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 2015 randomized trial found that influenza vaccine was safe for patients in remission with anti-neutrophil cytoplasmic antibody-associated vasculitis 4, and a 2016 prospective observational study found that vaccinations had no significant clinical impact on patients with systemic necrotizing vasculitis 5.
A 2015 VSD study found that vaccination was associated with a decrease in incidence of the vascular disorder known as Kawasaki disease 6, and a 2017 systematic review concluded that evidence is lacking for a causal relationship between immunization and Kawasaki disease 7.
A 2018 French case-crossover study found no association between vaccination and childhood immunoglobulin A vasculitis 8.
A 2016 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) 9.
Two 2018 US cohort studies found no increased risk of Kawasaki disease in infants receiving rotavirus vaccine 10,11.
A 2020 Taiwanese self-controlled case series analysis found a potential delayed increased risk of Kawasaki disease after rotavirus vaccination 12.
A 2017 South Korean nationwide cohort study found no associations between HPV vaccination and 33 predefined serious adverse events (including vasculitis) 13.
A 2020 systematic review and meta-analysis found no association between HPV vaccines and many autoimmune or other rare diseases (including vasculitis) 14.
A 2019 VSD study found no association between 13-valent pneumococcal conjugate vaccine (PCV13) and Kawasaki disease 15.
A 2019 self-controlled case series analysis of hospitalization data from Singapore found no association between PCV13 and overall Kawasaki disease; a marginal association with complete Kawasaki disease after the first dose of PCV13 in children younger than two years was found, though this could have been a chance finding given no adjustment was made for multiple comparisons 16,17.
A 2020 self-controlled case series analysis using national English data found no increased risk of Kawasaki disease after pneumococcal conjugate or meningococcal B vaccine 18. Analyses of safety surveillance data from the Vaccine Safety Datalink found no significant associations between mRNA COVID-19 vaccines and 23 serious health outcomes (including Kawasaki disease) 19.
Proposed Biological Mechanism
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 20, and three cases of PAN after hepatitis B vaccine 21-24; 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.
* These conclusions do not necessarily consider vaccines recommended only for special populations in the United States such as Yellow Fever vaccine (international travelers) or Smallpox vaccine (military personnel), or vaccines no longer recommended to the public such as the Janssen (J&J) COVID-19 vaccine.
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