Synonym: temporal arteritis, cranial arteritis
Giant cell arteritis (GCA) is a systemic immune-mediated vasculitis affecting medium-sized and large-sized arteries, particularly the carotid artery and its extracranial branches.
GCA can cause sudden and potentially bilateral vision loss in the elderly. Therefore it is considered a medical emergency and a significant cause of morbidity in an increasingly ageing population.
The aetiology is unknown but the pathogenesis involves a chronic inflammatory process, predominantly of large arteries.
The clinical connections between polymyalgia rheumatica (PMR) and GCA have suggested that they are different manifestations of the same disease process.
- GCA occurs in 2.2 per 10,000 patient years in the UK.
- The reported rates for GCA are highest in Northern European countries.
- Women are affected two to three times more often than men.
- Increased prevalence of PMR and GCA exists in individuals with a European background, and a decreased incidence and prevalence is noted in African Americans.
- Most patients with PMR or GCA present after their sixth decade and peak incidence occurs in patients aged 60-80 years.
- Genetic factors: PMR and GCA may aggregate in families.
GCA typically presents with recent onset of temporal headache, myalgia, malaise or fever. Typical features may be absent or subtle. GCA should be suspected in anyone over the age of 50 years with headache, scalp tenderness, transient visual symptoms or unexplained facial pain.
Acute severe sight impairment occurs in up to 20% of patients. Delay in diagnosis and treatment may explain the high incidence of irreversible loss of vision. Jaw or tongue claudication occurs in a minority of cases but indicates a high risk of ischaemic complications.
Symptoms moderately predictive of a positive biopsy result include:
- Jaw claudication (pain comes on gradually during chewing, whereas temporomandibular pain or dental pain is immediate).
- Any abnormality on palpation of the temporal artery (absent pulse, beaded, tender or enlarged).
Other useful predictive features include:
- Temporal headache.
- Scalp tenderness.
- ESR significantly elevated.
The history is usually short and the most common symptoms include:
- Headache: present in more than 85% of patients. It tends to be of recent onset, or represents a change in character from previous headaches. It is often in the temporal or occipital region and is described as severe by most patients. It may be worse at night.
- Scalp tenderness - may be pronounced, making simple tasks such as combing hair, or resting the head on a pillow extremely painful.
- Jaw claudication - particularly prominent when the patient is talking or eating; it is present in more than half of patients with GCA.
- Visual disturbances:
- Due to inflammation of the branches of the ophthalmic artery, leading to ischaemic optic neuritis.
- Occur in around 50% of cases.
- Central retinal artery thrombosis can also occur.
- Visual manifestations include blurred vision, amaurosis fugax, transient or permanent visual loss, or diplopia (due to third, fourth, or sixth cranial nerve palsy).
- These symptoms can occur in the absence of, or before the development of, headache.
- If GCA remains untreated, the second eye may become affected within 1-2 weeks.
- Systemic symptoms (similar to those of PMR) include: anorexia, weight loss, fever, sweats, malaise, fatigue and depression. About 50% of patients with GCA have features of PMR: proximal stiffness, soreness and pain.
- Thoracic aorta and aortic root involvement: occurs in about 15%. This is more common in women and younger patients. Thoracic aneurysms can develop as late as 15 years after the diagnosis and successful treatment of GCA.
- Occasionally, symptoms relate to intermittent or persistent brain ischaemia, due to a subclavian steal syndrome (SSS), narrowing of other aortic arch vessels or intracerebral vascular disease. About 1% of cases present with symptoms of brain stem stroke.
- GCA often involves the aorta and its major branches and may lead to aortic aneurysm/dissection as well as large artery stenoses. Some patients with large-vessel GCA, predominantly upper extremity arterial vasculitis, may have variable clinical presentations and diagnostic delay.
Examination may be normal but palpation of the temporal artery is often abnormal.
- There may be few signs but there is usually ocular and funduscopic evidence of ischaemic disease present in patients with symptoms of visual loss.
- Temporal arteries may be prominent, beaded, tender and pulseless but a normal appearance does not exclude the diagnosis.
- Bruits may be heard over the carotid, axillary, or brachial arteries.
- Patients may present with fever.
- Muscles and joints may be tender.
The American College of Rheumatology classification criteria for GCA:
- Age at disease onset: development of symptoms or findings beginning at the age of ≥50 years.
- New headache: new onset of or new type of localised pain in the head.
- Temporal artery abnormality: temporal artery tenderness to palpation or decreased pulsation, unrelated to arteriosclerosis of cervical arteries.
- Elevated ESR: ESR ≥50 mm/hour.
- Abnormal artery biopsy: biopsy specimen with artery showing vasculitis characterised by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells.
A patient is said to have GCA if at least three of these five criteria are present.
- Tension-type headache
- Trigeminal neuralgia
- Takayasu's arteritis
- Polyarteritis nodosa
Once GCA is suspected, patients should be referred urgently for temporal artery biopsy, which needs to be done within two weeks of starting steroids.
- Elevation in the acute phase reactants: 4% of patients have a normal ESR; 83% have a rate above 50 mm/hour. A normal ESR does not therefore exclude the diagnosis.
- CRP can sometimes be elevated in the presence of a normal ESR.
- Normocytic normochromic anaemia and thrombocytosis are common.
- Auto-antibody and complement levels are normal. Cryoglobulins and monoclonal immunoglobulins are absent. Muscle enzyme levels - eg, creatine kinase and aldolase - are normal.
- LFTs, especially the alkaline phosphatase, may be elevated.
- Temporal artery biopsy:
- The sensitivity of temporal biopsy is not known but has been estimated to be 87%.
- Biopsy should be taken on the symptomatic side.
- Colour duplex ultrasonography has been shown to be relatively accurate for diagnosing GCA.
16-21% of patients with PMR have GCA on temporal artery biopsy and symptoms of PMR are present in 40-60% of patients with GCA.
Urgent referral for specialist evaluation is recommended for all patients with suspected GCA but this should not delay promptly starting high-dose steroid treatment.
If temporal artery biopsy is negative (either due to the presence of skip lesions or suboptimal biopsy), patients should be managed as having GCA if there is a typical clinical and laboratory picture and response to glucocorticosteroids, or typical findings on ultrasound, or ischaemic complications typical of GCA (such as anterior ischaemic optic neuritis).
- Once the diagnosis is suspected, treat with high-dose corticosteroid immediately:
- 40 mg prednisolone daily unless the patient has ischaemic symptoms (jaw or tongue claudication, or visual symptoms).
- Claudication symptoms: give 60 mg prednisolone daily.
- If the patient has visual symptoms, admit for treatment with intravenous methylprednisolone.
- Once symptoms and abnormal test results resolve, the dose can be reduced in 10 mg steps each two weeks to 20 mg, then in 2.5 mg steps.
- Flare-ups and relapses usually respond to corticosteroid increases to the level at which symptoms previously were controlled. Protracted courses of therapy are often necessary.
- Once the diagnosis is suspected, treat with high-dose corticosteroid immediately:
- Low-dose aspirin:
- Start aspirin 75 mg daily unless there are contra-indications - eg, active peptic ulceration or a bleeding disorder.
- Start gastroprotection with a proton pump inhibitor in view of the added risk of peptic ulceration with high-dose steroids and aspirin.
- Low-dose aspirin has been shown to decrease the rate of visual loss and strokes in patients with GCA.
- Glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Osteoporosis prophylaxis is required for patients on long-term steroid treatment.
- Various steroid-sparing agents have been tried but robust scientific evidence of their efficacy and safety is still lacking. However, tocilizumab - a monoclonal antibody against the interleukin-6 receptor - has been shown to be effective in the induction and maintenance of remission in patients with GCA.
- Loss of vision. Permanent visual loss, partial or total, occurs in up to 20% of patients and is often the first manifestation of the disease.
- Aneurysms, dissections and stenotic lesions of the aorta and its major branches.
- Central nervous system disease: seizures, cerebral vascular accidents. SSS and brain ischaemia. Intracranial vessels are involved only rarely. Peripheral nerve involvement is also rare.
- Steroid-related complications are common; morbidity from steroid therapy is often worse than the underlying disease. Potential steroid-related complications include osteoporosis, corticosteroid myopathy, bruising, emotional symptoms (eg, insomnia, restlessness, hypomania, depression), hypertension, diabetes, elevated cholesterol and fluid retention.
- Visual damage is often irreversible. Partial or complete loss of vision occurs in about 15-20% of patients. Severe sight impairment in both eyes is rare.
- Patients experience relief with treatment but spontaneous relapses are common and unpredictable within the first years of the disease.
- Most patients are able to stop taking steroids by two years.
- Factors that predict the need for prolonged therapy and increased relapse risk are older age at diagnosis, female sex, higher baseline ESR and initial rapid reduction of prednisolone dose.
Further reading and references
Kale N, Eggenberger E; Diagnosis and management of giant cell arteritis: a review. Curr Opin Ophthalmol. 2010 Nov21(6):417-22. doi: 10.1097/ICU.0b013e32833eae8b.
Chacko JG, Chacko JA, Salter MW; Review of Giant cell arteritis. Saudi J Ophthalmol. 2015 Jan-Mar29(1):48-52. doi: 10.1016/j.sjopt.2014.10.001. Epub 2014 Nov 1.
Salvarani C, Cantini F, Hunder GG; Polymyalgia rheumatica and giant-cell arteritis. Lancet. 2008 Jul 19372(9634):234-45.
Hassan N, Dasgupta B, Barraclough K; Giant cell arteritis. BMJ. 2011 May 23342:d3019. doi: 10.1136/bmj.d3019.
Liozon E, Ouattara B, Rhaiem K, et al; Familial aggregation in giant cell arteritis and polymyalgia rheumatica: a comprehensive literature review including 4 new families. Clin Exp Rheumatol. 2009 Jan-Feb27(1 Suppl 52):S89-94.
Muratore F, Kermani TA, Crowson CS, et al; Large-vessel giant cell arteritis: a cohort study. Rheumatology (Oxford). 2015 Mar54(3):463-70. doi: 10.1093/rheumatology/keu329. Epub 2014 Sep 5.
BSR and BHPR guidelines for the management of giant cell arteritis; British Society for Rheumatology (March 2010)
Weyand CM, Goronzy JJ; Clinical practice. Giant-cell arteritis and polymyalgia rheumatica. N Engl J Med. 2014 Jul 3371(1):50-7. doi: 10.1056/NEJMcp1214825.
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 Aug33(8):1122-8.
Ball EL, Walsh SR, Tang TY, et al; Role of ultrasonography in the diagnosis of temporal arteritis. Br J Surg. 2010 Dec97(12):1765-71. doi: 10.1002/bjs.7252.
Unwin B, Williams CM, Gilliland W; Polymyalgia rheumatica and giant cell arteritis. Am Fam Physician. 2006 Nov 174(9):1547-54.
Giant cell arteritis; NICE CKS, July 2014 (UK access only)
Nesher G, Berkun Y, Mates M, et al; Low-dose aspirin and prevention of cranial ischemic complications in giant cell arteritis. Arthritis Rheum. 2004 Apr50(4):1332-7.
Ponte C, Rodrigues AF, O'Neill L, et al; Giant cell arteritis: Current treatment and management. World J Clin Cases. 2015 Jun 163(6):484-94. doi: 10.12998/wjcc.v3.i6.484.
Villiger PM, Adler S, Kuchen S, et al; Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet. 2016 May 7387(10031):1921-7. doi: 10.1016/S0140-6736(16)00560-2. Epub 2016 Mar 4.
Ness T, Bley TA, Schmidt WA, et al; The diagnosis and treatment of giant cell arteritis. Dtsch Arztebl Int. 2013 May110(21):376-85
Guida A, Tufano A, Perna P, et al; The thromboembolic risk in giant cell arteritis: a critical review of the literature. Int J Rheumatol. 20142014:806402. doi: 10.1155/2014/806402. Epub 2014 May 20.