Severe somatoform and dysautonomic syndromes after HPV vaccination: case series and review of literature

Beniamino Palmieri, Dimitri Poddighe, Maria Vadalà, Carmen Laurino, Carla Carnovale, Emilio Clementi, Beniamino Palmieri, Dimitri Poddighe, Maria Vadalà, Carmen Laurino, Carla Carnovale, Emilio Clementi

Abstract

Human papilloma virus (HPV) is recognized as a major cause for cervical cancer among women worldwide. Two HPV vaccines are currently available: Gardasil® and Cervarix®. Both vaccines enclose viral antigenic proteins, but differ as to the biological systems of culture and the adjuvant components. Recently, a collection of symptoms, indicating nervous system dysfunction, has been described after HPV vaccination. We retrospectively described a case series including 18 girls (aged 12-24 years) referred to our "Second Opinion Medical Network" for the evaluation of "neuropathy with autonomic dysfunction" after HPV vaccination. All girls complained of long-lasting and invalidating somatoform symptoms (including asthenia, headache, cognitive dysfunctions, myalgia, sinus tachycardia and skin rashes) that have developed 1-5 days (n = 11), 5-15 days (n = 5) and 15-20 days (n = 2) after the vaccination. These cases can be included in the recently described immune dysfunction named autoimmune/inflammatory syndrome induced by adjuvants (ASIA). HPV vaccine, through its adjuvant component, is speculated to induce an abnormal activation of the immune system, involving glia cells in the nervous system too. Further researches should aim at defining the pathological and clinical aspects of these post-vaccination diseases and identifying a genetic background predisposing to these adverse reactions.

Keywords: ADR; ASIA; Adjuvant; Autoimmune syndrome; HPV; Symptoms; Vaccine.

References

    1. Shiller JT, Lowy DR. Virus infections and human cancer: an overview. Recent Results Cancer Res. 2014;193:1–10. doi: 10.1007/978-3-642-38965-8_1.
    1. Malik H, Khan FH, Ahsan H. Human papillomavirus: current status and issues of vaccination. Arch Virol. 2014;159:199–205. doi: 10.1007/s00705-013-1827-z.
    1. Schiller JT, Lowy DR, Markowitz LE. Vaccine immunology. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6th ed. Philadelphia: Saunders; 2013. p. 235–56.
    1. O’Hagan DT. Preparation methods and research protocols. In: Vaccine adjuvants. Humana Press; 2000. p. 1–342.
    1. Bryan JT. Developing an HPV vaccine to prevent cervical cancer and genital warts. Vaccine. 2007;25(16):3001–3006. doi: 10.1016/j.vaccine.2007.01.013.
    1. Arnheim-Dahlstrom L, Pasternak B, Svanstrom H, Sparen P, Hviid A. Autoimmune, neurological, and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study. BMJ. 2013;347:f5906. doi: 10.1136/bmj.f5906.
    1. Nicol AF, de Andrade CV, Russomano FB, Rodrigues LS, Oliveira NS, Provance DW, Jr, Nuovo GJ. HPV vaccines: their pathology-based discovery, benefits, and adverse effects. Ann Diagn Pathol. 2015;19(6):418–422. doi: 10.1016/j.anndiagpath.2015.07.008.
    1. Stratton K, Ford A, Rusch E, Clayton EW. Adverse effects of vaccines, evidence and causality. The National Academies Press; 2012. p. 1–866.
    1. Gatto M, Agmon-Levin N, Soriano A, Manna R, Maoz-Segal R, Kivity S, Doria A, Shoenfeld Y. Human papillomavirus vaccine and systemic lupus erythematosus. Clin Rheumatol. 2013;32(9):1302–1307. doi: 10.1007/s10067-013-2266-7.
    1. Hariri S, Bennett NM, Niccolai LM, Schafer S, Park IU, Bloch KC, et al. Reduction in HPV 16/18-associated high grade cervical lesions following HPV vaccine introduction in the United States—2008–2012. Vaccine. 2015;33(13):1608–1613. doi: 10.1016/j.vaccine.2015.01.084.
    1. Paavonen J, Jenkins D, Bosch FX, Naud P, Salmerón J, Wheeler CM, et al. Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial. Lancet. 2007;369(9580):2161–2170. doi: 10.1016/S0140-6736(07)60946-5.
    1. Joura EA, Leodolter S, Hernandez-Avila M, Wheeler CM, Perez G, Koutsky LA, et al. Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials. Lancet. 2007;369(9574):1693–1702. doi: 10.1016/S0140-6736(07)60777-6.
    1. Centers for Disease Control and Prevention (CDC) National and state vaccination coverage among adolescents aged 13–17 years–United States, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(34):685–693.
    1. Tabrizi SN, Brotherton JM, Kaldor JM, Skinner SR, Cummins E, Liu B, et al. Fall in human papillomavirus prevalence following a national vaccination program. J Infect Dis. 2012;206(11):1645–1651. doi: 10.1093/infdis/jis590.
    1. Hutchinson DJ, Klein KC. Human papillomavirus disease and vaccines. Am J Health Syst Pharm. 2008;65:2105–2112. doi: 10.2146/ajhp070627.
    1. Petrosky E, Bocchini JA, Jr, Hariri S, Chesson H, Curtis CR, Saraiya M, et al. Use of 9-valent human papillomavirus (HPV) vaccine: updated HPV vaccination recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2015;64(11):300–304.
    1. Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007;356(19):1928–1943. doi: 10.1056/NEJMoa061760.
    1. McCormack PL. Quadrivalent human papillomavirus (types 6, 11, 16, 18) recombinant vaccine (gardasil): a review of its use in the prevention of premalignant anogenital lesions, cervical and anal cancers, and genital warts. Drugs. 2014;74(11):1253–1283. doi: 10.1007/s40265-014-0255-z.
    1. 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. 2015;15(3):284–287. doi: 10.1038/tpj.2014.57.
    1. 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):736–741. doi: 10.1016/j.autrev.2014.01.054.
    1. Pellegrino P, Clementi E, Radice S. On vaccine’s adjuvants and autoimmunity: current evidence and future perspectives. Autoimmun Rev. 2015;14(10):880–888. doi: 10.1016/j.autrev.2015.05.014.
    1. Shoenfeld Y, Agmon-Levin N. ASIA—Autoimmune/inflammatory syndrome induced by adjuvants. J Autoimm. 2011;36:4–8. doi: 10.1016/j.jaut.2010.07.003.
    1. Poddighe D, Castelli L, Marseglia GL, Bruni P. A sudden onset of a pseudo-neurological syndrome after HPV-16/18 AS04-adjuvated vaccine: might it be an autoimmune/inflammatory syndrome induced by adjuvants (ASIA) presenting as a somatoform disorder? Immunol Res. 2014;60(2–3):236–246. doi: 10.1007/s12026-014-8575-3.
    1. Stubgen JP. A review on the association between inflammatory myopathies and vaccination. Autoimmun Rev. 2014;13(1):31–39. doi: 10.1016/j.autrev.2013.08.005.
    1. Karussis D, Petrou P. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes. Autoimmun Rev. 2014;13(3):215–224. doi: 10.1016/j.autrev.2013.10.003.
    1. Plotkin SL, Plotkin SA. A short history of vaccination. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6th ed. Philadelphia: Saunders; 2013. p. 1–13.
    1. Fine P. Science and society: vaccines and public health. Public Health. 2014;128:686–692. doi: 10.1016/j.puhe.2014.06.021.
    1. Van der Laan JW, Gould S, Tanir JY. Safety of vaccine adjuvants: focus on autoimmunity. Vaccine. 2015;33(13):1507–1514. doi: 10.1016/j.vaccine.2015.01.073.
    1. Wraith DC, Goldman M, Lambert PH. Vaccination and autoimmune disease: what is the evidence. Lancet. 2003;362:1659–1666. doi: 10.1016/S0140-6736(03)14802-7.
    1. Grimaldi-Bensouda L, Guillemot D, Godeau B, Bénichou J, Lebrun-Frenay C, Papeix C, et al. Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects. J Intern Med. 2014;275(4):398–408. doi: 10.1111/joim.12155.
    1. Offit PA, De Stefano F. Vaccine safety. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6th ed. Philadelphia: Saunders; 2013. p. 1464–80.
    1. Rajantie J, Zeller B, Treutiger I, Rosthöj S. Vaccination associated thrombocytopenic purpura in children. Vaccine. 2007;25:1838–1840. doi: 10.1016/j.vaccine.2006.10.054.
    1. Tozzi A. Field evaluation of vaccine safety. Vaccine. 2004;22:2091–2095. doi: 10.1016/j.vaccine.2004.01.013.
    1. Guimarães LE, Baker B, Perricone C, Shoenfeld Y. Vaccines, adjuvants and autoimmunity. Pharmacol Res. 2015;100:190–209. doi: 10.1016/j.phrs.2015.08.003.
    1. Soriano A, Nesher G, Shoenfeld Y. Predicting post-vaccination autoimmunity: who might be at risk? Pharmacol Res. 2015;92:8–22. doi: 10.1016/j.phrs.2014.08.002.
    1. Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat Immunol. 2011;12(6):509–517. doi: 10.1038/ni.2039.
    1. Kuroda E, Coban C, Ishii KJ. Particulate adjuvants and innate immunity: past achievements, present findings and future prospects. Int Rev Immunol. 2013;32:209–220. doi: 10.3109/08830185.2013.773326.
    1. Mohan T, Verma P, Rao DN. Novel adjuvants & delivery vehicles for vaccines development: a road ahead. Indian J Med Res. 2013;138(5):779–795.
    1. Perricone C, Colafrancesco S, Mazor RD, Soriano A, Agmon-Levin N, Shoenfeld Y. Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) 2013: unveiling the pathogenic, clinical and diagnostic aspects. J Autoimm. 2013;47:1–16. doi: 10.1016/j.jaut.2013.10.004.
    1. Cruz-Tapias P, Agmon-Levin N, Israeli E, Anaya JM, Shoenfeld Y. Autoimmune (auto-inflammatory) Syndrome Induced by Adjuvants (ASIA)—Animal models as proof of concept. Curr Med Chem. 2013;20(32):4030–4036. doi: 10.2174/09298673113209990253.
    1. Shoenfeld Y. Video Q&A: what is ASIA? An interview with Yehuda Shoenfeld. BMC Med. 2013;11:118.
    1. Zafrir Y, Agmon-Levin N, 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;21:146–152. doi: 10.1177/0961203311429318.
    1. Pellegrino P, Perrone V, Pozzi M, Carnovale C, Perrotta C, Clementi E, Radice S. The epidemiological profile of ASIA syndrome after HPV vaccination: an evaluation based on the Vaccine Adverse Event Reporting Systems. Immunol Res. 2015;61(1–2):90–96. doi: 10.1007/s12026-014-8567-3.
    1. Donegan K, Beau-Lejdstrom R, King B, Seabroke S, Thomson A, Bryan P. Bivalent human papillomavirus vaccine and the risk of fatigue syndromes in girls in the UK. Vaccine. 2013;31:4961–4967. doi: 10.1016/j.vaccine.2013.08.024.
    1. European Medicine Agency (EMA): Pharmacovigilance Risk Assessment Committee (PRAC). Assessment report EMA/762033/2015:Human papillomavirus (HPV) vaccines. Pharmacovigilance Risk Assessment Committee (PRAC). . Accessed 19 Mar 2016.
    1. Blitshteyn S. Postural tachycardia syndrome following human papillomavirus vaccination. Eur J Neurol. 2014;21:135–139. doi: 10.1111/ene.12272.
    1. Martinez-Lavin M. Fibromyalgia-like illness in 2 girls after human papillomavirus vaccination. J Clin Rheumatol. 2014;20:392–393. doi: 10.1097/RHU.0000000000000089.
    1. Martínez-Lavín M. Hypothesis: Human papillomavirus vaccination syndrome—small fiber neuropathy and dysautonomia could be its underlying pathogenesis. Clin Rheumatol. 2015;34:1165–1169. doi: 10.1007/s10067-015-2969-z.
    1. Kinoshita T, Abe RT, Hineno A, Tsunekawa K, Ikeda S. Peripheral sympathetic nerve dysfunction in adolescent Japanese girls following immunization with the human papillomavirus vaccine. Intern Med. 2014;53:2185–2200. doi: 10.2169/internalmedicine.53.3133.
    1. Brinth L, Theibel AC, Pors K, Mehlsen J. Suspected side effects to the quadrivalent human papilloma vaccine. Dan Med J. 2015;62(4):A5064.
    1. Martínez-Lavín M, Martínez-Martínez LA, Reyes-Loyola P. HPV vaccination syndrome. A questionnaire-based study. Clin Rheumatol. 2015;34:1981–1983. doi: 10.1007/s10067-015-3070-3.
    1. List des effects indesirables suite a la vaccination HPV en France. Confidential document received by the corresponding author.
    1. Asociacion de afectadas por la vacuna del papiloma (AAVP). Spanish AAVP database of HPV vaccine affected girls. Confidential document received by the corresponding author.
    1. Association of HPV Vaccine Injured Daughters (AHVID). Database of HPV vaccine affected girls. Confidential document received by the corresponding author.
    1. The Netherlands Pharmacovigilance Centre Lareb. Long-lasting adverse events following immunization with Cervarix. 2015:1–21. . Accessed 19 Mar 2016.
    1. The Netherlands Pharmacovigilance Centre Lareb. Overview of reports of long-lasting fatigue following immunisation with Cervarix®. 2013:1–4. . Accessed 19 Mar 2016.
    1. Santuccio C, Trotta F, Felicetti P, Da Cas R, Menniti-Ippolito F, Raschetti R et al. Rapporto sulla sorveglianza postmarketing dei vaccini in Italia 2011:1–52. . Accessed 19 Mar 2016.
    1. Mitchell LA, et al. HLA-DR class II associations with rubella vaccine-induced joint manifestations. J Infect Dis. 1998;177(1):5–12. doi: 10.1086/513807.
    1. Ahmed SS, Schur PH, MacDonald NE, Steinman L. Narcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations: what is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants. J Autoimmun. 2014;50:1–11. doi: 10.1016/j.jaut.2014.01.033.
    1. Partinen M, Kornum BR, Plazzi G, Jennum P, Julkunen I, Vaarala O. Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination. Lancet Neurol. 2014;13(6):600–613. doi: 10.1016/S1474-4422(14)70075-4.
    1. Faust H, Toft L, Sehr P, Müller M, Bonde J, Forslund O, et al. Human Papillomavirus neutralizing and cross-reactive antibodies induced in HIV-positive subjects after vaccination with quadrivalent and bivalent HPV vaccines. Vaccine. 2016;34(13):1559–1565. doi: 10.1016/j.vaccine.2016.02.019.
    1. Göppert TM, Müller RH. Polysorbate-stabilized solid lipid nanoparticles as colloidal carriers for intravenous targeting of drugs to the brain: comparison of plasma protein adsorption patterns. J Drug Target. 2005;13(3):179–187. doi: 10.1080/10611860500071292.
    1. Masserini M. Nanoparticles for brain drug delivery. ISRN Biochem. 2013;2013:238428. doi: 10.1155/2013/238428.

Source: PubMed

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