Clinical Rheumatology

, Volume 34, Issue 7, pp 1165–1169

Hypothesis: Human papillomavirus vaccination syndrome—small fiber neuropathy and dysautonomia could be its underlying pathogenesis

Review Article

Abstract

Vaccination has been one of the most effective public health measures in the history of medicine. However, seemingly inexplicit adverse reactions have been described after the injection of the newer vaccines vs. human papillomavirus (HPV). The symptoms more often reported are chronic pain with paresthesias, headaches, fatigue, and orthostatic intolerance. Adverse reactions appear to be more frequent after HPV vaccination when compared to other type of immunizations. Different isolated cases and small series have described the development of complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome (POTS), and fibromyalgia after HPV vaccination. These are illnesses often difficult to diagnose that have overlapping clinical features. Sympathetic nervous system dysfunction seems to play a major role in the pathogenesis of these syndromes. Also, small fiber neuropathy has been recently recognized in CRPS, POTS, and fibromyalgia. This article forwards the hypothesis that small fiber neuropathy and dysautonomia could be the common underlying pathogenesis to the group of rare, but severe reactions that follow HPV vaccination. Clinicians should be aware of the possible association between HPV vaccination and the development of these difficult to diagnose painful dysautonomic syndromes.

Keywords

Complex regional pain syndrome Dysautonomia Fibromyalgia HPV vaccination Postural orthostatic tachycardia syndrome Small fiber neuropathy Sympathetic pain 

References

  1. 1.
    World Health Organization (2013) Weekly Epidemiological Record 88: 301–312. http://www.who.int/wer/2013/wer8829.pdf?ua=1
  2. 2.
    Kinoshita T, Abe RT, Hineno A, Tsunekawa K, Nakane S, Ikeda S (2014) Peripheral sympathetic nerve dysfunction in adolescent Japanese girls following immunization with the human papillomavirus vaccine. Intern Med 53:2185–2200PubMedCrossRefGoogle Scholar
  3. 3.
    Blitshteyn S (2014) Postural tachycardia syndrome following human papillomavirus vaccination. Eur J Neurol 21:135–139PubMedCrossRefGoogle Scholar
  4. 4.
    Brinth L, Theibel AC, Pors K, Mehlsen J (2015) Suspected side effects to the quadrivalent human papilloma vaccine. Dan Med J 62:A5064Google Scholar
  5. 5.
    Geier DA, Geier MR (2014) A case–control study of quadrivalent human papillomavirus vaccine-associated autoimmune adverse events. Clin Rheumatol. doi:10.1007/s10067-014-2846-1
  6. 6.
  7. 7.
    Buttery JP, Madin S, Crawford NW, Elia S, La Vincente S, Hanieh S, Smith L, Bolam B (2008) Mass psychogenic response to human papillomavirus vaccination. Med J Aust 189:261–262Google Scholar
  8. 8.
    Martinez-Lavin M (2014) Fibromyalgia-like illness in 2 girls after human papillomavirus vaccination. J Clin Rheumatol 20:392–393PubMedGoogle Scholar
  9. 9.
    Nishioka K, Yokota S, Matsumoto Y (2014) Clinical features and preliminary diagnostic criteria of human papillomavirus vaccination associated with neuroimmunopathic syndrome (HANS). Int J Rheu Dis 17(suppl 2):6, AbstractGoogle Scholar
  10. 10.
    Hadler NM (2003) “Fibromyalgia” and the medicalization of misery. J Rheumatol 30:1668–1670PubMedGoogle Scholar
  11. 11.
    Del Piñal F (2013) Editorial. I have a dream … reflex sympathetic dystrophy (RSD or Complex Regional Pain Syndrome - CRPS I) does not exist. J Hand Surg Eur 38:595–597CrossRefGoogle Scholar
  12. 12.
    Goldstein DS, Robertson D, Esler M, Straus SE, Eisenhofer G (2002) Dysautonomias: Clinical disorders of the autonomic nervous system. Ann Intern Med 137:753–763PubMedCrossRefGoogle Scholar
  13. 13.
    Tavee J, Zhou L (2009) Small fiber neuropathy: a burning problem. Cleve Clin J Med 76:297–305PubMedCrossRefGoogle Scholar
  14. 14.
    Levine TD, Saperstein DS (2015) Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients. Clin Rheumatol 34:413–417PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Ramírez MD, Martínez-Martínez LA, Hernández-Quintela E, Velazco-Casapía J, VargasA, Martínez-Lavín M (2015) Small fiber neuropathy in women with fibromyalgia An in vivo assessment using corneal confocal bio-microscopy. Semin Arthritis Rheum. doi:10.1016/j.semarthrit.2015.03.003
  16. 16.
    Rodríguez-Galán MA, Pérez-Vilar S, Díez-Domingo J, Tuells J, Gomar-Fayos J, Morales-Olivas F, Pastor-Villalba E (2014) Adverse reactions to human papillomavirus vaccine in the Valencian Community (2007–2011)]. An Pediatr (Barc) 81:303–309CrossRefGoogle Scholar
  17. 17.
    Thieben MJ, Sandroni P, Sletten DM et al (2007) Postural orthostatic tachycardia syndrome: the Mayo Clinic experience. Mayo Clin Proc 82:308–313PubMedCrossRefGoogle Scholar
  18. 18.
    Freeman R, Wieling W, Axelrod FB et al (2011) Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res 21:69–72PubMedCrossRefGoogle Scholar
  19. 19.
    Birklein F (2005) Complex regional pain syndrome. J Neurol 252:131–138PubMedCrossRefGoogle Scholar
  20. 20.
    Richards S, Chalkiadis G, Lakshman R, Buttery JP, Crawford NW (2012) Complex regional pain syndrome following immunisation. Arch Dis Child 97:913–915PubMedCrossRefGoogle Scholar
  21. 21.
    Martinez-Lavin M (2012) Fibromyalgia when distress becomes (un)sympathetic pain. Pain Res Treat 981565. doi:10.1155/2012/981565
  22. 22.
    Martinez-Lavin M (2007) Biology and therapy of fibromyalgia. Stress, the stress response system, and fibromyalgia. Arthritis Res Ther 9:216–219PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Vargas-Alarcon G, Alvarez-Leon E, Fragoso JM, Vargas A, Martinez A, Vallejo M, Martinez-Lavin M (2012) A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia. BMC Musculoskeletal Dis 13:23CrossRefGoogle Scholar
  24. 24.
    Schlereth T, Drummond PD, Birklein F (2014) Inflammation in CRPS: Role of the sympathetic supply. Auton Neurosci 182:102–107PubMedCrossRefGoogle Scholar
  25. 25.
    Vallejo M, Martínez-Martínez LA, Grijalva-Quijada S, Olguín-Ruvalcaba HM, Salas E, Hermosillo AG, Cárdenas M, Martínez-Lavín M (2013) Prevalence of fibromyalgia in vasovagal syncope. J Clin Rheumatol 19:111–114PubMedCrossRefGoogle Scholar
  26. 26.
    Maleki J, LeBel AA, Bennett GJ et al (2000) Patterns of spread in complex regional pain syndrome, type I (reflex sympathetic dystrophy). Pain 88:259–266PubMedCrossRefGoogle Scholar
  27. 27.
    Haensch CA, Tosch M, Katona I, Weis J, Isenmann S (2014) Small-fiber neuropathy with cardiac denervation in postural tachycardia syndrome. Muscle Nerve 50:956–961PubMedCrossRefGoogle Scholar
  28. 28.
    Oaklander AL, Rissmiller JG, Gelman LB, Zheng L, Chang Y, Gott R (2006) Evidence of focal small-fiber axonal degeneration in complex regional pain syndrome-I (reflex sympathetic dystrophy). Pain 120:235–243PubMedCrossRefGoogle Scholar
  29. 29.
    Gilbert MR, Harding BL, Hoffman PN, Griffin JW, Price DL, Troncoso JC (1992) Aluminum-induced neurofilamentous changes in cultured rat dorsal root ganglia explants. J Neurosci 12:1763–1771PubMedGoogle Scholar
  30. 30.
    Shoenfeld Y, Agmon-Levin N (2011) ‘ASIA’—autoimmune/inflammatory syndrome induced by adjuvants. J Autoimmun 36:4–8PubMedCrossRefGoogle Scholar
  31. 31.
    Gherardi RK, Coquet M, Chérin P et al (1998) Macrophagic myofasciitis: an emerging entity. Groupe d’Etudes et Recherche sur les Maladies Musculaires Acquises et Dysimmunitaires (GERMMAD) de l’Association Française contre les Myopathies (AFM). Lancet 352:347–352PubMedCrossRefGoogle Scholar
  32. 32.
    zur Hausen H (2009) Papillomaviruses in the causation of human cancers—a brief historical account. Virology 384:260–265PubMedCrossRefGoogle Scholar
  33. 33.
    Harper DM, Vierthaler SL, Santee JA (2010) Review of gardasil. J Vaccines Vaccin 23:(107). doi:10.4172/2157-7560.1000107
  34. 34.
    Guo F, Hirth JM, Berenson AB (2015) Comparison of HPV prevalence between HPV-vaccinated and non-vaccinated young adult women (20–26 years) [abstract] In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research, Philadelphia, {Abstract # 844}. http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=7f019f73-accb-484e-becc-5ecc405f8ec5%26cKey=e2313b32-d6ac-4443-ab2d-49c368ea3b89%26mKey=%7b19573A54-AE8F-4E00-9C23-BD6D62268424%7d

Copyright information

© International League of Associations for Rheumatology (ILAR) 2015

Authors and Affiliations

  1. 1.Rheumatology DepartmentInstituto Nacional de Cardiología Ignacio ChávezMexico CityMexico

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