Giant cell arteritis (GCA), along with polymyalgia rheumatica (PMR), are autoimmune disorders involving the medium and large arteries which have muscular walls and vasa vasorum in their adventitial coats.
What is GCA?
GCA is one form of vascular inflammatory disorder that affects the large aortic branches, especially those of the carotid arteries that supply the spine (vertebral), upper limb (subclavian), and extracranial branches. Sometimes, the aorta is also involved.
It is seen after the age of 50 years and accounts for most vasculitic disorders in this group. It becomes increasingly common as age advances.
The epidemiology of GCA
North Europeans are predisposed to GCA, with about 20 people being affected in every 100 000 in this population after 50 years. The male: female ratio is about 1:2 or 1:3.
The exact etiology is unknown, but it is related to T cell activation, which results in the release of inflammatory cytokines as well as macrophage activation. The smooth muscle cells within the blood vessels are also affected, leading to the typical signs and symptoms of the disease. These are brought about by changes in vascular shape and diameter, local interruption of blood supply, and a cascading production of more cytokines and metalloproteinase enzymes.
What are the signs and symptoms of GCA?
GCA symptoms are classified into:
- Features of cranial arteritis
- Those of extracranial arteritis
- Systemic features
- PMR
ACR classification of GCA
The American College of Rheumatology issued classification criteria in 1990, which have a sensitivity and specificity of 91%, but are not routinely used for diagnosis:
- Patient age 50 years or up
- New-onset headache
- Abnormal temporal arteries (tender with decreased pulsation)
- High ESR of 50 mm per hour or above
- Abnormal biopsy of the artery showing mononuclear or granulomatous cell inflammation, typically with giant cells
Cranial arteritis
The most common presenting feature is a temporal headache, on one or both sides, with swollen or tender temporal arteries. Constant or intermittent pain may be felt. Some patients report pain during chewing, as well as pain in the scalp and face.
3% to 7% of GCA patients have strokes. The involvement of other nerves is rare. Arteritic anterior ischemic optic neuropathy, or A-AION, is seen in 5% to 15% of GCA patients and can cause blindness. Sudden vision loss may be the first symptom.
Other signs include slow-onset hearing loss, tinnitus and vertigo.
Extracranial arteritis
Vascular symptoms due to the occlusion of large chest and limb arteries are not common. Aortic aneurysms are twice as common in GCA patients.
Systemic features
One-third to two-thirds of patients show systemic signs like low-grade fever, loss of appetite, and weight loss, sometimes without any other features.
Symptoms of PMR
These include aching pain in the limb girdles and neck, perhaps due to inflammation of the large joints and their associated bursae.
What is polymyalgia rheumatica?
Polymyalgia rheumatica (PMR) is similar to GCA in many ways, including the patient population, gender profile, and the ethnic origin. Scientists think that both PMR and GCA may be related to a single factor which may express itself differently as GCA or PMR or both. They may both occur together or separated by longer intervals.
What causes PMR?
PMR is thought to be related to T cell activation and consequent cytokine production leading to inflammation. In PMR, an arterial biopsy may appear normal, but the concentration of inflammatory cytokines is increased within the temporal arteries. However, IFN-γ producing cells are not recruited to the vessel wall, perhaps explaining the lack of overt vasculitis.
What are the features of PMR?
Typically, PMR presents with aching pain of the limb girdles, namely, the shoulder and hip girdles, and in the neck, with morning stiffness. Systemic features of PMR occur in a third of patients, and include low-grade fever, feeling of being unwell, and loss of appetite. Some PMR patients have joint pain or synovial inflammation of the hand and knee joints.
How are GCA and PMR diagnosed?
Both GCA and PMR are diagnosed clinically. Laboratory testing shows high levels of CRP and ESR, the acute-phase reactants. Inflammatory parameters are also positive.
The only way to confirm GCA is temporal artery biopsy showing the presence of vasculitis. Giant cells or other mononuclear cells infiltrate the arterial tissue in the inflamed segments. Because of segmental inflammation, biopsy may be negative in up to a third of GCA patients.
Imaging techniques like high-resolution contrast-enhanced magnetic resonance imaging (MRI) or color duplex ultrasound scanning of the temporal arteries may help with the diagnosis. Other tests include angiography of the aortic arch and branches, or PET for non-invasive diagnosis.
What are the complications of GCA?
GCA may cause vascular complications like stroke, coronary artery occlusion, thoracic aortic aneurysms and rupture, and aortic dissection, and severe infections.
Management of GCA and PMR
Glucocorticoids are used to treat GC and PMR, and typically result in symptom relief within 1-3 days. No steroid-sparing therapies to modify the disease course are available. However, treatment is usually only required for a few weeks for an acute disease manifestation. Patients may need intermittent treatment over the course of several years, but lifelong treatment is usually not needed.
In GCA, emergency management is required if impending vision loss or stroke is diagnosed, and requires initial high-dose steroid therapy. Rapid improvement characteristically occurs.
Surgery may sometimes be required if thoracic or other arteries are involved.
Further Reading