Giant cell arteritis: An updated review of an old disease
Release date: July 1, 2019
Expiration date: June 30, 2020
Estimated time of completion: 1 hour
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ABSTRACT
Giant cell arteritis is a common systemic vasculitis that affects the elderly and has a variable clinical presentation. Physicians should be aware of its different clinical phenotypes so that they can recognize it early and promptly initiate glucocorticoids, the mainstay of therapy. Clinicians should also be familiar with the toxicity of glucocorticoids and how to manage adverse effects. Tocilizumab, an interleukin 6 receptor inhibitor, is emerging as a glucocorticoid-sparing treatment, though its long-term safety and efficacy are still under study.
KEY POINTS
- Giant cell arteritis can present with cranial symptoms, extracranial large-vessel involvement, or polymyalgia rheumatica.
- Temporal artery biopsy is the standard for diagnosis.
- Adverse effects of glucocorticoid treatment, particularly bone loss, need to be managed.
- In patients treated with glucocorticoids alone, the relapse rate is high when the drugs are tapered; thus, prolonged treatment is required.
RELAPSE OF DISEASE
Suspect a relapse of GCA if the patient’s initial symptoms recur, if inflammatory markers become elevated, or if classic symptoms of GCA or polymyalgia rheumatica occur. Elevations in inflammatory markers do not definitely indicate a flare of GCA, but they should trigger close monitoring of the patient’s symptoms.
Relapse is treated by increasing the glucocorticoid dosage as appropriate to the nature of the relapse. If vision is affected or the patient has symptoms of GCA, then increments of 30 to 60 mg of prednisone are warranted, whereas if the patient has symptoms of polymyalgia rheumatica, then increments of 5 to 10 mg of prednisone are usually used.
The incidence of relapses of GCA in multiple tertiary care centers has been reported to vary between 34% and 75%.23,24 Most relapses occur at prednisone dosages of less than 20 mg orally daily and within the first year after diagnosis. The most common symptoms are limb ischemia, jaw claudication, constitutional symptoms, headaches, and polymyalgia rheumatica. In a review of 286 patients,25 213 (74%) had at least 1 relapse. The first relapse occurred in the first year in 50%, by 2 years in 68%, and by 5 years in 79%.
,ADVERSE EFFECTS OF GLUCOCORTICOIDS
In high doses, glucocorticoids have well-known adverse effects. In a population-based study of 120 patients, each patient treated with glucocorticoids experienced at least 1 adverse effect (cataract, fracture, infection, osteonecrosis, diabetes, hypertension, weight gain, capillary fragility, or hair loss).26 The effects were related to aging and cumulative dosage of prednisone but not to the initial dosage.
Glucocorticoids can affect many organs and systems:
- Eyes (cataracts, increased intraocular pressure, exophthalmos)
- Heart (premature atherosclerotic disease, hypertension, fluid retention, hyperlipidemia, arrhythmias)
- Gastrointestinal system (ulcer, gastrointestinal bleeding, gastritis, visceral perforation, hepatic steatosis, acute pancreatitis)
- Bone and muscle (osteopenia, osteoporosis, osteonecrosis, myopathy)
- Brain (mood disorder, psychosis, memory impairment)
- Endocrine system (hyperglycemia, hypothalamic-pituitary-adrenal axis suppression)
- Immune system (immunosuppression, leading to infection and leukocytosis).
Patients receiving a glucocorticoid dose equivalent to 20 mg or more of prednisone daily for 1 month or more who also have another cause of immunocompromise need prophylaxis against Pneumocystis jirovecii pneumonia.27 They should also receive appropriate immunizations before starting glucocorticoids. Live-virus vaccines should not be given to these patients until they have been off glucocorticoids for 1 month.
Glucocorticoids and bone loss
Glucocorticoids are associated with bone loss and fracture, which can occur within the first few months of use and with dosages as low as 2.5 to 7.5 mg orally daily.28 Therefore, glucocorticoid-induced bone loss has to be treated aggressively, particularly in patients who are older and have a history of fragility fracture.
For patients with GCA who need glucocorticoids in doses greater than 5 mg orally daily for more than 3 months, the following measures are advised to decrease the risk of bone loss:
- Weight-bearing exercise
- Smoking cessation
- Moderation in alcohol intake
- Measures to prevent falls29
- Supplementation with 1,200 mg of calcium and 800 IU of vitamin D.30
Pharmacologic therapy should be initiated in men over age 50 who have established osteoporosis and in postmenopausal women with established osteoporosis or osteopenia. For men over age 50 with established osteopenia, risk assessment with the glucocorticoid-corrected FRAX score (www.sheffield.ac.uk/FRAX) should be performed to identify those at high risk in whom pharmacologic therapy is warranted.31
Bisphosphonates are the first-line therapy for glucocorticoid-induced osteoporosis.32
Teriparatide is the second-line therapy and is used in patients who cannot tolerate bisphosphonates or other osteoporosis therapies, and in those who have severe osteoporosis, with T scores of –3.5 and below if they have not had a fracture, and –2.5 and below if they have had a fragility fracture.33
Denosumab, a monoclonal antibody to an osteoclast differentiating factor, may be beneficial for some patients with glucocorticoid-induced osteoporosis.34
To assess the efficacy of therapy, measuring bone mineral density at baseline and at 1 year of therapy is recommended. If density is stable or improved, then repeating the measurement at 2- to 3-year intervals is suggested.
