Temporal arteritis
By James Goodwin MD (Dr. Goodwin of the University of Illinois at Chicago has no relevant financial relationships to disclose.)
Originally released May 14, 1996; last updated September 21, 2016; expires September 21, 2019
Introduction
This article includes discussion of temporal arteritis, arteritis of the aged, Bagratuni syndrome, cranial arteritis, giant
cell arteritis, polymyalgia arteritica, Rumbold disease, senile rheumatic gout, and polymyalgia rheumatica. The
foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.
Overview
Temporal arteritis is an important cause of ischemic complications in elderly patients and timely diagnosis can prevent
important morbidity, most notably blindness from either anterior ischemic optic neuropathy or central retinal artery
occlusion. These patients, left untreated, are also at increased risk for ischemic stroke. Treatment with high-dose
corticosteroids is effective in preventing these complications, and initial treatment with intravenous pulse
corticosteroids leads to more sustained clinical remission and lower subsequent oral corticosteroid dosage
requirement. Other adjunctive immunosuppressant drugs are also currently being used in this setting as steroidsparing agents. In this update, the author cites studies showing increased risk for a variety of ischemic cardiovascular
complications among patients with temporal arteritis and patients who were taking statin drugs, which had a
somewhat lesser incidence of these complications. He also reviews advances in biological treatment of giant cell
arteritis with monoclonal antibodies with and without concomitant corticosteroid treatment.
Key points
• Temporal arteritis is a systemic vascular disease in which inflammation, usually with giant
cells, affects the internal elastic lamina, adventitia, and adjacent media of medium and large
arteries with a predilection for those in the head and neck.
• It is a disease almost exclusively in the elderly (older than 60 years) and usually presents
with headache along with manifestations of ischemia in tissues of the head including most
commonly pain, ulceration, and necrosis involving the scalp and oral mucosa.
• Ischemia of the temporalis and masseter muscles produces a distinctive syndrome called
jaw claudication with crescendo pain in the mandibular region while chewing solid food and
gradual relief after cessation of muscular activity in the involved muscles.
• The most common serious complication is vision loss from ischemic optic neuropathy or
central retinal artery occlusion.
• Ischemic stroke can occur secondary to emboli from involved extracranial carotid and
vertebral arteries—intracranial segments of the arteries are not involved, possibly because
they lack an internal elastic lamina.
• Serious complications can be prevented by treatment with systemic corticosteroids in
adequate doses over prolonged periods.
Historical note and terminology
The earliest case report of what was probably temporal arteritis is attributed to Ali Ibn Isa, a 10th century oculist
(Woods 1936). Hutchinson described another early case in a man of 80 named Rumbold, who presented with painful,
swollen, and reddened temporal arteries in the apparent absence of systemic symptoms. The inflammation subsided
gradually and left the arteries as "pulseless impervious cords" (Hutchinson 1889). Some authors have since referred to
temporal arteritis as Rumbold disease.
Credit for the earliest complete description of the disease with pathologic documentation of characteristic
inflammation and giant cells in the temporal artery must be accorded to Horton and colleagues from the Mayo Clinic.
The following is their succinct clinical description derived from examining 2 patients:
Both patients were admitted to the Clinic in the spring of 1931 because of fever,
weakness, anorexia, loss of weight, anemia, mild leukocytosis, and painful, tender areas
over the scalp and along temporal vessels. These manifestations had been present for 4
weeks to 6 weeks. Temporal artery biopsy in these 2 cases yielded granulomatous
arteritis and periarteritis (Horton et al 1932).
Since this report, temporal artery biopsy has remained as the mainstay of pathologic diagnosis, though biopsy of other
accessible cranial vessels has occasionally been advocated.
As cases accumulated, it became apparent that temporal arteritis usually presents with headache and symptoms of
systemic illness exclusively in elderly persons. Another painful syndrome, now called "polymyalgia rheumatica" after
Barber (Barber 1957), shares with temporal arteritis the strong predilection for the elderly and the association with
signs and symptoms of systemic illness. In the mid-1950s the concept that temporal arteritis and polymyalgia
rheumatica are but 2 clinical manifestations of the same basic disease process was introduced (Paulley and Hughes
1960). Hamrin and Ostberg both provided landmark publications, the former reporting his series of 93 cases of
polymyalgia rheumatica with analysis of the relationship with temporal arteritis and underlying vascular pathology,
and the latter reporting an autopsy study that revealed the link between the clinical syndrome called "polymyalgia
rheumatica and giant cell arteritis of the aorta and its main branches" (Hamrin 1972; Ostberg 1973).
Clinical manifestations
Presentation and course
New headache or dramatic change in pattern of longstanding headache in an elderly patient is the most common
presentation of temporal arteritis. The pain may have a local component along the temporal and other external carotid
branches, but often the character of the headache is nonspecific (Hamilton et al 1971). Only a few individuals have
localized pain, induration, and tenderness over the temporal arteries or erythematous nodules along the vessels,
though it is worth looking for these physical signs. In some cases the temporal arteries are palpably indurated and may
show a "ropy" appearance beneath the skin.
The incidence of headache in temporal arteritis is about 80% in large series, so one cannot dismiss the diagnosis
entirely in the absence of headache. Severity of the headache is variable, and headache was the symptom that led to
referral of only 41 patients of 175 patients in the 1960 Mayo Clinic series. The typical headache, if one can be said to
occur, is maximal over the temples and suboccipital region. Occipital arteries as well as branches of the external
carotid artery are commonly involved, and pain in these vessels should be sought during the history and by palpation.
Tenderness specifically along extracranial branches of the carotid system is particularly useful in diagnosis when
present. Momentary stabbing or ice pick headache accompanying new-onset persistent headache in an elderly person
may be a useful indicator of temporal arteritis as the cause (Rozen 2010).
Diffuse tenderness of the scalp, face, or oral mucosa results from ischemia secondary to widespread arteritic
involvement of extracranial vessels. Some patients describe "head pains" rather than headache, indicating the
relatively superficial character of the discomfort (Paulley and Hughes 1960). Patients should be asked if they are
experiencing new tenderness when they comb their hair, or if a hat or the temple pieces of their glasses are causing
new pain in 1 or both temples. The pain in the vessel may be dependent on pulsatile blood flow and may cease with
thrombosis of the vessel. Similarly, the pain may be relieved when an involved segment of temporal artery is removed
for biopsy. When present, pain relief after biopsy is a strong element favoring the diagnosis, and patients should be
asked about this a few days after the biopsy when the local pain from the surgery has subsided.
Pain and ulceration of the oral mucosa tongue or scalp is an especially useful sign favoring temporal arteritis. Scalp
necrosis and ulceration can be mistaken for herpes zoster. The histopathology in temporal arteritis consists of
lymphocytic vasculitis, scarring with myxoid degeneration, and fat necrosis in the dermis (Ghaffar and Todd 2010).
Ischemia of the tongue can be misdiagnosed as glossitis with beefy enlargement and loss of taste sensation. In a
review, the mean interval between onset of temporal arteritis and scalp necrosis was 3 months in 19 patients who had
not been started on corticosteroids.
Jaw claudication is nearly pathognomonic for temporal arteritis, though it can be present on the basis of severe
atherosclerosis of the external and internal carotid arteries in rare instances. Both the internal and external carotid
systems must be affected together to produce jaw claudication, as each system provides collateral flow to the other
when occlusive disease involves only 1. Jaw claudication must be distinguished from other causes of pain around the
lower face and dentition. The pain of claudication builds progressively with the muscular activity of chewing rather
than occurring with the pressure of biting down, whereas dental pain occurs even with the first bite and pain occurs
with any jaw movement with pathology in the temporomandibular joint. As with claudication elsewhere, the pain is
relieved with rest and usually requires at least a few seconds to dissipate when the patient stops chewing. Careful
history taking is the only way to elicit these fine points and correctly identify claudication or ischemia as the
mechanism of pain.
Many patients with temporal arteritis have low-grade fever, leukocytosis, or mild anemia either at presentation or
during the course of the illness. Depression, listlessness, and general malaise are common complaints among the
elderly, but increased intensity of 1 or more of these symptoms may signal the onset of temporal arteritis. Nonspecific
complaints like these have been shown to precede the more specific symptoms, even for several months, in up to half
the patients. Weight loss, weakness, and inanition may be profound in the occasional patient.
Isolated psychiatric symptoms with psychotic features can be a presenting feature of temporal arteritis. Sudden onset
of psychosis in the elderly may warrant a short course of corticosteroids. Prompt remission of symptoms with steroid
treatment is another important factor in diagnosis.
Low back pain can be the presenting symptom of abdominal aortic giant cell arteritis, and 18 FDG-PET is useful to
identify the aortic involvement in this setting (Fernandez-Lopez et al 2007).
Occasionally, ischemic complications can appear before any of the systemic signs or symptoms of illness, making
diagnosis extremely difficult. Some authors have called this type of presentation "occult temporal arteritis" (Cullen
1963).
Although the signs and symptoms of temporal arteritis are variable, once they have begun they are usually continuous
or progressive until effective treatment is established, but Purvin and Kawasaki described 4 cases with spontaneous
remission of symptoms and signs (Purvin and Kawasaki 2007).
Because of its greater-than-chance association with temporal arteritis, it is important to be aware of the signs and
symptoms of polymyalgia rheumatica. It is not uncommon for patients with polymyalgia to develop additional
symptoms of temporal arteritis after they have had the original illness for some time, sometimes years.
Polymyalgia, like temporal arteritis, almost exclusively affects persons over the age of 50 years. The clinical picture
consists of pain and stiffness in the shoulder or pelvic girdles. Pain and limited motion of the axial skeleton including
the cervical and thoracic spine are common. Pain and stiffness are often worse on arising in the morning, with some
improvement of mobility as the day proceeds. Onset may be insidious or acute. Severity of symptoms can be
asymmetric, but the disorder is invariably bilateral. There may be mild swelling of the shoulders and even distal joints
in the extremities, but as a rule no articular deformity is manifest either clinically or by radiographic examination.
Pain is almost always accompanied by systemic symptoms identical to those encountered in temporal arteritis.
Headache, jaw claudication, and scalp pain or tenderness define the clinical transition from polymyalgia to temporal
arteritis and determine the need for more aggressive corticosteroid or immunosuppressive management. Axillary
artery bruit can be a presenting sign of transition to giant cell arteritis in patients with polymyalgia rheumatica (Czihal
et al 2011). The authors point out that axillary artery bruit is very uncommon in atherosclerosis.
On physical examination there are few findings in patients with polymyalgia. One prominent characteristic feature is
that the passive range of motion in neck or pelvis far exceeds the active range. That is, the examiner can slowly move
the patient's neck through a greater range than the patient can by using his or her own neck muscles. Patients with
polymyalgia have an increased incidence of arterial bruits over the large arteries of the arms and legs as well as over
the carotid and subclavian vessels.
Polymyalgia rheumatica may have a range of atypical presentations including peripheral synovitis, mild weakness, and
normal sedimentation rate. In fact, there is considerable overlap between polymyalgia rheumatica and seronegative
rheumatoid.
The duration of polymyalgia has ranged in various reports from 6 months to as long as 14 years, but most patients are
ill with it for 1 to 3 years.
Prognosis and complications
Although the patient is often most interested in pain relief, the possibility of an ischemic complication is, for the
physician, the most compelling component of temporal arteritis. Because it is impossible to know when an ischemic
event might occur, it is necessary to make the diagnosis and initiate corticosteroid treatment quickly.
The most common ischemic complications of temporal arteritis involve the eye and vision. In an earlier review of large
series, I found that visual loss occurs in a third to half of patients (Goodwin 1980). Sudden total binocular blindness has
been reported, and in many cases the second eye becomes involved only hours to days after the first ischemic event.
The threat of rapid progression to binocular blindness constitutes the emergency in treatment of temporal arteritis.
Some clinicians believe that simultaneous occurrence of ischemic optic neuropathy and central retinal artery occlusion
in the same eye or in opposite eyes is pathognomonic for temporal arteritis. Multiple attacks of amaurosis fugax
alternating between eyes are also a strong indicator of temporal arteritis and do not often occur in atherosclerotic
carotid artery disease. Most ischemic visual events occur after several weeks of symptoms, but usually less than 6
months from onset of symptoms.
Font and colleagues found that among 146 patients with biopsy proven temporal arteritis, 23 (15.75%) had visual loss
(Font et al 1997). All of the patients who lost vision had had classic symptoms of temporal arteritis for an average of
1.3 months or of polymyalgia rheumatica for an average of 10.8 months prior to vision loss. Also, it is important to
note that 65.2% of these patients had had premonitory visual symptoms for an average of 8.5 days prior to permanent
vision loss. These statistics provide support for the urgency of correct diagnosis and prompt initiation of treatment in
temporal arteritis and in polymyalgia rheumatica.
In a study of 90 biopsy-positive cases of temporal arteritis, univariate analysis showed that the most common risk
factors for progressive visual loss were older age, elevated C-reactive protein, and disc swelling (Loddenkemper et al
2007).
The most frequent cause of blindness in temporal arteritis is anterior ischemic optic neuropathy, but central retinal
artery occlusion accounts for a significant number of blind eyes, sometimes in conjunction with anterior ischemic optic
neuropathy. In 1958 Wagener and Hollenhorst studied 100 affected eyes in 58 patients at the Mayo Clinic and found
anterior ischemic optic neuropathy in 64% of the eyes and ischemic changes in the distribution of the central retinal
artery in 7% (Wagener and Hollenhorst 1958). In that series a total of 54 of 122 (44%) had visual impairment from
temporal arteritis. Thirty years later, Caselli and colleagues found permanent visual loss in only 14 of 166 (8.4%) of
biopsy-positive patients in the Mayo Clinic cohort, of whom 12 lost vision in 1 eye and 2 in both (Caselli et al 1988).
The incidence of visual complications was assessed in a population-based study of temporal arteritis in Denmark
(Fledelius and Nissen 1992). Ten of 264 (3.8%) patients with temporal arteritis from a county sample and a hospitalbased series had significant visual impairment. The authors acknowledged that the rate of visual impairment is lower
than in published series from other parts of the world. They also speculate that the diagnosis is made earlier in
Denmark and that early steroid treatment may be preventing permanent complications in more patients than
elsewhere.
An important long-term prospective study of 170 patients between 1973 and 1995 was reported by Hayreh. Fifty
percent of the patients presented with visual symptoms, of which 97.7 had vision loss, 30% amaurosis fugax, and 6%
diplopia. Of those with vision loss, the etiology was anterior ischemic optic neuropathy in 81%, central retinal artery
occlusion in 14%, cilioretinal artery occlusion in 22% (12 of 55 patients with fluorescein angiogram), posterior ischemic
optic neuropathy (disc not swollen) in 7%, and ocular ischemia in 1 patient (Hayreh et al 1998). Retabulation of 114
eyes in 84 consecutive patients from the same clinic between 1974 and 1999 indicated anterior ischemic optic
neuropathy in 91%, central retinal artery occlusion in 10.5%, cilioretinal artery occlusion in 10%, and posterior
ischemic optic neuropathy (no disc edema acutely) in 4% either alone or in different combinations (total >100)
(Hayreh et al 2002). Galor and Lee provide a well-documented case of slowly progressive blindness in 1 eye secondary
to choroidal ischemia in a 93 year old man with biopsy positive giant cell temporal arteritis who happened to be on
Coumadin for atrial fibrillation. After a month, vision in that eye had dropped to finger counting but returned to 20/50 a
day after treatment with IV solumedrol (methylprednisolone) was begun. The authors suggest the rate of visual
progressive loss may have been slowed because of the Coumadin and cite other references suggesting a beneficial
effect of anticoagulation for visual loss in temporal arteritis (Galor and Lee 2006).
The incidence of visual complications in any cohort of patients with temporal arteritis is subject to tremendous
potential bias from many factors. For instance, a review of 47 patients with biopsy positive temporal arteritis done at
an ophthalmologic hospital in Switzerland found vision loss in 33 patients (70%). Obviously, the denominator in their
fraction, the patients referred to an eye hospital are likely to include an inflated percent with eye complications. Of the
33 patients with vision loss, 22 (66%) had anterior ischemic optic neuropathy and 7 (21%) had central retinal artery
occlusion, consistent with earlier series.
Anterior ischemic optic neuropathy presents with sudden visual loss, commonly with "altitudinal" or upper and lowerhalf loss of visual field and pale swelling of the optic nerve head. A rare posterior ischemic optic neuropathy presents
with the same visual deficit but with no optic disc edema.
The physiologic cup is a normal depression in the central surface of the optic disc that is typically enlarged in
glaucoma (cupping of the disc). Various reports have described cupping as a late manifestation of anterior ischemic
optic neuropathy. In a review of fundus photographs, the size of the physiologic cup was compared between 2 groups
of patients with anterior ischemic optic neuropathy: 92 patients with arteritic anterior ischemic optic neuropathy and
102 patients with nonarteritic anterior ischemic optic neuropathy. Cupping was present in 92% of eyes with arteritic
disease and in only 2% of eyes with nonarteritic disease (Danesh-Meyer et al 2001).
Central retinal artery occlusion is characterized by sudden loss of visual function, either with total blindness or with
predilection for the upper or lower altitudinal half visual field, as in ischemic optic neuropathy. During the first few
minutes blood flow may cease in the arteries, leaving only the appearance of white threadlike "ghost" vessels until
flow is reestablished, usually within just a few minutes. The fundus may then appear normal despite ongoing blindness
or dense visual field loss. Within 12 to 24 hours the infarcted inner retinal layers develop edema that appears white
and opaque, obscuring retinal vessel segments and underlying structures. The edema is often most apparent at the
fovea, which appears unnaturally red against the surrounding abnormally white retina. This is because the retina is
thin at the fovea and the whiteness is much less intense there. This appearance has been called the relative cherry red
spot. Within 2 to 3 weeks the retinal edema fades, leaving the fundus looking relatively normal again. Within a few
months Wallerian degeneration of axons in the retinal nerve fiber layer reaches the optic nerve head, causing pallor
and loss of capillaries that accompany atrophy of the neural tissue.
Temporal arteritis may cause ischemia of the entire globe, either unilateral or bilateral; this may be refractory, even to
intensive treatment with pulse intravenous methylprednisolone followed by high-dose oral prednisone treatment
(Hwang et al 1999).
Caselli and colleagues analyzed the neurologic complications in 166 consecutive cases of biopsy-proven temporal
arteritis at the Mayo Clinic and found that overall 31% of the patients followed for a median of 17 months (ranging
from 15 to 19 months) had some form of neurologic impairment, either transient or permanent (Caselli et al 1988).
They found a total of 5 (3%) patients who had brain infarction, 3 in the carotid artery distribution and 2
vertebrobasilar. The authors comment that this hardly exceeds the expected rate of cerebral infarction from
atherosclerosis in the age group of the cohort, and that the relation to arteritis remains unproved. Large-artery
disease, defined as the presence of bruit or diminished pulse amplitude, was found in 54 patients. The carotid arteries
were affected in 31, upper limb arteries in 29, and lower limb arteries in 15. This relative frequency follows closely the
distribution of arterial involvement demonstrated in an autopsy study of patients with polymyalgia rheumatica
reported by Ostberg (Ostberg 1973) and in the accompanying clinical analysis by Hamrin (Hamrin 1972). A
retrospective analysis of stroke among 98 patients with giant cell arteritis at a single hospital found that stroke had
occurred at initial presentation in 6 patients, 3 of which involved the vertebrobasilar territory, and there were no
additional strokes during follow-up of these patients (Zenone and Puget 2013).
Pupillary dilatation is sometimes encountered in temporal arteritis, usually from ischemia involving the third cranial
nerve. Prasad and colleagues describe isolated pupillary mydriasis in an 85-year-old man who had biopsy-positive
temporal arteritis with the development of denervation supersensitivity with meiosis in response to 0.125%
pilocarpine. The patient also had segmental pupillary sphincter involvement, and the overall picture was most
consistent with tonic pupil. The authors favor ischemia of the ciliary ganglion or the postganglionic parasympathetic
fibers as the etiology (Prasad et al 2009).
The Mayo Clinic group studied the patterns of tissue-specific inflammatory response in a group of 23 patients with
typical inflammatory lesions in temporal artery specimens (Weyand et al 1997). They found that those with ischemic
complications expressed higher concentrations of IFN gamma mRNA (P=0.008) and IL-1 beta mRNA (P=0.02).
Formation of giant cells was associated with local synthesis of IFN gamma (P=0.003). Tissue from patients with
concomitant polymyalgia rheumatica had higher levels of IL-2 mRNA transcripts (P=0.001). In a preliminary way, this
work shows that the characteristics of the inflammatory lesion may, in the future, allow patients to be chosen for more
intense treatment based on patterns of inflammatory response that indicate a higher likelihood of developing ischemic
complications. Along these same lines, a study of a group of 36 patients with temporal arteritis from Barcelona found
relatively higher expression of interleukin-1beta, tumor necrosis factor alpha and interleukin-6 mRNA in temporal
arteries from patients who went on to have longer time to first remission on steroids, higher steroid dose
requirements, and longer required duration of steroid treatment (Hernandez-Rodriguez et al 2004).
Various measures of neovascularization or ischemia induced angiogenesis in patients with temporal arteritis have
shown that higher levels of this response to ischemia correlated significantly with having fewer ischemic
complications. This suggests that the capacity to mount vigorous new vessel formation may be an effective
compensatory mechanism in temporal arteritis (Cid et al 2002).
Death from ischemia in temporal arteritis is rare but has been reported on occasion, usually from vertebral artery
occlusion and brainstem infarction or from coronary occlusion and myocardial infarction (Sheehan et al 1993; Freddo
et al 1999). A particularly dramatic death was reported secondary to aortoduodenal fistula that developed in a patient
with temporal arteritis (Lagrand et al 1996). Though death from temporal arteritis is dramatic and usually precipitates
a case report, an epidemiologic study indicated that life expectancy of patients with temporal arteritis is not
significantly less than that of age-matched controls (Matteson et al 1996). An analysis of the Mayo Clinic series of
patients with temporal arteritis followed over the past 50 years found 46 incident cases of large-artery complications
among 168 patients in the cohort. These complications included 30 cases of aortic aneurysm and 21 cases of large
artery stenosis (Nuenninghoff et al 2003a). In general, the survival in this group of temporal arteritis patients with
large vessel complications was not different from the total group of temporal arteritis patients. The exception was the
development of aortic dissection, which markedly increased mortality (Nuenninghoff et al 2003b).
The presence of traditional risk factors for atherosclerosis at the time of temporal arteritis diagnosis was found to
significantly increase the risk of developing an ischemic complication, especially hypertension (Gonzalez-Gay et al
2004b).
Among 103 giant cell arteritis patients followed for 48.9 ± 14.8 months, the incidence rate ratios of patients versus
controls were 12-fold greater for peripheral vascular disease and 5-fold greater for coronary artery disease, and it was
found that being on a statin drug reduced the incidence of cardiovascular hospitalizations among these temporal
arteritis patients (Pugnet et al 2016).
A meta-analysis of 7 studies showed that among temporal arteritis patients compared with controls the relative risk for
venous thromboembolism was 2.26, 95% confidence interval (1.38 to 3.71) (Ungprasert et al 2016).
The incidence of aortic aneurysm is dramatically increased in patients with temporal arteritis as compared with an
age-matched general population. Gonzalez-Gay and colleagues found that 20 (9.5%) of 210 biopsy-proven temporal
arteritis patients in northwestern Spain had aortic aneurysms (16 thoracic and 6 abdominal). The population incidence
of aortic aneurysm and dissection in their region was 18.9 per 1000 person years at risk, which was similar to that in
Olmsted County as published by the Mayo Clinic group. Hypertension and polymyalgia rheumatica with a marked
inflammatory response at the time of diagnosis were the most predictive characteristics for later development of aortic
disease (Gonzalez-Gay et al 2004a).
Another study from Spain involved a cohort of 54 patients with biopsy-proven giant cell arteritis who were screened for
aortic structural damage, and significant damage was found in 12 patients (22.5%) after a median follow-up of 5.4
years after initial diagnosis (Garcia-Martinez et al 2008). Prospective follow-up of the 36 remaining patients from this
original group of 54 giant cell arteritis patients was carried out with repeat aortic screening every 4 years for a median
of 10.3 years (Garcia-Martinez et al 2014). Thirty-six patients were screened a second time, and 14 were available for
a third screening at 8 years. Twelve (33.3%) of the 36 patients had developed aortic structural damage, all but 1 in the
thoracic aorta at final screening. Ascending and descending aortic diameters significantly increased over time. One
patient died from aortic dissection. The authors concluded that aortic structural damage is maximal within the first 5
years of diagnosis but continues over time, and dilatation continues, but without persistence of detectable disease
activity. Surgical repair of these arteritic aortic aneurysms is extremely hazardous but can be carried out successfully
(Atluri and Woo 2007).
Marie and co-workers reviewed records at the Internal Medicine Department of the University of Rouen and found 66
patients with nonatherosclerotic aortic complications, including aortitis, aortic ectasia, and aortic aneurysm; of these,
48 had associated temporal arteritis (Marie et al 2009). Seventy-seven percent of these arteritic cases were without
symptoms referable to the aorta (no dysphagia, dyspnea, thoracic or abdominal pain, or back pain). Aortic helical
computed tomography demonstrated either isolated aortitis manifest by circumferential thickening of the aortic wall in
41 cases, aortitis with aortic ectasia in 3 cases, and aortic thoracic aneurysm with thoracic and abdominal aortitis in
another 3 cases. One case had both aortic abdominal aneurysm and aortitis. Aortitis was most commonly identified at
the time of temporal artery diagnosis (41 cases) but was identified after initial diagnosis in 7 patients. After 6 months
of treatment, 34 cases had repeat aortic helical computed tomography. This demonstrated complete disappearance of
aortitis in nearly 9%, improved aortitis in 47%, unchanged findings in 41%, and deterioration of aortic thoracic
aneurysm in 1 patient. Because of the high prevalence of potentially catastrophic aortic involvement, the authors
recommend screening with aortic helical computed tomography on an annual basis.
An analysis of the prevalence, timing, and characteristics of relapses in patients with temporal arteritis in a cohort of
106 patients followed longitudinally for 7.8 ± 3.3 years (Alba et al 2014). Sixty-eight patients (64%) had at least 1
relapse, and 38 patients (36%) had 2 or more. First relapse was characterized as polymyalgia rheumatic in 51%,
cranial symptoms in 31%, and systemic symptoms in 18%. Relapses occurred predominantly in the first 2 years of
treatment. The time required to achieve maintenance prednisone dosages was significantly longer, and the cumulative
prednisone dose required during the first treatment year was significantly higher in patients with relapses than those
without.
Clinical vignette
CL is a 78-year-old woman who presented with a 2-month history of malaise, poor appetite with weight loss, and
generalized weakness. For 2 weeks she had also had frequent vertex headaches that were often severe and kept her
from sleeping. In fact, she also had trouble combing her hair in the morning because it caused pain in the scalp.
She consulted her dentist because chewing caused pain in the mandibular area, but he could find no dental cause for
this. On further questioning she specified that the pain in her jaw would start a few seconds after she began to chew
solid food and grow in severity over another 10 to 20 seconds to the point that she would have to stop chewing, after
which the pain would subside over another 5 to 15 seconds. She was also having pain in the hips and stiffness of the
legs that made walking difficult.
On the day of her office visit she had experienced a brief episode of visual loss in her left eye that she described as a
"shade being pulled down" over the upper half of the visual field. For about 20 seconds she lost all vision in the left
eye, and then sight returned first in the lower half of the field and then the upper half, with full return of vision within 1
to 2 minutes. No pain was associated with this episode.
Examination revealed a frail-looking elderly woman in some distress. There was evidence of recent weight loss, and
she had trouble rising from the waiting room chair to enter the office. Her gait appeared painful and stiff, and she held
her head rigidly in the straight-ahead position as she walked. When asked to bend her neck forward or back or to turn
her head to either side she winced with pain. The examiner was able to move her head and neck in all directions
passively, but it required slow steady movement to avoid causing pain.
Blood pressure was 180/95 taken from her right arm and 140/80 from the left arm. There was a loud left subclavian
bruit. An ulcer was noted in the buccal mucosa next to the left lower teeth.
There were no localizing findings on neurologic examination. Active and passive flexion of either leg caused pain in the
hips and upper thighs. Visual acuity was 20/30 either eye, and there was no subjective red desaturation either eye on
viewing a red bottle cap with either eye singly. Visual fields were full to confrontation testing (finger counting in each
quadrant).
Complete blood count revealed moderate normochromic, normocytic anemia, and the Westergren erythrocyte
sedimentation rate was 89 in the first hour. Carotid Duplex blood flow examination showed insignificant stenosis on
either side, but ocular plethysmography showed reduced pulse amplitude in both eyes. Left temporal artery biopsy
was performed, and methylprednisolone 1 gram was infused intravenously immediately afterward. She was instructed
to return for an additional infusion of intravenous methylprednisolone 1 gram for the next 2 days, after which she was
placed on oral prednisone at a dose of 80 mg each morning.
Microscopic examination of the temporal artery tissue revealed areas of intimal proliferation, fragmentation of the
internal elastic lamina, and adjacent to disrupted segments of the elastic lamina, the media was infiltrated with
lymphocytes, plasma cells, epithelioid cells, and multinucleated giant cells.
Within 48 hours of treatment onset she was free of pain, and within 2 weeks her body weight and strength had
returned to premorbid status. After 3 weeks the prednisone dosage was gradually tapered in decrements of 5 mg/day
each month.
Biological basis
Etiology and pathogenesis
The etiology is unknown.
Temporal arteritis is a granulomatous vasculitis with preferential involvement of the aorta and its large primary
branches, including the carotid and vertebral arteries that supply the brain and eyes (Ostberg 1973). In a populationbased study, it was found that patients with temporal arteritis were 17.3 times more likely to develop thoracic aortic
aneurysm and 2.4 times more likely to develop abdominal aortic aneurysm than age- and sex-matched controls (Evans
et al 1995). Lie found that of 72 cases of aortic and extracranial giant cell arteritis, 25% did not have the clinical
manifestations of temporal arteritis. The ascending aorta and arch were most frequently involved (39%), followed by
subclavian and axillary (26%) as well as femoropopliteal arteries (18%), paralleling the distribution found by Ostberg in
his much earlier and smaller study (Ostberg 1973; Lie 1995).
Further investigation of the variable distribution of giant cell arteritis in a cohort of patients in the Mayo Clinic series
supports the concept that there is a fundamental biological difference between patients with cranial giant cell arteritis
and those with similar histologic presentation primarily in the aortic arch and great vessels (Brack et al 1999). These
authors compared 74 patients with subclavian and axillary giant cell arteritis, with 74 patients having cranial giant cell
arteritis. The incidence of arteritis in the temporal artery biopsy was lower in the subclavian and axial group (negative
biopsy in 42%) compared with the cranial arteritis group (100% positive biopsy). Subclavian and axial arteritis was
biologically different from cranial arteritis cases in having higher concentrations of interleukin-2 gene transcripts in the
artery tissue and over-representation of the HLA-DR beta 1*0404 allele.
The cause and pathogenesis are unknown, but considerable attention has been focused on the immunologic
characteristics of the cellular infiltrate, which is dominated by mononuclear cells and multinucleated giant cells (Lie
1990). Immunohistochemical studies have shown most of the lymphocytes in the infiltrate are of the CD4+ "helper"
variety. Activation of T cells requires that the inciting antigen be presented to the lymphocyte by a specific autologous
human leukocyte antigen molecule. The responsible antigen is unknown, but it has been thought likely to derive from
some component of the internal elastic lamina of the involved arteries, as the granulomatous infiltrate is most intense
adjacent to this part of the artery wall, and the lamina is usually fragmented and otherwise damaged where the
inflammation is intense (Kimmelstiel et al 1952). Also, the relative frequency of inflammation in different portions of
the arteries correlates positively with the amount of elastic tissue in the media and adventitia. Thus, although the
carotid and vertebral arteries are often involved, the inflammation ceases at the point where these arteries penetrate
the dura to become intracranial vessels, which is also the anatomic point at which the internal elastic lamina
disappears from the vessel wall (Wilkinson and Russell 1972). Nordborg and Nordborg provided evidence that the
inflammatory cells and other inflammatory markers, such as interleukin-2, are concentrated at the border between the
arterial adventitia and the media using monoclonal antibody against inflammatory markers. They suggest that the
cellular infiltrate enters the media from the adventitial vasa vasora and migrate to the internal elastic lamina and
intima (Nordborg and Nordborg 1998).
Weyand and colleagues studied allelic human leukocyte antigen polymorphisms important in determining
immunoresponsiveness to exogenous antigens in the cellular infiltrate from temporal arteries of 42 patients with
biopsy-proven temporal arteritis (Weyand et al 1992). The authors summarize their results as follows: "The giant cell
arteritis patients shared a sequence motif spanning amino acid positions 28 to 31 of the HLA-DR beta 1 chain. In the
structural model for HLA-DR molecules, this sequence motif can be mapped to the antigen-binding site of the HLA
complex, suggesting a crucial role of antigen selection and presentation in giant cell arteritis."
It is interesting to note that although 60% of the temporal arteritis patients carried 1 of the closely related allelic
variants at HLA-DR beta 1-*0401 and *0401/8, all of the patients who experienced ischemic optic neuropathy and
visual loss carried the *0404 or *0401/8 allele, suggesting that these may be markers for increased disease severity.
The same authors later found that the distribution of HLA-DR beta 1 alleles among patients with polymyalgia
rheumatica resembles that of patients with temporal arteritis and that the profile of patients with rheumatoid arthritis
is different at that locus. This finding means that the HLA-DR beta 1 allele profile does not distinguish which of the
patients with polymyalgia are destined to develop concomitant temporal arteritis (Weyand et al 1994). Conversely, in a
population of patients with polymyalgia rheumatica in a Mediterranean country, Salvarani and colleagues found no
significant differences in the frequencies of HLA-DRB1 types and in the expression of HLA-DRB 70-74 shared motif
between polymyalgia rheumatica patients and controls (Salvarani et al 1999). Also, a series of 86 patients with
polymyalgia rheumatica in Northwest Spain were found to be associated with HLA-DRB1*13/14 with only marginal
increase in the frequency of HLA-DRB1*0401 and *0404 compared with controls. Sixty-two cases of biopsy-proven
temporal arteritis from the same series demonstrated an association with HLA-DRB1*04 alleles, particularly *0401 and
*0404 (Dababneh et al 1998). Thus, there may be population specific differences in HLA types in patients with both
temporal arteritis and polymyalgia rheumatica.
The specific predilection of temporal arteritis for the elderly prompted Martinez-Taboada and others to study agerelated changes in the T cell receptor repertoire in peripheral blood CD8+ T cells. They found a distinct Jbeta2.7+
CD8+ clonotype only among patients and suggested that age-related emergence of such clonotypes predisposes
elderly patients to develop both polymyalgia and temporal arteritis (Martinez-Taboada et al 1996).
In a striking departure from previous ideas, Petursdottir and colleagues suggested that, based on study of aortic tissue
from 3 autopsy cases and 4 surgical specimens from patients with temporal arteritis, the primary event in giant cell
arteritis is loss of smooth muscle cells. They used alpha-smooth muscle actin immunoreactivity to identify smooth
muscle cells in the media of these specimens. There was subtotal loss of smooth muscle in regions most remote from
inflammation, but these areas gave way to zones with total loss of muscle cells next to calcified, acellular areas that
were surrounded by variable granulomatous inflammation (Petursdottir et al 1996).
There has been speculation about the role a virus might play in the pathogenesis of giant cell arteritis, but there has
been little proof until more recently. In a multicenter study Duhaut and colleagues investigated 305 new cases of
temporal arteritis, of which 159 were biopsy proven and 76 cases of polymyalgia rheumatica, using serologic tests for
IgG and IgM, directed against a number of viruses. There was a strong predominance of antibodies against
parainfluenza type 1 virus in patients versus controls, the difference being larger in the biopsy positive cases (43% of
patients vs. 20.9% of controls; odds ratio with controls 2.89; p+0.000006). There was no significant difference
between patients and controls in the incidence of antibodies against the other viruses screened. The authors
concluded that parainfluenza virus type 1 is associated with the onset of giant cell arteritis in a subset of patients
(Duhaut et al 1999a). On the other hand, Gabriel, studying temporal artery biopsy tissue from 30 patients with
temporal arteritis, found parvovirus B19 DNA more likely to be present in the temporal arteries of patients with
temporal arteritis (29 out of 30) than in the temporal arteries of control subjects (Gabriel et al 1999).
Angiotensin I receptors were found to be increased in the vascular smooth muscle within the media of temporal
arteries from patients with temporal arteritis as compared with control arteries (Dimitrijevic et al 2009). The authors
suggest that treatment of temporal arteritis with angiotensin receptor blockers might be an alternative or adjunct to
corticosteroids in this condition.
Studies indicate that 2 distinct pathogenetic mechanisms can be distinguished in temporal arteritis (Weyand and
Goronzy 2003; Deng et al 2010). One, mediated by Th17 T-cells that produce interleukin 17, serves systemic
inflammation with manifestations such as fever, malaise, anorexia, and headache and is corticosteroid responsive. The
other, mediated by Th1 T-cells that produce interferon-gamma, mediates vascular wall inflammation and is
corticosteroid resistant. It is suggested that new therapeutic approaches to the steroid-resistant inflammatory process
in the large vessels, possibly involving manipulation of specific inflammatory cytokines and other inflammatory
mediators, is needed.
A new thread in the etiology-pathogenesis concept of temporal arteritis is the role of varicella zoster virus. This was
the subject of an extensive study by Gilden and coworkers (Gilden et al 2015a). They found varicella zoster virus
antigen in 61 of 82 (74%) of temporal arteritis pathologically-positive temporal artery specimens and in only 1 of 13
(8%) normal arteries. Earlier work had showed varicella zoster virus antigen and DNA in localized patches of the
arteries that were called “skip areas” in pathologically-negative temporal artery specimens and reexamination of the
virus-positive segments demonstrated typical pathologic findings of temporal arteritis (Nagel et al 2013), and this
larger study also found the virus in isolated patches or “skip areas.”
Gilden and colleagues provided a compelling clinical perspective to this work by describing a woman in her 70s with
clinical features of both temporal arteritis and Takayasu aortitis with normal erythrocyte sedimentation rate,
marginally elevated C-reactive protein, and initially negative temporal artery biopsy (Gilden et al 2015b). Her
symptoms progressed despite treatment with high-dose (60 mg/day initially) prednisone. After steady clinical decline
for 16 months, the original temporal artery specimen was found to be positive for varicella zoster virus and she was
treated with intravenous acyclovir for 2 weeks followed by oral acyclovir and underwent a dramatic and lasting
remission of all symptoms and signs of disease.
Epidemiology"
Analysis of epidemiologic studies in temporal arteritis is hindered by the variability of diagnostic criteria and
differences in population bases in the various studies. In general the incidence is relatively high in northern regions
including the United States, Scandinavia, and European countries, whereas a much lower incidence is reported in
southern European countries. Genetic factors are probably important in view of the predilection of temporal arteritis to
occur in Caucasians and the association with the HLA-DR4 genotype, at least in some studies.
Baldursson and colleagues reported a total population-based study of the epidemiology of temporal arteritis in Iceland
between 1984 and 1990 (Baldursson et al 1994). During the study interval the authors identified 133 confirmed cases
of new temporal arteritis in Iceland; 94 were women and 39 men, giving a female-to-male ratio of 2.4. The age- and
sex-adjusted incidence of temporal arteritis was calculated to be 27 in 100,000 per year overall, 36 in 100,000 per
year for women, and 18 in 100,000 per year for men. As expected, the age incidence increased into the eighth decade
of life.
The mean age at diagnosis was 71.9 years (range 50 to 97), with no significant difference between men and women.
Only 19 patients (14.3%) had visual symptoms, of which only 1 developed permanent blindness of 1 eye, but there
was information on visual symptoms in only 63.9% of the cases. Also, this was not a longitudinal study of the cohort at
risk for visual loss, so this information probably cannot be taken as representative of the disease.
Machado and others at the Mayo Clinic published data indicating a rising incidence of temporal arteritis during the
interval from 1950 to 1985 (Machado et al 1988). The overall incidence in Minnesota during that interval was lower
than the Icelandic figures cited above, 17 in 100,000 per year, with age-adjusted rates 3 times higher for women (23.4
in 100,000 per year) than for men (7.4 in 100,000 per year). This is despite the similar ethnic mix in Iceland and
Olmsted County, Minnesota, suggesting a role for environmental and other factors. The trend toward rising incidence
over the interval was true only for women (35.4 in 100,000 per year in 1980 to 1985); the incidence for men dropped
significantly (6.5 in 100,000 per year in 1980 to 1985), having reached a peak in the mid-1970s (15.4 in 100,000 per
year in 1970 to 1974). The authors believe that this rise in incidence may be partly explained by changes in disease
awareness among physicians and by other extraneous factors, but that a biological change is likely occurring as well.
They point out the interesting fact that the preponderance of women increases in the older age groups, unlike other
rheumatic and inflammatory diseases, where the predilection for women decreases with advancing age. Petersdottir
and colleagues also found that the annual incidence increased significantly with time (P<0.001) for both men and
women in a study of biopsy proven temporal arteritis between 1976 and 1995 in Goteborg, Sweden (Petursdottir et al
1999). In that study the average incidence was 22.2/100000 inhabitants over 50 years of age (women 29.8, men 12.5).
Significant annual fluctuation was also found, with peak incidence in late winter and autumn. These seasonal
fluctuations and the rising incidence suggested to the authors that an extrinsic triggering factor, such as infection may
be involved. Gonzalez-Gay and colleagues found a rising annual incidence of biopsy-positive temporal arteritis in
northwestern Spain between 1981 and 2005 but did not find peaks or valleys in the annual incidence or any seasonal
variation in incidence (Gonzalez-Gay et al 2007). On the other hand, in Israel, Bas-Lando and colleagues found
fluctuation in the annual incidence from 1980 to 2004 with 3 distinct peaks 8 to 10 years apart—evidence of a possible
infectious etiology, the authors suggest (Bas-Lando et al 2007).
The highest incidence figures come from South Norway where 322 patients with either temporal arteritis or
polymyalgia rheumatica were identified between 1987 and 1994. Two hundred fifty-six patients had polymyalgia
rheumatica and 66 had temporal arteritis, so the majority of the high incidence was attributable to polymyalgia
rheumatica, which the authors felt was due to the design of their study with higher ascertainment rates for
polymyalgia rheumatica than previous studies. The annual incidence of temporal arteritis in persons aged 50 years or
older was 29.0 per 100,000 (39.9 in women and 16.3 in men), figures that are fairly similar to earlier series.
In a case control study of 400 patients with giant cell arteritis, Duhaut and colleagues found that histories of smoking
and previous atherosclerotic disease were significant "risk factors" for developing giant cell arteritis in women but not
men (Duhaut et al 1998). Women who smoked had an overall 6-fold increased risk for arteritis compared with age- and
sex-matched controls; the relative risk rose to 17-fold among heavy smokers. Duhaut and colleagues also carried out a
case control study (285 incident female cases of temporal arteritis and 186 age-matched, population-based female
controls) seeking to determine if alloimmunization during pregnancy might predispose to the disease later in life.
These workers found, on the contrary, that the incidence of pregnancy was significantly lower in cases compared with
controls "(nulliparous: 21.55% vs. 12.90%; and 4 or more pregnancies: 16.25% vs. 27.42%; Wilcoxon rank sum test:
P=0.0019)." The authors suggest that the hyperestrogenic state that accompanies pregnancy may have a prolonged
protective effect on arteries. The transfusion histories were the same in the 2 groups, and there was no evidence that
alloimmunization plays a role in the later development of temporal arteritis (Duhaut et al 1998). A case control study
from Norway involving 398 patients with temporal arteritis or polymyalgia rheumatica and 1592 controls found no
increased frequency of malignant tumors in patients versus controls (Myklebust et al 2002).
Studies of the clinical patterns and incidence of temporal arteritis in Spain and Israel prior to about 1980 and
subsequent to that date have shown, in both countries, that the average age at presentation has risen along with the
overall incidence. Also, the proportion of patients with "classic" symptoms has fallen, and atypical presentation has
become more common. An attractive explanation of these changes is that the disease has become more widely
recognized and is being diagnosed earlier in the course than prior to 20 years ago (Nesher et al 1999; Gonzalez-Gay et
al 2001).
Despite the trend for the disease to occur only in the elderly, individual case reports document more or less typical
temporal arteritis in young people. One of these rare individuals presented with a tender pulsatile aneurysm involving
the frontal branch of the temporal artery on his forehead. He had a history of chronic asthma, juvenile rheumatoid
arthritis, and positive serum ANA. Biopsy demonstrated lymphocytic infiltration of the temporal artery that was most
intense at the internal elastic lamina, intimal hypertrophy, and sparse multinucleated giant cells (Pipinos et al 2006).
Differential diagnosis
Other disorders that present with headache along with systemic symptoms and signs include metastatic and primary
malignant tumors involving the brain, meninges, and skull, and a variety of infections and other inflammatory
diseases. Neoplasms that may elevate the erythrocyte sedimentation rate and cause both local and systemic
symptoms are prevalent in the older age group, which is also selectively susceptible to developing temporal arteritis,
so the differential diagnosis may be somewhat difficult on clinical grounds alone. MRI and CT should rule out tumors
that confound the clinical diagnosis. On occasion, however, lumbar puncture and CSF examination may be needed to
rule out inflammatory (granulomatous), infectious, and neoplastic meningeal infiltrative diseases. Rarely, paranasal
sinus infection might mimic both the local and systemic symptoms of temporal arteritis, but this will be identified by
cranial imaging studies. The symptoms of polymyalgia rheumatica were refractory to standard treatment in a 59-yea-old woman but were promptly relieved by removal of a large hepatic cavernous hemangioma (Kadry et al 2000). The
mechanism by which this lesion caused the symptoms in this case is unclear.
On the other hand, temporal arteritis may mimic other diseases and be missed as the underlying cause. Ascending
aortic aneurysm has been shown histologically to be caused by underlying temporal arteritis (Hamano et al 1999).
Myocardial infarction can complicate known temporal arteritis or may rarely be the presenting feature of the disease
(Freddo et al 1999). Temporal arteritis presenting as subclavian artery stenosis has also been described (Sato et al
1993). Cases of temporal arteritis presenting as orbital inflammatory pseudotumor (de Heide and Talsma 1999) and
panuveitis (Rajesh and Cole 2000) have been recorded as well. Temporal arteritis was found to be the most frequent
specific multisystem disease in an elderly population presenting as fever of unknown origin (Tal et al 2002). A case of
giant cell arteritis involving the ovaries and adjacent tissues in a 75-year-old woman who was asymptomatic for the
disease was discovered during surgery to remove an ovarian cyst. Temporal artery biopsy subsequently demonstrated
active temporal arteritis in the woman (Onuma et al 2007).
In 1990 Hunder and colleagues published The American College of Rheumatology 1990 criteria for the classification of
giant cell arteritis (Hunder et al 1990). To qualify for diagnosis patients must meet 3 of the following 5 criteria: (1) age
over 50 years, (2) new onset of localized headache, (3) temporal artery tenderness or decreased temporal artery
pulse, (4) erythrocyte sedimentation rate greater than or equal to 50 mm/hour, or (5) positive temporal artery biopsy.
Murchison and colleagues performed a study to determine if the American College of Rheumatology classification
criteria can accurately establish the diagnosis of giant cell arteritis without performing temporal artery biopsy. The
study cohort consisted of 112 patients who underwent adequate (minimum 2 cm) temporal artery biopsy prior to, or
no more than 5 days after, starting corticosteroid treatment. All patients also had ischemic visual loss involving 1 or
both eyes (central retinal artery occlusion or anterior ischemic optic neuropathy). They found that 9 of 35 patients with
positive biopsy would not have been diagnosed as having giant cell arteritis using the criteria alone and another 16
patients met only 2 of the criteria and would have needed the biopsy to diagnose giant cell arteritis. In addition, 11 of
39 patients with negative biopsies met the criteria for diagnosis, which could mean only that temporal artery biopsy
may be false negative in the presence of active giant cell arteritis. The authors conclude that data indicate that
temporal artery biopsy is indicated in all patients suspected of having giant cell arteritis (Murchison et al 2012).
Diagnostic workup
The most frequently used tests for the diagnosis of temporal arteritis include Westergren erythrocyte sedimentation
rate, plasma electrophoresis, and temporal artery biopsy. Interest has focused on the diagnostic utility of measuring
choroidal blood flow using either newly developed methods for noninvasive measurement, such as ocular
plethysmography, or timed fluorescein angiography.
Marked elevation of the erythrocyte sedimentation rate is the most characteristic laboratory abnormality in patients
with temporal arteritis. Mild anemia is common, as are various degrees of leukocytosis, sometimes with a left shift.
Serum protein electrophoresis is characterized by rise of "acute phase reactants" (alpha and beta globulins) in the
early stages and elevated gamma globulin in the more chronic phases; both of these will act to elevate the erythrocyte
sedimentation rate. Although erythrocyte sedimentation rate elevation is found at presentation in a high proportion of
patients with temporal arteritis, review of large series indicates that the erythrocyte sedimentation rate is relatively
normal in at least 10% of presenting patients (Goodwin 1980). A study of 167 patients with a firm clinical diagnosis of
temporal arteritis confirmed that the erythrocyte sedimentation rate was less than 40 mm/hour at diagnosis in 9
patients. These 9 patients had less frequent systemic and visual symptoms than the others, and no patient with low
erythrocyte sedimentation rate developed blindness (Salvarani and Hunder 2001). Therefore, a normal erythrocyte
sedimentation rate does not rule out the diagnosis when other features are highly suggestive.
The Westergren method, which uses a longer tube than the Wintrobe procedure, is preferred because the result is not
affected as much by anemia. The degree of erythrocyte sedimentation rate elevation in temporal arteritis and
polymyalgia rheumatica is often extreme (greater than 100 mm in the first hour). Unfortunately, other conditions,
some of which produce systemic symptoms similar to temporal arteritis, also elevate the erythrocyte sedimentation
rate. A review of the literature showed that the sedimentation rate is nonspecific and has been found to be elevated in
a wide variety of clinical conditions unrelated to temporal arteritis, even some noninflammatory conditions such as
stroke, coronary artery disease, and prostate cancer.
Another problem is establishing the normal erythrocyte sedimentation rate range in the elderly. Review of several
large series leads to the conclusion that a value greater than 40 mm (first hour) should be considered elevated in
those aged 65 years and older. Values between 20 and 40 are "suspect" but far from diagnostic.
Studies have sought to find better biological markers for clinical activity of the disease and markers to differentiate
temporal arteritis from other rheumatological conditions. Elevation of anticardiolipin antibodies in sera of patients with
temporal arteritis has attracted considerable attention. In a prospective study of 86 patients with biopsy-positive
temporal artery biopsy and 50 controls, Liozon and colleagues' group found anticardiolipin antibody in 50% of patients
but only 8% of controls. The presence of antibody did not select for patients who were destined to have ischemic
complications. IgG class antibodies declined with treatment and increased with exacerbations, making this a better
indicator of disease activity than IgM class antibodies (Liozon et al 1995). Espinosa and colleagues found similar
incidences of antiphospholipid antibodies among 86 patients with giant cell arteritis, including those with temporal
arteritis and others with polymyalgia rheumatica alone or combined with temporal arteritis. Forty-four patients (67%)
had ischemic events, but there was no significant correlation between the presence of antiphospholipid antibody and
these events (Espinosa et al 2001).
Chakravarty and colleagues assayed anticardiolipin antibody levels at presentation and at 6 monthly intervals in 98
patients with either polymyalgia rheumatica (64 patients), temporal arteritis (12 patients), or both (22 patients), as
well as 100 controls. Five of 11 patients with polymyalgia and elevated anticardiolipin developed temporal arteritis,
whereas only 5 of 53 polymyalgia patients without antibody did so, a striking difference. Also, 3 of the 5 with temporal
arteritis and antibodies developed severe ischemic complications, whereas none of the remainder without antibody did
so (Chakravarty et al 1995). In this respect their study differed from those of Liozon and colleagues as well as of
Espinosa and colleagues.
Meyer and colleagues also studied 19 patients with temporal arteritis, 16 of whom also had polymyalgia rheumatica,
and 3 patients with isolated polymyalgia using an ELISA assay for anticardiolipin IgG antibodies (Meyer et al 1996).
Antibodies were demonstrated in 8 patients (36%), all of whom had temporal arteritis with or without concomitant
polymyalgia. Serial determinations showed that the anticardiolipin activity disappeared within a few weeks of steroid
treatment. The authors suggest that presence of anticardiolipin antibody or anti-beta 2 glycoprotein I antibody in a
patient with polymyalgia rheumatica should suggest the additional presence of temporal arteritis.
Sorbi and colleagues looked for degradation products of intercellular matrix and elastin in serum samples and in tissue
from temporal artery biopsy from 12 patients with temporal arteritis and 12 healthy controls. Gelatinase activity, and
specifically matrix metalloproteinase 9 levels, was "substantially elevated" in sera from the patients but not the
controls. Matrix metalloproteinase 9 RNA was found in the media of inflamed vascular segments. It was suggested that
further work should be done to determine if this could be made into a clinically useful marker of disease activity (Sorbi
et al 1996).
Hayreh and colleagues reexamined the sensitivity and specificity of the erythrocyte sedimentation rate and C-reactive
protein levels in diagnosis of temporal arteritis (Hayreh et al 1997). The values for these 2 tests were compared
between a group of 106 patients with positive temporal artery biopsy and another group of 247 patients with negative
biopsy. These authors concluded that the laboratory criteria most strongly suggestive of temporal arteritis included Creactive protein above 2.45 mg/dl and erythrocyte sedimentation rate of 47 mm/hr or more, in that order. C-reactive
protein was more sensitive (100%) than erythrocyte sedimentation rate (92%) for detection of temporal arteritis. The
combination of C-reactive protein and erythrocyte sedimentation rate above the cutoff values gave the best specificity
(97%).
Comparing a group of 121 biopsy proven temporal arteritis patients with 287 patients with nonarteritic anterior
ischemic optic neuropathy, Costello and colleagues found that in addition to high erythrocyte sedimentation rate and
C-reactive protein, there was significant elevation of platelet count and white blood count in the arteritis patients
compared with the nonarteritic patients (Costello et al 2004). Erythrocyte sedimentation rate was a better predictor of
temporal arteritis than platelet count and the combination of erythrocyte sedimentation rate and platelet count was a
better predictor than erythrocyte sedimentation rate alone.
Demonstration of the inflammatory granulomatous lesion of temporal arteritis has made temporal artery biopsy a
mainstay in establishing the diagnosis with assurance. The typical lesion is a granulomatous inflammatory reaction
concentrated at the innermost part of the vascular media near zones of fragmented and reduplicated internal elastic
lamina with adjacent intimal proliferation, sometimes to the point of occluding the lumen. Multinucleated giant cells
are classically present but are not necessary for the diagnosis.
The philosophy behind obtaining a temporal artery biopsy requires some special comments. There are many cases of
active temporal arteritis in which an entire temporal artery or segments of the artery are not involved; these were
called "skip lesions" by Klein and colleagues (Klein et al 1976). To compensate for the patchy nature of the pathologic
process, these authors suggested that the length of the biopsy segment should measure at least 2.5 cm, and if frozen
section of samples from that specimen are all normal, that the other temporal artery be biopsied at the same surgical
session. On the other hand, Chakrabarty and colleagues report that in a reexamination of 172 temporal artery biopsy
specimens, only 1 of the 132 initially normal cases, and 2 of 14 diagnosed with periarterial lymphocytic infiltration,
revealed giant cell arteritis after examining the tissue at multiple levels. The authors concluded that "routinely
examining a temporal artery biopsy at multiple levels does not increase the diagnostic yield of the test, although
selective further examination may be indicated in some cases" (Chakrabarty and Franks 2000).
Among 5 series on temporal artery biopsy, the average rate of positive result for temporal arteritis was 19%, ranging
from 11% to 27% in various series. These series contrast sharply with the large epidemiologic studies in which the
biopsy positivity rate exceeds 80% (Allison and Gallagher 1984; Lie and members and consultants of the American
College of Rheumatology Subcommittee on Classification of Vasculitis 1990; Baldursson et al 1994). One obvious factor
that would influence the percentage of positive biopsies is the clinical rigor with which candidates were chosen for
biopsy, and this factor is usually not thoroughly described in the clinical reports.
Another factor would be the potential effect of corticosteroid treatment on the histologic characteristics of the biopsy
specimen. Allison and Gallagher presented evidence suggesting that corticosteroid treatment prior to biopsy results in
a significant reduction in the rate of positive results. Of the patients biopsied before steroid treatment, 82% (50 of 61)
were positive, but this figure fell to 59% (30 of 51) with 1 week or less of prebiopsy treatment, and to only 20% (4 of
20, 2 of whom had only "healed vasculitis") when prebiopsy steroid treatment exceeded 1 week.
Chmelewski and colleagues analyzed 98 patients who underwent temporal artery biopsy and found that only 30 (31%)
were positive, but that the percentage that were positive did not decline with the duration of previous corticosteroid
therapy (Chmelewski et al 1992). Six of 16 (37%) patients still had positive biopsies after more than 2 weeks on
corticosteroids. The dosage at time of biopsy and before was not specified, but for the entire series the average
starting prednisone dose was 68 mg/dL.
Achkar and colleagues assessed the effect of corticosteroid treatment on biopsy positivity among 535 patients
biopsied at the Mayo Clinic between 1988 and 1991, taking into account the dosage and duration of treatment (Achkar
et al 1994). The patients who had received corticosteroid treatment for 1 to 7 days prior to biopsy had a somewhat
higher positivity rate (46 of 107, 43%) than those who had not received treatment (89 of 286, 31%). More of the
treated patients had classic symptoms and signs, such as tender or pulseless temporal artery or jaw claudication, than
the untreated patients, probably indicating that they had more intense disease activity. Also, the positivity rate was
higher for those who had been treated for less than 7 days (46 of 107, 43%) than for those treated for 8 to 14 days (3
of 10, 30%) or longer (9 of 32, 28%), which suggests either that the duration of corticosteroid treatment is important
for its effect on the histopathology or that the perceived urgency for treatment and rapid biopsy (and, therefore, the
disease intensity) was highest for those biopsied right away. The percentage of positive biopsies that were atypical
(having no giant cells or location of inflammation in the adventitia rather than the media) rose strikingly with the
duration of corticosteroid prebiopsy treatment. An earlier study of the same patient cohort from the Mayo Clinic looked
at follow-up data for a median of 6 years and determined that only 9% of the biopsy-negative cases were later treated
for temporal arteritis, and none of this group had ischemic complications (Hall et al 1983). It should be kept in mind,
however, that the standard practice at the Mayo Clinic is to biopsy artery segments longer than 2.5 cm as well as the
opposite temporal artery if the frozen sections of the first artery are all negative. This intensive approach probably
increases the reliability of a negative biopsy, but is probably not matched in most institutions. A smaller study found
no difference in the percent of positive biopsies with duration of corticosteroid treatment at the time of biopsy, at least
up to 4 weeks: 82% positive overall, 86% positive biopsied 4 or more weeks after treatment started (Ray-Chaudhuri et
al 2002).
Chmelewski and colleagues also tabulated the fate of their 68 patients with negative temporal artery biopsies and
found that their presenting symptoms and signs could not be distinguished from those of patients whose biopsies were
positive. The eventual diagnosis was still temporal arteritis in 14 of 68 (21%), whereas the other patients eventually
carried a wide array of other diagnoses, the most frequent being primary neurologic disorders (22%), polymyalgia
rheumatica (21%), or other rheumatologic syndromes (15%) (Chmelewski et al 1992). Duhaut found that the clinical
course and other parameters of temporal arteritis were generally more severe in patients with biopsy positivity as
compared with biopsy negative cases (Duhaut et al 1999b).
Occasionally, a temporal artery biopsy specimen shows small-vessel vasculitis surrounding a spared temporal artery
and the significance of this is unclear. When the clinical picture is typical for temporal arteritis and the histology of the
vasculitis in the smaller arteries is typical of the disorder including the presence of giant cells, this small vessel
involvement is probably as good evidence of temporal arteritis as is involvement of the main vessel. This means that
the small branches attached to the temporal artery specimen should be looked at histologically and not discarded from
the specimen (Chiu et al 2004).
Esteban and colleagues studied 28 patients who had temporal artery biopsy showing this pattern of small-vessel
vasculitis and found that 13 of them probably had temporal arteritis on analysis of the entire clinical picture. Three of
them had systemic necrotizing vasculitis in these involved small vessels and demonstrated significantly more fibrinoid
necrosis than the others. The authors looked for small-vessel vasculitis in 30 temporal artery specimens from patients
with biopsy-proven giant cell arteritis. No difference was found in the pattern of small vessel involvement surrounding
histologically spared temporal or involved arteries among patients with clinically or histologically diagnosed temporal
arteritis (Esteban et al 2001). Another study found that perivascular inflammation in the absence of arteritis in
temporal artery biopsy specimens did not increase the likelihood of having temporal arteritis over patients with no
inflammation on biopsy (Corcoran et al 2001).
Some have claimed that finding evidence of scarring and other changes interpreted as residua of healed arteritis in a
temporal artery specimen that does not show any active inflammation can be used as evidence of temporal arteritis;
others have argued that these changes are nonspecific and may reflect arteriosclerosis. Cox and colleagues carried
out a retrospective study of 47 temporal artery biopsy specimens and compared them with 10 control temporal
arteries from autopsies on patients who had no clinical evidence of vasculitis. They found that apart from
inflammation, no histologic findings were specific for temporal arteritis. In other words, structural changes other than
inflammation do not allow reliable differentiation between healed or quiescent temporal arteritis and arteriosclerosis
(Cox and Gilks 2001).
A large survey of U.S. specialists in the fields of ophthalmic plastic and reconstructive Surgery (n=127), neuroophthalmology (n=119), rheumatology (n=799), and other (n=28) was carried out in 2010 and reported in 2013
(Schallhorn et al 2013). Sixty-six percent of respondents favored initial unilateral temporal artery biopsy, 18% bilateral
biopsy in all cases, and 16% unilateral or bilateral biopsy depending on the degree of clinical suspicion.
Rheumatologists were 4.5 times more likely to favor initial bilateral biopsy than the other 2 groups. Most believed that
biopsy results were not rendered falsely negative with immunosuppressive treatment for up to 2 weeks.
Each physician must deal with negative biopsy results based on the adequacy of the specimen submitted and the
intensity with which the biopsy material is studied in his or her own institution. Also, the strength of the clinical
presentation must be weighed, and if the signs and symptoms are typical and fairly specific (jaw claudication, tender
arteries) then patients should not be denied prompt treatment based on negative biopsy results.
Gillanders and colleagues introduced the idea of using selective angiography of the temporal artery in the diagnosis of
temporal arteritis (Gillanders 1969). The study was used to identify abnormal-appearing segments of the vessels both
as an indication of the diagnosis and as a guide to which segments should yield a positive biopsy. Fifteen patients with
temporal arteritis or polymyalgia rheumatica were studied using temporal artery biopsy and angiography. The vascular
lumen in temporal arteritis was characterized by long alternating stenotic and dilated segments having smooth
transitions between the two. Other segments showed more abrupt transitions to different caliber, giving a more
beaded appearance. The biopsy was positive in 5 patients, 2 of whom also had positive angiograms. Remarkably, the
angiogram was considered characteristic of temporal arteritis in 2 patients with negative biopsy of the same vessel.
Elliott and colleagues at the Mayo Clinic carried out a more extensive study (Elliott et al 1972). As a preliminary, the
authors studied 100 normal angiograms and, when possible, correlated the findings with autopsy injections of the
vessels. These studies were compared with angiograms on 34 patients with temporal arteritis or polymyalgia
rheumatica, all of whom had the vessel biopsied. Seven of the angiograms were considered diagnostic for arteritis,
whereas the biopsies were positive in only 5 of these. Gillanders' earlier finding of an occasional positive biopsy from
angiographically normal segments was corroborated in this study: in 1 patient the angiographic abnormality was distal
to the site from which a positive biopsy was obtained. Moncada and colleagues reported an essentially similar
experience, finding 5 abnormal temporal artery angiograms in 20 patients with polymyalgia rheumatica, only 1 of
which was histologically abnormal (Delecoeuillerie et al 1988).
All of the workers who reported on the use of temporal artery angiography to diagnose temporal arteritis concurred
that the characteristic gentle alternations between stenotic and dilated segments are not seen with any frequency in
atherosclerotic vessels, which may, however, look beaded and irregular. There have been no reports of invasive
angiography in the diagnosis of temporal arteritis, probably because sophisticated noninvasive methods have since
emerged to quantify flow velocity and direction in both the external carotid and internal carotid systems.
Kraft, using newly developed color Doppler techniques to study 10 patients with temporal arteritis, 8 with polymyalgia
rheumatica and 23 controls, reported that the superficial temporal artery showed a characteristic hypoechoic halo
around the lumen of an often stenosed or occluded segment in the patients but in none of the controls (Kraft et al
1996). The authors comment that the sensitivity and specificity of this finding has yet to be determined, and that
study of more patients is needed. Lauwerys and colleagues used color Doppler sonography to study 11 patients with
temporal arteritis, 21 with polymyalgia rheumatica, and 32 controls (Lauwerys et al 1997). They found significant
reduction in the peak velocity at both the proximal and distal segments of the superficial temporal arteries of temporal
arteritis patients as compared with polymyalgia rheumatica patients and controls. They found hypoechoic temporal
artery thickening in only 2 patients. Follow-up of 6 patients with temporal arteritis under treatment showed significant
recovery of peak velocity at the distal temporal artery site. A prospective color duplex study of 30 patients with
temporal arteritis, 37 with polymyalgia rheumatica, 15 with final diagnoses other than temporal arteritis or
polymyalgia rheumatica, and 30 age- and sex-matched controls found that 28 of the 30 (92%) temporal arteritis
patients had superficial temporal artery stenoses, occlusions, or dark halo (edematous artery?), whereas none of the
82 patients without temporal arteritis had these findings. The authors found the dark halo to be the most specific of
the abnormalities. Also using color Doppler techniques, Vecsei and colleagues found abnormal flow characteristics in
the central retinal artery, ophthalmic artery, and lateral short posterior ciliary arteries during symptom-free intervals in
patients with amaurosis fugax and giant cell arteritis, but normal flow in these vessels between attacks in nonarteritic
cases of amaurosis fugax (Vecsei et al 1999). Currently the largest study of duplex ultrasonography of the temporal
arteries examined 86 patients suspected of having temporal arteritis or polymyalgia rheumatica. The dark
(hypoechoic) halo sign was present in only 40% and showed a specificity of 79% for correct diagnosis of biopsy proven
temporal arteritis. Temporal artery abnormalities on physical examination had higher sensitivity and specificity
(Salvarani et al 2002). Similar conclusions about the value of the dark halo sign were reached in another study of 69
patients (Nesher et al 2002). These findings indicate the potential usefulness of color Doppler investigation in elderly
patients with amaurosis fugax.
Studies have demonstrated reduced ocular and choroidal perfusion in patients with temporal arteritis, even before
ischemic visual loss has occurred, and it has been suggested that this type of measurement is a reliable diagnostic
marker for the arteritic form of retinal and optic nerve ischemia. Bosley and colleagues used ocular plethysmography
to measure the pulse amplitudes in the fellow-eyes of patients with anterior ischemic optic neuropathy (Bosley et al
1989). Pulse amplitudes were significantly lower in the fellow-eyes of 9 patients with biopsy-documented temporal
arteritis and anterior ischemic optic neuropathy, as compared with 112 fellow-eyes in patients with nonarteritic,
presumed atherosclerotic anterior ischemic optic neuropathy as well as fellow-eyes in another 9 biopsy-negative
patients suspected to have temporal arteritis. In the authors' study group the test had a sensitivity of 100% and a
specificity of 93.4%, with diagnostic accuracy of 93.9% in temporal arteritis.
Slavin and Barondes reported on 3 patients who presented with visual loss in 1 eye but had a normal fundus exam. All
3 patients had significantly delayed choroidal filling on fluorescein angiography. Only 1 patient had symptoms of
temporal arteritis, but the other 2 had diagnostic-positive temporal artery biopsy (Slavin and Barondes 1994).
Siatkowski and colleagues used fluorescein angiography to study 35 patients with anterior ischemic optic neuropathy,
of whom 16 (46%) had biopsy-positive temporal arteritis as well. These authors found that the arteritic group of
patients had higher erythrocyte sedimentation rates, larger physiologic cup-to-disc diameter ratios, and significantly
delayed fluorescein dye appearance and choroidal filling times as compared with the patients with nonarteritic,
presumed atherosclerotic anterior ischemic optic neuropathy (Siatkowski et al 1993). In a similar study, Mack and
colleagues performed timed fluorescein angiography on 13 patients with temporal arteritis (biopsy-positive) and visual
symptoms, of whom 11 had anterior ischemic optic neuropathy, and 2 had only transient visual loss (Mack et al 1991).
They also studied a group of 33 patients with nonarteritic anterior ischemic optic neuropathy and 23 eyes from 23 agematched normal subjects. The arteritic group had significant delay of filling time (mean=69 seconds), as compared
with the nonarteritic patients with anterior ischemic optic neuropathy (mean=5.8 seconds) and the control eyes
(mean=5.5 seconds). Indocyanine green ocular angiography, which shows choroidal circulation preferentially, was not
found to increase the diagnostic precision over standard fluorescein angiography (Valmaggia et al 1999).
Joelson and colleagues reported on the MRI findings in a patient with biopsy proven temporal arteritis. They described
multifocal dural enhancement, which was characterized histologically by perivascular inflammatory infiltrates and
enhancement of the temporalis muscle (Joelson et al 2000). Lee and colleagues described MRI optic nerve gadolinium
enhancement in 3 patients with anterior ischemic optic neuropathy caused by temporal arteritis and commented that
nonarteritic anterior ischemic optic neuropathy has not been reported with gadolinium enhancement on MRI (Lee et al
1999). Liu and Chesnutt also reported 2 cases of biopsy-positive giant cell arteritis with MRI-documented perineural
enhancement of both optic nerves (Liu and Chesnutt 2013). The authors cited the earlier Lee paper and a publication
by Morgenstern (Morgenstern et al 2003) indicating that pathologic examination of an optic nerve from a patient with
giant cell arteritis showed an inflammatory infiltrate in the small perineural meningeal blood vessels, including
infiltration with giant cells.
In a patient with biopsy-proven temporal arteritis, fludeoxyglucose[F18] PET showed striking uptake of
fludeoxyglucose[F18] in the walls of the entire aorta and left main coronary artery as well as the subclavian, carotid,
and common iliac arteries on both sides. These findings normalized after 2 weeks treatment with corticosteroids
(Turlakow et al 2001).
Ultrasound and PET can be used to demonstrate arteritis in the large arteries of the chest and neck in patients with
temporal arteritis. Both procedures agree on the distribution of these changes in patients with large-vessel giant cell
arteritis and these changes are most often clinically silent. Hypoechoic halo around arteries indicating mural edema is
the most useful ultrasound feature (Schmidt and Blockmans 2005; Habib et al 2012).
Habib and colleagues, using color Doppler ultrasound, studied 32 patients suspected of temporal arteritis of which 16
were eventually diagnosed as having temporal arteritis with positive temporal artery biopsy. Of the 16 with biopsyproven disease, the color Doppler exam showed hypoechoic dark halos surrounding the perfused lumen of the
temporal artery in 13 patients (81%). The finding was unilateral in 7 patients and bilateral in 6 patients. Halos were
detected in 2 patients outside the temporal arteritis group, 1 with polymyalgia rheumatica and the other with
Takayasu arteritis. None of 30 age- and gender-matched control subjects had halos detected (Habib et al 2012).
Because interpretation of [18]F FDG-PET requires subjective judgment and experience, Hautzel and colleagues sought
to demonstrate an objective measure that could with sensitivity distinguish significant [18]F-fluorodeoxyglucose
uptake in the aorta by quantifying the relationship between aorta and liver uptake in a group of 23 patients suspected
of having temporal arteritis and in a control group. They found that a “receiver operating characteristic”-based cutoff
ratio of 1.0 led to a sensitivity of 88.9%, specificity of 95.1%, and accuracy of 94.4%. This aorta-to-liver ratio applied to
the control group resulted in specificity of 95.6%, thus, providing a reliable, investigator-independent indicator of giant
cell arteritic involvement of the aorta (Hautzel et al 2008).
Another study of 46 patients with temporal arteritis showed that those with [18]F-fluorodeoxyglucose uptake in the
aorta had significantly larger diameter ascending, descending, and thoracic aorta at CT scan done a mean of 46
months later (Blockmans et al 2008).
Danve and O'Dell undertook an in-depth review of the role played by 18F-fluorodeoxyglucose positron emission
tomography in the diagnosis and management of systemic vasculitis (Danve and O'Dell 2015). They pointed out that
this study is not particularly useful in cases of temporal arteritis with vascular involvement limited to the superficial
temporal arteries because of the masking effect of the underlying glucose-metabolizing brain, but it is extremely
effective in plotting the extent of involvement of other large vessels and the aorta in patients with giant cell arteritis.
They also pointed out that 18-fluorodeoxyglucose shows uptake in the shoulder and hip joints but that a significant
number of them also have uptake in the large vessels of the thorax and neck, indicating subclinical large vessel
vasculitis. Pertinent to this is a retrospective study of 167 patients with temporal arteritis in which 18 (11%) had
symptoms limited to those of polymyalgia rheumatic for at least the first 3 months (Narvaez et al 2015). The mean
time to temporal arteritis diagnosis was 9 months (range 3-39 months). At the time of temporal arteritis diagnosis,
severe ischemic complications had occurred in half (9/18) and late inflammation in the aorta and its main branches
was present in 4 (22%).
Another addition to the armamentarium for diagnosing vascular inflammation is 3-Tesla MRA, which can demonstrate
not only segmental areas of lumen narrowing, but wall thickening and enhancement that are characteristic of large
vessel vasculitis (Bley et al 2005).
Among 59 patients with giant cell arteritis who had both high-resolution MRI and color-coded duplex sonography of the
temporal arteries within 10 days of each other and in the first 2 weeks of corticosteroid treatment, investigators in
Hamburg found rapidly declining sensitivity of both procedures to demonstrate arteritic changes in the vessels during
just the first few days of corticosteroid treatment. Temporal artery biopsy was done in 41 patients and was positive in
24 of these (59%). Comparing duplex exam/MRI against biopsy results in these 24 patients, the sensitivity was
92%/90% after 0 to 1 day of steroid treatment, 80%/78% after 2 to 4 days of treatment and 50%/64% among patients
who had received corticosteroids for more than 4 days when studied. The results were very similar when comparing
MRI and duplex sensitivity against final diagnosis in the larger group of 59 patients (Hauenstein et al 2012).
A European multicenter prospective study of the diagnostic accuracy of contrast enhanced magnetic resonance
imaging of superficial cranial arteries in diagnosing temporal arteritis enrolled 185 patients suspected of having this
disease, of which 98 had temporal artery biopsy (Klink et al 2014). Contrast enhanced T1 weighted images of the
superficial cranial arteries were graded from 0 through 3 based on arterial wall thickening and contrast enhancement:
grade 0 normal thickness, no enhancement; grade 1 normal thickness, slight enhancement; grade 2 mild wall
thickening, significant enhancement; and grade 3 marked wall thickening, marked enhancement. Grades 0 and 1 were
considered physiologic and grades 2 and 3 were considered diagnostic. The MRI diagnosis was compared with the final
clinical diagnosis for all patients (reference standard) and with the temporal artery biopsy diagnosis in the cohort with
this information. Sensitivity of MR imaging was 78.4%, and specificity was 90.4% for the entire study cohort.
Diagnostic accuracy remained high for the first 5 days of corticosteroid treatment but declined in those who received
corticosteroids for 6 to 14 days.
Siemonsen and colleagues used 3-Tesla MRI pre- and post-contrast to assess the extent of intradural arterial
involvement with giant cell arteritis in a prospective study of 28 temporal arteritis suspects (Siemonsen et al 2015). In
the final analysis, 20 patients had the disease, 9 of whom had positive temporal artery biopsies (Siemonsen et al
2015). Vessel wall enhancement of extracranial arteries was found in 16 patients, and vessel wall enhancement of
intracranial arteries was found in 10 patients. Vessel stenosis or occlusion was found at the site of vascular
enhancement in the intradural vertebral arteries in 4 patients and in the intradural carotid artery in 1 patient.
Management
The classic recommendation for initial treatment of temporal arteritis has been to commence with prednisone at a
dosage of 40 to 80 mg/day, though 60 mg/day or above has been more commonly described than lower doses. This
relatively high dose is usually maintained for 3 to 4 weeks, following which the dose is gradually reduced over many
weeks to months, watching for reemergence of clinical symptoms (headache, jaw claudication, etc.) or rising
erythrocyte sedimentation rate. Sometimes side effects require that the dose be reduced earlier than 4 weeks, but this
must be individualized to suit each patient's special needs. Patients with polymyalgia rheumatica but no headache or
other specific signs of temporal arteritis can be safely managed with 15 mg/day or less prednisone from the outset and
seem not to be liable to get ischemic complications. If headache or other signs of temporal arteritis emerge during the
course of polymyalgia rheumatica, however, it is important to increase the prednisone dosage to the levels
recommended for initial treatment of temporal arteritis.
Temporal arteritis tends to remain active for at least 1 year, and usually longer, an average of 3 to 4 years in some
series, but with a with wide range among the various studies (Kyle and Hazleman 1993), so tapering the dose of
prednisone too early commonly results in recurrence of headache and other symptoms that signal the threat of
ischemic complications. Recurring symptoms can usually be brought under control by reestablishing the original high
dose followed by another tapering interval. This is, however, cumbersome and does not afford full protection from
ischemic complications. It is better to taper slowly and avoid reactivation of the disease. It is important to note that
alternate-day steroid therapy has never been considered acceptable for these patients. Return of headache on the off
day suggests that the patient is not adequately protected by this regimen.
Since the introduction of high-dose corticosteroid therapy for temporal arteritis in the 1950s by Shick and colleagues
(Shick et al 1950), new visual loss has only infrequently been reported in patients who had been taking the
recommended high initial dose for at least 7 days. Because corticosteroid treatment has been so markedly effective in
preventing complications in temporal arteritis, it will be difficult if not impossible to conduct controlled clinical trials
even of promising other medications, even though the high frequency of steroid side effects would make alternative
treatment highly desirable.
Delecoeuillerie and colleagues suggested that previous dosage recommendations were unnecessarily high even for
initiation of therapy (Delecoeuillerie et al 1988). They correlated the clinical outcome with starting dosage of
corticosteroids in 132 patients with polymyalgia rheumatica and 78 with temporal arteritis. Their findings were in
accord with others that doses higher than 15 mg/day are unnecessary in polymyalgia rheumatica. As for primary
temporal arteritis, they found that 5 patients initially treated with less than 20 mg/day of prednisone had no greater
visual or other ischemic morbidity than 53 patients treated with standard high-dose prednisone at the outset. As might
be expected, the lower dose resulted in fewer steroid side effects and complications. Over the course of treatment,
which averaged 31 months, 15 patients (19%) had visual or neurologic complications. Myles and colleagues analyzed
the course of 96 patients with temporal arteritis, of whom 51 also had polymyalgia rheumatica (Myles et al 1992).
They tabulated the initial dosage of prednisolone and the dose being administered at the time of visual symptom onset
in 6 temporal arteritis patients and 3 polymyalgia patients having complications and found no correlation between
either dosage and the presence or absence of ischemic visual symptoms. Only 1 patient (with temporal arteritis) had
lasting visual loss; the others all had "amaurosis fugax." These recommendations for low-dose safety were made based
on the clinical course of only 5 patients in the earlier study and 1 in the later study (Myles et al 1992).
Kyle and Hazleman found that of 35 patients with temporal arteritis, all but 2 were successfully treated with 40 mg/day
of prednisone as initial dose (Kyle and Hazleman 1989). After 5 days at 40 mg/day the patients were divided into a
"low-dosage" group (taking 20 mg/day for 4 weeks, 15 mg/day for another 2 weeks, and 10 mg/day for another 2
weeks) and a "high-dosage" group (taking 40 mg/day for 4 weeks, 30 mg/day for 2 weeks, and 20 mg/day for another
2 weeks). The temporal arteritis cohort consisted of 18 patients with only temporal arteritis and another 17 with
symptoms of both temporal arteritis and polymyalgia (35 total).
The same authors later reported on the long-term (median 60 weeks) follow-up of the same cohort of patients,
tabulating relapses of both polymyalgia and temporal arteritis (Kyle and Hazleman 1993). It is notable (and atypical of
other reports) that only 1 long-term follow-up patient lost vision permanently in 1 eye. The only other patient to lose
vision did so early in the course and went on to die in the eighth week of treatment. Episodes of transient visual
symptoms were recorded a total of 14 times, 10 in patients with symptoms of both temporal arteritis and polymyalgia
and 1 in a patient with only temporal arteritis, but 3 instances were found in a patient (or patients) with polymyalgia
alone. It is useful to note that most of the relapses occurred during the first year and 50% between the third and the
sixth month. Only 50% of relapses occurred after reduction of the steroid dosage.
Nesher and colleagues compared outcomes in 77 temporal arteritis patients divided into 3 prednisone initial dosage
groups: (1) group A started at 30 to 40 mg/day, (2) group B started at 40 to 60 mg/day and (3) group C started at
doses greater than 60 mg/day (Nesher et al 1997). All 3 groups fared equally well as measured by cumulative cure
rates at years 1, 2, and 3 as well as by relapse rate (though group C had more relapses during the first year than the
other groups). Group A had significantly lower incidence of steroid side effects (36%) as compared with groups B (78%)
and C (88%).
There have been proponents of intravenous pulse methylprednisolone therapy at doses of 1 to 2 g/day to initiate
treatment in temporal arteritis in cases where visual loss has occurred in 1 or both eyes. Occasional cases have
demonstrated marked visual return with this type of treatment, although a secondary goal is simply to prevent visual
involvement of the second eye (Matzkin et al 1992). In a randomized, double-blind, placebo-controlled study in which
14 patients with biopsy-positive temporal arteritis received IV methylprednisolone (15 mg/kg of ideal body weight/day)
and 13 other patients received IV saline for 3 consecutive days together with long-term oral prednisone starting at a
dose of 40 mg/day, follow-up for a total of 78 weeks showed highly significant long-term benefit for the group that had
received pulse IV corticosteroid initially. Those who had been treated initially with pulse IV corticosteroids 1) had a
higher percentage at 36 through 78 weeks taking oral prednisone at a dose of less than or equal to 5 mg/day
(P=0.0003); 2) required a cumulative dose of oral prednisone, excluding the IV methylprednisolone dose, of 5636 mg
compared with 7860 mg in the IV saline-treated group (P=0.001); and 3) had a higher number of sustained remissions
after discontinuation of treatment and a lower median daily dose of prednisone at 78 weeks (P=0.0004) (Mazlumzadeh
et al 2006).
Some have claimed that treatment with corticosteroids improves vision in eyes already affected by ischemic damage.
This contention was not supported by Hayrey and colleagues in their survey of 114 eyes in 84 patients treated with IV
pulse followed by oral corticosteroids or high-dose oral corticosteroid alone, in which only 4% showed improvement of
visual acuity > 2 lines Snellen) and central visual field (Hayreh et al 2002).
There has been interest in adding immunosuppressant drugs to the treatment regimen in an effort to spare steroid
dose requirements. Krall and colleagues reported that addition of methotrexate in doses between 7.5 and 12.5
mg/week controlled symptoms in 3 patients who relapsed as prednisone was tapered. Van der Veen and colleagues,
however, submitted the addition of methotrexate 7.5 mg/week to a double-masked placebo-controlled trial carried out
on 40 patients with polymyalgia rheumatica, 6 of whom also had temporal arteritis. When comparing values of initial
remission, relapse frequency, and prednisone dose necessary to maintain remission, there was no significant
difference between the group randomly selected to receive placebo and the group selected to receive methotrexate
(van der Veen et al 1996). In addition, a multicenter, randomized, double-blind, placebo-controlled trial of adjuvant
methotrexate for treatment of temporal arteritis could not demonstrate any advantage for the drug over placebo in
addition to corticosteroids. Outcome measures included frequency of relapse and cumulative corticosteroid dose in the
2 groups (Hoffman et al 2002).
It has also been claimed that azathioprine spares steroid requirements in temporal arteritis (De Silva and Hazleman
1986). A survey of hospital-based consultants in England found that 6 of 19 (32%) were using azathioprine to lessen
the steroid requirement in patients with temporal arteritis (Chakravarty et al 1994).
Intravenous cyclophosphamide pulses of 0.5 to 1.0 g given weekly for 3 weeks allowed a significant reduction in
concomitant corticosteroid requirement in 4 patients during the initial treatment of temporal arteritis (de Vita et al
1992).
The effectiveness of oral cyclophosphamide in daily doses of 1.5 to 2.0 mg/kg per day along with medium- to highdose glucocorticoid (0.3 to 1.0 mg/kg per day) was studied in 19 patients with giant cell arteritis. Patients received
cyclophosphamide until clinical symptoms remitted and laboratory inflammatory markers normalized and for a
maximum of 12 months. Fifteen of the patients started cyclophosphamide after the symptoms and labs proved
refractory to glucocorticoids (5 patients) or after clinical symptoms returned during glucocorticoid tapering (10
patients). Complete remission of symptoms and normalization of inflammatory lab markers was the definition of
efficacy for cyclophosphamide and this was achieved in 15 of the 19 patients (78.9%). Cyclophosphamide treatment
was sustained for a mean of 5.2 months with discontinuation because of either inefficacy or side effects. Of the 15
patients for whom cyclophosphamide was efficacious, 13 were observed for at least 6 months after cessation of
cyclophosphamide therapy, during which time methotrexate 10 to 20 mg/week was administered to 14 of the patients.
Four of these 13 patients had clinical relapses; 1 relapse occurred 1 month after stopping the drug and 3 relapses
occurred more than 24 months after cessation of cyclophosphamide. Cyclophosphamide was effective in 2 relapsed
patients who were treated with this agent again (Quartuccio et al 2012).
Another 31 patients with giant cell arteritis who had persisting symptoms despite taking glucocorticoids and either
methotrexate or azathioprine for at least 3 months, and could not reduce the corticosteroid dose below 10 mg/day
prednisolone equivalent, were treated with cyclophosphamide administered either intravenously at various intervals or
orally on a daily basis. Twenty-eight of the 31 patients were “responders” in that there was sustained cessation of
symptoms and normalization of erythrocyte sedimentation rate and C-reactive protein. Relapses occurred in 12
patients after a median of 20.5 months after cessation of the first cyclophosphamide treatment and all responded to
retreatment with the same drug. Adverse effects of cyclophosphamide included transient leucopenia, infections, and 1
case of hemorrhagic cystitis (Loock et al 2012).
In the mid-1980s reports began to appear suggesting that Dapsone could be used either in conjunction with
corticosteroid or alone to treat temporal arteritis. Although this drug seems to allow dose reduction of corticosteroids,
its toxicity is prohibitive. Anemia, neuropathy, toxicoderma, and agranulocytosis have all been encountered.
Infliximab, a tissue necrosis factor inhibitor, proved ineffective in reducing the corticosteroid dose required to prevent
relapse in a study of 44 patients with newly diagnosed, biopsy-positive patients with temporal arteritis. The outcome
was assessed after 22 weeks of treatment in 16 patients randomized to receive corticosteroids and placebo compared
with 16 patients who received corticosteroids and infliximab. The authors admit that the study is too small to preclude
some benefit from infliximab, but they judge that the benefit would likely be relatively minor if subjected to a larger
study (Hoffman et al 2007).
However, another tissue necrosis factor inhibitor, etanercept, was shown to reduce the cumulative dose of
corticosteroid required to keep temporal arteritis in clinical remission over the course of a 1-year study, and a larger
proportion of patients given etanercept were able to remain in remission without corticosteroid at 1 year compared
with a placebo control group. The advantages of etanercept did not reach statistical significance, but the effect was
considered substantial enough to warrant evaluation in a larger study (Martinez-Taboada et al 2008). Fujita and
colleagues describe a 67-year-old man with giant cell arteritis who refused high-dose corticosteroids but who went on
to have 5 clinical relapses on low-dose steroids and sequential steroid-sparing agents, including methotrexate,
mizoribine, and cyclosporine (Fujita et al 2016). Etanercept was then added to low-dose corticosteroid plus
cyclosporine. The corticosteroid (prednisolone) was tapered from 20 mg/day to 5 mg/day over the next 10 months and
then cyclosporine was discontinued. Two months later remission persisted on etanercept, and repeat imaging showed
resolution of previously demonstrated temporal arterial wall thickening.
Conway and coworkers performed a proof of concept study of an IL-12/IL-23-blocking monoclonal antibody,
ustekinumab, in 14 patients with “refractory” giant cell arteritis that was defined as having had more than 2 relapses
requiring more than 10 mg/day glucocorticoids (Conway et al 2016). During a median follow up interval of 13.5 months
(range 7 to 26), none of the patients had relapses while on ustekinumab. Four patients (29%) were able to stop taking
glucocorticoids, and 11 (92%) stopped other immunosuppressants.
Another study included 5 patients with refractory Takayasu arteritis and 5 with giant cell arteritis who continued to
have relapses despite treatment with corticosteroids plus methotrexate (N=5), cyclophosphamide (N=3), or
mycophenolate mofetil (N=3) (Vinicki et al 2016). Four patients received infliximab, and 1 received tocilizumab. One
had infliximab as monotherapy; the rest of the patients also received methotrexate or mycophenolate mofetil. All
remained in remission during a mean follow up interval of 59.6 (± 27.2) months, and the glucocorticoid dose was
reduced by 79%.
Gabriel and others at the Mayo Clinic reviewed the morbidity of long-term corticosteroid and nonsteroidal
antiinflammatory drugs used to treat a cohort of 232 patients with polymyalgia rheumatica, of whom 30 also had
temporal arteritis. Though the dosage used was probably lower than would be the case for a group of patients with
temporal arteritis, the figures give a good indication of the significant drug-related problems for these patients. It was
found that the risks for diabetes mellitus and various bone fractures were 2 to 5 times greater among the polymyalgia
rheumatica patients as compared with age-matched controls. Proportional hazards modeling showed that the following
3 factors independently increased the number of adverse events: (1) higher age at diagnosis, (2) cumulative dose of
prednisone greater than or equal to 1800 mg, and (3) female sex.
One of the most serious side effects of long-term corticosteroid treatment is osteoporosis. Various authors have
generally recommended prophylactic treatment for osteoporosis using calcium and phosphate compounds, but there
has been little proof of their effectiveness. Mulder and Struys found that pulse treatment with etidronate resulted in
significantly greater bone density in a group of postmenopausal women being treated with long-term corticosteroids
for temporal arteritis, as compared with a control group on comparable doses of corticosteroids alone (Mulder and
Struys 1994).
The erythrocyte sedimentation rate is the most common laboratory parameter to follow during follow-up to signal
relapses. Kyle and Hazleman found that the erythrocyte sedimentation rate correlated better than C-reactive protein
with relapses, and that only "a minimal increase in alpha 1-antichymotrypsin was seen in 27% of clinical relapses"
(Kyle and Hazleman 1993). Pountain and colleagues later reported that alpha 1-antichymotrypsin levels remained
elevated during treatment for up to 18 months, well after the erythrocyte sedimentation rate and the C-reactive
protein had normalized; a significant secondary rise in erythrocyte sedimentation rate or C-reactive protein did not
accompany relapses. They found that if the alpha 1-antichymotrypsin was less than or equal to 0.7 g/L at 18 months
follow-up, there was a significantly reduced risk of subsequent relapse (P=-0.006) (Pountain et al 1994).
Studies have identified some other markers that respond in a sensitive way to successful treatment of temporal
arteritis. Johansen and colleagues reported on YKL-40, a mammalian member of the family 18 glycosyl hydrolases,
which is secreted by activated macrophages. They found that serum YKL-40 levels were increased over controls
patients with temporal arteritis, and the levels returned to normal during prednisolone treatment. The serum levels
were not elevated in patients with polymyalgia rheumatica (Johansen et al 1999). Weyand and colleagues studied 25
patients with biopsy proven temporal arteritis prospectively and demonstrated plasma interleuken-6 (IL-6) to be a
much more sensitive measure of disease activity than erythrocyte sedimentation rate. These authors also found that
the IL-6 levels did not return to normal when all clinical indicators suggested favorable response; they suggested that
incomplete suppression of arterial inflammation in most patients puts them at risk for progressive vascular disease
(Weyand et al 2000).
The effects of aspirin and corticosteroids (dexamethasone) were studied in severe combined immunodeficiency mice
into which inflamed temporal arteries were engrafted. Corticosteroids repressed nuclear factor kappaB, but aspirin was
much more effective in suppressing interferon gamma production by T-cell clones, suggesting that there may be
synergistic relation between the 2 agents in treating temporal arteritis (Weyand et al 2002). This has yet to be tested
clinically.
Whatever ultimate course of treatment is selected, it is important to emphasize the critical need to initiate effective
treatment as soon after the diagnosis is suspected as possible to minimize blindness and other severe ischemic
complications. On this point, Diamantopoulos and coworkers described the utility of an out-patient fast-track clinic
dedicated to the diagnosis of temporal arteritis using color Doppler ultrasound of the temporal arteries in place of
temporal artery biopsy with immediate institution of high dose prednisone treatment in those with typical symptoms
and confirmatory ultrasound results (Diamantopoulos et al 2016). There were in all 75 patients diagnosed with
temporal arteritis of which 32 were evaluated conventionally and 43 were in the fast-track group. The risk of
developing permanent visual loss was 88% lower in the fast-track than in the conventionally diagnosed group.
Special considerations
Pregnancy
All of the patients are beyond their childbearing years.
Anesthesia
There is no indication of particular interaction between temporal arteritis and any anesthetic agent. These patients
might be considered to be at higher risk than the average person of the same age for ischemic complications, should
there be an episode of systemic hypotension during anesthesia. It makes sense to take precautions to prevent this.
References cited
Achkar AA, Lie JT, Hunder GG, O'Fallon WM, Gabriel SE. How does previous corticosteroid treatment affect the biopsy
findings in giant cell (temporal) arteritis. Ann Intern Med 1994;120:987-92. PMID 8185147
Alba MA, Garcia-Martinez A, Prieto-Gonzalez S, et al. Relapses in patients with giant cell arteritis: prevalence,
characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients. Medicine (Baltimore)
2014;93(5):194-201. PMID 25181312
Allison M, Gallagher P. Temporal artery biopsy and corticosteroid treatment. Ann Rheum Dis 1984;43:416-7. PMID
6742903
Atluri P, Woo YJ. High-risk repair of ascending aortic aneurysm due to giant cell aortitis. Asian Cardiovasc Thorac Ann
2007;15(3):252-4. PMID 17541000
Baldursson O, Steinsson K, Bjornsson J, Lie JT. Giant cell arteritis in Iceland. An epidemiologic and histopathologic
analysis. Arthritis Rheum 1994;37:1007-12. PMID 8024610
Barber HS. Myalgic syndrome with constitutional effects. Polymyalgia rheumatica. Ann Rheum Dis 1957;16:230-7.
PMID 13445065
Bas-Lando M, Breuer GS, Berkun Y, Mates M, Sonnenblick M, Nesher G. The incidence of giant cell arteritis in Jerusalem
over a 25-year period: annual and seasonal fluctuations. Clin Exp Rheumatol 2007;25(1 Suppl 44):S15-7. PMID
17428357
Bley TA, Wieben O, Uhl M, et al. Integrated head-thoracic vascular MRI at 3T: assessment of cranial, cervical and
thoracic involvement of giant cell arteritis. MAGMA 2005;18:193-200. PMID 16133594
Blockmans D, Coudyzer W, Vanderschueren S, et al. Relationship between fluorodeoxyglucose uptake in the large
vessels and late aortic diameter in giant cell arteritis. Rheumatology (Oxford) 2008;47(8):1179-84. PMID 18515868
Bosley TM, Savino PJ, Sergott RC, Eagle RC, Sandy R, Gee W. Ocular plethysmography can help in the diagnosis of
giant-cell arteritis. Arch Ophthalmol 1989;107:379-81. PMID 2923561
Brack A, Martinez-Taboada V, Stanson A, Goronzy JJ, Weyand CM. Disease pattern in cranial and large-vessel giant cell
arteritis. Arthritis Rheum 1999;42:311-7. PMID 10025926
Caselli RJ, Hunder GG, Whisnant JP. Neurologic disease in biopsy-proven giant cell (temporal) arteritis. Neurology
1988;38:352-9. PMID 3347337
Chakrabarty A, Franks AJ. Temporal artery biopsy: is there any value in examining biopsies at multiple levels. J Clin
Pathol 2000;53(2):131-6. PMID 10767829
Chakravarty K, Elgabani SH, Scott DG, Merry P. A district audit on the management of polymyalgia rheumatica and
giant cell arteritis. Br J Rheumatol 1994;33:152-6. PMID 8162481
Chakravarty K, Pountain G, Merry P, Byron M, Hazleman B, Scott DG. A longitudinal study of anticardiolipin antibody in
polymyalgia rheumatica and giant cell arteritis. J Rheumatol 1995;22:1694-7. PMID 8523347
Chiu CS, Dryja TP, Lessell S. A "negative" temporal artery biopsy, positive for arteritis. Arch Ophthalmol
2004;122(7):1074-5. PMID 24359803
Chmelewski WL, McKnight KM, Agudelo CA, Wise CM. Presenting features and outcomes in patients undergoing
temporal artery biopsy. A review of 98 patients. Arch Intern Med 1992;152:1690-5. PMID 1497403
Cid MC, Hernandez-Rodriguez J, Esteban MJ, Cebrian M, Gho YS, Font C. Tissue and serum angiogenic activity is
associated with low prevalence of ischemic complications in patients with giant-cell arteritis. Circulation
2002;106(13):1664-71. PMID 12270860
Conway R, O'Neill L, O'Flynn E, et al. Ustekinumab for the treatment of refractory giant cell arteritis. Ann Rheum Dis
2016;75(8):1578-9. PMID 27143653
Corcoran GM, Prayson RA, Herzog KM. The significance of perivascular inflammation in the absence of arteritis in
temporal artery biopsy specimens. Am J Clin Pathol 2001;115(3):342-7. PMID 11242789
Costello F, Zimmerman MB, Podhajsky PA, Hayreh SS. Role of thrombocytosis in diagnosis of giant cell arteritis and
differentiation of arteritic from non-arteritic anterior ischemic optic neuropathy. Eur J Ophthalmol 2004;14(3):245-57.
PMID 15206651
Cox M, Gilks B. Healed or quiescent temporal arteritis versus senescent changes in temporal artery biopsy specimens.
Pathology 2001;33(2):163-6. PMID 11358048
Cullen JF. Occult temporal arteritis. Trans Ophthalmol Soc U K 1963;83:725-36. PMID 14123189
Czihal M, Brendel T, Seibold C, Reincke M, Hoffmann U. Listen to the axillary artery: diagnosis of occult giant cell
arteritis. J Clin Rheumatol 2011;17:214-5. PMID 21617546
Dababneh A, Gonzalez-Gay MA, Garcia-Porrua C, Hajeer A, Thomson W, Ollier W. Giant cell arteritis and polymyalgia
rheumatica can be differentiated by distinct patterns of HLA class II association. J Rheumatol 1998;25(11):2140-5.
PMID 9818656
Danesh-Meyer HV, Savino PJ, Sergott RC. The prevalence of cupping in end-stage arteritic and nonarteritic anterior
ischemic optic neuropathy. Ophthalmology 2001;108(3):593-8. PMID 11237915
Danve A, O'Dell J. The role of 18f fluorodeoxyglucose positron emission tomography scanning in the diagnosis and
management of systemic vasculitis. Int J Rheum Dis 2015;18(7):714-24. PMID 26177990
de Heide LJ, Talsma MA. Giant-cell arteritis presenting as an orbital pseudotumor. Neth J Med 1999;55:196-8. PMID
10555437
Delecoeuillerie D, Joly P, Cohen DE, Lara A, Paolaggi JB. Polymyalgia rheumatica and temporal arteritis; a retrospective
analysis of prognostic features and different corticosteroid regimens (11 year survey of 210 patients). Ann Rheum Dis
1988;477:33-9. PMID 3178314
Deng J, Younge BR, Olshen RA, Goronzy JJ, Weyand CM. Th17 and Th1 T-cell responses in giant cell arteritis. Circulation
2010;121(7):906-15. PMID 20142449
De Silva M, Hazleman BL. Azathioprine in giant cell arteritis/polymyalgia rheumatica: a double-blind study. Ann Rheum
Dis 1986;451:36-8. PMID 3511861
de Vita S, Tavoni A, Jeracitano G, Gemignani G, Dolcher MP, Bombardieri S. Treatment of giant cell arteritis with
cyclophosphamide pulses [letter]. J Intern Med 1992;232:373-5. PMID 1402645
Diamantopoulos AP, Haugeberg G, Lindland A, Myklebust G. The fast-track ultrasound clinic for early diagnosis of giant
cell arteritis significantly reduces permanent visual impairment: towards a more effective strategy to improve clinical
outcome in giant cell arteritis? Rheumatology (Oxford) 2016;55(1):66-70. PMID 26286743
Dimitrijevic I, Malmsjo M, Andersson C, Rissler P, Edvinsson L. Increased angiotensin II type 1 receptor expression in
temporal arteries from patients with giant cell arteritis. Ophthalmology 2009;116(5):990-6. PMID 19410957
Duhaut P, Pinede L, Bornet H, et al. Biopsy proven and biopsy negative temporal arteritis: differences in clinical
spectrum at the onset of the disease. Groupe de Recherche sur l'Arterite a Cellules Geantes. Ann Rheum Dis
1999a;58:335-41. PMID 10340957
Duhaut P, Pinede L, Demolombe-Rague S, et al. Giant cell arteritis and cardiovascular risk factors: a multicenter,
prospective case-control study. Groupe de Recherche sur l'Arterite a Cellules Geantes 1998;41:1960-5. PMID 9811050
Duhaut P, Pinede L, Demolombe-Rague S, et al. Giant cell arteritis and polymyalgia rheumatica: are pregnancies a
protective factor. A prospective, multicentre case-control study. GRACG (Groupe de Recherche sur l'Arterite a Cellules
Geantes). Rheumatology (Oxford) 1999b;38:118-23. PMID 10342623
Elliott PD, Baker HL, Brown AL. Superficial temporal artery arteriogram. Radiology 1972;102:635-8. PMID 5060174
Espinosa G, Tassies D, Font J, et al. Antiphospholipid antibodies and thrombophilic factors in giant cell arteritis. Semin
Arthritis Rheum 2001;31(1):12-20. PMID 11503135
Esteban MJ, Font C, Hernandez-Rodriguez J, et al. Small-vessel vasculitis surrounding a spared temporal artery: clinical
and pathological findings in a series of twenty-eight patients. Arthritis Rheum 2001;44(6):1387-95. PMID 11407699
Evans JM, O'Fallon WM, Hunder GG. Increased incidence of aortic aneurysm and dissection in giant cell (temporal)
arteritis. A population-based study. Ann Intern Med 1995;122:502-7. PMID 7872584
Fernandez-Lopez MJ, Wamen S, Karmali R, Peretz A, Gonzalez-Gay MA, Bentin J. Low back pain as presenting
manifestation of giant cell arteritis associated to abdominal aortitis. Clin Exp Rheumatol 2007;25(1 Suppl 44):S31-3.
PMID 17428361
Fledelius HC, Nissen KR. Giant cell arteritis and visual loss. A 3-year retrospective hospital investigation in a Danish
county. Acta Ophthalmol (Copenh) 1992;70:801-5. PMID 1488891
Font C, Cid MC, Coll-Vinent B, Lopez-Soto A, Grau JM. Clinical features in patients with permanent visual loss due to
biopsy-proven giant cell arteritis. Br J Rheumatol 1997;36(2):251-4. PMID 9133940
Freddo T, Price M, Kase C, Goldstein MP. Myocardial infarction and coronary artery involvement in giant cell arteritis.
Optom Vis Sci 1999;76:14-8. PMID 10030611
Fujita M, Tabuchi Y, Yagita M. Successful treatment of refractory giant cell arteritis with etanercept. Rheumatol Int
2016;36(8):1177-9. PMID 27368671
Gabriel SE, Espy M, Erdman DD, Bjornsson J, Smith TF, Hunder GG. The role of parvovirus B19 in the pathogenesis of
giant cell arteritis: a preliminary evaluation. Arthritis Rheum 1999;42:1255-8. PMID 10366119
Galor A, Lee MS. Slowly progressive vision loss in giant cell arteritis. Arch Ophthalmol 2006;124:416-8. PMID 16534064
Garcia-Martinez A, Arguis P, Prieto-Gonzalez S, et al. Prospective long term follow-up of a cohort of patients with giant
cell arteritis screened for aortic structural damage (aneurysm or dilatation). Ann Rheum Dis 2014;73(10):1826-32.
PMID 23873881
Garcia-Martinez A, Hernandez-Rodriguez J, Arguis P, et al. Development of aortic aneurysm/dilatation during the
followup of patients with giant cell arteritis: a cross-sectional screening of fifty-four prospectively followed patients.
Arthritis Rheum 2008;59(3):422-30. PMID 18311764
Ghaffar SA, Todd PM. Scalp necrosis secondary to giant-cell arteritis. Clin Exp Dermatol 2010;35(3):e40-1. PMID
20500172
Gilden D, White T, Khmeleva N, et al. Prevalence and distribution of VZV in temporal arteries of patients with giant cell
arteritis. Neurology 2015a;84(19):1948-55. PMID 25695965
Gilden D, White TM, Nagae L, Gurdin WH, Boyer PJ, Nagel MA. Successful antiviral treatment of giant cell arteritis and
Takayasu arteritis. JAMA Neurol 2015b;72(8):943-6. PMID 26258736
Gillanders LA. Temporal arteriography. Clin Radiol 1969;20:149-56. PMID 5781760
Gonzalez-Gay MA, Garcia-Porrua C, Pineiro A, Pego-Reigosa R, Llorca J, Hunder GG. Aortic aneurysm and dissection in
patients with biopsy-proven giant cell arteritis from northwestern Spain: a population-based study. Medicine
(Baltimore) 2004a;83(6):335-41. PMID 15525845
Gonzalez-Gay MA, Garcia-Porrua C, Rivas MJ, Rodriguez-Ledo P, Llorca J. Epidemiology of biopsy proven giant cell
arteritis in northwestern Spain: trend over an 18 year period. Ann Rheum Dis 2001;60(4):367-71. PMID 11247867
Gonzalez-Gay MA, Miranda-Filloy JA, Lopez-Diaz MJ, et al. Giant cell arteritis in northwestern Spain: a 25-year
epidemiologic study. Medicine (Baltimore) 2007;86(2):61-8. PMID 17435586
Gonzalez-Gay MA, Pineiro A, Gomez-Gigirey A, et al. Influence of traditional risk factors of atherosclerosis in the
development of severe ischemic complications in giant cell arteritis. Medicine (Baltimore) 2004b;83(6):342-7. PMID
15525846
Goodwin JA. Temporal arteritis. In: Vinken PJ, Bruyn GW, Klawans HL, editors. Neurological manifestations of systemic
diseases. Part II. New York: North-Holland, 1980:313-42.
Habib HM, Essa AA, Hassan AA. Color duplex ultrasonography of temporal arteries: role in diagnosis and follow-up of
suspected cases of temporal arteritis. Clin Rheumatol 2012;31(2):231-7. PMID 21743987
Hall S, Persellin S, Lie JT, O'Brien PC, Kurland LT, Hunder GG. The therapeutic impact of temporal artery biopsy. Lancet
1983;212:17-20. PMID 6139569
Hamano K, Gohra H, Katoh T, et al. An ascending aortic aneurysm caused by giant cell arteritis: report of a case. Surg
Today 1999;29:957-9. PMID 10489146
Hamilton CR, Shelley WM, Tumulty PA. Giant cell arteritis. Including temporal arteritis and polymyalgia rheumatica.
Medicine (Baltimore) 1971;50:1-27. PMID 5101106
Hamrin B. Polymyalgia arteritica with morphological changes in the large arteries. Acta Med Scand 1972;533(Suppl):4164.
Hauenstein C, Reinhard M, Geiger J, et al. Effects of early corticosteroid treatment on magnetic resonance imaging and
ultrasonography findings in giant cell arteritis. Rheumatology (Oxford) 2012;51(11):1999-2003. PMID 22772317
Hautzel H, Sander O, Heinzel A, Schneider M, Muller HW. Assessment of Large-Vessel Involvement in Giant Cell Arteritis
with 18F-FDG PET: Introducing an ROC-Analysis-Based Cutoff Ratio. J Nucl Med 2008;49(7):1107-1113. PMID 18552151
Hayreh SS, Podhajsky PA, Raman R, Zimmerman B. Giant cell arteritis: validity and reliability of various diagnostic
criteria. [Comments]. Am J Ophthalmol 1997;123(3):285-96. PMID 9063237
Hayreh SS, Podhajsky PA, Zimmerman B. Ocular manifestations of giant cell arteritis. Am J Ophthalmol 1998;125:50920. PMID 9559737
Hayreh SS, Zimmerman B, Kardon RH. Visual improvement with corticosteroid therapy in giant cell arteritis. Report of
a large study and review of literature. Acta Ophthalmol Scand 2002;80(4):355-67. PMID 12190776
Hernandez-Rodriguez J, Segarra M, Vilardell C, et al. Tissue production of pro-inflammatory cytokines (IL-1{beta},
TNF{alpha} and IL-6) correlates with the intensity of the systemic inflammatory response and with corticosteroid
requirements in giant-cell arteritis. Rheumatology (Oxford) 2004;43(3):294-301. PMID 14679293
Hoffman GS, Cid MC, Hellmann DB, et al. A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant
methotrexate treatment for giant cell arteritis. Arthritis Rheum 2002;46(5):1309-18. PMID 12115238
Hoffman GS, Cid MC, Rendt-Zagar KE, et al. Infliximab for maintenance of glucocorticosteroid-induced remission of
giant cell arteritis: a randomized trial. Ann Intern Med 2007;146(9):621-30. PMID 17470830
Horton BT, Magath TB, Brown GE. An undescribed form of arteritis of the temporal vessels. Proc Mayo Clin 1932;7:7001.
Hunder G, Bloch D, Michel B, et al. The American College of Rheumatology 1990 criteria for the classification of giant
cell arteritis. Arthritis Rheum 1990;33:1122-8. PMID 2202311
Hutchinson J. Disease of the arteries. Arch Surg 1889;1:323-9.
Hwang JM, Girkin CA, Perry JD, Lai JC, Miller NR, Hellmann DB. Bilateral ocular ischemic syndrome secondary to giant
cell arteritis progressing despite corticosteroid treatment. Am J Ophthalmol 1999;127:102-4. PMID 9933015
Joelson E, Ruthrauff B, Ali F, Lindeman N, Sharp FR. Multifocal dural enhancement associated with temporal arteritis.
Arch Neurol 2000;57:119-22. PMID 10634458
Johansen JS, Baslund B, Garbarsch C, et al. YKL-40 in giant cells and macrophages from patients with giant cell
arteritis. Arthritis Rheum 1999;42:2624-30. PMID 10616010
Kadry Z, Mentha G, Cereda JM. Polymyalgia rheumatica as a manifestation of a large hepatic cavernous hemangioma. J
Hepatol 2000;32(2):358-60. PMID 10707879
Kimmelstiel P, Gilmour MT, Hodges HH. Degeneration of elastic fibers in granulomatous giant cell arteritis (temporal
arteritis). Arch Pathol 1952;541:57-68. PMID 14943348
Klein RG, Campbell RJ, Hunder GG, Carney JA. Skip lesions in temporal arteritis. Proc Mayo Clin 1976;51:504-10. PMID
950804
Klink T, Geiger J, Both M, et al. Giant cell arteritis: diagnostic accuracy of MR imaging of superficial cranial arteries in
initial diagnosis-results from a multicenter trial. Radiology 2014;273(3):844-52. PMID 25102371
Kraft HE, Moller DE, Volker L, Schmidt WA. Color Doppler ultrasound of the temporal arteries-a new method for
diagnosing temporal arteritis. Klin Monatsbl Augenheilkd 1996;208:93-5. PMID 8648993
Kyle V, Hazleman BL. Treatment of polymyalgia rheumatica and giant cell arteritis. I. Steroid regimens in the first two
months. Ann Rheum Dis 1989;48:658-61. PMID 2782975
Kyle V, Hazleman BL. The clinical and laboratory course of polymyalgia rheumatica/giant cell arteritis after the first two
months of treatment. Ann Rheum Dis 1993;52:847-50. PMID 8311533
Lagrand WK, Hoogendoorn M, Bakker K, te Velde J, Labrie A. Aortoduodenal fistula as an unusual and fatal
manifestation of giant-cell arteritis. Eur J Vasc Endovasc Surg 1996;11:502-3. PMID 8846191
Lauwerys BR, Puttemans T, Houssiau FA, Devogelaer JP. Color Doppler sonography of the temporal arteries in giant cell
arteritis and polymyalgia rheumatica. J Rheumatol 1997;24(8):1570-4. PMID 9263153
Lee AG, Eggenberger ER, Kaufman DI, Manrique C. Optic nerve enhancement on magnetic resonance imaging in
arteritic ischemic optic neuropathy. J Neuroophthalmol 1999;19:235-7. PMID 10608674
Lie JT. Illustrated histopathologic classification criteria for selected vasculitis syndromes. American College of
Rheumatology Subcommittee on Classification of Vasculitis. Arthritis Rheum 1990;33(8):1074-87. PMID 1975173
Lie JT. Aortic and extracranial large vessel giant cell arteritis: a review of 72 cases with histopathologic documentation.
Semin Arthritis Rheum 1995;24:422-31. PMID 7667646
Liozon F, Jauberteau-Marchan MO, Boutros-Toni F, et al. Anticardiolipin antibodies and Horton disease. Ann Med Interne
(Paris) 1995;146:541-7. PMID 8734078
Liu KC, Chesnutt DA. Perineural optic nerve enhancement on magnetic resonance imaging in giant cell arteritis. J
Neuroophthalmol 2013;33(3):279-81. PMID 23845995
Loddenkemper T, Sharma P, Katzan I, Plant GT. Risk factors for early visual deterioration in temporal arteritis. J Neurol
Neurosurg Psychiatry 2007;78(11):1255-9. PMID 17504884
Loock J, Henes J, Kotter I, et al. Treatment of refractory giant cell arteritis with cyclophosphamide: a retrospective
analysis of 35 patients from three centres. Clin Exp Rheumatol 2012;30(1 Suppl 70):S70-6. PMID 22640650
Machado E, Michet C, Ballard D, et al. Trends in incidence and clinical presentation of temporal arteritis in Olmsted
County, Minnesota, 1950-1985. Arthritis Rheum 1988;31:745-9. PMID 3382448
Mack HG, O'Day J, Currie JN. Delayed choroidal perfusion in giant cell arteritis. J Clin Neuroophthalmol 1991;11:221-7.
PMID 1838538
Marie I, Proux A, Duhaut P, et al. Long-term follow-up of aortic involvement in giant cell arteritis: a series of 48
patients. Medicine (Baltimore) 2009;88(3):182-92. PMID 19440121
Martinez-Taboada VM, Goronzy JJ, Weyand CM. Clonally expanded CD8 T cells in patients with polymyalgia rheumatica
and giant cell arteritis. Clin Immunol Immunopathol 1996;79:263-70. PMID 8635285
Martinez-Taboada VM, Rodriguez-Valverde V, Carreno L, et al. A double-blind placebo controlled trial of etanercept in
patients with giant cell arteritis and corticosteroid side effects. Ann Rheum Dis 2008;67(5):625-30. PMID 18086726
Matteson EL, Gold KN, Bloch DA, Hunder GG. Long-term survival of patients with giant cell arteritis in the American
College of Rheumatology giant cell arteritis classification criteria cohort. Am J Med 1996;100:193-6. PMID 8629654
Matzkin DC, Slamovits TL, Sachs R, Burde RM. Visual recovery in two patients after intravenous methylprednisolone
treatment of central retinal artery occlusion secondary to giant-cell arteritis. Ophthalmology 1992;99:68-71. PMID
1741143
Mazlumzadeh M, Hunder GG, Easley KA, et al. Treatment of giant cell arteritis using induction therapy with high-dose
glucocorticoids: a double-blind, placebo-controlled, randomized prospective clinical trial. Arthritis Rheum
2006;54(10):3310-8. PMID 17009270
Meyer O, Nicaise P, Moreau S, et al. Antibodies to cardiolipin and beta 2 glycoprotein I in patients with polymyalgia
rheumatica and giant cell arteritis. Rev Rhum Engl Ed 1996;63:241-7. PMID 8738442
Morgenstern KE, Ellis BD, Schochet SS, Linberg JV. Bilateral optic nerve sheath enhancement from giant cell arteritis. J
Rheumatol 2003;30(3):625-7. PMID 12610827
Mulder H, Struys A. Intermittent cyclical etidronate in the prevention of corticosteroid-induced bone loss. Br J
Rheumatol 1994;33:348-50. PMID 8156307
Murchison AP, Gilbert ME, Bilyk JR, et al. Validity of the American College of Rheumatology Criteria for the diagnosis of
giant cell arteritis. Am J Ophthalmol 2012;154(4):722-9. PMID 22809782
Myklebust G, Wilsgaard T, Jacobsen BK, Gran JT. No increased frequency of malignant neoplasms in polymyalgia
rheumatica and temporal arteritis. A prospective longitudinal study of 398 cases and matched population controls. J
Rheumatol 2002;29(10):2143-7. PMID 12375324
Myles AB, Perera T, Ridley MG. Prevention of blindness in giant cell arteritis by corticosteroid treatment. Br J Rheumatol
1992;31:103-5. PMID 1737222
Nagel MA, Khmeleva N, Boyer PJ, Choe A, Bert R, Gilden D. Varicella zoster virus in the temporal artery of a patient
with giant cell arteritis. J.Neurol.Sci 2013;335(1-2):228-30. PMID 24125020
Narvaez J, Estrada P, Lopez-Vives L, et al. Prevalence of ischemic complications in patients with giant cell arteritis
presenting with apparently isolated polymyalgia rheumatica. Semin Arthritis Rheum 2015;45(3):328-33. PMID
26186807
Nesher G, Gur H, Ehrenfeld M, Rubinow A, Sonnenblick M. The changing clinical presentation of temporal arteritis in
Israel: a multicenter study. Isr Med Assoc J 1999;1(1):17-9. PMID 11370115
Nesher G, Rubinow A, Sonnenblick M. Efficacy and adverse effects of different corticosteroid dose regimens in
temporal arteritis: a retrospective study. Clin Exp Rheumatol 1997;15(3):303-6. PMID 9177927
Nesher G, Shemesh D, Mates M, Sonnenblick M, Abramowitz HB. The predictive value of the halo sign in color Doppler
ultrasonography of the temporal arteries for diagnosing giant cell arteritis. J Rheumatol 2002;29(6):1224-6. PMID
12064840
Nordborg E, Nordborg C. The inflammatory reaction in giant cell arteritis: an immunohistochemical investigation. Clin
Exp Rheumatol 1998;16:165-8. PMID 9536393
Nuenninghoff DM, Hunder GG, Christianson TJ, McClelland RL, Matteson EL. Incidence and predictors of large-artery
complication (aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients with giant cell arteritis: a
population-based study over 50 years. Arthritis Rheum 2003a;48(12):3522-31. PMID 14674004
Nuenninghoff DM, Hunder GG, Christianson TJ, McClelland RL, Matteson EL. Mortality of large-artery complication
(aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients with giant cell arteritis: a population-based
study over 50 years. Arthritis Rheum 2003b;48(12):3532-7. PMID 14674005
Onuma K, Chu CT, Dabbs DJ. Asymptomatic giant-cell (temporal) arteritis involving the bilateral adnexa: case report
and literature review. Int J Gynecol Pathol 2007;26(3):352-5. PMID 17581424
Ostberg G. On arteritis with special reference to polymyalgia arteritica. Acta Pathol Microbiol Scand 1973;237:1-59.
PMID 4151114
Paulley JW, Hughes JP. Giant-cell arteritis, or arteritis of the aged. Br Med J 1960;2:1562-7. PMID 13733499
Petursdottir V, Johansson H, Nordborg E, Nordborg C. The epidemiology of biopsy-positive giant cell arteritis: special
reference to cyclic fluctuations. Rheumatology (Oxford) 1999;38:1208-12. PMID 10587547
Petursdottir V, Nordborg E, Nordborg C. Atrophy of the aortic media in giant cell arteritis. APMIS 1996;104:191-8. PMID
8611193
Pipinos II, Hopp R, Edwards WD, Radio SJ. Giant-cell temporal arteritis in a 17-year-old male. J Vasc Surg 2006;43:10535. PMID 16678704
Pountain GD, Calvin J, Hazleman BL. Alpha 1-antichymotrypsin, C-reactive protein and erythrocyte sedimentation rate
in polymyalgia rheumatica and giant cell arteritis. Br J Rheumatol 1994;33(6):550-4. PMID 8205403
Prasad S, Baccon J, Galetta SL. Mydriatic pupil in giant cell arteritis. J Neurol Sci 2009;284(1-2):196-7. PMID 19427648
Pugnet G, Sailler L, Fournier JP, Bourrel R, Montastruc JL, Lapeyre-Mestre M. Predictors of cardiovascular hospitalization
in giant cell arteritis: effect of statin exposure. A French population-based study. J Rheumatol 2016. [Epub ahead of
print] PMID 27585686
Purvin V, Kawasaki A. Giant cell arteritis with spontaneous remission. Clin Experiment Ophthalmol 2007;35(1):59-61.
PMID 17300573
Quartuccio L, Maset M, De MG, et al. Role of oral cyclophosphamide in the treatment of giant cell arteritis.
Rheumatology (Oxford) 2012;51(9):1677-86. PMID 22627726
Rajesh CV, Cole M. Panuveitis as a presenting feature of giant cell arteritis [letter]. Br J Ophthalmol 2000;84:340. PMID
10744385
Ray-Chaudhuri N, Kine DA, Tijani SO, et al. Effect of prior steroid treatment on temporal artery biopsy findings in giant
cell arteritis. Br J Ophthalmol 2002;86(5):530-2. PMID 11973248
Rozen TD. Brief Sharp Stabs of Head Pain and Giant Cell Arteritis. Headache 2010;50(9):1516-9. PMID 20561065
Salvarani C, Boiardi L, Mantovani V, et al. HLA-DRB1 alleles associated with polymyalgia rheumatica in northern Italy:
correlation with disease severity. Ann Rheum Dis 1999;58:303-8. PMID 10225816
Salvarani C, Hunder GG. Giant cell arteritis with low erythrocyte sedimentation rate: frequency of occurrence in a
population-based study. Arthritis Rheum 2001;45(2):140-5. PMID 11324777
Salvarani C, Silingardi M, Ghirarduzzi A, et al. Is duplex ultrasonography useful for the diagnosis of giant-cell arteritis.
Ann Intern Med 2002;137(4):232-8. PMID 12186513
Sato M, Takeda A, Hagiwara S, et al. Giant cell arteritis and polymyalgia rheumatica presenting as subclavian artery
obstruction. Ryumachi 1993;33:330-4. PMID 8235915
Schallhorn J, Haug SJ, Yoon MK, Porco T, Seiff SR, McCulley TJ. A national survey of practice patterns: temporal artery
biopsy. Ophthalmology 2013;120(9):1930-4. PMID 23622876
Schmidt WA, Blockmans D. Use of ultrasonography and positron emission tomography in the diagnosis and assessment
of large-vessel vasculitis. Curr Opin Rheumatol 2005;17(1):9-15. PMID 15604899
Sheehan MM, Keohane C, Twomey C. Fatal vertebral giant cell arteritis. J Clin Pathol 1993;46:1129-31. PMID 8282839
Shick RM, Baggenstoss AH, Fuller BF, Polley HF. Effects of cortisone and ACTH on periarteritis nodosa and cranial
arteritis. Mayo Clin Proc 1950;25:492-4. PMID 15440931
Siatkowski RM, Gass JD, Glaser JS, Smith JL, Schatz NJ, Schiffman J. Fluorescein angiography in the diagnosis of giant
cell arteritis. Am J Ophthalmol 1993;115:57-63. PMID 8420379
Siemonsen S, Brekenfeld C, Holst B, Kaufmann-Buehler AK, Fiehler J, Bley TA. 3T MRI reveals extra- and intracranial
involvement in giant cell arteritis. AJNR Am J Neuroradiol 2015;36(1):91-7. PMID 25169925
Slavin ML, Barondes MJ. Visual loss caused by choroidal ischemia preceding anterior ischemic optic neuropathy in giant
cell arteritis. Am J Ophthalmol 1994;117:81-6. PMID 8291597
Sorbi D, French DL, Nuovo GJ, Kew RR, Arbeit LA, Gruber BL. Elevated levels of 92-kd type IV collagenase (matrix
metalloproteinase 9) in giant cell arteritis. Arthritis Rheum 1996;39:1747-53. PMID 8843867
Tal S, Guller V, Gurevich A, Levi S. Fever of unknown origin in the elderly. J Intern Med 2002; 252(4):295-304. PMID
12366602
Turlakow A, Yeung HW, Pui J, et al. Fludeoxyglucose positron emission tomography in the diagnosis of giant cell
arteritis. Arch Intern Med 2001;161(7):1003-7. PMID 11295964
Ungprasert P, Koster MJ, Thongprayoon C, Warrington KJ. Risk of venous thromboembolism among patients with
vasculitis: a systematic review and meta-analysis. Clin Rheumatol 2016;35(11):2741-7. PMID 27572522
Valmaggia C, Speiser P, Bischoff P, Niederberger H. Indocyanine green versus fluorescein angiography in the
differential diagnosis of arteritic and nonarteritic anterior ischemic optic neuropathy. Retina 1999;19:131-4. PMID
10213239
van der Veen MJ, Dinant HJ, van Booma-Frankfort C, van Albada-Kuipers GA, Bijlsma JW. Can methotrexate be used as
a steroid sparing agent in the treatment of polymyalgia rheumatica and giant cell arteritis. Ann Rheum Dis
1996;55:218-23. PMID 8733437
Vecsei PV, Kircher K, Nagel G, Egger SF, Schneider B. Retrobulbar hemodynamics in amaurosis fugax; investigation by
color Doppler velocity. Acta Ophthalmol Scand 1999;77:19-22. PMID 10071141
Vinicki JP, Garcia-Vicuna R, Arredondo M, et al. Sustained remission after long-term biological therapy in patients with
large vessel vasculitis: an analysis of ten cases. Reumatol Clin 2016. [Epub ahead of print]
Wagener HP, Hollenhorst RW. The ocular lesions of temporal arteritis. Am J Ophthalmol 1958;45:617-30. PMID
13533472
Weyand CM, Fulbright JW, Hunder GG, Evans JM, Goronzy JJ. Treatment of giant cell arteritis: interleukin-6 as a biologic
marker of disease activity. Arthritis Rheum 2000;43(5):1041-8. PMID 10817557
Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med 2003;349(2):160-9. PMID 12853590
Weyand CM, Hicok KC, Hunder GG, Goronzy JJ. The HLA-DRB1 locus as a genetic component in giant cell arteritis.
Mapping of a disease-linked sequence motif to the antigen binding site of the HLA-DR molecule. J Clin Invest
1992;90:2355-61. PMID 1469092
Weyand CM, Hunder NN, Hicok KC, Hunder GG, Goronzy JJ. HLA-DRB1 alleles in polymyalgia rheumatica, giant cell
arteritis, and rheumatoid arthritis. Arthritis Rheum 1994;37:514-20. PMID 8147928
Weyand CM, Kaiser M, Yang H, Younge B, Goronzy JJ. Therapeutic effects of acetylsalicylic acid in giant cell arteritis.
Arthritis Rheum 2002;46(2):457-66. PMID 11840449
Weyand CM, Tetzlaff N, Bjornsson J, Brack A, Younge B, Goronzy JJ. Disease patterns and tissue cytokine profiles in
giant cell arteritis. Arthritis Rheum 1997;40(1):19-26. PMID 9008596
Wilkinson IM, Russell RW. Arteries of the head and neck in giant cell arteritis: a pathologic study to show the pattern of
involvement. Arch Neurol 1972;27:378-91. PMID 5078894
Woods CA, editor. Memorandum book of a 10th century oculist. Chicago: Northwestern University, 1936.
Zenone T, Puget M. Characteristics of cerebrovascular accidents at time of diagnosis in a series of 98 patients with
giant cell arteritis. Rheumatol Int 2013;33(12):3017-23. PMID 23873329
**References especially recommended by the author or editor for general reading.
ICD and OMIM codes
ICD codes
ICD-9:
Giant cell arteritis: 446.5
Polymyalgia rheumatica: 725
ICD-10:
Other giant cell arteritis: M31.6
Polymyalgia rheumatica: M35.3
OMIM numbers
Temporal arteritis: 187360
Profile
Age range of presentation
45-64 years
65+ years
Sex preponderance
female>male, >2:1
female>male, >1:1
Family history
none
Heredity
heredity may be a factor
Population groups selectively affected
Caucasians
Occupation groups selectively affected
none selectively affected
Differential diagnosis list
metastatic tumors
primary malignant tumors
neoplasms
granulomatous infectious infiltrative diseases
neoplastic meningeal infiltrative diseases
paranasal sinus infection
hepatic cavernous hemangioma
ascending aortic aneurysm
myocardial infarction
subclavian artery stenosis
orbital inflammatory pseudotumor
panuveitis
Other topics to consider
Ischemic optic neuropathy
Optic neuritis
Periarteritis nodosa
Prednisone
Copyright© 2001-2016 MedLink Corporation. All rights reserved.