Giant cell arteritis and polymyalgia rheumatica: usefulness of vascular magnetic resonance imaging studies in the diagnosis of aortitis

J. Narváez, J. A. Narváez1, J. M. Nolla, E. Sirvent, D. Reina and J. Valverde

Department of Rheumatology and 1 Department of Magnetic Resonance Imaging (IDI), Hospital Universitari de Bellvitge IDIBELL, Hospitalet de LLobregat, Barcelona, Spain.

Correspondence to: J. Narváez, C/ Torrent de l’Olla, no. 226 3° 1a, Barcelona 08012, Spain. E-mail: 31577edd{at}comb.es


    Abstract
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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Objectives. One of the unresolved challenges posed in giant cell (temporal) arteritis (GCA) is the detection and monitoring of large-artery complications, particularly aortitis. Recent investigations support vascular magnetic resonance imaging (MRI) studies in this issue. We report our preliminary experience with this imaging technique in the study of the aorta and its proximal branches in patients with GCA and/or polymyalgia rheumatica (PMR).

Methods. Between 2000 and 2003, six patients with GCA and/or PMR seen in our department were diagnosed with aortitis using vascular MRI studies. In all cases, the study was performed according to a specifically designed protocol that included MRI and MR angiography (MRA).

Results. MRI was a hepful non-invasive method for diagnosis of aortitis in all cases, providing accurate information about its extent. In particular, MRI had a higher ability to detect earlier stages of vasculitis disclosing subclinical aortitis in five of the six patients. The main signs of early vascular inflammation observed were vessel wall thickness and oedema (six cases) and increased mural enhancement on postcontrast T1-weighted images (four cases). MRA disclosed lumen changes (stenosis) in two patients. On follow-up studies, whereas vascular stenosis and vessel wall thickness remained invariable, vascular wall oedema and contrast enhancement improved significantly when disease activity decreased.

Conclusion. MRI may be a useful technique for diagnosing patients with occult major artery involvement in GCA, whether presenting with classic symptoms of temporal arteritis or PMR. Its utility for monitoring the course of the disease and response to treatment requires further confirmation.

KEY WORDS: Polymyalgia rheumatica, Giant cell (temporal) arteritis, Aortitis, Magnetic resonance imaging


    Introduction
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Temporal arteritis or giant-cell arteritis (GCA) and polymyalgia rheumatica (PMR) are related conditions that seem to represent different clinical expressions of the same underlying vasculitic disorder [1]. The symptomatology of GCA is quite varying. Whereas previously thought to affect primarily the temporal arteries and other cranial arteries, GCA is now thought of as a disease in which large-vessel arteritis and aortitis are frequent [2–5]. Aortitis is particularly severe because fatal aortic dissection or aneurysmal rupture can occur at any time during the course of the disease [2–5]. Given the potential severity of aortic involvement and its frequency, the need for routine detection of aortic lesions is open to discussion.

Because early diagnosis and treatment may impact morbidity and mortality substantially, current radiological research aims to increase the sensitivity of imaging techniques to early vascular inflammatory changes. Vessel wall thickness and oedema, as well as mural contrast enhancement, are features of vasculitis that are present early in disease, before lumen changes are apparent angiographically [6–10]. Recent investigations support the use of certain MRI sequences in the detection of these abnormalities, especially in the aorta and its proximal branches [6–10]. However, whereas the utility and limitations of MRI have been increasingly investigated in Takayasu arteritis [6–10], limited data are available regarding the usefulness of vascular MRI studies in GCA [11–13]. Although sparse, these data are generally promising.

We here report our preliminary experience with this imaging technique in the study of the aorta and its proximal branches in patients with GCA and/or PMR, and review the scant data available in the literature.


    Material and methods
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Between 2000 and 2003, six patients with GCA and/or PMR seen in our department were diagnosed with aortitis using vascular MRI studies. The diagnosis of GCA was made according to the 1990 ACR criteria [14]. The diagnosis of PMR was based on the criteria proposed by Healey et al. [15]. In patients with GCA, all MRI studies were authorized by a consultant rheumatologist based on the following criteria: (i) the presence of signs or symptoms suggestive of aortitis; (ii) a chest radiograph suggesting an aortic aneurysm; and (iii) to investigate the possibility of subclinical aortitis as the cause of unexplained persistence of raised acute-phase reactants in patients in apparent clinical remission. In PMR patients, the study was performed in order to disclose clinically occult vasculitis in those cases who failed to respond to habitual doses of corticosteroids (CS).

MRI technique
In all cases the protocol of study included electrocardiography- and respiratory-gated black blood T1- or proton density-weighted images, and black blood T2 fat-suppressed and/or STIR turbo spin echo images, obtaining transaxial sections from the pulmonary apex to the level of the diaphragm. Additionally, MR angiography (MRA) was performed using a contrast-enhanced three-dimensional spoiled gradient-recalled steady-state (SPGR) sequence oriented in either the coronal plane or oblique sagittal along the aortic long axis plane. After MRA acquisition, axial electrocardiography-gated T1-weighted spin-echo sequences were obtained in cases 2, 4, 5 and 6 in order to investigate mural contrast enhancement. The contrast agent used was gadolinium diethylamine triamine pentacetic acid.

This study has been approved by the ethical committee of our hospital. All patients signed an informed consent before the MRI study.


    Results
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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
Of the six patients included (five women, one man), four had biopsy-proven GCA (isolated GCA in three cases and GCA + PMR in one case); the other two patients were initially diagnosed as having only isolated PMR because none presented with clinical evidence of GCA at the time of diagnosis and had a prompt response to low-dose corticosteroid therapy (20 mg daily of prednisone) with initial normalization of the acute phase-reactants.

The main clinical and laboratory data of these patients are summarized in Table 1. Mean age at time of diagnosis for all patients was 74 ± 8 yr (mean ± S.D.). The mean disease duration before diagnosis of aortitis was 42 ± 25 months (3.5 ± 2 yr). Among patients with GCA, only in one case did the clinical features led to the diagnosis of aortitis (painful upper limb claudication in patient 1); in the remaining cases, the possibility of subclinical aortitis was considered as part of the differential diagnosis of patients who were in apparent clinical remission and who had unexplained persistence of raised acute-phase reactants. In the two patients originally diagnosed with PMR, the possibility of underlying occult vasculitis was explored as a cause of failure to respond to habitual doses of CS (despite the favourable initial response, both patients presented persistence of raised laboratory inflammatory markers during follow-up and frequent relapses in the setting of tapering prednisone dosage); this fact has been previously documented in a similar case [16]. In one of these patients, a temporal artery biopsy (TAB) was performed after the detection of abnormalities on MRI/MRA, and was negative; the other refused the biopsy. Of interest, only in one of the six patients with evidence of aortitis on MRI did the chest radiograph showed aortic abnormalities suggesting this complication.


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TABLE 1. Clinical features and MRI findings of patients with GCA/PMR and aortitis

 
The main MRI findings of all patients are also summarized in Table 1. All patients were initially studied with MRI/MRA. In view of the MRI findings, the CS dose was increased to 30–50 mg of prednisone daily, with normalization of acute-phase reactants. Several months after increasing the CS dose (mean 5 ± 1 months), a follow-up MRI/MRA was performed using the same protocol of study in four patients in order to evaluate the response to treatment. All MRI studies were reviewed, with particular attention to the presence of signs of early vascular inflammation (including vessel wall thickness, oedema and contrast enhancement; see Fig. 1), as well as for the presence of lumen changes (stenosis, occlusions, dilatations and aneurysms). As shown in Table 1, whereas vascular stenosis and vessel wall thickening remained invariable on follow-up, vascular wall oedema and mural enhancement on postcontrast T1-weighted imaging improved significantly when disease activity decreased.



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FIG. 1. Axial STIR MRI scan of patient 1 shows (A) vessel wall thickness in supra-aortic arteries with increased signal intensity corresponding to mural oedema (arrows), more marked in innominate artery and left subclavian artery (E, oesophagus; T, trachea). Axial STIR MRI at the level of the aortic arch (B) demonstrates circumferential wall thickening, with mural oedema changes (arrows).

 

    Discussion
 Top
 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 
One of the unresolved challenges posed in GCA is the detection and monitoring of large-artery complications, particularly aortitis. The aortic lesions are mainly located in the thoracic segment. In most patients, this complication is asymptomatic, but some may develop an aortic arch syndrome, aortic aneurysm, sudden rupture of the aorta, aortic dissection and aortic valve insufficiency. Aortic involvement has been estimated to occur in 18% of patients, but, because of clinical silence, this involvement may be more frequent [2, 3, 5]. A population-based study from the Mayo clinic found that patients with GCA were 17.3 times more likely to develop a thoracic aortic aneurysm and 2.4 times more likely to develop an abdominal aortic aneurysm than the general population [3]. Of note, 54% of patients with thoracic aortic aneurysm in that study died suddenly of thoracic aortic dissection. Recent investigations have confirmed increased mortality due to thoracic aortic dissection in GCA [17].

Thus, aortitis is of concern because it is a relatively frequent complication of GCA that carries a risk of fatal dissection or rupture. Furthermore, this complication is often difficult to recognize in the early stages because of its indolent course in most patients and the poor specificity of the symptoms and physical examination. In this clinical scenario, non-invasive methods are frequently requested in GCA to confirm ongoing vasculitis, to monitor its course and to disclose subclinical inflammation during apparent clinical remission.

Is MRI potentially useful in these issues? Although based on small number of patients, our experience suggests that MRI may be a useful technique for the detection of vasculitis in cases with involvement of the aorta and its proximal branches, providing accurate information about its extent and intensity. In particular, MRI has a higher ability to detect earlier stages of vasculitis, disclosing, as in our patients, subclinical aortitis. These cases illustrate that occult aortitis should be considered in patients with GCA in apparent clinical remission and unexplained persistence of raised acute-phase reactants. Like conventional angiography, MRI provides detailed lumen information with high sensitivity and specificity for detection of stenosis, occlusions, dilatations and aneurysms [18, 19]. Imaging data are obtained non-invasively in a multitude of planes, avoiding the risks of arterial puncture, iodinated contrast load and radiation exposure. Moreover, in contrast to conventional angiography, MRI also provides complementary information about vessel wall thickness, oedema and mural contrast enhancement. These abnormalities seem to represent the early vascular inflammation that precedes the development of lumen changes [6–10]. Their detection can be of great clinical value, since it is assumable that early diagnosis and prompt treatment may prevent mortality and improve morbidity substantially. It is likely that most, if not all, patients with GCA have aortic inflammation at some point [5, 20]. Persistent aortitis may increase the risk of aortic dissection and rupture even in the absence of an aortic aneurysm. Assessment for persistent aortitis should then go beyond that for possible aneurysm only, and should include assessment for possible inflammatory wall changes.

The value of these paremeters in the diagnosis and assessment of disease activity has been explored in Takayasu arteritis. Vessel wall thickening, which can also be assessed by computed tomography (CT), is thought to be caused by inflammatory tissue proliferation [6–10]. The presence of a thickened aortic wall confirms the ongoing vasculitis, although this finding alone cannot distinguish active inflammation from chronic fibrotic lesions [6, 8–10]. Identification of vessel wall oedema on certain MRI pulse sequences (mainly STIR and fat-suppressed T2-weighted sequences) seems to be a parameter potentially important in monitoring response to therapy [6–10]. However, a recent study by Tso and collagues [7] has cast doubt on the reliability of this parameter as a measure of disease activity. Increased mural enhancement on postcontrast T1-weighted images reflects increased vascularity and/or excessive leakage of contrast out of the vasa vasorum, although histopathological correlation is not currently available [6, 8, 9]. There are some studies demonstrating a positive correlation between raised acute-phase reactants and increased vessel wall enhancement [8, 9], which is the best of these parameters to evaluate the disease activity. In general, active inflammation is assumed to be present if vessel wall enhancement is equal to or greater than the myocardial tissue signal [8, 9]. In our series, all patients with evidence of vessel wall thickness and oedema presented raised acute-phase reactants. In four of these patients, postcontrast T1-weighted images were obtained, and in all cases the thickened arterial wall showed increased contrast enhancement. Of interest, as suggested by the improvement of the vascular wall oedema and contrast enhancement in our patients, it would seem that the MRI results coincide with disease activity, although this finding requires further confirmation.

Available data on the evaluation of vascular MRI studies in GCA is sparse. There are some additional data supporting the usefulness of MRI in the diagnosis of aortitis in GCA, including one series of 14 patients with early GCA and aortitis studied with MRI and 18-fluorodeoxyglucose positron emission tomography (18-FDG PET) [11–13]. As in GCA, few reports have been devoted to exploration of the role of vascular MRI studies in PMR. Marzo-Ortega et al. reported the case of a patient with PMR which was difficult to treat with low doses of CS and was found to have underlying vasculitis involving the brachial artery on an MRI study of the shoulder, a finding which can explain the requirement for higher doses of steroids [16]. This report led us to investigate the possibility of an underlying vasculitis in two similar patients with PMR; in both cases the MRI/MRA study disclosed subclinical aortitis. These observations highlight the close link between PMR and GCA, and clearly illustrate that failure to respond to habitual doses of CS in PMR may reflect an underlying vasculitic process that may require higher doses of steroid treatment. This vasculitis process can be detected non-invasively by MRI or 18-FDG PET [11, 20], especially outside the classically recognized temporal artery distribution. Its identification helps in decisions about treatment. In fact, we cannot discard the possibility these patients had classic GCA, although the extent of the vasculitis was not detected at diagnosis (in none of them was a TAB initially performed). Thus, about 10% of patients originally presenting with isolated PMR have vasculitis on histological examination, requiring a change in diagnosis to GCA [1]. Moreover, some investigators have suggested that GCA may take on a large-vessel form associated with PMR, with a low frequency of temporal artery involvement (this could explain the negativity of the TAB performed after the detection of abnormalities on MRI/MRA) [21].

Both helical CT with contrast enhancement [22] and 18-FDG PET [11, 20] are surfacing as viable alternatives to MRI in the study of aortitis in GCA. Advantages of MRI over CT include safer contrast media with no nephrotoxicity, no ionizing radiation, and multiple acquisition planes, as well as increased sensitivity in the detection of oedema. Whole-body 18-FDG PET can identify vascular lesions that are not detected using MRI and seems to be more reliable than MRI in monitoring disease activity [11, 20], but currently this is still a research tool and needs to be further validated in prospective studies.

In conclusion, although based on a small number of patients, there is some evidence to suggest that MRI may be a useful technique for diagnosing patients with occult major artery involvement in GCA, whether presenting with classic symptoms of temporal arteritis or PMR. Its utility for monitoring the course of the disease and response to treatment remains to be determined. Although sparse, our preliminary experience in this issue is promising, but this question should be further examined in appropriately designed studies.

The authors have declared no conflicts of interest.


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 Abstract
 Introduction
 Material and methods
 Results
 Discussion
 References
 

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Submitted 21 June 2004; revised version accepted 9 November 2004.



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