Do Vaccines Cause Vasculitis or Polyarteritis Nodosa?

Updated November 10, 2023



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.

Epidemiological evidence

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.


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.

2.         Stassen PM, Sanders JS, Kallenberg CG, Stegeman CA. Influenza vaccination does not result in an increase in relapses in patients with ANCA-associated vasculitis. Nephrol Dial Transplant 2008; 23(2): 654-8.

3.         Holvast A, Stegeman CA, Benne CA, Huckriede A, Wilschut JC, Palache AM, Kallenberg CG, Bijl M. Wegener’s granulomatosis patients show an adequate antibody response to influenza vaccination. Ann Rheum Dis 2009; 68(6): 873-8.

4.         Jeffs LS, Peh CA, Jose MD, Lange K, Hurtado PR. Randomized trial investigating the safety and efficacy of influenza vaccination in patients with antineutrophil cytoplasmic antibody-associated vasculitis. Nephrology (Carlton, Vic) 2015; 20(5): 343-51.

5.         Kerneis S, Turbelin C, Pagnoux C, Launay O, Mahr AD, Guillevin L, Boelle PY, Hanslik T. Do vaccinations affect the clinical course of systemic necrotising vasculitis? A prospective observational web-based study. Clinical and experimental rheumatology 2016; 34(3 Suppl 97): S89-92.

6.         Abrams JY, Weintraub ES, Baggs JM, McCarthy NL, Schonberger LB, Lee GM, Klein NP, Belongia EA, Jackson ML, Naleway AL, Nordin JD, Hambidge SJ, Belay ED. Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006. Vaccine 2015; 33(2): 382-7.

7.         Phuong LK, Bonetto C, Buttery J, Pernus YB, Chandler R, Felicetti P, Goldenthal KL, Kucuku M, Monaco G, Pahud B, Shulman ST, Top KA, Trotta F, Ulloa-Gutierrez R, Varricchio F, de Ferranti S, Newburger JW, Dahdah N, Singh S, Bonhoeffer J, Burgner D. Kawasaki disease and immunisation: A systematic review. Vaccine 2017; 35(14): 1770-9.

8.         Piram M, Gonzalez Chiappe S, Madhi F, Ulinski T, Mahr A. Vaccination and Risk of Childhood IgA Vasculitis. Pediatrics 2018; 142(5).

9.         Da Dalt L, Zerbinati C, Strafella MS, Renna S, Riceputi L, Di Pietro P, Barabino P, Scanferla S, Raucci U, Mores N, Compagnone A, Da Cas R, Menniti-Ippolito F. Henoch-Schonlein purpura and drug and vaccine use in childhood: a case-control study. Italian journal of pediatrics 2016; 42(1): 60.

10.       Layton JB, Butler AM, Panozzo CA, Brookhart MA. Rotavirus vaccination and short-term risk of adverse events in US infants. Paediatric and perinatal epidemiology 2018; 32(5): 448-57.

11.       Hoffman V, Abu-Elyazeed R, Enger C, Esposito DB, Doherty MC, Quinlan SC, Skerry K, Holick CN, Basile P, Friedland LR, Praet N, Wéry S, Willame C, Dore DD, Rosillon D. Safety study of live, oral human rotavirus vaccine: A cohort study in United States health insurance plans. Human vaccines & immunotherapeutics 2018; 14(7): 1782-90.

12.       Huang WT, Juan YC, Liu CH, Yang YY, Chan KA. Intussusception and Kawasaki disease after rotavirus vaccination in Taiwanese infants. Vaccine 2020; 38(40): 6299-303.

13.       Yoon D, Lee JH, Lee H, Shin JY. Association between human papillomavirus vaccination and serious adverse events in South Korean adolescent girls: nationwide cohort study. BMJ (Clinical research ed) 2021; 372: m4931.

14.       Willame C, Gadroen K, Bramer W, Weibel D, Sturkenboom M. Systematic Review and Meta-analysis of Postlicensure Observational Studies on Human Papillomavirus Vaccination and Autoimmune and Other Rare Adverse Events. The Pediatric infectious disease journal 2020; 39(4): 287-93.

15.       Baker MA, Baer B, Kulldorff M, Zichittella L, Reindel R, DeLuccia S, Lipowicz H, Freitas K, Jin R, Yih WK. Kawasaki disease and 13-valent pneumococcal conjugate vaccination among young children: A self-controlled risk interval and cohort study with null results. PLoS medicine 2019; 16(7): e1002844.

16.       Yung CF, Ma X, Cheung YB, Oh BK, Soh S, Thoon KC. Kawasaki Disease following administration of 13-valent pneumococcal conjugate vaccine in young children. Scientific reports 2019; 9(1): 14705.

17.       Yung CF, Ma X, Cheung YB, Oh BK, Soh S, Thoon KC. Author Correction: Kawasaki Disease following administration of 13-valent pneumococcal conjugate vaccine in young children. Scientific reports 2021; 11(1): 8368.

18.       Stowe J, Andrews NJ, Turner PJ, Miller E. The risk of Kawasaki disease after pneumococcal conjugate & meningococcal B vaccine in England: A self-controlled case-series analysis. Vaccine 2020; 38(32): 4935-9.

19.       Klein NP, Lewis N, Goddard K, Fireman B, Zerbo O, Hanson KE, Donahue JG, Kharbanda EO, Naleway A, Nelson JC, Xu S, Yih WK, Glanz JM, Williams JTB, Hambidge SJ, Lewin BJ, Shimabukuro TT, DeStefano F, Weintraub ES. Surveillance for Adverse Events After COVID-19 mRNA Vaccination. Jama 2021; 326(14): 1390-9.

20.       Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K, Haber P. Safety of trivalent inactivated influenza vaccines in adults: background for pandemic influenza vaccine safety monitoring. Vaccine 2009; 27(15): 2114-20.

21.       Begier EM, Langford CA, Sneller MC, Wise RP, Ball R. Polyarteritis nodosa reports to the vaccine adverse event reporting system (VAERS): implications for assessment of suspected vaccine-provoked vasculitis. The Journal of rheumatology 2004; 31(11): 2181-8.

22.       Bourgeais AM, Dore MX, Croue A, Leclech C, Verret JL. [Cutaneous polyarteritis nodosa following hepatitis B vaccination]. Ann Dermatol Venereol 2003; 130(2 Pt 1): 205-7.

23.       De Keyser F, Naeyaert JM, Hindryckx P, Elewaut D, Verplancke P, Peene I, Praet M, Veys E. Immune-mediated pathology following hepatitis B vaccination. Two cases of polyarteritis nodosa and one case of pityriasis rosea-like drug eruption. Clin Exp Rheumatol 2000; 18(1): 81-5. 24.       Ventura F, Antunes H, Brito C, Pardal F, Pereira T, Vieira AP. Cutaneous polyarteritis nodosa in a child following hepatitis B vaccination. Eur J Dermatol 2009; 19(4): 400-1.