Sex: F
Vaccine: HPV2
Symptoms: Altered visual depth perception, Anti-NMDA antibody positive, Anti-thyroid antibody, Anti-thyroid antibody negative, Antinuclear antibody negative
Clinical narrative: This case was reported in a literature article and described the occurrence of postural orthostatic tachycardia syndrome in a 18-year-old female patient who received CERVARIX. Co-suspect products included CERVARIX. On an unknown date, the patient received the 1st dose of CERVARIX and the 2nd dose of CERVARIX. On an unknown date, 2 days after receiving CERVARIX and not applicable after receiving CERVARIX, the patient experienced postural orthostatic tachycardia syndrome, delayed gastric emptying (serious criteria GSK medically significant), condition aggravated, sore throat, difficulty sleeping, nocturnal awakening, visual disturbance, confusion, disturbance in attention, chronic fatigue syndrome, distorted vision, altered visual depth perception, blurred vision, bedridden, fatigue, presyncope, dizziness and nausea. The patient was treated with prednisone. On an unknown date, the outcome of the postural orthostatic tachycardia syndrome, delayed gastric emptying, condition aggravated, sore throat, difficulty sleeping, nocturnal awakening, visual disturbance, confusion, disturbance in attention, chronic fatigue syndrome, distorted vision, altered visual depth perception, blurred vision, bedridden, fatigue, presyncope, dizziness and nausea were unknown. The reporter considered the postural orthostatic tachycardia syndrome, fatigue, presyncope, dizziness and nausea to be possibly related to CERVARIX. The reporter considered the delayed gastric emptying, condition aggravated, sore throat, difficulty sleeping, nocturnal awakening, visual disturbance, confusion, disturbance in attention, chronic fatigue syndrome, distorted vision, altered visual depth perception, blurred vision and bedridden to be possibly related to CERVARIX. Additional information was provided. This case was reported in a literature article and described the occurrence of postural orthostatic tachycardia syndrome (POTS) in 18-year-old female patient who was vaccinated with CERVARIX (GlaxoSmithKline). The patient was previously healthy. No information on patient's family history or concurrent condition or concomitant medication was provided. On an unspecified date, the patient received the 1st dose of CERVARIX (administration route and site unspecified; batch number not provided). Age of vaccination was not provided. 48 hours after vaccination with 1st dose of CERVARIX, the patient developed fatigue, pre-syncope, dizziness and nausea. The symptoms were initially mild and were not attributed to vaccination. On an unspecified date, 6 weeks after the 1st injection, the patient received the 2nd dose of CERVARIX (administration route and site unspecified; batch number not provided). Age of vaccination was not provided. On an unspecified date, immediately after vaccination, the patient's symptoms intensified, and she became bed-bound with pre-syncope, dizziness, nausea, sore throat, difficulty falling asleep, frequent awakenings during the night, visual disturbance, transient episodes of confusion and difficulty concentrating. She was unable to attend school and after seeing numerous specialists was diagnosed with chronic fatigue syndrome. Over the following 3 years, the patient received no specific treatment, and her symptoms fluctuated in severity with some periods when she was able to attend school part-time. Eventually, a tilt table test was performed demonstrating an increase in heart rate from 54 bpm supine to 108 bpm within 10 min of standing, without changes in blood pressure (supine blood pressure 96/54; 10 min after the tilt, blood pressure 110/68), consistent with a diagnosis of POTS. Deep breathing test and Valsalva maneuver were unremarkable, and Quantitative Sudomotor Axon Reflex Test (QSART) showed no evidence of small fiber neuropathy. A gastric emptying test demonstrated mildly delayed gastric emptying. Magnetic resonance imaging (MRI) of the brain, MRI of the cervical and thoracic spine, electroencephalogram (EEG), electromyography (EMG) and visual evoked potentials were all unremarkable. Ophthalmology evaluation for complaints of recurrent visual distortion, recurrent visual depth perception abnormalities and blurry vision showed no evidence of optic neuritis or visual field defect. Autoimmune markers were negative for antinuclear antibodies (ANA), anti-SSA (anti-Sjogren's-syndrome-related antigen A) and anti-SSB (anti-Sjogren's syndrome type B (SSB) antibodies), anti-TPO (anti-thyroid peroxidase) antibodies, anti-thyroglobulin antibodies, anti-phospholipid antibodies and anti-DS DNA antibodies, but positive for low level of anti-NMDAR (N-methyl-D-aspartate receptor) Ab. Further testing demonstrated positive beta 2 adrenergic and M2 muscarinic receptor antibodies. A paraneoplastic panel, including ganglionic AchR antibody, was negative. Serum anti-NMDA Ab were repeated 2 months later and were once again mildly elevated. To rule out a paraneoplastic syndrome with positive anti-NMDA Ab, a pelvic ultrasound was obtained and did not reveal any ovarian or pelvic masses. Subsequently, a full body fluorodeoxyglucose (FDG)-positron emission tomography (PET) (FDG-PET) scan was performed and was also unremarkable. Cerebrospinal fluid (CSF) analysis was negative for anti-NMDA Ab and other neuronal antibodies and showed normal cell count, glucose and protein. The patient did not have evidence of encephalitis, based on her clinical features, unremarkable MRI of the brain and normal CSF analysis, which was negative for CSF anti-NMDAR Ab. The patient received 5 treatments with plasmapheresis followed by a daily dose of prednisone, and her symptoms improved significantly for about 7 weeks after the treatment. When plasmapheresis was stopped and prednisone was tapered, the symptoms recurred. Following plasmapheresis and prednisone treatment, a repeat serum anti-NMDAR Ab were negative. The outcome of the event was not reported. The author commented, "We believe that, based on the temporal association between vaccination with CERVARIX and the onset of the symptoms, coupled with evidence of re-challenge, whereas symptoms worsened after the second dose of the vaccine, both POTS and anti-NMDAR Ab were most likely precipitated by vaccination." The author stated, "POTS is a heterogeneous disorder of the autonomic nervous system, and although anti-NMDAR encephalitis can manifest with autonomic symptoms, POTS is not a associated with acute encephalitis and is not considered in the spectrum of the anti-NMDAR Ab clinical phenotypes. The intriguing and unique aspects of this case are the finding of anti-NMDAR Ab in a patient with POTS following vaccination with HPV vaccine, subsequent symptomatic improvement with immunomodulatory therapy, and recurrence of symptoms once immunomodulatory therapy was discontinued. These facts suggest an autoimmune etiology of POTS in our patient. Whether the presence of anti-NMDAR Ab is coincidental or causative in this patient is unknown. Testing a cohort of patient with POTS for anti-NMDAR Ab may help determine whether POTS can be associated with anti-NMDAR Ab or whether our patient represents an isolated case."