Risk of Stroke after Herpes Zoster - Evidence from a German Self-Controlled Case-Series Study

Abstract

Background: Herpes zoster (HZ) is caused by reactivation of the latent varicella-zoster virus (VZV). A severe complication of HZ is VZV vasculopathy which can result in ischemic or hemorrhagic stroke. The aims of our study were to assess the risk of stroke after the onset of HZ and to investigate the roles of stroke subtype, HZ location and the time interval between HZ onset and stroke.

Methods: A self-controlled case-series study was performed on a cohort of patients with incident stroke recorded in the German Pharmacoepidemiological Research Database (GePaRD), which covers about 20 million persons throughout Germany. We estimated adjusted incidence rate ratios (IRR) by comparing the rate of stroke in risk periods (i.e., periods following HZ) with the rate of stroke in control periods (i.e., periods without HZ) in the same individuals, controlling for both time-invariant and major potentially time-variant confounders.

Results: The cohort included 124,462 stroke patients, of whom 6,035 (5%) had at least one HZ diagnosis identified in GePaRD either as main hospital discharge diagnosis or as HZ treated with antivirals. The risk of stroke was about 1.3 times higher in the risk periods 3 months after HZ onset, than in the control periods (IRR: 1.29; 95% confidence interval: 1.16-1.44). An elevated risk of similar magnitude was observed for ischemic and unspecified stroke, but a 1.5-fold higher risk was observed for hemorrhagic stroke. A slightly stronger effect on the risk of stroke was also observed during the 3 months after HZ ophthalmicus (HZO) onset (1.59; 1.10-2.32). The risk was highest 3 and 4 weeks after HZ onset and decreased thereafter.

Conclusions: Our study corroborates an increased risk of stroke after HZ, which is highest 3 to 4 weeks after HZ onset. The results suggest that the risk is more pronounced after HZO and is numerically higher for hemorrhagic than for ischemic stroke.

Fig 1. Definition of risk periods: (a) for primary analysis; (b) split by age group; (c) additional stratification by potential confounders (here: myocardial infarction).

Fig 2. Incidence rate ratios (IRRs) with 95% confidence intervals for stroke after HZ as well as for stroke after HZO in time intervals < 2 weeks, week 3–4, month 2–3, month 4–6, and month 7–12.