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

Abstract

BackgroundHerpes 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.MethodsA 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.ResultsThe 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.ConclusionsOur 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.

Incidence of herpes zoster amongst adults varies by severity of immunosuppression

“…Decades later, the latent virus can be reactivated and result in herpes zoster (HZ) which is usually characterised by a painful skin rash 2 . Since the reactivation of the VZV is typically associated with a decline in cell-mediated immunity, older and immunocompromised (IC) individuals are at higher risk of developing HZ and its complications like postherpetic neuralgia (PHN) and VZV vasculopathy [2][3][4][5][6][7][8][9] . Accordingly, a recently published systematic review reported an HZ incidence rate (IR) between 6 and 8 per 1,000 person-years (py) in 60-year-olds and between 8 and 12 per 1,000 py at age 80 10 .…”

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

“…However, little is known about the epidemiology of HZ in Asian RA patients, and the association between HZ and immunosuppressive agents in RA patients is controversial. In addition, several epidemiologic studies have demonstrated an increased risk of stroke after HZ . A recent systematic review and meta‐analysis showed that the risk of stroke is higher in patients with RA than in the general population .…”

A systematic review and meta-analysis on herpes zoster and the risk of cardiac and cerebrovascular events

“…Table 1 presents an overview of the eight retrospective cohort studies [ 22 – 30 ] and three self-case controlled case series [ 31 – 33 ] included in this review. We included self-controlled case series since these studies have a design akin to that of an efficient cohort study that minimizes confounding and produces measures of association, unlike a traditional case series [ 34 ].…”

“…We included self-controlled case series since these studies have a design akin to that of an efficient cohort study that minimizes confounding and produces measures of association, unlike a traditional case series [ 34 ]. The studies sampled populations from six countries including enrollees of the national health insurance systems in Taiwan [ 23 , 25 , 28 , 29 ] and South Korea [ 24 ], Danish hospital and prescription drug users [ 26 ], British primary care patients [ 22 , 31 ], American Medicare enrollees 65 years and older [ 32 ], residents 50 years and older in Olmsted County (MN, US) [ 30 ], enrollees of four private insurers in Germany [ 33 ] and residents of Västra Götaland County, Sweden [ 27 ]. All included studies performed retrospective reviews of electronic medical record databases; no study prospectively followed patients.…”