Today, I review, link to, and excerpt from British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis: executive summary [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Rheumatology, Volume 59, Issue 3, March 2020, Pages 487-494, https://doi.org/10.1093/rheumatology/kez664
All that follows is from the above resource.
Introduction
GCA, or temporal arteritis, is a large-vessel vasculitis affecting older people [1]. Without high-dose glucocorticoid treatment, GCA can lead to occlusion of cranial blood vessels, which may result in blindness or stroke [2]. Most occurrences of blindness or stroke happen either before treatment or during the first week of treatment [3]. GCA is therefore a medical emergency requiring immediate treatment. Many patients with GCA have inflammation of the aorta and its proximal branches (extracranial large-vessel involvement), which can lead to aortic aneurysm, dissection or rupture [4]. Recent years have seen new evidence emerge regarding the diagnosis and treatment of GCA, requiring a major update of the 2010 British Society for Rheumatology (BSR) guideline [5].
Objectives: To provide guidance for clinicians in the diagnosis and treatment of GCA, supported by evidence where possible.
Target audience: This guideline is intended for doctors and allied health professionals who work in a primary or secondary care setting and manage patients with suspected and/or established GCA.
Areas not covered: Takayasu arteritis [6], isolated PMR [7, 8] and management of glucocorticoid-related complications such as osteoporosis [9].
For details concerning each section please refer to the full guideline published online.*
*British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis [Full-Text HTML] [Full-Text PDF]. Rheumatology, Volume 59, Issue 3, March 2020, Pages e1–e23, https://doi.org/10.1093/rheumatology/kez672
Resuming the executive summary:
General principles
‘General principles’ are not necessarily evidence-based but are a description of generally accepted best medical practice. Each general principle carries a consensus score (mean rating on a 0–10 scale). Further practical guidance for clinicians is also provided where relevant.
How should suspected GCA be treated?
1. Patients in whom GCA is strongly suspected should be immediately treated with high-dose glucocorticoids. Consensus score: 9.61.
‘Strongly suspected’ GCA means that in the assessing clinician’s judgement, GCA is a more likely explanation for the patient’s symptoms than any other condition. For doses, see Treatment of GCA, below.
How quickly should patients with suspected GCA be referred for evaluation?
2. GCA is a medical emergency. Each local healthcare organization should have information available to front-line clinicians, such as general practitioners and clinicians working in acute care, on how to refer patients with suspected GCA urgently for local specialist evaluation: patients should be evaluated by a specialist ideally on the same working day if possible and in all cases within 3 working days. Consensus score: 9.17.
GCA is a medical emergency and therefore ‘fast-track’ referral pathways for urgent specialist evaluation of suspected GCA are beneficial. On suspicion of GCA, primary care providers should initiate glucocorticoids alongside an urgent referral to the local GCA pathway.
To whom should patients with suspected GCA be referred?
3. Patients with suspected GCA should be evaluated by a clinician with appropriate specialist expertise, usually a rheumatologist. Patients presenting with a history of new visual loss (transient or permanent) or double vision should be evaluated as soon as possible on the same calendar day by an ophthalmologist. Consensus score: 9.61.
What evaluations should be performed when starting treatment?
4. When starting glucocorticoids for suspected GCA, diagnostically relevant symptoms and signs should be documented. Blood should be taken for full blood count, CRP and ESR before or immediately after commencing high-dose glucocorticoids. If GCA is strongly suspected, the first dose of glucocorticoid can be given without waiting for laboratory results. Consensus score: 9.61.
Diagnostically relevant symptoms and signs of GCA include headache; scalp tenderness/hyperaesthesia jaw or tongue claudication; temporal artery tenderness, nodularity or reduced pulsation; visual manifestations including diplopia or changes to colour vision; limb claudication; PMR (pain and stiffness of the shoulder and hip girdles) and fevers, sweats or weight loss. Less commonly, patients may have carotidynia, audiovestibular symptoms, dry cough or indications of tongue or scalp ischaemia that may precede necrosis. However, as none of these symptoms are entirely specific for GCA, each is of limited use if taken in isolation [11] and a differential diagnosis must also be considered. GCA causes an elevation in the platelet count, CRP and ESR. Plasma viscosity can be used where ESR is unavailable. These markers all decrease with glucocorticoid therapy, therefore all patients should have blood drawn prior to starting treatment, unless there is evidence of critical ischaemia, such as visual loss or diplopia, and no immediate access to phlebotomy.
What evaluations should be performed soon after starting treatment for GCA?
5. Patients treated for GCA should be evaluated for features of the disease relevant to prognosis, such as clinical and laboratory features of a marked inflammatory response at diagnosis, ischaemic manifestations such as transient visual loss or jaw/tongue claudication and signs or symptoms indicating involvement of the aorta and its proximal branches and for comorbidities relevant to treatment, such as diabetes mellitus, hypertension and bone fracture risk. Consensus score: 9.53.
Table 1 summarizes recommended assessments for patients with GCA. As well as confirmatory tests for GCA (see Key Recommendation 1), alternative explanations for patients’ symptoms should be considered, particularly if these confirmatory tests are negative.
It is best practice for the prescriber of glucocorticoid therapy to ensure that patients are evaluated for hypertension and hyperglycaemia (blood glucose for acute changes and/or haemoglobin A1c to identify patients that might be at greater risk) within the first 2 weeks of commencing high-dose glucocorticoids. Patients receiving high-dose glucocorticoids are at an elevated risk of osteoporosis and bone fracture; this risk should be managed appropriately.
In GCA, involvement of the aorta and its proximal branches is often asymptomatic but may cause vascular bruits or reduced blood pressure in one or both arms. Clinicians should be aware of an increased risk of thoracic aortic aneurysm and dilatation; this may occur at any time during the disease course [4]. However, routine aortic imaging for all GCA patients remains of uncertain cost-effectiveness. The optimal method and timing of imaging is still unclear [12]. Therefore clinicians are advised to use their own discretion regarding selection of patients for aortic imaging.
How should ongoing management of GCA be individualized?
6. Full assessment of the disease and comorbidities and consideration of the patient’s personal priorities should inform decisions about glucocorticoid tapering and initiation of additional treatments such as glucocorticoid-sparing therapies. Involvement of and clear communication with primary care physicians is critical, especially for management of multimorbidity. Consensus score: 9.67
Table 2 shows an example of glucocorticoid tapering for GCA. This is an example of glucocorticoid tapering based on that described in the 2010 BSR guidelines for GCA [5] and similar to the control arm of a recent clinical trial [13]. High-quality evidence comparing different glucocorticoid taper schedules in GCA is not available. Alternative approaches include, for example, reducing prednisolone by 10 mg/week in patients who are in remission on >20 mg daily and/or reducing the dose slower than stated here in patients who are on ≤5 mg daily. In all cases, taper schedules should be individualized based on the patient. For relapse management, see Table 3.
What education should patients be offered?
7. All patients with GCA should be provided with information about GCA and its treatment. Patients should receive advice on diet, physical activity and stopping smoking. Consensus score: 9.47.
Information should be available in a written format and ideally in multiple formats. Dietary considerations include mitigating the potential effects of glucocorticoid therapy on body weight, post-prandial glycaemia and bone fracture risk. Recommendations on physical activity in inflammatory arthritis and osteoarthritis [14] may be tailored to individual patients with GCA. Patients should be signposted to relevant patient support groups or charities as sources of peer support. Patients should be advised of potential symptoms of glucocorticoid withdrawal, although these are uncommon in practice. Patients should be advised about alteration of the glucocorticoid dose in intercurrent illness, especially including advice for seeking emergency attention if they suffer a vomiting illness necessitating parenteral glucocorticoid.
What plans should be made for possible future GCA relapses?
8. During glucocorticoid tapering and after glucocorticoid cessation, patients should be informed what symptoms may suggest GCA relapse and what action the patient should take in these circumstances, including first point of contact for medical advice and how to contact the team providing specialist care. Consensus score: 9.81.
Table 3 shows examples of symptoms that may signify relapse in patients with GCA and how they might be managed. This table outlines how new symptoms in GCA patients, in the absence of other risk factors or significant comorbidities, may influence management decisions. New visual loss or diplopia should be urgently evaluated by an ophthalmologist. Acute phase markers should be measured and, if found to be elevated, may increase the clinical suspicion of GCA relapse. At present, the only agents with any evidence for glucocorticoid-sparing in GCA are methotrexate and tocilizumab.
Key recommendations
The following evidence-based recommendations are graded as strong or conditional, with the quality of the evidence given as ++++ to + (unless no evidence was found) and a consensus score to indicate mean strength of agreement. Further essential elaboration is added below where necessary. The underlying evidence and additional explanatory notes are presented in more detail in the full guideline document.*
*British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis [Full-Text HTML] [Full-Text PDF]. Rheumatology, Volume 59, Issue 3, March 2020, Pages e1–e23, https://doi.org/10.1093/rheumatology/kez672
Resuming the executive summary:
Diagnostic tests for GCA
Which additional confirmatory diagnostic tests should be performed in all patients with suspected GCA? [Patient, Population or Problem, Intervention, Comparator, Outcome (PICO) 1, 2]
1. Strong recommendation: Patients with suspected GCA should have a confirmatory diagnostic test. This could be either a temporal artery biopsy at least 1 cm in length or an ultrasound of the temporal and axillary arteries, or both. Quality of evidence (QoE): +++. Consensus score: 9.33.
In selecting and interpreting the results of confirmatory diagnostic tests, pretest probability (established on clinical grounds) should be taken into account [15] (Fig. 1). A positive temporal artery biopsy showing features of inflammation characteristic of GCA, such as giant cells or panarteritis [16], confirms the diagnosis of GCA. Isolated vasa vasorum vasculitis is not diagnostic of GCA. Due to the possibility of skip lesions, the length of the biopsy should be at least 1 cm (post-fixation). Ultrasound is operator dependent and requires adequate training but has the advantage of access to both superficial temporal arteries in their entirety [15]. Where temporal artery histology findings are ambiguous (e.g. low-level inflammation restricted to the adventitia), discussion between the requesting clinician and the pathologist is desirable. In the absence of inflammatory infiltrate, a report of healed arteritis is not sufficient to diagnose GCA. If neither vascular ultrasound nor biopsy is possible, and local MRI facilities and radiology support are available, then high-resolution 3T MRI of the cranial arteries could be used instead [15].
Which tests can be used to evaluate involvement of the aorta and its proximal branches in GCA? (PICO 2, 3)
2. Conditional recommendation: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), magnetic resonance angiography (MRA), computed tomography angiography (CTA) or axillary artery ultrasound may be used to evaluate involvement of the aorta and its proximal branches. QoE: +. Consensus score: 9.36.
Since involvement of the aorta and its proximal branches in GCA may be asymptomatic or associated only with constitutional symptoms, in some circumstances directed vascular imaging of the aorta and its proximal branches can be useful to detect inflammation, stenosis or dilatation. FDG-PET can be useful for assessment of vascular inflammation, although it provides less detailed anatomic definition of the involved arteries compared with MRA or CTA. Imaging may also be useful for follow-up assessments. Additional advantages of FDG-PET and CT include potential value in the workup of alternative diagnoses such as malignancy and infection. Ultrasound can assess the axillary arteries, but ultrasound evaluation of the deeper arteries is more difficult.
Treatment of GCA
What is the best dose and route of initial glucocorticoid therapy for GCA in the absence of ischaemic visual manifestations? (PICO 1–3)
3. Conditional recommendation: The standard initial glucocorticoid dose for GCA is 40–60 mg oral prednis(ol)one per day. QoE: +. Consensus score: 9.44.
The vast majority of patients with GCA respond symptomatically within 1–7 days to a 40–60 mg daily dose of prednis(ol)one, apart from irreversible sequelae such as established visual loss, stroke or tissue necrosis. Failure to respond to this dose should prompt re-evaluation of the diagnosis.
What is the best dose and route of initial glucocorticoid therapy for GCA in the presence of ischaemic visual manifestations? (PICO 4)
4. Conditional recommendation: GCA patients with acute or intermittent visual loss may initially be given 500 mg–1 g intravenous methylprednisolone daily for up to 3 consecutive days before commencing oral prednis(ol)one therapy. If intravenous therapy is not immediately possible, this should not delay initiation of oral prednis(ol)one. QoE: +. Consensus score: 9.00.
Acute visual loss due to ocular ischaemia in GCA requires immediate action. If intravenous glucocorticoid therapy is not possible, 60–100 mg oral prednisolone may be given for up to 3 consecutive days. Clinical trials have not been conducted in patients with acute ocular ischaemia, but observational data indicate that the vast majority of visual loss in GCA occurs before initiation of glucocorticoid therapy [3].
How should glucocorticoid dose be tapered in GCA? (PICO 5)
5. Conditional recommendation: Glucocorticoid dose should be tapered to zero over 12–18 months, providing there is no return of GCA symptoms, signs or laboratory markers of inflammation. A more rapid dose reduction is appropriate for patients at high risk of glucocorticoid toxicity and/or those receiving concomitant glucocorticoid-sparing therapy. QoE: +. Consensus score: 8.81.
All taper schedules assume close and regular clinical follow-up and good communication between patients and care providers should symptoms change (see Tables 2 and 3).
What dosing frequency of oral glucocorticoid should be used in GCA? (PICO 6, 7)
6.Conditional recommendation: Patients should be prescribed a single daily dose of glucocorticoid rather than alternate-day dosing or divided daily dosing. QoE: +. Consensus score: 9.53.
