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Ultrasound imaging in spondyloarthropathies
Best Practice & Research Clinical Rheumatology 24 (2010) 693–700
Contents lists available at ScienceDirect
Best Practice & Research Clinical Rheumatology journal homepage: www.elsevierhealth.com/berh
9
Ultrasound imaging in spondyloarthropathies Maria Antonietta D’Agostino, MD, PhD * Rheumatology Department, Université Versailles St-Quentin en Yvelines, AP-HP, Ambroise Paré Hospital, Boulogne-Billancourt, and UPRES EA 4067, Necker Hospital, Paris, France
Keywords: ultrasound Doppler Spondyloarthritis enthesitis
Through recent technological advances, ultrasound allows highresolution visualisation of inflammatory and destructive changes in tendon and joint structures. Over the last few years, the added value of the use of ultrasound for evaluating entheseal involvement in spondyloarthritis (SpA) patients has been demonstrated. Several studies have described the ultrasound features of enthesitis in SpA, revealing the high frequency of clinically asymptomatic abnormal findings. It is, therefore, highly relevant to consider the validity of ultrasonographic measures of entheseal inflammation and damage. This article focusses on ultrasound appearance of peripheral enthesitis, and underlines the advantages and current limitations of the technique for the management of SpA. Ó 2010 Elsevier Ltd. All rights reserved.
Over the last few years, ultrasound has proved to be a highly sensitive and non-invasive tool, especially for assessing tendon and joint involvement [1,2]. Although most of the recent data are based on rheumatoid arthritis (RA), there is an increasing interest and evidence for the use of ultrasound for the evaluation of SpA. Ultrasound can visualise most of the relevant musculoskeletal SpA-associated pathologies such as enthesitis, bone erosions, synovitis, bursitis and tenosynovitis. The exception is osteitis, since the ultrasound beam is not able to penetrate the bone cortex. While conventional radiography allows a clear documentation of the later stages of inflammatory changes of joint involvement, ultrasound, both in grey scale and in power Doppler, is sensitive enough to also detect early inflammatory lesions. Ultrasound appearance of musculoskelal lesions of SpA Ultrasound manifestations of synovitis, erosions and tenosynovitis in SpA patients are not different from those observed in other inflammatory arthritis including RA. The main difference seems to relate to * Ambroise Paré Hospital, 9 avenue Charles de Gaulle, 92400 Boulogne-Billancourt, France. Tel.: þ33 (0) 149095687; Fax: þ33 (0) 149095865. E-mail address: [email protected] 1521-6942/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.berh.2010.05.003
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the ultrasound appearance of enthesitis, that is, inflammation at the insertion of tendons, ligaments and capsules into the bone, which is seen as a primary lesion that may underlie all SpA skeletal manifestations [3–5]. The extensive description of entheseal involvement by ultrasound in SpA patients was made, for the first time, by Lehtinen and colleagues in 1994 [6], followed by Balint and colleagues in 2002 [7] and D’Agostino and colleagues in 2003 [8]. The first two authors described in grey scale the ultrasound abnormalities of lower limb enthesitis of SpA, revealing the high frequency of asymptomatic findings. Grey-scale ultrasound permits the depiction of both signs of acute and chronic inflammation of enthesis as well as structural damage. Grey-scale enthesitis is characterised by the loss of normal fibrillar echogenicity of tendon insertion with or without an increase of the thickness, or by intralesional focal changes of tendon insertion, such as calcific deposits, fibrous scars and periosteal changes (erosions or new bone formation). Additionally, a clear involvement of the body of tendon, far from the enthesis, and of the adjacent bursae can be observed, even if these two processes can be seen in the absence of enthesitis in other inflammatory and non- inflammatory diseases. Recently, the use of power Doppler for visualising abnormal vascularisation and hyperaemia of soft tissues in inflammatory joint diseases was extensively demonstrated [9–11]. The first description of the utility of power Doppler ultrasound for studying enthesitis was published by D’Agostino and colleagues [8]. The landmark finding on power Doppler ultrasound of enthesitis in SpA patients was the presence of abnormal vascularisation at enthesis insertion (Figs. 1 and 2). Practice points Ultrasound permits assessment of all peripheral joint features in SpA -
synovitis bursitis tendinitis enthesitis cortical bone abnormalities (i.e., erosions, enthesophytes)
Can ultrasound be helpful for assessing SpA? The use of ultrasound in the management of SpA has remained less often evaluated than in RA. This discrepancy is probably due to the greater difficulty of assessing vascular blood flow with Doppler at the entheses compared to other tissues such as the synovium [12–17]. This difference can be explained
Fig. 1. Ultrasound appearance of grey-scale enthesitis of Achilles tendon enthesitis in a longitudinal scan. Enthesophytes (E) and hypoechogenicity (H).
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Fig. 2. Ultrasound appearance of grey-scale and power Doppler enthesitis of Achilles tendon enthesitis in a longitudinal scan: erosions (A), Doppler signal (B); Hypoechogenicity and incresead of thickness (C), enthesophites (D).
not only by a greater abundance of vessels in the inflamed synovium compared to the enthesis [12–14], but also by the possible presence of Doppler artefacts at the entheseal site, due to the close proximity of a highly reflecting surface, the cortical bone [18]. Another important limitation is the lack of criterion validity. Histological investigation is considered the gold standard for the demonstration of soft tissue inflammation. In SpA, due to the difficulties in obtaining entheses samples, there are no studies comparing histological evidence of inflammation and signs of enthesitis assessed with ultrasound. Magnetic resonance imaging (MRI) is usually used as reference for ultrasound in many rheumatic diseases, especially RA [19–22]; however, for the detection of enthesitis, MRI cannot be used because of lack of sensitivity for detecting entheseal involvement [23]. This is due to changes in the fibrous part of the enthesis, where fibroblast are tightly cross-linked with little scope for accumulation of water, and cannot easily be detected with MRI. Considering this context, three competences are critically needed for sonographers to optimise enthesitis assessment by power Doppler ultrasound: 1) specific knowledge of the anatomy of each enthesis (in particular, the localisation of normal nutrition vessels); 2) practical experience for distinguishing slow vascular flow (which is the hallmark of the inflammatory process in the enthesis) from artefacts, on power Doppler; and 3) the use of an ultrasound device adapted to study the superficial structures and small vessels, since the performance of power Doppler is related to the quality of machine used.
Can ultrasound be helpful for diagnosing SpA? Early or suspected disease Although manuscript titles may occasionally suggest so, no studies have truly investigated the diagnostic value of ultrasound in SpA. It would be expected that the ability of ultrasound to visualise intra- as well as extra-articular changes would translate into ultrasound’s ability to assist in the clinical process of diagnosing a specific rheumatologic condition, but this is not scientifically verified. The lack of information may partially be due to the relatively new use of ultrasound in SpA and a slow rate of disease progression [24]. Current knowledge strongly encourages testing this hypothesis, particularly in patients with early, unclassified arthritis. Prospective studies are ongoing to highlight the diagnostic predictive value of ultrasound findings indicative of peripheral enthesitis and synovitis.
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Established disease Several studies have tried to demonstrate a difference between SpA and other rheumatic diseases according to the pattern of joint involvement. There are a number of studies mainly focussing on the ability of ultrasound to differentiate SpA from RA [8,25–33]. The main target of these studies was enthesitis, except for two studies which investigated synovitis as well [27,28]. By using grey-scale ultrasound only, discordant data were published about the capability of ultrasound to differentiate between SpA and other pathologies including RA. This discordance is related to two main factors: the absence in some of these studies of a clear definition of enthesis involvement (most of these data also regarded the tendon and bursa involvement); and the difficulty to clearly define inflammatory changes by using grey-scale only. The diagnostic performance of ultrasound seems increased by the use of power Doppler. The first description was made by D’Agostino and colleagues, who showed a high frequency of abnormal peripheral enthesitis among SpA patients in comparison with controls. The landmark of enthesitis in SpA patients was the presence of abnormal vascularisation at enthesis insertion into the cortical bone detected by using power Doppler, which was exclusively observed in SpA. In control groups, composed of RA and mechanical back pain patients, vascularisation was exclusively found in the retrocalcaneal bursa, especially in RA patients. This original observation has now been confirmed by other studies outlining the capability of power Doppler ultrasound to reveal inflammation of enthesis in SpA patients, and leading to the proposal of several different scoring systems [34,35].
Practice points - Ultrasound permits the evaluation of both inflammation and structural damage at entheseal sites. - Vascularisation detected by power Doppler at the cortical bone insertion seems to be specific for the peripheral enthesitis associated with SpA. Follow-up of the disease course Until recently, the treatment options for SpA were limited. Thus, in the past, no attempts were made to search for an objective tool which might correlate with treatment response. Only two previous studies have investigated the value of ultrasound in following up SpA patients [26,36]. In those studies, ultrasound was used as a method of detecting improvement both at the entheses and also at the joint. The effect of sulphasalazine therapy on enthesitis was investigated in both studies, and they concluded that sulphasalazine was ineffective for this disease feature [26,36]. These results may be due to the ineffectiveness of the therapy, but results may also reflect the quality of equipment used where grey scale only was used to evaluate inflammation. Most recently, it has been convincingly demonstrated that the tumour necrosis factor (TNF)-alpha blocking agents have a strong and prompt effect on almost all features of SpA, such as clinical disease activity, physical function, spinal mobility, peripheral arthritis, enthesitis and levels of acute phase reactants [37–40]. Evidence supporting the possibility of using ultrasound combined with Doppler for monitoring pathological findings indicative of soft tissue involvement in patients with SpA has been provided by two case reports [41,42]. In these reports, improvements in vascularisation and structural changes were shown in the heel and the retrocalcaneal bursa with anti-TNF-alpha therapy or without any intervention. The main issue which needs to be addressed is how to quantify this improvement and which kind of ultrasound findings to use. How to quantify enthesitis involvement by ultrasound? Quantification of disease still remains an important aspect in the management of SpA, both for activity and structural damage. For this purpose, scoring systems are relevant for monitoring changes.
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Scoring systems can be qualitative, semi-quantitative or quantitative. Semi-quantitative scoring systems are usually used for quantifying ultrasound lesions. The first and still most commonly accepted ultrasound scoring system on enthesitis, the Glasgow enthesitis scoring system (GUESS), was developed by Balint and colleagues in 2002 [7]. GUESS was designed to assess five entheseal sites in the lower limb and only grey-scale findings were included. However, the application of GUESS in monitoring response to sulphasalazine therapy failed to detect any differences [26]. This failure may well have reflected the issue that sulphasalazine is an ineffective therapy for this feature. Different enthesitis scoring systems have been developed since then: a) The D’Agostino scoring system which combined abnormalities in grey scale and Doppler, and in which the severity is weighted according to the severity of Doppler signal and the presence of structural damage [8]. b) the Spanish enthesitis index (SEI), developed as a global (i.e., patient level) scoring system which uses grey-scale abnormalities only [43]. This scoring system, however, does not differentiate between involvement of enthesis, body of tendon and bursa. c) The Madrid sonographic enthesitis index (MASEI), which combines abnormalities in grey scale and Doppler and which also includes the involvement of the bursa [34]. All of these scoring systems combine inflammatory signs (in grey-scale alone or with power Doppler) and structural signs (erosions, enthesophytes, etc.). This combination could be helpful for diagnostic purpose, but probably is not sensitive enough for follow-up purposes. The GUESS and D’Agostino scoring systems were developed for grading enthesis involvement (i.e., enthesitis level). The MASEI and SEI were developed as enthesitis indices at patient level. For that reason, these scoring systems cannot be compared. Actually, there is still a need to reach a consensus on the best system to use. Practice points - Quantification of entheseal involvement by ultrasound is best undertaken by using semiquantitative scoring systems, which combine both inflammatory and structural damage signs. Open questions are: - should different scoring systems be used (i.e., for activity and damage, for diagnostic and follow-up purposes)? - can we use a target entheses? or should we examine several sites? Prognosis No ultrasound data are as yet available about the potential prognostic value of ultrasound in SpA. Standardisation and reliability Despite promising results, the use of power Doppler ultrasound in the management of SpA has remained less often evaluated than MRI, which has been widely promoted for the detection of axial inflammation. This discrepancy is probably due to the perception that ultrasound remains an unreliable imaging technique. Few studies have previously evaluated the overall reliability of power Doppler in rheumatology [44–46]. They all concerned the reliability of joint pathologies in general (i.e., synovitis, tenosynovitis, bursitis, enthesitis,.), instead of single elementary components of each pathology (i.e., increase in the thickness of tendon, synovial hyperthrophy, etc.). Their results were strongly dependent on the type of pathology and joint studied. All have underscored the need to achieve an agreement
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on the definition of elementary lesions and their scoring to obtain reliable results. Thus, technical and anatomical issues, combined with a lack of standardisation, may have hampered the development and validation of ultrasound techniques applied to the clinical practice or to multi-centre studies in SpA. Only few studies have tested the reproducibility of ultrasound in SpA and the majority of those studies evaluated the reliability of static images rather than the reliability of image acquisition, in which the experience of the sonographer in examining the structure is also important [34,35,43,47]. Most of the studies aimed at investigating the reproducibility of ultrasound on enthesitis tested as total score or unique entity, rather than single ultrasound abnormal findings separately. The real problem until now was the definition of enthesitis used and which elementary abnormal findings have been included in that definition. Preliminary ultrasound definitions of main pathological lesions have been worked out by the OMERACT Ultrasound group [48]. This was the first tentative effort to standardise ultrasound in rheumatic diseases by a group of experts. However, the proposed preliminary definition of ultrasound enthesitis includes both structural and inflammatory findings. Until now, only two published studies have evaluated the reliability of acquisition and detection of elementary lesions included in the definition of enthesitis. The first one by Filippucci and colleagues [49] was focussed on Achilles tendon enthesitis and showed that power Doppler signal was detected with a high agreement by each investigator, while low levels of agreement rates were found for grey-scale abnormalities such as bone irregularities and hypoechogenicity. In the second study by D’Agostino and colleagues [50], the improvement in detecting and scoring power Doppler signal and morphological abnormalities in grey scale at entheseal level of five sites was prospectively assessed. The implementation of consensus guidelines resulted in an improved reliability. This information is valuable and helps validate a reliable and reproducible scoring system for enthesitis. Conclusions and future perspectives Grey-scale ultrasound, coupled with power Doppler, seems to be a reliable imaging method to assess enthesitis in SpA patients. However, further validation is still needed as ultrasound is an evolving technique. Histological studies of enthesis combined with ultrasound imaging may clarify the importance of this technique for this particular use. Despite the concerns about being an operatordependent imaging modality, all studies have supported the good reproducibility of ultrasound. It should be kept in mind though that differing ultrasound equipment with different settings, as well correct knowledge of anatomy of enthesis and a good definition of enthesitis, may have influence on the ability of ultrasound as much as the operator. The OMERACT Ultrasound group plays an important role in this development but much is still to be done, both in this forum but at least as importantly in the individual research centres. Future research agenda on ultrasound and enthesitis - Pursue standardisation of technique. - Continue to develop a severity score for both activity and damage and for diagnostic and follow-up purposes. - Quantification of Doppler signals. - Testing sensitivity to change in longitudinal studies. - Testing the diagnostic and prognostic value of power Doppler ultrasound in longitudinal multi-centre studies of suspected and early spondylarthropathies. - Continuous testing of new ultrasound technical developments, that is, contrast agents, threedimensional (3D) and 4D technology. References [1] D’Agostino MA, Breban M. Ultrasonography in inflammatory joint disease: why should rheumatologists pay attention? Joint, Bone, Spine 2002;69:252–5. [2] Grassi W, Salaffi F, Filippucci E. Ultrasound in rheumatology. Best Practice & Research. Clinical Rheumatology 2005;19: 467–85. [3] Ball J. The enthesopathy of ankylosing spondylitis. British Journal of Rheumatology 1983;22:25–8.
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Contents lists available at ScienceDirect
Best Practice & Research Clinical Rheumatology journal homepage: www.elsevierhealth.com/berh
9
Ultrasound imaging in spondyloarthropathies Maria Antonietta D’Agostino, MD, PhD * Rheumatology Department, Université Versailles St-Quentin en Yvelines, AP-HP, Ambroise Paré Hospital, Boulogne-Billancourt, and UPRES EA 4067, Necker Hospital, Paris, France
Keywords: ultrasound Doppler Spondyloarthritis enthesitis
Through recent technological advances, ultrasound allows highresolution visualisation of inflammatory and destructive changes in tendon and joint structures. Over the last few years, the added value of the use of ultrasound for evaluating entheseal involvement in spondyloarthritis (SpA) patients has been demonstrated. Several studies have described the ultrasound features of enthesitis in SpA, revealing the high frequency of clinically asymptomatic abnormal findings. It is, therefore, highly relevant to consider the validity of ultrasonographic measures of entheseal inflammation and damage. This article focusses on ultrasound appearance of peripheral enthesitis, and underlines the advantages and current limitations of the technique for the management of SpA. Ó 2010 Elsevier Ltd. All rights reserved.
Over the last few years, ultrasound has proved to be a highly sensitive and non-invasive tool, especially for assessing tendon and joint involvement [1,2]. Although most of the recent data are based on rheumatoid arthritis (RA), there is an increasing interest and evidence for the use of ultrasound for the evaluation of SpA. Ultrasound can visualise most of the relevant musculoskeletal SpA-associated pathologies such as enthesitis, bone erosions, synovitis, bursitis and tenosynovitis. The exception is osteitis, since the ultrasound beam is not able to penetrate the bone cortex. While conventional radiography allows a clear documentation of the later stages of inflammatory changes of joint involvement, ultrasound, both in grey scale and in power Doppler, is sensitive enough to also detect early inflammatory lesions. Ultrasound appearance of musculoskelal lesions of SpA Ultrasound manifestations of synovitis, erosions and tenosynovitis in SpA patients are not different from those observed in other inflammatory arthritis including RA. The main difference seems to relate to * Ambroise Paré Hospital, 9 avenue Charles de Gaulle, 92400 Boulogne-Billancourt, France. Tel.: þ33 (0) 149095687; Fax: þ33 (0) 149095865. E-mail address: [email protected] 1521-6942/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.berh.2010.05.003
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the ultrasound appearance of enthesitis, that is, inflammation at the insertion of tendons, ligaments and capsules into the bone, which is seen as a primary lesion that may underlie all SpA skeletal manifestations [3–5]. The extensive description of entheseal involvement by ultrasound in SpA patients was made, for the first time, by Lehtinen and colleagues in 1994 [6], followed by Balint and colleagues in 2002 [7] and D’Agostino and colleagues in 2003 [8]. The first two authors described in grey scale the ultrasound abnormalities of lower limb enthesitis of SpA, revealing the high frequency of asymptomatic findings. Grey-scale ultrasound permits the depiction of both signs of acute and chronic inflammation of enthesis as well as structural damage. Grey-scale enthesitis is characterised by the loss of normal fibrillar echogenicity of tendon insertion with or without an increase of the thickness, or by intralesional focal changes of tendon insertion, such as calcific deposits, fibrous scars and periosteal changes (erosions or new bone formation). Additionally, a clear involvement of the body of tendon, far from the enthesis, and of the adjacent bursae can be observed, even if these two processes can be seen in the absence of enthesitis in other inflammatory and non- inflammatory diseases. Recently, the use of power Doppler for visualising abnormal vascularisation and hyperaemia of soft tissues in inflammatory joint diseases was extensively demonstrated [9–11]. The first description of the utility of power Doppler ultrasound for studying enthesitis was published by D’Agostino and colleagues [8]. The landmark finding on power Doppler ultrasound of enthesitis in SpA patients was the presence of abnormal vascularisation at enthesis insertion (Figs. 1 and 2). Practice points Ultrasound permits assessment of all peripheral joint features in SpA -
synovitis bursitis tendinitis enthesitis cortical bone abnormalities (i.e., erosions, enthesophytes)
Can ultrasound be helpful for assessing SpA? The use of ultrasound in the management of SpA has remained less often evaluated than in RA. This discrepancy is probably due to the greater difficulty of assessing vascular blood flow with Doppler at the entheses compared to other tissues such as the synovium [12–17]. This difference can be explained
Fig. 1. Ultrasound appearance of grey-scale enthesitis of Achilles tendon enthesitis in a longitudinal scan. Enthesophytes (E) and hypoechogenicity (H).
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Fig. 2. Ultrasound appearance of grey-scale and power Doppler enthesitis of Achilles tendon enthesitis in a longitudinal scan: erosions (A), Doppler signal (B); Hypoechogenicity and incresead of thickness (C), enthesophites (D).
not only by a greater abundance of vessels in the inflamed synovium compared to the enthesis [12–14], but also by the possible presence of Doppler artefacts at the entheseal site, due to the close proximity of a highly reflecting surface, the cortical bone [18]. Another important limitation is the lack of criterion validity. Histological investigation is considered the gold standard for the demonstration of soft tissue inflammation. In SpA, due to the difficulties in obtaining entheses samples, there are no studies comparing histological evidence of inflammation and signs of enthesitis assessed with ultrasound. Magnetic resonance imaging (MRI) is usually used as reference for ultrasound in many rheumatic diseases, especially RA [19–22]; however, for the detection of enthesitis, MRI cannot be used because of lack of sensitivity for detecting entheseal involvement [23]. This is due to changes in the fibrous part of the enthesis, where fibroblast are tightly cross-linked with little scope for accumulation of water, and cannot easily be detected with MRI. Considering this context, three competences are critically needed for sonographers to optimise enthesitis assessment by power Doppler ultrasound: 1) specific knowledge of the anatomy of each enthesis (in particular, the localisation of normal nutrition vessels); 2) practical experience for distinguishing slow vascular flow (which is the hallmark of the inflammatory process in the enthesis) from artefacts, on power Doppler; and 3) the use of an ultrasound device adapted to study the superficial structures and small vessels, since the performance of power Doppler is related to the quality of machine used.
Can ultrasound be helpful for diagnosing SpA? Early or suspected disease Although manuscript titles may occasionally suggest so, no studies have truly investigated the diagnostic value of ultrasound in SpA. It would be expected that the ability of ultrasound to visualise intra- as well as extra-articular changes would translate into ultrasound’s ability to assist in the clinical process of diagnosing a specific rheumatologic condition, but this is not scientifically verified. The lack of information may partially be due to the relatively new use of ultrasound in SpA and a slow rate of disease progression [24]. Current knowledge strongly encourages testing this hypothesis, particularly in patients with early, unclassified arthritis. Prospective studies are ongoing to highlight the diagnostic predictive value of ultrasound findings indicative of peripheral enthesitis and synovitis.
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Established disease Several studies have tried to demonstrate a difference between SpA and other rheumatic diseases according to the pattern of joint involvement. There are a number of studies mainly focussing on the ability of ultrasound to differentiate SpA from RA [8,25–33]. The main target of these studies was enthesitis, except for two studies which investigated synovitis as well [27,28]. By using grey-scale ultrasound only, discordant data were published about the capability of ultrasound to differentiate between SpA and other pathologies including RA. This discordance is related to two main factors: the absence in some of these studies of a clear definition of enthesis involvement (most of these data also regarded the tendon and bursa involvement); and the difficulty to clearly define inflammatory changes by using grey-scale only. The diagnostic performance of ultrasound seems increased by the use of power Doppler. The first description was made by D’Agostino and colleagues, who showed a high frequency of abnormal peripheral enthesitis among SpA patients in comparison with controls. The landmark of enthesitis in SpA patients was the presence of abnormal vascularisation at enthesis insertion into the cortical bone detected by using power Doppler, which was exclusively observed in SpA. In control groups, composed of RA and mechanical back pain patients, vascularisation was exclusively found in the retrocalcaneal bursa, especially in RA patients. This original observation has now been confirmed by other studies outlining the capability of power Doppler ultrasound to reveal inflammation of enthesis in SpA patients, and leading to the proposal of several different scoring systems [34,35].
Practice points - Ultrasound permits the evaluation of both inflammation and structural damage at entheseal sites. - Vascularisation detected by power Doppler at the cortical bone insertion seems to be specific for the peripheral enthesitis associated with SpA. Follow-up of the disease course Until recently, the treatment options for SpA were limited. Thus, in the past, no attempts were made to search for an objective tool which might correlate with treatment response. Only two previous studies have investigated the value of ultrasound in following up SpA patients [26,36]. In those studies, ultrasound was used as a method of detecting improvement both at the entheses and also at the joint. The effect of sulphasalazine therapy on enthesitis was investigated in both studies, and they concluded that sulphasalazine was ineffective for this disease feature [26,36]. These results may be due to the ineffectiveness of the therapy, but results may also reflect the quality of equipment used where grey scale only was used to evaluate inflammation. Most recently, it has been convincingly demonstrated that the tumour necrosis factor (TNF)-alpha blocking agents have a strong and prompt effect on almost all features of SpA, such as clinical disease activity, physical function, spinal mobility, peripheral arthritis, enthesitis and levels of acute phase reactants [37–40]. Evidence supporting the possibility of using ultrasound combined with Doppler for monitoring pathological findings indicative of soft tissue involvement in patients with SpA has been provided by two case reports [41,42]. In these reports, improvements in vascularisation and structural changes were shown in the heel and the retrocalcaneal bursa with anti-TNF-alpha therapy or without any intervention. The main issue which needs to be addressed is how to quantify this improvement and which kind of ultrasound findings to use. How to quantify enthesitis involvement by ultrasound? Quantification of disease still remains an important aspect in the management of SpA, both for activity and structural damage. For this purpose, scoring systems are relevant for monitoring changes.
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Scoring systems can be qualitative, semi-quantitative or quantitative. Semi-quantitative scoring systems are usually used for quantifying ultrasound lesions. The first and still most commonly accepted ultrasound scoring system on enthesitis, the Glasgow enthesitis scoring system (GUESS), was developed by Balint and colleagues in 2002 [7]. GUESS was designed to assess five entheseal sites in the lower limb and only grey-scale findings were included. However, the application of GUESS in monitoring response to sulphasalazine therapy failed to detect any differences [26]. This failure may well have reflected the issue that sulphasalazine is an ineffective therapy for this feature. Different enthesitis scoring systems have been developed since then: a) The D’Agostino scoring system which combined abnormalities in grey scale and Doppler, and in which the severity is weighted according to the severity of Doppler signal and the presence of structural damage [8]. b) the Spanish enthesitis index (SEI), developed as a global (i.e., patient level) scoring system which uses grey-scale abnormalities only [43]. This scoring system, however, does not differentiate between involvement of enthesis, body of tendon and bursa. c) The Madrid sonographic enthesitis index (MASEI), which combines abnormalities in grey scale and Doppler and which also includes the involvement of the bursa [34]. All of these scoring systems combine inflammatory signs (in grey-scale alone or with power Doppler) and structural signs (erosions, enthesophytes, etc.). This combination could be helpful for diagnostic purpose, but probably is not sensitive enough for follow-up purposes. The GUESS and D’Agostino scoring systems were developed for grading enthesis involvement (i.e., enthesitis level). The MASEI and SEI were developed as enthesitis indices at patient level. For that reason, these scoring systems cannot be compared. Actually, there is still a need to reach a consensus on the best system to use. Practice points - Quantification of entheseal involvement by ultrasound is best undertaken by using semiquantitative scoring systems, which combine both inflammatory and structural damage signs. Open questions are: - should different scoring systems be used (i.e., for activity and damage, for diagnostic and follow-up purposes)? - can we use a target entheses? or should we examine several sites? Prognosis No ultrasound data are as yet available about the potential prognostic value of ultrasound in SpA. Standardisation and reliability Despite promising results, the use of power Doppler ultrasound in the management of SpA has remained less often evaluated than MRI, which has been widely promoted for the detection of axial inflammation. This discrepancy is probably due to the perception that ultrasound remains an unreliable imaging technique. Few studies have previously evaluated the overall reliability of power Doppler in rheumatology [44–46]. They all concerned the reliability of joint pathologies in general (i.e., synovitis, tenosynovitis, bursitis, enthesitis,.), instead of single elementary components of each pathology (i.e., increase in the thickness of tendon, synovial hyperthrophy, etc.). Their results were strongly dependent on the type of pathology and joint studied. All have underscored the need to achieve an agreement
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on the definition of elementary lesions and their scoring to obtain reliable results. Thus, technical and anatomical issues, combined with a lack of standardisation, may have hampered the development and validation of ultrasound techniques applied to the clinical practice or to multi-centre studies in SpA. Only few studies have tested the reproducibility of ultrasound in SpA and the majority of those studies evaluated the reliability of static images rather than the reliability of image acquisition, in which the experience of the sonographer in examining the structure is also important [34,35,43,47]. Most of the studies aimed at investigating the reproducibility of ultrasound on enthesitis tested as total score or unique entity, rather than single ultrasound abnormal findings separately. The real problem until now was the definition of enthesitis used and which elementary abnormal findings have been included in that definition. Preliminary ultrasound definitions of main pathological lesions have been worked out by the OMERACT Ultrasound group [48]. This was the first tentative effort to standardise ultrasound in rheumatic diseases by a group of experts. However, the proposed preliminary definition of ultrasound enthesitis includes both structural and inflammatory findings. Until now, only two published studies have evaluated the reliability of acquisition and detection of elementary lesions included in the definition of enthesitis. The first one by Filippucci and colleagues [49] was focussed on Achilles tendon enthesitis and showed that power Doppler signal was detected with a high agreement by each investigator, while low levels of agreement rates were found for grey-scale abnormalities such as bone irregularities and hypoechogenicity. In the second study by D’Agostino and colleagues [50], the improvement in detecting and scoring power Doppler signal and morphological abnormalities in grey scale at entheseal level of five sites was prospectively assessed. The implementation of consensus guidelines resulted in an improved reliability. This information is valuable and helps validate a reliable and reproducible scoring system for enthesitis. Conclusions and future perspectives Grey-scale ultrasound, coupled with power Doppler, seems to be a reliable imaging method to assess enthesitis in SpA patients. However, further validation is still needed as ultrasound is an evolving technique. Histological studies of enthesis combined with ultrasound imaging may clarify the importance of this technique for this particular use. Despite the concerns about being an operatordependent imaging modality, all studies have supported the good reproducibility of ultrasound. It should be kept in mind though that differing ultrasound equipment with different settings, as well correct knowledge of anatomy of enthesis and a good definition of enthesitis, may have influence on the ability of ultrasound as much as the operator. The OMERACT Ultrasound group plays an important role in this development but much is still to be done, both in this forum but at least as importantly in the individual research centres. Future research agenda on ultrasound and enthesitis - Pursue standardisation of technique. - Continue to develop a severity score for both activity and damage and for diagnostic and follow-up purposes. - Quantification of Doppler signals. - Testing sensitivity to change in longitudinal studies. - Testing the diagnostic and prognostic value of power Doppler ultrasound in longitudinal multi-centre studies of suspected and early spondylarthropathies. - Continuous testing of new ultrasound technical developments, that is, contrast agents, threedimensional (3D) and 4D technology. References [1] D’Agostino MA, Breban M. Ultrasonography in inflammatory joint disease: why should rheumatologists pay attention? Joint, Bone, Spine 2002;69:252–5. [2] Grassi W, Salaffi F, Filippucci E. Ultrasound in rheumatology. Best Practice & Research. Clinical Rheumatology 2005;19: 467–85. [3] Ball J. The enthesopathy of ankylosing spondylitis. British Journal of Rheumatology 1983;22:25–8.
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