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Herpes Zoster as a Risk Factor for Incident Giant Cell Arteritis.

ABSTRACT: OBJECTIVE:Histopathologic studies have implicated herpes zoster (HZ) as a causative organism of giant cell arteritis (GCA). The purpose of this study was to assess the epidemiologic association of HZ events with incident GCA. METHODS:We performed a retrospective cohort study in 2 large independent US administrative data sets: Medicare 5% and Truven Health Analytics MarketScan. Eligible subjects had 12 months of continuous coverage, were >50 years old, and had no history of GCA or polymyalgia rheumatica. HZ events (complicated and uncomplicated) and GCA were identified by the presence of International Classification of Diseases, Ninth Revision, Clinical Modification codes from physician visit or hospital discharge records. Antiviral therapies and vaccinations were identified from prescription claims and drug codes. Risk of incident GCA was calculated using multivariable Cox proportional hazards regression. RESULTS:Among 16,686,345 subjects, a total of 5,942 GCA cases occurred, with 3.1% (MarketScan) and 6.0% (Medicare) having preceding HZ events. Unadjusted GCA incidence rates were highest in the groups with complicated and uncomplicated HZ. After multivariable adjustment, complicated HZ was associated with an increased risk of GCA (hazard ratio [HR] 1.99 [95% confidence interval (95% CI) 1.32-3.02] in the Medicare cohort and 2.16 [95% CI 1.46-3.18] in the MarketScan cohort), as was uncomplicated HZ (HR 1.42 [95% CI 1.02-1.99] and HR 1.45 [95% CI 1.05-2.01] in the respective cohorts). Vaccination and antiviral treatment were not consistently associated with GCA risk, although antiviral treatment was marginally associated with a decreased risk of GCA in the Medicare cohort (HR 0.67 [95% CI 0.46-0.99]). CONCLUSION:HZ is associated with an increased risk of GCA. The infrequency of HZ in GCA patients suggests that it is only one potential trigger for GCA. Antivirals and vaccination did not consistently mitigate this risk.

SUBMITTER: England BR

PROVIDER: S-EPMC5711552 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Herpes Zoster as a Risk Factor for Incident Giant Cell Arteritis.

England Bryant R BR Mikuls Ted R TR Xie Fenglong F Yang Shuo S Chen Lang L Curtis Jeffrey R JR

Arthritis & rheumatology (Hoboken, N.J.) 20171109 12

<h4>Objective</h4>Histopathologic studies have implicated herpes zoster (HZ) as a causative organism of giant cell arteritis (GCA). The purpose of this study was to assess the epidemiologic association of HZ events with incident GCA.<h4>Methods</h4>We performed a retrospective cohort study in 2 large independent US administrative data sets: Medicare 5% and Truven Health Analytics MarketScan. Eligible subjects had 12 months of continuous coverage, were >50 years old, and had no history of GCA or ...[more]

PMID: 28853238

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Project description:IntroductionHerpes zoster, which can have a major impact on quality of life, results from reactivation of a latent varicella zoster virus (VZV) infection. We hypothesized that giant cell arteritis (GCA) patients are at increased risk of herpes zoster because of treatment with high-dose glucocorticoids and advanced age. Aim of the study, therefore, was to determine cell-mediated and humoral immunity to VZV in patients with GCA, patients with closely related disease polymyalgia rheumatica (PMR; treated with lower doses of glucocorticoids) and healthy controls (HCs).MethodsCell-mediated immunity to VZV was determined by performing interferon-γ (IFNγ) enzyme-linked immunospot and intracellular cytokine flow cytometry measurements in 11 GCA and 15 PMR patients and in 26 age/sex-matched HCs. Immunoglobulin G antibodies to VZV glycoprotein (VZV-IgG) were measured in serum samples of 35 GCA and 26 PMR patients at different times of follow-up and in 58 age and sex-matched HCs by an enzyme-linked immunosorbent assay.ResultsThe number of VZV-specific IFNγ spot-forming cells was significantly lower in GCA patients on treatment, than in age-matched HCs (p = 0.029), but was not different in PMR patients on treatment. Similar levels of VZV-IgG were found in GCA and PMR patients at baseline, compared to HCs.ConclusionThe finding of a decreased cell-mediated immunity to VZV, known to be of great importance in defense to the virus, indicates an increased herpes zoster risk in GCA patients compared to an already at-risk elderly population. Herpes zoster vaccination is, therefore, of special importance in GCA patients, and would ideally be administered at time of diagnosis. Interestingly, as VZV was suggested to be the trigger in GCA pathogenesis, similar levels of VZV-IgG were found in GCA patients at time of diagnosis and age-matched HCs, indicating that GCA patients did not experience herpes zoster substantially more often in the months preceding diagnosis than controls.

Project description:Giant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV).To analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals.A cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years.Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers.Varicella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk [RR]?=?2.86; 95% CI, 1.75-5.31; P?<?.001). Extension of our earlier study revealed VZV antigen in 68 of 93 GCA-positive TAs (73%), compared with 11 of 49 normal TAs (22%) (RR?=?3.26; 95% CI, 2.03-5.98; P?<?.001). Compared with normal TAs, VZV antigen was more likely to be present in the adventitia of both GCA-negative TAs (RR?=?2.43; 95% CI, 1.82-3.41; P?<?.001) and GCA-positive TAs (RR?=?2.03; 95% CI, 1.52-2.86; P?<?.001). Varicella-zoster virus antigen was frequently found in perineurial cells expressing claudin-1 around nerve bundles. Of 45 GCA-negative participants whose TAs contained VZV antigen, 1 had histopathological features characteristic of GCA, and 16 (36%) showed adventitial inflammation adjacent to viral antigen; no inflammation was seen in normal TAs.In patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

Dataset Information

Herpes Zoster as a Risk Factor for Incident Giant Cell Arteritis.

Publications

Herpes Zoster as a Risk Factor for Incident Giant Cell Arteritis.

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