Original article
Immunosuppressive medication use and risk of herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE): A nationwide case-control study

https://doi.org/10.1016/j.jaad.2015.12.059Get rights and content

Background

The association between immunosuppressive medication use and herpes zoster (HZ) in patients with systemic lupus erythematosus (SLE) has not been clearly defined.

Objective

We evaluated the risk of HZ in patients with SLE treated with different immunosuppressants.

Methods

A nationwide population-based case-control study was conducted using the Taiwanese National Health Insurance Research Database. Cases (1555 patients with SLE who developed HZ) and controls (3049 age- and sex-matched patients with SLE but without HZ) were analyzed for use of various immunosuppressive medications in the preceding 3-month period, and dose-response relationships were determined. Logistic regression was performed to estimate the adjusted odds ratio for HZ development.

Results

Medications associated with greater HZ risk in patients with SLE included oral corticosteroids, intravenous methylprednisolone, hydroxychloroquine, oral cyclophosphamide, intravenous cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil. Combination immunosuppressive therapy was common in patients with SLE and was associated with greatly increased HZ risk. For oral corticosteroids and hydroxychloroquine, the risk of HZ was strongly dependent on the medication dose.

Limitations

This study is retrospective in nature.

Conclusion

Recent immunosuppressive medication use is associated with increased HZ risk in patients with SLE, particularly those receiving high-dose oral corticosteroids and multiagent immunosuppressive therapy.

Section snippets

Data source

A nationwide population-based case-control study was performed using the Taiwanese National Health Insurance Research Database (NHIRD). The Taiwanese National Health Insurance program is a mandatory universal health insurance scheme that covers more than 98% of Taiwan's 23 million population. The NHIRD database contains the demographic information, diagnostic codes, inpatient and outpatient physician claims, and prescription drug claims from this health insurance system, and has been used

Clinical features of patients

A total of 10,581 patients with SLE were identified from the Catastrophic Illness Registry of the NHIRD. In all, 255 patients with a diagnosis of HZ before the first diagnosis of SLE were excluded. In addition, 1465 patients with rheumatoid arthritis; 339 patients with systemic sclerosis, dermatomyositis, or polymyositis; and 112 patients with psoriasis were excluded. The SLE cohort therefore consisted of 8410 patients; of these, 1555 developed HZ infection. The 1555 patients with SLE who

Discussion

Previous studies investigating the relationship between immunosuppressive medication use and development of HZ in patients with SLE were limited and produced conflicting results.9, 10, 11, 12, 13, 14, 15, 16 Using a large nationwide population-based database, we found that patients with SLE receiving various types of immunosuppressive medications (including systemic corticosteroids, hydroxychloroquine, cyclophosphamide, azathioprine, methotrexate, and mycophenolate mofetil) had significantly

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      Citation Excerpt :

      Among patients with SLE, use of prednisone (hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.24–4.23) and mycophenolate mofetil (HR, 5.0; 95% CI, 1.4–17.6) within the past 6 months placed patients at higher risk for developing HZ. Another case-control study of HZ in SLE performed in a nationwide sample from Taiwan found that use of any immunomodulatory or immunosuppressant medication, including hydroxychloroquine, increased the risk of HZ in a dose-dependent manner.24 Studies are generally mixed, with some showing HZ incidence increasing with immunosuppression, whereas others found a high rate of HZ among patients with SLE with quiescent disease on little to no immunosuppression.12,15,21,25

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    Supported by grants from Kaohsiung Medical University Hospital (KMUH103-3T02, KMUH104-4T01, KMUH104-4R49).

    Conflicts of interest: None declared.

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