Risk of Shingles in Adults with Primary Sjogren’s Syndrome and Treatments: A Nationwide Population-Based Cohort Study

<div><p>Background</p><p>Primary Sjögren's syndrome (pSS) is associated with immunological dysfunctions—a well-known risk factor of shingles. This study aimed to examine the incidence and risk of shingles in adults with pSS and pharmacological treatments.</p><p>Methods</p><p>This retrospective population-based cohort study was conducted using National Health Insurance claims data. Using propensity scores, 4,287 pSS adult patients and 25,722-matched cohorts by age, gender, selected comorbidities and Charlson comorbidity index scores were identified. Kaplan-Meier analysis and Cox regression were conducted to compare the differences in developing shingles. In pSS, oral and eye dryness are treated with substitute agents. Extraglandular features are often treated with pharmacological drugs including steroids and immunosuppressants. pSS patients were grouped as follows: no pharmacological drugs, steroids alone; immunosuppressants alone; combined therapies.</p><p>Results</p><p>During the follow-up, 463 adults with pSS (10.80%) and 1,345 control cohorts (5.23%) developed shingles. The cumulative incidence of shingles in pSS patients (18.74/1,000 patient-years) was significantly higher than controls (8.55/1,000 patient-years). The adjusted hazard ratio (HR) of shingles was 1.69 (95% confidence interval (CI) 1.50–1.90). In age-subgroup analyses, incidences of shingles in pSS increased with age and peaked in pSS patients aged ≧60; however, adjusted HRs decreased with age. Compared to control cohorts with no drugs, adjusted HRs for shingles in pSS patients were ranked from high to low as: combined therapies (4.14; 95% CI 3.14–5.45) > immunosuppressants alone (3.24; 95% CI 2.36–4.45) > steroids alone (2.54; 95% CI 2.16–2.97) > no pharmacological drugs (2.06; 95% CI 1.76–2.41). Rates of shingles-associated hospitalization and postherpetic neuralgia were 5.62% and 24.41%, both of which were significantly higher than those (2.60%; 13.01%) in the control cohorts.</p><p>Conclusions</p><p>Adults with pSS were at greater risk for shingles than control cohorts. Drug exposures significantly increased the risk of shingles in pSS.</p></div

Demographic characteristics for pSS adults and the control cohorts in Taiwan between 2001 and 2008.

<p>pSS: primary Sjogren’s syndrome; SD: standard deviation.</p><p>Categorical variable was estimated by chi-square test and continuous variable was estimated by student’s t-test.</p><p><i>P</i> < 0.05, statistical significance.</p><p>Demographic characteristics for pSS adults and the control cohorts in Taiwan between 2001 and 2008.</p

Impact of pharmacological therapies on incidence of shingles for pSS adults and the control cohorts during the follow-up.

<p>HR: hazard ratio; CI: confidence interval.</p><p>^a Data are adjusted by age group, gender, comorbidities (malignancy, diabetes mellitus and hypertension), Charlson comorbidity index score, geographic region and income.</p><p>^b Data are adjusted by gender, comorbidities (malignancy, diabetes mellitus and hypertension), Charlson comorbidity index score, drugs, geographic region and income.</p><p><i>P</i> <0.05, statistical significance.</p><p>Impact of pharmacological therapies on incidence of shingles for pSS adults and the control cohorts during the follow-up.</p

Incidence of shingles for pSS adults <i>vs</i>. the control cohorts during the 11-year follow-up.

<p>pSS: primary Sjogren’s syndrome; HR: hazard ratio; CI: confidence interval.</p><p>^a Data are adjusted by age group, gender, comorbidities (malignancy, diabetes mellitus and hypertension), Charlson comorbidity index score, drugs, geographic region and income.</p><p>*<i>P</i> <0.05 for statistical significance.</p><p>Incidence of shingles for pSS adults <i>vs</i>. the control cohorts during the 11-year follow-up.</p

Age/gender subgroup analysis for incidence of shingles in pSS adults during the follow-up.

<p>HR: hazard ratio; CI: confidence interval.</p><p>^a Data are adjusted by gender, comorbidities (malignancy, diabetes mellitus and hypertension), Charlson comorbidity index score, drugs, geographic region and income.</p><p>^b Data are adjusted by age, comorbidities (malignancy, diabetes mellitus and hypertension), Charlson comorbidity index score, drugs, geographic region and income.</p><p><i>P</i> <0.05, statistical significance.</p><p>Age/gender subgroup analysis for incidence of shingles in pSS adults during the follow-up.</p

Cumulative incidences of shingles for pSS adults and the control cohorts from 2001 to 2011.

<p>Cumulative incidences of shingles for pSS adults and the control cohorts from 2001 to 2011.</p