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Possible Association of Guillain-Barre Syndrome and Hepatitis A Vaccination

Danith Blumenthal, MD; Dario Prais, MD; Efrat Bron-Harlev, MD; Jacob Amir, MD

Pediatr Infect Dis J 23(6):586-588, 2004. © 2004 Lippincott Williams & Wilkins

Posted 06/21/2004

Abstract and Introduction

Abstract

We report a case of Guillain-Barré syndrome in a previously healthy child who received a hepatitis A vaccination (HAVRIX) 5 days before onset of symptoms. No other precipitating factor could be identified. The relevant literature is reviewed and discussed.

Introduction

The precipitating cause of Guillain-Barré syndrome is not always obvious. In most cases, a flu-like illness induced by a variety of pathogenic agents precedes the neurologic symptoms by ~10 days. Campylobacter jejuni is the most commonly reported pathogen involved in adults, followed by cytomegalovirus, Epstein-Barr virus and Mycoplasma pneumoniae. Infection with hepatitis A virus (HAV) and hepatitis B virus has also been implicated. Other known precipitating factors include immunization against influenza, tetanus and hepatitis B.

We report a temporal association between hepatitis A vaccine (HAVRIX) and Guillain-Barré syndrome in a previously healthy child.

Case Report

A 1 1/2-year-old previously healthy child was hospitalized for progressive weakness for 5 days. Ten days before admission, he received the first dose of the hepatitis A vaccine (HAVRIX 720). Five days later, he refused to walk, was weak and anorexic and had a low grade fever. No history of febrile illness was reported during the previous month. The patient first presented to another hospital after developing flaccid paralysis associated with respiratory symptoms. He was provided airway support and was transferred to our facility. After admission to the Intensive Care Unit, the patient was sedated and breathed through a nasotracheal tube with an oxygen saturation of 100%. Vital signs were: pulse, 189 bpm; blood pressure, 117/76 mm Hg; respiratory rate, 21 breaths/min and temperature, 36°C.

The child was somewhat somnolent with normal cranial nerve findings except for tongue fasciculations and weak gag reflex. The pupils were equal and reactive to light. There was moderate symmetric weakness in the upper limbs (strength 2/5), and severe symmetric weakness in the lower limbs (strength 1/5). There were no sensory abnormalities. Normal symmetric tendon reflexes in the upper limbs and absence of reflexes in the lower limbs were present. The remainder of the examination was unremarkable.

Laboratory studies showed a white blood cell count of 19,510/mm3; serum electrolyte, renal and liver function tests were normal. Lumbar puncture revealed no white blood cells, 107 mg/dl protein and 102 mg/dl glucose. Cerebrospinal fluid (CSF) culture was negative for enteroviruses and bacteria and stool culture was negative for C. jejuni and polioviruses. Serologic tests for C. jejuni, human immunodeficiency virus, Venereal Disease Research Laboratory test, Epstein-Barr virus and M. pneumoniae were negative; cytomegalovirus IgM was negative and IgG was positive; hepatitis B virus serology was positive for hepatitis B surface antibodies and negative for HBc antibodies. Serologic study for HAV was not done. Nerve conduction and electromyographic examination revealed demyelination and axonal damage. Spinal magnetic resonance imaging scan was normal.

On the basis of the clinical and laboratory findings, the child was diagnosed as having Guillain-Barré syndrome. Supportive treatment included mechanical ventilation, nasogastric tube feeding, and physiotherapy. Daily doses of intravenous immunoglobulin 1 g/kg and pulses of methylprednisolone 10 mg/kg were administered for 2 days. Despite treatment, the patient became tetraplegic and lost the gag reflex, and spontaneous breathing stopped. Another dose of intravenous immunoglobulin 1 g/kg was given on day 7 of hospitalization. On day 20 he began to move his right hand, and on day 30 mechanical ventilation was stopped. His neurologic status improved slowly. The course was complicated by postintubation subglottic obstruction requiring tracheostomy. Several operations were performed for laryngeal reconstruction. Four months after admission, the patient was walking unaided and was discharged. Aside from absent tendon reflexes in the lower limbs, physical examination was normal.

Discussion

We present a case of Guillain-Barré syndrome in a child who received hepatitis A vaccine 5 days before onset of the clinical symptoms.

Approximately 75% of all cases of Guillain-Barré syndrome are preceded in the prior 1-3 weeks by an acute infection, usually respiratory or gastrointestinal.[1-3] Recent immunization has also been associated with the syndrome. The underlying pathophysiology is presumed to involve an immune cascade induced by the precedent agent, leading to demyelinization of the large nerve fibers.

Tabor[4] reported the appearance of Guillain-Barré syndrome after serologically proven HAV infection in 7 patients (6 male, 1 female, ages 25-49 years). All had symptoms of acute hepatitis and IgM antibodies to HAV. CSF fluid was examined for IgM anti-HAV in 1 patient during the acute phase and found to be positive. The interval between the first clinical symptoms of infection (headache, fatigue, myalgia and jaundice) and the appearance of Guillain-Barré syndrome ranged from 3 to 14 days. CSF protein was either high or normal, and nerve conduction was usually slowed with prolonged latency. Five similar single case reports of Guillain-Barré syndrome associated with HAV infection are summarized in Table 1.

A summary of patients in whom vaccines were associated with Guillain-Barré syndrome is shown in Table 2. The best known cluster of cases, reported by Schonberger et al.,[10] occurred in the United States in 1976, following vaccination with A/New Jersey influenza vaccine. The association was supported by epidemiologic evidence and the significantly elevated rate of attacks in the vaccinated versus the unvaccinated population. The estimated attributable risk of vaccine-related Guillain-Barré syndrome was <1 case per 100,000 vaccinations. The period of increased risk was 5 weeks after vaccination. Other reported vaccines associated with Guillain-Barré syndrome include tetanus-diphtheria toxoid, Calmette-Guérin bacillus and hepatitis B (Table 2).

In our patient, the association of Guillain-Barré syndrome with hepatitis A vaccine is supported by temporal proximity of the vaccination with the onset of symptoms, lack of other precipitating factors and the immune-mediated nature of the manifestation. Hepatitis A vaccine consists of inactivated hepatitis A viruses that cause an immune response similar to that caused by the infection. In view of earlier reports of a relationship between HAV infection and Guillain-Barré syndrome, we assume there may also be a relationship between the HAV vaccine and Guillain-Barré syndrome.

It is not surprising that the first report of this association comes from Israel, the first country to initiate a universal vaccination program in 1999 for hepatitis A (at 18 and 24 months of age). About 350,000 children have received the vaccine to date as part of the general immunization program. Whether the illness was triggered by the hepatitis A vaccine will become clearer only if and when additional cases are reported.

Tables

Table 1. Patients with Hepatitis A Virus Infection and Guillain-Barré Syndrome: Literature Review

Table 2. Some Vaccines Associated with Guillain-Barré Syndrome

References

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