Do Vaccines Cause Vasculitis or Polyarteritis Nodosa?

Conclusion | Epidemiological Evidence | Proposed Biological Mechanism | Archives | References

Polyarteritis nodosa (PAN) has been reported as a rare complication of natural infection with hepatitis B virus. Thus, hepatitis B vaccine prevents PAN by protecting against natural infection. Vaccines currently routinely recommended to the general population in the U.S.* have not been shown to cause vasculitis or PAN.

The 2012 report by the Institute of Medicine (IOM) [1], now called the National Academy of Medicine (NAM), described two studies assessing exacerbation of vasculitis and influenza vaccine [2, 3], but these studies did not provide convincing evidence due to a lack of validity and precision. The IOM found no relevant studies of quality in the literature assessing onset of vasculitis or PAN and influenza or hepatitis B vaccines, or exacerbation of vasculitis and hepatitis B vaccine [1].

Since the IOM report, a randomized trial found that influenza vaccine was safe for patients in remission with anti-neutrophil cytoplasmic antibody-associated vasculitis [4], and a prospective observational study found that vaccinations had no significant clinical impact on patients with systemic necrotising vasculitis [5]. An Italian case-control study found an increased risk of Henoch-Schonlein purpura, a common childhood vasculitis, within 12 weeks of MMR vaccination (odds ratio 3.4; 95% CI 1.2-10.0) [6]. A large VSD study found that vaccination was associated with a decrease in incidence of the vascular disorder known as Kawasaki disease [7], and a 2017 systematic review concluded that evidence is lacking for a causal relationship between immunization and Kawasaki disease [8].

PAN has been reported as a rare complication of natural infection with hepatitis B virus. Formation of immune complexes has been suggested as a potential mechanism for vasculitis or PAN after hepatitis B vaccine. Another possible mechanism is activation of the complement system, in which a cascade of proteolysis and successive release of cytokines functions to amplify the immune response but can damage host cells if not properly regulated. Other mechanisms that could contribute to vasculitis include autoantibodies or T cells [1].

The 2012 IOM report described two cases of exacerbation of vasculitis after influenza vaccine that showed recurrence of symptoms after vaccine re-challenge [9], and three cases of PAN after hepatitis B vaccine [10-13]; however, even when considering knowledge about the aforementioned natural infections, the IOM concluded that this mechanistic evidence was weak. The IOM also concluded that there was no mechanistic evidence for an association between PAN and influenza vaccine, between exacerbation of vasculitis and hepatitis B vaccine, or between onset of vasculitis and influenza vaccine or hepatitis B vaccine [1].

1. Institute of Medicine. In: Stratton K, Ford A, Rusch E, Clayton EW, eds. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2012.
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