Case of Clinical Mimicry: Atherosclerosis Masquerading as Giant Cell Arteritis

We describe a case of an elderly man with severe systemic atherosclerosis that affected internal and external carotid arteries whose clinical presentation mimicked that of giant cell arteritis (GCA) reminding us that systemic atherosclerosis should be on a differential diagnosis of patients presenting with a clinical picture of GCA.

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Case of Clinical Mimicry: Atherosclerosis Masquerading as Giant Cell Arteritis Ryan Mason, MD, PhD, Trishal Jeeva-Patel, MD, Daniel Mandell, MD, PhD, Patrick Shannon, MD, Edward A. Margolin, MD W e describe a case of an elderly man with severe systemic atherosclerosis that affected internal and external carotid arteries whose clinical presentation mimicked that of giant cell arteritis (GCA) reminding us that systemic atherosclerosis should be on a differential diagnosis of patients presenting with a clinical picture of GCA. A 92-year-old man presented with a sudden loss of vision in the right eye (RE). He admitted to a history of bilateral jaw pain escalating while he was chewing that led him to stop eating all solid foods for the past month. On examination, visual acuity was hand motions in the RE and 20/25 in the left eye (LE). He had a brisk right relative afferent pupillary defect. On ophthalmoscopy, the right optic nerve head demonstrated pallid swelling. The erythrocyte sedimentation rate (ESR) was 63 mm/hr, and C-reactive protein (CRP) was 28 mg/L (normal ,5). Three-day course of intravenous Solu-Medrol (1 g per day) was initiated, followed by 60 mg of oral prednisone. This has resulted in improvement in jaw claudications but no change in visual acuity. Right temporal artery biopsy (TAB) was performed at an outside institution, specimen was 1.6 cm in length, and the report stated that there were no features of temporal arteritis. As the clinical suspicion for GCA was very high and because of the concern for a skip lesion not detected on previous biopsy, a decision was made to proceed with contralateral TAB. Surprisingly, a 2.1-cm specimen revealed a circumferential calcified atherosclerotic plaque (with preserved internal elastic lamina) nearly completely occluding the arterial lumen (Fig. 1). A computed tomography (CT) angiogram of the brain and neck revealed widespread atherosclerotic plaques in the internal and external branches of carotid arteries and calcification of the superficial temporal arteries (Fig. 2). After multiple deep cuts of both temporal arteries were re-examined with no features of Departments of Ophthalmology and Vision Sciences (RM, TJ-P, EAM), Medical Imaging (DM), and Laboratory Medicine (PS), University of Toronto, Toronto, Canada; and Division of Neurology (EAM), Department of Medicine, University of Toronto, Toronto, Canada. The authors report no conflicts of interest. Address correspondence to Edward A. Margolin, MD, Department of Ophthalmology and Visual Sciences, University of Toronto, Suite 304 —801 Eglinton Avenue West, Toronto, ON, M5N 2M7, Canada; E-mail: [e-mail] Mason et al: J Neuro-Ophthalmol 2022; 42: e359-e361 FIG. 1. Cross-section of temporal artery demonstrating pinpoint lumen (L) with subintimal hyperplasia and medial and subintimal distortion by masses of calcified atherosclerotic plaque (arrowheads). The elastic lamina is generally either preserved (arrow) or incorporated into the plaques. The medial and subintimal clefts are artefact. temporal arteritis seen, a conclusion was made that widespread atherosclerosis has caused an occlusion of the ophthalmic artery producing severe visual loss with pallid optic nerve head edema and that atherosclerosis of the external carotid branches supplying masticatory muscles was responsible for jaw claudication. Widespread atherosclerosis was also most likely responsible for elevated inflammatory markers. Because of the very small diameter of the ophthalmic artery, we could not accurately assess it on the CTA. Corticosteroids were tapered off over the next month, and medical management of atherosclerosis was optimized. Atherosclerotic lesions in the branches of internal and external carotid arteries causing GCA-like symptoms were first described in a patient presenting with a constellation of amaurosis fugax, ipsilateral frontotemporal headache, jaw claudication, and a pulseless temporal artery in 1987 (1). Since then there have been numerous case reports of individual GCA symptoms attributed to atherosclerosis: jaw claudication due to atherosclerosis of external carotid branches have been well described to mimic the same symptom in giant cell arteritis, and temporal pain due to atherosclerosis of external carotid artery branches has also been described. A case of atherosclerosis in the ophthalmic artery producing severe visual loss was published as well. The e359 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 2. Imaging of the carotid and superficial temporal arteries. CT angiogram (A), sagittal image shows the left common carotid artery (*) bifurcation into the external (left side of image) and internal (right side of image) carotid arteries, with an extensive calcified atherosclerotic plaque (long arrows) and severe narrowing at the external carotid artery origin (short arrows). Nonenhanced CT head (B), sagittal maximum intensity projection shows the left superficial temporal artery (*) bifurcation into frontal (left side of image) and parietal (right side of image) branches with extensive calcification (arrows) of these branches. combinations of all the symptoms classic in giant cell arteritis in one patient (jaw claudication, severe visual loss with anterior ischemic optic neuropathy, and elevated inflammatory markers), however, have not been all described to our knowledge. The presence of very severe atherosclerosis in the temporal artery biopsy that almost entirely occluded the lumen of the artery was a pathological confirmation that atherosclerosis can perfectly mimic giant cell arteritis in the same patient. It is well documented that atherosclerosis of temporal arteries is often seen on temporal artery biopsies, although the exact incidence is difficult to determine given that many pathological descriptions combine atherosclerosis where vessel lumen is narrowed by the plaque consisting of cholesterol and fat, with the more common and less specific arteriosclerosis denoting stiffening and thickening of the vessel wall. In one series of 135 patients suspected to have GCA, 5% of temporal artery biopsies demonstrated features of atherosclerosis (2), whereas in another series of 100 patients it was seen in only 1% biopsies (3). Atherosclerosis is an inflammatory disease affecting mostly large and medium-sized elastic and muscular arteries where accumulation of inflammatory cells in the cell wall leads to proliferation of smooth muscle cells (4). Lymphocytes and macrophages within the lesion release hydrolytic enzymes, cytokines, chemokines, and growth factors that eventually lead to cellular necrosis within the lesion. Eventually, a fibrous cap forms on the surface of the atherosclerotic lesion containing lipids and necrotic tissue. Activated platelets within the lesion then cause the formation of vasoconstricting and plateletattracting substances further promoting the inflammatory response. The enlarging lesion eventually compromises the blood flow in the vessel’s lumen and when the e360 fibrous cup breaks off, adhesion of platelets to the ruptured plaque can lead to its rapid growth, obliterating the lumen of the affected vessel and leading to tissue ischemia (4). Given the role of arterial inflammation in atherosclerosis, circulating biochemical markers of inflammation are often elevated in patients with atherosclerosis and increased levels of ESR and CRP (5) have been reported to be strong predictors of cardiovascular morbidity and mortality (5,6). However, both inflammatory markers are typically not as elevated in atherosclerosis as they are in patients with GCA. Jaw claudication, elicited from our patient’s history, is a symptom commonly associated with GCA and other forms of generalized vasculitis. In addition to vasculitis, it can rarely be caused by atherosclerosis of the external carotid branches where chewing causes increased metabolic demand in masticatory muscles thus increasing muscle ischemia and causing pain (1,7,8). This is possibly because of the propensity of the masticatory muscles to develop an adequate collateral vascular supply over time thus decreasing the incidence of claudication symptoms and sometimes leading to their spontaneous resolution before more invasive investigations such as angiography can confirm a diagnosis. Stenosis of the ophthalmic artery has been shown to cause transient vision loss even in the absence of pathology in larger proximal vessels (9,10). This may be due to impeded forward blood flow because of lumen narrowing or even an “ophthalmic steal” where retrograde flow occurs as the result of stenosis elsewhere (11). This can present similarly to the vision loss found in GCA. In one report of ischemic retinopathy, balloon angioplasty of the ophthalmic artery was required to restore vision (12). We postulate that atherosclerosis of the ophthalmic artery and resultant ophthalmic artery occlusion were the Mason et al: J Neuro-Ophthalmol 2022; 42: e359-e361 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence likely cause of vision loss in our patient, but because of the very small diameter of the ophthalmic artery, we could not accurately assess it on the CTA. Pathologically, in GCA there is scarring in the involved vessel wall leading to thinning of the medial and loss of internal elastic lamina. In atherosclerosis, the media of the vessel is largely preserved, although might demonstrate areas of focal loss. Most importantly, the atherosclerotic plaque would encase the elastica that remained well preserved. The main pathological finding in atherosclerosis is subendothelial hyperplasia and some medial injury as opposed to the main finding of medial injury with only minor subendothelial hyperplasia in GCA. Symptoms of acute vision loss, scalp tenderness, and jaw claudication accompanied by elevated systemic inflammatory markers are often considered to be highly suggestive of GCA. However, temporal artery biopsy remains the gold standard for establishing the diagnosis, and in patients with risk factors for atherosclerosis with features of atherosclerosis rather than GCA on temporal artery biopsy, atherosclerosis should be considered as a unifying cause of the abovementioned symptoms and laboratory abnormalities. Computed tomography angiogram is a useful adjunct to temporal artery biopsy to help confirm the diagnosis of widespread atherosclerosis. In such instances, a clinical response to corticosteroids is expected to be limited and treatment would consist of ongoing optimization of cardiovascular risk factors. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: E. A. Margolin, R. Mason, D. Mandell, T. Jeeva-Patel, and P. Shannon; b. Acquisition of data: E. A. Margolin, R. Mason, D. Mandell, T. Jeeva-Patel, and P. Shannon; c. Analysis and interpre- Mason et al: J Neuro-Ophthalmol 2022; 42: e359-e361 tation of data: E. A. Margolin, R. Mason, D. Mandell, T. Jeeva-Patel, and P. Shannon. Category 2: a. Drafting the manuscript: E. A. Margolin, R. Mason, D. Mandell, T. Jeeva-Patel, and P. Shannon; b. Revising it for intellectual content: E. A. Margolin, R. Mason, D. Mandell, T. JeevaPatel, and P. Shannon. Category 3: a. Final approval of the completed manuscript: E. A. Margolin, R. Mason, D. Mandell, T. Jeeva-Patel, and P. Shannon. REFERENCES 1. Venna N, Goldman R, Tilak S, Sabin TD. 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