NORD gratefully acknowledges Andy Nguyen, NORD Editorial Intern from the Massachusetts College of Pharmacy and Health Sciences, and Bhaskar Dasgupta, MD, Professor of Medicine, Department of Rheumatology, Southend University Hospital, Westcliff, Essex, UK, for assistance in the preparation of this report.
Giant cell arteritis (GCA) is the most common blood vessel disorder in persons over 50 years old that causes inflammation of medium and large-sized arteries in the body (vasculitis). GCA causes changes in blood vessel walls leading to poor blood circulation. Arteries most affected in giant cell arteritis are the temporal artery and other cranial arteries (now called cranial-GCA), but inflammation of the aorta and other large arteries in the body can occur as well and may present differently (now called large vessel-GCA). If left untreated, this can lead to a medical emergency where sudden blindness occurs without early detection and treatment. Signs and symptoms when the temporal or other cranial arteries are involved include arm pain, pulsing headaches on one side or on the back of the head, jaw pain, scalp tenderness, double vision or other visual disturbances, bulging temporal artery that is tender with skin edema and redness. It can also present with constitutional symptoms such as polymyalgia, fevers, anorexia, and weight loss, a presentation of LV-GCA. The cause of giant cell arteritis is still unknown but is thought to be from the immune system causing damage to the body’s own blood vessels. Polymyalgia rheumatica is an inflammatory disorder that is closely related to giant cell arteritis and occurs in 40% to 60% of patients with giant call arteritis. 15% to 20% of persons with polymyalgia rheumatica will have giant cell arteritis. Treatments available include steroids (corticosteroids) that will help with symptoms and reoccurrence and medications that weaken the immune system.
Common symptoms when the temporal arteries (located on each side of the head) are affected are headaches with the artery being tender, thicker, nodular, and pulsating early-on but may become blocked later-on. Headaches are present in more than 60% of patients. The temporal artery and its parietal and frontal branches may bulge while appearing twisted/ knotted under the scalp and feel tender with skin edema and redness and may become pulseless.
Visual disturbances like double vision or transient loss of vision can occur in one or both eyes that are not long lasting. However, serious complications can occur such as blindness that occurs in 15% to 30% of patients that is not reversible with steroids. Blindness in just one eye occurs as well, but if left untreated 25% to 50% of patients can experience loss of vision in the other eye.
Arteries in other parts of the body can be affected as well. The aorta, the largest artery in the body can be affected as well and cause arm pain or increase risk for severe complications such as thinning of arterial wall in the artery leading to aneurysm and rarely arterial dissection. Risk for stroke and nervous system disorders can occur but is uncommon.
Inflammation throughout the body is common as well and can present with fever, fatigue, weight loss, discomfort, night sweats, depression, and anemia. Respiratory symptoms can also occur with dry non-mucus cough.
The cause of giant cell arteritis is still not fully known, however, studies linking genetic factors and infections have shown that the body’s immune system may play a role in the inflammation. Giant cell arteritis is thought to be an autoimmune disorder, where the body’s defense system used against invading organisms is used instead to attack normal healthy tissues. These immune cells come together at the site where they are attacking the body and form giant cells. These giant cells produce substances that damage walls of the artery and lead to further inflammation.
Studies have shown genetic variations in human leukocyte antigens (HLA), which is part of the immune response are related to how likely you are to have giant cell arteritis. There are other genetic variations that have been found to be associated with giant cell arteritis and they play a role a person’s autoimmunity response.
Giant cell arteritis most commonly affects those over 50 years old (mostly above 65 years) and is more common in Caucasians, people of Nordic or northern European descent, and others in northern latitudes. Women are 2 to 3 times more likely to develop GCA than men in persons of northern European descent while there is no higher risk for women from Spain, Israel, Turkey, other Mediterranean countries, and India. Specifically, about 20 per 100,000 people among whites in northern European populations are affected, 10 per 100,000 people affected among southern European populations, and about 1 per 100,000 people affected among American populations of Asian or African descent.
There are no universally accepted diagnostic criteria and giant cell arteritis may be diagnosed by laboratory evaluation or physical examination. The American College of Rheumatology developed provisional classification criteria which requires at least 3 of the following: age of more than 50 years, localized headache that had not happened before, temporal artery abnormalities like tenderness or pulsations, increased time it takes red blood cells to settle (erythrocyte sedimentation rate) of greater than or equal to 50mm per hour, and or abnormal arterial biopsy. Confirmation of the diagnosis can be done by obtaining a temporal artery biopsy up to 14 days after the start of treatment, however, some patients can be positive for giant cell arteritis and respond to treatment and have a negative biopsy result. The use of ultrasound and magnetic resonance are becoming more reliable to help confirm or establish early diagnosis to prevent vision loss. Internationally, the European League Against Rheumatism (EULAR) guidelines have similar recommendations with vascular ultrasound as the first diagnostic test and if not available, the temporal artery biopsy.
Clinical Testing and Work-Up
Blood tests are done to evaluate the erythrocyte sedimentation rate and the C-reactive protein. Patients are monitored for symptoms of headaches, jaw and tongue pain, abnormal pulsations of arteries, muscle pain/ stiffness, visual disturbance, and side effects of steroid treatment. Relapse testing is shown when there is a rise in erythrocyte sedimentation rate and c-reactive protein. Bone and chest x-ray testing is suggested every 2 years but there is little evidence of benefit for it. Follow-up appointments with doctors should be at 1 week, 3 weeks, and 6 weeks, 3 months, 9 months, and 12 months for the first year or if new symptoms occur. The important objectives of the follow up assessments is to monitor disease activity, damage, adverse events and stratification into remitting, relapsing, refractory disease.
As soon as a diagnosis is made the start of steroid (corticosteroid) therapy is recommended and should not be delayed due to waiting for confirmation with other tests like biopsies or imaging. Most patients start with prednisolone. For patients with visual or cerebral symptoms, intravenous methylprednisolone should be considered and then changed to oral dosing. Steroid therapy can also be started at higher doses and then lowered (tapering) in order to reduce the reoccurrence of giant cell arteritis. Inflammation should return to normal after 2 to 4 weeks of therapy and treatment would usually last up to 24 months, but some patients may require years of therapy.
Steroids have a risk of bone loss, so medications may be recommended for bone protection. Studies have shown that medications for bone health (bisphosphonates) can reduce the risk of fractures while taking steroids for inflammation. Patients receiving sulfamethoxazole-trimethoprim or dapsone for prevention and also taking methotrexate for treatment are advised to take folate or leucovorin on days after methotrexate treatment.
In 2017, the U.S Food and Drug Administration (FDA) approved Actemra (tocilizumab) for use in giant cell arteritis after a study showed increased remission rates and reduced steroid use over 1 year in adults. This approval provided another treatment alternative for patients that are not able to take steroids or experience relapses with steroids.
Relapses can occur and are usually treated with higher doses of steroid therapy and may require treatment with medications such as methotrexate, leflunomide or Actemra (tocilizumab).
Studies have shown that medications that weaken or target the immune system may slow giant cell arteritis recurrence when steroids cannot or when they become too toxic. Some medications like methotrexate, azathioprine, and dapsone have shown improvements in reducing the need for steroids but the size of the studies is too few and small to be able to recommend them as alternative treatments. Adalimumab and infliximab taken with steroids do not seem to increase remission rate or reduce the need for steroids based on recent studies.
Abatacept is another medication that was found in a small study to treat giant cell arteritis better than the standard steroid treatment, but since it was a small study, more study is needed. Other trials currently in progress are evaluating mavrilumab ( a monoclonal antibody that blocks GM-CSF), sarilumab (blocks the inflammatory cytokine interleukin-6) and JAK inhibitors such as upadacitinib.
Giant cell arteritis can also narrow the arteries and increase risk of them being blocked. Low-dose aspirin has been studied and may reduce the risk of reduced blood flow in vessels (ischemia), but additional study is needed to confirm this.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
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Giant cell arteritis. Genetic and Rare Diseases Information Center. Last updated September 21, 2018. https://rarediseases.info.nih.gov/diseases/9615/giant-cell-arteritis Accessed March 29, 2019.
Giant cell arteritis (including temporal arteritis). DynaMed Plus Web site. Updated April 4, 2019. https://www.dynamed.com/topics/dmp~AN~T115154 Accessed March 29, 2019.
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