Age: 19.0
Sex: F
Vaccine: HPV4
Symptoms: Central nervous system lesion, Demyelination, Hypoaesthesia, Neurological examination abnormal, Nuclear magnetic resonance imaging brain 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 administrations 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 first case- a 19 year old woman who received two doses of GARDASIL, 3 months apart, and approximately 1 month after the second dose, she developed numbness to the right foot that within 1 day extended to the contralateral foot and was associated with mid-thoracic back pain. Her neurological examination was only significant for the altered perception to touch to the feet. Deep tendon reflexes were normal and plantar reflexes in flexion. MRI of cervical and thoracic spine revealed a total of three lesions with characteristic demyelinating appearance, one of those in the thoracic spine was contrast-enhancing. MRI brain demonstrated one additional white matter lesion also consistent with a demyelinating process. Antinuclear antibody titres and serology for Treponema pallidum and Borrelia burgdorferi were negative; ACE levels, vitamin B12 and folate levels were normal. CSF was never tested. The patient was treated in the acute setting with high doses of intravenous methylprednisolone and clinical improvement ensued. Demyelinating disease was felt to be the likely diagnosis and approximately 4 months later treatment with natalizumab was initiated. The patient has remained clinically asymptomatic afterwards but the repeated MRI brain at 1 year showed new lesions in the white matter of both hemispheres and a small contrast enhancing area in the right frontal lobe. The patient tested positive for anti-natalizumab antibodies and the medication was discontinued. Alternative therapy for MS has been instituted. 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 HPV vaccines have been distributed and 7802 adverse events were recorded. Of the 10 confirmed cases of Guillain-Barre syndrome, five had 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 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 vaccines are undeniable as several diseases can only be treated by active vaccinations. HPV is the causative agent of a potentially highly 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. Upon internal review, the patient's adverse event was determined to be other important medical event since it was treated with intravenous methylprednisolone. Additional information has been requested. This is one of several reports received from the same source. The second patient was captured in WAES# 1110USA01072.