British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis: executive summary

NICE has accredited the process used by the BSR to produce its guideline on the diagnosis and treatment of giant cell arteritis. Accreditation is valid for 5 years from 29 May 2019. More information on accreditation can be viewed at www.nice.org.uk/accreditation. For full details on our accreditation visit: www.nice.org.uk/accreditation. 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. This guideline was developed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) to produce evidence-based recommendations [10]. ‘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. 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. 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. 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. 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. 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. A proposed list of clinical assessments that could be carried out at or near diagnosis of GCA Height and weight Features of GCA relevant to prognosis: fever, sweats or weight loss; ischaemic manifestations (jaw claudication, tongue claudication) Signs and symptoms indicating involvement of extracranial arteries, e.g. bruits, different blood pressures in the two arms, limb claudication Ophthalmological evaluation for patients with transient or permanent visual loss or diplopia History of comorbidities and medications that might predispose to glucocorticoid-related adverse effects: infection, hypertension, diabetes, osteoporosis, low-trauma fracture, dyslipidaemia, peptic ulcer, psychiatric adverse effects Features that may suggest alternative diagnosis, e.g. neurological deficits, very severe constitutional symptoms or localized ear, nose and throat signs Measures of activity of GCA: laboratory markers of inflammation (CRP for all patients, plus either ESR or plasma viscosity) and full blood count (platelet count may be elevated in GCA) Consider serum protein electrophoresis and urine Bence–Jones protein/serum free light chains if ESR elevated out of proportion to CRP Baseline laboratory tests of major organ system function (plasma glucose, renal and liver function tests, calcium and alkaline phosphatase) Screening tests for risk of serious infectiona (may include urine dipstick, chest radiograph, tests for latent tuberculosis according to local or national protocol) Screening tests for osteoporosis riska [may include TSH, vitamin D, bone density test (DXA)] Height and weight Features of GCA relevant to prognosis: fever, sweats or weight loss; ischaemic manifestations (jaw claudication, tongue claudication) Signs and symptoms indicating involvement of extracranial arteries, e.g. bruits, different blood pressures in the two arms, limb claudication Ophthalmological evaluation for patients with transient or permanent visual loss or diplopia History of comorbidities and medications that might predispose to glucocorticoid-related adverse effects: infection, hypertension, diabetes, osteoporosis, low-trauma fracture, dyslipidaemia, peptic ulcer, psychiatric adverse effects Features that may suggest alternative diagnosis, e.g. neurological deficits, very severe constitutional symptoms or localized ear, nose and throat signs Measures of activity of GCA: laboratory markers of inflammation (CRP for all patients, plus either ESR or plasma viscosity) and full blood count (platelet count may be elevated in GCA) Consider serum protein electrophoresis and urine Bence–Jones protein/serum free light chains if ESR elevated out of proportion to CRP Baseline laboratory tests of major organ system function (plasma glucose, renal and liver function tests, calcium and alkaline phosphatase) Screening tests for risk of serious infectiona (may include urine dipstick, chest radiograph, tests for latent tuberculosis according to local or national protocol) Screening tests for osteoporosis riska [may include TSH, vitamin D, bone density test (DXA)] Screening tests for infection and osteoporosis to be considered in light of relevant local and national guidelines. TSH: thyroid stimulating hormone; DXA: dual-energy X-ray absorptiometry. A proposed list of clinical assessments that could be carried out at or near diagnosis of GCA Height and weight Features of GCA relevant to prognosis: fever, sweats or weight loss; ischaemic manifestations (jaw claudication, tongue claudication) Signs and symptoms indicating involvement of extracranial arteries, e.g. bruits, different blood pressures in the two arms, limb claudication Ophthalmological evaluation for patients with transient or permanent visual loss or diplopia History of comorbidities and medications that might predispose to glucocorticoid-related adverse effects: infection, hypertension, diabetes, osteoporosis, low-trauma fracture, dyslipidaemia, peptic ulcer, psychiatric adverse effects Features that may suggest alternative diagnosis, e.g. neurological deficits, very severe constitutional symptoms or localized ear, nose and throat signs Measures of activity of GCA: laboratory markers of inflammation (CRP for all patients, plus either ESR or plasma viscosity) and full blood count (platelet count may be elevated in GCA) Consider serum protein electrophoresis and urine Bence–Jones protein/serum free light chains if ESR elevated out of proportion to CRP Baseline laboratory tests of major organ system function (plasma glucose, renal and liver function tests, calcium and alkaline phosphatase) Screening tests for risk of serious infectiona (may include urine dipstick, chest radiograph, tests for latent tuberculosis according to local or national protocol) Screening tests for osteoporosis riska [may include TSH, vitamin D, bone density test (DXA)] Height and weight Features of GCA relevant to prognosis: fever, sweats or weight loss; ischaemic manifestations (jaw claudication, tongue claudication) Signs and symptoms indicating involvement of extracranial arteries, e.g. bruits, different blood pressures in the two arms, limb claudication Ophthalmological evaluation for patients with transient or permanent visual loss or diplopia History of comorbidities and medications that might predispose to glucocorticoid-related adverse effects: infection, hypertension, diabetes, osteoporosis, low-trauma fracture, dyslipidaemia, peptic ulcer, psychiatric adverse effects Features that may suggest alternative diagnosis, e.g. neurological deficits, very severe constitutional symptoms or localized ear, nose and throat signs Measures of activity of GCA: laboratory markers of inflammation (CRP for all patients, plus either ESR or plasma viscosity) and full blood count (platelet count may be elevated in GCA) Consider serum protein electrophoresis and urine Bence–Jones protein/serum free light chains if ESR elevated out of proportion to CRP Baseline laboratory tests of major organ system function (plasma glucose, renal and liver function tests, calcium and alkaline phosphatase) Screening tests for risk of serious infectiona (may include urine dipstick, chest radiograph, tests for latent tuberculosis according to local or national protocol) Screening tests for osteoporosis riska [may include TSH, vitamin D, bone density test (DXA)] Screening tests for infection and osteoporosis to be considered in light of relevant local and national guidelines. TSH: thyroid stimulating hormone; DXA: dual-energy X-ray absorptiometry. 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. 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. An example of glucocorticoid tapering for GCA An example of glucocorticoid tapering for GCA Examples of symptoms that may signify relapse of GCA during glucocorticoid taper that require further evaluation and, if judged to be due to GCA relapse, escalation of glucocorticoid treatment Examples of symptoms that may signify relapse of GCA during glucocorticoid taper that require further evaluation and, if judged to be due to GCA relapse, escalation of glucocorticoid treatment 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. 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. 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. 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]. A possible approach to using rapid-access vascular ultrasound to assist in clinical diagnostic decision making in suspected cranial GCA 1 a possible approach to using rapid-access vascular if available, in suspected GCA. of the probability of GCA is based on all information available laboratory tests and alternative explanations for the clinical and can be based on new information results of temporal and axillary ultrasound and/or results of temporal artery This assessment is based on clinical and should ideally be by an individual with specialist that for a probability of GCA, may be to an ultrasound prior to in the biopsy is negative. For a clinical probability of GCA, a positive ultrasound may be as in these cases is still to a biopsy in to ultrasound in to further increase diagnostic In the absence of clinical features of cranial GCA, temporal artery biopsy can still be but imaging of the extracranial may be considered instead or in temporal artery clinical have proposed to assist clinicians in the of probability of the of a clinical developed in setting should ideally be using local prior to into local clinical practice. If rapid-access vascular ultrasound is not available, patients treated for suspected GCA should all have a temporal artery of these tests should the of high-dose glucocorticoid therapy for patients with strongly suspected GCA. 2. recommendation: or axillary artery ultrasound may be used to involvement of the aorta and its proximal Consensus score: involvement of the aorta and its proximal branches in GCA may be asymptomatic or only with constitutional symptoms, in vascular imaging of the aorta and its proximal branches can be to or can be for assessment of vascular although of the arteries with or may also be for of and include potential in the of alternative such as and Ultrasound can the axillary arteries, but ultrasound evaluation of the arteries is more 3. recommendation: The glucocorticoid dose for GCA is mg Consensus score: The of patients with GCA within to a mg daily dose of from such as established visual stroke or necrosis. to to this dose should of the 4. recommendation: GCA patients with acute or visual loss may be given daily for to 3 before commencing If therapy is not immediately possible, this should not initiation of Consensus score: Acute visual loss due to ischaemia in GCA requires immediate If glucocorticoid therapy is not possible, mg prednisolone may be given for to 3 days. have not in patients with acute ischaemia, but indicate that the of visual loss in GCA before initiation of glucocorticoid therapy [3]. 5. recommendation: dose should be to providing there is no of GCA symptoms, signs or laboratory markers of A more dose is appropriate for patients at risk of glucocorticoid and/or receiving glucocorticoid-sparing Consensus score: All taper schedules and clinical and communication between patients and care providers should symptoms (see 2 and recommendation: Patients should be a daily dose of glucocorticoid than or daily Consensus score: 9.53. can be for the use of in the treatment of GCA. Consensus score: 8. recommendation: might be considered for GCA, in with a glucocorticoid in patients at risk of glucocorticoid or who relapse. is evidence to any other in GCA, including or Consensus score: which may be given or by has used at of mg in clinical and to mg in clinical practice. On the of in patients with GCA, the evidence for methotrexate as a glucocorticoid-sparing in GCA remains of the evidence In other and have not in clinical The potential of or is likely to any possible and their use is not Strong recommendation: can be considered for GCA in with a glucocorticoid especially in patients at risk of glucocorticoid or who relapse. are not recommended in GCA. +++. Consensus score: 9.61. was for GCA by the and in on the of two clinical of 1 of alongside tapering glucocorticoid therapy, for in GCA. was both in and GCA, the of a glucocorticoid-sparing therapy in GCA is likely to be in with GCA and in GCA patients for whom the dose to control disease activity the glucocorticoid dose for that for example, due to comorbidities such as glucocorticoid-related adverse or diabetes should be aware that at the time of a limited of therapy for GCA has by the and by for patient into account available at the time of the by the for and of have to in GCA. trial of for GCA has but there is evidence to a treatment for this The routine use of or agents for GCA is not Consensus score: is a of evidence for the use of or agents for GCA. and guidelines for the secondary of and other vascular should be The routine use of agents such as for GCA is not Consensus score: 9.53. is a of evidence for the use of agents for GCA. and guidelines for the secondary of and other vascular should be The British Society for Rheumatology provided support for this of of the of the PMR of the for the trial of for GCA and for for GCA local and clinical for an trial of for GCA, at supported by and from and first of imaging recommendations in first of recommendations for management of of management recommendations for and from and for and from of the The of the work is by in the of local and national guidelines for GCA in The Involvement in the GCA which is by for on GCA. and/or from and and support from and of from and from and in clinical by and in of work by for for GCA. of for in from of the BSR of the and support for from and from from and and support from and and from from the of of the GCA guideline and of the GCA guideline of on working on imaging in from and for and and in for and for on for trial as well as from and as well as ultrasound to of health a about GCA and The are of the and not necessarily of the for or the of and

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