Herpes Zoster and the Risk of Stroke in Patients With Autoimmune Diseases

Abstract

Background Herpes zoster (HZ) is an opportunistic infection caused by varicella zoster virus (VZV), and observed with increasing frequency in patients on immunosuppressive therapies. Prior literature has suggested that the risk of stroke may increase shortly after herpes zoster, but little is known about this association for patients with autoimmune (AI) diseases, who are at increased risk both for zoster and stroke. Methods Medicare data (2006–2013) was used to identify patients with autoimmune diseases. The outcome of interest was hospitalized stroke. The hypothesis tested was that the incidence of stroke immediately following HZ was increased compared to the incidence of stroke at later time points. Secondary analysis included assessment of the impact of antiviral therapy on subsequent stroke as well as the influence of VZV-related complications on stroke incidence. Results The crude incidence of stroke ranged from a high of 2.30 (0.96–5.52) per 100 patient years within 90 days of HZ in patients who had HZ-related cranial nerve complications and did not receive treatment to a low of 0.87 (0.75–1.02) per 100py (>1 year after uncomplicated HZ). After multivariable adjustment for multiple stroke-related factors, the incidence rate ratio (IRR) for stroke in the first 90 days after HZ was 1.36 (1.10–1.68) compared to stroke >1 year after HZ. The risk was greater for patients with zoster with cranial nerve complications (IRR 2.08, 95%CI 0.99–4.36). Prompt antiviral therapy was associated with lower incidence of subsequent stroke (IRR 0.83, 95% CI 0.70–0.98). Conclusion In patients with autoimmune diseases, incident HZ was associated with up to a two-fold increased risk for stroke in the subsequent few months. These data provide urgency for developing strategies to reduce the risk of VZV.

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

“…Additionally, a further increase of stroke risk was observed in RA patients with HZ neurological complications (aHR=1.54, P =0.015). Furthermore, our results showed a 2.3‐fold increased risk of stroke within 90 days after HZ occurrence in RA patients compared with those without HZ ( P =0.02), which is consistent with a recent study for HZ‐related stroke in patients with autoimmune diseases in the United States . Increasing evidence showed that VZV vasculopathy and stroke were associated with HZ .…”

“…The diagnosis of HZ was required to have been made after the RA identification index date. The complication of HZ was in accordance with a diagnosis code (Table ) . The diagnosis of HZ‐related stroke was required to have been made after the HZ identification index date and was defined by patients with a diagnosis code of stroke (ICD‐9‐CM codes 430‐438).…”

“…Therefore, we excluded patients who had received a stroke diagnosis before the HZ diagnosis date. HZ complications and stroke were tracked during the 365‐ and 730‐day periods after the HZ index date, separately …”

Herpes Zoster as a Risk Factor for Incident Giant Cell Arteritis

“…Our study also does not address whether HZ selectively increases the risk of only GCA. The potential for HZ to trigger other diseases has been previously demonstrated, with HZ events being associated with an increased risk of stroke in the general population and among patients with autoimmune disease . While it is important to understand whether the risk of PMR is also increased following HZ events, we anticipated that administrative data sets would also be prone to misclassification of PMR, given that 1 study found a false‐positive rate of >20% for diagnostic codes of PMR .…”

“…HZ events were identified by ICD‐9‐CM code 053.xx from either a hospital discharge or physician visit record. HZ was further classified as complicated (i.e., HZ with meningitis, other nervous system, ophthalmic, or other complications; ICD‐9‐CM codes 053.0–053.8) or uncomplicated (code 053.9), similar to an HZ classification used in previous analyses . HZ treatment was identified by a combination of an HZ event and an accompanying outpatient pharmacy claim for acyclovir, famciclovir, valacyclovir, ganciclovir, or foscavir within 7 days before or after the HZ event date.…”