Anne Bull Haaversen1
Lene Kristin Brekke2Gunnstein Bakland3Erik Rødevand4Geirmund Myklebust5Andreas P. Diamantopoulos6*- 1Department of Rheumatology, Martina Hansens Hospital, Bærum, Norway
- 2Department of Rheumatology, Hospital for Rheumatic Diseases, Haugesund, Norway
- 3Department of Rheumatology, University Hospital of Northern Norway, Tromsø, Norway
- 4Department of Rheumatology, St. Olav’s University Hospital, Trondheim, Norway
- 5Department of Research, Hospital of Southern Norway, Kristiansand, Norway
- 6Department of Infectious Diseases, Division of Internal Medicine, Akershus University Hospital, Lørenskog, Norway
Objective: To provide clinical guidance to Norwegian Rheumatologists and other clinicians involved in diagnosing and treating patients with giant cell arteritis (GCA).
Methods: The available evidence in the field was reviewed, and the GCA working group wrote draft guidelines. These guidelines were discussed and revised according to standard procedures within the Norwegian Society of Rheumatology. The European Alliance of Associations for Rheumatology (EULAR) recommendations for imaging and treatment in large vessel vasculitis and the British Society for Rheumatology (BSR) guidelines for diagnostics and treatment in GCA informed the development of the current guidelines.
Results: A total of 13 recommendations were developed. Ultrasound is recommended as the primary diagnostic test. In patients with suspected GCA, treatment with high doses of Prednisolone (40–60 mg) should be initiated immediately. For patients with refractory disease or relapse, Methotrexate (MTX) should be used as the first-line adjunctive therapy, followed by tocilizumab (TCZ).
Conclusion: Norwegian recommendations for diagnostics and treatment to improve management and outcome in patients with GCA were developed.
Introduction
Background
Giant cell arteritis (GCA) is the most common systemic vasculitis in adults and has a spectrum of possible presentations (1, 2). The main subsets include isolated cranial arteritis (c-GCA), isolated large vessel vasculitis (LV-GCA), and coexisting cranial and large vessel vasculitis (mixed-GCA) (2). Polymyalgia rheumatica (PMR) and GCA are closely related, and some argue that PMR lies within the spectrum of GCA. However, these conditions may occur simultaneously or independently of each other (3–5).
Giant cell arteritis occurs almost exclusively in people older than 50 years of age, with a peak in onset between 70 and 80 years of age and with a female predominance (6, 7). The majority of epidemiological studies on GCA have investigated European or North American populations, and the highest incidence has been reported in Nordic countries or North-American people of Scandinavian descent (8). Data on GCA occurrence in Africa, Asia, the Middle East, South- and Latin America, and Oceania are sparse and suggest that the condition is less common in non-Caucasians.
The annual incidence rate for GCA in Norway was recently estimated to be 22.5 per 100,000 persons ≥50 years of age (7).
Giant cell arteritis’ etiopathogenesis is not fully understood but is considered to involve a combination of genetic and environmental factors (9). Different compositions of genetic background may contribute to global differences. There is also evidence that lifestyle factors such as body mass index, glucose levels, and smoking may influence the risk of GCA (10–14).
Objectives of the guidelines
These recommendations aim to provide clinical guidance to Rheumatologists and other clinicians involved in diagnosing and treating GCA patients. The guidelines cover individuals older than 50 years of age suspected to have GCA. The guidelines aim to harmonize the diagnostic and treatment procedures across specialists and departments in the Norwegian Healthcare System.
Methods
The Norwegian GCA working group (the members are the authors of these guidelines) developed the recommendations by reviewing the available evidence and writing the draft guidelines. The draft guidelines were discussed and revised according to standard procedures within the Norwegian Society of Rheumatology.
The European Alliance of Associations for Rheumatology (EULAR) recommendations for imaging and treatment in large vessel vasculitis (15, 16) and The British Society for Rheumatology (BSR) guidelines for diagnostics and treatment in GCA (17) served as the basis to the development of current guidelines. As the American College of Rheumatology guidelines recommend the use of Tocilizumab very early in the treatment of GCA patients, which is not refunded by the Norwegian Health Authorities, we chose not to incorporate these guidelines in the Norwegian guidelines (18). Also, the evidence on diagnostics and treatment of GCA published after 2018 was reviewed and included in this work. The PubMed and a combination of the search terms Giant cell arteritis and treatment and/or diagnosis were used. The review of individual studies was restricted to randomized controlled studies or prospective observational studies with >50 participants. The guidelines were proposed, discussed, revised, and accepted by voting/reaching an agreement by the majority of the members of the working group and the professional council (in Norwegian: Fagrådet) of the Norwegian Society of Rheumatology. The method used to obtain consensus was voting among members during meetings of the working group.
The present guidelines are the foundation upon which clinical practice should be based. Guidelines, unlike some types of policies, are not mandatory. Individual patient circumstances may influence clinical decisions, and clinicians should work alongside patients to make care-based shared decisions. Thus, failure to adhere to these guidelines should not necessarily be considered negligent. These guidelines should not be used to limit access to other diagnostic or treatment options.
Results
Diagnosis
Recommendation 1
In patients with suspected GCA, a thorough history should be obtained, including inquiry about polymyalgia symptoms, new-onset headache, tongue- or jaw-claudication, vision disturbances, arm or leg claudication, constitutional symptoms (fatigue, fever, and weight loss). Additionally, a thorough clinical examination and laboratory workup should be performed including heart and lung auscultation, blood pressure in both arms, temperature, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and full blood count (Table 1).
Table 1. Clinical symptoms and findings and laboratory results in giant cell arteritis (GCA) patients.
Recommendation 2
Patients suspected of having GCA, should be directly referred to a Fast-Track Clinic (FTC) or a rheumatologist for further evaluation, treatment, and follow-up within 24 h. In cases where FTC- or rheumatology consult is unavailable within 24 h the patient may be referred to other relevant specialists (e.g., neurologist, ophthalmologist, and internist). FTC consists of an evaluation by ultrasound or other imaging modality which can confirm the diagnosis immediately (19). Diagnostic work-up should not delay the initiation of treatment.
Recommendation 3
In patients with suspected GCA, ultrasound of at least temporal and axillary arteries (20) should be performed by an ultrasonographer experienced in vascular ultrasound using high-end ultrasound equipment (21) (Tables 2, 3). Ultrasound of the facial artery further increases the sensitivity to diagnose GCA (20). If ultrasound is not available or inconclusive, a biopsy of the temporal artery should be considered. The length of the biopsy should be >1 cm after fixation. Giant cells in the biopsy are not obligate for the diagnosis of GCA, but appropriate pathological findings should be present (Table 4). Alternatively, Magnetic Resonance Angiography (MRA) of temporal arteries or Positron Emission Tomography (PET-CT) may be performed. In addition, ultrasound of large vessels (carotid, vertebral, and subclavian) (22) or CT of large vessels or MRA or PET-CT depending on the availability is recommended. It is essential to recognize the disease extent as early as possible as large vessel involvement may indicate difficult-to-treat disease, while temporal artery involvement has been associated with a higher risk for visual loss (23, 24). The choice of imaging modality depends on the local availability.
Table 2. Ultrasonographic findings in giant cell arteritis (GCA) patients (33).
Table 3. Threshold intima media thickness (IMT) values in ultrasound examination (34).
Table 4. Histological findings in patients with giant cell arteritis (GCA) (35).
Recommendation 4
In a patient with high clinical suspicion of GCA and a positive diagnostic test (biopsy or imaging modality), no further test is required to confirm the diagnosis. In patients with low clinical suspicion of GCA and a negative diagnostic test (biopsy or imaging modality), the probability for GCA is low. In other cases, an individual assessment will be necessary for further diagnostics.
Recommendation 5
In patients with GCA and visual symptoms, referral to an ophthalmologist is highly recommended. Initiation of treatment should not be delayed while waiting for this evaluation (Figure 1 and Table 5).
Figure 1. Diagnostic algorithm for giant cell arteritis (GCA).
Table 5. Summary of the Norwegian society of rheumatology’s recommendations on diagnosis and treatment of patients with giant cell arteritis (GCA).
Treatment
Recommendation 6
In patients with suspected GCA, glucocorticoids should be immediately initiated. The diagnostic work-up should not delay the initiation of treatment. For patients without visual manifestations we recommend a starting dose of 40 mg Prednisolone/day. In patients with visual involvement (visual loss, diplopia, amaurosis fugax, and blurred vision), we recommend starting with 60 mg Prednisolone/day. A single dose of 500 mg × 1 methylprednisolone iv followed by Prednisolone 60 mg/day may be individually considered, but the evidence is sparse (25–27).
Recommendation 7
In patients with GCA, Prednisolone should be tapered by 5 mg every 2nd week till 20 mg/day, after that with 2.5 mg every 3rd week till 10 mg/day, and after that with 1.25 mg every 3rd week to 5 mg/day. We recommend continuing treatment with 5 mg/day at least for 1 year after initiation of Prednisolone. Further tapering can be considered on an individual basis if the patient has been in remission for at least 1 year. When starting with dose 60 mg/day, Prednisolone should be tapered by 10 mg every week till 40 mg/day, thereafter tapering as described above (Table 6).
Table 6. Prednisolone tapering.
Recommendation 8
If the patients suffers a relapse, we recommend an increase in Prednisolone dose to the last effective dose, or a higher dose based on the severity of the relapse and an individual assessment. In patients with refractory disease or a major relapse (Table 7), initiation of Methotrexate (MTX), preferably subcutaneously, 20 mg/week, should be considered. The dose should be adjusted according to the patient’s age and kidney function. Tocilizumab (TCZ) 162 mg/week sc should be considered if the patient is not tolerating MTX or suffer a relapse while on MTX (according to the Norwegian Tender System). Leflunomide or Azathioprine may be considered, but evidence supporting their use is scarce. There is currently no robust evidence supporting the use of TNF-α inhibitors or other biologics than TCZ in patients with GCA.
Table 7. Definitions of disease activity (16).
Recommendation 9
Giant cell arteritis patients with new-onset disease should be referred to a measurement of bone mass density. In patients with GCA and high risk for osteoporosis, treatment according to the Norwegian guidelines for osteoporosis should be initiated (28).
Recommendation 10
In patients with GCA, we do not routinely recommend using Acetylsalicylic acid unless cardiovascular reasons support its use (Figure 2).
Figure 2. Treatment algorithm for giant cell arteritis (GCA).
Follow up
Recommendation 11
In GCA patients, follow-up should be continued every month until remission is achieved. Thereafter follow-up at 3 months, 6 months, and thereafter yearly.
Recommendation 12
In GCA patients who suffer a relapse, the relapse should, if possible, be confirmed by an imaging modality, preferably ultrasound, and/or laboratory tests (29, 30). Modified Kerr’s (NIH) criteria (originally developed for Takayasu arteritis) may be used to monitor disease activity (31) (Tables 7, 8).
Table 8. Modified Kerr’s criteria: >1 point indicates active disease (31).
Recommendation 13
In GCA patients with relapsing or refractory disease, alternative diagnoses should be considered (e.g., malignancy, autoinflammatory syndromes).
Data availability statement
The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.
Author contributions
AH prepared the manuscript. AD, LB, GB, GM, and ER contributed equally to the manuscript. All authors contributed to the article and approved the submitted version.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher’s note
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Keywords: giant cell arteritis (GCA), large vessel vasculitis, guidelines, diagnosis, treatment
Citation: Haaversen AB, Brekke LK, Bakland G, Rødevand E, Myklebust G and Diamantopoulos AP (2023) Norwegian society of rheumatology recommendations on diagnosis and treatment of patients with giant cell arteritis. Front. Med. 9:1082604. doi: 10.3389/fmed.2022.1082604
Received: 28 October 2022; Accepted: 12 December 2022;
Published: 06 January 2023.
Edited by:
Ryu Watanabe, Osaka Metropolitan University, JapanReviewed by:
Alojzija Hocevar, University Medical Center Ljubljana, SloveniaHubert De Boysson, Centre Hospitalier Universitaire de Caen, France
Marcin Milchert, Pomeranian Medical University, Poland
Copyright © 2023 Haaversen, Brekke, Bakland, Rødevand, Myklebust and Diamantopoulos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Andreas P. Diamantopoulos, 
adiamanteas@gmail.com