Age: 18.0
Sex: F
Vaccine: HPV4
Symptoms: Papilloedema, Paraesthesia, Vision blurred, Visual acuity tests abnormal
Clinical narrative: Information has been received from a published literature article. Since its inception, the polyvalent vaccine against the human papilloma virus (HPV), GARDASIL, has generated some controversies as a temporal relationship between the administration of the vaccine and the development of a few autoimmune diseases, such as acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS) and Guillain-Barre syndrome have been reported. There are two cases whose initial presentation of CNS demyelination followed in close time relationship the administration of GARDASIL. The patient in this report is the second case-an 18 year old woman who was involved in a motor vehicle accident without head trauma and presented to her paediatrician complaining of left shoulder and neck pain. A MENACTRA was administered and pain medications were prescribed. At the follow-up visit 3 weeks later, she reported improvement of the left shoulder pain but complained of right arm and right-sided high thoracic back pain. The first dose of GARDASIL was administered at that time. Approximately 6 weeks later she noted blurriness of the vision in both eyes that in a few days evolved into right optic neuritis. When she was hospitalised, her visual acuity was 20/200 in the right eye and 20/40 in the left eye, and right arm paraesthesias were present. On fundoscopic examination, bilateral disc swelling consistent with acute bilateral optic neuritis was observed. MRI of the brain detected white matter lesions suggestive of a demyelinating disease. MRI of the spine also showed two contrast enhancing lesions at the cervical level. CSF demonstrated a white cell count of 205/mm3, elevated IgG index at 3.5 and myelin basic protein 8.5 ng/ml. Oligoclonal bands were not tested. No improvements were observed after a 5 day course of 1000 mg/day of methylprednisolone, and intravenous immunoglobulins at 1 g/kg for 2 consecutive days were administered. The patient's sensory symptoms started to lessen and vision slowly recovered. One month later, the patient complained of new paraesthesias involving the upper abdomen and on repeated MRI of the spine a contrast enhancing demyelinating lesion was detected at the T3 level. The patient received an additional course of intravenous methylprednisolone followed by another dose of immunoglobulins. Therapy with glatiramer acetate was initiated. However, MRI scan 2 months later showed several new enhancing lesions, indicative of an ongoing, active demyelinating process. Since FDA approval in June 2006, GARDASIL has been implicated in the development of acute inflammatory polyneuropathy, MS and ADEM. It has been reported that 12 million doses of GARDASIL have been distributed in the country and 7802 adverse events were recorded. Of the 10 confirmed cases of Guillain-Barre syndrome, five have received concurrent administration of MENACTRA. The first case reported here is concerning for causality, as no medical problems were present prior to the administration of the vaccine and the McDonald criteria for the diagnosis of MS are met on follow-up MRI scan. In the second case, the development of sensory symptoms approximately 3 weeks before exposure to GARDASIL poses the question of a pre-existing condition, unmasked by the trauma, reaching its full expression in coincidence with the vaccination. Administration of GARDASIL exacerbated the clinical course of three patients who had already manifested neurological symptoms consistent with clinically isolated syndrome and converted to clinically definite MS after the vaccination. A case of ADEM following exposure to HPV vaccine was recently reported and under the assumption that ADEM and MS share some pathophysiological and clinical features, it is conceivable that an immunological stimulus capable of inducing a monophasic deregulated immune response in the CNS could potentially lead to a relapsing-remitting chronic course. It is plausible that in genetically predisposed individuals, the immunological stimulus of a vaccine or even some immunomodulatory therapies may lead to a deranged immune response that could theoretically trigger an autoimmune disease. In this view, the particularly aggressive course of disease demonstrated by the patient in case No 2 could be the result of such a stimulation that could not be controlled with a firstline immunomodulatory therapy. GARDASIL has raised no concerns about the risks of transmission of the HPV and the benefits of vaccine are undeniable as several diseases can only be treated by active vaccinations. HPV is the causative agent of a potentially high morbid illness and its prevention will have a large social impact. Considering the overall limited number of adverse events recorded thus far, it is likely that the benefits outweigh the risks of complications. However, we feel that collecting long term data on the effectiveness of the HPV vaccine and documenting the adverse events is imperative. Additional information has been requested. This is one of several reports received from the same source. The second patient was captured in WAES# 1110USA00902.