Incidence of Giant Cell Arteritis Following Herpes Zoster Ophthalmicus: A Multicenter Retrospective Cohort Study

Objective: To evaluate the long-term risk of incident giant cell arteritis (GCA) following herpes zoster ophthalmicus (HZO). Design: Retrospective cohort study. Participants and Controls: Adults aged ≥50 years with a diagnosis of HZO (ICD-10 B02.3) between May 2005 and April 2024 were identified from the TriNetX Global Collaborative Network and compared to controls without any history of zoster. All patients had ≥6 months of data before and after the index date. Individuals with prior diagnoses of GCA, polymyalgia rheumatica, HIV, or transplant status were excluded. Methods: Propensity score matching (PSM) was applied in a 1:1 ratio to balance baseline characteristics. Time-to-event analysis was performed using a Cox proportional hazards model and a log-rank test, with cumulative incidence illustrated by a Kaplan–Meier curve. Sensitivity analyses evaluated the impact of antiviral therapy and prior zoster vaccination. Main Outcome Measures: Incident GCA (ICD-10 M31.5 or M31.6), assessed beginning 30 days after index diagnosis. The E-value was calculated to assess robustness against unmeasured confounding. Results: After matching, 18 154 patients were included in each cohort (mean age, 66.6 years; 57.5% female). During 10 years of follow-up, GCA occurred in 42 HZO patients and 14 controls, corresponding to incidence rates of 49.9 vs 16.2 per 100 000 person-years (log-rank P < .001). HZO was associated with a more than threefold increased risk of GCA (HR, 3.09; 95% CI, 1.69–5.65). The E-value was 5.63 for the HR and 2.77 for the lower confidence limit. In sensitivity analyses, antiviral therapy initiated within 7 days of HZO diagnosis was not associated with a reduced risk of GCA (HR, 0.86; 95% CI, 0.43–1.68), and herpes zoster vaccination administered ≥1 month before HZO diagnosis showed no protective association (HR, 1.60; 95% CI, 0.55–4.66). Conclusions: In this large real-world cohort, HZO was associated with an increased risk of incident GCA, although the absolute risk remained low. Further research is needed to clarify pathophysiologic mechanisms and the potential impact of antiviral or vaccine-based interventions.