Skip to main content
SpringerLink
Log in

Involvement of chronic epipharyngitis in autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA)

  • Environment and Autoimmunity
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

The epipharynx is an immunologically active site even under normal conditions, and enhanced immunologic activation is prone to occur in response to an upper respiratory infection, air pollution, and possibly to vaccine adjuvants. Due to the potential link between the central nervous system and immune function, a relationship between epipharyngitis and autonomic nervous disturbance as well as autoimmune disease has been suggested. Various functional somatic symptoms have been described after human papillomavirus (HPV) vaccination, although a causal relationship has not been established. We examined the epipharynx in young women showing functional somatic symptoms following HPV vaccination. Surprisingly, despite having minimal symptoms involving the pharynx, all patients were found to have severe epipharyngitis. In addition, significant improvement in symptoms was seen in most patients who underwent epipharyngeal treatment. Thus, we speculate that the chronic epipharyngitis potentially caused by the vaccine adjuvant may be involved in the pathogenesis of functional somatic syndrome (FSS) post-HPV vaccination. Further, we suggest that epipharyngeal treatment may be effective for various types of FSS regardless of the initial cause, as well as for some autoimmune diseases, and that this may be an important direction in future research.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

HPV:

Human papillomavirus

FSS:

Functional somatic syndrome

HPA:

Hypothalamic–pituitary–adrenal

ASIA:

Autoimmune/inflammatory syndrome induced by adjuvant

References

  1. Horiguchi S. The discovery of the nasopharyngitis and its influence on general diseases. Acta Otolaryngol Suppl. 1975;329:1–120.

    Article  Google Scholar 

  2. WHO. Human papillomavirus vaccines: WHO position paper. Biologicals. 2009;37:338–44.

    Article  CAS  PubMed  Google Scholar 

  3. Fesefeld M, Hutubessy R, Jit M. Cost-effectiveness of human papillomavirus vaccination in low and middle income countries: a systemic review. Vaccine. 2013;31:3786–804.

    Article  Google Scholar 

  4. Kinoshita T, Abe RT, Hineno A, Tsunekawa K, Nakane S, Ikeda S. Peripheral sympathetic nerve dysfunction in adolescent Japanese girls following immunization with the human papillomavirus vaccine. Intern Med. 2014;53:2185–200.

    Article  PubMed  Google Scholar 

  5. Larson HJ, Wilson R, Hanley S, Parys A, Paterson P. Tracking the global spread of vaccine sentiments: the global response to Japan’s suspension of its HPV vaccine recommendation. Hum Vaccin Immunother. 2014;10:2543–50.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Pellegrino P, Perrone V, Pozzi M, Carnovale C, Perrotta C, Clementi E, et al. The epidemiological profile of ASIA syndrome after HPV vaccination: an evaluation based on the Vaccine Adverse Event Report Systems. Immunol Res. 2015;61:90–6.

    Article  CAS  PubMed  Google Scholar 

  7. Martinez-Lavin M. Fibromyalgia-like illness in 2 girls after human papillomavirus vaccination. J Clin Rheumatol. 2014;20:392–3.

    Article  PubMed  Google Scholar 

  8. Danish Health and Medicines Authority. Danish Pharmacovigilance Update, 29 Jan 2014 [Internet] [cited 2014 Nov 15]. http://sundhedsstyrelsen.dk/en/news/2014/~/media/0540230CC7344D6589018F88BB171F51.ashx.

  9. Hotta O. Chronic epipharyngitis and its possible focal-infection role. Stomato-pharyngol. 2013;23:37–42.

    Google Scholar 

  10. Neumann H, Fujishiro M, Wilcox CM, Mönkemüllerx K. Present and future perspectives of virtual chromoendoscopy with i-scan and optical enhancement technology. Dig Endosc. 2014;26(Suppl 1):43–51.

    Article  PubMed  Google Scholar 

  11. Hotta O, Tanaka A, Tani S. Epipharyngeal treatment in systemic disease: anticipated breakthrough. Stomato-pharyngol. 2016;29:99–106.

    Google Scholar 

  12. Kaneko T, Mii A, Fukui M, Nagahama K, Shimizu A, Tsuruoka S. IgA nephropathy and psoriatic arthritis that improved with steroid pulse therapy and mizoribine in combination with treatment for chronic tonsillitis and epipharyngitis. Intern Med. 2015;54:1085–90.

    Article  PubMed  Google Scholar 

  13. Arnson Y, Shoenfeld Y, Amital H. Effects of tobacco smoke on immunity, inflammation and autoimmunity. J Autoimmun. 2010;34:258–65.

    Article  Google Scholar 

  14. Farhat SC, Silva CA, Orione MA, Campos LM, Sallum AM, Braga AL. Air pollution in autoimmune rheumatic diseases: a review. Autoimmun Rev. 2011;11:14–21.

    Article  CAS  PubMed  Google Scholar 

  15. Perricone C, Versini M, Ben-Ami D, Gertel S, Watad A, Segel MJ, et al. Smoke and autoimmunity: the fire behind the disease. Autoimmun Rev. 2016. doi:10.1016/j.autrev.2016.01.001.

    Google Scholar 

  16. Hotta O, Tanaka A, Torigoe A, Imai K, Ieiri N. Chronic fatigue syndrome following human papilloma virus vaccination: is chronic epipharyngitis to blame? Isr Med Assoc J. (in press).

  17. Agmon-Levin N, Zafrir Y, Kivity S, Balofsky A, Amital H, Shoenfeld Y. Chronic fatigue syndrome and fibromyalgia following immunization with the hepatitis B vaccine: another angle of the ‘autoimmune (auto-inflammatory) syndrome induced by adjuvants’ (ASIA). Immunol Res. 2014;60:376–83.

    Article  CAS  PubMed  Google Scholar 

  18. Voigt K, Nagel A, Meyer B, Langs G, Braukhaus C, Löwe B. Toward positive diagnosis criteria: a systemic review of somatoform disorder diagnoses and suggestions for future classification. J Psycosom Res. 2010;68:403–14.

    Article  Google Scholar 

  19. Shoenfeld Y, Agmon-Levin N. ‘ASIA’: autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36:4–8.

    Article  CAS  PubMed  Google Scholar 

  20. Colafrancesco S, Perricone C, Priori R, Valesini G, Shoenfeld Y. Sjögren’s syndrome: another facet of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). J Autoimmun. 2014;51:10–6.

    Article  CAS  PubMed  Google Scholar 

  21. Poddighe D, Castelli L, Marseglia GL, Bruni P. A sudden onset of pseudo-neurological syndrome after HPV-16/18 AS04-ajuvanted vaccine: might it be an autoimmune/inflammatory syndrome induced by adjuvants (ASIA) presenting as a somatoform disorder? Immunol Res. 2014;60:236–46.

    Article  CAS  PubMed  Google Scholar 

  22. Agmon-Levin N, Arango MT, Kivity S, Katzav A, Gilburd B, Blank M, et al. Immunization with hepatitis B vaccine accelerates SLE-like disease in murine model. J Autoimmun. 2014;54:21–32.

    Article  CAS  PubMed  Google Scholar 

  23. Papadopoulos AS, Cleare AJ. Hypothalamic–pituitary–adrenal axis dysfunction in chronic fatigue syndrome. Nat Rev Endocrinol. 2011;8:22–32.

    Article  PubMed  Google Scholar 

  24. Tanriverdi F, Karaca Z, Unluhizarci K, Kelestimur F. The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and fibromyalgia syndrome. Stress. 2007;10:13–25.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Professors Kensuke Joh and Prof. Yehuda Shoenfeld for their encouragement. We also appreciate Dr. Yoshiteru Aida and Mr. Tatsushi Ohsawa for their contribution to this research.

Author information

Authors and Affiliations

  1. Division of Internal Medicine, Hotta Osamu Clinic, 2-39 Rokuchounome-minamimachi, Wakabayashi-ku, Sendai, Miyagi, 984-0013, Japan

    Osamu Hotta, Akira Torigoe & Norio Ieiri

  2. Tanaka ENT Clinic, Osaka, Japan

    Ayaki Tanaka

  3. Mirai Clinic, Fukuoka, Japan

    Kazuaki Imai

Authors
  1. Osamu Hotta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ayaki Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akira Torigoe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazuaki Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Norio Ieiri
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

on behalf of the Japanese Focal Inflammation Research Group

Corresponding author

Correspondence to Osamu Hotta.

Ethics declarations

Conflict of interest

Osamu Hotta, Ayaki Tanaka, Akira Torigoe, Kazuaki Imai, and Norio Ieiri declare that they have no conflict of interest in this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hotta, O., Tanaka, A., Torigoe, A. et al. Involvement of chronic epipharyngitis in autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). Immunol Res 65, 66–71 (2017). https://doi.org/10.1007/s12026-016-8859-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-016-8859-x

Keywords

Search

Navigation