GM 2013, April  

Dr Upul Fernando ST7 Geriatric medicine, Walsall Manor Hospital

Dr Elliot Epstein Consultant Physician, Walsall Manor Hospital






The aetiology of giant cell arteritis (GCA) is unknown; however, observations show that increasing age, genetic and ethnic background and infection may have causative roles.6  Interestingly, the cyclic occurrences of GCA, with peak incidence rates every seven years, suggest a possible infectious cause or triggering event.7 An association has been made between GCA and infection with parvovirus B19.8

The humoral and cellular immune systems have been implicated in the pathogenesis of GCA.6 The production of cytokines, in particular interleukin (IL)-6, closely correlates with disease activity.9

An unknown initial factor or antigen initiates immune reactions causing inflammation of large and medium sized blood vessels.  This, in turn, causes intimal thickening and thrombosis at the sites of active inflammation. These inflammatory lesions tend to involve arteries in a
patchy fashion.3,6


The disease almost never occurs before age 50 years and its incidence rises steadily thereafter with peak incidence between age 70 and 80 years.3 An American study has shown that the incidence in the community is 17.8 cases per 100,000 persons.10 Evidence suggest, that the incidence increases with increasing latitude with the highest incidence in Scandavian countries.11

Clinical manifestations

Usually the onset of symptoms in GCA tends to be gradual, but abrupt presentations occur in some patients.3,5,12 Patients can present with non-specific or systemic symptoms including fever, fatigue, and weight loss. Fever may be the presenting feature.13 The main symptom of GCA is headache, located in temporal regions and some patients may complain of scalp tenderness and pain on combing hair.5 Less commonly the headache is in the occipital region and approximately one third of patients report no headache.5

Other features of GCA include jaw claudication, witnessed in nearly 50% of patients14 and  tongue claudication. Certain patients experience visual symptoms that may be described as “mistiness” of vision, transient loss of vision (ameurosis fugax) or visual loss in part of the visual field. Visual symptoms in one eye may progress to involve the second eye and permanent blindness may result. In patients with transient or progressive visual loss, urgent treatment is essential to prevent permanent visual loss.3,14

Approximately 50–70% of patients with GCA have associated polymyalgia rheumatica (PMR) and may complain of aching and morning stiffness in the shoulder and hip girdles, neck, and torso.3 In about 10% of cases, the subclavian and axillary arteries can become sufficiently narrowed to produce arm claudication, bruits and diminished or absent pulses.15-17 Rare manifestations include transient ischaemic attack, stroke, polyneuropathy, mononeuropathy and coronary artery involvement leading to myocardial infarction. Thoracic aneurysm may occur several years after initial presentation as a
late complication.18

On examination, the temporal artery may be prominent, beaded, tender, pulseless and may occasionally demonstrate an erythematous appearance. In patients with acute visual loss from acute ischaemic optic neuritis (AION), fundoscopic examination shows changes of a swollen pale disc and blurred margins.13 In patients with PMR, active range of motion of the shoulders, neck, and hips is limited due to pain and local tenderness may be present on examination.


Important initial investigations include full blood count, biochemical profile and inflammatory markers (ESR and CRP).  In most patients with GCA the erythrocyte sedimentation rate (ESR) is elevated, often exceeding 100mm/h; however, values of less than 40mm/h or within the normal range do not exclude the diagnosis.19 Normochromic normocytic anaemia and mild derangement of liver function tests are frequently present.5

If there is sufficient suspicion of GCA based upon the history, physical examination and laboratory features, a temporal artery biopsy should be performed. Temporal artery biopsies are generally obtained on an outpatient basis under local anaesthesia. Negative temporal artery biopsy occurs in up to 10–30% of patients with suspected GCA mainly due to skip lesions.3,5 Timing of temporal artery biopsy should never interfere with the start of treatment in a patient with a high likelihood of GCA, since the inflammatory infiltrate remains present two to six weeks after treatment.1

Although Doppler ultrasonography has been studied,3 this technique is highly operator-dependent and does not replace temporal artery biopsy as the gold standard for diagnosis.

Differential diagnosis

Giant cell arteritis may present with symptoms of a non-specific nature hence may mimic several other conditions (box 2). GCA usually responds rapidly to steroids; therefore, failure to respond should prompt the physician to consider an alternative diagnosis such as underlying malignancy. Elevated ESR has many causes including multiple myeloma, tuberculosis and connective tissue disease. Headaches may be caused by many conditions such as cervical spine disease, space occupying lesion and migraine. Visual loss may be caused by transient ischaemic attacks and the neurological manifestations of GCA, such as hemiparesis, may mimic stroke. The physician may require a high index of suspicion to diagnose GCA.


Glucocorticoid treatment should be started promptly once the diagnosis of GCA is strongly suspected, even before it is confirmed.1-2 A temporal artery biopsy should be obtained as soon as possible, but treatment should not be withheld or delayed whilst awaiting the performance or the results of the biopsy.1-2 If the temporal biopsies reveal no evidence of arteritis but clinical suspicion of GCA remains strong, glucocorticoid treatment should

In the setting of evolving visual loss or transient visual loss (eg. amaurosis fugax), guidelines recommend high-dose parenteral glucocorticoid therapy (methylprednisolone) in the hope of preventing further acute disease complications (1000mg intravenously each day for three days.1-2 This is then followed by oral prednisolone 60mg/day.

In cases of uncomplicated GCA, an initial dose of 40–60mg of prednisolone is appropriate.1-2

Glucocorticoid tapering can begin once the disease has been controlled adequately. In general, practitioners may reduce prednisolone by 10mg every two weeks to reach a dose of 20mg per day.1-2 Subsequently, prednisolone may be reduced by 2.5mg every 2-4 weeks to 10mg. After reaching a daily prednisone dose of 10mg, further tapering of 1mg every one to two months decrements is appropriate. Disease activity should be carefully monitored, guided by the patient’s symptoms and inflammatory markers (ESR and CRP). Relapse of disease may necessitate increase in the dose
of steroids.

The recommended duration of corticosteroid therapy is controversial. In many cases treatment should be tapered over the course of 18–24 months.3,5

Low dose aspirin should be considered in all patients with GCA, provided no contra-indications exist, since it has been shown to reduce the rate of visual loss and cerebrovascular accidents in GCA.20 Patients with GCA are susceptible to corticosteroid induced osteoporosis hence it is important to consider bone protection in the form of a bisphosphonate with calcium/vitamin D.1-2 The medical practitioner may consider prescribing a proton pump inhibitor for the purpose of gastro protection.1-2

In recurrent or resistant GCA, methotrexate or other immunosuppressives (eg azathioprine or leflunomide) may be used as adjuvant therapy to allow reduction in the cumulative glucocorticosteroid dose. 1-2

Conflict of interest: none declared



1    Giant Cell Arteritis Guideline Development Group. Concise guidance: diagnosis and management of giant cell arteritis. London: Royal College of Physicians, 2010. Accessed 20th October 2012.

2.   BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatology. 2010; 49(8): 1594–97

3    Salvarni C, Cantini F, Boiarda L, Hunder GG. Polymyalgia Rheumatica and Giant Cell Arteritis. NEJM 2002; 347: 261–71

4    Hellmann DB, Hunder GG. Giant cell arteritis and polymyalgia rheumatica. In: Harris ED, Budd RC, Firestein GS, Genovese MC, et al Kelley’s Textbook of Rheumatology, 7th Edition. Philadelphia: WB Saunders Company, 2005

5    Hazelman BL. Polymyalgia rheumatic and giant cell arteritis. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH. Rheumatology. Third Edition. Edinburgh: Mosby, 2003

6.   Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med 2003; 349: 160–69

7    Salvarani C, Gabriel SE, O’Fallon WM, Hunder GG. The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern. Ann Intern Med 1995; 123(3): 192.

8.   Gabriel SE, Espy M, Erdman DD, et al. The role of parvovirus B19 in the pathogenesis of giant cell arteritis: a preliminary evaluation. Arthritis Rheum 1999; 42: 1255–8

9    Weyand CM, Fulbright JW, Hunder GG, Evans JM, Goronzy JI. Treatment of giant cell arteritis: interleukin-6 as a biologic marker of disease activity. Arthritis Rheum 2000; 43(5):

10. Salvarani C, Gabriel SE, O’Fallon WM, Hunder GG. The incidence of giant cell arteritis in Olmsted County, Minnesota: apparent fluctuations in a cyclic pattern. Ann Intern Med 1995; 123(3): 192

11. Watts RA. The Epidemiology of Giant Cell Arteritis. Rheumatology. 2005;

      (Suppl 3) 44Pp iii2 doi: 10.1093/rheumatology/keh729 (accessed 21st October 2012)

12. Salvarani C Cantini F, Hunder GG. Polymyalgia rheumatic and giant cell arteritis. Lancet 2008; 372: 234-45

13. Calamia KT Hunder GG. Giant cell arteritis (temporal arteritis) presenting as fever of undetermined origin. Arthritis Rheum 1881; 24: 1414–18

14 Calamia KT, Hunder GG. Clinical manifestations of giant cell arteritis. Clin Rheum Dis 1980; 6: 389–403

15. Klein RG, Hunder GG, Stanson AW, Sheps SG. Large artery involvement in giant cell (temporal) arteritis. Ann Intern Med 1975; 83: 806–12

16. Brack A, Martinez-Taboada V, Stanson A, et al. Disease pattern in cranial and large-vessel giant cell arteritis. Arthritis Rheum 1999; 42 : 311–7

17. 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 2003; 48: 3522-31

18 Salvarani C, Hunder GG. Giant cell arteritis with low erythrocyte sedimentation rate: frequency of occurence in a population-based study 2001; 45: 140–45

19 Hunder GG, Bloch DA, Michel BA, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum 1990; 33: 1122–28

20. Nesher G, Berkun Y,Mates M et al. Low-dose aspirin and prevention of cranial ischemic complications in giant cell arteritis. Arthritis Rheum 2004; 50: 1332–37