Giant Cell (Cranial) Arteritis

Synonym: temporal arteritis, cranial arteritis

Giant cell arteritis (GCA) is a systemic, inflammatory, vascular syndrome that predominantly affects the aorta and its extracranial branches.¹ 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.¹

• The incidence of giant cell arteritis increases progressively after 50 years of age and is in the region of 20 per 100,000 people older than 50 years.
• The reported rates for giant cell arteritis are highest in Northern European countries.
• Women are affected two to three times more often than men.

Risk factors

• 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.²

The American College of Rheumatology's criteria for diagnosing giant cell arteritis are:³

• Age >50 years
• New headache
• Abnormalities of the temporal arteries
• ESR >50 mm/hour
• Positive temporal artery biopsy

The presence of three or more criteria has a sensitivity of 97% and a specificity of 79% for a diagnosis of giant cell arteritis.³

Symptoms

The possible presentations are diverse, as the underlying vasculitis may affect a wide range of arteries, including branches of the carotid system, the cranial arteries, the aorta and its branches, and the coronary arteries.⁴ 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, and is present in more than half of patients with temporal arteritis.
• 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 polymyalgia rheumatica) 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%. 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 brainstem stroke.
• Abdominal aorta involvement can occur, with symptoms of aortic aneurysms and intestinal infarction. Renal involvement is rare.

Signs

• 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.

• Migraine
• Tension headache
• Trigeminal neuralgia
• Takayasu's arteritis
• Polyarteritis nodosa
• Polymyositis

• Elevation in the acute phase reactants: the ESR is usually in excess of 50 mm/hour and may exceed 100 mm/hour. A normal ESR does not exclude the diagnosis.⁵ 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, e.g. creatine kinase and aldolase, are normal.
• Liver function tests, especially the alkaline phosphatase, may be elevated.
• Temporal artery biopsy:
  • Is the gold standard investigation for diagnosing temporal arteritis, although is still only 60-80% accurate due to the possibility of skip lesions.⁶
  • Biopsy should be taken on the symptomatic side.
  • The confirmatory biopsy can be performed after treatment is started, without major alteration in the diagnostic histology, for up to 10 days.⁷
• Colour duplex ultrasound of the temporal artery:
  • A normal colour duplex ultrasound of the temporal artery makes giant cell arteritis unlikely.
  • The negative predictive value of a normal colour duplex ultrasound is greater than 95% (i.e. the chance that someone with a normal colour duplex ultrasound has giant cell arteritis is less than 5%).⁸
• Thoracic or abdominal ultrasound: aortic aneurysms. Because cases of aortic aneurysms may develop many years after the patient no longer requires steroid therapy, follow-up chest X-rays and thoracic or abdominal ultrasound may be needed over time.

• About 50% of patients with giant cell arteritis also have polymyalgia rheumatica.

• Steroids:
  • Prednisone: normally controlled on 40 mg prednisolone/day but patients with persistent visual symptoms may need 60-80 mg.¹⁰ Alternate-day therapy is not effective in preventing vision loss. Parenteral methylprednisolone is often used when acute visual changes are present.
  • Do not delay treatment in patients with visual symptoms or signs, e.g. amaurosis fugax, partial or complete visual loss, when GCA is strongly suggested.
  • High risk of corticosteroid-induced osteoporosis: start all patients on calcium and vitamin D2. All patients should have a bone density scan and treatments such as bisphosphonates considered accordingly.
  • Once the patient is on steroids, the symptoms of giant cell arteritis should improve in one or two weeks. Steroid therapy has no effect on biopsy results for up to four weeks after initiation.¹¹
  • Relapse is common (25-60%) and most common in the first year of treatment:¹² The steroid dosage can be decreased for nearly all patients, but occasionally the dose may need temporarily to be increased because of fluctuations in the inflammatory process.
  • Maintain high-dose steroid therapy only long enough for symptoms to resolve (ideally the dose should be reduced after one to two months of treatment) and then reduce the dose by 5 mg increments and aim to have the patient on 10 mg daily within six months. Further reduce the dose by 1 mg every one or two months. Both clinical signs and the ESR (or CRP) assist in monitoring the patient's response.
  • Patients with visual involvement usually require slower tapering of corticosteroids. Steroids can often be reduced to 7.5-10 mg per day after six months, with discontinuation within two to three years.
  • 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.¹¹
  • Methotrexate may be useful in patients with disease resistant to steroid treatment.¹³ One trial showed that it helped prevent relapses and reduce the dose of prednisolone, but other trials have not confirmed this. Tumour necrosis factor antagonists have been used to treat patients with resistant giant cell arteritis.¹⁴
• Low-dose aspirin:
  • Start aspirin 75 mg daily unless there are contra-indications, e.g. active peptic ulceration or a bleeding disorder.⁹
  • Start gastroprotection with a proton pump inhibitor in view of added risk of peptic ulceration with high-dose steroids and aspirin.⁹
  • Low-dose aspirin has been shown to decrease the rate of visual loss and strokes in patients with GCA.¹⁵

• Loss of vision.
• 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 (e.g. insomnia, restlessness, hypomania, depression), hypertension, diabetes, elevated cholesterol and fluid retention.¹¹

• Visual damage is often irreversible. Partial or complete loss of vision occurs in about 15 to 20% of patients. Blindness in both eyes is rare.¹¹
• The average duration of treatment is two years; however, some patients require treatment for five years or more. Patients experience relief with treatment, but spontaneous relapses are common and unpredictable within the first years of the disease.¹¹
• 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 prednisone dose.