ISSN 0017-8748 doi: 10.1111/head.12425 Published by Wiley Periodicals, Inc.
Headache © 2014 American Headache Society
Review Article Giant Cell Arteritis Jonathan H. Smith, MD; Jerry W. Swanson, MD
Giant cell arteritis (GCA) is a medium and large-vessel vasculitis, which is an important cause of secondary headache in older adults. While GCA has a classic presentation occurring after the age of 50, atypical presentations (eg, fever of unknown origin, cough, low or normal erythrocyte sedimentation rate) may lead to a delay in diagnosis. The topography of vascular involvement has implications for disease-related complications, which can result in neurologic disease at multiple levels of the nervous system. The most feared complication, vision loss, fortunately becomes uncommon after initiation of corticosteroids. Corticosteroid treatment should not be withheld while waiting the results of a temporal artery biopsy (TAB), which remains the gold standard for GCA diagnosis. Newer diagnostic modalities, including ultrasound, magnetic resonance imaging, and positron emission tomography can play an important role in directing treatment in cases with negative TAB. After successful control of the disorder, patients should be gradually tapered off corticosteroids, with careful monitoring using both clinical and laboratory parameters to assess for relapse. Corticosteroid-related treatment complications are not uncommon in GCA. There is mixed evidence for use of adjunct corticosteroid-sparing agents (eg, methotrexate), although these should be initiated in the setting of corticosteroid-related morbidity and/or cases with frequent relapse. Key words: giant cell arteritis, temporal arteritis, cranial arteritis, secondary headache, older adult, elderly (Headache 2014;••:••-••)
Giant cell arteritis (GCA), also known as temporal arteritis, is arguably the most important secondary cause of headache among older adults. This statement is justified by the fact that GCA has a characteristic clinical presentation, is simple and cost-effective to screen for, is treatable, and if not treated, can result in significant morbidity, including blindness, and death. As the number of older adults in the population is expected to triple over the next 50 years, the burden of this disorder will also increase, necessitating improved care by both general practitioners and specialists, alike.
The classic presentation of GCA is captured by the 1990 American College of Rheumatology criteria, which require fulfillment of 3 out of 5 core features.1 These include age of 50 years or older at onset, a new headache, a clinical temporal artery abnormality, an elevated erythrocyte sedimentation rate (ESR) of at least 50 millimeter/hour, and an abnormal temporal artery biopsy (TAB). Accordingly, GCA is generally regarded as a cranial arteritis, although 20% to 30% of patients will also have radiographic evidence for involvement of the aortic trunk and branches.2 This latter information is critical for appropriate recognition and management of vascular complications. In this article, we will provide a comprehensive review of GCA diagnosis and management, which at times does not conform to the classically described paradigm. Familiarity with both diagnostic
From the Kentucky Neuroscience Institute, University of Kentucky, Lexington, KY, USA (J.H. Smith); Department of Neurology, Mayo Clinic, Rochester, MN, USA (J.W. Swanson). Address all correspondence to J.H. Smith, University of Kentucky, 740 S. Limestone, L445, Lexington, KY 40536, USA. Accepted for publication June 8, 2014.
Conflict of Interest: The authors report no conflicts of interest.
1
2 complexities and longitudinal management strategies are important for the headache specialist.
HISTORY OF GIANT CELL ARTERITIS Some have speculated that the history of temporal arteritis dates back to 1350 B.C., citing artwork, referred to as the “blind harpist,” on the Egyptian tomb of Pa-Aton-Em-Heb.3 This drawing depicts an older adult with an elevated, broken line in the region of the temporal artery, and closed swollen eyes.3 The first definite clinical description of GCA was provided by Jonathan Hutchinson in 1890, who reported on an “old man” with inflamed, bilateral temporal arteries.4 In 1931, Max Schmidt5 reported the case of a 69-yearold man with headache, fever, body pain, and monocular vision loss, but erroneously attributed the observations to an intracranial aneurysm. A more complete description of the disorder did not emerge until 1932, when Bayard T. Horton at Mayo Clinic obtained the first TAB and described the associated histopathology.4 However, he originally suspected that the granulomatous inflammation was due to an actinomyces infection. Horton was also the first to describe jaw claudication in GCA, and to attempt treatment with cortisone.4 Jennings6 was the first to describe both elevation of the ESR, and vision loss as a complication in a 1938 report. In 1941, Gilmour7 suggested a relationship between chronic aortitis and temporal arteritis based on autopsy cases. Despite the original description of polymyalgia rheumatica (PMR) dating back to 1888, an association with GCA was not appreciated until the second half of the 20th century.8 The pathophysiologic relationship between these conditions continues to be debated today. EPIDEMIOLOGY The incidence of GCA increases with age, occurring in 29.6 per 100,000 per year among individuals aged 70 to 79, comparable to overall estimates for intracerebral hemorrhage.9,10 GCA has a 3-fold tendency to preferentially affect women (24.2 [confidence interval (CI), 19.5 to 28.9]) over men (8.2 [CI, 4.8 to 11.6]).11 The overall incidence has been felt to be generally stable over time.12,13 A higher incidence has been noted in Scandinavian, as opposed to other
white, Japanese, or black populations.13,14 The literature is mixed with regards to whether there is a seasonal occurrence to GCA incidence.11,13 GCA prevalence has been estimated to be at 440 cases per 1 million inhabitants greater than or equal to 50 years of age in northern Germany in 2006.15 An even greater prevalence estimate of 2230 cases per million has been reported using data from Olmsted County, Minnesota.16 In marked contrast, prevalence estimates from Japan are extremely low, reported as 1.47 cases per 10 million people over the age of 50.17 As reported in 1973, a minority of individuals (
Headache © 2014 American Headache Society
Review Article Giant Cell Arteritis Jonathan H. Smith, MD; Jerry W. Swanson, MD
Giant cell arteritis (GCA) is a medium and large-vessel vasculitis, which is an important cause of secondary headache in older adults. While GCA has a classic presentation occurring after the age of 50, atypical presentations (eg, fever of unknown origin, cough, low or normal erythrocyte sedimentation rate) may lead to a delay in diagnosis. The topography of vascular involvement has implications for disease-related complications, which can result in neurologic disease at multiple levels of the nervous system. The most feared complication, vision loss, fortunately becomes uncommon after initiation of corticosteroids. Corticosteroid treatment should not be withheld while waiting the results of a temporal artery biopsy (TAB), which remains the gold standard for GCA diagnosis. Newer diagnostic modalities, including ultrasound, magnetic resonance imaging, and positron emission tomography can play an important role in directing treatment in cases with negative TAB. After successful control of the disorder, patients should be gradually tapered off corticosteroids, with careful monitoring using both clinical and laboratory parameters to assess for relapse. Corticosteroid-related treatment complications are not uncommon in GCA. There is mixed evidence for use of adjunct corticosteroid-sparing agents (eg, methotrexate), although these should be initiated in the setting of corticosteroid-related morbidity and/or cases with frequent relapse. Key words: giant cell arteritis, temporal arteritis, cranial arteritis, secondary headache, older adult, elderly (Headache 2014;••:••-••)
Giant cell arteritis (GCA), also known as temporal arteritis, is arguably the most important secondary cause of headache among older adults. This statement is justified by the fact that GCA has a characteristic clinical presentation, is simple and cost-effective to screen for, is treatable, and if not treated, can result in significant morbidity, including blindness, and death. As the number of older adults in the population is expected to triple over the next 50 years, the burden of this disorder will also increase, necessitating improved care by both general practitioners and specialists, alike.
The classic presentation of GCA is captured by the 1990 American College of Rheumatology criteria, which require fulfillment of 3 out of 5 core features.1 These include age of 50 years or older at onset, a new headache, a clinical temporal artery abnormality, an elevated erythrocyte sedimentation rate (ESR) of at least 50 millimeter/hour, and an abnormal temporal artery biopsy (TAB). Accordingly, GCA is generally regarded as a cranial arteritis, although 20% to 30% of patients will also have radiographic evidence for involvement of the aortic trunk and branches.2 This latter information is critical for appropriate recognition and management of vascular complications. In this article, we will provide a comprehensive review of GCA diagnosis and management, which at times does not conform to the classically described paradigm. Familiarity with both diagnostic
From the Kentucky Neuroscience Institute, University of Kentucky, Lexington, KY, USA (J.H. Smith); Department of Neurology, Mayo Clinic, Rochester, MN, USA (J.W. Swanson). Address all correspondence to J.H. Smith, University of Kentucky, 740 S. Limestone, L445, Lexington, KY 40536, USA. Accepted for publication June 8, 2014.
Conflict of Interest: The authors report no conflicts of interest.
1
2 complexities and longitudinal management strategies are important for the headache specialist.
HISTORY OF GIANT CELL ARTERITIS Some have speculated that the history of temporal arteritis dates back to 1350 B.C., citing artwork, referred to as the “blind harpist,” on the Egyptian tomb of Pa-Aton-Em-Heb.3 This drawing depicts an older adult with an elevated, broken line in the region of the temporal artery, and closed swollen eyes.3 The first definite clinical description of GCA was provided by Jonathan Hutchinson in 1890, who reported on an “old man” with inflamed, bilateral temporal arteries.4 In 1931, Max Schmidt5 reported the case of a 69-yearold man with headache, fever, body pain, and monocular vision loss, but erroneously attributed the observations to an intracranial aneurysm. A more complete description of the disorder did not emerge until 1932, when Bayard T. Horton at Mayo Clinic obtained the first TAB and described the associated histopathology.4 However, he originally suspected that the granulomatous inflammation was due to an actinomyces infection. Horton was also the first to describe jaw claudication in GCA, and to attempt treatment with cortisone.4 Jennings6 was the first to describe both elevation of the ESR, and vision loss as a complication in a 1938 report. In 1941, Gilmour7 suggested a relationship between chronic aortitis and temporal arteritis based on autopsy cases. Despite the original description of polymyalgia rheumatica (PMR) dating back to 1888, an association with GCA was not appreciated until the second half of the 20th century.8 The pathophysiologic relationship between these conditions continues to be debated today. EPIDEMIOLOGY The incidence of GCA increases with age, occurring in 29.6 per 100,000 per year among individuals aged 70 to 79, comparable to overall estimates for intracerebral hemorrhage.9,10 GCA has a 3-fold tendency to preferentially affect women (24.2 [confidence interval (CI), 19.5 to 28.9]) over men (8.2 [CI, 4.8 to 11.6]).11 The overall incidence has been felt to be generally stable over time.12,13 A higher incidence has been noted in Scandinavian, as opposed to other
white, Japanese, or black populations.13,14 The literature is mixed with regards to whether there is a seasonal occurrence to GCA incidence.11,13 GCA prevalence has been estimated to be at 440 cases per 1 million inhabitants greater than or equal to 50 years of age in northern Germany in 2006.15 An even greater prevalence estimate of 2230 cases per million has been reported using data from Olmsted County, Minnesota.16 In marked contrast, prevalence estimates from Japan are extremely low, reported as 1.47 cases per 10 million people over the age of 50.17 As reported in 1973, a minority of individuals (
