A 68-year-old woman presented to the hospital with a 2-day history of left-eye blindness and a discolored lower lip and tongue. One week prior she presented to her dentist complaining her dentures were not fitting correctly and was treated for thrush. She was previously in good health and never had visual or oral complaints.

Figures 83-1 and 83-2 demonstrate how giant cell arteritis (GCA) can present with nonspecific findings yet cause significant ischemia and organ damage. Below is a comparison demonstrating how GCA and Takayasu arteritis (TA) are points on a continuum of an inflammatory clinical process differing by age of onset, pathogenic mechanism, and the vascular beds commonly affected.

Giant Cell Arteritis

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  Increasing frequency with age and average age of diagnosis 72 years.¹

  
  
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  Women are more likely affected than men.²

  
  
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  Prevalence up to 1 in 500 among individuals older than 50 years.²

  
  
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  Northern European ancestry living in the United States or Europe.³

  
  
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  History of smoking and atheromatous disease increase risk in women.⁴

  
  
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  Human leukocyte antigen (HLA)-DR4 positivity.⁴

Takayasu Arteritis

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  80% to 90% of cases are in women between the ages of 10 and 40.

  
  
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  Greatest prevalence in Asia. Japan reports 150 new cases per year compared to one to three new cases per million people in the United States and Europe.⁵

  
  
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  Additional risk factors: HLA-B52, HLA-B39 positivity.

Giant Cell Arteritis

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  The pathogenic mechanism of GCA is unknown. However, current understanding implicates a foreign antigen in a cascade of events that under-standing results in arterial inflammation.

  
  
  
  
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    An antigenic stimulant activates dendritic cells, which in turn activate CD4 T lymphocytes that produce interferon-gamma (INF-γ), which has significant effects on macrophage activation and function.

    
    
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    This leads to further cytokine and chemokine production, especially interleukin 1 (IL-1), IL-6, transforming growth factor, and monocyte chemoattractant protein 1 (MCP-1).

    
    
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    These processes cause immune activation in the adventitia, which ultimately leads to inflammatory changes including granuloma formation, multinucleated giant cells, growth factors, and reactive oxygen intermediates.

    
    
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    This entire process subsequently leads to remodeling of the luminal wall caused by matrix digestion, smooth muscle loss, proliferation of myofibroblast, and intimal hyperplasia.

    
    
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    All of the above processes contribute to luminal occlusion.

Takayasu Arteritis

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  The etiology and pathogenesis of TA remains unknown, but like GCA is thought to be antigen driven. Several differentiating observations separate TA from GCA that includes the role of gamma delta (γδ) T cells and CD8 T cells in TA.

  
  
  
  
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    HLA class I molecules, in particular HLA-B52, are more prevalent in TA patients.⁶ This is of interest since HLA class I molecules bound to antigens are required for CD8 T-cell recognition.

    
    
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    Pathology in TA reveals granulomas and multinucleated giant cells in the media of the blood vessels. There is also proliferation of fibroblasts in the smooth muscle layer.

    
    
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    The release of perforin and granzyme B by CD8 T cells in the smooth muscle layer is thought to lead to smooth muscle cell destruc-tion.⁷ The fibrotic deposition in this layer leads to vessel wall dilation and aneurysm formation.

    
    
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    Intimal thickening can lead to luminal narrowing and vessel occlusion.

Giant Cell Arteritis

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  American College of Rheumatology (ACR) classification criteria, which is not used in diagnosis but is useful as a research tool to separate GCA from other vasculitides include age greater than 50, new-onset localized headaches, tenderness or decreased pulse of the temporal artery, erythrocyte sedimentation rate (ESR) greater than 50 mm/h, or biopsy demonstrating multinucleated giant cells in a granulomatous process or a necrotizing arteritis with predominance of mononuclear cells.⁸ Patients are said to have GCA if they have three out of five of the above crite-ria.

Takayasu Arteritis

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  ACR criteria: age less than 40, claudication of the extremities, decreased pulsation of one or both brachial arteries, difference of at least 10 mm Hg in systolic blood pressure between the arms, bruit over one or both subclavian arteries or the abdominal aorta, or arteriographic narrowing or occlusion of the entire aorta, its primary branches or large arteries in the proximal upper or lower extremities, not due to arteriosclerosis, fibromuscular dysplasia, or other causes. Three of the six are required to make the diagnosis.⁵

Giant Cell Arteritis

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  Systemic symptoms such as fever, weight loss, malaise, and fatigue. A significant number of patients with GCA have polymyalgia-type symptoms characterized by morning stiffness, gelling (stiffness that occurs after being stationary), and proximal muscle pain.

  
  
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  Cranial arteritis

  
  
  
  
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    Often presents with a sudden-onset throbbing, sharp or dull headache, mostly localized to the temporal region but it can affect other areas. Patients also often complain of scalp tenderness. One of the most serious complications of GCA is permanent vision loss, which is sudden and painless. Occasionally patients complain of preceding transient vision blurring (amaurosis fugax) or diplopia.

    
    
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    Additional neurologic complaints include visual hallucinations depending on the degree and the location of central nervous system (CNS) involvement.

    
    
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    Jaw claudication or pain in the masseter and temporalis muscles with prolonged use is reported in half of GCA patients. Claudication of the tongue as well as tongue infarctions have been reported as well (Figures 83-1 and 83-2).

    
    
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    Physical examination may reveal firm nodularity or tenderness over the temporal arteries, with or without decreased pulse. GCA patients may have a carotid bruit and/or murmur of aortic insufficiency.

  
  
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  Large vessel arteritis: Up to 15% of GCA patients have involvement of larger vessels in addition to cranial vessels. The most commonly affected vessels are the carotid, subclavian, and axillary arteries. Consequently, patients will often complain of claudication, numbness, or tingling of extremities. This may make the clinical presentation difficult to differentiate from TA.

Takayasu Arteritis

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  The patient may be asymptomatic; however, the initial presentation often reflects systemic inflammation that manifests as fevers, night sweats, weight loss, and muscle aches.

  
  
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  The clinical manifestations reflect the vascular bed affected.

  
  
  
  
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    Visual symptoms, dizziness, headache, syncope, carotidynia, or stroke may be seen in patients with carotid and vertebral artery disease.

    
    
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    Inflammation of the subclavian and brachiocephalic arteries may lead to ischemia and claudication.

    
    
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    Patients may develop congestive heart failure, arrhythmias, myocardial infarction, or aortic insufficiency.

    
    
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    Other effects include severe renovascular hypertension from renal artery stenosis or suprarenal abdominal coarctation.

    
    
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    Patients can present with the manifestations of chronic mesenteric ischemia typically in association with severe superior mesenteric artery stenosis.

    
    
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    Pulmonary hypertension from pulmonary artery stenosis may occur.

    
    
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    Aneurysmal rupture has been reported mostly in patients from Japanese descent.