Given our increasing aging population and recognition that VZV reactivation manifesting as zoster is a risk factor for stroke and myocardial infarction, recognition of VZV as a potential cause of vascular disease with or without associated zoster rash is essential to decrease associated morbidity and mortality because VZV vasculopathy can be treated with antiviral therapy. Powell DR 2nd, Patel S, Franco-Paredes C. Am J Med Sci. It acts to suppress the immune system through interaction with its receptor, programmed cell death protein 1 (PD-1), which is expressed specifically on activated T cells, B cells, and macrophages. VZV infection of various vascular cells in vitro lead to downregulation of PD-L1 expression, which only occurred after the VZV-mediated downregulation of major histocompatibility complex-I (MHC-I). Curr Neurol Neurosci Rep. 2016 Feb;16(2):12. doi: 10.1007/s11910-015-0614-5. Gilden DH, Kleinschmidt-DeMasters BK, Wellish M, Hedley-Whyte ET, Rentier B, Mahalingam R. Langan SM, Minassian C, Smeeth L, Thomas SL. The best test for diagnosis in these suspected cases is a lumbar puncture and examination of CSF for the presence of anti-VZV antibodies and VZV DNA as noted above. 2017 Jul 15;308:112-117. doi: 10.1016/j.jneuroim.2017.03.014. This work is part of a supplement sponsored by the Royal Society of Medicine (Royal Charter number RC000525) funded through unrestricted educational grants from Merck, Sanofi Pasteur MSD, The Research Foundation for Microbial Diseases of Osaka University, Seqirus and GlaxoSmithKline. Furthermore, antiviral therapy during zoster appears to decrease this stroke risk [5], whereas zoster vaccination did not [6]. Herpes zoster (HZ) corresponds to the reactivation of varicella zoster virus (VZV). Ma-Krupa W, Jeon MS, Spoerl S, Tedder TF, Goronzy JJ, Weyand CM. Supplement sponsorship. Increased levels of IL-8 and IL-6 along with MMP-2 could contribute to the inflammation and vascular wall damage that are hallmarks of VZV vasculopathy. VZV DNA was detected by PCR in many VZV antigen-positive sections, as well as herpesvirus particles by electron microscopy [19]. Finally, downregulation of PD-L1 in VZV-infected vascular cells may contribute to the persistence of inflammatory cells and downregulation of MHC-1 may prevent effective viral antigen presentation to immune cells. Get the latest public health information from CDC: https://www.coronavirus.gov. GCA is the most common systemic vasculitis in the elderly and is characterized by a constellation of symptoms including severe headache, scalp tenderness, and vision loss, as well as a history of jaw claudication, polymyalgia rheumatica, fever, night sweats, weight loss, fatigue, and elevated inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]). Our enzyme-linked immunosorbent assay (ELISA)-based laboratory test for the presence of anti-VZV IgG and IgM antibodies on paired CSF and serum samples is conducted by the Measles, Mumps, Rubella and Herpesvirus Laboratory Branch/ National Center for Immunization and Respiratory Disease at the Centers for Disease Control and Prevention, Atlanta, Georgia. Inflammatory cells were absent in control arteries. The burden of disease is significant given that 50% of individuals reactivate and develop zoster by 85 years of age. Long-term antiviral drugs are far less risky than long-term corticosteroids. Case Rep Transplant. N2 - Two patients with varicella-zoster virus leukoencephalitis and acquired immunodeficiency syndrome are described. Characteristic features include imaging and angiographic abnormalities involving both large and small vessels. VZV vasculopathy can cause ischaemic infarction of the brain and spinal cord, as well as aneurysm, subarachnoid and cerebral haemorrhage, carotid dissection, and, rarely, peripheral arterial disease. Recent studies failed to detect VZV in GCA-positive TAs at the frequency of the aforementioned studies. Finally, two-thirds of the VZV vasculopathy patients stabilized or improved with antiviral therapy. eCollection 2019 Nov. Mayo Clin Proc. In children, postvaricella stroke is usually monophasic, typically presenting as an acute hemiparesis at, on average, 4 months after varicella [8]. Studies of patients with VZV vasculopathy have identified key clinical, imaging, and laboratory features to assist in diagnosis and treatment. Of 23 patients analyzed by angiography, 70% had abnormalities predominantly in both large and small arteries (50%), small arteries exclusively (37%), and large arteries exclusively (13%). The clinical manifestations of varicella-zoster virus (VZV) infections of the central nervous system (CNS) include aseptic meningitis, encephalitis, cerebral infarction associated with granulomatous vasculitis, myelitis, and multiple cranial neuropathies [1, 2, 3, 4].In these patients, viral antigens or DNA are often detected in the cerebrospinal fluid (CSF) or the sites of pathology. Flores Rosario K, Michelis KC, Bjorkman C, Araj FG. ... Varicella zoster virus (VZV) is a ubiquitous, exclusively human alphaherpesvirus that produces varicella then becomes latent in ganglionic neurons. VZV DNA was also not detected. Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus that infects more than 95% of the US population. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide, This PDF is available to Subscribers Only. J Neuroimmunol. eCollection 2020. In conjunction with activated MMPs directly secreted by VZV-infected vascular cells [38], these enzymes can lead to extracellular matrix breakdown, weakening of the vessel wall, and aneurysm formation [39–41]. Adventitial inflammation was seen adjacent to viral antigen in 26 (52%) of 58 GCA-negative subjects whose TAs contained VZV antigen and no inflammation was seen in normal TAs containing VZV antigen, most likely reflecting subclinical reactivation in some people over age 50 or early disease, which may be influenced by host and other exogenous factors. NIH Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (, Lessons from BCG for SARS-CoV-2 vaccine candidates, Association between fatty liver and cirrhosis, hepatocellular carcinoma, and HBsAg seroclearance in chronic hepatitis B, Malaria is associated with Kaposi sarcoma-associated herpesvirus (KSHV) seroconversion in a cohort of western Kenyan children, Serum protein profiling reveals a specific upregulation of the immunomodulatory protein progranulin in COVID-19, Cerebrospinal fluid features in COVID-19 patients with neurologic manifestations: correlation with brain MRI findings in 58 patients, About the Infectious Diseases Society of America, CLINICAL FEATURES, LABORATORY ABNORMALITIES, DIAGNOSIS, AND TREATMENT OF VZV VASCULOPATHY, GRANULOMATOUS ARTERITIS OF THE AORTA AND TAKAYASU ARTERITIS, https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model, Receive exclusive offers and updates from Oxford Academic, 2′-Fluoro-5-Iodoarabinosylcytosine, a New Potent Antiviral Agent: Efficacy in Immunosuppressed Individuals with Herpes Zoster, The Adjuvanted Recombinant Zoster Vaccine in Adults Aged ≥65 Years Previously Vaccinated With a Live-Attenuated Herpes Zoster Vaccine, The Epidemiology of Herpes Zoster in Immunocompetent, Unvaccinated Adults ≥50 Years Old: Incidence, Complications, Hospitalization, Mortality, and Recurrence, Varicella-Zoster Virus and the Enteric Nervous System. Get the latest research from NIH: https://www.nih.gov/coronavirus. For recurrent disease, a second course may be required, particularly in immunocompromised patients, followed by oral antivirals for several months. Thus, in these challenging cases, VZV vasculopathy should be on the differential diagnosis because antiviral treatment can potentially improve outcomes. An improved animal model for herpesvirus encephalitis in humans. Often, the diagnosis of VZV vasculopathy is missed, and hence antiviral treatment is not administered, due to the lengthy time between the occurrence of rash and stroke, the absence of rash, or the absence of a pleocytosis and VZV DNA in CSF. Immunologic Treatments of Seizures and Status Epilepticus. 2015 Sep;350(3):243-5. doi: 10.1097/MAJ.0000000000000327. Varicella zoster virus vasculopathy: The expanding clinical spectrum and pathogenesis. Varicella Zoster Vasculopathy Jyotsna Mareedu, MD1, Raghu Gowda Hanumaiah, MD1, Elizabeth Hale, MD1, and Eyassu Habte-Gabr, MD1 Abstract Varicella-zoster virus can cause neurological disease in primary and reactivated latent forms, with a wide spectrum of disorders The presence of neutrophils in the arterial adventitia in early VZV vasculopathy is consistent with their presence in the CSF of patients with neurological disease due to VZV [31–33]. Objective: Varicella zoster virus (VZV) is an under-recognized yet treatable cause of stroke. Learn about the other conditions caused by herpes zoster, also called varicella zoster, that can be more dangerous than chicken pox or shingles. VZV antigen-positive slides were scraped, DNA extracted, and PCR attempted to amplify low-quality VZV DNA from formalin-fixed tissue. COVID-19 is an emerging, rapidly evolving situation. In elderly and immunocompromised individuals, VZV reactivates and typically produces herpes zoster. 33 Gilden D. The ever-widening spectrum of varicella zoster virus vasculopathy. However, both intracranial and extracranial arteries are now known to be associated with VZVV. Good Fences Make Good Neighbors: Human Immunodeficiency Virus and Vascular Disease. Owing to scarcity of data of VZV-induced vasculopathy and lack of awareness about this condition and its diagnostic test, these cases may be easily missed.