Guideline sources The following summarized guidelines for the evaluation and management of giant cell arteritis (GCA) are prepared by our editorial team based on guidelines from the American Heart Association (AHA/ACC 2022), the Vasculitis Foundation (VF/ACR 2021), the American Heart Association (AHA/ASA 2021), the British Society for Rheumatology (BSR 2020), the European League Against Rheumatism (EULAR 2020; 2018), the Swedish Society of Rheumatology (SSR 2019), the French Study Group for Large Vessel Vasculitis (GEFA 2016), the British Society for Rheumatology (BSR/BHPR 2010), and the Society for Cardiovascular Angiography and Interventions (SCAI/STS/SVM/AATS/SCA/AHA/ACR/ACC/ASA/SIR 2010). 1 2 3 4 5 6 7 8 9 10 11 12 13 13 14 Definition GCA is an inflammatory vasculitis affecting medium and large-sized arteries, with a predilection for the temporal arteries. 11 https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 1/11 7/1/23, 12:02 AM Giant cell arteritis Pathway Epidemiology In patients with GCA, the interaction of genetic and epigenetic factors causes pathologic activation of vascular dendritic cells, CD4 T cells, and macrophages, leading to granulomatous inflammation of the adventitia and hyperplasia of the intima. These vascular changes cause ischemic complications in tissues fed by medium and large-sized vessels. 13 Pathophysiology In the United States, the incidence of GCA is estimated at 18.9 cases per 100,000 person-years, while the prevalence is estimated at 228 persons per 100,000 population. 12 Disease course Ophthalmoplegia, vertebrobasilar insufficiency, central vision loss, stroke, and aortic aneurysm and rupture may occur as direct complications of vascular involvement. 13 Prognosis and risk of recurrence Permanent vision loss occurs in approximately 15-20% of patients of GCA. 14 Guidelines 1. Screening and diagnosis Diagnosis: As per EULAR 2018 guidelines: Consider establishing the diagnosis of GCA without obtaining additional tests (biopsy or further imaging) in patients with high clinical suspicion and a positive imaging. C Recognize that the diagnosis of GCA is unlikely in patients with a low clinical probability and a negative imaging. Make additional efforts towards a diagnosis in all other cases. B As per BSR 2010 guidelines: Suspect large-vessel GCA in patients with prominent systemic symptoms, limb claudication or persistently high inflammatory markers despite adequate corticosteroid therapy. B Assess for the predictive features of ischemic neuro-ophthalmic complications of GCA. B 2. Diagnostic investigations Diagnostic imaging: As per ACC 2022 guidelines, obtain prompt evaluation of the entire aorta and branch vessels with MRI or CT, with or without 18F-FDG-positron emission tomography, in patients with large vessel vasculitis. B As per ACR 2021 guidelines: https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 2/11 7/1/23, 12:02 AM Giant cell arteritis Pathway Consider obtaining noninvasive vascular imaging of the large vessels with a clinical assessment to aid in diagnosis in patients with suspected GCA and negative temporal artery biopsy results. C Consider obtaining noninvasive vascular imaging to evaluate large vessel involvement in patients with newly diagnosed GCA. C As per BSR 2020 guidelines: Obtain a confirmatory diagnostic test in patients with suspected GCA. Consider either obtaining an ultrasound of the temporal and axillary arteries or performing a temporal artery biopsy, or both. B Consider obtaining 18F-FDG-positron emission tomography, MRA, CT angiography, or axillary artery ultrasound for the evaluation of the involvement of the aorta and its proximal branches. C As per EULAR 2020 guidelines, obtain ultrasound (1b, A) or MRI to confirm the diagnosis of temporal arteritis. B As per EULAR 2018 guidelines, obtain early imaging in patients with suspected GCA to complement the clinical criteria for diagnosis, assuming high expertise and prompt availability of the imaging technique. Do not delay treatment because of imaging. A Show 7 more As per AHA 2010 guidelines, obtain CT angiography or MRA of the thoracic aorta and branch vessels to assess for aneurysms or arterial occlusion in the initial evaluation of GCA. B Initial investigations: as per BSR 2010 guidelines, obtain the following initial investigations in patients with suspected or confirmed GCA: CBC serum creatinine and urea serum electrolytes LFTs CRP and ESR urinalysis CXR other relevant investigations to exclude mimicking conditions. Assessment of comorbidities: screen patients with large vessel vasculitis for treatment-related and cardiovascular comorbidities. Offer prophylaxis and life-style advice to reduce cardiovascular risk and treatment-related complications. 3. Diagnostic procedures Temporal artery biopsy: As per ACR 2021 guidelines, consider performing an initial unilateral rather than bilateral temporal artery biopsy in patients with suspected GCA. C https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 3/11 7/1/23, 12:02 AM Giant cell arteritis Pathway Show 3 more As per BSR 2020 guidelines, consider either performing a temporal artery biopsy at least 1 cm in length or obtaining an ultrasound of the temporal and axillary arteries, or both, to confirm the diagnosis in patients with suspected GCA. B As per EULAR 2020 guidelines, perform a temporal artery biopsy to confirm the diagnosis of temporal arteritis. B 4. Medical management General principles: manage patients with large vessel vasculitis based on a shared decision between the patient and the rheumatologist, considering efficacy, safety and costs. Setting of care: As per EULAR 2020 guidelines, refer all patients presenting with signs and symptoms suggestive of GCA urgently to a specialist team for further multidisciplinary diagnostic work-up and management. B As per BSR 2010 guidelines, consider referring all patients with GCA urgently for specialist evaluation. C Corticosteroids: As per ACC 2022 guidelines, initiate high-dose corticosteroids as initial medical therapy in patients with active GCA. B As per ACR 2021 guidelines, consider initiating high-dose oral corticosteroids in patients with newly diagnosed GCA without manifestations of cranial ischemia. C Show 5 more As per BSR 2020 guidelines, initiate oral prednisone/prednisolone at an initial dose of 40-60 mg/day in patients with GCA. B Show 4 more As per EULAR 2020 guidelines: Initiate high dose corticosteroids (40-60 mg/day prednisone-equivalent) immediately for induction of remission in patients with active GCA. B Taper corticosteroid dose to a target dose of 15-20 mg/day within 2-3 months and after 1 year to 5 mg/day. B As per SSR 2019 guidelines, initiate corticosteroids at an initial daily dose corresponding to 40- 60 mg of prednisolone in patients with uncomplicated GCA (without jaw claudication or visual complications). E Show 2 more Tocilizumab: As per ACC 2022 guidelines, initiate tocilizumab as adjunctive therapy to corticosteroids, with methotrexate as an alternative, in patients with GCA with evidence of active aortitis. B https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 4/11 7/1/23, 12:02 AM Giant cell arteritis Pathway As per ACR 2021 guidelines, consider initiating tocilizumab in addition to oral corticosteroids in patients with newly diagnosed GCA. B As per BSR 2020 guidelines: Consider initiating tocilizumab in combination with a corticosteroid taper in patients with GCA, especially in patients at high risk of corticosteroid toxicity or presenting with a relapse. B Do not use TNF inhibitors in patients with GCA. D As per EULAR 2020 guidelines, initiate tocilizumab as an adjunctive therapy in selected patients with GCA, including with refractory or relapsing disease, presence or an increased risk of corticosteroid-related adverse effects, and complications. B As per SSR 2019 guidelines, initiate tocilizumab in addition to corticosteroids in patients meeting all of the following criteria: relapse during corticosteroid treatment or relapse after the completion of corticosteroid treatment large vessel arteritis established with biopsy or imaging of large vessels (MRI, positron emission tomography-CT, or CT angiography) clinically active GCA elevated CRP and ESR obvious side effects of corticosteroid treatment or great risk of such side effects from future treatment with corticosteroids. E Show 5 more Methotrexate: As per ACR 2021 guidelines, consider initiating a non-corticosteroid immunosuppressive agent in addition to oral corticosteroids in patients with GCA with active extracranial large vessel involvement. C As per BSR 2020 guidelines: Consider initiating methotrexate in combination with a corticosteroid taper in patients with GCA at high risk of corticosteroid toxicity or presenting with a relapse. C Insufficient evidence to support the use of other oral immunosuppressive agents (including azathioprine, leflunomide, or mycophenolate mofetil) in patients with GCA. I As per EULAR 2018 guidelines, consider initiating methotrexate as an alternative to tocilizumab as an adjunctive therapy in selected patients with GCA, including with refractory or relapsing disease, presence or an increased risk of corticosteroid-related adverse effects, and complications. B Antithrombotics: As per ACR 2021 guidelines, consider initiating aspirin in patients with GCA having critical or flow-limiting involvement of the vertebral or carotid arteries. C As per BSR 2020 guidelines, do not use routine antiplatelet or anticoagulant agents for GCA. As per EULAR 2020 guidelines: https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 5/11 7/1/23, 12:02 AM Giant cell arteritis Pathway Do not use routine antiplatelet or anticoagulant therapy for the treatment of patients with large vessel vasculitis unless it is indicated for other reasons (such as coronary heart disease or cerebrovascular disease etc). D Consider initiating antiplatelet or anticoagulant therapy on an individual basis in special situations, such as vascular ischemic complications or high risk of CVD. C As per SSR 2019 guidelines, consider initiating low-dose aspirin in patients with newly diagnosed GCA, in the absence of contraindications, to reduce the risk of ischemic complications. E Lipid-lowering agents: As per ACR 2021 guidelines, avoid using statins specifically for the treatment of patients with newly diagnosed GCA. D As per BSR 2020 guidelines, do not use routine cholesterol-lowering agents (including statins) for the treatment of patients with GCA. 5. Surgical interventions Reconstructive surgery: As per ACC 2022 guidelines, consider performing elective endovascular or open surgical intervention to treat aortic and branch vessel complications in patients with GCA in remission. C As per ACR 2021 guidelines, decide on the type and timing of intervention in patients requiring surgical vascular intervention for GCA based on a collaborative decision between the vascular surgeon and rheumatologist. As per EULAR 2020 guidelines: Perform elective endovascular interventions or reconstructive surgery in phases of stable remission of large vessel vasculitis. B Refer patients with arterial vessel dissection or critical vascular ischemia to a vascular team urgently. B 6. Specific circumstances Patients with stroke or TIA: initiate immediate oral high-dose corticosteroids to reduce recurrent stroke risk in patients with ischemic stroke or TIA and symptoms attributed to GCA. B Show 2 more 7. Patient education Patient education: As per EULAR 2020 guidelines, ensure that patients have access to education focusing on the impact of large vessel vasculitis, its key warning symptoms and treatment (including treatment- https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 6/11 7/1/23, 12:02 AM Giant cell arteritis Pathway related complications). As per BSR 2010 guidelines, provide education in patients with GCA. B 8. Follow-up and surveillance Assessment of treatment response: As per ACC 2022 guidelines, assess treatment efficacy periodically by monitoring clinical symptoms, inflammatory serum markers (CRP and ESR), and imaging (CT, MRI, or 18F-FDG- positron emission tomography) in patients with active GCA. B As per SSR 2019 guidelines, assess treatment response based on clinical evaluation (medical history and clinical assessment of possible GCA symptoms) combined laboratory tests (ESR, CRP, and blood counts). E Show 2 more Follow-up: As per ACC 2022 guidelines, consider obtaining annual surveillance imaging with CT, MRI, or 18F-FDG-positron emission tomography in patients with GCA and aortic involvement in remission. C As per ACR 2021 guidelines: Obtain long-term clinical monitoring in patients with GCA in apparent clinical remission. B Consider obtaining clinical observation and monitoring without escalation of immunosuppressive therapy in patients with GCA having an increase in levels of inflammation markers alone. C As per EULAR 2020 guidelines, obtain regular follow-up and monitoring of disease activity in patients with large vessel vasculitis, primarily based on symptoms, clinical findings and ESR/CRP. B As per SSR 2019 guidelines: Avoid obtaining imaging in the follow-up and assessment of disease activity after treatment. D Obtain follow-up with CT angiography in patients with known aortic dilatation caused by GCA. E As per EULAR 2018 guidelines, consider obtaining MRA, CT angiography and/or ultrasound for long-term monitoring of structural damage, particularly to detect stenosis, occlusion, dilatation and/or aneurysms in patients with GCA. C Show 2 more As per BSR 2010 guidelines, schedule a follow-up assessment at weeks 0, 1, 3, 6, and then at months 3, 6, 9 and 12. Arrange extra unscheduled visits in the event of relapse or adverse events. Show 2 more Management of relapse: https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 7/11 7/1/23, 12:02 AM Giant cell arteritis Pathway As per ACR 2021 guidelines, consider adding a non-corticosteroid immunosuppressive agent in patients with GCA experiencing disease relapse while receiving moderate-to-high-dose corticosteroids. E Show 3 more As per BSR 2020 guidelines: Consider initiating methotrexate in combination with a corticosteroid taper in patients with a relapse. C Consider initiating tocilizumab in combination with a corticosteroid taper in patients with a relapse. B As per EULAR 2020 guidelines, re-institute or escalate dose of corticosteroids as recommended for new onset disease in patients with major relapse (either with signs or symptoms of ischemia or progressive vascular inflammation). B Show 2 more As per SSR 2019 guidelines, consider adding methotrexate in cases of late relapse without major inflammatory activity or with marked corticosteroid side effects, when the patient does not meet the criteria for tocilizumab treatment. E Show 2 more As per BSR 2010 guidelines, refer patients with relapse of GCA for specialist assessment. Show 3 more Clinical findings Patient demographics Symptoms Elderly age Claudication of limb Female sex Cough Northern European Difficulty chewing Dysphagia Past medical history Fatigue Fever Blindness Headache Depression Hearing loss Myocardial infarction Jaw claudication Osteoporosis Jaw pain Polymyalgia rheumatica Loss of appetite Neurological exam Malaise Night sweats Peripheral neuropathy Temporal headache Vision loss Head and neck exam Weight loss Scalp tenderness Vascular exam Tongue claudication https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 8/11 7/1/23, 12:02 AM Giant cell arteritis Pathway Asymmetric pulse Hematological findings Beaded temporal artery Anemia Tender temporal artery WBC count Ocular exam blood platelet count Amaurosis fugax Central vision loss Lab findings Abnormal serum LFTs ESR serum CRP Imaging findings AR Halo sign Likelihood Ratios Pertinent positives The following findings increase the probability of giant cell arteritis in adults. 14 15 Finding LR+ Value Presence of halo sign 9.2 Presence of beaded temporal artery 4.6 History of jaw claudication 4.2 Presence of tender temporal artery 2.6 Show 4 more Pertinent negatives The following findings decrease the probability of giant cell arteritis in adults. 14 15 Finding LR- Value Absence of halo sign 0.5 No history of jaw claudication 0.7 No history of headache 0.7 No history of temporal headache 0.8 Show 4 more References https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 9/11 7/1/23, 12:02 AM Giant cell arteritis Pathway 1. Sarah L Mackie, Christian Dejaco, Simone Appenzeller et al. British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis. Rheumatology Oxford). 2020 Mar 1;59 3):e1-e23. Open 2. Mehrdad Maz, Sharon A Chung, Andy Abril et al. 2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Giant Cell Arteritis and Takayasu Arteritis. Arthritis Care Res Hoboken). 2021 Aug;73 8 1071 1087. Open 3. Bernhard Hellmich, Ana Agueda, Sara Monti et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020 Jan;79 1 19 30. Open 4. B Bienvenu, K H Ly, M Lambert et al. Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis GEFA . Rev Med Interne. 2016 Mar;37 3 154 65. Open 5. Dasgupta B, Borg FA, Hassan N et al. BSR and BHPR guidelines for the management of giant cell arteritis. Rheumatology Oxford). 2010 Aug;49 8 1594 7. Open 6. Eric M Isselbacher, Ourania Preventza, James Hamilton Black rd et al. 2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation. 2022 Nov 2. Open 7. Dawn O Kleindorfer, Amytis Towfighi, Seemant Chaturvedi et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2021 Jul;52 7):e364-e467. Open 8. Christian Dejaco, Sofia Ramiro, Christina Duftner et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis. 2018 May;77 5 636 643. Open 9. Turesson C, B rjesson O, Larsson K et al. Swedish Society of Rheumatology 2018 guidelines for investigation, treatment, and follow-up of giant cell arteritis. Scand J Rheumatol. 2019 Jul;48 4 259 265. Open 10. Hiratzka LF, Bakris GL, Beckman JA et al. 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with Thoracic Aortic Disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, American Association for Thoracic Surgery, American College of Radiology, American Stroke Association, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of Thoracic Surgeons, and Society for Vascular Medicine. Circulation. 2010 Apr 6;121 13):e266 369. Open 11. Weyand CM, Goronzy JJ. Clinical practice. Giant-cell arteritis and polymyalgia rheumatica. N Engl J Med. 2014 Jul 3;371 1 50 7. Open 12. Babigumira JB, Li M, Boudreau DM et al. Estimating the Cost of Illness of Giant Cell Arteritis in the United States. Rheumatol Ther. 2017 Jun;4 1 111 119. Open 13. Weyand CM, Liao YJ, Goronzy JJ. The immunopathology of giant cell arteritis: diagnostic and therapeutic implications. J Neuroophthalmol. 2012 Sep;32 3 259 65. Open 14. Chacko JG, Chacko JA, Salter MW. Review of Giant cell arteritis. Saudi J Ophthalmol. 2015 Jan- Mar;29 1 48 52. Open 15. Smetana GW, Shmerling RH. Does this patient have temporal arteritis?. JAMA. 2002 Jan 2;287 1 92 101. Open https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 10/11 7/1/23, 12:02 AM Giant cell arteritis Pathway 16. Karassa FB, Matsagas MI, Schmidt WA et al. Meta-analysis: test performance of ultrasonography for giant-cell arteritis. Ann Intern Med. 2005 Mar 1;142 5 359 69. Open 17. Stone JH, Tuckwell K, Dimonaco S et al. Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med. 2017 Jul 27;377 4 317 328. Open 18. Cristina Ponte, Peter C Grayson, Joanna C Robson et al. 2022 American College of Rheumatology/EULAR Classification Criteria for Giant Cell Arteritis. Arthritis Rheumatol. 2022 Dec;74 12 1881 1889. Open https://web.pathway.md/diseases/recGiLqtcZ9r8gvkM 11/11