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Giant Cell (Temporal) Arteritis

Essentials

  • 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 at 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 of the ophthalmic artery and its branches.
  • The aortic arch and the large vessels emerging from it may also 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 women. It is encountered almost exclusively in patients over 50 years of age. Peak incidence is at the age of 70.

Symptoms

  • Giant cell arteritis may cause many kinds of symptoms but the most common symptoms are headaches, tenderness to touch over the temple, visual disturbances and general symptoms (such as fatigue, fever).
  • Severe headache not experienced earlier or presenting with new features, most typically localized in one or both temples
    • The headache is stabbing or sometimes throbbing.
    • It is typically constant and often particularly severe at night.
    • Paroxysmal headaches are not typical of giant cell arteritis.
  • The scalp is tender to touch at the temples and often more extensively.
  • 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.
    • The most common cause of visual disturbances detected in ophthalmological examination by a specialist is anterior ischaemic optic neuropathy (AION; in 80-90%).
  • General symptoms, such as fatigue, weight loss, loss of appetite, fever and depression are common and may predominate the clinical picture.
    • Prolonged fever may be the first and only symptom of giant cell arteritis.
  • Polymyalgic symptoms, i.e. pain and stiffness in the shoulder, hip and neck regions (in about 50%).
  • Inflammation in vertebral arteries may lead to vertigo, tinnitus and, very rarely, even rapidly progressing sensorineural hearing loss. Inflammation in vertebral arteries may also lead to a cerebrovascular disorder, most typically appearing as a posterior circulation cerebral infarction.
  • Inflammation in the subclavian, carotid and brachial arteries may lead to aortic arch syndrome that presents with disturbances in the cerebral blood circulation or with upper extremity claudication.
  • In some cases, active giant cell arteritis may involve other ischaemic symptoms such as claudication in the lower extremities, abdominal pain (intestinal ischaemia), angina pectoris or myocardial infarction.

Findings

  • Swelling, erythema, nodularity, tenderness, weak or absent pulse over the temporal artery or other superficial artery of the head (facial or occipital artery)
  • Visual signs and symptoms
    • Impaired vision, scotomata
    • Diplopia
    • At ophthalmoscopy, papilloedema and paleness of the optic papilla 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

  • If giant cell arteritis is suspected based on patient history and status, and the patient has jaw claudication, visual or other ischaemic symptoms, the patient should be referred to specialized care for emergency assessment, primarily to emergency services for internal diseases or, in the case of acute loss of vision and in the absence of other symptoms, to emergency services for eye diseases.
  • Otherwise, the patient can be examined in primary health care and referred for assessment in internal medicine or rheumatology within 1-7 days.
  • The diagnosis of giant cell arteritis is based on the clinical picture, laboratory test findings and imaging studies, as well as on temporal artery biopsy.
    • If a diagnosis can be made by imaging, temporal artery biopsy is not necessary.

Investigations in primary health care

  • In suspected giant cell arteritis, ESR, CRP, basic blood count with platelet count, ALP, ALT, plasma creatinine and chemical screening of urine
  • ESR is usually elevated, at least 40 mm/h, often close to 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 above 10 but often clearly higher, 75 on average. CRP is normal in only 3% of patients. 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

  • Doppler ultrasonography of the temporal and axillary arteries is the primary diagnostic imaging method.
    • Performing the ultrasonography requires sufficient expertise and experience. According to local practice, the examination can be performed either by a rheumatologist or by a radiologist with expertise in ultrasound imaging of temporal arteries.
  • The typical finding in arterial ultrasonography is a hypoechoic ring around the vessel lumen, the halo sign, which is caused by an oedematous fluid-containing arterial wall.
    • The examination can be supplemented with the compression test: when pressing the vessel with the probe, a normal artery can be easily occluded, but an inflamed arterial wall remains visible as a hypoechoic oval structure.
    • In the areas of the common temporal artery and its parietal and frontal branches, wall thicknesses exceeding 0.42 mm and 0.3 mm, respectively, are considered pathological.
    • In axillary arteries, the halo phenomenon can be seen, and a thickened (> 1 mm) arterial wall is often visible even in grey scale imaging.
    • It is recommended that both temporal arteries be examined, including the parietal and frontal branches and the axillary arteries.
  • If doppler ultrasonography findings are typical of giant cell arteritis, and the patient has symptoms typical of the disease, 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 glucocorticoid therapy already started (see here below) should be continued and a temporal artery biopsy should be performed within 2 weeks (if possible).
    • If the clinical suspicion is weak and the ultrasonography finding negative, the glucocorticoid therapy can be discontinued without further investigations.
  • Positron emission tomography (PET-CT) is the primary imaging method if ultrasonography is not available or yields inconclusive results.
    • PET-CT is useful, particularly if inflammation of the aorta or its main branches is suspected.
  • Although clearly less sensitive, magnetic resonance angiography can also be used if ultrasonography or PET-CT are not available.
  • The sensitivity of all imaging methods clearly decreases already after 3 days of glucocorticoid treatment. Nevertheless, in case of strong suspicion imaging must not delay the beginning of treatment.
  • In some patients, the arterial wall remains chronically thick despite effective and successful treatment. So far, there are limited data available on the usefulness of routine follow-up of imaging findings during treatment.

Temporal artery biopsy

  • Temporal artery biopsy is recommended if the diagnosis cannot be confirmed by imaging.
  • 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 1-2 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.
    • As the sensitivity of temporal artery biopsy is 50-60% only, a negative biopsy finding does not exclude the possibility of arteritis.
  • Biopsy should be taken within a few days of giant cell arteritis first being suspected and the start of treatment. However, a two-week glucocorticoid treatment would not yet significantly impede the interpretation of the biopsy.

Treatment

  • High-dose glucocorticoid therapy with prednisolone (or prednisone) 40-60 mg/day should be started without delay when, based on symptoms and clinical assessment, giant cell arteritis is first suspected.
    • High doses, e.g. methylprednisolone 0.5-1 g i.v. on three consecutive days, are given especially if the patient has had acute loss of vision or amaurosis fugax or if they are diagnosed with cerebral infarction due to giant cell arteritis.
  • Symptoms will be alleviated and laboratory findings are normalized within a few weeks, after which the dose of glucocorticoid can be reduced.
    • Headache will be relieved within a few days.
    • Temporary and partial visual disturbances are often reversible, total loss of vision is irreversible.
    • Inflammatory changes in the arterial walls clearly disappear more slowly.
  • The dose of prednisolone or prednisone in further treatment is based on the clinical response and laboratory parameters.
    • The glucocorticoid should be given for at least 1 year, typically 1.5 to 2 years.
    • If prednisolone is combined with tocilizumab (see below), the glucocorticoid can be tapered off within 6 months.
  • If a glucocorticoid is used alone, the dose can be reduced according to the following schedule, for example.
    • The initial dose of 40-60 mg/day is continued until the symptoms subside and the abnormal inflammatory markers are corrected but always for at least 2 to 4 weeks.
    • The dose is then reduced by 10 mg every 2 weeks until the dose is 20 mg/day.
    • After this the dose is reduced by 2.5 mg every 2 to 4 weeks until the dose is 10 mg/day.
    • Finally, the dose is reduced by 2.5 mg at about 3-month intervals, provided the disease does not recur.
    • The risks of the disease and of the treatment should be evaluated patient by patient, and the dose reduction should be carried out individually.
  • Tocilizumab (an interleukin-6 inhibitor) Tocilizumab for Giant Cell Arteritis increases the number of permanent remissions and reduces the need for glucocorticoids.
    • Check local reimbursement policy. Special indications may include a history of sustained serious adverse effects from glucocorticoids or a high risk of such effects (such as osteoporosis, diabetes, cardiovascular diseases, glaucoma). Tocilizumab should also be considered in patients with refractory disease or in those whose disease is prone to reactivation.
    • Tocilizumab should be combined with a glucocorticoid for at least 6 months from diagnosis because with tocilizumab alone, the risk of disease reactivation is higher, and there is insufficient evidence for IL-6 inhibition reducing the risk of visual loss.
  • A combination of methotrexate and glucocorticoids can be considered if the latter involve particular risks for the patient, such as diabetes or osteoporosis, or if the dose of the glucocorticoid cannot be reduced according to plan and treatment is clearly prolonged.
    • There is little scientific evidence for the benefit of using methotrexate in the treatment of giant cell arteritis.
  • Due to an increased risk of bleeding, aspirin or anticoagulants are not routinely recommended unless there are other indications for their use.
  • Statins are only recommended if there is another indication for this, such as coronary artery disease.

Prevention of glucocorticoid-induced adverse effects Bisphosphonates for Steroid Induced Osteoporosis

Follow-up

  • Treatment aims at remission (having no symptoms and calming down of systemic inflammation).
  • During follow-up, attention should be paid to symptoms suggesting recurrence of the disease, complications and on adverse effects of glucocorticoid treatment Pharmacological Glucocorticoid Treatment.
  • Follow-up is initially carried out in specialized care and continued with collaboration between specialized and primary health care.
  • The laboratory tests to be monitored include ESR, CRP, basic blood count with platelet count, plasma creatinine, blood glucose, HbA1c, lipids and electrolytes.
    • Tocilizumab effectively prevents CRP levels increasing. In association with treatment with tocilizumab, CRP is unreliable in assessing response to treatment.
  • 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 if the disease recurs.
    • In the context of an increase in CRP levels, the possibility of an infection should be assessed before intensifying glucocorticoid therapy.
    • Specialized care should be consulted for treatment of relapse.

Prognosis

  • The inflammatory process of arteritis usually gradually subsides within 1-2 years, and in most patients all medication can be withdrawn.
  • Reactivation of the disease is very common when glucocorticoid doses are reduced. An average of one in two patients with giant cell arteritis have at least one relapse requiring intensification of treatment during the follow-up period.
    • A relapse may occur even after medication has been withdrawn.
  • It is important that the physician treating the patient is aware of the disease, otherwise, the symptoms may be attributed to arteriosclerosis.
  • If despite effective medication an aortic aneurysm, for example, develops, endovascular/surgical treatment may be required. This is carried out at the remission stage of the disease, with the exception of acute situations, such as aortic dissection.

    References

    • Dejaco C, Ramiro S, Bond M, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice: 2023 update. Ann Rheum Dis 2024;83(6):741-751 [PubMed]
    • Dejaco C, Kerschbaumer A, Aletaha D, et al. Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica. Ann Rheum Dis 2024;83(1):48-57 [PubMed]
    • Kauppi M, Karjalainen A, Pirilä L, et al. (Eds.). [Rheumatic diseases]. Duodecim Publishing Company Ltd, 2023.
    • Galli E, Muratore F, Boiardi L, et al. Significance of inflammation restricted to adventitial/periadventitial tissue on temporal artery biopsy. Semin Arthritis Rheum 2020;50(5):1064-1072 [PubMed]
    • Schäfer VS, Juche A, Ramiro S, et al. Ultrasound cut-off values for intima-media thickness of temporal, facial and axillary arteries in giant cell arteritis. Rheumatology (Oxford) 2017;56(9):1479-1483 [PubMed]
    • Stone JH, Tuckwell K, Dimonaco S ym. Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med 2017;377(4):317-328. [PubMed]
    • Salvarani C, Muratore F. Diagnosis of giant cell arteritis. In: UpToDate, Connor RF (Ed), Wolters Kluwer (viitattu 9.9.2024). Saatavilla internetissä: http://www.uptodate.com/contents/diagnosis-of-giant-cell-arteritis (vaatii käyttäjätunnuksen).