Controlled Observational Studies


Controlled Clinical Trials

None of the clinical trials reviewed by the committee contained information regarding hepatitis B vaccine and anaphylaxis.

Causality Argument

The possibility of a causal relation between hepatitis B vaccination and anaphylaxis is supported by biologic plausibility, by the temporal sequence of observed events following vaccination, and by the observation of a spectrum of host responses to the hepatitis B vaccine that follow a logical biologic gradient from true anaphylaxis to milder hypersensitivity reactions. Biologic plausibility derives from the knowledge that injection of foreign protein into humans can be expected to elicit, in some percentage of recipients, IgE-mediated responses that present as anaphylaxis. Chapter 4 provides the criteria for accepting the diagnosis of anaphylaxis, including cardiovascular collapse and documented hypotension occurring within 4 hours after injection of the vaccine. Only cases meeting these criteria were included as cases of hepatitis B virus-associated anaphylaxis in this report.

In the VAERS reports of suspected anaphylactic reactions, however, a logical biologic gradient can be observed, in that, in addition to the five well-documented reports of anaphylaxis following administration of hepatitis B vaccine, five additional cases of apparent anaphylaxis following hepatitis B vaccination that did not meet the strict criteria applied in this report and an additional eight cases of anaphylactic-type reactions (cardiovascular collapse associated with wheezing) were described.

The evidence concerning a possible relation between hepatitis B vaccination and anaphylaxis is based on VAERS reports. On the basis of these reports, the evidence indicates that anaphylaxis can occur after vaccination against hepatitis B virus and that such an occurrence is an exceedingly rare event. Nonetheless the timing and the unmistakable classic presentation of anaphylaxis, together with the spectrum of host responses that follow a logical biologic gradient from mild to severe following hepatitis B vaccination, indicate that hepatitis B vaccines can cause anaphylaxis.


The evidence establishes a causal relation between hepatitis B vaccine and anaphylaxis. Because the conclusion is not based on controlled studies,

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