Giant cell arteritis

Giant cell arteritis is a sight-threatening vasculitis characterised by inflammation of medium and large sized arteries.

Giant cell arteritis (GCA), otherwise known as temporal arteritis, is a type of vasculitis. Vasculitis refers to inflammation of blood vessels. It is considered a medical emergency because without prompt recognition and treatment it can lead to visual loss.

In the UK, the annual incidence is estimated at 20 per 100,000 people. The peak onset occurs in patients aged 70-79 and the condition is rarely seen before the age of 50. The condition is more prevalent in white Northern European patients and is 2-3 times more common in women.

The exact cause of GCA is currently unknown.

There is some association between environmental and genetics factors, which includes genetic variation in the human leucocyte antigens (HLAs). HLAs are involved in antigen processing by immune cells as part of the adaptive immune response. Several alleles have been linked to GCA including HLA-DRB1*04 and HLA-DQA1*03.

GCA results in granulomatous inflammation of blood vessel walls.

GCA leads to inflammation of medium and large sized arteries with preferential involvement of branches of the carotid artery including temporal, ophthalmic and occipital. However, GCA can affect many other arteries including vertebral, carotid, subclavian and even aorta.

GCA is characterised by granulomatous inflammation that refers to the presence of granulomas on microscopy, which are a collection of macrophages. The inflammatory process is complex, but can be conceptualised in a number of steps. 

• Initial inflammatory event: activation of innate and adaptive immune responses leads to local vessel inflammation and recruitment of macrophages into the vessel wall. 
• Vessel wall damage: infiltration of immune cells and release of cytokines leads to damage of the vessel wall. In particular, damage to the internal elastic lamina.
• Growth and angiogenic factors: tissue injury leads to release of growth and angiogenic factors that promote new blood vessel formation, proliferation of myofibroblasts and marked thickening of the internal vessel layer (i.e. tunica intima). 
• Narrowing and ischaemia: hyperplasia and expansion of the intimal layer leads to vessel narrowing and subsequent ischaemia to the area supplied by the artery. This causes the characteristic features of GCA.

The signs of symptoms of GCA are dependent on the vessel affected by inflammation.

The characteristic features of GCA are unilateral headache, jaw claudication (fatigue with chewing), scalp tenderness and constitutional symptoms (fever, weight loss, fatigue).  

Symptoms

• Unilateral headache: typically temporal
• Scalp pain: difficulty combing hair
• Jaw and tongue claudication
• Visual symptoms: blurring, amaurosis fugax (temporary monocular blindness), diplopia
• Constitutional symptoms: fever, weight loss, fatigue
• Polymyalga symptoms (see chapter on diagnosis)

Signs

• Abnormal temporal artery: typically thickened, tender with reduced or absent pulse
• Scalp tenderness on palpation
• Transient or permanent visual loss
• Visual field defects
• Optic disc changes: pale, swollen optic disc (anterior ischaemic optic neuritis)
• Retinal changes: pale retina with cherry red spot (central retinal artery occlusion)
• Other: cranial nerve palsies, asymmetrical pulses (if large vessel involvement – subclavian)

NOTE: consider GCA in any older patient (> 50 years) with a new-onset unilateral headache.

The diagnosis of GCA is based on the American College of Rheumatology Classification.

Early diagnosis and treatment of GCA is essential to prevent long-term complication such as loss of sight, which occurs in one-fifth of patients.

GCA can be diagnosed when three of the following criteria are met:

• Age at disease onset ≥50 years
• New headache
• Temporal artery abnormality
• Elevated ESR (> 50 mm/hr)
• Abnormal temporal artery biopsy (typical vasculitis features)

Polymyalgia rheumatica

GCA is closely linked to another condition termed polymyalgia rheumatic (PMR). PMR is another incompletely understood inflammatory disorder that is characterised by aching and morning stiffness in the shoulder, hip girdle, neck and torso. 

PMR occurs in approximately 40-50% of patients with GCA. Conversely, only 10% of patients with PMR will develop GCA. Both conditions are managed with steroids.

Temporal artery biopsy is the principle investigation in GCA.

Any patient with suspected GCA should be immediately assessed according to the local GCA pathway. Key investigations include inflammatory markers (i.e. ESR/CRP), which are characteristically high, and a temporal artery biopsy (TAB).

In patients with a strong clinical suspicion of GCA (i.e. characteristic features or threatened sight), treatment should not be delayed whilst awaiting TAB. In fact, treatment with steroids can even be initiated before biochemistry results if the suspicion is high.

Bloods

• FBC
• U&E
• LFT
• ESR/CRP: typically elevated but may be normal at presentation (<5%). Keep a high index of suspicion.

Temporal artery biopsy

Sampling of a small piece of tissue from the temporal artery. Due to the presence skip lesions, a negative biopsy does not exclude GCA.

Duplex ultrasonography

Increasingly used to look for characteristic features of GCA including hypoechoic ‘halo’, occlusions and stenosis. However, it currently does not replace TAB for the diagnosis of cranial GCA.

Positron emission tomography (PET)

PET imaging may be useful in patients with large vessel inflammation (i.e. subclavian arteries, carotid arteries, aorta). 

Ophthalmic assessment

Any patient with visual symptoms relating to suspected GCA require a formal ophthalmic assessment with slit-lamp examination the same day. The characteristic finding is anterior ischaemic optic neuritis, which is seen as a pale, swollen optic disc.

Prompt treatment with high-dose corticosteroids is the cornerstone of treatment in GCA.

The treatment of GCA is the initiation of high dose corticosteroids.

Steroid regimen

• With visual symptoms: 60-100 mg one off dose prednisolone until further ophthalmic assessment (same day). Alternatively, intravenous methylprednisolone 500-1000 mg for three consecutive days, then oral prednisolone (~60 mg daily).
• Without visual symptoms: 40-60 mg prednisolone daily (minimum 0.75 mg/kg). 

Patients with GCA should have a rapid response to steroids and this should be assessed within 48 hours. If there isn’t a significant response, an alternative diagnosis should be considered. 

Steroid-related complications

Steroids can be associated with numerous complications including steroid-induced hyperglycaemia, mood changes, insomnia, gastrointestinal bleeding, immunosuppression, weight gain, Cushingoid appearance, osteoporosis and adrenal cortex suppression.

Patients starting steroids will usually need a long course with slow tapering over several months or years. Therefore, from the outset they need bone protection (e.g. bisphosphonates and vitamin D supplementation), gastric protection (e.g. proton pump inhibitors) and monitoring blood sugar (at risk of steroid-induced diabetes or worsening of glycemic control in known diabetics).

Ongoing management 

Patients require regular monitoring of symptoms and a steroid-reducing plan. Follow-up is guided by local practice, but is generally offered every 2-8 weeks for the first six months then less frequent intervals. Each review should take into account current steroid dose, symptoms, signs of relapse and side-effects from steroids. 

Steroid reducing regimen:

• Initiation: prednisolone (40-60 mg) continued for four weeks
• First dose reduction: reduce prednisolone by 10 mg every two weeks until at 20 mg
• Second dose reduction: reduce prednisolone by 2.5 mg every 2-4 weeks until at 10 mg
• Third dose reduction: reduce prednisolone by 1 mg every 1-2 months, provided no relapse

Patients are at risk of relapse (especially within first two years), which may be related to steroids being tapered too quickly. Patients with significant side-effects from steroids or inability to taper the dose may be considered for steroid-sparing immunosuppressive agents. 

Aspirin

The use of aspirin is controversial. At present the routine use of aspirin is not recommenced by NICE when it is solely started for GCA. Furthermore, the European League Against Rheumatism guidance for the treatment of large vessel vasculitis also advise against routine prescription unless indicated for other reasons (i.e. cardiovascular prevention). 

The major complication of GCA is visual loss, so any visual symptoms should be taken seriously.

• Visual loss: 20% of patients, little chance of recovery once lost
• Large arterial complications: aortic aneurysm, aortic dissection, large artery stenosis
• Cardiovascular disease: more common in patients with GCA
• Steroid-related complications (see chapter on management)