fee of this manuscript, all the PFAPA patients with their families met in the last decade, the Associazione Italiana Febbri Periodiche and the many colleagues with whom we have intensely collaborated in these years.

Funding

The Journal’s Rapid Service Fee was funded by Novartis.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

Disclosures

Ludovico Luca Sicignano, Donato Rigante, Beatrice Moccaldi, Maria Grazia Massaro, Stefano Delli Noci, Isabella Patisso, Giovanna Capozio, Elena Verrecchia and Raffaele Manna have nothing to disclose.

Compliance With Ethics Guidelines

Anonymous retrospective data were collected during conventional clinical practices and analyzed according to the principles of the Helsinki Declaration, and accordingly no formal informed consent was required. All adult patients and pediatric patients' parents gave their assent to use anonymous data for this study; therefore, a direct involvement of the ethics committee was not required.

Data Availability

Specific material referred to this article can be available for those interested in evaluating raw data.

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Correspondence to Donato Rigante.

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Sicignano, L.L., Rigante, D., Moccaldi, B. et al. Children and Adults with PFAPA Syndrome: Similarities and Divergences in a Real-Life Clinical Setting. Adv Ther 38, 1078–1093 (2021). https://doi.org/10.1007/s12325-020-01576-8

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Keywords

  • auto-inflammation
  • auto-inflammatory disorder
  • Corticosteroid
  • Innovative biotechnologies
  • Periodic fever
  • Personalized medicine
  • PFAPA syndrome
  • Recurrent fever