Abstract

Objectives:To study the prevalence and risk factors of herpes zoster (HZ) infection in patients with rheumatic diseases.Methods:Medical records of patients with rheumatic diseases who attended our out-patient rheumatology clinics between 2019 March and 2019 August were retrospectively reviewed. Patients who were using biological or targeted DMARDs were excluded. Episodes of HZ infection since disease diagnosis were identified and the prevalence over time was calculated. Laboratory parameters (total white cell count, neutrophil-to-lymphocyte ratio, serum albumin, globulin & creatinine), history of diabetes mellitus and the highest doses of immunosuppressive medications within 6 months of the first episode of HZ infection were compared with those within 6 months of last follow-up in patients who did not have HZ infection. Cox regression analysis was performed to identify factors associated with the first HZ infection in all patients.Results:1542 patients were studied (88% women, age 46.4±15.0 years). The underlying diseases were systemic lupus erythematosus (SLE) (38%), rheumatoid arthritis (26%) and other rheumatic diseases (36%). After a total follow-up of 11,515 patient-years since diagnosis (7.5±7.0 years), 122 (7.9%) patients developed 146 episodes of HZ infection, giving an overall prevalence of 1.27/100-patient years. The prevalence rates of HZ in SLE, RA and non-SLE/RA patients were 1.70, 0.64 and 0.76 per 100 patient-years, respectively. Patients who experienced HZ reactivation were younger (41.6±14.7 vs 46.8±15.0 years; p<0.001), more likely to have SLE (74% vs 35%; p<0.001) and diabetes mellitus (17% vs 7.3%; p=0.01), and had a significantly lower albumin (38.6±5.6 vs 41.3±3.5; p<0.001) and higher neutrophil-to-lymphocyte ratio (4.9±6.2 vs 2.8±2.6; p<0.001). More patients with HZ reactivation were treated with prednisolone (54% vs 22%; p<0.001), azathioprine (20% vs 8%; p<0.001), mycophenolate mofetil [MMF] (21% vs 12%; p=0.006), cyclophosphamide [CYC] (4.9% vs 0.1%; p<0.001) and hydroxychloroquine (48% vs 34%; p=0.002) in the preceding 6 months compared with those who did not have HZ infection. Among those using immunosuppressive drugs, the doses of MMF (1.42±0.64 vs 1.02±0.31g; p=0.005) and prednisolone (15.6±15.9 vs 5.5±4.5mg; p<0.001) were significantly higher in those with HZ infection. The cumulative risk of having HZ reactivation in SLE patients at 24 and 48 months since diagnosis was 5.9% and 8.6%, respectively, which was significantly higher than that in non-SLE patients (1.9% and 2.5%, respectively; p<0.001 by log rank test). Cox regression analysis revealed that having a diagnosis of SLE (HR 1.97 [1.17-3.31]), albumin level (HR 0.93 [0.90-0.97] per g/L; p=0.001), serum creatinine (HR 0.995 [0.990-1.00] per umol/L), higher neutrophil/lymphocyte ratio (HR 1.08 [1.05-1.11]) and the use of CYC (HR 6.69 [2.56-17.5]) and prednisolone (HR 1.61 [1.02-2.45]) in the preceding 6 months were independently associated with the development of HZ infection.Conclusion:Reactivation of HZ is fairly common in patients with rheumatic diseases. Underlying SLE, prednisolone/cyclophosphamide therapy and the neutrophil/lymphocyte ratio, but not age, sex or other laboratory parameters, are the major risk factors for HZ reactivation.Disclosure of Interests:None declared

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