Large-vessel involvement and aortic dilation in giant-cell arteritis. A multicenter study of 549 patients

doi:10.1016/j.autrev.2017.11.029

Autoimmunity Reviews

Volume 17, Issue 4, April 2018, Pages 391-398

https://doi.org/10.1016/j.autrev.2017.11.029 Get rights and content

Highlights

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Patients with GCA-related large-vessel involvement showed distinct features.
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Aortic dilation more likely occurs on inflammatory aorta segment.
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Patients with GCA-related large-vessel involvement have to control aorta morphology.

Abstract

Objectives

Large-vessel involvement (LVI) can occur in giant-cell arteritis (GCA) and may represent a distinct disease subgroup with a higher risk for aortic dilation. This study aimed to better characterize the presentation and evolution of LVI in patients with GCA.

Patients and methods

A retrospective multicenter study enrolled 248 GCA patients with LVI and 301 GCA patients without LVI on imaging. Factors associated with aortic dilation were identified in a multivariable model.

Results

The patients with LVI were younger (p < 0.0001), more likely to be women (p = 0.01), and showed fewer cephalic symptoms (p < 0.0001) and polymyalgia rheumatica (p = 0.001) but more extracranial vascular symptoms (p = 0.05) than the patients without LVI. Glucocorticoids (GC) management did not differ between the two groups, but the GC discontinuation rate was lower in the patients with LVI (p = 0.0003). Repeated aortic imaging procedures were performed at 19 months [range: 5–162 months] and 17 months [range: 6–168 months] after diagnosis in 154 patients with LVI and 123 patients without LVI, respectively, of whom 21% and 7%, respectively, presented new aortic dilations (p = 0.0008). In the patients with LVI, aortic dilation occurred on an aorta segment shown to be inflammatory on previous imaging in 94% of patients. In the multivariate analysis, LVI was the strongest predictor of aortic dilation (hazard ratio: 3.16 [range: 1.34–7.48], p = 0.009).

Conclusions

LVI represents a distinct disease pattern of GCA with an increased risk of aortic dilation. Control of the aortic morphology during follow-up is required.

Introduction

Giant-cell arteritis (GCA) is a systemic vasculitis affecting patients older than 50 years [1]. In addition to the mainly affected branches of the external carotid that explain the polymorphic and typical cephalic manifestations of GCA, the aorta and its main branches are also affected in 40% to 80% of cases, even though they do not frequently induce symptoms [[2], [3], [4], [5], [6], [7], [8], [9]]. The 1990 criteria from the American College of Rheumatology (ACR) are still used in clinical practice to classify the disease [10]. GCA diagnosis is highly probable in the presence of at least 3 of the 5 following criteria: 1) age > 50 years; 2) an erythrocyte sedimentation rate (ESR) > 50 mm (and, by extension, high inflammatory parameters such as increased C-reactive protein (CRP)); 3) recent onset of headaches; 4) abnormalities of the temporal artery; and 5) a positive temporal artery biopsy (TAB) showing transmural inflammation with the presence of giant cells. These criteria do not take into consideration the presence of clinical or radiological large-vessel involvement (LVI).

Over the past few decades, the proportion of GCA patients described with LVI has increased, mainly because of a wider use of imaging methods such as computed tomography angiography (CTA) [2,8], magnetic resonance angiography (MRA) of the aorta [[11], [12], [13]], or positron emission tomography with computed tomography (PET/CT) [3,9,[14], [15], [16], [17]]. Previous studies indicate some differences regarding the clinical presentations [5,6,[18], [19], [20], [21], [22]] and outcomes [5,15] in patients with LVI, especially a higher risk for cardiovascular events such as aortic dilation. Although no guidelines have defined which type of GCA patients require large-vessel screening, the research of LVI in the setting of GCA is currently performed and is even used in some large studies as a means to affirm the diagnosis instead of using TAB [23,24].

To better identify patients who may require large-vessel exploration, we conducted a retrospective multicenter study and compared patients with LVI demonstrated on imaging at diagnosis or during follow-up to patients without LVI. We also compared the long-term outcomes of both of the subgroups, focusing on the development of aortic dilation and factors associated with this development.

Section snippets

Patients

We retrospectively enrolled patients from the departments of internal medicine at 6 tertiary hospitals located in 6 large cities in France (Paris, Marseille, Lille, Dijon, Limoges and Caen).

All of the patients were diagnosed with GCA between 2000 and 2016 based on the presence of at least 3 criteria of the ACR [10] or 2 criteria associated with the demonstration of LVI on imaging. For the purpose of this study, we enrolled GCA patients who performed at least one large-vessel imaging scan (aorta

Study population

Five hundred forty-nine patients [385 (70%) women; median age: 72 years [range: 50–91 years]] were enrolled, including 248 patients with LVI.

GCA diagnosis was proven by biopsy in 324 (59%) patients, and all of them had high inflammatory parameters, except for eight (who had a positive TAB).

Fig. 1 shows the types of imaging methods that demonstrated LVI. These imaging methods were performed at diagnosis in 398 patients and during follow-up in the 151 others (median duration of delay between

Discussion

Our study provides new insights regarding GCA-related LVI. We identified and confirmed some demographical and clinical factors that are more frequently associated with LVI. Moreover, LVI was the strongest independent predictor for aortic dilation in multivariate analysis, regardless of the clinical status of the disease or the time of the aortic morphology assessment. Aortic dilation in patients with LVI occurred on a previously affected inflammatory segment in >90% of the patients.

GCA is a

Conclusions

This study suggests that LVI in GCA represents a distinct epidemiologic, clinical and prognostic spectrum of the disease with a higher risk of aortic dilation, especially in previously inflamed vascular segments. Prospective studies should help confirm these findings and define the best rhythm, type and duration of aortic morphology follow-up. Additionally, further work is necessary to identify the most adapted therapeutic strategy in this pattern of the disease.

Funding sources

None.

Disclosures

None.

Ethics and consent

This study was conducted in compliance with good clinical practices and the Declaration of Helsinki principles. At the time of this study, in accordance with French public health law (Art. L 1121-1-1, Art. L 1121-1-2), formal approval from an ethics committee was not required for this type of observational study. Our local ethics committee confirmed the observational non-interventional retrospective nature of our cohort.

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Evolution and outcomes of aortic dilations in giant cell arteritis
2024, European Journal of Internal Medicine
To identify factors associated with the progression of giant cell arteritis (GCA)-related or associated aortic dilations.
In this retrospective study, 47 GCA patients with aortic dilation were longitudinally analyzed. Each patient underwent ≥2 imaging scans of the aorta during the follow-up. Three progression statuses of aortic dilations were distinguished: fast-progressive (FP) defined by a progression of the aortic diameter ≥5 mm/year or ≥1 cm/2 years, slow progressive (SP) by a progression of the aortic diameter >1 mm during the follow-up, and not progressive (NP) when aortic diameter remained stable.
Among the 47 patients with aortic dilation, the thoracic section was involved in 87 % of patients. Within a total follow-up of 89 [6–272] months, we identified 13 (28 %) patients with FP dilations, and 16 (34 %) and 18 (38 %) patients with SP and NP dilations, respectively. No differences regarding baseline characteristics, cardiovascular risk factors or treatments were observed among the 3 groups. However, FP patients more frequently showed atheromatous disease (p = 0.04), with a more frequent use of statins (p = 0.04) and antiplatelet agents (p = 0.02). Among the 27 (57 %) patients with aortitis, aortic dilation developed on an inflammatory segment in 23 (85 %). Among the FP patients who underwent aortic surgery with available histology (n = 3), all presented active vasculitis.
This study suggests that aortic inflammation, as well as atheromatous disease, might participate in the fast progression of aortic dilation in GCA.
Early referral of patients with suspected polymyalgia rheumatica – A systematic review
2023, Seminars in Arthritis and Rheumatism
Prompt diagnosis and treatment of polymyalgia rheumatica (PMR) is crucial to prevent long-term complications and improve patient outcomes. However, there is currently no standardized approach to referral of suspected PMR patients to rheumatologists, leading to inconsistent management practices. The objective of this systematic review was to clarify the existing evidence regarding the following aspects of early management strategies in patients with suspected PMR: diagnostic strategies, GCA screening, glucocorticoid initiation prior to referral, value of shared care and value of fast track clinic.
Two authors performed a systematic literature search, data extraction and risk of bias assessment independently. The literature search was conducted in Embase, MEDLINE (PubMed) and Cochrane. Studies were included if they contained cohorts of suspected PMR patients and evaluated the efficacy of different diagnostic strategies for PMR, screening for giant cell arteritis (GCA), starting glucocorticoids before referral to secondary care, shared care, or fast-track clinics.
From 2,437 records excluding duplicates, 14 studies met the inclusion criteria. Among these, 10 studies investigated the diagnostic accuracy of various diagnostic strategies with the majority evaluating different clinical approaches, but none of them showed consistently high performance. However, 4 studies on shared care and fast-track clinics showed promising results, including reduced hospitalization rates, lower starting doses of glucocorticoids, and faster PMR diagnosis.
This review emphasizes the sparse evidence of early management and referral strategies for patients with suspected PMR. Additionally, screening and diagnostic strategies for differentiating PMR from other diseases, including concurrent GCA, require clarification. Fast-track clinics may have potential to aid patients with PMR in the future, but studies will be needed to determine the appropriate pre-referral work-up.
Clinical phenotype and complications of large vessel giant cell arteritis: A systematic review and meta-analysis
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L’artérite à cellules géantes est une vascularite granulomateuse systémique hétérogène qui touche l’aorte et ses principales collatérales. Bien que l’atteinte des gros vaisseaux soit de plus en plus connue, les études qui décrivent l’incidence, les caractéristiques et les complications de l’artérite à cellules géantes touchant les gros vaisseaux ont des résultats contradictoires en raison d’incohérences dans les définitions de la maladie, de différences méthodologiques et de l’étendue du spectre des présentations cliniques. L’objectif de cette revue systématique de la littérature était de mieux définir l’artérite à cellules géantes avec atteinte des gros vaisseaux à partir des publications disponibles et d’identifier des caractéristiques distinctives pouvant permettre de différencier les patients atteints de cette forme d’artérite de ceux dont la maladie est limitée aux vaisseaux crâniens.
Les études publiées indexées dans Medline et Embase entre la création de la base de données et le 7 mai 2021 ont été recherchées. Ont été incluses celles qui présentaient des données longitudinales ou transversales sur au moins 25 patients atteints d’artérite à cellules géantes avec atteinte des gros vaisseaux. Les groupes témoins ont été utilisés lorsqu’il existait des données sur les patients atteints d’artérite à cellules géantes limitées aux vaisseaux crâniens. Une synthèse quantitative des données a été effectuée par méta-régression avec un modèle à effets aléatoires, à l’aide du logiciel Stata.
La recherche a identifié 3488 études, dont 46 ont été incluses. Les critères de diagnostic de l’artérite à cellules géantes avec atteinte des gros vaisseaux différaient entre les articles mais reposaient généralement sur l’imagerie ou l’histopathologie. Les patients présentant une atteinte des gros vaisseaux étaient globalement plus jeunes au moment du diagnostic que ceux dont la maladie était limitée aux vaisseaux crâniens (différence d’âge moyenne –4,53 ans), le délai avant leur diagnostic était plus long (différence moyenne 3,03 mois) et leurs taux de positivité de la biopsie de l’artère temporale étaient plus faibles (OR 0,52 [IC 95 % 0,3 à 0,91]). Les patients atteints d’artérite à cellules géantes avec atteinte des gros vaisseaux présentant des manifestations crâniennes étaient moins nombreux et seuls 53 % remplissaient les critères de classification de 1990 de l’ACR pour l’artérite à cellules géantes. La vascularite était détectée le plus souvent dans l’aorte thoracique, puis dans les artères sous-clavières, le tronc brachiocéphalique et les artères axillaires. La dose cumulée moyenne de prednisolone à 12 mois était de 6056,5 mg chez les patients présentant une atteinte des gros vaisseaux, les taux de récidive étaient similaires entre les deux formes et 12 % des décès de patients atteints d’artérite à cellules géantes avec atteinte des gros vaisseaux ont pu être directement attribués à une complication touchant les gros vaisseaux.
Les caractéristiques de la maladie diffèrent entre les formes d’artérite à cellules géantes touchant les gros vaisseaux et uniquement les vaisseaux crâniens, ce qui a des implications sur le diagnostic, les stratégies de traitement et la surveillance des séquelles à long terme.
Giant cell arteritis (GCA) is a heterogenous systemic granulomatous vasculitis involving the aorta and any of its major tributaries. Despite increased awareness of large vessel (LV) involvement, studies reporting incidence, clinical characteristics and complications of large-vessel GCA (LV-GCA) show conflicting results due to inconsistent disease definitions, differences in study methodologies and the broad spectrum of clinical presentations. The aim of this systematic literature review was to better define LV-GCA based on the available literature and identify distinguishing characteristics that may differentiate LV-GCA patients from those with limited cranial disease.
Published studies indexed in MEDLINE and EMBASE were searched from database inception to 7 May 2021. Studies were included if they presented cohort or cross-sectional data on a minimum of 25 patients with LV-GCA. Control groups were included if data was available on patients with limited cranial GCA (C-GCA). Data was quantitatively synthesised with application of a random effects meta-regression model, using Stata.
The search yielded 3488 studies, of which 46 were included. Diagnostic criteria for LV-GCA differed between papers, but were typically dependent on imaging or histopathology. Patients with LV-GCA were generally younger at diagnosis compared to C-GCA patients (mean age difference –4.53 years), had longer delay to diagnosis (mean difference 3.03 months) and lower rates of positive temporal artery biopsy (OR : 0.52 [95% CI : 0.3, 0.91]). Fewer LV-GCA patients presented with cranial manifestations and only 53% met the 1990 ACR Classification Criteria for GCA. Vasculitis was detected most commonly in the thoracic aorta, followed by the subclavian, brachiocephalic trunk and axillary arteries. The mean cumulative prednisolone dose at 12-months was 6056.5 mg for LV-GCA patients, relapse rates were similar between LV- and C-GCA patients, and 12% of deaths in LV-GCA patients could be directly attributed to an LV complication.
Patients with LV-GCA have distinct disease features when compared to C-GCA, and this has implications on diagnosis, treatment strategies and surveillance of long-term sequalae.
Persistent aortic inflammation in patients with giant cell arteritis
2023, Autoimmunity Reviews
To investigate the clinicopathologic features of patients with giant cell arteritis (GCA) who had thoracic aorta aneurysm or dissection surgery.
Patients who had thoracic aorta surgery between January 1, 2000, and December 31, 2021, at the Mayo Clinic, Rochester, Minnesota, were identified with current procedural terminology (CPT) codes. The identified patients were screened for a prior diagnosis of GCA with diagnostic codes and electronic text search. The available medical records of all the patients of interest were manually reviewed. Thoracic aorta tissues obtained during surgery were re-evaluated in detail by pathologists. The clinicopathologic features of these patients were analyzed. Overall observed survival was compared with lifetable rates from the United States population.
Of the 4621 patients with a CPT code for thoracic aorta surgery, 49 had a previous diagnosis of GCA. Histopathologic evaluation of the aortic tissue revealed active aortitis in most patients with GCA (40/49, 82%) after a median (IQR) of 6.0 (2.6–10.3) years from GCA diagnosis. All patients were considered in clinical remission at the time of aortic surgery. The overall mortality compared to age and sex-matched general population was significantly increased with a standardized mortality ratio of 1.55 (95% CI, 1.05–2.19).
Histopathologic evaluation of the thoracic aorta obtained during surgery revealed active aortitis in most patients with GCA despite being considered in clinical remission several years after GCA diagnosis. Chronic, smoldering aortic inflammation likely contributes to the development of aortic aneurysm and dissection in GCA.
Clinical phenotype and complications of large vessel giant cell arteritis: A systematic review and meta-analysis
2023, Joint Bone Spine
Giant Cell Arteritis (GCA) is a heterogenous systemic granulomatous vasculitis involving the aorta and any of its major tributaries. Despite increased awareness of large vessel (LV) involvement, studies reporting incidence, clinical characteristics and complications of large-vessel GCA (LV-GCA) show conflicting results due to inconsistent disease definitions, differences in study methodologies and the broad spectrum of clinical presentations. The aim of this systematic literature review was to better define LV-GCA based on the available literature and identify distinguishing characteristics that may differentiate LV-GCA patients from those with limited cranial disease.
Published studies indexed in MEDLINE and EMBASE were searched from database inception to 7th May 2021. Studies were included if they presented cohort or cross-sectional data on a minimum of 25 patients with LV-GCA. Control groups were included if data was available on patients with limited cranial GCA (C-GCA). Data was quantitatively synthesised with application of a random effects meta-regression model, using Stata.
The search yielded 3488 studies, of which 46 were included. Diagnostic criteria for LV-GCA differed between papers, but was typically dependent on imaging or histopathology. Patients with LV-GCA were generally younger at diagnosis compared to C-GCA patients (mean age difference –4.53 years), had longer delay to diagnosis (mean difference 3.03 months) and lower rates of positive temporal artery biopsy (OR: 0.52 [95% CI: 0.3, 0.91]). Fewer LV-GCA patients presented with cranial manifestations and only 53% met the 1990 ACR Classification Criteria for GCA. Vasculitis was detected most commonly in the thoracic aorta, followed by the subclavian, brachiocephalic trunk and axillary arteries. The mean cumulative prednisolone dose at 12-months was 6056.5 mg for LV-GCA patients, relapse rates were similar between LV- and C-GCA patients, and 12% of deaths in LV-GCA patients could be directly attributed to an LV complication.
Patients with LV-GCA have distinct disease features when compared to C-GCA, and this has implications on diagnosis, treatment strategies and surveillance of long-term sequalae.
Hospitalization for infection in patients treated for giant cell arteritis: A single-centre retrospective study
2023, Revue de Medecine Interne
Les infections sont responsables de morbimortalité des patients souffrant d’artérite à cellules géantes (ACG). Le but de ce travail était double : l’identification de facteurs prédisposant au risque infectieux et la description des patients hospitalisés pour une infection survenant pendant la période de traitement de l’ACG.
Nous avons mené une étude rétrospective monocentrique chez les patients ACG en comparant les patients hospitalisés pour infection avec des patients sans infection. L’analyse a porté sur 21/144 (14,6 %) patients ayant présenté 26 infections (cas), auxquels 42 témoins ont été appariés sur le sexe, l’âge et l’année du diagnostic d’ACG
Les deux groupes étaient similaires en dehors d’une sérite au diagnostic plus fréquente chez les cas (15 % vs 0 %, p = 0,03). Les rechutes d’ACG étaient moins fréquentes chez les cas (23,8 % vs 50,0 %, p = 0,041). Une hypogammaglobulinémie était présente lors de l’infection. Plus de la moitié des infections (53,8 %) survenaient la première année du suivi sous une posologie moyenne de 15 mg/jour de prednisone. Les infections étaient surtout pulmonaires (46,2 %) et cutanées (26,9 %).
Des facteurs associés au risque infectieux ont été identifiés. Ce travail préliminaire monocentrique va se poursuivre par une étude nationale multicentrique.
Infections are associated with morbimortality of patients with giant cell arteritis (GCA). The aim of this work was twofold: the identification of factors predisposing to the risk of infection and the description of patients hospitalized with an infection occurring during the treatment period of CAG.
A monocentric retrospective study was conducted in GCA patients, comparing patients hospitalized for infection with patients without infection. The analysis included 21/144 (14.6%) patients with 26 infections (cases) and 42 control matched on sex, age, and diagnosis of GCA.
Both groups were similar except for a higher frequency of seritis in cases (15% vs. 0%, p = 0.03). Relapses of GCA were less common in cases (23.8% vs 50.0%, p = 0.041). Hypogammaglobulinemia was present during infection. More than half of the infections (53.8%) occurred in the first year of follow-up with an average dose of 15 mg/day of corticosteroids. Infections were mainly pulmonary (46.2%) and cutaneous (26.9%).
Factors associated with infectious risk were identified. This preliminary monocentric work will continue with a national multicentre study.

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ReviewLarge-vessel involvement and aortic dilation in giant-cell arteritis. A multicenter study of 549 patients

Highlights

Abstract

Objectives

Patients and methods

Results

Conclusions

Introduction

Section snippets

Patients

Study population

Discussion

Conclusions

Funding sources

Disclosures

Ethics and consent

Autoimmun Rev

Autoimmun Rev

Lancet

Autoimmun Rev

Chest

Am J Med

Giant cell arteritis: a review of classification, pathophysiology, geoepidemiology and treatment

Autoimmun Rev

Aortic involvement in recent-onset giant cell (temporal) arteritis: a case-control prospective study using helical aortic computed tomodensitometric scan

Arthritis Rheum

Repetitive 18F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a prospective study of 35 patients

Arthritis Rheum

18F-fluorodeoxyglucose positron emission tomography and the risk of subsequent aortic complications in giant-cell arteritis: a multicenter cohort of 130 patients

Medicine

Large-vessel involvement in giant cell arteritis: a population-based cohort study of the incidence-trends and prognosis

Ann Rheum Dis

Large-vessel giant cell arteritis: a cohort study

Rheumatology (Oxford)

Large vessel involvement in biopsy-proven giant cell arteritis: prospective study in 40 newly diagnosed patients using CT angiography

Ann Rheum Dis

Positron emission tomography assessment of large vessel inflammation in patients with newly diagnosed, biopsy-proven giant cell arteritis: a prospective, case-control study

Ann Rheum Dis

The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis

Arthritis Rheum

Diagnostic value of contrast-enhanced magnetic resonance angiography in large-vessel vasculitis

Swiss Med Wkly

Diagnostic value of high-resolution MR imaging in giant cell arteritis

AJNR Am J Neuroradiol

Review
Large-vessel involvement and aortic dilation in giant-cell arteritis. A multicenter study of 549 patients