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

J Am Acad Dermatol. 2016 Jul;75(1):49-58. doi: 10.1016/j.jaad.2015.12.059. Epub 2016 Mar 4.

Abstract

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.

Keywords: National Health Insurance Research Database; case-control study; epidemiology; herpes zoster; immunosuppressive medications; systemic corticosteroids; systemic lupus erythematosus.

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects
  • Adult
  • Azathioprine / administration & dosage
  • Azathioprine / adverse effects
  • Case-Control Studies
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dose-Response Relationship, Drug
  • Female
  • Herpes Zoster / chemically induced
  • Herpes Zoster / epidemiology*
  • Humans
  • Hydroxychloroquine / administration & dosage
  • Hydroxychloroquine / adverse effects
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Lupus Erythematosus, Systemic / drug therapy*
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Methylprednisolone / administration & dosage
  • Methylprednisolone / adverse effects
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Retrospective Studies
  • Risk Factors
  • Taiwan / epidemiology
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Hydroxychloroquine
  • Cyclophosphamide
  • Mycophenolic Acid
  • Azathioprine
  • Methylprednisolone
  • Methotrexate