RESUMEN
PURPOSE OF REVIEW: Giant cell arteritis (GCA) is a severe form of vasculitis in the elderly. The recent discovery of varicella zoster virus (VZV) in the temporal arteries and adjacent skeletal muscle of patients with GCA, and the rationale and strategy for antiviral and corticosteroid treatment for GCA are reviewed. RECENT FINDINGS: The clinical features of GCA include excruciating headache/head pain, often with scalp tenderness, a nodular temporal arteries and decreased temporal artery pulsations. Jaw claudication, night sweats, fever, malaise, and a history of polymyalgia rheumatica (aching and stiffness of large muscles primarily in the shoulder girdle, upper back, and pelvis without objective signs of weakness) are common. ESR and CRP are usually elevated. Diagnosis is confirmed by temporal artery biopsy which reveals vessel wall damage and inflammation, with multinucleated giant cells and/or epithelioid macrophages. Skip lesions are common. Importantly, temporal artery biopsies are pathologically negative in many clinically suspect cases. This review highlights recent virological findings in temporal arteries from patients with pathologically verified GCA and in temporal arteries from patients who manifest clinical and laboratory features of GCA, but whose temporal artery biopsies (Bx) are pathologically negative for GCA (Bx-negative GCA). Virological analysis revealed that VZV is present in most GCA-positive and GCA-negative temporal artery biopsies, mostly in skip areas that correlate with adjacent GCA pathology. SUMMARY: The presence of VZV in Bx-positive and Bx-negative GCA temporal arteries indicates that VZV triggers the immunopathology of GCA. However, the presence of VZV in about 20% of temporal artery biopsies from non-GCA postmortem controls also suggests that VZV alone is not sufficient to produce disease. Treatment trials should be performed to determine if antiviral agents confer additional benefits to corticosteroids in both Bx-positive and Bx-negative GCA patients. These studies should also examine whether oral antiviral agents and corticosteroids are as effective as intravenous acyclovir and corticosteroids. Appropriate dosage and duration of treatment also remain to be determined.
Asunto(s)
Arteritis de Células Gigantes/virología , Herpes Zóster/complicaciones , Herpesvirus Humano 3/aislamiento & purificación , Antivirales/uso terapéutico , Aortitis/virología , Biopsia , Arteritis de Células Gigantes/tratamiento farmacológico , Arteritis de Células Gigantes/inmunología , Arteritis de Células Gigantes/patología , Herpes Zóster/tratamiento farmacológico , Herpes Zóster/patología , Humanos , Arterias Temporales/patología , Arterias Temporales/virologíaRESUMEN
PURPOSE OF REVIEW: Giant cell arteritis (GCA) is a serious disease and the most common cause of vasculitis in the elderly. Here, studies describing the recent discovery of varicella zoster virus (VZV) in the temporal arteries of patients with GCA are reviewed. RECENT FINDINGS: GCA is characterized by severe headache/head pain and scalp tenderness. Many patients also have a history of vision loss, jaw claudication, polymyalgia rheumatica, fever, night sweats, weight loss, and fatigue. The erythrocyte sedimentation rate and C-reactive protein are usually elevated. Diagnosis is confirmed by temporal artery biopsy, which reveals vessel wall damage and inflammation, with multinucleated giant cells and/or epithelioid macrophages. Skip lesions are common. Importantly, temporal artery biopsies are pathologically negative in many clinically suspect cases. The present review highlights recent virological findings in temporal arteries from patients with pathologically verified GCA and in temporal arteries from patients who manifest clinical and laboratory features of GCA but whose temporal artery biopsies are pathologically negative for GCA. Virological analysis revealed that VZV is present in most GCA-positive and GCA-negative temporal artery biopsies, particularly in skip areas that correlate with adjacent GCA disease. SUMMARY: The presence of VZV in GCA-positive and GCA-negative temporal arteries reflects the possible role of VZV in triggering the immunopathology of GCA and indicates that both groups of patients should be treated with antivirals in addition to corticosteroids. Whether oral antiviral agents and steroids are as effective as intravenous acyclovir and steroids, and the dosage and duration of treatment, remain to be determined.
Asunto(s)
Arteritis de Células Gigantes , Infecciones por Herpesviridae , Herpesvirus Humano 3 , Arterias Temporales/virología , Anciano , Anciano de 80 o más Años , Femenino , Arteritis de Células Gigantes/inmunología , Arteritis de Células Gigantes/virología , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/virología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Giant cell arteritis (GCA) is an immune-mediated disease of unknown etiology. Varicella zoster virus (VZV) antigen was found in all of 4 GCA-positive temporal arteries (TAs) but was not present in any of 13 normal TAs. All 4 GCA-positive TAs contained viral antigen in skip areas, mostly in the adventitia and media and least in the intima. Despite formalin fixation, VZV DNA was detected in 2 of 4 GCA-positive, VZV antigen-positive TAs. Skeletal muscle was attached to 3 of 4 TAs, and VZV antigen was found in 2 and VZV DNA in 1. VZV may cause GCA.
Asunto(s)
Arteritis de Células Gigantes/virología , Herpesvirus Humano 3/química , Arterias Temporales/virología , Anticuerpos Antivirales/análisis , Antígenos Virales/análisis , Arteritis de Células Gigantes/inmunología , Herpesvirus Humano 3/inmunología , Herpesvirus Humano 3/aislamiento & purificación , Histocitoquímica , Humanos , Persona de Mediana Edad , Arterias Temporales/química , Arterias Temporales/patologíaRESUMEN
Giant cell arteritis is an inflammatory vasculopathy that preferentially affects medium-sized and large arteries. A viral cause has been suspected but not confirmed in polymyalgia rheumatica and giant-cell arteritis. We report the case of a 81-year-old female who suffered from chronic active Epstein-Barr virus infection and developed giant cell temporal arteritis.
Asunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Arteritis de Células Gigantes/etiología , Anciano de 80 o más Años , Biopsia , Enfermedad Crónica , ADN Viral/aislamiento & purificación , Femenino , Arteritis de Células Gigantes/virología , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Arterias Temporales/patología , Arterias Temporales/virologíaRESUMEN
BACKGROUND AND OBJECTIVES: Varicella zoster virus (VZV) antigen has been detected in temporal arteries (TAs) of individuals with giant cell arteritis (GCA), the most common systemic vasculitis in older adults. Thus, we explored the contribution of VZV to GCA pathogenesis. METHODS: Formalin-fixed, paraffin-embedded TA sections from biopsy-positive GCA participants with VZV antigen (GCA/VZV-positive; n = 20) and without (GCA/VZV-negative, n = 20) and from normal participants with VZV antigen (control/VZV-positive, n = 11) and without (control/VZV-negative, n = 20) were analyzed by targeted RNA sequencing of the whole human transcriptome (BioSpyder TempO-Seq). Ingenuity pathway analysis and R-computational program were used to identify differentially expressed genes and pathways between groups. RESULTS: Compared with control/VZV-negative TAs, GCA/VZV-negative and GCA/VZV-positive TAs were significantly enriched for human transcripts specific for pathways involved in viral infections, including viral entry, nuclear factor kappa B activation by viruses, and other pathogen-related immune activation pathways. Similarly, human gene sets supporting viral infection were found in control/VZV-positive TAs that showed no morphological signs of inflammation, suggesting that the enriched pathways were not nonspecific signatures of infiltrating immune cells. All GCA TAs and control/VZV-positive TAs showed enrichment of transcripts involved in vascular remodeling, including smooth muscle cell migration. DISCUSSION: The detection of viral and immune activation pathways in GCA TAs supports a role for virus infection in GCA pathogenesis. In addition, the detection of viral pathways in control/VZV-positive TAs, along with vascular remodeling pathways, suggests that these samples may represent early infection with progression to clinical disease, depending on host and other environmental factors.
Asunto(s)
Antígenos Virales/aislamiento & purificación , ADN Viral/aislamiento & purificación , Arteritis de Células Gigantes/virología , Herpesvirus Humano 3 , Arterias Temporales/virología , Anciano , Femenino , Formaldehído , Perfilación de la Expresión Génica , Arteritis de Células Gigantes/patología , Humanos , Masculino , Persona de Mediana Edad , Adhesión en Parafina , Análisis de Secuencia de ARN , Arterias Temporales/patología , Fijación del TejidoRESUMEN
OBJECTIVE: A variety of infectious agents, including varicella zoster virus (VZV), have been hypothesized to play a role in the pathogenesis of giant cell arteritis (GCA). The detectability of the virus in patients with GCA is debatable. To further investigate an association between GCA and VZV infection, 10 years of GCA cases were evaluated for VZV by immunohistochemistry (IHC). METHODS: All temporal artery biopsies and ascending aortic resections positive for GCA from 2007 to 2017 at Brigham and Women's Hospital were immunostained using a VZV antibody cocktail (SG1-1, SG1-SG4, NCP-1, and IE-62). RESULTS: Forty-one temporal artery biopsies and 47 ascending aortic resections positive for GCA were identified, all of which were found to be negative for VZV by IHC. Twelve temporal artery biopsies in this cohort were previously analyzed by unbiased metagenomics sequencing and were negative for VZV DNA. CONCLUSION: These results argue against a clinically relevant association between VZV infection and GCA, and support neither routine testing for VZV nor treatment with antiviral drugs.
Asunto(s)
Aorta/virología , Arteritis de Células Gigantes/virología , Herpesvirus Humano 3/aislamiento & purificación , Arterias Temporales/virología , Anciano , Anciano de 80 o más Años , Aorta/patología , Femenino , Arteritis de Células Gigantes/patología , Humanos , Masculino , Persona de Mediana Edad , Arterias Temporales/patologíaRESUMEN
OBJECTIVE: Data on the presence of varicella-zoster virus (VZV) in temporal arteries of patients with giant cell arteritis (GCA) are controversial. We analyzed VZV infection in temporal arteries from Italian patients with temporal artery biopsy (TAB)-positive GCA, TAB-negative GCA, and controls. METHODS: A total of 79 formalin-fixed, paraffin-embedded (FFPE) TABs performed between 2009 and 2012 at a single institution from 34 TAB-positive GCA patients, 15 TAB-negative GCA patients, and 30 controls were retrieved. Six 5-µm sections of all FFPE TABs were cut. The first section was analyzed by immunohistochemistry using mouse monoclonal anti-VZVgE IgG1 antibody. DNA was extracted from the remaining five sections and analyzed by real-time polymerase chain reaction (PCR) for the presence of VZV DNA. For 10 of the 34 TAB-positive GCA patients, an additional 2-mm piece of frozen TAB was available. DNA was extracted from the entire 2-mm length frozen specimen and analyzed by PCR for the presence of VZV DNA. Thirty additional 5-µm sections were cut from the FFPE TABs of these 10 patients and analyzed by immunohistochemistry for the presence of VZV antigen. RESULTS: Immunohistochemical analysis detected VZV antigen in 1/34 (3%) TAB-positive GCA, 0/15 TAB-negative GCA, and 0/30 controls, and in none of the 300 sections cut from the 10 FFPE TABs positive for GCA for which the frozen specimens were available. DNA obtained from all TABs was amplifiable. VZV DNA was neither found in any of the FFPE TABs nor found in frozen TABs. CONCLUSION: Our data do not support in Italian patients a possible role for VZV infection in the etiopathogenesis of GCA.
Asunto(s)
Arteritis de Células Gigantes/virología , Herpesvirus Humano 3/aislamiento & purificación , Arterias Temporales/virología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Recent analysis of archived temporal arteries (TAs) acquired from 13 pathology laboratories in the US, Canada, Iceland, France, Germany and Israel from patients with pathologically-verified giant cell arteritis (GCA-positive) and TAs from patients with clinical features and laboratory abnormalities of GCA but whose TAs were pathologically negative (GCA-negative) revealed VZV antigen in most TAs from both groups. Despite formalin-fixation, VZV DNA was also found in many VZV-antigen positive sections that were scraped, subjected to DNA extraction, and examined by PCR with VZV-specific primers. Importantly, in past studies, the pathological diagnosis (GCA-positive or -negative) was known to the neurovirology laboratory. Herein, GCA-positive and GCA-negative TAs were provided by an outside institution and examined by 4 investigators blinded to the pathological diagnoses. VZV antigen was found in 3/3 GCA-positive TAs and in 4/6 GCA-negative TAs, and VZV DNA in 1/3 VZV antigen-positive, GCA-positive TAs and in 3/4 VZV antigen-positive, GCA-negative TAs. VZV DNA was also detected in one GCA-negative, VZV-antigen negative TA. Overall, the detection of VZV antigen in 78% of GCA-positive and GCA-negative TAs is consistent with previous reports on the prevalence of VZV antigen in patients with clinically suspect GCA.
Asunto(s)
ADN Viral/genética , Arteritis de Células Gigantes/patología , Herpes Zóster/patología , Herpesvirus Humano 3/metabolismo , Arterias Temporales/virología , Arteritis de Células Gigantes/metabolismo , Arteritis de Células Gigantes/virología , Herpes Zóster/virología , Herpesvirus Humano 3/genética , Humanos , Arterias Temporales/patología , Proteínas Virales/genética , Proteínas Virales/inmunologíaRESUMEN
Giant cell arteritis (GCA) affecting the cranial arteries is a disease of unknown cause that causes blindness, stroke, and other morbidity. Its sudden onset and segmental distribution are suggestive of diseases that involve viral reactivation, and cranial arteries are known to be innervated by ganglia that harbor herpes simplex virus (HSV). We used a high-sensitivity polymerase chain reaction assay to test for HSV DNA in specimens from 39 consecutive temporal artery biopsies performed for suspected GCA. HSV DNA was detected in 21 (88%) of 24 histologically positive and 8 (53%) of 15 histologically negative specimens (P = .027; Fisher exact test). Analysis of 10 renal artery samples from age-matched control subjects using the same assay showed no detectable HSV DNA. We conclude that detectable HSV DNA is correlated with histologically confirmed GCA in this patient population.
Asunto(s)
Arteritis de Células Gigantes/virología , Herpes Simple/complicaciones , Simplexvirus/aislamiento & purificación , Arterias Temporales/virología , Anciano , Anciano de 80 o más Años , Biopsia , ADN Viral/análisis , Femenino , Arteritis de Células Gigantes/patología , Herpes Simple/patología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Arteria Renal/patología , Arteria Renal/virología , Simplexvirus/genética , Arterias Temporales/patologíaRESUMEN
OBJECTIVE: Varicella-zoster virus (VZV) infection may trigger the inflammatory cascade that characterizes giant cell arteritis (GCA). METHODS: Formalin-fixed, paraffin-embedded GCA-positive temporal artery (TA) biopsies (50 sections/TA) including adjacent skeletal muscle and normal TAs obtained postmortem from subjects >50 years of age were examined by immunohistochemistry for presence and distribution of VZV antigen and by ultrastructural examination for virions. Adjacent regions were examined by hematoxylin & eosin staining. VZV antigen-positive slides were analyzed by PCR for VZV DNA. RESULTS: VZV antigen was found in 61/82 (74%) GCA-positive TAs compared with 1/13 (8%) normal TAs (p < 0.0001, relative risk 9.67, 95% confidence interval 1.46, 63.69). Most GCA-positive TAs contained viral antigen in skip areas. VZV antigen was present mostly in adventitia, followed by media and intima. VZV antigen was found in 12/32 (38%) skeletal muscles adjacent to VZV antigen-positive TAs. Despite formalin fixation, VZV DNA was detected in 18/45 (40%) GCA-positive VZV antigen-positive TAs, in 6/10 (60%) VZV antigen-positive skeletal muscles, and in one VZV antigen-positive normal TA. Varicella-zoster virions were found in a GCA-positive TA. In sections adjacent to those containing VZV, GCA pathology was seen in 89% of GCA-positive TAs but in none of 18 adjacent sections from normal TAs. CONCLUSIONS: Most GCA-positive TAs contained VZV in skip areas that correlated with adjacent GCA pathology, supporting the hypothesis that VZV triggers GCA immunopathology. Antiviral treatment may confer additional benefit to patients with GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.
Asunto(s)
Encefalitis por Varicela Zóster/epidemiología , Encefalitis por Varicela Zóster/virología , Arteritis de Células Gigantes/epidemiología , Arteritis de Células Gigantes/virología , Herpesvirus Humano 3/aislamiento & purificación , Arterias Temporales/virología , Anciano , Anciano de 80 o más Años , Enfermedades Arteriales Cerebrales/epidemiología , Enfermedades Arteriales Cerebrales/virología , Comorbilidad , Femenino , Humanos , Internacionalidad , Masculino , Persona de Mediana Edad , Prevalencia , Factores de RiesgoRESUMEN
IMPORTANCE: 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). OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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.
Asunto(s)
Arteritis de Células Gigantes , Herpes Zóster , Herpesvirus Humano 3/patogenicidad , Arterias Temporales , Anciano , Anciano de 80 o más Años , Biopsia , Estudios Transversales , Femenino , Arteritis de Células Gigantes/inmunología , Arteritis de Células Gigantes/patología , Arteritis de Células Gigantes/virología , Herpes Zóster/inmunología , Herpes Zóster/patología , Herpes Zóster/virología , Herpesvirus Humano 3/inmunología , Humanos , Masculino , Persona de Mediana Edad , Arterias Temporales/inmunología , Arterias Temporales/patología , Arterias Temporales/virologíaRESUMEN
PURPOSE: The purpose of this study was to determine whether an association exists between giant cell arteritis (GCA) and the presence of varicella-zoster virus (VZV), by using histologic, molecular, immunohistochemical, and ultrastructural analyses of temporal artery biopsy specimens. METHODS: In a randomized masked study, 64 temporal artery biopsy specimens were analyzed by PCR for VZV DNA. The samples included 35 specimens histologically positive and 29 specimens histologically negative for GCA. Immunohistochemical staining for VZV viral antigen IE-63 was performed on seven of the specimens positive for GCA and five negative specimens. Transmission electron microscopy (TEM) was performed on five of the specimens positive for GCA. RESULTS: PCR was positive for VZV DNA in 9 (26%) temporal arteries tested that showed histologic evidence of GCA. The remaining 26 histologically positive temporal arteries and all 29 histologically negative arteries tested gave negative PCR results for VZV DNA. Statistical analysis (z-test) comparing the association of VZV DNA between the specimens that were positive and negative for GCA showed a significant difference (P = 0.010). Immunohistochemical studies were positive in several biopsy specimens within adventitial histiocytes-macrophages, but these results did not correlate with either the presence or absence of VZV DNA or with the histologic evidence of GCA. No viral particles were observed by TEM. CONCLUSIONS: This study showed a significant association of VZV DNA to temporal artery biopsy samples positive for GCA compared with the negative specimens. The results support the hypothesis that VZV may play a role in the pathogenesis of some cases of GCA. However, PCR, immunohistochemical, and electron microscopic findings suggest the virus is present at extremely low quantities, is abortively replicating, or is latent.
Asunto(s)
ADN Viral/análisis , Arteritis de Células Gigantes/virología , Herpesvirus Humano 3/aislamiento & purificación , Arterias Temporales/virología , Biopsia , Método Doble Ciego , Arteritis de Células Gigantes/patología , Herpesvirus Humano 3/genética , Humanos , Técnicas para Inmunoenzimas , Estudios Prospectivos , Estudios Retrospectivos , Arterias Temporales/ultraestructuraRESUMEN
BACKGROUND: Compelling arguments exist for a role of infectious agent in giant cell arteritis (GCA). Parvovirus B19 and several herpesviruses have focussed the attention in recent years, but the few studies to date have yielded inconsistent results. OBJECTIVES: To study the relationship between the presence of parvovirus B19 DNA or major known herpesviruses and the histopathological features of GCA. STUDY DESIGN: Between January 1997 and March 2002, 147 consecutive temporal artery biopsies were performed in our center because of a clinical suspicion of GCA. Using polymerase chain reaction (PCR) procedures validated by the World Health Organization and employed routinely by our laboratory, we examined the paraffin-embedded specimens for DNA from parvovirus B19, herpes simplex viruses (HSV) 1 and 2, Epstein-Barr virus (EBV), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and human herpesvirus 6 (HHV-6). We investigated positive results further with immunohistochemistry studies. RESULTS: Fifty of the 147 temporal artery biopsies (34%) showed histological features of GCA. Three biopsies (2.5%) were initially PCR positive for parvovirus B19. None of the herpesvirus PCR assays were positive. Upon repeat testing by both PCR and immunohistochemistry, none of the three initially positive parvovirus B19 assays were confirmed. The results of both positive and negative control assays in these studies validated these findings. We confirmed the presence of amplifiable DNA in the temporal artery biopsy specimens using PCR primers for beta-globin and indoleamine 2,3-dioxygenase (IDO). CONCLUSIONS: The results of our study do not support a role in the etiopathogenesis of GCA for either parvovirus B19 or any of these six herpesviruses.
Asunto(s)
ADN Viral/análisis , Arteritis de Células Gigantes/virología , Herpesviridae/aislamiento & purificación , Parvovirus B19 Humano/aislamiento & purificación , Anciano , Biopsia , Femenino , Arteritis de Células Gigantes/etiología , Globinas/genética , Herpesviridae/genética , Infecciones por Herpesviridae/virología , Humanos , Inmunohistoquímica , Indolamina-Pirrol 2,3,-Dioxigenasa , Masculino , Infecciones por Parvoviridae/virología , Parvovirus B19 Humano/genética , Reacción en Cadena de la Polimerasa , Arterias Temporales/patología , Arterias Temporales/virología , Triptófano Oxigenasa/genéticaRESUMEN
PURPOSE: To present a case of herpes zoster vasculitis presenting as giant cell arteritis. DESIGN: Interventional case report. METHODS: A 77-year-old woman presented with sudden onset of diplopia associated with temple headaches and a previous history of herpes zoster ophthalmicus. A temporal artery biopsy was obtained and in-situ hybridization performed for herpes zoster DNA. RESULTS: The patient presented with a bilateral internuclear ophthalmoplegia. Initial diagnostic evaluation, including erythrocyte sedimentation rate, C-reactive protein, and temporal artery biopsy, was consistent with giant cell arteritis. However, in-situ hybridization of the temporal artery specimen was positive for herpes zoster DNA. CONCLUSIONS: Herpes zoster vasculitis may mimic giant cell arteritis and should be considered in the differential of any patient with presumed giant cell arteritis with suspicious findings, central nervous system involvement, or previous herpes zoster infection.
Asunto(s)
Arteritis de Células Gigantes/diagnóstico , Herpes Zóster Oftálmico/diagnóstico , Trastornos de la Motilidad Ocular/diagnóstico , Anciano , ADN Viral/análisis , Diagnóstico Diferencial , Diplopía/etiología , Movimientos Oculares , Femenino , Arteritis de Células Gigantes/etiología , Cefalea/etiología , Herpes Zóster Oftálmico/complicaciones , Humanos , Hibridación in Situ , Trastornos de la Motilidad Ocular/etiología , Arterias Temporales/patología , Arterias Temporales/virología , Agudeza VisualRESUMEN
It has been suggested that Varicella-Zoster virus (VZV) may play a role in the pathogenesis of giant cell arteritis (GCA). We therefore used both in situ hybridisation and in situ Polymerase Chain Reaction amplification techniques in an attempt to identify VZV DNA in 15 temporal arteries from histologically proven GCA. We did not detect evidence of VZV DNA in the arteries of any of these subjects, nor in temporal arteries obtained from seven normal control subjects. VZV was detected, however, in neurons in a human trigeminal ganglion. While sampling variation and sensitivity issues are likely to play a role in the discrepancies observed in different studies of VZV in GCA, this study does not provide further support for the notion that VZV is playing a significant part in causing GCA.
Asunto(s)
ADN Viral/análisis , Arteritis de Células Gigantes/virología , Herpesvirus Humano 3/genética , Herpesvirus Humano 3/aislamiento & purificación , Arterias Temporales/virología , Arteritis de Células Gigantes/genética , Arteritis de Células Gigantes/patología , Humanos , Arterias Temporales/química , Arterias Temporales/patologíaRESUMEN
We describe a 54-year-old diabetic woman who developed ischemic optic neuropathy followed by acute retinal necrosis and multiple areas of focal venous beading. Vitreous fluid contained amplifiable VZV DNA but not HSV-1, CMV or toxoplasma DNA. The clinical presentation was remarkable for jaw claudication and intermittent scalp pain, prompting a temporal artery biopsy that was pathologically negative for giant cell arteritis, but notable for VZV antigen. The current case adds to the clinical spectrum of multifocal VZV vasculopathy. The development of acute VZV retinal necrosis after ischemic optic neuropathy supports the notion that vasculitis is an important additional mechanism in the development of VZV retinal injury.
Asunto(s)
Exantema , Herpes Zóster/diagnóstico , Herpesvirus Humano 3 , Neuropatía Óptica Isquémica/diagnóstico , Síndrome de Necrosis Retiniana Aguda/dietoterapia , Arterias Temporales/virología , Femenino , Herpes Zóster/complicaciones , Humanos , Neuropatía Óptica Isquémica/complicaciones , Síndrome de Necrosis Retiniana Aguda/complicaciones , Arterias Temporales/patologíaRESUMEN
We recently detected varicella zoster virus (VZV) in the temporal arteries (TA) of 5/24 patients with clinically suspect giant cell arteritis (GCA) whose TAs were GCA-negative pathologically; in those GCA-negative, VZV+TAs, virus antigen predominated in the arterial adventitia, but without medial necrosis and multinucleated giant cells. During our continuing search for VZV antigen in GCA-negative TAs, in the TA of one subject, we found abundant VZV antigen, as well as VZV DNA, in multiple regions (skip areas) of the TA spanning 350 µm, as well as in skeletal muscle adjacent to the infected TA. Additional pathological analysis of sections adjacent to those containing viral antigen revealed inflammation involving the arterial media and abundant multinucleated giant cells characteristic of GCA. Detection of VZV in areas of the TA with pathological features of GCA warrants further correlative pathological-virological analysis of VZV in GCA.
Asunto(s)
Arteritis de Células Gigantes/etiología , Arteritis de Células Gigantes/patología , Herpes Zóster/complicaciones , Arterias Temporales/patología , Anciano , ADN Viral/metabolismo , Femenino , Arteritis de Células Gigantes/virología , Humanos , Imagen por Resonancia Magnética , Bulbo Raquídeo/patología , Bulbo Raquídeo/virología , Puente/patología , Puente/virología , Arterias Temporales/virologíaRESUMEN
OBJECTIVE: Pathologic changes in varicella-zoster virus (VZV)-infected arteries include inflammation, thickened intima, and paucity of smooth muscle cells. Since no criteria have been established for early vs late VZV vasculopathy, we examined inflammatory cells and their distribution in 6 normal arteries, and 2 VZV-infected arteries 3 days after onset of disease (early) and 10 months after protracted neurologic disease (late). METHODS: VZV-infected temporal artery obtained 3 days after onset of ischemic optic neuropathy from an 80-year-old man, VZV-infected middle cerebral artery (MCA) obtained 10 months after protracted disease from a 73-year-old man, and 5 MCAs and 1 temporal artery from normal subjects, age 22-60 years, were examined histologically and immunohistochemically using antibodies against VZV and inflammatory cell subsets. RESULTS: In both early and late VZV vasculopathy, T cells, activated macrophages, and rare B cells were found in adventitia and intima. In adventitia of early VZV vasculopathy, neutrophils and VZV antigen were abundant and a thickened intima was associated with inflammatory cells in vaso vasorum vessels. In media of late VZV vasculopathy, viral antigen, but not leukocytes, was found. VZV was not seen in inflammatory cells. Inflammatory cells were absent in control arteries. CONCLUSIONS: Both VZV and neutrophils exclusively in adventitia in early VZV vasculopathy indicate that disease begins there. Late VZV vasculopathy is distinguished by viral antigen without inflammation in media, revealing a human virus in an immunoprivileged arterial media. Association of thickened intima and inflammation in vaso vasorum vessels in early VZV vasculopathy support the role of virus-induced inflammation in vessel wall remodeling.
Asunto(s)
Herpesvirus Humano 3/inmunología , Arteria Cerebral Media/inmunología , Arterias Temporales/inmunología , Enfermedades Vasculares/inmunología , Virosis/inmunología , Adulto , Adventicia/inmunología , Anciano , Anciano de 80 o más Años , Linfocitos B/inmunología , Estudios de Casos y Controles , Femenino , Humanos , Inflamación/inmunología , Inflamación/patología , Inflamación/virología , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/patología , Arteria Cerebral Media/virología , Neutrófilos/inmunología , Linfocitos T/inmunología , Arterias Temporales/patología , Arterias Temporales/virología , Túnica Íntima/inmunología , Túnica Íntima/patología , Enfermedades Vasculares/patología , Enfermedades Vasculares/virología , Virosis/patología , Virosis/virologíaRESUMEN
OBJECTIVE: To address the incidence of varicella-zoster virus (VZV) infection in patients with biopsy-negative giant cell arteritis (GCA), we examined archived biopsy-negative temporal arteries from subjects with clinically suspected GCA for the presence of VZV antigen. METHODS: Formalin-fixed, paraffin-embedded temporal arteries that were pathologically negative for GCA and normal temporal arteries were analyzed immunohistochemically for VZV and herpes simplex virus-1 (HSV-1) antigen. RESULTS: Five (21%) of 24 temporal arteries from patients who were clinically suspect but biopsy negative for GCA revealed VZV but not HSV-1 by immunohistochemical analysis. Thirteen normal temporal arteries did not contain VZV or HSV-1 antigen. All 5 subjects whose temporal arteries contained VZV antigen presented with clinical and laboratory features of GCA and early visual disturbances. CONCLUSION: Multifocal VZV vasculopathy can present with the full spectrum of clinical features and laboratory abnormalities characteristically seen in GCA.
Asunto(s)
Arteritis de Células Gigantes/patología , Arteritis de Células Gigantes/virología , Herpes Zóster/diagnóstico , Herpesvirus Humano 3/patogenicidad , Arterias Temporales/patología , Arterias Temporales/virología , Enfermedades Vasculares/patología , Enfermedades Vasculares/virología , Adulto , Diagnóstico Diferencial , Femenino , Arteritis de Células Gigantes/diagnóstico , Herpes Zóster/epidemiología , Herpes Zóster/patología , Humanos , Incidencia , Inflamación/diagnóstico , Inflamación/patología , Inflamación/virología , Masculino , Persona de Mediana Edad , Enfermedades Vasculares/diagnósticoRESUMEN
OBJECTIVE: To demonstrate varicella zoster virus (VZV) infection in an asymptomatic extracranial (temporal) artery in a patient with ischemic optic neuropathy produced by VZV vasculopathy in whom the pathological changes were mistakenly identified as giant cell arteritis. DESIGN: Case report. SETTING: Teaching hospital, pathology and virology laboratory. PATIENT: An 80-year-old man with left ophthalmic distribution zoster who developed left ischemic optic neuropathy. INTERVENTION: An ipsilateral temporal artery biopsy revealed inflammation that was mistakenly identified as giant cell arteritis. The patient was initially treated with steroids but his condition did not improve. When the diagnosis of VZV vasculopathy was confirmed virologically and the patient was treated with intravenous acyclovir, his vision improved. RESULTS: Pathological and virological studies provided proof of VZV vasculopathy in the asymptomatic temporal artery. Varicella zoster virus antigen was abundant in arterial adventitia and scattered throughout the media. With intravenous antiviral therapy, the patient's vision improved. CONCLUSION: Although in previously studied patients who died of chronic VZV vasculopathy after 10 to 12 months, VZV antigen was present exclusively in the intima, collective analyses of chronic cases and the asymptomatic VZV-infected temporal artery suggest that virus enters arteries through the adventitia and spreads transmurally to the intima.