**Abstract**

Giant cell arteritis (GCA) is a granulomatous vasculitis affecting large- and medium-sized arteries in the elderly and potentially causes visual loss. In an elderly patient presenting with acute pain in the distribution of the external carotid artery (e.g., headache, scalp tenderness); polymyalgia rhematica; or acute/transient visual loss or diplopia; a possibility of GCA should be considered in one of the differential diagnosis. Urgent laboratory evaluation (e.g., ESR, CRP, platelet count), followed immediately by empiric high-dose corticosteroid therapy is warranted in patients suspected of having GCA. Although ultrasound techniques are sensitive for the diagnosis of GCA, TAB remains the best confirmatory test. Patients with GCA often require long durations of steroid therapy and steroid-related complications are common. Multidisciplinary care and the use of steroid-sparing regimens are warranted in case of relapse.

**Keywords:** Giant cell arteritis, Pathogenesis, Advances, Management

### **1. Introduction**

Giant cell arteritis (GCA) is a granulomatous vasculitis affecting medium to large sized arteries, it most commonly involves the aorta, branches of the ophthalmic artery, and extracranial branches of the carotid arteries [1–5]. From a clinical perspective, GCA is a medical emergency because if undiagnosed and treated early, ischemic complications may cause permanent vision loss in up to 15–25% of cases [6]. Early diagnosis and initiation of treatment is essential to improve visual and systemic prognosis in patients with GCA [1, 7, 8]. The complications of GCA result from ischemic injury, systemic inflammation, and aneurysm formation and rupture. Early initiation of corticosteroids in patients with suspected GCA has been found to significantly reduce the risk of permanent visual loss in various studies [6–8]. In this review we provide a brief overview regarding the pathogenesis, clinical features, investigations and management of GCA from a Neurologist's perspective.

### **2. Pathophysiology**

GCA is immune-mediated inflammatory vasculitis affecting the medium and large-size arteries. The immunological cascade is triggered by an unknown antigen that begins with the dendritic cell processing the antigen and presenting it to T cells via the major histocompatibility complex II interaction with the T cell receptors [1, 2, 6, 9]. In this inflammatory cascade, there is downstream activation and differentiation of T cells to TH1 and TH17 cells, which in turn express interferon γ, a potent macrophage activator. This macrophage activation causes further release of chemokines including but not limited to IL-6 and tumor necrosis factor (TNF) alpha. A large number of inflammatory cells are recruited with production of reactive oxygen species (ROS) and matrix metalloproteinases (MMPs), which then primarily attack the internal elastic lamina of blood vessels. This mechanism damages the vessel wall leading to abnormal vascular remodeling and ultimately occlusion of the vessel lumen [10, 11].

### **2.1 Risk factors**

GCA generally affects elderly population, with the average age of presentation being 74–76 years, and peak incidence at 80 years [3, 5, 9]. While GCA can occur in both men and women, it is more common in women. Women have an increased risk ranging from 2.3 to 2.6 times compared to men [1, 3, 9]. Additionally, It has been found to be affecting Caucasian ethnicity more especially those of Scandinavian, Nordic, or Northern-European ancestry [1, 3, 9]. Other important independent risk factors are smoking, early menopause and low body mass index [9, 12].

### **2.2 Clinical symptoms and examination findings**

The symptoms of GCA include both systemic and ocular. New-onset headache is the most common systemic symptom and the systemic symptoms often precede the ocular manifestations. Fifty percent of patients with GCA have systemic symptoms and these include myalgias, headaches, scalp and temporal artery tenderness, jaw and rarely arm claudication, and constitutional symptoms (e.g., fever, anorexia, and weight loss) [1, 5]. Polymyalgia rheumatica (PMR) is present in approximately 50% of patients with biopsy-proven GCA [5]. The characteristic symptoms of PMR include: persistent pain for at least 1 month with episodes of aching and morning stiffness that lasts at least 30 minutes in the neck, shoulder, or pelvic girdle and an elevated ESR of at least 40 mm/h [5].

The most severe ocular manifestation of GCA is visual loss, with 50% of patients complaining of ocular involvement ranging from eye pain to amaurosis fugax. 19 Ocular involvement is more commonly seen in elderly patients compared to younger individuals, with no gender predilection [9, 13]. The ocular complaints include visual loss of varying severity, amaurosis fugax, diplopia, and eye pain [13]. Amaurosis fugax, precedes permanent vision loss in 44% of GCA patients [5]. Vision loss is usually mono-ocular to begin with and if left untreated, contralateral eye involvement commonly occurrs between 1 and 14 days after initial onset with the longest interval being 9 months [5, 13]. When treated early and adequately with corticosteroids, GCA-mediated blindness is preventable in majority of cases [9, 13].

In a case of suspected giant cell arteritis, the following clinical approach is recommended [4]:


• Detailed ophthalmological exam is warranted – look for transient or permanent visual loss, visual field defect, relative afferent pupillary defect, anterior ischemic optic neuritis, central retinal artery occlusion.
