01 Should we vaccinate all SLE patients against papillomavirus and herpes zoster

The dysregulated host immune system and treatment with immunosuppressive medications predisposes patients with systemic lupus erythematosus (SLE) to increased risk of infections such as Human Papilloma Virus (HPV) and Herpes Zoster (HZ). HPV causes genital warts and malignancy including cervical, penile, and anogenital cancers. In a recent meta-analysis, the prevalence of HPV in SLE was found to be significantly higher than controls, with an odds ratio (OR)= 2.87.1 SLE is associated with the highest rate of HZ infection in all age strata below 70 years, with an age-adjusted incidence of 12.0/1000 person-years (hazard ratio 1.7).2 The use of cyclophosphamide and mycophenolate mofetil with glucocorticoids in lupus is associated with a seven-fold increase in HZ reactivation. Similarly, the use of anifrolumab in SLE clinical trials was associated with OR = 4.089 of HZ infection.3 Immunization against common pathogens can potentially be very beneficial in preventing infections in SLE. However, safety and efficacy of vaccines for patients with SLE generate perennial controversy. Concerns are fueled by case reports of de novo development of autoimmune disease or flares of existing autoimmune disease after administration of vaccines. In addition, theoretical concerns about inadequate host immune responses to vaccines raise doubts about their effectiveness in protecting patients with SLE from infection. Overall, HPV vaccines seem to be safe and immunogenic in patients with SLE. A study of 210 patients with SLE, HPV vaccine was found to be immunogenic in ~90% of patients with no serious side effects or increased lupus flare at one-year follow-up.4 The use of cyclophosphamide was associated with low rates of HPV seroconversion. The live-attenuated HZ vaccine was also found to be safe and immunogenic with no increase in incidence of herpes zoster in patients with SLE on milder immunosuppressants.5 6 There is still no data regarding the efficacy of the subunit and inactivated HZ vaccines in SLE patients, but studies in other immunocompromised populations showed it to be safe and immunogenic. Vaccination against HPV and HZ in SLE patients resulted in significantly lower rates of infections. Overall, HPV and HZ vaccines appear to be safe and effective in patients with stable lupus on low intensity immunosuppressants. Learning Objectives Describe the high incidence of human papillomavirus and herpes zoster infections in patients with SLE Address concerns associated with vaccination administration in SLE Explain the safety, efficacy, and limitations of data from studies of HPV and HZ vaccines in SLE patients Acknowledgements This research was supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. References Garcia-Carrasco M, Mendoza-Pinto C, Rojas-Villarraga A, et al. Prevalence of cervical HPV infection in women with systemic lupus erythematosus: A systematic review and meta-analysis. Autoimmun Rev. 2019;18(2):184–91. Chakravarty EF, Michaud K, Katz R, Wolfe F. Increased incidence of herpes zoster among patients with systemic lupus erythematosus. Lupus. 2013;22(3):238–44. Lee YH, Song GG. Anifrolumab for the treatment of active systemic lupus erythematosus: a meta-analysis of randomized controlled trials. Z Rheumatol. 2020. Rotstein Grein IH, Pinto NF, Lobo A, et al. Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in patients with childhood systemic lupus erythematosus: a real-world interventional multi-centre study. Lupus. 2020;29(8):934–42. Guthridge JM, Cogman A, Merrill JT, et al. Herpes zoster vaccination in SLE: a pilot study of immunogenicity. J Rheumatol. 2013;40(11):1875–80. Mok CC, Chan KH, Ho LY, et al. Safety and immune response of a live-attenuated herpes zoster vaccine in patients with systemic lupus erythematosus: a randomised placebo-controlled trial. Ann Rheum Dis. 2019;78(12):1663–8.