Pediatr Infect Vaccine.  2019 Dec;26(3):179-187. 10.14776/piv.2019.26.e20.

Clinical Manifestations of PFAPA (Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis) Syndrome from a Single Center

Affiliations
  • 1Department of Pediatrics, Seoul National University Children's Hospital, Seoul, the Republic of Korea. msh-0827@hanmail.net

Abstract

PURPOSE
Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is a leading cause of periodic fever in children. This study describes the clinical characteristics of PFAPA syndrome in patients from a single center.
METHODS
Thirteen children diagnosed with PFAPA syndrome at Seoul National University Children's Hospital were included in this study. Retrospective medical chart reviews were performed.
RESULTS
Among the 13 patients, 8 (61.5%) were male. The median follow-up duration was 3.3 years (range, 10 months-8.3 years). The median age of periodic fever onset was 3 years (range, 1-6 years). All patients had at least 5 episodes of periodic fever and pharyngitis, managed with oral antibiotics, before diagnosis. The median occurrence of fever was every 3.9 weeks and lasted for 4.2 days. All patients had pharyngitis and 12 (92.3%) had cervical lymphadenitis. Blood tests were performed for 12 patients, and no patients had neutropenia. Both the C-reactive protein and erythrocyte sedimentation rate were elevated at medians of 4.5 mg/dL (range, 0.4-13.2 mg/dL) and 29 mm/hr (range, 16-49 mm/hr), respectively. Throat swab cultures and rapid streptococcal antigen tests were negative. Nine (69.2%) patients received oral prednisolone at a median dose of 0.8 mg/kg, and in 6 (66.7%) patients, fever resolved within a few hours. Three (23.1%) patients received tonsillectomy and adenoidectomy.
CONCLUSIONS
PFAPA syndrome should be considered when a child presents with periodic fever along with aphthous stomatitis, pharyngitis, or cervical lymphadenitis. Glucocorticoid administration is effective for fever resolution and can reduce unnecessary use of antibiotics.

Keyword

Fever; Aphthous stomatitis; Pharyngitis; Adenitis; Children

MeSH Terms

Adenoidectomy
Anti-Bacterial Agents
Blood Sedimentation
C-Reactive Protein
Child
Diagnosis
Fever*
Follow-Up Studies
Hematologic Tests
Humans
Lymphadenitis
Male
Neutropenia
Pharyngitis*
Pharynx
Prednisolone
Retrospective Studies
Seoul
Stomatitis, Aphthous*
Tonsillectomy
Yemen
Anti-Bacterial Agents
C-Reactive Protein
Prednisolone

Reference

1. Marshall GS, Edwards KM, Butler J, Lawton AR. Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr. 1987; 110:43–46.
Article
2. Marshall GS, Edwards KM, Lawton AR. PFAPA syndrome. Pediatr Infect Dis J. 1989; 8:658–659.
Article
3. Thomas KT, Feder HM Jr, Lawton AR, Edwards KM. Periodic fever syndrome in children. J Pediatr. 1999; 135:15–21.
Article
4. Feder HM, Salazar JC. A clinical review of 105 patients with PFAPA (a periodic fever syndrome). Acta Paediatr. 2010; 99:178–184.
Article
5. Hofer M, Pillet P, Cochard MM, Berg S, Krol P, Kone-Paut I, et al. International periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome cohort: description of distinct phenotypes in 301 patients. Rheumatology (Oxford). 2014; 53:1125–1129.
Article
6. Kolly L, Busso N, von Scheven-Gete A, Bagnoud N, Moix I, Holzinger D, et al. Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome is linked to dysregulated monocyte IL-1β production. J Allergy Clin Immunol. 2013; 131:1635–1643.
Article
7. Kang HR, Kim SW, Bae GB, Park JH, Kang YM, Lee JM, et al. A case of PFAPA (Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome. Korean J Infect Dis. 2001; 33:219–222.
8. Chae JH, Hwang AR, Park SH, Suh BK. A case of PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome. Korean J Pediatr. 2006; 49:991–995.
Article
9. Hong SP, Shin HJ, Kim YH, Choe BK, Choi WJ, Kim AS, et al. A case of PFAPA syndrome mimicking cyclic vomiting syndrome. Korean J Pediatr Gastroenterol Nutr. 2006; 9:85–91.
Article
10. Song J, Hong S, Kweon Y, Jung S, Cha S. A case of PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome. Korean J Pediatr Infect Dis. 2007; 14:194–198.
Article
11. Renko M, Lantto U, Tapiainen T. Towards better diagnostic criteria for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome. Acta Paediatr. 2019; 108:1385–1392.
Article
12. Dale DC, Welte K. Cyclic and chronic neutropenia. Cancer Treat Res. 2011; 157:97–108.
Article
13. Ben-Chetrit E, Touitou I. Familial mediterranean fever in the world. Arthritis Rheum. 2009; 61:1447–1453.
Article
14. Butbul Aviel Y, Harel L, Abu Rumi M, Brik R, Hezkelo N, Ohana O, et al. Familial mediterranean fever is commonly diagnosed in children in Israel with periodic fever aphthous stomatitis, pharyngitis, and adenitis syndrome. J Pediatr. 2019; 204:270–274.
Article
15. Gattorno M, Caorsi R, Meini A, Cattalini M, Federici S, Zulian F, et al. Differentiating PFAPA syndrome from monogenic periodic fevers. Pediatrics. 2009; 124:e721–8.
Article
16. Dytrych P, Krol P, Kotrova M, Kuzilkova D, Hubacek P, Krol L, et al. Polyclonal, newly derived T cells with low expression of inhibitory molecule PD-1 in tonsils define the phenotype of lymphocytes in children with periodic fever, aphtous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Mol Immunol. 2015; 65:139–147.
Article
17. Cheung MS, Theodoropoulou K, Lugrin J, Martinon F, Busso N, Hofer M. Periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome is associated with a CARD8 variant unable to bind the NLRP3 inflammasome. J Immunol. 2017; 198:2063–2069.
Article
18. Di Gioia SA, Bedoni N, von Scheven-Gête A, Vanoni F, Superti-Furga A, Hofer M, et al. Analysis of the genetic basis of periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Sci Rep. 2015; 5:10200.
Article
19. Renko M, Salo E, Putto-Laurila A, Saxen H, Mattila PS, Luotonen J, et al. A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. J Pediatr. 2007; 151:289–292.
Article
20. Abramson JS, Givner LB, Thompson JN. Possible role of tonsillectomy and adenoidectomy in children with recurrent fever and tonsillopharyngitis. Pediatr Infect Dis J. 1989; 8:119–120.
21. Garavello W, Romagnoli M, Gaini RM. Effectiveness of adenotonsillectomy in PFAPA syndrome: a randomized study. J Pediatr. 2009; 155:250–253.
Article
22. Lantto U, Koivunen P, Tapiainen T, Renko M. Long-term outcome of classic and incomplete PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome after tonsillectomy. J Pediatr. 2016; 179:172–177.e1.
Article
23. Peridis S, Pilgrim G, Koudoumnakis E, Athanasopoulos I, Houlakis M, Parpounas K. PFAPA syndrome in children: A meta-analysis on surgical versus medical treatment. Int J Pediatr Otorhinolaryngol. 2010; 74:1203–1208.
Article
Full Text Links
  • PIV
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr