Treatment of Giant Cell Arteritis

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Treatment of giant cell arteritis

Author: William P Docken, MD
Section Editors: Jonathan Trobe, MD, Eric L Matteson, MD, MPH
Deputy Editor: Monica Ramirez Curtis, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2020. | This topic last updated: Jan 02, 2020.
INTRODUCTION
Giant cell arteritis (GCA, also known as Horton disease, cranial arteritis, and temporal arteritis) is
the most common systemic vasculitis in North America and Europe [1,2]. GCA affects only older
adults, with a peak incidence between ages 70 and 79 [3]. Many of the clinical features of the
disease result from vascular inflammation of the small extracranial branches of the carotid
arteries. The disease can be generalized, however, and involve the aorta, leading to aneurysms
of the thoracic and abdominal aorta, and large arteries, resulting in ischemic symptoms of the
extremities.
The treatment and prognosis of GCA are reviewed here. The clinical manifestations and
diagnosis of this disorder are discussed separately. (See "Clinical manifestations of giant cell
arteritis" and "Diagnosis of giant cell arteritis".)
MANAGEMENT
Overall approach
Patients with positive biopsy or imaging — High-dose systemic glucocorticoids are the

mainstay of therapy and should be instituted promptly once the diagnosis of giant cell arteritis
(GCA) is strongly suspected, especially in patients with recent or threatened visual loss. A
temporal artery biopsy or other diagnostic procedure should be obtained as soon as possible,
but treatment should not be withheld while awaiting the performance or results (see "Diagnosis
of giant cell arteritis"). In patients who have developed or are at high risk for adverse effects of
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prednisone, glucocorticoid-sparing strategies include the addition of tocilizumab (TCZ) or

methotrexate (MTX). (See 'Glucocorticoid-sparing agents' below.)
Patients with negative biopsy and imaging — In cases where the clinical scenario for GCA
is compelling but the diagnostic workup is negative, the diagnosis of GCA may be arrived at on
clinical grounds. Workup should have included negative temporal artery biopsy or biopsies
and/or color-coded duplex ultrasonography, and, as indicated, imaging studies for large vessel
involvement. Alternative diagnoses (eg, malignancy and infection) should have been excluded.
If both biopsy and extensive imaging tests are negative, a diagnosis of GCA is not likely, and the
decision to retain this diagnosis in the face of such a workup should be carefully considered.
Patients with a clinical but unproven diagnosis of GCA are generally treated the same as
patients with documented GCA. In patients with only a clinical diagnosis of GCA, the
management of recurring headache, constitutional symptoms, or elevations of the acute phase
reactants during the course of a glucocorticoid taper can be problematic.
Systemic glucocorticoids
Efficacy — Though never studied in a placebo-controlled manner, the effectiveness of

glucocorticoids for the management of GCA has been well established by decades of clinical
experience. Glucocorticoids produce prompt improvement in systemic symptoms and signs
and, if expeditiously administered, can prevent the most sinister potential complication of GCA,
that of sight loss.
The efficacy of glucocorticoid therapy for the prevention of visual loss was shown in a
retrospective study of 245 patients with biopsy-proven GCA, all treated with glucocorticoids [4].
Permanent visual loss was found in 34 patients (14 percent), which had occurred in 32 of the 34
patients before initiation of glucocorticoids. Of the two cases of de novo visual loss that
developed after glucocorticoids were started, one occurred eight days into treatment, and the
other occurred three years after glucocorticoids were first administered and one year after their
discontinuation when the erythrocyte sedimentation rate (ESR) was normal, and was therefore
unlikely related to GCA. In another study of 144 patients with biopsy-proven GCA described in
the ophthalmologic literature, none of the 53 patients with normal vision at presentation lost
vision after initiation of glucocorticoids [5]. Of the 91 patients with sight loss at presentation,
nine experienced further visual loss after beginning glucocorticoids, all within five days of the
start of treatment. Thus, if vision is intact at the time of the diagnosis of GCA, treatment with
glucocorticoids effectively reduces the risk of sight loss to less than 1 percent.
Treatment of GCA requires daily glucocorticoid administration. The importance of daily dosing
was demonstrated in the course of a study on the use of MTX for the management of GCA in

which a rapid glucocorticoid taper to an alternate-day dose was associated with new sight loss
in 8 of 98 patients [6]. In another study of regimens for glucocorticoid dosing, daily doses were
more effective than alternate-day doses for symptomatic management [7].
Initial dose — Though the efficacy of glucocorticoids for the treatment of GCA is

indisputable, an optimal regimen for a starting dose and subsequent taper (one that would
prevent visual loss and minimize glucocorticoid-related side effects) has not been formally
evaluated. Published recommendations in this regard are consensus-based [8-10].
● Without visual loss at diagnosis – If there are no symptoms or signs of ischemic organ
damage (eg, visual loss), we suggest initial treatment with the equivalent of prednisone 1
mg/kg (maximum 60 mg/day) administered in a single daily dose. A population-based study
with 120 patients with GCA found that all patients responded rapidly to a median initial
dose of 60 mg of prednisone daily [11]. Earlier studies found doses in the range of 20 to 30
mg of prednisone per day to be effective [12,13]. In a retrospective study including 230
patients with either polymyalgia rheumatica (PMR) or GCA, a subgroup analysis of patients
with GCA stratified by three different prednisone dose ranges (10 to 20 mg daily, over 20
and under 60 mg daily, and 60 to 90 mg daily) found no differences in terms of the number
of remission, relapse rates, and progression of visual complications once treatment was
started [12]. Ophthalmologists have tended to recommend higher doses, in the range of 80
mg/day [14]. If potentially reversible symptoms persist or worsen, the dose can be
increased until symptomatic control is achieved.
There is insufficient evidence to justify the upfront use of intravenous pulse glucocorticoids
in patients with GCA, although they may be used in patients with visual loss at presentation.
A randomized trial with 164 patients with GCA (without ocular involvement at presentation)
found no differences in the cumulative glucocorticoid doses or the number of GCA
complications when comparing three different glucocorticoid protocols, two of which
consisted of different pulse glucocorticoid regimens on a background of oral prednisone
(240 mg intravenous pulse of methylprednisolone followed by 0.7 mg/kg/day oral
prednisone or 240 mg intravenous pulse methylprednisolone followed by 0.5 mg/kg/day)
and the other of which consisted of only oral prednisone (0.7 mg/kg/day) [15]. Another
small randomized study of 27 patients without ocular involvement found that adding initial
pulse glucocorticoid therapy resulted in a reduced total exposure to glucocorticoids and a
lower relapse rate [16]. Neither of these randomized trials, however, was designed to assess
the outcome of ocular complications.
Patients usually report dramatic improvements of many GCA-related symptoms (eg,

headache, fever, malaise) within 24 to 48 hours of glucocorticoid administration. Laboratory

measures of disease activity such as the ESR and C-reactive protein (CRP) usually improve
substantially within a few days of the institution of therapy, as well; the CRP declines much
more rapidly than the ESR. The diagnosis of GCA should be reevaluated in patients who are
resistant to adequate glucocorticoid therapy, especially in situations where temporal artery
biopsy and imaging studies have been negative.
● Threatened or established visual loss at diagnosis – If there is a strong suspicion of GCA

as the cause of visual symptoms or signs, we suggest the use of intravenous "pulses" of
methylprednisolone, customarily administered as 500 to 1000 mg intravenously each day
for three days, followed by oral therapy with prednisone 1 mg/kg/day (maximum of 60
mg/day), as recommended above for uncomplicated GCA. Patients with presumed or
proven GCA and incident diplopia should also be treated with an initial intravenous pulse of
high-dose glucocorticoids.
Though not validated in rigorous studies, this approach is used because of the crucial
importance of preventing visual impairment due to GCA, which, once established, is rarely
reversible [16]. The stark reality of such visual loss is that patients seldom recover useful
vision in an affected eye. In a retrospective review of 84 patients (114 eyes) with variable
degrees of GCA-associated visual loss (due to anterior ischemic optic neuropathy [AION] in
over 90 percent of patients), there were no differences in improvement in visual acuity
when comparing patients who received intravenous glucocorticoids followed by oral
therapy (41 patients) with patients who received only oral glucocorticoids (43 patients).
Improvement in visual acuity was only observed in 4 percent of eyes (three patients treated
with intravenous glucocorticoids and two with oral glucocorticoids), as judged by
improvement in both visual acuity and central visual field (by kinetic perimetry and Amsler
grid) [17]. Numerous other studies testify to this poor outcome [18,19]. Of note,
improvement perceived by patients and noted on visual acuity tests may not reflect true
recovery of retinal or optic nerve function but rather eccentric compensation for acquired,
permanent visual deficits.
Preexisting sight loss can progress, despite initiation of glucocorticoid therapy, in

approximately 10 percent of patients, usually within the first week of treatment [5].
Glucocorticoid tapering
Approach to dose reduction — We maintain the starting dose of high-dose prednisone

for at least two, but not more than four, weeks. Although symptoms are typically controlled
promptly by therapy, disease flares are the rule if the glucocorticoids are tapered too quickly. If
the initial dose of prednisone is 60 mg/day, it can generally be reduced to 50 mg/day after two

weeks and to 40 mg/day at the end of four weeks, assuming symptoms and signs have receded
and the ESR and CRP have declined to normal or near-normal ranges. Subsequently, the dose
can gradually be reduced by 5 mg every two weeks to 20 mg/day and then by 2.5 mg every two
weeks to 10 mg/day if there are no flares of disease activity. After achieving a daily dose of 10
mg, the prednisone taper should be slowed, such that patients remain on progressively
decreasing doses over the ensuing 6 to 12 months. Tapering by 1 mg decrements each month
once the daily dose is less than 10 mg can be considered.
Relapses of disease are unusual at doses higher than 20 mg/day but become more frequent at
doses below that level. (See 'Relapse' below.)
Monitoring disease activity — One of the most challenging aspects of GCA treatment is

the accurate identification of relapses in the setting of the glucocorticoid taper. Acute phase
reactants such as the ESR and CRP can be useful adjuncts to clinical decision making. Especially
during initial treatment, measurements of the ESR and CRP prior to each decrease in
glucocorticoid dose are ideal.
If elevations of the ESR or CRP are not accompanied by symptoms or findings suggestive of
recrudescent GCA, reflexive changes in the glucocorticoid dose based upon the test results
alone can prolong the period of glucocorticoid therapy unnecessarily, increase the cumulative
glucocorticoid dose, and heighten the likelihood of treatment-related adverse effects.
Both the ESR and CRP are imperfect biomarkers in GCA. The ESR usually rises with age (a value
of 40 mm/hour may be normal for an 80-year-old), and, in some patients, abnormalities of
serum proteins unrelated to GCA can spuriously elevate the ESR. Examples include monoclonal
gammopathies and hypergammaglobulinemia secondary to liver disease. Though the ESR and
CRP have not been directly compared for the assessment of disease activity in GCA, clinical
experience argues strongly that the CRP is more useful. (See "Clinical manifestations of giant
cell arteritis", section on 'Erythrocyte sedimentation rate and C-reactive protein' and "Acute
phase reactants", section on 'Clinical use'.)
Relapse — Relapse of GCA should be suspected when patients have a return of symptoms

that recall their original presentations, when new symptoms compatible with the diagnosis of
GCA or PMR occur, or when there is a striking elevation of acute phase reactants. Elevations of
the ESR or CRP do not always indicate a disease flare, but their occurrence should trigger close
clinical follow-up and questioning of patients about symptoms of recurring disease.
For relapses of disease activity, an increase in the glucocorticoid dose should be appropriate to
the nature of the relapse. For visual symptoms attributable to GCA (generally occurring within
the first weeks of the initial diagnosis of disease), an increase of the prednisone dose to 30 to 60

mg/day and even pulse doses may be needed. Much smaller increments in the daily dose of
prednisone, between 5 to 7.5 mg/day, are appropriate for PMR symptoms.
Reports on the incidence of relapses in GCA, all assembled from tertiary care centers, vary
widely, from 34 to 74 percent [20-24]. This range is due in part to a lack of consensus regarding
the definition of what constitutes a relapse. In some analyses, asymptomatic rises in the acute
phase reactants were counted as a flare of GCA, and, in others, a recrudescence of symptoms
only, unaccompanied by rises in the acute phase reactants, was included. All studies construed
the appearance of PMR as a relapse of GCA.
Notwithstanding the heterogeneity of the data collection, there is agreement on several clinical
points. The majority of relapses in GCA occur at doses of prednisone below 20 mg/day and are
most prevalent during the first year of treatment. Headache and PMR are the most common
symptomatic expressions of relapse. Other symptoms include jaw claudication, the
development of ischemic limb symptoms, and the recurrence of constitutional symptoms.
Persisting elevations of the acute phase reactants in the absence of alternative explanations
and especially if accompanied by constitutional symptoms should prompt consideration of
underlying large vessel vasculitis and advanced diagnostic imaging. Finally, and importantly, the
occurrence of sight loss after an initial course of high-dose glucocorticoid treatment,
administered daily, is exceptional. (See 'Efficacy' above.)
An initially intense acute phase response, as manifested by anemia and significant elevations of
the ESR and CRP [21,22], has been associated with an increased risk of relapse.
Late relapses (and recurrences) of GCA are described, leading to protracted glucocorticoid
treatment. In one study, one-half of patients were still on treatment after five years [23]. Other
estimates of the total duration of glucocorticoid treatment are in the range of one to two years
[25,26], which is more consonant with clinical practice.
Risks of glucocorticoid therapy — The risks of high-dose and of chronic glucocorticoid

therapy are well known. A population-based study of 120 GCA patients diagnosed between 1950
and 1991 found that 86 percent experienced at least one adverse event, which included
posterior subcapsular cataracts, fractures, infections, hypertension, diabetes mellitus, and
osteonecrosis [11]. The median duration of treatment to reach a prednisone dose of 7.5 mg/day
was six months. Adverse events correlated with increased age and cumulative glucocorticoid
dose but not with a higher initial dose. Other side effects of glucocorticoids, less frequently
enumerated but of no less concern, or even explicit morbidity for the patient, include weight
gain, hair loss, and capillary fragility. The latter can be especially problematic in older adults on
antiplatelet or anticoagulant therapies. (See "Major side effects of systemic glucocorticoids".)

It is the potential toxicities of glucocorticoids, despite their unquestionable value in the

treatment of GCA, particularly for the prevention of sight loss, that has led to the search for
glucocorticoid-sparing strategies.
GLUCOCORTICOID-SPARING AGENTS
Adjunctive treatment for giant cell arteritis (GCA) may be used in situations where
glucocorticoid-related toxicities have ensued or are anticipated. Options include tocilizumab
(TCZ) or methotrexate (MTX).
Indications — Indications for the addition of a glucocorticoid-sparing agent include:
● The presence of significant premorbid diseases

● The emergence of significant glucocorticoid-related side effects during the course of
treatment
● A relapsing course necessitating protracted glucocorticoid use
Preexisting diabetes mellitus on treatment, osteoporosis, and significant obesity should prompt
consideration for the early implementation of a concurrent glucocorticoid-sparing strategy.
Symptoms such as recurring headache that require only lesser adjustments in the
glucocorticoid dose or a minor slowing of the glucocorticoid taper are not grounds for
adjunctive treatment. The same is true for the emergence of polymyalgia rheumatica (PMR),
which needs only low-dose glucocorticoids for treatment. Recurring symptoms should be clearly
attributable to GCA and other diagnoses excluded before adding a glucocorticoid-sparing
agent.
Choice of agent and practical considerations — TCZ or MTX are options for use as
glucocorticoid-sparing agents. On the basis of published data and clinical experience, we favor
TCZ as a glucocorticoid-sparing agent if there are no contraindications. (See 'Tocilizumab'
below.)
A pragmatic concern with the use of TCZ in the management of GCA pertains to its effects on
the acute phase reactants. Interleukin (IL)-6 is a major driver of the acute phase response
through its induction of hepatic synthesis of acute phase proteins (see "Acute phase reactants").
Blockade of IL-6 usually completely normalizes the erythrocyte sedimentation rate (ESR) and C-
reactive protein (CRP), with the result that the assessment of GCA in a patient on TCZ must rely
on clinical evaluation and, in the case of large vessel involvement, periodic imaging studies.
There continues to be an unfulfilled need for a reliable marker for active disease in GCA.

Whether TCZ should be deployed for the routine care of all patients with GCA (that is, at the
start of treatment, simultaneous with glucocorticoids) is an evolving issue. Though in the
randomized controlled study of TCZ, the drug was initiated at the start of treatment, additional
studies are needed to fully define the drug's long-term safety and efficacy (see 'Tocilizumab'
below). At this time, we reserve TCZ for the management of individual patients who are at high
risk for glucocorticoid toxicity, who incur glucocorticoid-related side effects during the course of
treatment, or who experience relapsing disease.
Though MTX is of but modest efficacy, its use can be supported in the individual patient.
Concurrent use of MTX and higher glucocorticoid doses warrants use of prophylaxis for
Pneumocystis jirovecii pneumonia (PCP) (see 'Prevention of opportunistic infections' below). The
routine addition of MTX to glucocorticoid therapy for GCA is not recommended.
Treatment options
Tocilizumab — The use of TCZ, an IL-6 receptor antagonist, for the treatment of GCA was
suggested by evidence that IL-6 is important in disease pathogenesis. TCZ can be administered
using the same dosing regimen as that for rheumatoid arthritis (see "Treatment of rheumatoid
arthritis in adults resistant to initial conventional nonbiologic DMARD therapy", section on
'Methotrexate plus IL-6 inhibitor/IL-6 inhibitor monotherapy'). The optimal timing and duration
of therapy are as yet unknown.
The beneficial effects of TCZ as a glucocorticoid-sparing intervention have been demonstrated

in two randomized trials [27,28]. In an industry-sponsored trial, 251 patients with GCA were
randomly assigned to receive either weekly or every-other-week subcutaneous TCZ injections,
combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over
a period of either 26 weeks or 52 weeks [28]. Patients with evidence of critical optic ischemia
were not enrolled in the study. Sustained remission at 52 weeks occurred in 56 percent of the
weekly TCZ group and in 53 percent of the every-other-week TCZ group, compared with 14
percent of the placebo group who tapered over 26 weeks and 18 percent of the placebo
(prednisone-only) group who tapered over 52 weeks. The cumulative median prednisone dose
over the 52-week period in each TCZ group was 1862 mg, as compared with 3296 mg in the
placebo group on the 26-week taper and 3818 mg in the placebo group on the 52-week taper.
Serious adverse events were more common in the placebo groups, most of which were related
to infection. One patient in the group receiving TCZ every other week had an episode of anterior
ischemic optic neuropathy (AION) that resolved with glucocorticoid treatment.
The optimal duration of therapy with TCZ is unknown, and information about long term effects
of TCZ treatment on the disease course are limited [27,28]. A small prospective observational

study followed 17 of the patients from the TCZ arm of the phase 2 trial who were in remission
after the 52-week treatment [27,29]. Approximately half of the patients relapsed (8 of 17) after a
mean of 6 months, while the other patients stayed in remission during the mean follow-up of 28
months. Magnetic resonance angiography (MRA) was performed in all patients, and wall
enhancement of the descending aorta persisted in all patients at follow-up.
It remains to be seen whether TCZ has a fundamental, rather than suppressive, effect on the
underlying pathophysiology of GCA. In a case report, a patient with GCA in apparent remission
on TCZ died of a postoperative myocardial infarction and was found on postmortem
examination to have active arteritis of the aorta, subclavian arteries, and right superficial
temporal artery [30].
TCZ carries a black box warning about the risk of opportunistic infection.
Methotrexate — Three randomized trials comparing MTX with placebo in patients with GCA
treated with glucocorticoids reached divergent conclusions [6,31,32]. Of note, the doses of MTX
used in the trials were low by contemporary standards, only 10 mg to 15 mg per week. A meta-
analysis of the individual patient-level data of 161 patients from these three trials suggested
that the add-on use of MTX resulted in a statistically significant reduction in the cumulative dose
of glucocorticoids over the 48 weeks following randomization (cumulative dose reduction of
prednisone or equivalent of 842 mg), a decreased rate of first and second relapse, and a higher
probability of achieving a glucocorticoid-free remission [33]. There were no differences in
adverse effects between the two treatment groups. The superiority of MTX over placebo
appeared only after 24 to 36 weeks. A systematic review of the methodology of the three
studies concluded that it was the trial of highest quality that reported benefit for adjunctive MTX
[34].
These results are consistent with clinical experience, and suggest that MTX, at best, is only
moderately effective for the management of GCA.
Other agents — Several other glucocorticoid-sparing agents have been reported as having

efficacy as adjunctive treatment for GCA, but their use cannot be endorsed because of small
effect, potential toxicity, lack of controls, or small numbers of patients studied.
● Abatacept – A trial of abatacept, a blocker of T-cell costimulation, was proposed on the basis
of the presence of activated CD4+ T cells in the typical inflammatory infiltrate of the
temporal artery in GCA [35] (see "Pathogenesis of giant cell arteritis"). In a phase 2
randomized, double-blind study of patients with newly diagnosed or relapsing GCA, 49
patients were enrolled and treated with prednisone and intravenous abatacept,
administered on days 1, 15, 29, and 56. At week 12, 41 patients were in remission and were

randomized to continue treatment with monthly abatacept or placebo. Prednisone was

tapered by a standardized schedule and discontinued by week 28. The rate of sustained
remission at 12 months in patients treated with abatacept compared with placebo was of
borderline significance, 48 versus 31 percent (p = 0.049). There was no difference in adverse
events, including infection, between the two groups.
Further study is needed to determine a possible role for abatacept as adjunctive treatment
for GCA.
● Azathioprine – In a study from a single center of 31 patients with GCA, PMR, or both, a
double-blind randomized controlled study of azathioprine, 150 mg/day, versus placebo
showed a small but statistically significant reduction in mean prednisolone dose at 52
weeks (1.9 mg/day ± 0.84 versus 4.2 mg/day ± 0.58) [36]. Only 20 patients completed the
study.
● Ustekinumab – T helper (Th)1 and Th17 cells are believed to play key roles in the
pathogenesis of GCA [37] (see "Pathogenesis of giant cell arteritis"). Ustekinumab blocks IL-
12, a Th1-promoting cytokine, and IL-23, a Th17-promoting cytokine, providing a theoretical
basis for its use in the treatment of GCA. In an open-label study of ustekinumab in 14
patients with refractory GCA, the prednisolone dose was decreased from a median of 20
mg/day to 5 mg/day; four patients discontinued glucocorticoid therapy entirely [38].
● Cyclophosphamide – Cyclophosphamide has been widely used in the treatment of systemic

vasculitis. A few small, uncontrolled studies have suggested that it may be useful in GCA in
patients at high risk of glucocorticoid-related adverse effects who have not responded
adequately to other immunosuppressive or immunomodulatory glucocorticoid-sparing
treatments [39-41]. A systematic review identified 103 published cases for analysis [41]. The
major indications for cyclophosphamide, administered either orally or intravenously,
included glucocorticoid-dependency or relapsing disease. Most of the reported patients (86
percent) responded, but 22 percent relapsed despite maintenance immunosuppressive
therapy. Adverse effects were described in one-third of the patients, and 12.5 percent
discontinued the therapy because of infections and cytopenias. One death due to hepatitis
was reported.
● Others – Small, uncontrolled, retrospective series have proposed benefit for dapsone [42],
leflunomide [43], and IL-1 blockade [44] for the management of GCA.
Lack of benefit of anti-TNF therapy — Because GCA is characterized by granulomatous

inflammation, tumor necrosis factor (TNF) inhibition would appear to be an appropriate
approach to treatment. However, several small randomized trials of TNF inhibition have found

that infliximab, etanercept, and adalimumab are ineffective in patients with GCA [45-47]. As an
example, 44 patients were studied in a multicenter, randomized, placebo-controlled trial of
infliximab for the maintenance of remission [45]. After prednisone-induced remission, patients
were randomly assigned in a 2:1 ratio to infliximab 5 mg/kg or placebo. An interim analysis at
week 22 demonstrated that infliximab did not reduce the proportion of patients with relapses
(43 versus 50 percent on placebo). In addition, infliximab did not increase the proportion of
patients whose prednisone dose could be tapered to 10 mg/day without relapse (61 versus 75
percent). Consequently, the trial was stopped early. Through the follow-up period, no
differences between the treatment groups were observed in the proportion of relapse-free
patients, the cumulative dose of prednisone, or the incidence of adverse events.
GENERAL MEASURES IN ALL PATIENTS
Additional monitoring and interventions to prevent complications of disease and therapy should
be implemented at the beginning of treatment. Screening tests for tuberculosis and
immunizations against influenza and pneumococcal pneumonia must be up to date.
Routine follow-up — Monthly follow-up visits for the first six months of treatment are
desirable, though their frequency will be subject to the exigencies of logistical issues.
Laboratory data, which can be tracked even if the patient resides a long distance from the
clinician, should be monitored at least as frequently. Subsequent follow-up visits can be spaced
out to every three months. Ultimately, all matters of follow-up (the interval between clinician
visits, the frequency of laboratory monitoring, and the speed of the glucocorticoid taper) are
governed by the clinical course of the given patient and must be individualized accordingly.
Patients should be counseled to be watchful for symptoms of polymyalgia rheumatica (PMR) or
giant cell arteritis (GCA) and should be encouraged to seek medical attention immediately if any
symptoms are noted. At each visit, patients should routinely be asked about cranial symptoms
(eg, headache, visual symptoms, jaw claudication) as well as any new or worsening symptoms of
large vessel involvement (eg, limb claudication).
Patients should also be monitored for glucocorticoid-related adverse effects including

osteoporosis, infection, diabetes, and ocular complications such as posterior subcapsular
cataracts and glaucoma [11]. (See "Major side effects of systemic glucocorticoids".)
Antiplatelet therapy — In view of the conflicting observational data, the use of low-dose
aspirin in patients with newly diagnosed GCA should be guided by current recommendations for
the management of atherosclerosis [9]. If low-dose aspirin is used, a proton pump inhibitor
should also be administered as aspirin, age, and high-dose glucocorticoids are all risk factors

for gastrointestinal bleeding. (See "NSAIDs (including aspirin): Primary prevention of

gastroduodenal toxicity", section on 'Proton pump inhibitors'.)
Retrospective analyses disagree on the value of low-dose aspirin in the management of GCA. In
two cohorts, the odds ratios of so-called cranial ischemic events (sight loss and stroke) were
reduced in GCA patients on antiplatelet therapy or anticoagulants, mainly the former, compared
with patients on no such treatment [48,49]. In these studies, the majority of the aspirin-treated
patients had been taking low-dose aspirin for the management of preexisting cardiovascular or
cerebrovascular disease prior to the diagnosis of GCA and initiation of glucocorticoid therapy.
Three other studies found no effect of established platelet inhibition on the occurrence of visual
loss or stroke in newly diagnosed GCA [49-51]. None of the reports found an increased risk of
gastrointestinal bleeding in the aspirin-treated patients.
Osteoporosis prevention — Because of the length of the course of glucocorticoid treatment

for GCA, osteoporosis prevention should be aggressively pursued at the start of therapy.
Adequate dietary calcium and vitamin D intake should be encouraged. Determination of bone
mineral density near the time that treatment is begun is essential for guiding management of
bone loss. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".)
Prevention of opportunistic infections — Among the familiar risks of high-dose glucocorticoid

use is infection. A study using administrative data found that patients with GCA, compared with
a matched historical cohort, had increased rates of lower respiratory tract infections, urinary
tract infections, and serious infections (defined as pneumonias, upper urinary tract infections,
and sepsis) [52]. As would be expected, the increased rate of infections was highest during the
first six months after the diagnosis of GCA, during the period of greatest glucocorticoid
exposure.
There are rare reports of P. jirovecii pneumonia (PCP) in GCA. In a 32-year study from a tertiary
care center, seven GCA patients with PCP were identified, two of whom had received concurrent
treatment with methotrexate (MTX) [53]. In another report from a single center, 4 of 62 patients
with GCA developed PCP, all of whom were under treatment with concurrent glucocorticoids
and MTX [54]. Numerous clinical trials of treatments for GCA have contained no reported cases
of PCP.
As opportunistic infection with P. jirovecii in GCA patients receiving only glucocorticoid therapy is
exceptional, we do not recommend routine PCP prophylaxis in this situation. If MTX is used
concurrently with high-dose glucocorticoids, then PCP prophylaxis should be deployed.
When to refer to a rheumatologist — Because of the potential toxicities inherent in the use of

high-dose glucocorticoid therapy in older adults, formal rheumatologic consultation can be

considered at the start of treatment for patients with newly diagnosed GCA, especially if the
clinician lacks experience with the disease. Rheumatology consultation must be obtained if the
initial workup for GCA is negative and a diagnosis of biopsy-negative disease is contemplated, if
the glucocorticoid taper is marked by recurring symptoms or glucocorticoid-related side effects,
or if there is consideration for implementing a glucocorticoid-sparing strategy.
LARGE VESSEL GCA
Overall approach — Large vessel giant cell arteritis (GCA) refers to involvement of the aorta
and the great vessels, most commonly the subclavian arteries and distally to the axillary and
brachial arteries. We initially manage patients with large vessel GCA with glucocorticoid therapy
in a manner similar to those with cranial GCA, and likewise utilize glucocorticoid-sparing agents
(ie, for patients with an initial high risk of glucocorticoid toxicity, the emergence of
glucocorticoid-induced side effects, or relapsing disease).
Whether large vessel involvement may require more protracted or intensive treatment is
unclear. One retrospective cohort study compared 120 patients with large vessel GCA, as
defined by evidence of subclavian involvement on imaging, with 240 patients with cranial GCA.
The patients with large vessel GCA had a higher cumulative glucocorticoid dose after one year
of treatment, relapsed more frequently, and received more adjunctive immunosuppressant
therapies [55].
Imaging studies have shown that large vessel involvement in GCA is common in patients with
cranial arteritis and can be demonstrated in 30 to 80 percent of patients, depending on
methodology [56-60]. The finding of such involvement, if asymptomatic or uncomplicated, is not
a priori grounds for escalation of treatment. (See "Diagnosis of giant cell arteritis", section on
'Imaging modalities' and "Clinical manifestations of giant cell arteritis", section on 'Large vessel
involvement'.)
Specific manifestations
Aortic aneurysms — Clinical studies that would inform the management of aortic

aneurysms in GCA are lacking.
Prospective imaging studies have shown evidence for aortitis in 45 to 65 percent of GCA
patients [56,61]. The development of aneurysms, especially of the thoracic aorta, is less
common, of which a small number dissect or rupture [62-64]. Risk factors for the development
and progression of aortic aneurysms in GCA, however, have not been clarified. Additionally, the
effects of glucocorticoid therapy and glucocorticoid-sparing therapies have not been

retrospectively or prospectively studied, so whether treatment affects the two critical clinical
outcomes of aortic aneurysm (progression and dissection or rupture) remains undefined.
Management of aortic aneurysms in GCA thus remains problematic.
For aortic aneurysms between 3 and 5 cm in diameter that are enlarging and whose presence is
associated with increased acute phase reactants, resumption or an increase in glucocorticoid
therapy should be considered. Additional medical management of thoracic aortic aneurysm and
dissections are discussed in detail separately. (See "Management of thoracic aortic aneurysm in
adults" and "Management of acute aortic dissection".)
Ischemic limb symptoms — Most ischemic limb symptoms improve or stabilize with medical
management in GCA. Vasculitic narrowing of large arteries, such as the subclavian artery, is
usually gradual and accompanied by the development of an extensive web of collateral vessels (
image 1). With treatment of the underlying inflammatory process, the collateral circulation is
commonly adequate to maintain the viability of distal tissues, even though there is some
incident limb ischemia or diminished or absent peripheral arterial pulsations (brachial, radial,
and ulnar). In one report of 53 treated patients with subclavian involvement due to GCA,
symptoms and signs of ischemia resolved in 15 (27 percent), improved in 30 (55 percent), and
were unchanged in 8 (15 percent) [65].
Revascularization of arteries to the extremities (eg, angioplasty, stent placement, or bypass

surgery) is seldom required. If indicated, stenting or angioplasty should be undertaken when
clinical evidence for inflammation has been suppressed with treatment. Restenosis is not
infrequent [65].
Monitoring disease activity of large vessel GCA — As markers of disease activity for large
vessel GCA, the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have the same
utilitarian value and are accompanied by the same caveats as they do for the cranial phenotype.
Repeat imaging of a newly discovered or enlarging aortic aneurysm should be considered at six
months of follow-up; if stable, the interval between imaging studies can be lengthened to an
annual basis. The choice of an imaging modality will vary by institution and individual patient
(see "Diagnosis of giant cell arteritis", section on 'Imaging modalities'). Assessment of disease
activity by any of the different imaging modalities (computed tomography [CT], CT angiography
[CTA], magnetic resonance imaging [MRI], MR angiogram [MRA], and positron emission
tomography [PET] with CT) requires careful consultation between the clinician and the
radiologist.
Role of screening for large vessel disease — The role of screening for large vessel
involvement in patients who present with cranial GCA is unsettled. Examples of such screening

could involve a PET CT scan or chest CT scan at the time of initial diagnosis or serial CT
examinations following diagnosis to assess for the development of aortic aneurysm. Because of
the uncertainties regarding the prognosis of aortic aneurysm in GCA and the lack of evidence
with respect to the effects of treatment, a program of routine screening for large vessel
involvement in all GCA patients is not currently endorsed (see "Diagnosis of giant cell arteritis",
section on 'Role of screening for large vessel GCA'). Patients should be evaluated for screening
on a case-by-case basis. As the incidence of aortic aneurysm in GCA increases over time, clinical
vigilance should be maintained [66].
Patients with an incidental diagnosis of aortitis — Aortitis of the ascending aorta can come
unexpectedly to clinical attention following surgery for an aneurysm of the ascending aorta (see
"Clinical manifestations of giant cell arteritis", section on 'Large vessel involvement'). The
histopathology of resected aneurysm is similar to that of GCA, including the presence of giant
cells.
A diagnostic workup requires a careful history and physical examination and laboratory
evaluation as indicated for underlying disease. Measurement of the acute phase reactants
immediately postoperation is useless, as the ESR and CRP are certain to be significantly
elevated. The vascular tree should be completely imaged for evidence of involvement of other
segments of the aorta and of other large arteries. Temporal artery biopsy or ultrasonography of
the temporal arteries can be considered. In approximately 20 percent of cases, systemic
rheumatic disease can be identified (classic GCA, spondyloarthropathy, Behçet syndrome, and
others), for which treatment is then pursued as appropriate [67,68].
In some patients, however, there will be no evidence for associated disease or for other vascular
involvement, and a diagnosis of idiopathic ascending noninfectious aortitis will remain. Whether
this entity lies along the spectrum of classic GCA remains unclear. In these situations, it can be
appropriate to withhold treatment (ie, glucocorticoids) as some patients will not manifest
subsequent disease activity, but attentive clinical follow-up and repeat imaging studies are
essential.
OVERALL PROGNOSIS
Giant cell arteritis (GCA) is a disease of variable duration. In some, it may have a course of one
to two years, while in others the disease is more chronic. The glucocorticoid dose can eventually
be reduced and discontinued in the majority of patients, although some patients require low
doses of prednisone for a number of years to control symptoms.

GCA does not adversely affect overall survival, excepting the subset of patients with aortic
involvement and dissection [66,69,70].
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Giant cell arteritis and
polymyalgia rheumatica".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics."
The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading
level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: Polymyalgia rheumatica and giant cell arteritis (The
Basics)")
● Beyond the Basics topics (see "Patient education: Vasculitis (Beyond the Basics)" and
"Patient education: Polymyalgia rheumatica and giant cell arteritis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
● Glucocorticoid treatment is central to the management of giant cell arteritis (GCA, also
known as Horton disease, cranial arteritis, and temporal arteritis). If vision is intact at the
time appropriate glucocorticoid treatment is initiated, the risk of sight loss is reduced to
less than 1 percent. (See 'Systemic glucocorticoids' above.)

● For all patients with GCA, we recommend initial treatment with high-dose systemic
glucocorticoids to preserve vision (Grade 1C) as well as to treat other clinical symptoms
associated with GCA (Grade 2B). Treatment should be initiated promptly once the diagnosis
is confirmed or there is a high index of suspicion for GCA. Our practice for initial dosing
glucocorticoids is as follows (see 'Initial dose' above):
• For patients without visual loss at presentation: prednisone 1 mg/kg or equivalent, not
to exceed 60 mg, given in a single daily dose
• For patients with threatened or established visual loss at presentation:

methylprednisolone 500 to 1000 mg intravenous daily, for three days
● Symptoms and signs of GCA usually respond quickly, permitting a taper of the prednisone
dose to 50 mg/day after two weeks and to 40 mg/day after another two weeks. The dose
can subsequently be reduced by 5 mg decrements every two weeks to 20 mg/day, at which
point the speed of the glucocorticoid taper is slowed. It is axiomatic that glucocorticoid
dosing be tailored to the individual patient's clinical course. (See 'Glucocorticoid tapering'
above.)
● Relapses of disease activity are most common at prednisone doses less than 20 mg/day and
are treated with increases in the glucocorticoid dose appropriate to the nature of the
relapse. Relapses usually do not result in major adverse events such as visual loss. (See
'Approach to dose reduction' above.)
● Monitoring of disease activity requires careful clinical follow-up and regular tracking of the
acute phase reactants (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]).
Minor fluctuations of the ESR and CRP are common during the course of the glucocorticoid
taper and do not of themselves mandate increases in the glucocorticoid dose. Significant
increases in the ESR and CRP warrant close clinical follow-up and consideration for a
reduction in the speed of the taper. (See 'Monitoring disease activity' above.)
● Patients should be regularly assessed for the presence of glucocorticoid-related side

effects. Measures to maintain bone health should be implemented in all patients. Low-dose
aspirin should be administered as indicated by current guidelines for management of
atherosclerosis. Routine prophylaxis against Pneumocystis jirovecii pneumonia (PCP) is not
advised. (See 'General measures in all patients' above.)
● Whether a glucocorticoid-sparing should be used for the routine care of all patients with
GCA is an evolving issue. We use an individualized approach for patients who may benefit
from a glucocorticoid-sparing agent. For patients with relapsing disease requiring a

protracted course of glucocorticoids, we suggest the addition of tocilizumab (TCZ) rather

than continuing monotherapy with glucocorticoids (Grade 2B). We also use TCZ for patients
who are at higher risk for severe glucocorticoid toxicity (eg, preexisting diabetes mellitus or
osteoporosis) or who develop significant glucocorticoid-related toxicities during treatment.
The dosing of TCZ is the same as is used for rheumatoid arthritis. Methotrexate (MTX) is an
alternative glucocorticoid-sparing agent for patients unable to take TCZ, but limited
available data and clinical experience suggest it is less effective. (See 'Glucocorticoid-
sparing agents' above.)
● The treatment strategies for large vessel GCA are similar to those used for cranial GCA. (See
'Large vessel GCA' above.)
● The management of aortic aneurysm identified during the course of GCA is hampered by
uncertainty as to the impact of treatment on progressive dilatation and dissection or
rupture. Owing to this uncertainty, screening for aortic aneurysms is not routinely
recommended but can be considered on a case-by-case basis. (See 'Role of screening for
large vessel disease' above.)
● Patients in whom a clinical diagnosis of GCA is posited after negative workup are treated
similar to those with proven GCA. (See 'Patients with negative biopsy and imaging' above.)
● GCA is a disease of variable duration. Length of treatment may extend from one to multiple
years. Glucocorticoid treatment can eventually be discontinued in the majority of patients.
(See 'Overall prognosis' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate would like to acknowledge Gene G Hunder, MD, who contributed
to an earlier version of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 8240 Version 27.0

GRAPHICS
Narrowing of the left subclavian artery in giant cell arteritis
Angiogram of the left subclavian artery in GCA, showing several areas of severe vascular
narrowing but a proliferation of small blood vessels forming excellent collateral circulation. The
long, smooth arterial tapering in large vessel GCA is often not amenable to revascularization
interventions such as angioplasty or stent placement. Those types of interventions are rarely
necessary.
GCA: giant cell arteritis.
Courtesy of John H Stone, MD, MPH.
Graphic 73553 Version 8.0

Contributor Disclosures
William P Docken, MD Nothing to disclose Jonathan Trobe, MD Nothing to disclose Eric L Matteson,
MD, MPH Grant/Research/Clinical Trial Support: Sun Pharmaceutical Industries, Ltd [Basic science
investigation concentrating on rheumatoid lung disease]. Consultant/Advisory Boards: Boehringer-
Ingelheim [Interstitial lung disease]; Gilead Sciences [Rheumatoid arthritis]; TympoBio [Autoimmune
hearing loss]; Arena Pharmaceuticals [Autoimmune Diseases]. Speaker's Bureau: Practice Point
Communications [Treatment of rheumatoid arthritis]. Other Financial Interest: SAB Biotherapeutics, Inc –
Data and Safety Monitoring Board [Infectious diseases/viral neutralizing antibodies]. Monica Ramirez
Curtis, MD, MPH Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
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Patients with positive biopsy or imaging — High-dose systemic glucocorticoids are the

https://www.uptodate.com/contents/treatment-of-giant-cell-arteritis/print?search=epidemiology giant cell arteritis&topicRef=8225&source=see_link 1/26

prednisone, glucocorticoid-sparing strategies include the addition of tocilizumab (TCZ) or

Efficacy — Though never studied in a placebo-controlled manner, the effectiveness of

https://www.uptodate.com/contents/treatment-of-giant-cell-arteritis/print?search=epidemiology giant cell arteritis&topicRef=8225&source=see_link 2/26

Initial dose — Though the efficacy of glucocorticoids for the treatment of GCA is

Patients usually report dramatic improvements of many GCA-related symptoms (eg,

https://www.uptodate.com/contents/treatment-of-giant-cell-arteritis/print?search=epidemiology giant cell arteritis&topicRef=8225&source=see_link 3/26

● Threatened or established visual loss at diagnosis – If there is a strong suspicion of GCA

Preexisting sight loss can progress, despite initiation of glucocorticoid therapy, in

Approach to dose reduction — We maintain the starting dose of high-dose prednisone

https://www.uptodate.com/contents/treatment-of-giant-cell-arteritis/print?search=epidemiology giant cell arteritis&topicRef=8225&source=see_link 4/26

Monitoring disease activity — One of the most challenging aspects of GCA treatment is

Relapse — Relapse of GCA should be suspected when patients have a return of symptoms

https://www.uptodate.com/contents/treatment-of-giant-cell-arteritis/print?search=epidemiology giant cell arteritis&topicRef=8225&source=see_link 5/26

Risks of glucocorticoid therapy — The risks of high-dose and of chronic glucocorticoid

https://www.uptodate.com/contents/treatment-of-giant-cell-arteritis/print?search=epidemiology giant cell arteritis&topicRef=8225&source=see_link 6/26

It is the potential toxicities of glucocorticoids, despite their unquestionable value in the

Indications — Indications for the addition of a glucocorticoid-sparing agent include:

● The presence of significant premorbid diseases

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The beneficial effects of TCZ as a glucocorticoid-sparing intervention have been demonstrated

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Other agents — Several other glucocorticoid-sparing agents have been reported as having

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randomized to continue treatment with monthly abatacept or placebo. Prednisone was

● Cyclophosphamide – Cyclophosphamide has been widely used in the treatment of systemic

Lack of benefit of anti-TNF therapy — Because GCA is characterized by granulomatous

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GENERAL MEASURES IN ALL PATIENTS

Patients should also be monitored for glucocorticoid-related adverse effects including

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for gastrointestinal bleeding. (See "NSAIDs (including aspirin): Primary prevention of

Osteoporosis prevention — Because of the length of the course of glucocorticoid treatment

Prevention of opportunistic infections — Among the familiar risks of high-dose glucocorticoid

When to refer to a rheumatologist — Because of the potential toxicities inherent in the use of

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LARGE VESSEL GCA

Aortic aneurysms — Clinical studies that would inform the management of aortic

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Revascularization of arteries to the extremities (eg, angioplasty, stent placement, or bypass

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SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

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• For patients with threatened or established visual loss at presentation:

● Patients should be regularly assessed for the presence of glucocorticoid-related side

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protracted course of glucocorticoids, we suggest the addition of tocilizumab (TCZ) rather

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2. González-Gay MA, García-Porrúa C. Systemic vasculitis in adults in northwestern Spain,

9. Bienvenu B, Ly KH, Lambert M, et al. Management of giant cell arteritis: Recommendations

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36. De Silva M, Hazleman BL. Azathioprine in giant cell arteritis/polymyalgia rheumatica: a

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43. Diamantopoulos AP, Hetland H, Myklebust G. Leflunomide as a corticosteroid-sparing

47. Martínez-Taboada VM, Rodríguez-Valverde V, Carreño L, et al. A double-blind placebo