Skip to main content

The epidemiological profile of ASIA syndrome after HPV vaccination: an evaluation based on the Vaccine Adverse Event Reporting Systems

Abstract

The term “ASIA—Autoimmune/inflammatory Syndrome Induced by Adjuvants” describes an umbrella of clinical conditions sharing similar signs or symptoms, including post-vaccination phenomena. No information is available on the epidemiology of the ASIA syndrome, especially following HPV vaccination. We carried out an analysis of the VAERS database to retrieve all cases of suspected ASIA syndrome according to the Shoenfeld and Agmon-Levin’s guideline for the diagnosis. After causality assessment and case validation, 2,207 cases were considered probably or possibly related to vaccination. These represent the largest ASIA cohort ever reported and allowed us to estimate epidemiological and clinical characteristic of this syndrome. The commonest clinical manifestation observed were pyrexia (58 %), myalgia (27 %) and arthralgia or arthritis (19 %), and the estimated reporting rate was of 3.6 cases per 100,000 doses of HPV vaccine distributed (95 % CI 3.4–3.7). This study presents the first systematic estimation of ASIA incidence and expands the knowledge on this pathology. Further analyses are needed to identify genetic and non-genetic risk factors for ASIA syndrome.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. 1.

    Shoenfeld Y, Agmon-Levin N. ‘ASIA’: autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun. 2011;36(1):4–8. doi:10.1016/j.jaut.2010.07.003.

    CAS  PubMed  Article  Google Scholar 

  2. 2.

    Meroni PL. Autoimmune or auto-inflammatory syndrome induced by adjuvants (ASIA): old truths and a new syndrome? J Autoimmun. 2011;36(1):1–3. doi:10.1016/j.jaut.2010.10.004.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Carvalho JF, Barros SM. ASIA or Shoenfeld’s syndrome: a novel autoimmune syndrome? Rev Bras Reumatol. 2010;50(5):487–8.

    PubMed  Article  Google Scholar 

  4. 4.

    Carvalho JF, Barros SM, Branco JC, Fonseca JE. Asia or Shoenfeld’s syndrome: highlighting different perspectives for diffuse chronic pain. Acta Reumatol Port. 2011;36(1):10–2.

    CAS  PubMed  Google Scholar 

  5. 5.

    Agmon-Levin N, Hughes GR, Shoenfeld Y. The spectrum of ASIA: ‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’. Lupus. 2012;21(2):118–20. doi:10.1177/0961203311429316.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Perricone C, Shoenfeld Y. Hepatitis B vaccination and undifferentiated connective tissue disease: another brick in the wall of the autoimmune/inflammatory syndrome induced by adjuvants (Asia). J Clin Rheumatol. 2013;19(5):231–3. doi:10.1097/RHU.0b013e31829d56f1.

    PubMed  Article  Google Scholar 

  7. 7.

    Toubi E. ASIA-autoimmune syndromes induced by adjuvants: rare, but worth considering. Isr Med Assoc J. 2012;14(2):121–4.

    PubMed  Google Scholar 

  8. 8.

    Zafrir Y, Agmon-Levin N, Paz Z, Shilton T, Shoenfeld Y. Autoimmunity following hepatitis B vaccine as part of the spectrum of ‘Autoimmune (Auto-inflammatory) Syndrome induced by Adjuvants’ (ASIA): analysis of 93 cases. Lupus. 2012;21(2):146–52. doi:10.1177/0961203311429318.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Pellegrino P, Carnovale C, Perrone V, Antoniazzi S, Pozzi M, Clementi E, et al. No evidence of a link between multiple sclerosis and the vaccine against the human papillomavirus. Eur J Epidemiol. 2013;28(8):705–7. doi:10.1007/s10654-013-9830-y.

    PubMed  Article  Google Scholar 

  10. 10.

    Pellegrino P, Carnovale C, Pozzi M, Antoniazzi S, Perrone V, Salvati D, et al. On the relationship between human papilloma virus vaccine and autoimmune diseases. Autoimmun Rev. 2014;13(7):736–41. doi:10.1016/j.autrev.2014.01.054.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Perricone C, Agmon-Levin N, Valesini G, Shoenfeld Y. Vaccination in patients with chronic or autoimmune rheumatic diseases: the ego, the id and the superego. Joint Bone Spine. 2012;79(1):1–3. doi:10.1016/j.jbspin.2011.10.006.

    PubMed  Article  Google Scholar 

  12. 12.

    Pellegrino P, Carnovale C, Perrone V, Antoniazzi S, Pozzi M, Clementi E, et al. Can HPV immunisation cause ADEM? Two case reports and literature review. Mult Scler. 2014;20(6):762–3. doi:10.1177/1352458513502114.

    PubMed  Article  Google Scholar 

  13. 13.

    Pellegrino P, Carnovale C, Perrone V, Salvati D, Gentili M, Antoniazzi S, et al. Human papillomavirus vaccine in patients with systemic lupus erythematosus. Epidemiology. 2014;25(1):155–6. doi:10.1097/EDE.0000000000000033.

    PubMed  Article  Google Scholar 

  14. 14.

    Pellegrino P, Carnovale C, Perrone V, Salvati D, Gentili M, Brusadelli T, et al. On the association between human papillomavirus vaccine and primary ovarian failure. Am J Reprod Immunol. 2014;71(4):293–4. doi:10.1111/aji.12190.

    PubMed  Article  Google Scholar 

  15. 15.

    Loughlin AM, Marchant CD, Adams W, Barnett E, Baxter R, Black S, et al. Causality assessment of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS). Vaccine. 2012;30(50):7253–9. doi:10.1016/j.vaccine.2012.09.074.

    PubMed  Article  Google Scholar 

  16. 16.

    Harper DM, Irons BB, Alexander NM, Comes JC, Smith MS, Heutinck MA, et al. Quantifying the decisional satisfaction to accept or reject the Human Papillomavirus (HPV) vaccine: a preference for cervical cancer prevention. PLoS One. 2014;9(2):e88493. doi:10.1371/journal.pone.0088493.

    PubMed Central  PubMed  Article  Google Scholar 

  17. 17.

    Szarewski A, Skinner SR, Garland SM, Romanowski B, Schwarz TF, Apter D, et al. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against low-risk HPV types (PATRICIA randomized trial): an unexpected observation. J Infect Dis. 2013;208(9):1391–6. doi:10.1093/infdis/jit360.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  18. 18.

    Harper DM, Vierthaler SL. Next generation cancer protection: the bivalent HPV vaccine for females. ISRN Obstet Gynecol. 2011;2011:457204. doi:10.5402/2011/457204.

    PubMed Central  PubMed  Article  Google Scholar 

  19. 19.

    Wheeler CM, Castellsague X, Garland SM, Szarewski A, Paavonen J, Naud P, et al. Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012;13(1):100–10. doi:10.1016/S1470-2045(11)70287-X.

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Pellegrino P, Carnovale C, Cattaneo D, Perrone V, Antoniazzi S, Pozzi M, et al. Pharmacovigilance knowledge in family paediatricians. A survey study in Italy. Health Policy. 2013;113(1–2):216–20. doi:10.1016/j.healthpol.2013.08.006.

    PubMed  Article  Google Scholar 

  21. 21.

    Blank M, Israeli E, Shoenfeld Y. When APS (Hughes syndrome) met the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Lupus. 2012;21(7):711–4. doi:10.1177/0961203312438115.

    CAS  PubMed  Article  Google Scholar 

  22. 22.

    Cruz-Tapias P, Agmon-Levin N, Israeli E, Anaya JM, Shoenfeld Y. Autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA): animal models as a proof of concept. Curr Med Chem. 2013;20(32):4030–6.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Perricone C, Colafrancesco S, Mazor RD, Soriano A, Agmon-Levin N, Shoenfeld Y. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: unveiling the pathogenic, clinical and diagnostic aspects. J Autoimmun. 2013;47:1–16. doi:10.1016/j.jaut.2013.10.004.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Soriano A, Butnaru D, Shoenfeld Y. Long-term inflammatory conditions following silicone exposure: the expanding spectrum of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Clin Exp Rheumatol. 2014;32(2):151–4.

    CAS  PubMed  Google Scholar 

  25. 25.

    Pellegrino P, Carnovale C, Perrone V, Pozzi M, Antoniazzi S, Clementi E, et al. Acute disseminated encephalomyelitis onset: evaluation based on vaccine adverse events reporting systems. PLoS One. 2013;8(10):e77766. doi:10.1371/journal.pone.0077766.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  26. 26.

    Pellegrino P, Carnovale C, Perrone V, Salvati D, Gentili M, Brusadelli T, et al. On the possible interaction between vaccines and drugs. Eur J Clin Pharmacol. 2014;70(3):369–71. doi:10.1007/s00228-013-1616-3.

    PubMed  Article  Google Scholar 

  27. 27.

    Pellegrino P, Clementi E, Radice S. Infections, vaccinations, drugs and interactions. Eur J Clin Pharmacol. 2014;. doi:10.1007/s00228-014-1689-7.

    Google Scholar 

  28. 28.

    Pellegrino P, Carnovale C, Radice S, Clementi E. Influenza-like illness after yellow fever vaccination. J Clin Virol. 2014;. doi:10.1016/j.jcv.2014.03.015.

    PubMed  Google Scholar 

  29. 29.

    Posteraro B, Pastorino R, Di Giannantonio P, Ianuale C, Amore R, Ricciardi W, et al. The link between genetic variation and variability in vaccine responses: systematic review and meta-analyses. Vaccine. 2014;32(15):1661–9. doi:10.1016/j.vaccine.2014.01.057.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Ovsyannikova IG, Jacobson RM, Poland GA. Variation in vaccine response in normal populations. Pharmacogenomics. 2004;5(4):417–27. doi:10.1517/14622416.5.4.417.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Pellegrino P, Falvella FS, Perrone V, Carnovale C, Brusadelli T, Pozzi M, et al. The first steps towards the era of personalised vaccinology: predicting adverse reactions. Pharmacogenomics J. 2014;. doi:10.1038/tpj.2014.57.

    PubMed  Google Scholar 

  32. 32.

    Pellegrino P, Clementi E, Capuano A, Radice S. Can vaccines interact with drug metabolism? Pharmacol Res. 2014. doi:10.1016/j.phrs.2014.09.003.

  33. 33.

    Pellegrino P, Carnovale C, Perrone V, Pozzi M, Antoniazzi S, Radice S, et al. Efficacy of vaccination against influenza in patients with multiple sclerosis: the role of concomitant therapies. Vaccine. 2014;32(37):4730–5. doi:10.1016/j.vaccine.2014.06.068.

    PubMed  Article  Google Scholar 

  34. 34.

    Pellegrino P, Carnovale C, Borsadoli C, Danini T, Speziali A, Perrone V, et al. Two cases of hallucination in elderly patients due to a probable interaction between flu immunization and tramadol. Eur J Clin Pharmacol. 2013;69(8):1615–6. doi:10.1007/s00228-013-1517-5.

    PubMed  Article  Google Scholar 

  35. 35.

    Kennedy RB, Ovsyannikova IG, Lambert ND, Haralambieva IH, Poland GA. The personal touch: strategies toward personalized vaccines and predicting immune responses to them. Expert Rev Vaccines. 2014;13(5):657–69. doi:10.1586/14760584.2014.905744.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Klein SL, Poland GA. Personalized vaccinology: one size and dose might not fit both sexes. Vaccine. 2013;31(23):2599–600. doi:10.1016/j.vaccine.2013.02.070.

    PubMed  Article  Google Scholar 

  37. 37.

    Mitchell LA, Tingle AJ, MacWilliam L, Horne C, Keown P, Gaur LK, et al. HLA-DR class II associations with rubella vaccine-induced joint manifestations. J Infect Dis. 1998;177(1):5–12.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Pellegrino P, Carnovale C, Perrone V, Salvati D, Gentili M, Brusadelli T, et al. Epidemiological analysis on two decades of hospitalisations for meningitis in the United States. Eur J Clin Microbiol Infect Dis. 2014;33(9):1519–24. doi:10.1007/s10096-014-2102-2.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Karussis D, Petrou P. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes. Autoimmun Rev. 2014;13(3):215–24. doi:10.1016/j.autrev.2013.10.003.

    PubMed  Article  Google Scholar 

  40. 40.

    Agmon-Levin N, Paz Z, Israeli E, Shoenfeld Y. Vaccines and autoimmunity. Nat Rev Rheumatol. 2009;5(11):648–52. doi:10.1038/nrrheum.2009.196.

    PubMed  Article  Google Scholar 

  41. 41.

    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 a murine model. J Autoimmun. 2014. doi:10.1016/j.jaut.2014.06.006.

Download references

Acknowledgments

This work was supported by grants from the Italian Medicines Agency (Agenzia Italiana del Farmaco) and the Ministry of Health (Ricerca Corrente 2014) to EC.

Conflict of interest

None.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Sonia Radice.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Pellegrino, P., Perrone, V., Pozzi, M. et al. The epidemiological profile of ASIA syndrome after HPV vaccination: an evaluation based on the Vaccine Adverse Event Reporting Systems. Immunol Res 61, 90–96 (2015). https://doi.org/10.1007/s12026-014-8567-3

Download citation

Keywords

  • Vaccine
  • ASIA
  • Adjuvants
  • Post-vaccination
  • HPV