We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS) with chronic fatigue 2 months following Gardasil vaccination.
This case fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA).
[A] thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended.
Due to the wide heterogeneity of symptoms and its frequent co-occurrence with other systemic autoimmune diseases, POTS is difficult to diagnose.
40% of patients with chronic fatigue syndrome (CFS) also suffer from POTS.
[I]t is becoming increasingly recognized that POTS and CFS can also be triggered by various medications (ie, antihypertensive drugs, antipsychotics) and vaccines.
A 14-year-old previously healthy girl presented with flu-like symptoms, sore throat, low-grade fever, fatigue, swollen glands, and intense headaches in February 2009, approximately 2 months after her second [quadrivalent] HPV vaccine injection.
The psychiatric evaluation in September 2009 ruled out the possibility that the patient’s symptom were of psychosomatic origin, and the subsequent evaluation in 2010 found no evident signs of panic and anxiety disorders.
These problems were never present prior to the onset of the illness in February 2009.
[I]n December 2009, she was finally diagnosed with vasovagal syncope and associated postural orthostatic tachycardia syndrome. In addition, her illness met the criteria for CSF given her persisting fatigue of over 6 months, new-onset disabling headaches, postexertional worsening of the fatigue, myalgias, cognitive dysfunction, and unrefreshing sleep.
An interval of 6 weeks between exposure and outcome is often used as evidence of a plausible causal association; however, immune and autoimmune diseases are chronic diseases that more often than not have a long incubation time.
[L]ong-term persistence of elevated titers of autoantibodies was necessary for the emergence of clinically overt signs and symptoms…
Notably, the accumulation of autoantibodies occurred while patients were still asymptomatic.
Similarly, postvaccination adverse immune phenomena can have long latency periods (ie, month to years following immunization).
[A]utoimmune neuropathies can occur 4 to 10 months following vaccination… [and] first manifest with vague symptoms… which were frequently deemed as insignificant and thus ignored. These symptoms, otherwise known as “bridging symptoms” and consistent with a mild subclinical disease, would progress slowly and insidiously until exposure to a secondary immune stimulus.
Consistent with these observations, we recently described several cases of autoimmunity (systemic lupus) following Gardasil where the nonspecific ASIA-related manifestations eventually progressed over time to a full-blown immune disease following subsequent vaccine reexposure.
It is possible… that some patients with POTS are simply undiagnosed or misdiagnosed with anxiety and panic-related disorders, which leads to underreporting and a paucity of data on the incidence of POTS and other autonomic system disorders following vaccination. The analysis of the US VAERS database substantiates this concern.
Another possible reason for the frequent misdiagnosis of POTS is that patients with this syndrome typically present with complaints that partially overlap with those seen in panic disorders or chronic anxiety.
Notably, none of these manifestations were present prior to the onset of her illness in February 2009 following Gardasil vaccination, indicating that the vaccine may have been the triggering, or at the very least, the exacerbating factor.
[V]accines have been reported to precede CFS mainly following exposure to multiple vaccinations and/or as an adverse response to the vaccine adjuvant.
[T]he safety trials for Gardasil (which is an aluminum-adjuvanted vaccine) did not include a true inactive placebo but rather an aluminum-adjuvant-containing placebo, despite much data showing that aluminum in vaccine-relevant exposures can be toxic to humans.
In years following licensure, numerous case reports of serious adverse reactions of the autoimmune origin associated with the qHPV vaccine Gardasil have raised concerns about the safety of the vaccine.
Due to the wide heterogeneity of symptoms and its frequent co-occurrence with other systemic autoimmune diseases, POTS is difficult to diagnose and hence many cases remain unreported.
The relatively high prevalence of POTS/CFS-related symptoms in young women vaccinated with HPV vaccines should alert physicians to a closer monitoring of post-HPV-related manifestations fitting the POTS/CFS criteria.