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Incidence and prevalence of vaccine preventable infections in adult patients with autoimmune inflammatory rheumatic diseases (AIIRD): a systemic literature review informing the 2019 update of the EULAR recommendations for vaccination in adult patients with AIIRD
  1. Victoria Furer1,2,
  2. Christien Rondaan3,4,
  3. Marloes Heijstek5,
  4. Sander van Assen6,
  5. Marc Bijl7,
  6. Nancy Agmon-Levin2,8,
  7. Ferdinand C Breedveld9,
  8. Raffaele D'Amelio10,
  9. Maxime Dougados11,
  10. Meliha Crnkic Kapetanovic12,
  11. Jacob M van Laar13,
  12. Annette Ladefoged de Thurah14,
  13. Robert Landewé15,16,
  14. Anna Molto11,
  15. Ulf Müller-Ladner17,
  16. Karen Schreiber18,19,
  17. Leo Smolar20,
  18. Jim Walker21,
  19. Klaus Warnatz22,
  20. Nico M Wulffraat23 and
  21. Ori Elkayam1,2
  1. 1 Department of Rheumatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
  2. 2 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  3. 3 Medical Microbiology and Infection Prevention, UMCG, Groningen, The Netherlands
  4. 4 Rheumatology and Clinical Immunology, UMCG, Groningen, The Netherlands
  5. 5 Internal Medicine and Allergology, Rheumatology and Clinical Immunology, UMC Utrecht, Utrecht, The Netherlands
  6. 6 Internal Medicine (Infectious Diseases), Treant Care Group, Hoogeveen, The Netherlands
  7. 7 Internal Medicine, Martini Hospital, Groningen, The Netherlands
  8. 8 Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer, Israel
  9. 9 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  10. 10 Dipartimento di Medicina Clinica e Molecolare, Sapienza University of Rome, Roma, Italy
  11. 11 Department of Rheumatology, Hôpital Cochin, Université Paris Descartes, Paris, France
  12. 12 Department of Clinical Sciences Lund, Section for Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden
  13. 13 Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands
  14. 14 Institute of Clinical Medicine, Section of Rheumatology, Aarhus University Hospital, Aarhus, Denmark
  15. 15 Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  16. 16 Department of Rheumatology, Zuyderland Medical Centre, Heerlen, The Netherlands
  17. 17 Department of Rheumatology and Clinical Immunology, Justus-Liebig-University, Giessen, Germany
  18. 18 Department of Rheumatology, King Christian X's Hospital for Rheumatic Diseases, Graasten, Denmark
  19. 19 Department of Thrombosis and Haemophilia, Guy's and St Thomas' Hospital, London, United Kingdom
  20. 20 Tel Aviv, Israel
  21. 21 Elgin, UK
  22. 22 Center for Chronic Immunodeficiency, Faculty of Medicine, University of Freiburg, University Medical Center Freiburg, Freiburg, Germany
  23. 23 Department of Pediatric Rheumatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to Dr Victoria Furer; furer.rheum{at}


Objectives The aims of this study were to update the evidence on the incidence and prevalence rates of vaccine preventable infections (VPI) in patients with autoimmune inflammatory rheumatic diseases (AIIRD) and compare the data to the general population when available.

Methods A literature search was performed using Medline, Embase and Cochrane library (October 2009 to August 2018). The primary outcome was the incidence or prevalence of VPI in the adult AIIRD population. Meta-analysis was performed when appropriate.

Results Sixty-three publications out of 3876 identified records met the inclusion criteria: influenza (n=4), pneumococcal disease (n=7), hepatitis B (n=10), herpes zoster (HZ) (n=29), human papillomavirus (HPV) infection (n=13). An increased incidence of influenza and pneumococcal disease was reported in patients with AIIRD. HZ infection-pooled incidence rate ratio (IRR) was 2.9 (95% CI 2.4 to 3.3) in patients with AIIRD versus general population. Among AIIRD, inflammatory myositis conferred the highest incidence rate (IR) of HZ (pooled IRR 5.1, 95% CI 4.3 to 5.9), followed by systemic lupus erythematosus (SLE) (pooled IRR 4.0, 95% CI 2.3 to 5.7) and rheumatoid arthritis (pooled IRR 2.3, 95% CI 2.1 to 2.6). HPV infection-pooled prevalence ratio was 1.6, 95% CI 0.7 to 3.4 versus general population, based on studies mainly conducted in the SLE population in Latin America and Asia. Pooled prevalence of hepatitis B surface antigen and hepatitis B core antibody in patients with AIIRD was similar to the general population, 3%, 95% CI 1% to 5% and 15%, 95% CI 7% to 26%, respectively.

Conclusion Current evidence shows an increased risk of VPI in patients with AIIRD, emphasising that prevention of infections is essential in these patients.

  • autoimmune diseases
  • epidemiology
  • infections
  • vaccination

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  • Contributors VF, with collaboration with OE, performed literature search and reviewed articles on the prevalence and/or incidence of vaccine preventable diseases in patients with autoimmune inflammatory rheumatic diseases. The systematic literature review (SLR) and meta-analysis, when applicable, was performed under the supervision by SvA, the expert in infectious diseases, and the methodologists, JMvL and RL. The results of the SLR were presented to all task force members, discussed and reviewed during the task force meetings. VF drafted and edited the manuscript, under the supervision of OE. All authors read and approved the final version of the manuscript.

  • Funding This project was supported by EULAR.

  • Competing interests MD reports grants and personal fees from Pfizer, grants and personal fees from Abbvie, grants and personal fees from UCB, grants and personal fees from Novartis, grants and personal fees from Lilly, grants and personal fees from Merck, grants and personal fees from Roche, grants from BMS, outside the submitted work. OE reports grants and personal fees from Pfizer, grants, personal fees from Abbvie, grants and personal fees from Roche, grants and personal fees from Janssen, personal fees from Novartis and Lilly. AM reports grants and personal fees from Abbvie, grants and personal fees from Pfizer, grants and personal fees from BMS, grants and personal fees from UCB, grants and personal fees from Merck, during the conduct of the study. KW reports personal fees from Pfizer, during the conduct of the study; grants and personal fees from Biotest, grants and personal fees from CSL Behring, personal fees from LFB, personal fees from Grifols, grants from BMS, personal fees from Baxter, personal fees from Roche, personal fees from Octapharma, outside the submitted work.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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