Giant cell arteritis Flashcards
what is the definition of GCA?
Giant cell arteritis (GCA) is a granulomatous vasculitis of large and medium-sized arteries. It primarily affects branches of the external carotid artery, and it is the most common form of systemic vasculitis in adults.
what is the epidemiology of GCA?
Over 50
Women more than men
what is the aetiology of GCA?
The exact cause remains unknown; however, genetic and environmental factors are thought to contribute to the development of GCA. The condition is probably triggered by an environmental cause in a genetically predisposed person. Genetic polymorphisms of the human leukocyte antigen (HLA) class II region are associated with susceptibility to GCA. Several infectious agents have been implicated, but conclusive evidence is lacking. These agents include Mycoplasma pneumoniae, parvovirus B19, parainfluenza virus, Chlamydia pneumoniae, and the varicella-zoster virus
what are the risk factors for GCA?
Aged over 50
Smoking
Atherosclerosis
Environmental factors
what is the pathophysiology of GCA?
Affected arteries contain inflammatory lesions arranged in granulomas composed of T cells and macrophages. Multinucleated giant cells are present in about 50% of cases, but they are not required to make the diagnosis of GCA.
The initial immune insult is thought to occur in the outer or adventitial layer of the arterial wall. Highly activated resident dendritic cells play a critical role by attracting and presenting antigen to T cells. CD4 T cells enter the artery through the vasa vasorum and, on activation, proliferate and undergo clonal expansion in the vessel wall. T cells release the cytokine interferon gamma, which in turn stimulates tissue-infiltrating macrophages and induces formation of multinucleated giant cells. Macrophages in the adventitia produce the inflammatory cytokines interleukin 1 and interleukin 6, which are responsible for systemic inflammation and the acute-phase response, resulting in elevation of inflammatory markers. In the muscular or medial layer of the artery, macrophages cause tissue damage by releasing matrix metalloproteinases and reactive oxygen species, resulting in oxidative stress. Consequently, the internal elastic lamina, which separates the intimal and medial layers, becomes fragmented. Multinucleated giant cells tend to lie at the media-intima border, often close to fragments of the internal elastic lamina.
In response to immunological injury, the artery releases growth and angiogenic factors (i.e., platelet-derived growth factor and vascular endothelial growth factor) that result in proliferation of myofibroblasts, new vessel formation, and marked thickening of the intimal or inner layer.
This process of intimal expansion and hyperplasia leads to narrowing and occlusion of the vessel lumen, ultimately causing tissue ischaemia.
what are the key presentations of GCA?
Presence of risk factors Headache Scalp pain Aching and stiffness Extremity claudication Loss of vision, jaw and tongue claudication, arterial tenderness, absent pulse, abnormal fundoscopy
what are the signs of GCA?
absent pulse
abnormal fundoscopy
Bruit on auscultation
Asymmetric blood pressure
what are the symptoms of GCA?
Headache Scalp pain Aching and stiffness Extremity claudication Loss of vision jaw and tongue claudication arterial tenderness Systemic symptoms Neurological symptoms Shoulder tenderness Limited range of motion in hips and shoulders
what are the first line and gold standard investigations for GCA?
CRP - high
ESR - high
FBC - normochromic, normocytic anaemia, normal WBC, high platelet count
Vascular ultrasonography - may show wall thickening (halo sign), stenosis, or occlusion; a non-compressible halo sign is the finding that most indicates GCA
Temporal artery biopsy - histopathology typically shows granulomatous inflammation; in about 50% of cases, multinucleated giant cells are present; inflammatory infiltrate may be focal and segmental. A positive biopsy showing features of inflammation characteristic of GCA (e.g., giant cells or panarteritis), confirms the diagnosis
Liver function tests - transaminases and alkaline phosphatase are sometimes mildly elevated
Renal function test - may be mildly abnormal but consider other causes
what are the differential diagnoses for GCA?
Polymyalgia rheumatica
Solid organ cancers
Takaasu’s arteritis
how is GCA managed?
Suspected:
Prednisolone, specialist treatment
Confirmed:
Prednisolone, consider tocilizumab or methotrexate, aspirin
how is GCA monitored?
During prednisolone taper, patients should be evaluated for toxicity and relapse with periodic clinical evaluation supported by inflammatory markers. Relapses should be diagnosed objectively as at diagnosis. Isolated elevation of inflammatory markers in the absence of clinical symptoms should not automatically result in escalation of therapy.
what are the complications of GCA?
Large vessel stenosis, aortic aneurysm, glucocorticoid related adverse effects
what is the prognosis of GCA?
The majority of patients respond rapidly to initial treatment with glucocorticoids, and vision loss in treated patients is rare. A treatment course of 1 to 2 years is often necessary, with some patients requiring low-dose prednisolone for several years.
