Introduction

Vaccination has been one of the most effective public health measures in the history of medicine. 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]. Adverse reactions appear to be more frequent after HPV vaccination when compared to other types of immunizations. A study done in the Valencian Community of Spain showed that the adverse HPV vaccination side effects reported by health professionals (doctors or nurses) to the health authorities have an approximate incidence rate of 1 per 1000 inoculations. This incidence was ten times higher than the ones described with other types of vaccines administered to girls of similar age. Thirty-two percent of the HPV vaccine adverse reaction was classified as “severe” [2]. Different isolated cases and small series have described the development of syncope, complex regional pain syndrome [3], postural orthostatic tachycardia syndrome [4, 5], and fibromyalgia [6] after HPV vaccination. These illnesses are difficult to diagnose and have overlapping clinical features. Recently published evidence suggests that dysautonomia and small fiber neuropathy may be the common underlying pathogenesis for these overlapping clinical entities [1].

There are three recently validated self-applied questionnaires that may help to appraise these syndromes: the 2010 American College of Rheumatology Fibromyalgia Diagnostic Criteria survey is able to detect the presence of fibromyalgia [7], COMPASS 31 evaluates the burden of autonomic symptoms [8], and S-LANSS questionnaire may suggest a neuropathic component in the pain experience [9].

Our objective was to use these questionnaires as tool to investigate if a patterned illness might develop after HPV vaccination.

Material and methods

The three validated questionnaires together with a “present illness” survey were e-mailed to individuals who had the onset of a chronic disease soon after HPV vaccination. The target population was identified with the help of HPV vaccine blog managers. Patients who had previously e-mailed us after publication of an article discussing this topic [1], and two cases personally seen by one of the authors [6] were also contacted. Individuals were asked to fill-out the questionnaire only if they have reasons to believe that the HPV vaccination was related to the onset of their chronic illness. The cases that had symptoms onset within 3 months post-vaccination were reviewed.

The protocol was approved by the Institutional Research and Ethics committees.

Results

The outstanding results of 45 filled questionnaires collected in a month’s period are summarized in Table 1. Patients reside in 13 different countries. Mean (±SD) age at vaccination time was 14 ± 5 years; all except 1 affected individual were female. The mean time span between vaccination and onset of symptoms was 2.3 ± 3.1 weeks. Twenty-nine percent of the cases had immediate (within 24 h) post-vaccination illness onset. The most common presenting complaints were musculoskeletal pain (66 %), fatigue (57 %), headache (57 %), dizziness/vertigo (43 %), paresthesias/allodynia (36 %), and nausea/vomiting (27 %). After a mean period of 4.2 ± 2.5 years post-HPV vaccination, all except two patients have escalating vexing symptoms. At this point in time, the most common reported symptoms were fatigue/tiredness (88 %), muscle pain (76 %), headache (74 %), muscle weakness (69 %), thinking or remembering problem (63 %), dizziness (63 %), pain/cramps in the abdomen (60 %), numbness/tingling (60 %), and nausea (60 %). Because of these symptoms, 93 % of patients are unable to regularly attend school or work.

Table 1 Outstanding features of 45 patients who describe adverse HPV vaccination reactions
Full size table

Fifty-three percent of affected individuals fulfill the fibromyalgia diagnostic criteria. COMPASS-31 score was 43 ± 21; these values imply advanced autonomic dysfunction. Eighty-three percent of the patients who had ongoing pain displayed S-LANSS values >12, suggesting a neuropathic component in their pain experience.

Discussion

These results suggest that a patterned illness of neuropathic pain and autonomic dysfunction may appear after HPV vaccination, The HPV post-vaccination cluster of symptoms described in this study from individuals residing in 13 different countries is analogous to the ones reported in 53 Danish patients by Brinth et al. Similar to our results, the most common complaints in the Danish study were headache (100 %), orthostatic intolerance (96 %), fatigue (96 %), cognitive dysfunction (89 %), and nausea (91 %) [5]. Likewise, the most common symptoms in 40 HPV-vaccinated Japanese girls published by Kinoshita et al were headache (70 %), fatigue (53 %), coldness of the legs (53 %), limb pain (50 %), and limb weakness (48 %) [3].

HPV vaccination syndrome bears resemblance to fibromyalgia, myalgic encephalomyelitis/chronic fatigue syndrome, ASIA syndrome, macrophagic myofasciitis, and to Gulf War Illness. These syndromes have overlapping clinical features and have been previously associated to other aluminum-containing vaccines [10–12]. The obvious difference is that HPV vaccination syndrome affects mostly girls in the initial period of their lives.

HPV vaccination syndrome appears to be a neurotoxic disease affecting mainly the sensory and the autonomic nervous system. Based on our previous research on fibromyalgia [13], we speculate that in susceptible individuals the vaccine recombinant virus-like particles adsorbed on aluminum-containing adjuvant may damage dorsal root ganglia. This damage may induce small fiber neuropathy and dysautonomia [1].

The clear limitation of our study is the lack of direct medical examination of affected individuals.

In conclusion, emerging evidence suggests that a disabling syndrome of chronic neuropathic pain, vexing fatigue, and profound autonomic dysfunction may appear after HPV vaccination.