Giant cell arteritis Author: Doctor José María Calvo-Romero1 Creation Date: June 2003 Scientific Editor: Professor Loic Guillevin 1Department of Internal Medicine, Hospital de Zafra, Antigua Ctra. Nacional 432, 06300 Zafra (Badajoz), Spain. [email protected] Abstract Key-words Disease names Definition Epidemiology Etiology Clinical manifestations Laboratory findings Diagnosis Treatment Prognosis References Abstract Giant cell arteritis (GCA) or temporal arteritis is a systemic vasculitis which involves large and medium- sized vessels, especially the extracranial branches of the carotid artery, usually in persons older than 50 years. Feared complications of GCA are permanent visual loss, ischaemic strokes and thoracic and abdominal aortic aneurysms. The treatment consists of high-dose steroids. Mortality in patients with GCA seems to be similar to that of controls, probably due to a correct diagnosis and management. GCA is the most common systemic vasculitis in Western countries. The incidence rates described in European countries are around 20:100 000 persons older than 50 years. Key-words vasculitis, giant cell arteritis, temporal arteritis, Horton’s arteritis, large and medium-sized vessels disorder. Disease names Table 1: The Chapel Hill Consensus Giant cell arteritis Conference on the Nomenclature of Systemic Temporal arteritis Vasculitis Horton’s arteritis Large Vessel Vasculitis Giant cell arteritis Definition Takayasu arteritis Giant cell arteritis (GCA) is a relatively common Medium Vessel Vasculitis systemic vasculitis in Europe. GCA involves Polyarteritis nodosa large and medium-sized vessels in patients Kawasaki’s disease usually older than 50 years. It is a Small Vessel Vasculitis granulomatous arteritis of the aorta and its major Wegener’s granulomatosis branches, especially the extracranial branches of Churg-Strauss syndrome Microscopic polyangiitis the carotid artery. Henoch-Schonlein purpura Cryoglobulinemic vasculitis Cutaneous leukocytoclastic vasculitis Calvo-Romero JM. Giant cell arteritis, Orphanet encyclopedia, June 2003. http://www.orpha.net/data/patho/GB/uk-GCA.pdf 1 Epidemiology preceded by amaurosis fugax, is found in 1- GCA almost exclusively affects persons older 15%. Predictors associated with an than 50 years. GCA is the most common increased risk of permanent visual loss are a systemic vasculitis in Western countries. The history of amaurosis fugax and highest incidence rates are described in cerebrovascular accidents, the absence of Scandinavian countries and in North American anaemia and a higher platelet count. The populations of the same descent (table 2). GCA presence of constitutional symptoms and is more common among women than men. In polymyalgia rheumatica are associated with the last years, a progressive increase in the a reduced risk. incidence has been reported. - Audiovestibular manifestations (nystagmus and hearing loss). Table 2: Incidence of GCA - Polymyalgia rheumatica, a clinical syndrome Country Years Incidence* characterized by pain and stiffness in neck, Norway (Aust Agder) 1987-94 29 shoulder girdle and pelvic girdle. Iceland 1984-90 27 Sweden (Goteborg) 1973-75 18 Uncommon clinical manifestations United States (Minnesota) 1950-85 17 - High-grade fever and unknown origin fever Spain (Lugo) 1988-97 11 - Carotidynia Israel (Jerusalem) 1980-91 10 - Enlarged or tender occipital, facial or France (Loire-Atlantique) 1970-79 9 postauricular arteries Italy (Reggio Emilia) 1980-88 7 - Claudication of the tongue or the swallowing * Incidence per 100.000 persons older than 50 years. - Necrosis of the tongue or the scalp - Ocular muscle paresis Etiology - Lower limb claudication and aortic arch GCA is a chronic inflammatory disorder involving syndrome resulting in arm claudication large and medium-sized arteries. Some familial - Thoracic and abdominal aortic aneurysms accumulation and the association with the HLA- - Coronary ischaemia DR4 haplotype suggest a genetic predisposition. - Pulmonary artery thrombosis Epidemiological observations may indicate an - Intestinal infarction infectious origin. Immunological research - Ischaemic strokes (affecting carotid or demonstrates an antigen-driven disease with vertebrobasilar territories), dementia, spinal local T-cell and macrophage activation in the cord infarction, mononeuropathies (e.g. vessel wall with an important role of the brachial plexopathy) and polyneuropathies proinflammatory cytokines. The initial process - Cough, sore throat, and hoarseness may be a foreign-body giant-cell attack on - Peripheral arthritis calcified internal elastic membrane in arteries. - Secondary amyloidosis The prerequisite of a calcified artery is a possible explanation for that GCA almost exclusively Laboratory findings affects persons older than 50 years. Although Erythrocyte sedimentation rate (ESR) is usually progress towards the understanding of GCA higher than 50 mm/hour, but a lower erythrocyte pathogenesis during the last decade are sedimentation rate is possible. However, a encouraging, the etiology remains unknown. completely normal erythrocyte sedimentation rate (< 30 mm/hour) is exceptional in GCA. C- Clinical manifestations reactive protein and fibrinogen is usually Most of these manifestations occur prior to elevated. steroid therapy, but they may also develop Anaemia, thrombocytosis, and abnormal liver- during the early phase of therapy, or during function tests are frequent. Rheumatoid factor tapering of the dose of steroids. and antinuclear antibodies are usually negative. Previous studies suggest that the circulating Common clinical manifestations CD8 T cells are reduced in patients with active - Constitutional syndrome (asthenia, anorexia, GCA. However, these findings have not been and weight loss) confirmed and the utility of this determination - Low-grade fever should be re-evaluated. Levels of interleukin-6 - A new onset headache or a new type may be an indicator of active disease. headache - Thickened, nodular, tender and Diagnosis erythematous temporal arteries with GCA should be confirmed by temporal artery decreased or absent pulses biopsy. Biopsy demonstrates a vasculitis - Jaw claudication characterized by a predominance of - Visual ischaemic complications are mononuclear infiltrates or granulomas, usually observed in about 25% of patients, and with multinucleated giant cells. A normal irreversible blindness, mainly due to anterior temporal artery biopsy does not exclude a GCA ischaemic optic neuropathy and frequently Calvo-Romero JM. Giant cell arteritis, Orphanet encyclopedia, June 2003. http://www.orpha.net/data/patho/GB/uk-GCA.pdf 2 since the lesions may be skipped. Routinely improvement, although there are contradictory examining a temporal artery biopsy at multiple results. Steroid therapy may be indicated to levels seems not to increase the diagnostic yield, prevent complications before confirmatory although selective further examination may be temporal artery biopsy. Moreover, temporal indicated in some cases. Patients without visual artery biopsy is useful several weeks after manifestations, abnormal temporal arteries on administration of steroids. Calcium and vitamin D examination or constitutional syndrome have a supplements must be provided to all patients low risk of having a positive temporal artery treated with steroids. Byphosphonates therapy biopsy. should be considered in patients with The American College of Rheumatology osteoporosis. proposed a list of criteria for diagnosis of GCA Methotrexate may be useful to control disease (table 3). The presence of three or more criteria activity or to decrease the cumulative dose and had a sensitivity of 97.5% and a specificity of toxicity of steroids. In a Spanish study, treatment 78.9% in a French study of patients in whom the with prednisone and methotrexate reduced the diagnosis of GCA was confirmed or ruled out by proportion of patients who experienced at least temporal artery biopsy. one relapse or multiple relapses, and the mean The presence of a halo sign or an inflammatory cumulative dose of prednisone was lower in the stenosis in the color duplex ultrasonography of patients with combined therapy. However, other the temporal arteries can effectively predict studies have not confirmed these results. which patient will need surgical biopsy and eliminate patients who would not benefit from Prognosis biopsy. It has been suggested that the lack of a Death due to cardiovascular diseases may halo sign can practically to rule out a GCA. increase in patients with GCA related to either However, ultrasonography may be equivalent to the steroid therapy itself or insufficient control of a careful physical examination. inflammation. However, mortality in patients with Although confirmatory studies are necessary, GCA seems to be similar to that of controls, positron emission tomography may contribute to probably due to a correct diagnosis and the noninvasive diagnosis of GCA and to the management. No increased frequency of evaluation of the extent of disease, response to malignant neoplasms in GCA has been reported therapy, and disease recurrence. A high in a recent prospective study. temporal 67-gallium uptake is observed in patients with GCA, and the uptake normalizes References during remission. Achkar AA, Lie JT, Gabriel SE, Hunder GG. Giant cell arteritis involving the facial artery. J Rheumatol 1995; 22:360-362. Table 3: The American College of Achkar AA, Lie TJ, Hunder GG, O’Fallon WM, Rheumatology criteria for diagnosis of GCA Gabriel SE. How does previous