Significant Associations of Neurological Complications of Herpes Zoster With Stroke in Rheumatoid Arthritis Patients

J Am Heart Assoc. 2017 Jul 19;6(7):e006304. doi: 10.1161/JAHA.117.006304.

Abstract

Background: Accumulating evidence suggests an increased risk of stroke after herpes zoster (HZ). This risk is elevated in immunocompromised patients. The incidence of HZ in Asia is higher than in Western countries. However, the epidemiology of HZ and HZ-related stroke among rheumatoid arthritis (RA) patients in Asia remains unclear.

Methods and results: We conducted a retrospective cohort study using a population-based database to investigate the epidemiology of HZ in RA patients in Taiwan during the period of 2000-2011. A total of 27 609 newly diagnosed and eligible RA cases were identified, and 110 436 non-RA cases were matched for age and sex at a ratio of 4:1. HZ risk increased by 2.53-fold (P<0.0001) in RA patients compared with the general population. Exposure to corticosteroids (adjusted odds ratio=1.73, P<0.0001), adalimumab (adjusted odds ratio=1.61, P=0.002), and rituximab (adjusted odds ratio=2.06, P=0.008) was associated with an increased risk of HZ in RA patients. A significant association between the use of methotrexate or corticosteroids and HZ risk was dose-dependent (Ptrend<0.0001). Elevated risk of stroke was observed in RA patients with HZ (adjusted hazard ratio=1.27, P=0.047), particularly in those with neurological complications (adjusted hazard ratio=1.54, P=0.015). A 2.30-fold significantly increased risk of stroke within 90 days after HZ occurrence was observed in RA patients compared with those without HZ (P=0.02). Furthermore, death risk increased in RA patients with HZ (adjusted hazard ratio=1.18, P=0.026).

Conclusions: The risk of HZ and HZ-related stroke has increased in RA patients. Monitoring the occurrence of HZ in RA patients and preventing HZ-related stroke or mortality during a specific immunosuppressive therapy are important.

Keywords: herpes zoster; immunosuppressive therapy; infectious disease; nervous system; neurological complications; rheumatoid arthritis; stroke.

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / mortality
  • Chi-Square Distribution
  • Databases, Factual
  • Female
  • Herpes Zoster / diagnosis
  • Herpes Zoster / immunology
  • Herpes Zoster / mortality
  • Herpes Zoster / virology*
  • Herpesvirus 3, Human / immunology
  • Herpesvirus 3, Human / pathogenicity*
  • Host-Pathogen Interactions
  • Humans
  • Immunocompromised Host
  • Immunosuppressive Agents / adverse effects*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Opportunistic Infections / diagnosis
  • Opportunistic Infections / immunology
  • Opportunistic Infections / mortality
  • Opportunistic Infections / virology*
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk Factors
  • Stroke / diagnosis
  • Stroke / immunology
  • Stroke / mortality
  • Stroke / virology*
  • Taiwan / epidemiology
  • Time Factors

Substances

  • Antirheumatic Agents
  • Immunosuppressive Agents