Herpes Zoster Ophthalmicus Associated With Increased Risk of Stroke

Fran Lowry

March 04, 2010

March 4, 2010 — Patients with herpes zoster ophthalmicus (HZO) appear to have an increased risk of developing stroke, according to new research appearing online in the March 3 issue of Neurology.

In a large, population-based study conducted in Taiwan, investigators from Taipei Medical University and National Yang-Ming University in Taipei, Taiwan, found that HZO patients had more than a 4-fold higher risk of having a stroke within 1 year than a matched cohort of controls.

The rate of stroke development was similar between patients who had received systemic antiviral treatment and those who had not.

"Shingles may represent a marker for increased risk of stroke," senior investigator Jau-Der Ho, MD, PhD, said in a statement from the American Academy of Neurology.

Latent Infection Reactivation

HZO occurs when a latent infection of the trigeminal ganglion becomes reactivated and involves the ophthalmic division of the trigeminal nerve. Approximately 10% to 20% of herpes zoster cases have ophthalmic involvement, and of these, 20% to 70% have ocular involvement.

According to the investigators, studies are lacking concerning the rate of stroke development in adult patients after an HZO attack and the effects of systemic antiviral treatment on the stroke rate.

To address this lack of information, the investigators, led by Herng-Ching Lin, PhD, collected data from the Taiwan National Health Insurance Research Database (NHIRD) to assess the relationship between HZO and the risk of future stroke development.

The NHIRD "is one of the largest and most complete nationwide population-based datasets in the world, and it provides a unique opportunity to examine the risk of stroke occurring among patients with HZO," according to the investigators.

They identified 658 patients diagnosed as having HZO from January 1, 2003, through December 31, 2004, and compared them with 1974 randomly selected controls matched by age and sex. None of the study subjects had a history of stroke at baseline.

During the 1-year study period, stroke developed in 53 patients with HZO (8.1%) and 33 patients in the comparison group (1.7%), a significant difference (P < .001).

Further, a significant difference was found in the type of strokes between these 2 groups (P < .001). Six HZO patients (11%) had hemorrhagic strokes, 43 (81%) had ischemic strokes, and 4 (8%) had unspecified strokes. In comparison, of the patients in the non-HZO cohort, 6 (21%) had hemorrhagic strokes, 18 (55%) had ischemic strokes, and 9 (27%) had unspecified strokes.

After adjusting for age, sex, hypertension, diabetes, hyperlipidemia, coronary heart disease, chronic rheumatic heart disease, other forms of heart disease, and medication use, the hazard ratio for stroke during the 1-year follow-up period for patients with HZO was 4.52 (95% confidence interval [CI], 2.45 – 8.33; P < .001) compared with patients in the comparison cohort.

The investigators also found that systemic antiviral treatment had no effect on reducing the risk of stroke among HZO patients. The hazard ratios were 5.16 (95% CI, 2.40 – 11.10; P < .001) for patients who received systemic antiviral therapy and 4.29 (95% CI, 2.26 – 8.14; P < .001) for patients who did not receive systemic antiviral therapy, compared with patients in the comparison cohort. No significant difference was found in the rate of stroke development between patients who had received systemic antiviral treatment and those who had not (P = .235).

However, the investigators note that data on criteria for antiviral treatment, timing of the start and duration of treatment, and patient compliance were not available from the NHIRD dataset and call for further prospective, controlled studies to determine the efficacy of antiviral treatment on reducing stroke risk after an HZO attack.

Other Agents?

In an accompanying editorial, Maria Nagel, MD, from the University of Colorado School of Medicine in Denver, and Gustavo A. Ortiz, MD, from the University of Miami Miller School of Medicine in Florida, agree that there is a need for more studies.

"Even though this study did not show any impact of antiviral treatment on the risk of stroke, length and doses of treatment, as well as the use of high-doses anti-inflammatory agents (steroids), may also need to be evaluated in the future to better assess the correlation between treatment and prevention of stroke," they write.

Dr. Nagel and Dr. Ortiz note that it would also be important to examine the risk of stroke in HIV-positive individuals who have a significantly increased risk for herpes zoster.

"Finally, as we face an aging population with increased risk factors for stroke, the results of this study reinforce the importance of primary and secondary stroke prevention in older people who develop HZO," they conclude.

Strong Evidence

Commenting on the study, Howard S. Kirshner, MD, professor and vice-chair of the Department of Neurology at Vanderbilt University Medical Center, Nashville, Tennessee, said it offered strong evidence linking HZO and stroke and is the first, to his knowledge, to compare patients with HZO to control subjects in such a large series.

"The risk of stroke was 4 times that of controls, which definitely establishes the connection between this condition and stroke, though it should be kept in mind that only 8% of the HZO patients suffered a stroke," Dr. Kirshner told Medscape Neurology.

The increased risk of stroke is yet another argument in favor of the shingles vaccine, he added. "Herpes zoster ophthalmicus is a serious condition. It is painful, it can cause loss of vision, and in a small minority of patients it can lead to stroke. This study is important because it cements the association through a population study, which I don’t believe has been done before. There are many arguments for the vaccine. This adds another one."

Dr. Ho, Dr. Lin, Dr. Nagel, Dr. Ortiz, and Dr. Kirshner have disclosed no relevant financial relationships.

Neurology. Published online March 3, 2010.

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