Giant cell arteritis

Blood vessel inflammation in giant cell arteritis (GCA) most commonly affects the temporal arteries of the head, which are located on each side of the head. However, arteries in other areas of the body can also become inflamed, so symptoms may depend on which vessels are involved.^[1] The onset of symptoms may be sudden or develop more subtly over time.^[3]

Signs and symptoms of GCA may include:^[3]

• Non-specific symptoms such as fever, fatigue, and weight loss.
• Headaches, which most often occur over the temples. They may progressively worsen or they may sometimes go away and come back. They may be associated with tenderness of the scalp.
• Pain in the jaw when chewing (jaw claudication).
• Transient (not lasting) vision impairment, which most often occurs in one eye but sometimes in both.
• Partial or complete permanent vision loss, which is most often sudden and painless. Loss of vision in one or both eyes is reported in 15 to 20 percent of people with GCA.
• Polymyalgia rheumatica, a condition that causes muscle pain and stiffness in the neck, shoulders, and hips. This can occur with or without GCA but occurs in about 40% to 50% of people with GCA.
• Other musculoskeletal symptoms such as pain from inflammation of the tissues that line the joints (synovitis), swelling of the hands and/or feet, and pitting edema (noticeable swelling due to fluid build-up).
• Upper respiratory symptoms, particularly a dry cough.
• Symptoms specific to large vessel GCA, which refers to involvement of the aorta and its major proximal branches, especially in the arms. People with large vessel GCA are at increased risk for severe complications including aortic aneurysm and dissection.
• Central nervous system manifestations such as stroke (which is uncommon), and rarely, peripheral neuropathy, mononeuritis multiplex, myelopathy, dementia, or other symptoms.

While the exact cause of giant cell arteritis (GCA) is unknown, some studies have linked genetic factors, infections with certain virus or bacteria, high doses of antibiotics, and a prior history of cardiovascular disease to the development of GCA.^[4][2] These associations suggest GCA is caused by an abnormal immune response, where the body's immune system attacks the arteries.^[2]

The genetic factors currently linked to the development of GCA are not thought to directly cause GCA, but they may cause a genetic predisposition to the condition. This means that a person may carry a genetic variation (or more than one genetic variation) that increases their risk to develop GCA, but may also need one or more environmental triggers to develop GCA. Familial cases of GCA have been reported.^[5]

Recent studies have confirmed a strong association of GCA with genetic variations in the human leukocyte antigen (HLA) gene family, a cluster of genes on chromosome 6.^[6] The HLA gene family gives the body instructions to make a group of proteins known as the HLA complex. This complex helps the immune system distinguish between the body's own proteins and those made by foreign invaders such as viruses and bacteria.^[7] More specifically, GCA has been associated with genetic variations in the HLA class I and class II genes.^[6][8] HLA class I genes give the body instructions to make proteins that occur on the surface of almost all cells. HLA class II genes give instructions to make proteins that occur almost exclusively on the surface of certain immune system cells.^[7]

Variations in other genes, which are not part of the HLA gene family, have also been associated with an increased risk to develop GCA. These include the PTPN22, NLRP1, IL17A, IL33, and LRRC32 genes. Outside of the HLA-related genes, certain variations in the PTPN22 seem to be the most strongly associated with GCA. This gene is known as a common susceptibility gene in autoimmunity since different variations in the gene have been consistently associated with many autoimmune diseases.^[6]
Several additional factors are known to increase a person's risk to develop GCA. These include:

• Age - GCA affects older adults almost exclusively
• Sex - Females are about two times more likely than males to develop GCA
• Ethnicity - Higher rates of GCA occur in people with Northern European (especially Scandinavian) descent
• Polymyalgia rheumatica - About 15% of people with polymyalgia rheumatica also have GCA^[9]

While the exact cause of giant cell arteritis (GCA) is still being investigated, studies have linked both genetic and non-genetic factors to the development of GCA.^[4] Familial cases of GCA have been reported, and research indicates that some people with GCA may have a genetic predisposition to the condition. This means that a person may carry a genetic variation (or more than one genetic variation) that increases their risk to develop GCA, but it may not develop without environment triggers.^[5] Because GCA is thought to be caused by an interaction between several genetic and environmental factors, it is said to have multifactorial inheritance.

Giant cell arteritis (GCA) is typically treated with high doses of corticosteroids to reduce the inflammation in the arteries. Corticosteroids should be started promptly (perhaps even before the diagnosis is confirmed with a biopsy). If not treated, GCA may cause permanent vision loss or a stroke. The symptoms of GCA usually quickly disappear with treatment, but high doses of corticosteroids are typically maintained for 1 month. It is known that the treatment is working when the symptoms are gone and the sedimentation rate, also known as sed rate (a blood test that measures the level of inflammatory activity), is normal. The corticosteroid dose may gradually be reduced.^[1] Other medicines may help to reduce the doses of corticosteroids.^[2]

The U.S. Food and Drug Administration (FDA) approved the use of under the skin injection (subcutaneous) of tocilizumab (Brand name: Actemra) to treat adults with giant cell arteritis.^[10] Remember that only your doctor can prescribe a medication, so please talk to your doctor to find out if this medication may be right for you.

Symptoms of giant cell arteritis (GCA) generally improve within days of starting treatment, and blindness is now a rare complication. However, the course of GCA until full recovery can vary considerably. While the average duration of treatment is 2 years, some people need treatment for 5 years or more. The effects of steroid therapy are often worse than the symptoms of GCA.^[11] When GCA is properly treated, it rarely recurs.^[1] However, people with GCA carry a lifelong risk for the development of large vessel disease, particularly aortic aneurysms. Therefore, long-term followup is extremely important.^[11]

The outlook for people who are not treated is poor. Complications may include blindness or other eye and vision problems, or death from heart attack (myocardial infarction), stroke, or dissecting aortic aneurysm. Vision damage that occurs before starting therapy is often irreversible.^[11]