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Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis.

ABSTRACT: 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?

SUBMITTER: Nagel MA

PROVIDER: S-EPMC5110206 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis.

Nagel Maria A MA White Teresa T Khmeleva Nelly N Rempel April A Boyer Philip J PJ Bennett Jeffrey L JL Haller Andrea A Lear-Kaul Kelly K Kandasmy Balasurbramaniyam B Amato Malena M Wood Edward E Durairaj Vikram V Fogt Franz F Tamhankar Madhura A MA Grossniklaus Hans E HE Poppiti Robert J RJ Bockelman Brian B Keyvani Kathy K Pollak Lea L Mendlovic Sonia S Fowkes Mary M Eberhart Charles G CG Buttmann Mathias M Toyka Klaus V KV Meyer-ter-Vehn Tobias T Petursdottir Vigdis V Gilden Don D

JAMA neurology 20151101 11

<h4>Importance</h4>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).<h4>Objective</h4>To analyze VZV infection in TAs of patients with clinically suspected GCA who ...[more]

PMID: 26349037

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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:IntroductionTemporal artery (TA) biopsy is commonly used for the diagnosis of giant cell arteritis (GCA). However, a positive biopsy is no longer mandatory for diagnosis. This study aims to correlate the histopathological findings of TA biopsies in suspected cases of GCA to the clinical presentation in an ophthalmic tertiary eye care center to draw useful conclusions and advocate the possible implementation of guidelines for TA biopsy.MethodsData was collected from patients' medical records including, demographics, clinical data, and histopathological findings and diagnosis. The 2022 American College of Rheumatology/ European Alliance of Associations for Rheumatology (ACR/EULAR) criteria have been used and partially adopted as a guide to compare the variables between TA biopsy-positive and negative groups as well as the TA biopsy-positive group and the group of patients with TA biopsy showing atherosclerosis.ResultsOut of the total 35 patients who underwent a TA biopsy during the period of 23 years, 22.9% of patients had histopathological findings consistent with GCA and 42.9% had TA atherosclerotic changes, while the remaining 34.3% had histologically unremarkable TA. The mean age of all patients was 66 ± 10.9 years. Slightly more than half were females (54.3%) and the remaining were males (45.7%). In the group with positive TA biopsies, the mean age was 71 ± 8.4 years with a higher female predominance (female-to-male ratio of 5:3). The mean diagnostic clinical score used in our study was higher (7.5 ± 2.33) in the GCA-positive group when compared to the other groups with statistical significance (mean of 4.85 ± 2.01 in patients with overall GCA-negative biopsies and 5.13 ± 2.10 in the group with atherosclerosis). Other three clinical variables that were found to be statistically significant in the GCA biopsy-positive group were scalp tenderness, jaw claudication, and optic nerve pallor.DiscussionThe mean age (71 ± 8.4 years) and the female predominance of GCA in our group of patients with positive TA biopsy (62.5%) was like other reports. In our study 22.9% of performed TA biopsies over the period of the study were positive confirming the diagnosis of GCA on histological exam, which was similar to another report and is considered to be relatively low. The incorporation of increased clinically focused assessments and algorithms, with the aid of the ACR/EULAR criteria, may decrease the frequency of TA biopsies that carries unnecessary cost and risk of procedure-related morbidity. We highly recommend applying the age of ≥ 50 years as an initial criterion for diagnosis, followed by the consideration of the statistically significant clinical features: scalp tenderness, jaw claudication, and optic nerve pallor.

Project description:Although a temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis (GCA), there is considerable evidence that characteristic signs demonstrated by colour duplex sonography (CDS) of the temporal arteries may be of diagnostic importance. We aimed to test the hypothesis that CDS can replace biopsy in the algorithm for the approach to diagnose GCA. Bilateral CDS was performed in consecutive patients older than 50 years with clinically suspected GCA, as well as in 15 age- and gender-matched control subjects with diabetes mellitus and/or stroke and 15 healthy subjects, to assess flow parameters and the possible presence of a dark halo around the arterial lumen. Unilateral temporal artery biopsy was then performed in patients with suspected GCA, which was directed to a particular arterial segment in case a halo was detected in CDS. Final diagnoses, after completion of a 3-month follow-up in 55 patients, included GCA (n = 22), polymyalgia rheumatica (n = 12), polyarteritis nodosa, Wegener's, and Adamantiades-Behçet's diseases (n = 3), and neoplastic (n = 8) and infectious diseases (n = 10). A dark halo of variable size (0.7-2.0 mm) around the vessel lumen was evident at baseline CDS in 21 patients (in 12 and 9 uni- or bilaterally, respectively) but in none of the controls. The presence of unilateral halo alone yielded 82% sensitivity and 91% specificity for GCA, whereas the specificity reached 100% when halos were found bilaterally. Blood-flow abnormal parameters (temporal artery diameter, peak systolic blood-flow velocities, stenoses, occlusions) were common in GCA and non-GCA patients, as well as in healthy and atherosclerotic disease-control, elderly subjects. At follow-up CDS examinations performed at 2 and 4 weeks after initiation of corticosteroid treatment for GCA, halos disappeared in all 18 patients (9 and 9, respectively). We conclude that CDS, an inexpensive, non-invasive, and easy-to-perform method, allows a directional biopsy that has an increased probability to confirm the clinical diagnosis. Biopsy is not necessary in a substantial proportion of patients in whom bilateral halo signs can be found by CDS.

Dataset Information

Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis.

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Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis.

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