Journal of Autoimmunity xxx (2014) 1e3

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Journal of Autoimmunity
journal homepage: www.elsevier.com/locate/jautimm

The diagnosis and classification of giant cell arteritis

Gideon Nesher a, b, c, *
a
Department of Internal Medicine A, Shaare-Zedek Medical Center, Jerusalem, Israel
b
Hebrew University, Jerusalem, Israel
c
St. Louis University School of Medicine, St. Louis, MO, USA

a r t i c l e i n f o a b s t r a c t

Article history: Giant-cell arteritis (GCA) involves the major branches of the aorta with predilection for the extracranial
Received 7 October 2013 branches of the carotid artery. It occurs in individuals older than 50 years and the incidence increases
Accepted 13 November 2013 with age. The signs and symptoms of giant cell arteritis can be classified into four subsets: cranial
arteritis, extracranial arteritis, systemic symptoms and polymyalgia rheumatica. Patients may develop
Keywords: any combination of these manifestations, associated with laboratory evidence of an acute-phase reaction.
Temporal arteries
The only test that confirms GCA diagnosis is a temporal artery biopsy, showing vasculitis with mono-
Headache
nuclear cell inflammatory infiltrates, often with giant cells. Due to the focal and segmental nature of the
Sedimentation rate
Glucocorticoids
infiltrates, areas of inflammation may be missed by the biopsy and the histological examination is normal
Ultrasonography in about 15% of the cases. Some imaging modalities may aid in the diagnosis of GCA. Among those, color
Biopsy duplex ultrasonography of the temporal arteries is more commonly used. There are no independent
validating criteria to determine whether giant cell arteritis is present when a temporal artery biopsy is
negative. The American College of Rheumatology criteria for the classification of giant cell arteritis may
assist in the diagnosis. However, meeting classification criteria is not equivalent to making the diagnosis
in individual patients, and the final diagnosis should be based on all clinical, laboratory, imaging and
histological findings. Glucocorticoids are the treatment of choice for GCA. The initial dose is 40e60 mg/
day for most uncomplicated cases. Addition of low-dose aspirin (100 mg/d) has been shown to signifi-
cantly decrease the rate of vision loss and stroke during the course of the disease.
Ó 2014 Elsevier Ltd. All rights reserved.

1. Disease manifestations Among those, tender, prominent temporal arteries with absent
pulses, jaw claudication and diplopia have the highest positive
Giant-cell arteritis (GCA) involves the major branches of the likelihood ratios for GCA diagnosis [3,4]. Patients may develop any
aorta with predilection for the extracranial branches of the carotid combination of these manifestations. GCA patients with systemic
artery, including the temporal arteries. The aorta and other large symptoms and increased inflammatory response in laboratory
arteries may also be involved. testing such as very high erythrocyte sedimentation rate (ESR),
GCA is more common among people of North European decent anemia of inflammation and thrombocytosis, tend to present less
than among Mediterranean people, and is rare among African often with ischemic intracranial manifestations [5]. The onset of
Americans, Native Americans and Asians. GCA occurs in individuals GCA symptoms may be abrupt, but in most instances symptoms
older than 50 years and the incidence increases with age. The age- develop gradually over a period of several weeks. Elevated ESR is
specific incidence rates per 100,000 population increase from 2 in found in more than 90% of the patients, and in 30e60% it is very
the age group 50e59 years, to 52 in the age group 80 and older [1]. high (>100 mm/h). This and other abnormalities in laboratory tests
The estimated prevalence is about 1:750 persons older than 50 are elaborated in Table 2.
years [2]. Women are 2e3 times more commonly affected.
The signs and symptoms of GCA can be classified into four
subsets: manifestations of cranial arteritis, extracranial arteritis, 2. GCA diagnosis
systemic symptoms and polymyalgia rheumatica (PMR) (Table 1).
The diagnosis of GCA is made primarily on clinical grounds and
is bolstered by laboratory evidence of an acute phase reaction. The
* Department of Internal Medicine A, Shaare-Zedek Medical Center, P.O. Box
only test that confirms the diagnosis of GCA is a temporal artery
3235, Jerusalem 91031, Israel. Tel.: þ972 2 6666372; fax: þ972 2 6666049. biopsy, showing vasculitis with mononuclear cell infiltrates, often
E-mail address: [email protected]. with giant cells. GCA affects the vessels in segments, therefore areas

0896-8411/$ e see front matter Ó 2014 Elsevier Ltd. All rights reserved.
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Please cite this article in press as: Nesher G, The diagnosis and classification of giant cell arteritis, Journal of Autoimmunity (2014), http://
dx.doi.org/10.1016/j.jaut.2014.01.017
2 G. Nesher / Journal of Autoimmunity xxx (2014) 1e3

Table 1 comparable to color duplex ultrasonography [15]. Angiography of

Signs and symptoms of giant cell arteritis (GCA). the aortic arch and its branches may serve to diagnose large-vessel
Clinical feature Frequency involvement [16]. Non-invasive modalities, such as positron-
Cranial arteritis Headache, facial pain 70e85%
emission tomography may also be employed to detect large-
Scalp tenderness 20e40% vessel involvement [17].
Prominent or tender temporal arteries 30e60% Serological tests were not helpful in diagnosing GCA. A sub-
Jaw claudication 30e40% stantial number of patients (Table 2) are phospholipid antibody
Eye symptoms: sudden vision loss 15e45%
positive [18], but the specificity of this finding is low. Antibodies to
(transient or permanent), diplopia
or other ophthalmic manifestations lamin C were found in one-third of GCA patients and none of the
Stroke, transient ischemic attacks <15% controls [19]. Recently, antibodies to the ferritin heavy chain were
and other neuropsychiatric manifestations reported in 92% of untreated GCA patients, decreasing to 13% in
Vestibulo-auditory manifestations: 5e25%
patients during remission [20]. These antibodies were present also
hearing loss, tinnitus, vertigo
Tongue or scalp infarction <5%
in 29% of lupus patients, but in only 3% of rheumatoid arthritis
Extracranial Aortic arch syndrome, aortic-valve 5e20% patients and 1% of blood donors. Upon further testing, these anti-
arteritis insufficiency, aortic aneurysm or bodies may prove useful as a diagnostic marker of GCA.
dissection. There are no independent validating criteria to determine
Clinically significant involvement of 5e20%
whether GCA is present when a temporal artery biopsy is negative.
other arteries
Peripheral neuropathies <15% The American College of Rheumatology criteria for classification of
Respiratory symptoms (cough, sore <15% GCA [21] may assist in diagnosis (Table 3). However, it is important
throat, hoarseness) to note that these are not diagnostic criteria. Indeed, their validity
Systemic Fever, malaise, fatigue, anorexia, 30e60% in diagnosing GCA has been questioned [22]. Those classification
symptoms weight loss
PMR Bilateral aching and stiffness of the 20e65%
criteria serve mainly to differentiate GCA from other types of
shoulder girdle, sometimes the vasculitis. They cannot effectively serve to differentiate GCA from
neck and hip girdle. other disease conditions. Such classification criteria work best in
studying groups of patients with vasculitis, and less well when used
for diagnosing individual cases [23]. Meeting classification criteria
of vasculitis may be missed and the histological examination is is not equivalent to making the diagnosis in individual patients, and
normal in 10e30% of GCA patients (“biopsy-negative GCA”) [6,7]. A the final diagnosis should be based on all clinical, laboratory, im-
temporal artery biopsy length larger than 5 mm is associated with aging and histological findings.
increasing diagnostic yield, but the optimal length is probably
20 mm [8]. Biopsying both the left and the right temporal arteries 3. Therapy and disease course
may also increase the diagnostic yield: analysis of 7 studies showed
an average of 23% discordance rate between results of biopsies from Glucocorticoids are the treatment of choice for GCA [24]. The
the left and the right side, therefore half of these cases could have initial dose is 40e60 mg/day for most cases. Starting treatment
been misdiagnosed as biopsy-negative had a biopsy been done with intravenous methyl-prednisolone 500e1000 mg/d for 3 days
unilaterally [9]. It is preferable to perform the biopsy as soon as may be considered in patients with vision loss (transient or per-
possible, but the specimen may show signs of arteritis even after 2e manent), diplopia, transient ischemic attacks or stroke.
4 weeks of treatment [10]. Rapid improvement of clinical manifestations following treat-
Some imaging modalities may aid in the diagnosis of GCA. ment initiation is characteristic. Prompt treatment is crucial in GCA,
Among those, color duplex ultrasonography of the temporal ar- to prevent irreversible complications of acute vision loss and
teries is more commonly used. A peri-luminal hypo-echoic halo, stroke. Thus treatment may be started prior to confirming the
probably representing vessel-wall edema, was suggested to be diagnosis. The average duration of treatment is 2e3 years. Relapses
highly sensitive and specific for GCA [11]. However, results are are experienced by 25e65% of GCA patients. Most relapses are mild,
operator-dependent and technique-dependent, and vary consid- but some patients may develop vision loss or stroke while tapering
erably among studies examining the diagnostic value of color glucocorticoid dosage or after discontinuation of therapy. Addition
duplex ultrasonography [12,13]. of low-dose aspirin (100 mg/d) has been shown to significantly
High-resolution contrast-enhanced magnetic resonance imag- decrease the rate of vision loss and stroke during the course of the
ing (MRI) of the temporal arteries also enables evaluation of disease, probably mediated by its anti-platelet effect [25]. GCA
possible inflammation of the vessel wall. Preliminary results show patients may develop clinically-significant aortic involvement even
high sensitivity of this imaging modality [14], with diagnostic yield after completion of treatment, but indications for imaging of the
aorta in GCA have not been determined [26].
Table 2 Individual cases vary greatly, therefore the exact doses and the
Abnormalities in laboratory tests in giant cell arteritis. duration of treatment should be adjusted to the needs of the
Test Frequency

Acute phase Elevated erythrocyte 90e95% Table 3

reactants sedimentation rate (ESR) The American College of Rheumatology 1990 GCA classification criteria.
ESR  100 mm/h 30e60%
Elevated ESR and/or elevated >95% (1) Age at onset 50 years
C-reactive protein (CRP) (2) A new headache
Blood count Anemia 35e65% (3) Temporal artery abnormality such as tenderness to palpation or decreased
Thrombocytosis 30e60% pulsation
Leukocytosis 10e30% (4) Erythrocyte sedimentation rate  50 mm/h
Liver function tests Elevated alkaline phosphatase 30e60% (5) Abnormal artery biopsy showing vasculitis with mononuclear cell or
Low albumin 10e30% granulomatous inflammation, usually with giant cells.
Autoantibodies Anticardiolipin 30e60%
At least three of the five parameters must be present, which yields a sensitivity of
Anti-ferritin 92%
93% and a specificity of 91%, in relation to controls with other vasculitides.

Please cite this article in press as: Nesher G, The diagnosis and classification of giant cell arteritis, Journal of Autoimmunity (2014), http://
dx.doi.org/10.1016/j.jaut.2014.01.017
 G. Nesher / Journal of Autoimmunity xxx (2014) 1e3 3

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Please cite this article in press as: Nesher G, The diagnosis and classification of giant cell arteritis, Journal of Autoimmunity (2014), http://
dx.doi.org/10.1016/j.jaut.2014.01.017