Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Vaccination of patients with autoimmune inflammatory rheumatic diseases

Key Points

  • As patients with an autoimmune inflammatory rheumatic disease (AIRD) are at increased risk of infection, vaccination could be of paramount importance

  • Vaccination of patients with an AIRD is complicated by possible decreased efficacy of the vaccine and the risk of exacerbating underlying disease

  • Most vaccinations of patients with an AIRD seem to be effective; however, efficacy is dependent on the vaccine used, the type of AIRD and the medication regimen

  • Although some vaccines have been reported to induce autoimmune disorders, disease activity was not increased after vaccination in studies evaluating vaccination of patients with an AIRD

  • More research on vaccination of patients with an AIRD is needed, in particular regarding infections, adverse effects of vaccination and the influence of immunomodulatory therapies on vaccination efficacy

Abstract

Patients with autoimmune inflammatory rheumatic diseases (AIRDs) are at increased risk of infections. This risk has been further increased by the introduction of biologic agents over the past two decades. One of the most effective strategies to prevent infection is vaccination. However, patients with an AIRD have a compromised immune system, which is further impaired by medication. Another important issue is the possibility of triggering a broad nonspecific response by vaccination, potentially resulting in increased activity of the underlying autoimmune disease. In this Review, we provide an analysis of data on vaccination of patients with an AIRD. Both the efficacy and the safety of vaccination are addressed, together with the epidemiology of vaccine-preventable infectious diseases in different subgroups of adults with AIRDs. Special attention is given to vaccination of patients who are treated with biologic agents.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Treatment-related RR of herpes zoster in RA.
Figure 2: Recommended vaccinations for patients with an AIRD.

References

  1. 1

    Mandell, B. F. Vaccination: an option not to be ignored. Cleve. Clin. J. Med. 77, 151 (2010).

    PubMed  Article  Google Scholar 

  2. 2

    Plotkin, S. A. Vaccines: correlates of vaccine-induced immunity. Clin. Infect. Dis. 47, 401–409 (2008).

    PubMed  Article  Google Scholar 

  3. 3

    Touma, Z., Gladman, D. D. & Urowitz, M. B. Vaccination and auto-immune rheumatic diseases: lessons learnt from the 2009 H1N1 influenza virus vaccination campaign. Curr. Opin. Rheumatol. 25, 164–170 (2013).

    CAS  PubMed  Article  Google Scholar 

  4. 4

    Murdaca, G. et al. Influenza and pneumococcal vaccinations of patients with systemic lupus erythematosus: current views upon safety and immunogenicity. Autoimmun. Rev. 13, 75–84 (2014).

    CAS  PubMed  Article  Google Scholar 

  5. 5

    Van Assen, S. et al. Vaccination in adult patients with auto-immune inflammatory rheumatic diseases: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases. Autoimmun. Rev. 10, 341–352 (2011).

    CAS  PubMed  Article  Google Scholar 

  6. 6

    Hohensinner, P. J., Goronzy, J. J. & Weyand, C. M. Telomere dysfunction, autoimmunity and aging. Aging Dis. 2, 524–537 (2011).

    PubMed  PubMed Central  Google Scholar 

  7. 7

    Stampfli, M. R. & Anderson, G. P. How cigarette smoke skews immune responses to promote infection, lung disease and cancer. Nat. Rev. Immunol. 9, 377–384 (2009).

    PubMed  Article  CAS  Google Scholar 

  8. 8

    Listing, J., Gerhold, K. & Zink, A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford) 52, 53–61 (2013).

    CAS  Article  Google Scholar 

  9. 9

    Germano, V. et al. Infection risk in rheumatoid arthritis and spondyloarthropathy patients under treatment with DMARDs, corticosteroids and TNF-α antagonists. J. Transl. Med. http://dx.doi.org/10.1186/1479-5876-12-77.

  10. 10

    Sciascia, S., Cuadrado, M. J. & Karim, M. Y. Management of infection in systemic lupus erythematosus. Best Pract. Res. Clin. Rheumatol. 27, 377–389 (2013).

    PubMed  Article  Google Scholar 

  11. 11

    Curtis, J. R. et al. Risk of hospitalized bacterial infections associated with biologic treatment among US veterans with rheumatoid arthritis. Arthritis Care Res. (Hoboken) 66, 990–997 (2014).

    CAS  Article  Google Scholar 

  12. 12

    Ruiz-Irastorza, G. et al. Predictors of major infections in systemic lupus erythematosus. Arthritis Res. Ther. 11, R109 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  13. 13

    Nichol, K. L., Wuorenma, J. & von Sternberg, T. Benefits of influenza vaccination for low-, intermediate-, and high-risk senior citizens. Arch. Intern. Med. 158, 1769–1776 (1998).

    CAS  PubMed  Article  Google Scholar 

  14. 14

    Hak, E. et al. Influence of high-risk medical conditions on the effectiveness of influenza vaccination among elderly members of 3 large managed-care organizations. Clin. Infect. Dis. 35, 370–377 (2002).

    PubMed  Article  Google Scholar 

  15. 15

    Blumentals, W. A., Arreglado, A., Napalkov, P. & Toovey, S. Rheumatoid arthritis and the incidence of influenza and influenza-related complications: a retrospective cohort study. BMC Musculoskelet. Disord. 13, 158 (2012).

    PubMed  PubMed Central  Article  Google Scholar 

  16. 16

    Wotton, C. J. & Goldacre, M. J. Risk of invasive pneumococcal disease in people admitted to hospital with selected immune-mediated diseases: record linkage cohort analyses. J. Epidemiol. Community Health 66, 1177–1181 (2012).

    PubMed  Article  Google Scholar 

  17. 17

    Yee, A. M., Ng, S. C., Sobel, R. E. & Salmon, J. E. FcγRIIA polymorphism as a risk factor for invasive pneumococcal infections in systemic lupus erythematosus. Arthritis Rheum. 40, 1180–1182 (1997).

    CAS  PubMed  Article  Google Scholar 

  18. 18

    Klippel, J. H. et al. A controlled study of pneumococcal polysaccharide vaccine in systemic lupus erythematosus. Arthritis Rheum. 22, 1321–1325 (1979).

    CAS  PubMed  Article  Google Scholar 

  19. 19

    Naveau, C. & Houssiau, F. A. Pneumococcal sepsis in patients with systemic lupus erythematosus. Lupus 14, 903–906 (2005).

    CAS  PubMed  Article  Google Scholar 

  20. 20

    Lu, T. Y. et al. A retrospective seven-year analysis of the use of B cell depletion therapy in systemic lupus erythematosus at University College London Hospital: the first fifty patients. Arthritis Rheum. 61, 482–487 (2009).

    Article  Google Scholar 

  21. 21

    Favalli, E. G. et al. Serious infections during anti-TNFα treatment in rheumatoid arthritis patients. Autoimmun. Rev. 8, 266–273 (2009).

    CAS  PubMed  Article  Google Scholar 

  22. 22

    Strangfeld, A. et al. Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-α agents. JAMA 301, 737–744 (2009).

    CAS  PubMed  Article  Google Scholar 

  23. 23

    Antonelli, M. A., Moreland, L. W. & Brick, J. E. Herpes zoster in patients with rheumatoid arthritis treated with weekly, low-dose methotrexate. Am. J. Med. 90, 295–298 (1991).

    CAS  PubMed  Article  Google Scholar 

  24. 24

    McDonald, J. R. et al. Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis. Clin. Infect. Dis. 48, 1364–1371 (2009).

    PubMed  PubMed Central  Article  Google Scholar 

  25. 25

    Smitten, A. L. et al. The risk of herpes zoster in patients with rheumatoid arthritis in the United States and the United Kingdom. Arthritis Rheum. 57, 1431–1438 (2007).

    PubMed  Article  Google Scholar 

  26. 26

    Speerstra, F. et al. Side-effects of azathioprine treatment in rheumatoid arthritis: analysis of 10 years of experience. Ann. Rheum. Dis. 41, (Suppl. 1) 37–39 (1982).

    PubMed  PubMed Central  Article  Google Scholar 

  27. 27

    Wolfe, F., Michaud, K. & Chakravarty, E. F. Rates and predictors of herpes zoster in patients with rheumatoid arthritis and non-inflammatory musculoskeletal disorders. Rheumatology (Oxford) 45, 1370–1375 (2006).

    CAS  Article  Google Scholar 

  28. 28

    Garcia-Doval, I. et al. Incidence and risk of hospitalisation due to shingles and chickenpox in patients with rheumatic diseases treated with TNF antagonists. Ann. Rheum. Dis. 69, 1751–1755 (2010).

    CAS  PubMed  Article  Google Scholar 

  29. 29

    Winthrop, K. L. et al. Association between the initiation of anti-tumor necrosis factor therapy and the risk of herpes zoster. JAMA 309, 887–895 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30

    Ramiro, S. et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann. Rheum. Dis. 73, 529–535 (2014).

    CAS  PubMed  Article  Google Scholar 

  31. 31

    Kahl, L. E. Herpes zoster infections in systemic lupus erythematosus: risk factors and outcome. J. Rheumatol. 21, 84–86 (1994).

    CAS  PubMed  Google Scholar 

  32. 32

    Kang, T. Y., Lee, H. S., Kim, T. H., Jun, J. B. & Yoo, D. H. Clinical and genetic risk factors of herpes zoster in patients with systemic lupus erythematosus. Rheumatol. Int. 25, 97–102 (2005).

    PubMed  Article  Google Scholar 

  33. 33

    Manzi, S. et al. Herpes zoster in systemic lupus erythematosus. J. Rheumatol. 22, 1254–1258 (1995).

    CAS  PubMed  Google Scholar 

  34. 34

    Chakravarty, E. F., Michaud, K., Katz, R. & Wolfe, F. Increased incidence of herpes zoster among patients with systemic lupus erythematosus. Lupus 22, 238–244 (2013).

    CAS  PubMed  Article  Google Scholar 

  35. 35

    Ginzler, E. et al. Computer analysis of factors influencing frequency of infection in systemic lupus erythematosus. Arthritis Rheum. 21, 37–44 (1978).

    CAS  PubMed  Article  Google Scholar 

  36. 36

    Nagaoka, S. et al. Herpes zoster in patients with polymyositis and dermatomyositis. Kansenshogaku Zasshi 64, 1394–1399 (1990).

    CAS  PubMed  Article  Google Scholar 

  37. 37

    Nagasawa, K. et al. High incidence of herpes zoster in patients with systemic lupus erythematosus: an immunological analysis. Ann. Rheum. Dis. 49, 630–633 (1990).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  38. 38

    Wang, F., Chua, C. T. & Bosco, J. Herpes zoster in patients with systemic lupus erythematosus. Singapore Med. J. 24, 218–220 (1983).

    CAS  PubMed  Google Scholar 

  39. 39

    Dubois, E. L. & Tuffanelli, D. L. Clinical manifestations of systemic lupus erythematosus. Computer analysis of 520 cases. JAMA 190, 104–111 (1964).

    CAS  PubMed  Article  Google Scholar 

  40. 40

    Ishikawa, O., Abe, M. & Miyachi, Y. Herpes zoster in Japanese patients with systemic lupus erythematosus. Clin. Exp. Dermatol. 24, 327–328 (1999).

    CAS  PubMed  Article  Google Scholar 

  41. 41

    Janwityanuchit, S., Totemchokchyakarn, K., Krachangwongchai, K. & Vatanasuk, M. Infection in systemic lupus erythematosus. J. Med. Assoc. Thai. 76, 542–548 (1993).

    CAS  PubMed  Google Scholar 

  42. 42

    Moutsopoulos, H. M., Gallagher, J. D., Decker, J. L. & Steinberg, A. D. Herpes zoster in patients with systemic lupus erythematosus. Arthritis Rheum. 21, 798–802 (1978).

    CAS  PubMed  Article  Google Scholar 

  43. 43

    Borba, E. F. et al. Incidence, risk factors, and outcome of Herpes zoster in systemic lupus erythematosus. J. Clin. Rheumatol. 16, 119–122 (2010).

    PubMed  Article  Google Scholar 

  44. 44

    Della-Torre, E. et al. Individualized therapy provides better outcome in patients with proliferative lupus nephritis: follow up of a cohort of Italian patients [abstract]. Ann. Rheum. Dis. 68 (Suppl. 3), 247 (2009).

    Google Scholar 

  45. 45

    Tokunaga, M. et al. Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann. Rheum. Dis. 66, 470–475 (2007).

    CAS  Article  Google Scholar 

  46. 46

    Mak, A. et al. Mycophenolate mofetil is as efficacious as, but safer than, cyclophosphamide in the treatment of proliferative lupus nephritis: a meta-analysis and meta-regression. Rheumatology (Oxford) 48, 944–952 (2009).

    CAS  Article  Google Scholar 

  47. 47

    Merrill, J. T. et al. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 62, 222–233 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. 48

    Wung, P. K. et al. Herpes zoster in immunocompromised patients: incidence, timing, and risk factors. Am. J. Med. 118, 1416 (2005).

    PubMed  Article  Google Scholar 

  49. 49

    Tam, L. S., Chan, A. Y., Chan, P. K., Chang, A. R. & Li, E. K. Increased prevalence of squamous intraepithelial lesions in systemic lupus erythematosus: association with human papillomavirus infection. Arthritis Rheum. 50, 3619–3625 (2004).

    PubMed  Article  Google Scholar 

  50. 50

    Nath, R. et al. High risk of human papillomavirus type 16 infections and of development of cervical squamous intraepithelial lesions in systemic lupus erythematosus patients. Arthritis Rheum. 57, 619–625 (2007).

    CAS  PubMed  Article  Google Scholar 

  51. 51

    Lee, Y. H. et al. Prevalence of human papilloma virus infections and cervical cytological abnormalities among Korean women with systemic lupus erythematosus. J. Korean Med. Sci. 25, 1431–1437 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  52. 52

    Tam, L. S. et al. Natural history of cervical papilloma virus infection in systemic lupus erythematosus - a prospective cohort study. J. Rheumatol. 37, 330–340 (2010).

    PubMed  Article  Google Scholar 

  53. 53

    Stojanovich, L. Influenza vaccination of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Clin. Dev. Immunol. 13, 373–375 (2006).

    PubMed  PubMed Central  Article  Google Scholar 

  54. 54

    Kobashigawa, T. et al. Vaccination against seasonal influenza is effective in Japanese patients with rheumatoid arthritis enrolled in a large observational cohort. Scand. J. Rheumatol. 42, 445–450 (2013).

    CAS  PubMed  Article  Google Scholar 

  55. 55

    Kostianovsky, A. et al. Immunogenicity and safety of seasonal and 2009 pandemic A/H1N1 influenza vaccines for patients with autoimmune diseases: a prospective, monocentre trial on 199 patients. Clin. Exp. Rheumatol. 30 (1 Suppl. 70), S83–S89 (2012).

    PubMed  Google Scholar 

  56. 56

    De Jong, J. C. et al. Haemagglutination-inhibiting antibody to influenza virus. Dev. Biol. (Basel) 115, 63–73 (2003).

    CAS  Google Scholar 

  57. 57

    Chalmers, A. et al. Immunization of patients with rheumatoid arthritis against influenza: a study of vaccine safety and immunogenicity. J. Rheumatol. 21, 1203–1206 (1994).

    CAS  PubMed  Google Scholar 

  58. 58

    Del Porto, F. et al. Influenza vaccine administration in patients with systemic lupus erythematosus and rheumatoid arthritis. Safety and immunogenicity. Vaccine 24, 3217–3223 (2006).

    CAS  PubMed  Article  Google Scholar 

  59. 59

    Denman, E. J., Denman, A. M., Greenwood, B. M., Gall, D. & Heath, R. B. Failure of cytotoxic drugs to suppress immune responses of patients with rheumatoid arthritis. Ann. Rheum. Dis. 29, 220–231 (1970).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  60. 60

    Fomin, I. et al. Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying drugs, including TNF α blockers. Ann. Rheum. Dis. 65, 191–194 (2006).

    CAS  PubMed  Article  Google Scholar 

  61. 61

    Gelinck, L. B. et al. The effect of anti-tumour necrosis factor α treatment on the antibody response to influenza vaccination. Ann. Rheum. Dis. 67, 713–716 (2008).

    CAS  PubMed  Article  Google Scholar 

  62. 62

    Herron, A. et al. Influenza vaccination in patients with rheumatic diseases. Safety and efficacy. JAMA 242, 53–56 (1979).

    CAS  PubMed  Article  Google Scholar 

  63. 63

    Kaine, J. L., Kivitz, A. J., Birbara, C. & Luo, A. Y. Immune responses following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab. J. Rheumatol. 34, 272–279 (2007).

    CAS  PubMed  Google Scholar 

  64. 64

    Kubota, T. et al. Anti-tumor necrosis factor therapy does not diminish the immune response to influenza vaccine in Japanese patients with rheumatoid arthritis. Mod. Rheumatol. 17, 531–533 (2007).

    PubMed  Article  Google Scholar 

  65. 65

    Nii, T. et al. Reevaluation of antibody titers 1 year after influenza vaccination in patients with rheumatoid arthritis receiving TNF blockers. Mod. Rheumatol. 19, 216–218 (2009).

    PubMed  Article  Google Scholar 

  66. 66

    Turner-Stokes, L., Cambridge, G., Corcoran, T., Oxford, J. S. & Snaith, M. L. In vitro response to influenza immunisation by peripheral blood mononuclear cells from patients with systemic lupus erythematosus and other autoimmune diseases. Ann. Rheum. Dis. 47, 532–535 (1988).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. 67

    Van Assen, S. et al. Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum. 62, 75–81 (2010).

    CAS  PubMed  Article  Google Scholar 

  68. 68

    Elkayam, O. Safety and efficacy of vaccination against influenza in patients with rheumatoid arthritis. Clin. Dev. Immunol. 13, 349–351 (2006).

    PubMed  PubMed Central  Article  Google Scholar 

  69. 69

    Kapetanovic, M. C., Saxne, T., Nilsson, J. A. & Geborek, P. Influenza vaccination as model for testing immune modulation induced by anti-TNF and methotrexate therapy in rheumatoid arthritis patients. Rheumatology (Oxford) 46, 608–611 (2007).

    CAS  Article  Google Scholar 

  70. 70

    Kivitz, A. J. et al. Vaccine responses in patients with rheumatoid arthritis treated with certolizumab pegol: results from a single-blind randomized phase IV trial. J. Rheumatol. 41, 648–657 (2014).

    CAS  PubMed  Article  Google Scholar 

  71. 71

    Elkayam, O. et al. The effect of infliximab and timing of vaccination on the humoral response to influenza vaccination in patients with rheumatoid arthritis and ankylosing spondylitis. Semin. Arthritis Rheum. 39, 442–447 (2010).

    CAS  PubMed  Article  Google Scholar 

  72. 72

    Gelinck, L. B. et al. Poor serological responses upon influenza vaccination in patients with rheumatoid arthritis treated with rituximab. Ann. Rheum. Dis. 66, 1402–1403 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  73. 73

    Kapetanovic, M. C. Further evidence for influenza and pneumococcal vaccination in patients treated with disease modifying antirheumatic drugs and anti-tumor necrosis factor agents. J. Rheumatol. 41, 626–628 (2014).

    CAS  PubMed  Article  Google Scholar 

  74. 74

    Kapetanovic, M. C. et al. Impact of anti-rheumatic treatment on immunogenicity of pandemic H1N1 influenza vaccine in patients with arthritis. Arthritis Res. Ther. 16, R2 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  75. 75

    Oren, S. et al. Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response. Ann. Rheum. Dis. 67, 937–941 (2008).

    CAS  PubMed  Article  Google Scholar 

  76. 76

    Elkayam, O. et al. Efficacy and safety of vaccination against pandemic 2009 influenza A (H1N1) virus among patients with rheumatic diseases. Arthritis Care Res. (Hoboken) 63, 1062–1067 (2011).

    Article  Google Scholar 

  77. 77

    Mori, S. et al. Impact of tocilizumab therapy on antibody response to influenza vaccine in patients with rheumatoid arthritis. Ann. Rheum. Dis. 71, 2006–2010 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  78. 78

    Ribeiro, A. C. et al. Abatacept and reduced immune response to pandemic 2009 influenza A/H1N1 vaccination in patients with rheumatoid arthritis. Arthritis Care Res. (Hoboken) 65, 476–480 (2013).

    CAS  Article  Google Scholar 

  79. 79

    Williams, G. W. et al. Influenza immunization in systemic lupus eruthematosus. A double-blind trial. Ann. Intern. Med. 88, 729–734 (1978).

    CAS  PubMed  Article  Google Scholar 

  80. 80

    Holvast, A. et al. Safety and efficacy of influenza vaccination in systemic lupus erythematosus patients with quiescent disease. Ann. Rheum. Dis. 65, 913–918 (2006).

    CAS  PubMed  Article  Google Scholar 

  81. 81

    Mercado, U., Acosta, H. & Avendano, L. Influenza vaccination of patients with systemic lupus erythematosus. Rev. Invest. Clin. 56, 16–20 (2004).

    PubMed  Google Scholar 

  82. 82

    Wiesik-Szewczyk, E. et al. Anti-influenza vaccination in systemic lupus erythematosus patients: an analysis of specific humoral response and vaccination safety. Clin. Rheumatol. 29, 605–613 (2010).

    PubMed  Article  Google Scholar 

  83. 83

    Brodman, R., Gilfillan, R., Glass, D. & Schur, P. H. Influenzal vaccine response in systemic lupus erythematosus. Ann. Intern. Med. 88, 735–740 (1978).

    CAS  PubMed  Article  Google Scholar 

  84. 84

    Louie, J. S. et al. Clinical and antibody responses after influenza immunization in systemic lupus erythematosus. Ann. Intern. Med. 88, 790–792 (1978).

    CAS  PubMed  Article  Google Scholar 

  85. 85

    Pons, V. G., Reinertsen, J. L., Steinberg, A. D. & Dolin, R. Decreased cell-mediated cytotoxicity against virus-infected cells in systemic lupus erythematosus. J. Med. Virol. 4, 15–23 (1979).

    CAS  PubMed  Article  Google Scholar 

  86. 86

    Ristow, S. C., Douglas, R. G. Jr & Condemi, J. J. Influenza vaccination of patients with systemic lupus erythematosus. Ann. Intern. Med. 88, 786–789 (1978).

    CAS  PubMed  Article  Google Scholar 

  87. 87

    Abu-Shakra, M. et al. Specific antibody response after influenza immunization in systemic lupus erythematosus. J. Rheumatol. 29, 2555–2557 (2002).

    CAS  PubMed  Google Scholar 

  88. 88

    Crowe, S. R. et al. Influenza vaccination responses in human systemic lupus erythematosus: impact of clinical and demographic features. Arthritis Rheum. 63, 2396–2406 (2011).

    PubMed  PubMed Central  Article  Google Scholar 

  89. 89

    Holvast, A. et al. Effect of a second, booster, influenza vaccination on antibody responses in quiescent systemic lupus erythematosus: an open, prospective, controlled study. Rheumatology (Oxford) 48, 1294–1299 (2009).

    Article  Google Scholar 

  90. 90

    Holvast, A. et al. Wegener's granulomatosis patients show an adequate antibody response to influenza vaccination. Ann. Rheum. Dis. 68, 873–878 (2009).

    CAS  PubMed  Article  Google Scholar 

  91. 91

    Zycinska, K. et al. Antibody response to inactivated subunit influenza vaccine in patients with Wegener's granulomatosis. J. Physiol. Pharmacol. 58 (Suppl. 5), 819–828 (2007).

    PubMed  Google Scholar 

  92. 92

    Setti, M. et al. Flu vaccination with a virosomal vaccine does not affect clinical course and immunological parameters in scleroderma patients. Vaccine 27, 3367–3372 (2009).

    CAS  PubMed  Article  Google Scholar 

  93. 93

    Saad, C. G. et al. Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases. Ann. Rheum. Dis. 70, 1068–1073 (2011).

    PubMed  Article  Google Scholar 

  94. 94

    Gabay, C. et al. Impact of synthetic and biologic disease-modifying antirheumatic drugs on antibody responses to the AS03-adjuvanted pandemic influenza vaccine: a prospective, open-label, parallel-cohort, single-center study. Arthritis Rheum. 63, 1486–1496 (2011).

    CAS  PubMed  Article  Google Scholar 

  95. 95

    Iwamoto, M. et al. Low level of seroconversion after a novel influenza A/H1N1/2009 vaccination in Japanese patients with rheumatoid arthritis in the 2009 season. Rheumatol. Int. 32, 3691–3694 (2012).

    CAS  PubMed  Article  Google Scholar 

  96. 96

    Mathian, A. et al. Factors influencing the efficacy of two injections of a pandemic 2009 influenza A (H1N1) nonadjuvanted vaccine in systemic lupus erythematosus. Arthritis Rheum. 63, 3502–3511 (2011).

    CAS  PubMed  Article  Google Scholar 

  97. 97

    Lu, C. C. et al. A/H1N1 influenza vaccination in patients with systemic lupus erythematosus: safety and immunity. Vaccine 29, 444–450 (2011).

    PubMed  Article  Google Scholar 

  98. 98

    Pasoto, S. G. et al. Short and long-term effects of pandemic unadjuvanted influenza A(H1N1)pdm09 vaccine on clinical manifestations and autoantibody profile in primary Sjögren's syndrome. Vaccine 31, 1793–1798 (2013).

    CAS  PubMed  Article  Google Scholar 

  99. 99

    Arad, U. et al. The cellular immune response to influenza vaccination is preserved in rheumatoid arthritis patients treated with rituximab. Vaccine 29, 1643–1648 (2011).

    CAS  PubMed  Article  Google Scholar 

  100. 100

    Holvast, A. et al. Studies of cell-mediated immune responses to influenza vaccination in systemic lupus erythematosus. Arthritis Rheum. 60, 2438–2447 (2009).

    CAS  PubMed  Article  Google Scholar 

  101. 101

    Coulson, E. et al. Pneumococcal antibody levels after pneumovax in patients with rheumatoid arthritis on methotrexate. Ann. Rheum. Dis. 70, 1289–1291 (2011).

    CAS  PubMed  Article  Google Scholar 

  102. 102

    Visvanathan, S., Keenan, G. F., Baker, D. G., Levinson, A. I. & Wagner, C. L. Response to pneumococcal vaccine in patients with early rheumatoid arthritis receiving infliximab plus methotrexate or methotrexate alone. J. Rheumatol. 34, 952–957 (2007).

    CAS  PubMed  Google Scholar 

  103. 103

    Kapetanovic, M. C. et al. Influence of methotrexate, TNF blockers and prednisolone on antibody responses to pneumococcal polysaccharide vaccine in patients with rheumatoid arthritis. Rheumatology (Oxford) 45, 106–111 (2006).

    CAS  Article  Google Scholar 

  104. 104

    Bingham, C. O. 3rd et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 62, 64–74 (2010).

    CAS  PubMed  Article  Google Scholar 

  105. 105

    Elkayam, O. et al. Immunogenicity and safety of pneumococcal vaccination in patients with rheumatoid arthritis or systemic lupus erythematosus. Clin. Infect. Dis. 34, 147–153 (2002).

    PubMed  Article  Google Scholar 

  106. 106

    Elkayam, O., Caspi, D., Reitblatt, T., Charboneau, D. & Rubins, J. B. The effect of tumor necrosis factor blockade on the response to pneumococcal vaccination in patients with rheumatoid arthritis and ankylosing spondylitis. Semin. Arthritis Rheum. 33, 283–288 (2004).

    CAS  PubMed  Article  Google Scholar 

  107. 107

    Kapetanovic, M. C. et al. Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors. Arthritis Rheum. 63, 3723–3732 (2011).

    CAS  PubMed  Article  Google Scholar 

  108. 108

    Kapetanovic, M. C., Roseman, C., Jönsson, G. & Truedsson, L. Heptavalent pneumococcal conjugate vaccine elicits similar antibody response as standard 23-valent polysaccharide vaccine in adult patients with RA treated with immunomodulating drugs. Clin. Rheumatol. 30, 1555–1561 (2011).

    PubMed  Article  Google Scholar 

  109. 109

    Mori, S. et al. Pneumococcal polysaccharide vaccination in rheumatoid arthritis patients receiving tocilizumab therapy. Ann. Rheum. Dis. 72, 1362–1366 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  110. 110

    Bingham, C. O. 3rd et al. Humoral immune response to vaccines in patients with rheumatoid arthritis treated with tocilizumab: results of a randomised controlled trial (VISARA). Ann. Rheum. Dis. http://dx.doi.org/10.1136/annrheumdis-2013-204427.

  111. 111

    Croft, S. M. et al. Specific antibody response after in vivo antigenic stimulation in systemic lupus erythematosus. J. Rheumatol. 11, 141–146 (1984).

    CAS  PubMed  Google Scholar 

  112. 112

    Lipnick, R. N. et al. Pneumococcal immunization in patients with systemic lupus erythematosus treated with immunosuppressives. J. Rheumatol. 12, 1118–1121 (1985).

    CAS  PubMed  Google Scholar 

  113. 113

    Battafarano, D. F. et al. Antigen-specific antibody responses in lupus patients following immunization. Arthritis Rheum. 41, 1828–1834 (1998).

    CAS  PubMed  Article  Google Scholar 

  114. 114

    Jarrett, M. P., Schiffman, G., Barland, P. & Grayzel, A. I. Impaired response to pneumococcal vaccine in systemic lupus erythematosus. Arthritis Rheum. 23, 1287–1293 (1980).

    CAS  PubMed  Article  Google Scholar 

  115. 115

    McDonald, E., Jarrett, M. P., Schiffman, G. & Grayzel, A. I. Persistence of pneumococcal antibodies after immunization in patients with systemic lupus erythematosus. J. Rheumatol. 11, 306–308 (1984).

    CAS  PubMed  Google Scholar 

  116. 116

    Tarjan, P. et al. No short-term immunological effects of Pneumococcus vaccination in patients with systemic lupus erythematosus. Scand. J. Rheumatol. 31, 211–215 (2002).

    CAS  PubMed  Article  Google Scholar 

  117. 117

    Franco Salinas, G. et al. TNF blockade impairs T cell dependent antibody responses [abstract]. Ann. Rheum. Dis. 68 (Suppl. 3), 238 (2009).

    Google Scholar 

  118. 118

    Mease, P. J. et al. Pneumococcal vaccine response in psoriatic arthritis patients during treatment with etanercept. J. Rheumatol. 31, 1356–1361 (2004).

    CAS  PubMed  Google Scholar 

  119. 119

    Mercado, U., Acosta, H. & Diaz-Molina, R. Antibody response to pneumococcal polysaccharide vaccine in systemic sclerosis. J. Rheumatol. 36, 1549–1550 (2009).

    PubMed  Article  Google Scholar 

  120. 120

    Kuruma, K. A., Borba, E. F., Lopes, M. H., de Carvalho, J. F. & Bonfá, E. Safety and efficacy of hepatitis B vaccine in systemic lupus erythematosus. Lupus 16, 350–354 (2007).

    CAS  PubMed  Article  Google Scholar 

  121. 121

    Erkek, E., Ayaslioglu, E., Erkek, A. B., Kurtipek, G. S. & Bagci, Y. Response to vaccination against hepatitis B in patients with Behcet's disease. J. Gastroenterol. Hepatol. 20, 1508–1511 (2005).

    CAS  PubMed  Article  Google Scholar 

  122. 122

    Devey, M. E., Bleasdale, K. & Isenberg, D. A. Antibody affinity and IgG subclass of responses to tetanus toxoid in patients with rheumatoid arthritis and systemic lupus erythematosus. Clin. Exp. Immunol. 68, 562–569 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. 123

    Abe, T. & Homma, M. Immunological reactivity in patients with systemic lupus erythematosus. Humoral antibody and cellular immune responses. Acta Rheumatol. Scand. 17, 35–46 (1971).

    CAS  PubMed  Article  Google Scholar 

  124. 124

    Kashef, S., Ghazizadeh, F., Derakhshan, A., Farjadian, S. & Alyasin, S. Antigen-specific antibody response in juvenile-onset SLE patients following routine immunization with tetanus toxoid. Iran. J. Immunol. 5, 181–184 (2008).

    CAS  PubMed  Google Scholar 

  125. 125

    Nies, K., Boyer, R., Stevens, R. & Louie, J. Anti-tetanus toxoid antibody synthesis after booster immunization in systemic lupus erythematosus. Comparison of the in vitro and in vivo responses. Arthritis Rheum. 23, 1343–1350 (1980).

    CAS  PubMed  Article  Google Scholar 

  126. 126

    Askling, H. H. et al. Hepatitis A vaccine for immunosuppressed patients with rheumatoid arthritis: a prospective, open-label, multi-centre study. Travel Med. Infect. Dis. 12, 134–142 (2014).

    PubMed  Article  Google Scholar 

  127. 127

    Mok, C. C., Ho, L. Y., Fong, L. S. & To, C. H. Immunogenicity and safety of a quadrivalent human papillomavirus vaccine in patients with systemic lupus erythematosus: a case–control study. Ann. Rheum. Dis. 72, 659–664 (2013).

    CAS  PubMed  Article  Google Scholar 

  128. 128

    Soybilgic, A., Onel, K. B., Utset, T., Alexander, K. & Wagner-Weiner, L. Safety and immunogenicity of the quadrivalent HPV vaccine in female systemic lupus erythematosus patients aged 12 to 26 years. Pediatr. Rheumatol. Online J. 11, 29 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  129. 129

    Van Assen, S. et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann. Rheum. Dis. 70, 414–422 (2011).

    CAS  PubMed  Article  Google Scholar 

  130. 130

    Singh, J. A. et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care. Res. (Hoboken) 64, 625–639 (2012).

    CAS  Article  Google Scholar 

  131. 131

    Zhang, J. et al. Association between vaccination for herpes zoster and risk of herpes zoster infection among older patients with selected immune-mediated diseases. JAMA 308, 43–49 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. 132

    Guthridge, J. M. et al. Herpes zoster vaccination in SLE: a pilot study of immunogenicity. J. Rheumatol. 40, 1875–1880 (2013).

    CAS  PubMed  Article  Google Scholar 

  133. 133

    Shoenfeld, Y. & Agmon-Levin, N. 'ASIA' - autoimmune/inflammatory syndrome induced by adjuvants. J. Autoimmun. 36, 4–8 (2011).

    CAS  PubMed  Article  Google Scholar 

  134. 134

    Colafrancesco, S., Perricone, C., Priori, R., Valesini, G. & Shoenfeld, Y. Sjögren's syndrome: another facet of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). J. Autoimmun. 51, 10–16 (2014).

    CAS  PubMed  Article  Google Scholar 

  135. 135

    Perricone, C. et al. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: unveiling the pathogenic, clinical and diagnostic aspects. J. Autoimmun. 47, 1–16 (2013).

    CAS  PubMed  Article  Google Scholar 

  136. 136

    Borchers, A. T., Keen, C. L., Shoenfeld, Y., Silva, J. Jr & Gershwin, M. E. Vaccines, viruses, and voodoo. J. Investig. Allergol. Clin. Immunol. 12, 155–168 (2002).

    CAS  PubMed  Google Scholar 

  137. 137

    Bengtsson, C. et al. Common vaccinations among adults do not increase the risk of developing rheumatoid arthritis: results from the Swedish EIRA study. Ann. Rheum. Dis. 69, 1831–1833 (2010).

    CAS  PubMed  Article  Google Scholar 

  138. 138

    Grimaldi-Bensouda, L. et al. The risk of systemic lupus erythematosus associated with vaccines: an international case–control study. Arthritis Rheumatol. 66, 1559–1567 (2014).

    PubMed  Article  Google Scholar 

  139. 139

    Perdan-Pirkmajer, K. et al. Autoimmune response following influenza vaccination in patients with autoimmune inflammatory rheumatic disease. Lupus 21, 175–183 (2012).

    CAS  PubMed  Article  Google Scholar 

  140. 140

    Lu, C. C. et al. A/H1N1 influenza vaccination in patients with systemic lupus erythematosus: safety and immunity. Vaccine 29, 444–450 (2011).

    PubMed  Article  Google Scholar 

  141. 141

    Urowitz, M. B., Anton, A., Ibanez, D. & Gladman, D. D. Autoantibody response to adjuvant and nonadjuvant H1N1 vaccination in systemic lupus erythematosus. Arthritis Care Res. (Hoboken) 63, 1517–1520 (2011).

    CAS  Article  Google Scholar 

  142. 142

    Milanetti, F. et al. Safety and immunogenicity of co-administered MF59-adjuvanted 2009 pandemic and plain 2009–10 seasonal influenza vaccines in rheumatoid arthritis patients on biologicals. Clin. Exp. Immunol. 177, 287–294 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  143. 143

    Aikawa, N. E. et al. Effective seroconversion and safety following the pandemic influenza vaccination (anti-H1N1) in patients with juvenile idiopathic arthritis. Scand. J. Rheumatol. 42, 34–40 (2013).

    CAS  PubMed  Article  Google Scholar 

  144. 144

    Stassen, P. M., Sanders, J. S., Kallenberg, C. G. & Stegeman, C. A. Influenza vaccination does not result in an increase in relapses in patients with ANCA-associated vasculitis. Nephrol. Dial. Transplant. 23, 654–658 (2008).

    PubMed  Article  Google Scholar 

  145. 145

    Karsh, J., Pavlidis, N., Schiffman, G. & Moutsopoulos, H. M. Immunization of patients with Sjögren's syndrome with pneumococcal polysaccharide vaccine: a randomized trial. Arthritis Rheum. 23, 1294–1298 (1980).

    CAS  PubMed  Article  Google Scholar 

  146. 146

    Grimaldi-Bensouda, L. et al. Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects. J. Intern. Med. 275, 398–408 (2014).

    CAS  PubMed  Article  Google Scholar 

  147. 147

    Gatto, M. et al. Human papillomavirus vaccine and systemic lupus erythematosus. Clin. Rheumatol. 32, 1301–1307 (2013).

    PubMed  Article  Google Scholar 

  148. 148

    Soldevilla, H. F., Briones, S. F. & Navarra, S. V. Systemic lupus erythematosus following HPV immunization or infection? Lupus 21, 158–161 (2012).

    CAS  PubMed  Article  Google Scholar 

  149. 149

    Zhang, J. et al. The use, safety, and effectiveness of herpes zoster vaccination in individuals with inflammatory and autoimmune diseases: a longitudinal observational study. Arthritis Res. Ther. 13, R174 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  150. 150

    Heijstek, M. W. et al. EULAR recommendations for vaccination in paediatric patients with rheumatic diseases. Ann. Rheum. Dis. 70, 1704–1712 (2011).

    CAS  PubMed  Article  Google Scholar 

  151. 151

    Galloway, J. B. et al. Risk of skin and soft tissue infections (including shingles) in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Ann. Rheum. Dis. 72, 229–234 (2013).

    CAS  PubMed  Article  Google Scholar 

  152. 152

    Centers for Disease Control and Prevention. Recommendations on the use of quadrivalent human papillomavirus vaccine in males—Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report (MMWR) [online], (2011).

  153. 153

    Centers for Disease Control and Prevention. FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report (MMWR) [online], (2011).

Download references

Author information

Affiliations

Authors

Contributions

J.W. and S.v.A. researched data for the article. J.W., S.v.A. and M.B. substantially contributed to discussion of content and all authors contributed to writing and review/editing of the manuscript before submission.

Corresponding author

Correspondence to Marc Bijl.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Westra, J., Rondaan, C., van Assen, S. et al. Vaccination of patients with autoimmune inflammatory rheumatic diseases. Nat Rev Rheumatol 11, 135–145 (2015). https://doi.org/10.1038/nrrheum.2014.206

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing