A headache not to miss
Giant cell arteritis is an immune-mediated, ischaemic condition caused by inflammation in the wall of medium to large
arteries. While it can affect all medium to large arteries in the head, neck and upper torso, the involvement of the temporal
artery is usually the only artery in which physical changes are clinically apparent (giving rise to the alternative name
of temporal arteritis). It is the most common form of vasculitis in adults.1
Giant cell arteritis usually affects people aged over 50 years,2 and is only rarely seen in younger people.
It is most prevalent in Caucasians, particularly of Northern-European (e.g. Scandinavian) descent, and is two to three
times more common in females than males.3 Worldwide, incidence ranges between 10 – 20 cases per 100 000 people
aged over 50 years.3 A New Zealand study found a similar local incidence of 12 cases per year, per 100 000
people aged over 50 years.4
Symptoms of giant cell arteritis include headache, scalp tenderness, jaw claudication or other orofacial pain, neck
or shoulder pain, visual disturbances and systemic symptoms, such as sweats, fever and anorexia. There may be palpable
changes to the temporal artery on examination. An acute phase response is usually seen on laboratory assessment, and a
temporal artery biopsy will show inflammation and multinucleated cells with involvement of the internal elastic lamina.
If undetected, giant cell arteritis can result in catastrophic sequelae, such as irreversible visual loss, stroke and
aortic aneurysm. Visual loss, due to ischaemic optic neuropathy, is an early manifestation and can be a presenting symptom.
This occurs in 20 – 50% of people with giant cell arteritis if they are untreated.5, 6 Large-vessel stenosis,
and with it an increased risk of stroke, occurs in 10 – 15% of people.7, 8 Prompt treatment with corticosteroids
can markedly reduce these risks. For example, the likelihood of visual loss decreases from 20% to 1% in patients with
no preceding visual loss once treatment is initiated.7 Patients who already have some visual loss at the initial
presentation, however, have a poorer prognosis. One-quarter of patients develop further visual deterioration in the same
eye, and up to 10% lose vision in the other eye, usually within the first few days, despite treatment.9
Giant cell arteritis should be strongly considered in older patients presenting with a new type of headache, jaw pain
or visual disturbances (also see: "Making a diagnosis"). Whenever there is a reasonable suspicion
of the condition, discuss the patient with an Ophthalmologist or Rheumatologist (depending on local guidelines/protocols)
to organise referral for a temporal artery biopsy, and initiate same-day treatment with corticosteroids. Where there is
a strong clinical suspicion of giant cell arteritis, a delay in treatment will almost always have greater consequences
than an unnecessary dose of corticosteroids in someone who is later found to not to have the condition.
Pathology and aetiology: how does is happen?
In people with giant cell arteritis, inflammation, caused by an immune reaction, occurs within the arterial wall. The
inflammation is often irregular and is characterised by a granulomatous inflammatory infiltrate with the presence of large,
macrophage-induced multinuclear cells - the “giant cells” in giant cell arteritis.3, 7 This leads to a protective
response from the arteries, resulting in myofibroblast proliferation, new vessel formation and thickening of the artery
walls, culminating in potential infarction.3
The underlying cause of giant cell arteritis is largely unknown, but both genetic and external factors, e.g. infections,
are thought to play a role.3
Making a diagnosis of giant cell arteritis
Giant cell arteritis is diagnosed by identifying risk factors from the patient’s history and red flags from their clinical
presentation, followed by laboratory assessment and referral for a biopsy of the temporal artery. Most symptoms in people
with giant cell arteritis will develop gradually over one to two months, although rapid onset is possible.
The most significant risk factors for giant cell arteritis are:2, 7
- Age > 50 years
- A previous or current diagnosis of polymyalgia rheumatica
- Female gender
- European ethnicity
The patient’s description of their symptoms
Specifically enquire about the following symptoms:
- Scalp pain or tenderness
- Jaw claudication
- Visual symptoms
Abrupt onset of headache is the most frequent symptom of giant cell arteritis, and will be present
in approximately 75% of cases.2, 11 Any new onset or new type of headache in a person aged over 50 years should
be considered a red flag. In giant cell arteritis, the headache is typically unlike a normal headache for the patient,
and may be described as “head pain”.10 It is commonly unilateral, with a constant pain that may be severe
enough to disturb sleep.10 It is usually centred over the temporal or occipital area.12 Occasionally
the pain will be bilateral and diffuse.
Scalp pain or discomfort occurs in approximately one-quarter of patients with giant cell arteritis.5,10 The
patient may report pain when brushing their hair or when resting their head on a pillow.
Systemic features, including low-grade fever, anorexia and fatigue, are present in approximately half
of patients.5, 12 Giant cell arteritis may also be associated with weight loss and night sweats, however,
these symptoms may also suggest other possible diagnoses, such as a malignancy.10 In rare instances, systemic
symptoms will be the only clinical indication of giant cell arteritis, therefore, the diagnosis of giant cell arteritis
should be considered in any patient with systemic symptoms, raised inflammatory markers and no evidence of another cause,
such as infection.
Jaw claudication in the muscles of the tongue and jaw, e.g. while chewing, occurs in approximately
one-quarter of people with giant cell arteritis.4, 7 In severe cases, this may lead to numbness or infarction
of the scalp or the tongue. It is important to specifically ask patients about jaw claudication, as patients may not connect
this with their headache or other symptoms. Pain while chewing and the presence of jaw claudication strongly indicates
giant cell arteritis. Distinguishing between jaw pain from other causes (such as temporomandibular joint dysfunction)
and true jaw claudication is important – the pain in jaw claudication is a cramping pain occurring after prolonged chewing
Visual symptoms are less common at initial presentation, but are of critical importance. Symptoms may
include transient loss of vision in one eye, blurring and diplopia.12 Complete loss of vision can also occur.12
Limb claudication, particularly in the arms, may also be present, but is a rare finding.11 It
may indicate large-vessel giant cell arteritis (i.e. outside the cranial vessels).5
What to include in the examination
The clinical examination should include assessment of:
- Temporal arteries
- Visual acuity
- Pupillary response to light
- Neurological signs
- Peripheral pulses, blood pressure and bruits
Examine the temporal artery and its branches for unusual prominence and erythema.10 On
palpation these vessels may be thickened, hardened, nodular, beaded or have reduced or absent pulses.12 Tenderness
may be present on the scalp or over the vessels. A normal temporal artery, however, does not exclude giant cell arteritis.12
An eye exam should be performed, and should include visual acuity (using corrective distance glasses
if the patient has them, and excluding any residual refractive error using a pinhole), the pupillary light reflex, visual
field testing by finger confrontation and fundoscopy.12 With optic nerve involvement, the pupillary light
reflex may be sluggish or absent, and a swinging light test may indicate a relative afferent pupillary defect (the patient’s
pupils fail to contract, and therefore appear to dilate, when a light is swung from the unaffected eye to the affected
eye).12 Fundoscopy may reveal swelling or pallor of the optic disc with associated haemorrhage.5
A brief, but focused neurological exam should be performed depending on the patients presenting symptoms.
Neurological manifestations can occur in one-third of patients with giant cell arteritis, most commonly cranial nerve
palsies, peripheral neuropathies and, rarely, strokes in the region of the carotid or vertebrobasilar artery.5
Perform auscultation over the carotid, subclavian, axillary or brachial arteries as bruits can be present
and may indicate large-vessel involvement. Asymmetry of blood pressure or pulses in the neck and arms may be present,
and can indicate large-vessel stenosis.12 Auscultation over the patient’s chest may reveal secondary aortic
regurgitation (sometimes audible as a soft, high-pitched diastolic murmur best heard over the upper left sternal edge)
from a thoracic aortic aneurysm, which can occur as a late complication in people with giant cell arteritis.5
If the patient’s risk-factors, symptoms and signs suggest giant cell arteritis the following tests should be urgently
requested at the initial presentation:7
- C-reactive protein (CRP)
- Erythrocyte sedimentation rate (ESR)
- Full blood count (FBC)
- Liver function tests (LFTs)
While ESR and CRP are no longer routinely requested together for most conditions, either marker (or both) can be raised
in giant cell arteritis and given the significant potential for morbidity in people with giant cell arteritis, it is recommended
that both are requested in the initial presentation. This is consistant with most guidelines, as combining the two tests
marginally increases the sensitivity and specificity.5, 12 Any elevation of CRP or ESR is suggestive of giant
cell arteritis in a patient with signs and symptoms, although, typically, in acute cases, levels are significantly elevated.2 A
normal CRP or ESR does not exclude giant cell arteritis; up to 20% of people with confirmed giant cell arteritis have
only mildly raised inflammatory markers and a small number of patients will have levels within normal ranges on at least
one of the tests.5,10 If both CRP and ESR are normal, the likelihood of giant cell arteritis being present
is reduced, but cannot be ruled out.
A full blood count in people with giant cell arteritis will typically indicate anaemia with a mild leukocytosis and
an elevated platelet count.5
Liver function tests commonly indicate mildly elevated transaminases and alkaline phosphatase.5
Creatinine and electrolytes should also be tested (but do not need to be urgent) to provide a base-line for monitoring
in people who are likely to be treated with long-term corticosteroids.
Imaging tests may be requested in secondary care, after referral, if there is a suspicion of large-vessel involvement.
Ultrasound, computed tomography (CT) and magnetic resonance angiography are the most commonly used imaging techniques.
The most important differential diagnoses to consider in patients with symptoms suggestive of giant cell arteritis include:7,
- Migraine, intracranial haemorrhage and other causes of headache
- Herpes zoster
- Ear, nose and throat conditions, e.g. temporomandibular joint disorder, sinusitis
- Transient ischaemic attack
- Connective tissue diseases
- Cervical spine disease, e.g. spondylosis, radiculopathy causing cervicogenic headaches
- Other causes of acute visual loss, e.g. central retinal artery occlusion, non-arteritic ischaemic optic neuropathy
- Systemic vasculitides, e.g. Takayasu’s arteritis (rare)
- Other significant intracranial pathology, e.g. infiltrative retro-orbital or skull lesions
The management of giant cell arteritis
If the findings from the history and examination strongly indicate giant cell arteritis, after considering possible
differential diagnoses, urgent treatment and referral should be initiated. The first steps for most patients should be
to provide a prescription for corticosteroids and to contact either an Ophthalmologist or Rheumatologist (depending on
local referral criteria) to organise a temporal artery biopsy.
Organise a referral for biopsy
Urgent referral, i.e. within one week, to hospital for biopsy and an assessment of vision is required.12 If
the patient has symptoms of ischaemia, such as visual loss or diplopia, with or without jaw claudication, immediate referral
is recommended as these features can indicate the rapid development of permanent visual loss.
The need for biopsy should never delay treatment. A biopsy can usually still be performed and provide accurate results
two to six weeks after initiating corticosteroid treatment,12 although it should ideally be performed within
Most guidelines recommend oral prednisone 40 – 60 mg, once daily, for patients with giant cell arteritis, with the higher
dose used in patients with ischaemic symptoms.2, 12 In practice, as it can be difficult to rule out the presence
of ischaemic involvement in primary care, a dose of 60 mg, once daily, should be used in most patients with suspected
giant cell arteritis, and if necessary this can be adjusted once the patient has been assessed in secondary care. It is
recommended that the prednisone dose is not less than 0.75 mg/kg, therefore a higher dose, e.g. up to 80 mg, may be given
to a larger patient.
For patients who already have visual loss symptoms, consult with the Ophthalmologist or Rheumatologist about the possibility
of intravenous corticosteroid treatment. Methylprednisolone (e.g. 1 g IV, daily, for three days) may be used in patients
with visual loss at presentation or rapidly developing visual symptoms in order to halt their progression, however, evidence
that this approach to treatment is more effective is limited.
The first dose of prednisone should be taken as soon as reasonably possible. The response to treatment is usually rapid,
with resolution of most symptoms occuring within several days of starting the medicine. Therefore, a lack of response
is a strong indication that the initial diagnosis may have been incorrect.12
The initial dose of prednisone should be maintained for four weeks, or longer if symptoms and laboratory abnormalities
remain.12 Given the significant risk of morbidity associated with a relapse of giant cell arteritis, the prednisone
tapering regimen must be slow and cautious. Dose reduction intervals can be lengthened, based on the patient’s symptoms
and history of relapses with previous dose reductions. A treatment duration of at least one to two years, often longer,
should be expected.
As a general guide, the British Society for Rheumatology suggests that the daily dose of prednisone is tapered as follows:2
- Maintain the inital dose (40 – 60 mg) for at least four weeks, then;
- Reduce by 10 mg, every two weeks, down to 20 mg, then;
- Reduce by 2.5 mg, every two to four weeks, to 10 mg, then;
- Reduce by 1 mg, every four to eight weeks, provided there are no relapses
For further information on tapering long-term corticosteroids and adverse effects,
see "Polymyalgia rheumatica"
Aspirin, 100 mg, daily,* should be considered for patients without contraindications as there is some evidence that
it decreases the rate of visual loss and other cerebrovascular complications.2, 12
Vitamin D supplements and advice to maintain adequate calcium intake should be given to all patients in order to limit
the adverse effects of long-term prednisone treatement.13 Bisphosphonates should be prescribed to all patients
with evidence of reduced bone-mineral density.5
For further information on the bone sparing treatment in people treated with long-term
corticosteroids, see "Polymyalgia rheumatica".
A proton pump inhibitor (PPI), such as omeprazole may be considered for people who experience adverse gastrointestinal
affects when taking prednisone, particularly when a NSAID is taken concurrently.13
* Most guidelines recommend 75 mg daily, however, this dose formulation is not subsidised in New Zealand.
Follow-up and monitoring
A follow-up consultation should be scheduled to ensure there are no signs or symptoms of relapse of giant cell arteritis,
and to monitor the adverse effects of corticosteroid treatment. The first follow-up appointment should be scheduled within
a few days of the inital consultation. Further follow-ups should be scheduled one, three and six weeks later.12 Follow-up
appointments should then occur once every three months, for the duration of corticosteroid treatment.12
Advise the patient to return if symptoms of giant cell arteritis or corticosteroid-related adverse effects occur between
Each visit should include an assessment for any residual symptoms, a brief physical examination of the patient and consideration
given to testing:2, 7
- HbA1c (fasting serum glucose should be used for the first two months of treatment, as the rise
in blood glucose levels due to corticosteroid use is too rapid to be accurately measured with HbA1c)
- Creatinine and electrolytes (to monitior the potential adverse effects of steroid treatment)
If CRP was normal, and ESR raised, when giant cell arteritis was diagnosed, monitoring ESR instead of CRP may be more
Chest x-ray and abdominal ultrasound to assess for thoracic and abdominal aortic aneurysm is recommended annually, and
usually for at least ten years.2 Assessment of bone mineral density (to monitor the adverse effects of corticosteroid
treatment) should also be considered,2 however, regular bone mineral scans may not be available in all areas
of New Zealand.
Relapse is common in people with giant cell arteritis
Relapse of symptoms is relatively common in people with giant cell arteritis, particularly once the dose of prednisone
is low, e.g. under 15 mg per day. Relapse should be suspected in patients with a return of symptoms, ischaemic complications,
unexplained fever or polymyalgic symptoms.2 Relapse is managed by increasing the dose of prednisone (Table
If patients have three or more relapses or the dose of prednisone is unable to be tapered without complications, discuss
with an Ophthalmologist or Rheumatologist. In some cases, adjunctive treatments such as methotrexate may be considered.
For further information on the use of methotrexate, see "Polymyalgia
Table 1: The signs of potential relapse of giant cell arteritis and recommended treatment12
|A giant cell arteritis-suggestive headache
||Treat with the previous dose of prednisone, i.e. if the dose is lowered to 10 mg daily, and headaches occur, move
dose back to 12.5 mg daily
|Jaw claudication, with or without headache
||Return to 60 mg daily, and begin taper again
||Treat with 60 mg prednisone and arrange ophthalmology referral
Prognosis for people with giant cell arteritis
The majority of patients respond rapidly to the initial treatment with prednisone, and visual loss in treated patients
(without preceding visual symptoms) is rare, generally under 1%.2,7 A treatment course of two to three years
is often necessary, with some patients requiring low-dose prednisone for several years thereafter.2 Corticosteroid-related
adverse effects are therefore common, occurring in approximately 60% of patients.7 Major risks include the
development of diabetes mellitus and osteoporotic fractures.2 Patients should be informed of these adverse
effects and may need to be advised to make lifestyle changes to lower their risk of these complications.
The mortality rate of people with giant cell arteritis is not significantly different from the general population.7 However,
the risk of aortic aneurysm is reported to be 17 times greater in people who have had giant cell arteritis, when compared
to the general population of the same age and sex, even after timely and successful treatment.7 Annual monitoring
with chest x-ray and ultrasound, and the management of modifiable risk factors, such as hypertension, smoking and central
obesity, will help to reduce this risk.
Thank you to Dr Logan Mitchell, Consultant Ophthalmologist, Dunedin Hospital, Senior Lecturer, Dunedin
School of Medicine, University of Otago and Associate Professor Andrew Harrison, Rheumatologist, Clinical
Head of Department, Wellington Regional Rheumatology Unit and Wellington School of Medicine, University of Otago, Wellington
for expert review of this article.