Giant cell arteritis: Suspect it, treat it promptly
ABSTRACTGiant cell arteritis is the most common form of vasculitis affecting older people, and the diagnosis should be considered in older patients who present with the new onset of headache, visual dysfunction, polymyalgia rheumatica, or systemic inflammatory symptoms. Physicians should be familiar with its variety of clinical presentations and the abnormal laboratory findings associated with it.
KEY POINTS
- Giant cell arteritis is often associated with an intense acute-phase response and cranial symptoms.
- Large-vessel involvement is commonly present and may result in serious complications such as visual loss, stroke, limb claudication, and aortic aneurysm.
- The diagnosis is usually confirmed by an abnormal temporal artery biopsy.
- Symptoms of giant cell arteritis usually respond rapidly and completely to glucocorticoid therapy, still the mainstay of treatment. Most patients need prolonged therapy.
- Several studies have evaluated alternative drugs in an attempt to avoid toxicity from long-term use of glucocorticoids. Results have been mixed, and further study is needed.
TREATMENT
Glucocorticoid therapy remains the standard of care
Once the diagnosis of giant cell arteritis is established, glucocorticoid treatment should be started. Glucocorticoids are the standard therapy, and they usually bring about a prompt clinical response. Although never evaluated in placebo-controlled trials, these drugs have been shown to prevent progression of visual loss in a retrospective study.26
In patients with visual symptoms or imminent visual loss, therapy should be started promptly once suspicion of giant cell arteritis is raised; ie, one should not wait until the diagnosis is confirmed by biopsy.
Ideally, a glucocorticoid should be started after a temporal artery biopsy is done, but treatment should not be delayed, as it rapidly suppresses the inflammatory response and may prevent complications from tissue ischemia, such as blindness. Visual loss is usually irreversible.
There is still a role for obtaining a temporal artery biopsy up to several weeks after glucocorticoid therapy is started, as the pathological abnormalities of arteritis do not rapidly resolve.27
Glucocorticoid therapy is highly effective in inducing disease remission in patients with giant cell arteritis. Nearly all patients respond to 1 mg/kg (40–60 mg) per day of prednisone or its equivalent.
The initial dosing is usually maintained for 4 weeks and then decreased slowly. The duration of therapy varies; most patients remain on therapy for at least 1 year, and some cannot stop it completely without recurrence of symptoms.
If a patient is about to lose his or her vision or has lost all or some vision in one eye, a higher initial dose of a glucocorticoid is usually used (ie, a pulse of 500 or 1,000 mg of intravenous methylprednisolone) and may be beneficial.28
Although a rapid clinical response to therapy is usually seen within 48 hours, some patients may have a more delayed clinical improvement.
Alternate-day therapy was compared with daily therapy and was found to be less effective, and as a result it is not recommended.29
Glucocorticoid therapy can cause significant toxicity in patients with giant cell arteritis, as they commonly must take these drugs for long periods. The rate of relapse in those who discontinue therapy is quite high—as high as 77% within 12 months.30
Given the concern about glucocorticoid toxicity, several studies have evaluated alternative strategies and other immunosuppressive drugs. However, no study has concluded that other medications are effective in the treatment of giant cell arteritis.
Mazlumzadeh et al31 evaluated the initial use of intravenous pulse methylprednisolone therapy (15 mg/kg ideal body weight on 3 consecutive days) in an attempt to decrease the glucocorticoid requirement. Although the group receiving this therapy had a lower relapse rate than in the placebo group, and their cumulative dose of glucocorticoid was lower (all patients also received oral prednisone), there was no reduction in the rate of glucocorticoid-associated toxicity.31 Care must be taken to prevent and monitor for corticosteroid complications such as osteoporosis, glaucoma, diabetes mellitus, and hypertension.
Methotrexate: Mixed results in clinical trials
Methotrexate has been evaluated in three prospective randomized trials,30,32,33 with mixed results.
Spiera et al32 enrolled 21 patients in a double-blind placebo-controlled trial: 12 patients received low-dose methotrexate (7.5 mg/week) and 9 received placebo. In addition, all 21 received a glucocorticoid. There was no significant difference between the methotrexate- and placebo-treated patients in the cumulative dose of glucocorticoid, duration of glucocorticoid therapy, time to taper off the glucocorticoid to less than 10 mg of prednisone per day, or glucocorticoidrelated adverse effects.
Jover et al,33 in another double-blind placebo-controlled trial, studied 42 patients with giant cell arteritis, half of whom were randomized to receive methotrexate 10 mg/week, while the other half received placebo. All patients received prednisone. Patients in the methotrexate group had fewer relapses and a 25% lower cumulative dose of prednisone during follow-up. However, the incidence of adverse events was similar in both groups. Methotrexate was discontinued in 3 patients who developed drug-related adverse events.
Hoffman et al30 randomized 98 patients to receive either methotrexate (up to 15 mg/week) or placebo in a double-blind fashion. All patients also received prednisone at an initial dose of 1 mg/kg/day (up to 60 mg/day). At completion of the study, no differences between the groups were noted in the rates of relapse or treatment-related morbidity or in the cumulative dose of glucocorticoid. However, treatment with methotrexate appeared to lower the rate of recurrence of isolated polymyalgia rheumatica in a small number of patients.30
Comment. Differences in the results of these trials may be attributed to several factors, including different definitions of relapses and different glucocorticoid doses and tapering regimens.
A meta-analysis of these three trials34 showed a reduction in the risk of relapse: 4 patients would have to be treated to prevent one first relapse, 5 would have to be treated to prevent one second relapse, and 11 would need to be treated to prevent one first relapse of cranial symptoms in the first 48 weeks. However, the main goal of methotrexate therapy is to decrease the frequency of adverse events from glucocorticoids, and this meta-analysis found no difference in rates of glucocorticoid-related adverse events in patients treated with methotrexate.
The study raises the question of whether methotrexate should be further evaluated in in different patient populations and at higher doses.34
Infliximab is not recommended
In a prospective study, patients with giant cell arteritis were randomly assigned to receive either infliximab (Remicade) 5 mg/kg every 8 weeks or placebo, in addition to standard glucocorticoid therapy. The study showed no significant difference in the relapse rate and a higher rate of infection in the infliximab group (71%) than in the placebo group (56%). Given the lack of any benefit observed in this study, infliximab is not recommended in the treatment of patients with giant cell arteritis.35
Aspirin is recommended
Daily low-dose aspirin therapy has been shown in several studies to be effective in preventing ischemic complications of giant cell arteritis, including stroke and visual loss. It is currently recommended that all patients with giant cell arteritis without a major contraindication take aspirin 81 mg daily.36–38
