Abstract
Objectives
The objective was to study the prevalence and risk factors of herpes zoster (HZ) infection in patients with rheumatic diseases.
Methods
Consecutive patients with rheumatic diseases not receiving biologic/targeted DMARDs who attended our rheumatology clinics between March and August 2019 were retrospectively reviewed. Episodes of HZ infection since their first clinic attendance were identified. Laboratory results (total white cell count, neutrophil-to-lymphocyte ratio (NLR), serum albumin, globulin, and creatinine) and use of immunosuppressive medications were compared between those with (preceding infection) and without (preceding last visit) HZ infection. Cox regression analysis was performed to identify factors associated with the first HZ infection in all patients.
Results
1,479 patients were studied (88.3% women, age 45.0 ± 15.8 years). Systemic lupus erythematosus (SLE) (38.7%) and rheumatoid arthritis (28.3%) were the commonest rheumatic diseases. After a follow-up of 14,715 patient-years (9.9 ± 7.0 years), 219 (14.8%) patients developed 258 episodes of HZ infection, giving an overall prevalence of 1.75/100-patient years. The prevalence rates of HZ were highest in SLE and inflammatory myopathies (2.54 and 2.58 per 100 patient-years, respectively). Patients who experienced HZ reactivation were younger, more likely to have SLE, and had significantly lower serum albumin/globulin levels but higher NLR. Significantly more patients with HZ reactivation were using prednisolone and other immunosuppressive drugs in the visits preceding HZ infection. The cumulative risk of having HZ reactivation at 24 and 48 months was 4.9% and 7.6%, respectively. Cox regression analysis revealed that a diagnosis of SLE, increasing age, higher NLR, use of cyclophosphamide, and increasing doses of prednisolone, azathioprine, hydroxychloroquine and leflunomide were independently associated with HZ infection.
Conclusions
Reactivation of HZ is fairly common in patients with rheumatic diseases. Underlying SLE, age, neutrophil/lymphocyte ratio, and immunosuppressive therapies are independent risk factors.
Key Points • Herpes zoster (HZ) infection is fairly common in patients with rheumatic diseases undergoing conventional DMARD or immunosuppressive therapies. • Underlying SLE, increasing age, higher neutrophil/lymphocyte ratio and increasing dosages of immunosuppressive drugs are independent risk factors. • Patients with rheumatic diseases, particularly SLE, should be encouraged to receive HZ vaccination. |
Similar content being viewed by others
References
Le P, Rothberg M (2019) Herpes zoster infection. BMJ 364:k5095
Schutzer-Weissmann J, Farquhar-Smith P (2017) Post-herpetic neuralgia - a review of current management and future directions. Expert Opin Pharmacother 18:1739–1750
Johnson RW, Bouhassira D, Kassianos G, Leplège A, Schmader KE, Weinke T (2010) The impact of herpes zoster and post-herpetic neuralgia on quality-of-life. BMC Med 8:37
Kawai K, Yawn BP (2017) Risk factors for herpes zoster: a systematic review and meta-analysis. Mayo Clin Proc 92:1806–1821
Mareque M, Oyagüez I, Morano R, Casado MA (2019) Systematic review of the evidence on the epidemiology of herpes zoster: incidence in the general population and specific subpopulations in Spain. Public Health 167:136–146
Ryu HJ, Han JO, Lee SA, Seo MR, Choi HJ, Ko KP et al (2021) Risk factors for herpes zoster in patients with rheumatic diseases: a nationwide cohort study in Korea. Rheumatol (Oxford) 60:2427–2433
Redeker I, Albrecht K, Kekow J, Burmester GR, Braun J, Schäfer M et al (2022) Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register. Ann Rheum Dis 81:41–47
Liao TL, Chen YM, Liu HJ, Chen DY (2017) Risk and severity of herpes zoster in patients with rheumatoid arthritis receiving different immunosuppressive medications: a case-control study in Asia. BMJ Open 7:e014032
Pappas DA, Hooper MM, Kremer JM, Reed G, Shan Y, Wenkert D et al (2015) Herpes zoster reactivation in patients with rheumatoid arthritis: analysis of disease characteristics and disease-modifying antirheumatic drugs. Arthritis Care Res (Hoboken) 67:1671–1678
Wolfe F, Michaud K, Chakravarty EF (2006) Rates and predictors of herpes zoster in patients with rheumatoid arthritis and non-inflammatory musculoskeletal disorders. Rheumatol (Oxford) 45:1370–1375
Tanaka K, Kimura E, Oryoji K, Mizuki SI, Kobayashi T, Nishikawa A et al (2021) Hypertension and dyslipidemia are risk factors for herpes zoster in patients with rheumatoid arthritis: a retrospective analysis using a medical information database. Rheumatol Int 41:1633–1639
Winthrop KL, Harigai M, Genovese MC, Lindsey S, Takeuchi T, Fleischmann R et al (2020) Infections in baricitinib clinical trials for patients with active rheumatoid arthritis. Ann Rheum Dis 79:1290–1297
Winthrop KL, Nash P, Yamaoka K, Mysler E, Khan N, Camp HS et al (2022) Incidence and risk factors for herpes zoster in patients with rheumatoid arthritis receiving upadacitinib: a pooled analysis of six phase III clinical trials. Ann Rheum Dis 81:206–213
Buonacera A, Stancanelli B, Colaci M, Malatino L (2022) Neutrophil to lymphocyte ratio: an emerging marker of the relationships between the immune system and diseases. Int J Mol Sci 23:3636
Song M, Graubard BI, Rabkin CS, Engels EA (2021) Neutrophil-to-lymphocyte ratio and mortality in the United States general population. Sci Rep 11:464
Jung JY, Lee E, Suh CH, Kim HA (2019) Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio are associated with disease activity in polymyalgia rheumatica. J Clin Lab Anal 33:e23000
Chandrashekara S, Mukhtar Ahmad M, Renuka P, Anupama KR, Renuka K (2017) Characterization of neutrophil-to-lymphocyte ratio as a measure of inflammation in rheumatoid arthritis. Int J Rheum Dis 20:1457–1467
Mercan R, Bitik B, Tufan A, Bozbulut UB, Atas N, Ozturk MA et al (2016) The association between neutrophil/lymphocyte ratio and disease activity in rheumatoid arthritis and ankylosing spondylitis. J Clin Lab Anal 30:597–601
Yuksel M, Yildiz A, Oylumlu M, Turkcu FM, Bilik MZ, Ekinci A et al (2016) Novel markers of endothelial dysfunction and inflammation in Behçet’s disease patients with ocular involvement: epicardial fat thickness, carotid intima media thickness, serum ADMA level, and neutrophil-to-lymphocyte ratio. Clin Rheumatol 35:701–708
Zhang K, Li W, He C, He X, Hou J (2021) The ratio of neutrophil to lymphocyte predicts interstitial lung disease and its prognosis in patients with primary Sjögren’s syndrome: a retrospective analysis. Ann Palliat Med 10:6493–6501
Lee HN, Kim YK, Kim GT, Ahn E, So MW, Sohn DH et al (2019) Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio as predictors of 12-week treatment response and drug persistence of anti-tumor necrosis factor-α agents in patients with rheumatoid arthritis: a retrospective chart review analysis. Rheumatol Int 39:859–868
Sargin G, Senturk T, Yavasoglu I, Kose R (2018) Relationship between neutrophil-lymphocyte, platelet-lymphocyte ratio and disease activity in rheumatoid arthritis treated with rituximab. Int J Rheum Dis 21:2122–2127
Mok CC, Hamijoyo L, Kasitanon N, Chen DY, Chen S, Yamaoka K et al (2021) The Asia-Pacific League of Associations for Rheumatology consensus statements on the management of systemic lupus erythematosus. Lancet Rheumatol 3:e517–e531
Fanouriakis A, Kostopoulou M, Cheema K, Anders HJ, Aringer M, Bajema I et al (2020) 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis 79:713–723
Bansal P, Goyal A, Cusick A, Lahan S, Dhaliwal HS, Bhyan P et al (2021) Hydroxychloroquine: a comprehensive review and its controversial role in coronavirus disease 2019. Ann Med 53:117–134
Chakravarty EF, Michaud K, Katz R, Wolfe F (2013) Increased incidence of herpes zoster among patients with systemic lupus erythematosus. Lupus 22:238–244
Nagasawa K, Yamauchi Y, Tada Y, Kusaba T, Niho Y, Yoshikawa H (1990) High incidence of herpes zoster in patients with systemic lupus erythematosus: an immunological analysis. Ann Rheum Dis 49:630–633
Chen HH, Chen YM, Chen TJ, Lan JL, Lin CH, Chen DY (2011) Risk of herpes zoster in patients with systemic lupus erythematosus: a three-year follow-up study using a nationwide population-based cohort. Clinics (Sao Paulo) 66:1177–1182
Borba EF, Ribeiro ACM, Martin P, Costa LP, Guedes LKN, Bonfá E (2010) Incidence, risk factors, and outcome of Herpes zoster in systemic lupus erythematosus. J Clin Rheumatol 16:119–122
Kahl LE (1994) Herpes zoster infections in systemic lupus erythematosus: risk factors and outcome. J Rheumatol 21:84–86
Hata A, Kuniyoshi M, Ohkusa Y (2011) Risk of Herpes zoster in patients with underlying diseases: a retrospective hospital-based cohort study. Infection 39:537–544
Hu SCS, Lin CL, Lu YW, Chen GS, Yu HS, Wu CS et al (2013) Lymphopaenia, anti-Ro/anti-RNP autoantibodies, renal involvement and cyclophosphamide use correlate with increased risk of herpes zoster in patients with systemic lupus erythematosus. Acta Derm Venereol 93:314–318
Yun H, Yang S, Chen L, Xie F, Winthrop K, Baddley JW et al (2016) Risk of herpes zoster in autoimmune and inflammatory diseases: implications for vaccination. Arthritis Rheumatol 68:2328–2337
Chen D, Li H, Xie J, Zhan Z, Liang L, Yang X (2017) Herpes zoster in patients with systemic lupus erythematosus: Clinical features, complications and risk factors. Exp Ther Med 14:6222–6228
Mok CC, Tse SM, Chan KL, Ho LY (2020) Prevalence and risk factors of herpes zoster infection in patients with biopsy proven lupus nephritis undergoing immunosuppressive therapies. Lupus 29:836–844
Siu JYM, Fung TKF, Leung LHM (2019) Social and cultural construction processes involved in HPV vaccine hesitancy among Chinese women: a qualitative study. Int J Equity Health 18:147
Lau LHW, Lee SS, Wong NS (2020) The continuum of influenza vaccine hesitancy among nursing professionals in Hong Kong. Vaccine 38:6785–6793
Luk TT, Zhao S, Wu Y, Wong JYH, Wang MP, Lam TH (2021) Prevalence and determinants of SARS-CoV-2 vaccine hesitancy in Hong Kong: a population-based survey. Vaccine 39:3602–3607
Mok CC (2019) Herpes zoster vaccination in systemic lupus erythematosus: the current status. Hum Vaccin Immunother 15:45–48
Author information
Authors and Affiliations
Contributions
All authors contributed to the study design, data acquisition, and data interpretation. Data analysis was done by Mok CC.
Corresponding author
Ethics declarations
Disclosures
None.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Mok, C.C., Ho, L.Y., Tse, S.M. et al. Prevalence and risk factors of herpes zoster infection in patients with rheumatic diseases not receiving biologic or targeted therapies. Clin Rheumatol 42, 1019–1026 (2023). https://doi.org/10.1007/s10067-022-06450-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-022-06450-2