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Thursday, January 5, 2017

Human papillomavirus vaccination syndrome--small fiber neuropathy and dysautonomia

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.


Vaccination has been one of the most effective public health measures in the history of medicine http://www.cdc.gov/vaccines/ (accessed 6 April 2015). Terrible diseases such as smallpox or poliomyelitis have been practically eradicated. Nevertheless, it seems as the pendulum has swung too far. Nowadays, children are subjected to multiple vaccination protocols not only to prevent common infectious diseases but also to prevent the late appearance of cancer. The human papillomavirus (HPV) vaccine is the case in point [1]. Different adverse reactions have been reported from several parts of the world after HPV vaccination. A patterned illness of chronic pain and autonomic dysfunction seems to be emerging from these reports [2–5]. Kinoshita et al. [2] and Brinth et al. [4] have recently published well-documented evidence of different expressions of sympathetic dysfunction in sizable groups of girls that received the HPV vaccine.

There appears to be a disconnection between the self-reported severe reactions that frequently appear in the social media blogs http://sanevax.org (accessed 4 April 2015), in contrast with the opinion of health authorities that classify the purported side effects as coincidental or not specific for a definite diagnosis [6]. Some investigators have classified these post-vaccination responses as “mass psychogenic illness” [7]. Nevertheless, during the last months, the medical scientific literature has documented case reports and small series describing severe adverse reactions to the HPV vaccine that might have common underlying pathogenesis. HPV vaccine-induced illnesses include complex regional pain syndrome (CRPS) [2], postural orthostatic tachycardia syndrome (POTS) [2–4], and fibromyalgia [8, 9], among others. These illnesses are often difficult to recognize. Various traditional physicians deny the mere existence of these syndromes disregarding them as somatization disorders or psychogenic illnesses [10, 11].

This piece proposes that HPV vaccine-induced small fiber neuropathy and dysautonomia could be the common underlying pathogenesis to the group of rare, but severe, reactions that follow HPV vaccination.


Murine hypothalamic destruction with vascular cell apoptosis subsequent to combined administration of human papilloma virus vaccine and pertussis toxin.
Aratani S, Fujita H, Kuroiwa Y, Usui C, Yokota S, Nakamura I, Nishioka K, Nakajima T.
Sci Rep. 2016 Nov 11;6:36943. doi: 10.1038/srep36943.
PMID: 27833142 Free PMC Article

Current Safety Concerns with Human Papillomavirus Vaccine: A Cluster Analysis of Reports in VigiBase.
Chandler RE, Juhlin K, Fransson J, Caster O, Edwards IR, Norén GN.
Drug Saf. 2017 Jan;40(1):81-90. doi: 10.1007/s40264-016-0456-3.
PMID: 27638661

Involvement of chronic epipharyngitis in autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA).
Hotta O, Tanaka A, Torigoe A, Imai K, Ieiri N; Japanese Focal Inflammation Research Group..
Immunol Res. 2016 Sep 3. [Epub ahead of print]
PMID: 27592233

Postural tachycardia syndrome (POTS) with anti-NMDA receptor antibodies after human papillomavirus vaccination.
Blitshteyn S, Brook J.
Immunol Res. 2016 Aug 25. [Epub ahead of print]
PMID: 27561785

Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case-control assessment of the vaccine adverse event reporting system (VAERS) database.
Geier DA, Geier MR.
Immunol Res. 2016 Jul 13. [Epub ahead of print]
PMID: 27406735

Vaccinations and secondary immune thrombocytopenia with antiphospholipid antibodies by human papillomavirus vaccine.
Bizjak M, Bruck O, Kanduc D, Praprotnik S, Shoenfeld Y.
Semin Hematol. 2016 Apr;53 Suppl 1:S48-50. doi: 10.1053/j.seminhematol.2016.04.014.
PMID: 27312165

Investigating Reports of Complex Regional Pain Syndrome: An Analysis of HPV-16/18-Adjuvanted Vaccine Post-Licensure Data.
Huygen F, Verschueren K, McCabe C, Stegmann JU, Zima J, Mahaux O, Van Holle L, Angelo MG.
EBioMedicine. 2015 Jul 6;2(9):1114-21. doi: 10.1016/j.ebiom.2015.07.003.
PMID: 26501109 Free PMC Article

HPV vaccination syndrome. A questionnaire-based study.
Martínez-Lavín M, Martínez-Martínez LA, Reyes-Loyola P.
Clin Rheumatol. 2015 Nov;34(11):1981-3. doi: 10.1007/s10067-015-3070-3.
PMID: 26354426

[Neurologic Complications in HPV Vaccination].
Ikeda S.
Brain Nerve. 2015 Jul;67(7):835-43. doi: 10.11477/mf.1416200222. Japanese.
PMID: 26160812

A link between human papilloma virus vaccination and primary ovarian insufficiency: current analysis.
Gruber N, Shoenfeld Y.
Curr Opin Obstet Gynecol. 2015 Aug;27(4):265-70. doi: 10.1097/GCO.0000000000000183. Review.
PMID: 26125978

Prevalence, Incidence, and Clearance of Anogenital Warts in Kenyan Men Reporting High-Risk Sexual Behavior, Including Men Who Have Sex With Men.
Neme S, Wahome E, Mwashigadi G, Thiong'o AN, Stekler JD, Wald A, Sanders EJ, Graham SM.
Open Forum Infect Dis. 2015 May 12;2(2):ofv070. doi: 10.1093/ofid/ofv070.
PMID: 26110169 Free PMC Article

An Overview of Quadrivalent Human Papillomavirus Vaccine Safety: 2006 to 2015.
Vichnin M, Bonanni P, Klein NP, Garland SM, Block SL, Kjaer SK, Sings HL, Perez G, Haupt RM, Saah AJ, Lievano F, Velicer C, Drury R, Kuter BJ.
Pediatr Infect Dis J. 2015 Sep;34(9):983-91. doi: 10.1097/INF.0000000000000793. Review.
PMID: 26107345

Hypothesis: Human papillomavirus vaccination syndrome--small fiber neuropathy and dysautonomia could be its underlying pathogenesis.
Martínez-Lavín M.
Clin Rheumatol. 2015 Jul;34(7):1165-9. doi: 10.1007/s10067-015-2969-z. Review.
PMID: 25990003

Autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA) after quadrivalent human papillomavirus vaccination in Colombians: a call for personalised medicine.
Anaya JM, Reyes B, Perdomo-Arciniegas AM, Camacho-Rodríguez B, Rojas-Villarraga A.
Clin Exp Rheumatol. 2015 Jul-Aug;33(4):545-8.
PMID: 25962455

Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus.
Brinth LS, Pors K, Theibel AC, Mehlsen J.
Vaccine. 2015 May 21;33(22):2602-5. doi: 10.1016/j.vaccine.2015.03.098.
PMID: 25882168

A case-control study of quadrivalent human papillomavirus vaccine-associated autoimmune adverse events.
Geier DA, Geier MR.
Clin Rheumatol. 2015 Jul;34(7):1225-31. doi: 10.1007/s10067-014-2846-1.
PMID: 25535199 Free PMC Article


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