Elsevier

Vaccine

Volume 33, Issue 22, 21 May 2015, Pages 2602-2605
Vaccine

Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus

https://doi.org/10.1016/j.vaccine.2015.03.098Get rights and content

Abstract

Background

Infections with human papilloma virus (HPV) can result in cervical, oropharyngeal, anal, and penile cancer and vaccination programs have been launched in many countries as a preventive measure. We report the characteristics of a number of patients with a syndrome of orthostatic intolerance, headache, fatigue, cognitive dysfunction, and neuropathic pain starting in close relation to HPV vaccination.

Methods

Patients were referred for orthostatic intolerance following HPV vaccination. Symptoms of autonomic dysfunction were quantified by standardised questionnaire. The diagnosis of postural orthostatic tachycardia syndrome (POTS) rested on finding a sustained heart rate increment of >30 min−1 (>40 min−1 in adolescents) or to levels >120 min−1 during orthostatic challenge.

Results

35 women aged 23.3 ± 7.1 years participated. Twenty-five had a high level of physical activity before vaccination and irregular periods were reported by all patients not on treatment with oral contraception. Serum bilirubin was below the lower detection limit in 17 patients. Twenty-one of the referred patients fulfilled the criteria for a diagnosis of POTS (60%, 95%CI 43–77%). All patients had orthostatic intolerance, 94% nausea, 82% chronic headache, 82% fatigue, 77% cognitive dysfunction, 72% segmental dystonia, 68% neuropathic pain.

Conclusions

In a population referred for symptoms of orthostatic intolerance and other symptoms consistent with autonomic dysfunction that began in close temporal association with a quadrivalent HPV vaccination, we identified a 60% prevalence of POTS. Further work is urgently needed to elucidate the potential for a causal link between the vaccine and circulatory abnormalities and to establish targeted treatment options for the affected patients.

Section snippets

Patients and methods

We included 35 patients consecutively referred to our syncope unit for head-up tilt test under the diagnosis of orthostatic intolerance as a suspected adverse event following vaccination with the quadrivalent HPV vaccine (Gardasil®). Informed consent was obtained from all patients. Due to the retrospective nature of the study, approval by the authorities was not required.

The patients were interviewed with special focus on symptoms from the central and peripheral nervous system, exercise habits,

Statistics

Data are given as mean values and standard deviations. Comparisons between groups were made with the Student's t-test for unpaired data and calculations were made in IBM SPSS statistics version 19. A two sided significance level of 0.05 was used.

Results

The study included 35 females aged 23.3 ± 7.1 years (mean ± sd) (range 13–39). Seventeen per cent were aged between 12 and 15 years, 21% between 15 and 19 years, 37% between 19 and 27 years, and 25% were 27 years or older. Body weight and height were (mean + sd) 62.4 ± 15.7 kg and 168 ± 7.2 cm, respectively resulting in a BMI of 22.1 ± 4.7 kg/m2. The mean delay between vaccination and onset of symptoms was 9.3 days (range: 0–30). The mean age at onset of symptoms was 22.0 years (range: 12–39). Mean time

Discussion

The present study is a case review of patients referred to our unit for orthostatic intolerance and other symptoms consistent with autonomic dysfunction as suspected side effects to a quadrivalent vaccination against human papilloma virus. Patients stories were consistent as were the reported symptoms and hemodynamic response to tilt with a 60% prevalence of POTS. These patients are in many ways “typical” POTS-patients—both with regard to gender, age of symptom-onset and the presence of

Conclusions

The present study has reported on symptoms and signs in patients referred for orthostatic intolerance suspected to be secondary to vaccination against human papilloma virus. The patients were generally older than the current target population for HPV vaccination programs. We found remarkable consistency in the reported symptoms and in the hemodynamic responses to the upright posture. The patients were characterised by a high level of physical activity prior to vaccination and by signs of

Funding

None.

Conflict of interest statement

Jesper Mehlsen has received fees for speaking and for consulting from Merck, Sharpe & Dohme. Jesper Mehlsen has received fees for speaking from Sanofi Pasteur. The other authors have no competing interests related to the contents of this manuscript or part thereof.

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