Giant cell arteritis | |
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Other names | Temporal arteritis, cranial arteritis, [1] Horton disease, [2] senile arteritis, [1] granulomatous arteritis [1] |
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The arteries of the face and scalp | |
Specialty | Rheumatology, emergency medicine, Immunology |
Symptoms | Headache, pain over the temples, flu-like symptoms, double vision, difficulty opening the mouth [3] |
Complications | Blindness, aortic dissection, aortic aneurysm, polymyalgia rheumatica [4] |
Usual onset | Age greater than 50 [4] |
Causes | Inflammation of the small blood vessels within the walls of larger arteries [4] |
Diagnostic method | Based on symptoms and blood tests, confirmed by biopsy of the temporal artery [4] |
Differential diagnosis | Takayasu arteritis, [5] stroke, primary amyloidosis [6] |
Treatment | Steroids, bisphosphonates, proton-pump inhibitor [4] |
Prognosis | Life expectancy (typically normal) [4] |
Frequency | ~ 1 in 15,000 people a year (> 50 years old) [2] |
Giant cell arteritis (GCA), also called temporal arteritis, is an inflammatory autoimmune disease of large blood vessels. [4] [7] Symptoms may include headache, pain over the temples, flu-like symptoms, double vision, and difficulty opening the mouth. [3] Complications can include blockage of the artery to the eye with resulting blindness, as well as aortic dissection, and aortic aneurysm. [4] GCA is frequently associated with polymyalgia rheumatica. [4] It can be confirmed by biopsy of the temporal artery in about 90% of people.
The cause is unknown. [2] The underlying mechanism involves inflammation of the small blood vessels that supply the walls of larger arteries. [4] This mainly affects arteries around the head and neck, though some in the chest may also be affected. [4] [8] Diagnosis is suspected based on symptoms, blood tests, and medical imaging, and confirmed by biopsy of the temporal artery. [4] However, in about 10% of people the temporal artery is normal. [4]
Treatment is typical with high doses of steroids such as prednisone or prednisolone. [4] Once symptoms have resolved, the dose is decreased by about 15% per month. [4] Once a low dose is reached, the taper is slowed further over the subsequent year. [4] Other medications that may be recommended include bisphosphonates to prevent bone loss and a proton-pump inhibitor to prevent stomach problems. [4]
It affects about 1 in 15,000 people over the age of 50 per year. [2] The condition mostly occurs in those over the age of 50, being most common among those in their 70s. [4] Females are more often affected than males. [4] Those of northern European descent are more commonly affected. [5] Life expectancy is typically normal. [4] The first description of the condition occurred in 1890. [1]
Common symptoms of giant cell arteritis include:
The inflammation may affect blood supply to the eye; blurred vision or sudden blindness may occur. In 76% of cases involving the eye, the ophthalmic artery is involved, causing arteritic anterior ischemic optic neuropathy. [13]
Giant cell arteritis may present with atypical or overlapping features. [14] Early and accurate diagnosis is important to prevent ischemic vision loss. Therefore, this condition is considered a medical emergency. [14]
While studies vary as to the exact relapse rate of giant cell arteritis, relapse of this condition can occur. [15] It most often happens at low doses of prednisone (<20 mg/day), during the first year of treatment, and the most common signs of relapse are headache and polymyalgia rheumatica. [15]
The varicella-zoster virus (VZV) antigen was found in 74% of temporal artery biopsies that were GCA-positive, suggesting that the VZV infection may trigger the inflammatory cascade. [16]
The disorder may co-exist (in about half of cases) with polymyalgia rheumatica (PMR), [12] which is characterized by sudden onset of pain and stiffness in muscles (pelvis, shoulder) of the body and is seen in the elderly. GCA and PMR are so closely linked that they are often considered to be different manifestations of the same disease process. PMR usually lacks the cranial symptoms, including headache, pain in the jaw while chewing, and vision symptoms, that are present in GCA. [17]
Giant cell arteritis can affect the aorta and lead to aortic aneurysm and aortic dissection. [18] Up to 67% of people with GCA having evidence of an inflamed aorta, which can increase the risk of aortic aneurysm and dissection. [18] There are arguments for the routine screening of each person with GCA for this possible life-threatening complication by imaging the aorta. Screening should be done on a case-by-case basis based on the signs and symptoms of people with GCA. [18]
The pathological mechanism is the result of an inflammatory cascade that is triggered by an as of yet undetermined cause resulting in dendritic cells in the vessel wall recruiting T cells and macrophages to form granulomatous infiltrates. [18] These infiltrates erode the middle and inner layers of the arterial tunica media leading to conditions such as aneurysm and dissection. [18] Activation of T helper 17 (Th17) cells involved with interleukin (IL) 6, IL-17, IL-21 and IL-23 play a critical part; specifically, Th17 activation leads to further activation of Th17 through IL-6 in a continuous, cyclic fashion. [18] This pathway is suppressed with glucocorticoids, [19] and more recently it has been found that IL-6 inhibitors also play a suppressive role. [18]
The gold standard for diagnosing temporal arteritis is biopsy, which involves removing a small part of the vessel under local anesthesia and examining it microscopically for giant cells infiltrating the tissue. [22] However, a negative result does not definitively rule out the diagnosis; since the blood vessels are involved in a patchy pattern, there may be unaffected areas on the vessel and the biopsy might have been taken from these parts. Unilateral biopsy of a 1.5–3 cm length is 85-90% sensitive (1 cm is the minimum). [23] Characterised as intimal hyperplasia and medial granulomatous inflammation with elastic lamina fragmentation with a CD 4+ predominant T cell infiltrate, currently biopsy is only considered confirmatory for the clinical diagnosis, or one of the diagnostic criteria. [11]
Radiological examination of the temporal artery with ultrasound yields a halo sign. Contrast-enhanced brain MRI and CT are generally negative in this disorder. Recent studies have shown that 3T MRI using super high resolution imaging and contrast injection can non-invasively diagnose this disorder with high specificity and sensitivity. [24]
Women and men approximately 45 years old and who suffer from several complaints (at least 5 of the 16 symptoms) [25] listed below could have giant cell arteritis.
GCA is considered a medical emergency due to the potential of irreversible vision loss. [14] Corticosteroids, typically high-dose prednisone (1 mg/kg/day), should be started as soon as the diagnosis is suspected (even before the diagnosis is confirmed by biopsy) to prevent irreversible blindness secondary to ophthalmic artery occlusion. Steroids do not prevent the diagnosis from later being confirmed by biopsy, although certain changes in the histology may be observed towards the end of the first week of treatment and are more difficult to identify after a couple of months. [26] The dose of corticosteroids is generally slowly tapered over 12–18 months. [21] Oral steroids are at least as effective as intravenous steroids, [27] except in the treatment of acute visual loss where intravenous steroids appear to offer significant benefit over oral steroids. [28] Short-term side effects of prednisone are uncommon but can include mood changes, avascular necrosis, and an increased risk of infection. [29] Some of the side effects associated with long-term use include weight gain, diabetes mellitus, osteoporosis, avascular necrosis, glaucoma, cataracts, cardiovascular disease, and an increased risk of infection. [30] [31] It is unclear whether adding a small amount of aspirin is beneficial or not as it has not been studied. [32] Injections of tocilizumab may also be used. [33] Tocilizumab is a humanized antibody that targets the interleukin-6 receptor, which is a key cytokine involved in the progression of GCA. [34] Tocilizumab has been found to be effective at minimizing both recurrence, and flares of GCA when used both on its own and with corticosteroids. [34] Long term use of tocilizumab requires further investigation. [34] [35] Tocilizumab may increase the risk of gastrointestinal perforation and infections, however it does not appear that there are more risks than using corticosteroids. [34] [35]
Giant cell arteritis typically only occurs in those over the age of 50; [4] particularly those in their 70s. [21] It affects about 1 in 15,000 people over the age of 50 per year. [2] It is more common in women than in men, by a ratio of 2:1, [4] and more common in those of Northern European descent, as well as in those residing further from the Equator. [5]
Giant cell arteritis and its treatment impact on people's lives because of symptoms, adverse effects of GCs and disruption to normal life. [36] People with GCA have previously ranked ‘losing sight in both eyes permanently’, ‘having intense or severe pain’ and ‘feeling weak, tired or exhausted’ as important quality of life domains. [37] Generic measures of disease impact such as SF36 may not always capture the disease specific aspects of GCA impact such as visual loss or systemic complications. [38] The Outcome Measures in Rheumatology (OMERACT) Large Vessel Vasculitis Working Group have identified the need for a disease-specific patient-reported outcome measure (PROM) for GCA. [39] Recently, a new disease specific measure of health-related quality of life in GCA has been developed. [40] [41] The GCA-PRO has been shown to have robust validity and reliability in a cross-sectional study and can discriminate between different sub-groups of patients. This is likely going to help to capture the impact of disease and treatment in clinical trials and clinical practice. [41]
The terms "giant cell arteritis" and "temporal arteritis" are sometimes used interchangeably, because of the frequent involvement of the temporal artery. However, other large vessels such as the aorta can be involved. [42] Giant-cell arteritis is also known as "cranial arteritis" and "Horton's disease". [43] The name (giant cell arteritis) reflects the type of inflammatory cell involved. [44]
Rheumatology is a branch of medicine devoted to the diagnosis and management of disorders whose common feature is inflammation in the bones, muscles, joints, and internal organs. Rheumatology covers more than 100 different complex diseases, collectively known as rheumatic diseases, which includes many forms of arthritis as well as lupus and Sjögren's syndrome. Doctors who have undergone formal training in rheumatology are called rheumatologists.
The erythrocyte sedimentation rate is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. It is a common hematology test, and is a non-specific measure of inflammation. To perform the test, anticoagulated blood is traditionally placed in an upright tube, known as a Westergren tube, and the distance which the red blood cells fall is measured and reported in millimetres at the end of one hour.
Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis. Vasculitis is primarily caused by leukocyte migration and resultant damage. Although both occur in vasculitis, inflammation of veins (phlebitis) or arteries (arteritis) on their own are separate entities.
Kawasaki disease is a syndrome of unknown cause that results in a fever and mainly affects children under 5 years of age. It is a form of vasculitis, where medium-sized blood vessels become inflamed throughout the body. The fever typically lasts for more than five days and is not affected by usual medications. Other common symptoms include large lymph nodes in the neck, a rash in the genital area, lips, palms, or soles of the feet, and red eyes. Within three weeks of the onset, the skin from the hands and feet may peel, after which recovery typically occurs. The disease is the leading cause of acquired heart disease in children in developed countries, which include the formation of coronary artery aneurysms and myocarditis.
Takayasu's arteritis (TA), also known as aortic arch syndrome, nonspecific aortoarteritis, and pulseless disease, is a form of large vessel granulomatous vasculitis with massive intimal fibrosis and vascular narrowing, most commonly affecting young or middle-aged women of Asian descent, though anyone can be affected. It mainly affects the aorta and its branches, as well as the pulmonary arteries. Females are about 8–9 times more likely to be affected than males.
Arteritis is a vascular disorder characterized by inflammation of the walls of arteries, usually as a result of infection or autoimmune responses. Arteritis, a complex disorder, is still not entirely understood. Arteritis may be distinguished by its different types, based on the organ systems affected by the disease. A complication of arteritis is thrombosis, which can be fatal. Arteritis and phlebitis are forms of vasculitis.
Polymyalgia rheumatica (PMR) is a syndrome experienced as pain or stiffness, usually in the neck, shoulders, upper arms, and hips, but which may occur all over the body. The pain can be sudden or can occur gradually over a period. Most people with PMR wake up in the morning with pain in their muscles; however, cases have occurred in which the person has developed the pain during the evenings or has pain and stiffness all day long.
Posterior ischemic optic neuropathy (PION) is a medical condition characterized by damage to the retrobulbar portion of the optic nerve due to inadequate blood flow (ischemia) to the optic nerve. Despite the term posterior, this form of damage to the eye's optic nerve due to poor blood flow also includes cases where the cause of inadequate blood flow to the nerve is anterior, as the condition describes a particular mechanism of visual loss as much as the location of damage in the optic nerve. In contrast, anterior ischemic optic neuropathy (AION) is distinguished from PION by the fact that AION occurs spontaneously and on one side in affected individuals with predisposing anatomic or cardiovascular risk factors.
A giant cell is a mass formed by the union of several distinct cells, often forming a granuloma.
Myositis is a rarely-encountered medical condition characterized by inflammation affecting the muscles. The manifestations of this condition may include skin issues, muscle weakness, and the potential involvement of other organs. Additionally, systemic symptoms like weight loss, fatigue, and low-grade fever can manifest in individuals with myositis.
Arteritic anterior ischemic optic neuropathy is the cause of vision loss that occurs in temporal arteritis. Temporal arteritis is an inflammatory disease of medium-sized blood vessels that happens especially with advancing age. AAION occurs in about 15-20 percent of patients with temporal arteritis. Damage to the blood vessels supplying the optic nerves leads to insufficient blood supply (ischemia) to the nerve and subsequent optic nerve fiber death. Most cases of AAION result in nearly complete vision loss first to one eye. If the temporal arteritis is left untreated, the fellow eye will likely suffer vision loss as well within 1–2 weeks. Arteritic AION falls under the general category of anterior ischemic optic neuropathy, which also includes non-arteritic AION. AION is considered an eye emergency, immediate treatment is essential to rescue remaining vision.
Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, cytokine release syndrome, COVID‑19, and systemic sclerosis-associated interstitial lung disease (SSc-ILD). It is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Interleukin 6 (IL-6) is a cytokine that plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. Tocilizumab was jointly developed by Osaka University and Chugai, and was licensed in 2003 by Hoffmann-La Roche.
Aortitis is the inflammation of the aortic wall. The disorder is potentially life-threatening and rare. It is reported that there are only 1–3 new cases of aortitis per year per million people in the United States and Europe. Aortitis is most common in people 10 to 40 years of age.
AA amyloidosis is a form of amyloidosis, a disease characterized by the abnormal deposition of fibers of insoluble protein in the extracellular space of various tissues and organs. In AA amyloidosis, the deposited protein is serum amyloid A protein (SAA), an acute-phase protein which is normally soluble and whose plasma concentration is highest during inflammation.
Cerebral vasculitis is vasculitis involving the brain and occasionally the spinal cord. It affects all of the vessels: very small blood vessels (capillaries), medium-size blood vessels, or large blood vessels. If blood flow in a vessel with vasculitis is reduced or stopped, the parts of the body that receive blood from that vessel begins to die. It may produce a wide range of neurological symptoms, such as headache, skin rashes, feeling very tired, joint pains, difficulty moving or coordinating part of the body, changes in sensation, and alterations in perception, thought or behavior, as well as the phenomena of a mass lesion in the brain leading to coma and herniation. Some of its signs and symptoms may resemble multiple sclerosis. 10% have associated bleeding in the brain.
Inflammatory myopathy, also known as idiopathic inflammatory myopathy (IIM), is disease featuring muscle weakness, inflammation of muscles (myositis), and in some types, muscle pain. The cause of much inflammatory myopathy is unknown (idiopathic), and such cases are classified according to their symptoms and signs, electromyography, MRI, and laboratory findings. It can also be associated with underlying cancer. The main classes of idiopathic inflammatory myopathy are polymyositis (PM), dermatomyositis (DM), inclusion-body myositis (IBM), immune-mediated necrotising myopathy (IMNM), and focal autoimmune myositis.
Necrotizing vasculitis, also called systemic necrotizing vasculitis, is a general term for the inflammation of veins and arteries that develops into necrosis and narrows the vessels.
Cryofibrinogenemia refers to a condition classified as a fibrinogen disorder in which a person's blood plasma is allowed to cool substantially, causing the (reversible) precipitation of a complex containing fibrinogen, fibrin, fibronectin, and, occasionally, small amounts of fibrin split products, albumin, immunoglobulins and other plasma proteins.
Antisynthetase syndrome (ASS) is a multisystematic autoimmune disease associated with inflammatory myositis, interstitial lung disease, and antibodies directed against various synthetases of aminoacyl-transfer RNA. Other common symptoms include mechanic's hands, Raynaud's phenomenon, arthritis, and fever.
Acute visual loss is a rapid loss of the ability to see. It is caused by many ocular conditions like retinal detachment, glaucoma, macular degeneration, and giant cell arteritis, etc.