Skip to main content

Advertisement

SpringerLink
Log in

Probiotic use in the prophylaxis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a retrospective cohort study

  • Short Communication
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is an autoinflammatory recurrent fever syndrome that mainly affects children. Probiotics are currently used to prevent upper respiratory tract infections and flares of diseases associated with immune dysregulation. We aimed to evaluate the response to probiotic treatment in PFAPA patients. Patients with PFAPA syndrome who received probiotics and were followed between July 2019 and July 2021 were included in this retrospective study. Demographic and clinical features and response to probiotics were assessed. Twenty out of 111 children with PFAPA syndrome (F/M:1) were included. The median (min–max) ages at symptoms onset and diagnosis were 24 (3–72) and 51.5 (11–120) months, respectively. All 20 patients received probiotics during the disease course. The probiotic preparation they received included a combination of two lactobacilli as Lactobacillus plantarum HEAL9 (Lp HEAL9) and Lactobacillus paracasei 8700:2 (Lpa 8700:2). The median age at probiotic onset was 60 (33–192) months, while the duration of probiotic use was 4.5 (3–19) months. All patients except one experienced a decrease in attack frequency with probiotic use. After probiotic treatment, the median number of episodes during 3 months decreased from 3 to 1 (p < 0.001). Eight (40%) patients had no attacks during the 3 months after probiotic initiation. And, 5 (45%) of 11 patients who had ≥ 1 attacks on probiotics mentioned that the attack severity decreased significantly after probiotic initiation. Our results suggest that probiotic strains Lactobacillus plantarum HEAL9 and Lactobacillus paracasei 8700:2 could be beneficial in PFAPA patients by decreasing the attack frequency.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Data availability

The entire dataset used for this study can be accessed from the corresponding author upon reasonable request.

Abbreviations

Lpa 8700:2:

Lactobacillus paracasei 8700:2

Lp HEAL9:

Lactobacillus plantarum HEAL9

PFAPA:

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis

References

  1. Batu ED (2019) Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome: main features and an algorithm for clinical practice. Rheumatol Int 39:957–970

    Article  CAS  Google Scholar 

  2. Thomas KT, Feder HM Jr, Lawton AR, Edwards KM (1999) Periodic fever syndrome in children. J Pediatr 135:15–21

    Article  CAS  Google Scholar 

  3. Batu ED, Kara Eroglu F, Tsoukas P, Hausmann JS, Bilginer Y, Kenna MA, Licameli GR, Fuhlbrigge RC, Ozen S, Dedeoglu F (2016) Periodic fever, aphthosis, pharyngitis, and adenitis syndrome: analysis of patients from two geographic areas. Arthritis Care Res 68:1859–1865

    Article  Google Scholar 

  4. Wang A, Manthiram K, Dedeoglu F, Licameli GR (2021) Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a review. World J Otorhinolaryngol Head Neck Surg 7:166–173

    Article  CAS  Google Scholar 

  5. Tejesvi MV, Uhari M, Tapiainen T, Pirttila AM, Suokas M, Lantto U, Koivunen P, Renko M (2016) Tonsillar microbiota in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome. Eur J Clin Microbiol Infect Dis 35:963–970

    Article  CAS  Google Scholar 

  6. Forsvoll J, Oymar K (2018) The role of tonsillectomy in the Periodic Fever, Aphthous stomatitis, Pharyngitis and cervical Adenitis syndrome; a literature review. BMC Ear Nose Throat Disord 18:3

    Article  Google Scholar 

  7. Adrovic A, Sahin S, Barut K, Kasapcopur O (2019) Familial Mediterranean fever and periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: shared features and main differences. Rheumatol Int 39:29–36

    Article  Google Scholar 

  8. Butbul Aviel Y, Tatour S, Gershoni Baruch R, Brik R (2016) Colchicine as a therapeutic option in periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome. Semin Arthritis Rheum 45:471–474

    Article  CAS  Google Scholar 

  9. FAO/WHO (2002) Guidelines for the evaluation of probiotics in food. https://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf. Accessed 10 Jul 2021

  10. Francesco DPAC, Laura PM, Valeria A, Giovanni DV (2016) The use of Streptococcus salivarius K12 in attenuating PFAPA syndrome, a pilot study. Altern Integr Med 5:222

    Article  Google Scholar 

  11. Ahren IL, Hillman M, Nordstrom EA, Larsson N, Niskanen TM (2021) Fewer community-acquired colds with daily consumption of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2. A randomized, placebo-controlled clinical trial. J Nutr 151:214–222

    Article  Google Scholar 

  12. Berggren A, Lazou Ahren I, Larsson N, Onning G (2011) Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infections. Eur J Nutr 50:203–210

    Article  Google Scholar 

  13. Busch RGJ, Dudek S (2013) Randomised, double-blind, and placebo-controlled study using a combination of two probiotic lactobacilli to alleviate symptoms and frequency of common cold. Food Nutr Sci 4:13–20

    Google Scholar 

  14. Lazou Ahren I, Berggren A, Teixeira C, Martinsson Niskanen T, Larsson N (2020) Evaluation of the efficacy of Lactobacillus plantarum HEAL9 and Lactobacillus paracasei 8700:2 on aspects of common cold infections in children attending day care: a randomised, double-blind, placebo-controlled clinical study. Eur J Nutr 59:409–417

    Article  CAS  Google Scholar 

  15. Tsalik EL, Fiorino C, Aqeel A, Liu Y, Henao R, Ko ER, Burke TW, Reller ME, Bodinayake CK, Nagahawatte A, Arachchi WK, Devasiri V, Kurukulasooriya R, McClain MT, Woods CW, Ginsburg GS, Tillekeratne LG, Schughart K (2021) The host response to viral infections reveals common and virus-specific signatures in the peripheral blood. Front Immunol 12:741837

    Article  CAS  Google Scholar 

  16. Hakansson A, Andren Aronsson C, Brundin C, Oscarsson E, Molin G, Agardh D (2019) Effects of Lactobacillus plantarum and Lactobacillus paracasei on the peripheral immune response in children with celiac disease autoimmunity: a randomized, double-blind, placebo-controlled clinical trial. Nutrients 11:1925

    Article  Google Scholar 

  17. Oscarsson E, Hakansson A, Andren Aronsson C, Molin G, Agardh D (2021) Effects of probiotic bacteria Lactobacillaceae on the gut microbiota in children with celiac disease autoimmunity: a placebo-controlled and randomized clinical trial. Front Nutr 8:680771

    Article  Google Scholar 

  18. Stagi S, Bertini F, Rigante D, Falcini F (2014) Vitamin D levels and effects of vitamin D replacement in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. Int J Pediatr Otorhinolaryngol 78:964–968

    Article  Google Scholar 

Download references

Funding

No funding was received for this study.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Pediatrics, Faculty of Medicine, Hacettepe University, 06100, Ankara, Turkey

    Ezgi D. Batu, Ummusen Kaya Akca, Ozge Basaran, Yelda Bilginer & Seza Özen

Authors
  1. Ezgi D. Batu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ummusen Kaya Akca
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ozge Basaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yelda Bilginer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seza Özen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by EDB, UKA, OB, and YB. The first draft of the manuscript was written by EDB. SÖ critically revised the text. All authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ezgi D. Batu.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

The study was approved by the ethics committee of Hacettepe University (GO 20/635; approval date, 25th August 2020), and performed following the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consents were obtained from all parents/patients before inclusion in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Batu, E.D., Kaya Akca, U., Basaran, O. et al. Probiotic use in the prophylaxis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: a retrospective cohort study. Rheumatol Int 42, 1207–1211 (2022). https://doi.org/10.1007/s00296-021-05084-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-021-05084-y

Keywords

Search

Navigation