Remember the possibility of giant cell arteritis as a cause of headache, visual disturbances and disturbances in brain circulation.
Serious complications, such as loss of vision, have to be prevented.
A patient with suspected giant cell arteritis is referred to specialized care without delay, on an emergency basis if he/she has visual disturbances or other ischaemic complications.
General remarks
Giant cell arteritis (earlier temporal arteritis) is an inflammation in the walls of large and middle-sized arteries, usually affecting the external carotid artery and the extracranial branches of the internal carotid artery.
At least half of patients with giant cell arteritis have polymyalgia rheumatica Polymyalgia Rheumatica during some stage of the disease.
The disease usually starts insidiously, but an abrupt ischaemic event, e.g. loss of vision, may be the initial symptom.
Giant cell arteritis must be diagnosed and treated rapidly because of visual disturbances. Most visual disturbances are caused by inflammation and consequent ischaemia in arteria ophthalmica and its branches. Also the aorta and the big vessels emerging from the aorta may become affected. Neurological deficiency symptoms caused by brain infarction may develop.
The aetiology is unknown. Advanced age is the greatest risk factor.
Epidemiology
The incidence of giant cell arteritis is 170-240 cases per million people.
The disease is more common in females. It is encountered almost solely in patients over 50 years of age. Peak incidence is among 70-year-olds.
Symptoms
Severe headache not experienced earlier or presenting with new features, most typically localized in one or both temples, stabbing or sometimes throbbing, temporal tenderness of the scalp.
Masseter claudication (pain in the jaw provocated by chewing, stiffness of the masseter muscles), pain in the tongue and during swallowing. A gangrene may develop in the tongue.
Visual disturbances: partial or total, temporary or permanent, loss of vision in one or both eyes, double vision, scintillating cloud, scotomata, cortical blindness.
Temporary visual disturbances resemble amaurosis fugax and migraine.
Hearing loss, vertigo and tinnitus
Inflammation in the vertebral arteries may lead to transient stroke syndrome and vertigo.
Inflammation in the subclavian, carotid and brachial arteries may lead to the aortic arch syndrome that presents with disturbances in the cerebral blood circulation or with upper extremity claudication.
Claudication in the lower extremities, abdominal pain (intestinal ischaemia), angina pectoris and myocardial infarction
Polymyalgic symptoms, i.e. pain and stiffness in the shoulder, hip and neck regions (in about 50%).
General symptoms, i.e. fatigue, weight loss, loss of appetite, fever and depression are common and may predominate the clinical picture. Fever may be the first and only symptom of giant cell arteritis.
Clinical signs
Swelling, tenderness, nodularity, weak or absent pulse over the temporal artery or other superficial artery of the head (facial or occipital artery)
Visual signs
Blurred vision, scotomata
Diplopia
At ophthalmoscopy, swelling and paleness of the optic nerve may be observed, if the lesion is in the anterior part of the nerve.
Bleeding or paleness of the retina in case of occlusion.
In the aortic arch syndrome: asymmetric pulse or pulselessness and blood pressure gradient between upper limbs, bruits in large arteries
Inflammation of the aorta may lead to aortic dilatation, aneurysm formation and aortic regurgitation.
Diagnosis
The diagnosis of giant cell arteritis is based on the clinical picture, findings in laboratory examinations and imaging studies, as well as on temporal artery biopsy.
Temporal artery Doppler ultrasonography has become central when suspecting giant cell arteritis, but temporal artery biopsy still has an important role.
There are good experiences concerning so-called fast-track outpatient clinics whereby the aim is to assess the patient within 24 hours in specialized care and especially by Doppler ultrasonography.
Laboratory investigations
In suspected giant cell arteritis, the recommended laboratory investigations in primary health care include ESR, CRP and basic blood count with platelet count.
ESR is usually elevated, at least 40 mm/h, often > 100 mm/h (normal in 1-2% of patients). ESR is a good screening test when giant cell arteritis is suspected as the cause of headache.
Plasma CRP is nearly always markedly increased. CRP is a more sensitive indicator of disease activity than ESR.
Mild to moderate normocytic anaemia as well as thrombocytosis are common.
Plasma alkaline phosphatase may be increased.
Imaging
The role of imaging and especially temporal artery Doppler ultrasonography in diagnostics has grown in recent years.
Performing the ultrasonography requires sufficient expertise and experience.
The typical finding in the arterial ultrasonography is a hypoechoic ring around the vessel lumen, the halo sign, which is caused by oedematous arterial wall.
The examination can be supplemented with the compression test: when applying pressure on the vessel, a normal artery can be easily occluded by pressure, but an inflamed arterial wall remains visible as a hypoechoic oval structure.
It is recommended to examine both temporal arteries, including the parietal and frontal branches.
If the finding in the doppler ultrasonography is typical for giant cell arteritis, the diagnosis can be made without temporal artery biopsy.
If the ultrasonography finding is negative or inconclusive, but giant cell arteritis is clinically suspected, the already started glucocorticoid therapy is continued and a temporal artery biopsy should be performed within (if possible) 2 weeks.
If the clinical suspicion is weak and the ultrasonography finding negative, the glucocorticoid therapy can be discontinued without further investigations.
MR angiography, CT angiography as well as PET scanning are useful methods when inflammation of aorta and its main branches is suspected. In this case the finding in temporal artery biopsy may be negative in up to 40% of patients.
Temporal artery biopsy
Temporal artery biopsy (video Temporal Artery Biopsy) is an outpatient procedure but requires prior training.
The biopsy should be taken from the part of the artery with most pathological changes. Because the changes in the arterial walls are segmental, a sufficient length of the artery (at least 2-3 cm) should be extirpated for examination.
Biopsy may show changes suggesting arteritis even if the patient has no headache and the temporal artery is not tender on palpation.
A negative biopsy finding does not exclude the possibility of an arteritis. If the clinical signs strongly suggest the diagnosis, biopsy from the other side may be considered if the finding is negative.
In case of severe symptoms, like visual disturbances, treatment is started already before the biopsy, which preferably should be taken within a few days. However, a two-week glucocorticoid treatment does not yet significantly impede the interpretation of the biopsy.
High-dose glucocorticoid therapy with prednisolone (or prednisone) 40-60 mg/day should be started without delay when, based on symptoms and clinical assessment, suspicion of giant cell arteritis has arisen.
High doses, e.g. methylprednisolone0.25-1 g i.v. on three consecutive days, are given especially if the patient has had visual disturbances.
Symptoms alleviate and laboratory findings are normalized within a few weeks after which the dose of predniso(lo)ne is tapered gradually.
Headache is relieved within a few days.
Temporary and partial visual disturbances often disappear, total loss of vision is irreversible.
Inflammatory changes in the arterial walls disappear clearly slower.
The dose of prednisolone or prednisone in further treatment is based on the clinical response and laboratory parameters. The dosage can be gradually reduced e.g. according to the following schedule:
The initial dose of 40-80 mg/day is continued until the symptoms and the abnormal inflammatory markers are corrected (at least 3 to 4 weeks).
The dose is then reduced 10 mg every 2 weeks until the dose is 20 mg/day.
After this the dose reduction is 2.5 mg every 2 to 4 weeks until the dose is 10 mg/day.
Finally, the dose reduction is 2.5 mg at about 3-month intervals, provided the disease does not recur.
The risks of the disease and of the treatment are evaluated patient-by-patient, and the dose reduction is carried out individually.
The overall duration of treatment is 1½ years on the average, but some patients have a chronic or repeatedly recurring disease and they require glucocorticoids for several years or even permanently.
If the response to glucocorticoid is insufficient or if the drug is harmful (osteoporosis, diabetes), methotrexate or azathioprine can be added to it. Methotrexate may help in reducing the glucocorticoid dose.
The role of biological drugs in the treatment is growing. Inhibition of interleukin-6 with tocilizumab increases the rate of permanent remissions and enables reduction of glucocorticoid doseTocilizumab for Giant Cell Arteritis.
Find out about local policies concerning reimbursement of tocilizumab.
The available evidence on the effect of interleukin-6 inhibition in reducing the risk of visual loss is insufficient. Therefore, whenever there is a risk of visual loss in new or recurring disease, high-dose glucocorticoid should be included in the treatment alongside an IL-6 inhibitor.
The benefit of prophylactic use of aspirin in giant cell arteritis is uncertain. Due to increased risk of bleeding, its routine use is no longer recommended, unless it is already earlier indicated because of the patient's cardiovascular disease.
Elderly patients on long-term glucocorticoids are prone to complications caused by the treatment Pharmacological Glucocorticoid Treatment. Therefore, a properly confirmed diagnosis of giant cell arteritis is important.
Prophylactic therapy for osteoporosis is started when the decision about glucocorticoid treatment is made.
See Osteoporosis and local recommendations concerning osteporosis.
As the patients are aged and the estimated duration of glucocorticoid treatment is long, bone-protection medication with a bisphosphonate or some other specific anti-osteoporotic drug is in practice almost always indicated as well.
Withdrawal of the anti-osteoporotic drug can be considered when the glucocorticoid treatment is terminated.
Follow-up
During follow-up, attention is paid on symptoms suggesting recurrence of the disease, on complications and on adverse effects of glucocorticoid treatment.
Follow-up is initially carried out in specialized care and continued in cooperation between specialized and primary health care.
The laboratory tests to be monitored include ESR, CRP, basic blood count, creatinine, blood glucose and electrolytes.
Recurrence of giant cell arteritis should be suspected if the symptoms should reappear and ischaemic complications, fever of unknown origin or symptoms of polymyalgia should arise. ESR and CRP are usually increased as the disease recurs.
Prognosis
The inflammatory process of arteritis usually subsides within months or years, but relapses occur even after many years.
Symptoms may flare when glucocorticoid therapy is tapered or stopped.
It is important that the physician treating the patient is aware of the disease, otherwise the symptoms can be assigned to arteriosclerosis.
References
Stone JH, Tuckwell K, Dimonaco S ym. Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med 2017;377(4):317-328. [PubMed]