Bilateral Vision Loss From Varicella Zoster Virus-Associated Giant Cell Arteritis

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Bilateral Vision Loss From Varicella Zoster Virus– Associated Giant Cell Arteritis Jim S. Xie, BHSc, Stephanie P. Yang, MD, MSc, David G. Munoz, MD, Jonathan A. Micieli, MD, CM G iant cell arteritis (GCA) is a systemic vasculitis of medium and large arteries believed to involve a dendritic cell–initiated immunologic cascade that recruits T cells and macrophages and subsequently stimulates chemokine and cytokine production, resulting in granulomatous inflammation of the arterial wall (1). The inciting event for dendritic cell activation is not known, but viral causes have been suspected (2). Reactivation of varicella zoster virus (VZV) resulting in herpes zoster (HZ) has recently emerged as a potential GCA trigger (2). In this case report, we present a patient who developed temporal artery biopsy (TAB)-confirmed GCA shortly after herpes zoster ophthalmicus (HZO). An 81-year-old woman presented with bilateral vision loss. She had a medical history of hypertension, coronary artery disease, and gastroesophageal reflux disease. Her medications included bisoprolol, perindopril, lactulose, and sennosides. Six weeks before presentation, she developed right forehead pain and skin changes and was diagnosed with HZO. She was started on valacyclovir 1 g by mouth three times a day. Three weeks later, she developed new-onset temporal headache and jaw claudication. She was diagnosed with postherpetic neuralgia (PHN) and started on pregabalin while continuing valacyclovir. Two weeks later, she developed complete loss of vision in both eyes. This prompted her to go to sleep, and when she woke up, her vision returned. She was seen by an ophthalmologist the next day, and her visual function and dilated fundus examination were normal. She was found to have right anterior uveitis and was started on topical steroids. One week later, she lost vision in both Michael G. DeGroote School of Medicine (JSX), McMaster University, Hamilton, Canada; Division of Rheumatology (SPY), Department of Medicine, University of Toronto, Toronto, Canada; Department of Laboratory Medicine (DGM), Unity Health, Toronto, Canada; Department of Laboratory Medicine and Pathobiology (DGM), University of Toronto, Toronto, Canada; Department of Ophthalmology and Vision Sciences (JAM), University of Toronto, Toronto, Canada; Division of Neurology, Department of Medicine (JAM), University of Toronto, Toronto, Canada; and Kensington Vision and Research Centre (JAM), Toronto, Canada. The authors report no conflicts of interest. Address correspondence and reprint requests to: Jonathan A. Micieli, MD, CM, Kensington Vision and Research Centre, 340 College Street, Suite 501, Toronto, ON, Canada, M5T 3A9; E-mail: jonathanmicieli@ gmail.com. Xie et al: J Neuro-Ophthalmol 2023; 43: e109-e110 eyes and presented to the emergency room. Complete blood count showed a hemoglobin of 105 g/L, platelets of 593 · 109/L, erythrocyte sedimentation rate of 98 mm/ hour, and C-reactive protein of 244 mg/L (normal ,7). She was started on intravenous methylprednisolone 1 g daily for presumed GCA and referred to neuroophthalmology. Initial neuro-ophthalmic examination revealed a visual acuity of light perception (right) and no light perception (left). Dilated fundus examination showed diffuse retinal edema (right) and pallid optic disc edema with peripapillary hemorrhages (left; Fig. 1). A TAB was performed which showed a muscular artery with nearly circumferential inflammatory cell infiltrate accompanied by extensive fibrinoid necrosis (Fig. 2A). The infiltrate consisted of histiocytes and multinucleated giant cells centered on the internal elastic lamina, which was destroyed at multiple points (Fig. 2B). VZV was evaluated using immunohistochemistry (IHC) on the temporal artery specimen but was not detected. The patient was continued on prednisone 1 mg/kg, and her systemic symptoms promptly resolved. Her visual acuity remained the same at 1-month followup. This case demonstrates a very close relationship between HZO and biopsy-proven GCA that has rarely been reported, emphasizing the importance of keeping GCA in the differential diagnosis of headache and vision loss postHZ. Previous cases in the literature have described a close relationship between GCA and VZV infection. However, FIG. 1. Fundus photographs. Fundus photographs showing diffuse retinal edema and a cherry red spot in the right eye (left figure) indicative of a central retinal artery occlusion. The left eye (right figure) had pallid optic disc edema with a superior optic disc hemorrhage due to an anterior ischemic optic neuropathy. e109 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Temporal artery biopsy. A. Section of the left temporal artery stained with hematoxylin–phloxine–saffron, showing a severe vasculitis with fibrinoid necrosis (green arrow) leading to sectorial destruction of the internal elastic lamina (blue arrow). B. Higher power of the rectangle in A showing the inflammatory cell infiltrate, consisting of histiocytes (yellow arrow), some as multinucleated giant cells (inset), as well as the eosinophils (white arrow). Note another preserved fragment of the internal elastic lamina. none of these cases were associated with bilateral vision loss, and IHC was not consistently performed on the temporal artery specimen. Kosa et al (3) described an 80-year-old woman who developed TAB-positive GCA within 2 months after HZO diagnosis. This patient did not have any ocular manifestations from GCA, and neither polymerase chain reaction (PCR) nor IHC were performed on the temporal artery specimen. Buckingham et al (4) found that among 3 patients with GCA-positive and VZV antigen– positive TABs, a 78-year-old woman without vision loss had been diagnosed with HZO 3 weeks prior. In addition to HZO, GCA has also been reported as a sequela of a liveattenuated VZV vaccine, wherein VZV was not detected by PCR in the temporal artery specimen (5). In our case, we opted for IHC testing of the TAB because it is believed that VZV antigen rather than DNA is required to elicit an immune response resulting in GCA (4). Moreover, temporal arteries are known to be innervated by nerve fibers from ganglia that harbour latent VZV and PCR testing may pick up this bystander DNA of questionable significance (4). It is also known that formalin-fixed paraffine-embedded biopsies of temporal arteries are suboptimal for PCR testing (4). Given the absence of detectable VZV in the temporal artery specimen of this patient, a likely hypothesis is that VZV resulted in dendritic cell–initiated immunologic cascade culminating in GCA. However, large population-based studies have not found a relationship between VZV reactivation or VZV vaccination and GCA incidence (6–8). One of these studies examined over e110 16.5 million patients in 2 US administrative databases and found that only 4% (236/5,942) of GCA cases were preceded by HZ and that the time between HZ and GCA events ranged from more than 1 month to almost 2 years (8). The characteristic pathology and prompt response to steroids argues against this case being solely a VZV-related vasculitis. In conclusion, GCA may occur in close temporal relationship to HZO. Headaches can often be misconstrued for PHN which may result in undiagnosed GCA and catastrophic bilateral vision loss. It is important to keep GCA in the differential diagnosis of headaches and vision changes after HZ. STATEMENT OF AUTHORSHIP Conception and design: J. A. Micieli; Acquisition of data: J. Xie, D. G. Munoz, J. A. Micieli; Analysis and interpretation of data: J. Xie, S. P. Yang, D. G. Munoz, J. A. Micieli. Drafting the manuscript: J. Xie, J. A. Micieli; Revising it for intellectual content: J. Xie, S. P. Yang, D. G. Munoz, J. A. Micieli. Final approval of the completed manuscript: J. Xie, S. P. Yang, D. G. Munoz, J. A. Micieli. REFERENCES 1. Weyand CM, Liao YJ, Goronzy JJ. The immunopathology of giant cell arteritis: diagnostic and therapeutic implications. J Neuroophthalmol. 2012;32:259–265. 2. Liao YJ, Kedar S. Should antiviral/anti-varicella zoster virus treatment be used in patients with giant cell arteritis? J Neuroophthalmol. 2019;39:134–141. 3. Kosa SC, Younge BR, Kumar N. Headaches due to giant cell arteritis following herpes zoster ophthalmicus in an elderly patient. Cephalalgia. 2010;30:239–241. 4. Buckingham EM, Foley MA, Grose C, Syed NA, Smith ME, Margolis TP, Thurtell MJ, Kardon R. Identification of herpes zoster-associated temporal arteritis among cases of giant cell arteritis. Am J Ophthalmol. 2018;187:51–60. 5. Nichani P, Micieli JA. Granuloma annulare, scalp necrosis, and ischemic optic neuropathy from giant cell arteritis after varicella-zoster virus vaccination. J Neuroophthalmol. 2021;41:e145–8. 6. Lotan I, Steiner I. Giant cell arteritis following varicella zoster vaccination. J Neurol Sci. 2017;375:158–159. 7. Rhee RL, Grayson PC, Merkel PA, Tomasson G. Infections and the risk of incident giant cell arteritis: a population-based, casecontrol study. Ann Rheum Dis. 2017;76:1031–1035. 8. England BR, Mikuls TR, Xie F, Yang S, Chen L, Curtis JR. Herpes zoster as a risk factor for incident giant cell arteritis. Arthritis Rheumatol. 2017;69:2351–2358. Xie et al: J Neuro-Ophthalmol 2023; 43: e109-e110 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.