From ATLANTA Medicine, 2014, Vol. 85, No. 3
Giant Cell Arteritis (GCA), or Temporal Arteritis, is the most common primary vasculitis. The disease is characterized by inflammation of the large and medium-sized vessels, predominately favoring the branches of the proximal aorta.
GCA is a disease that typically occurs in people older than 50 years old, with a peak incidence in the seventh decade of life. GCA appears to be more common in Caucasians of Northern European descent (1, 2 and 3).
A study looking at the incidence of GCA in Shelby County, Tenn., revealed a decreased incidence in African Americans compared to Caucasians (4). The reported incidence in areas of southern Europe, Asia and North Africa was lower. Women appear to be affected more than men at a ratio of 3:1 (1, 2 and 3).
Experimental evidence supports a major role of a T-cell mediated process in the pathogenesis of GCA. Dendritic cells (DCs), located in the adventitia of medium and large-sized vessels, are activated via Toll-Like Receptor binding by specific ligands (including those resulting from infective agents).
These activated DCs, via release of chemokines, lead to recruitment and stimulation of CD4 T-cells and macrophages through the vasa vasorum into the vessel wall. These activated CD4 T-cells and macrophages then secrete pro-inflammatory cytokines. In particular, interactions between activated T-cells and the macrophages in the adventitia produce IL-1, IL-6 and Transforming Growth Factor beta, whereas in the media, they produce metalloproteinases and participate in oxidative damage. These factors then lead to fragmentation of the internal elastic lamina, intimal proliferation, thrombosis and possible vessel occlusion (5, 6, 7 and 8).
The clinical features of GCA could be broadly classified in two ways: those that are caused by systemic inflammation, and those that are a result of ischemia. Fevers, fatigue, weight loss, night sweats, Polymyalgia Rheumatica-like symptoms (pain and stiffness in the neck, shoulder/pelvic girdle area) and elevated acute phase reactants are common signs and symptoms that could be attributed to systemic inflammation. Peripheral synovitis can also occur, but usually less frequently (9, 10, 11, 12 and 13).
When looking at the features that result from vascular injury, headaches have been shown to be the most common, being present in 90 percent of patients. The headaches are usually located in the temporal or occipital areas and may be associated with scalp tenderness. Jaw claudication is also common (9, 10, 11, 12 and 13).
Ocular symptoms are feared complications of GCA. The most common ocular manifestation of GCA that leads to vision loss is Anterior Ischemic Optic Neuropathy (AION). AION results from occlusion of the posterior cilliary arteries. The vision loss is usually painless and acute. Amaurosis fugax and diplopia may precede the acute vision loss. Posterior Ischemic Optic Neuropathy and Central Retinal Artery Occlusion can also be seen. Fever, weight loss, jaw claudication, diplopia, transient visual loss and older age are predictors of worse visual prognosis (9, 10, 11, 12 and 13).
Limb claudication, and the alteration of peripheral pulses stemming from large-vessel involvement, occurs in less than 20 percent of patients. Cough and hoarseness can be seen in less than 10 percent of patients. Other infrequent manifestations (<5 percent of patients) may include: peripheral neuropathy, tongue claudication, ischemia of the central nervous system, tissue necrosis, and deafness (9, 10, 11, 12 and 13).
The temporal artery biopsy (TAB) is the most useful tool for diagnosing GCA. A biopsy is usually attempted on the symptomatic side. A contralateral biopsy, however, may be warranted in patients with a high suspicion for GCA and a negative, initial TAB. Given the potential focal positioning of the inflammatory infiltrate, it is important to obtain a sufficient sample of the temporal artery. Studies have shown that biopsy lengths of 0.5cm to 3cm are adequate for histologic analysis (12).
The stereotypic histologic morphology of GCA is a “panarteritis” or transmural inflammation of the vascular wall. The elastic lamina may be fragmented. In more chronic disease, intimal hyperplasia may cause arterial lumen occlusion (12).
Laboratory data are also very useful in the diagnosis of GCA. The erythrocyte sedimentation rate (ESR) and C-reactive protein are usually elevated. Weyand et al. noted that 25 percent of patients with positive temporal artery biopsies had normal ESRs prior to the initiation of glucocorticoids. Anemia and thrombocytosis can also be seen (13).
Imaging modalities, such as, ultrasound (US), magnetic resonance angiography (MRA), and computed tomography angiography (CTA) have been studied. Early inflammatory changes in the superficial branches of the aortic arch can be visualized with ultrasonography, while MRA and CTA are more useful in evaluating the thoracic and abdominal aorta.
Glucocorticoids have been the mainstay of treatment for GCA. Typically, in patients without end-organ damage, prednisone is initiated at 1mg/kg/day. The dose is then usually titrated down, only when a patient’s symptoms and inflammatory markers have normalized. Mazlumzadeh et al. were able to show that patients who received “pulse dose” intravenous steroids (15mg/kg of ideal body weight per day) tended to experience increased frequencies of sustained remission after treatment compared to patients who received a standard dose of 40mg/day of prednisone. In addition, over time, the patients who received the pulse-dose steroids were able to more rapidly taper their oral prednisone dose (15).
In an attempt to mitigate the various short-term and long-term complications of glucocorticoids, several trials utilizing various disease-modifying drugs have been performed. Unfortunately, trials using methotrexate, infliximab, adalimumab and etanercept were unable to show any glucocorticoid sparing effect (16).
Recently, interest has been shown in the humanized monoclonal antibody to IL-6 receptor, tocilizumab. Several case reports, as well as a case series reported by Unizony, et al., revealed promising clinical results. Long-term, randomized-control trials are currently in planning (17).
Retrospective reviews have shown the benefits of low-dose aspirin therapy in GCA, including the potential decrease in risk of ischemic events and vision loss. Appropriate bone protective measures should be taken with glucocorticoid treatment (16).
Despite treatment, 60 percent of patients will experience disease relapse (7). Vigilant monitoring of clinical signs and symptoms is needed to prevent long-term complications.
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