- Email: [email protected]
Imaging Evaluation of the Entheses
I m a g i n g Ev a l u a t i o n o f t h e E n t he s es Ultrasonography, MRI, and Scoring of Evaluation Maria Antonietta D’Agostino,
MD, PhD
a,b,
*, Lene Terslev,
MD, PhD
c
KEYWORDS Ultrasonography Enthesitis Spondyloarthritis MRI KEY POINTS Power Doppler ultrasonography (PDUS) and MRI have changed the management of spondyloarthritis (SpA). MRI and PDUS are key imaging modalities for evaluating disease activity at entheseal level. Recent advancement in MRI, as whole body MRI, may have potential in early diagnosis and better understanding of SpA; further testing and validation are warranted.
INTRODUCTION
Over the last 40 years, the concept of spondylarthritis (SpA) has evolved thanks to the introduction of new drugs and an earlier detection of the disease, owing to the introduction of new imaging techniques such as MRI and ultrasound imaging (US; Fig. 1). The latter have permitted to visualize what is considered the landmark lesion: the enthesitis.1–3 Understanding of the imaging findings of enthesitis hinges on the knowledge of the relevant joint anatomy.3–7 ENTHESIS, ENTHESOPATHY, AND ENTHESITIS
The term enthesis refers to the anatomic interface, or bony attachment, of tendons, ligaments, fascia, muscles, and joint capsules. The involvement of the entheses in any pathologic process, whatever the origin (ie, metabolic, inflammatory, traumatic or degenerative), is usually defined as “enthesopathy,” whereas “enthesitis” defines a
Rheumatology Department, APHP, Hoˆpital Ambroise Pare´, 9 avenue Charles, de Gaulle, Boulogne-Billancourt 92100, France; b INSERM U1173, Laboratoire d’Excellence INFLAMEX, UFR Simone Veil, 2 Avenue de la Source de la Bie`vre, Montigny-le-Bretonneux, VersaillesSaint-Quentin University, Saint-Quentin en Yvelines 78180, France; c Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Blegdamsvej 9, University of Copenhagen, 2100 Copenhagen, Denmark * Corresponding author. Rheumatology Department, APHP, Hoˆpital Ambroise Pare´, 9 avenue Charles de Gaulle, Boulogne-Billancourt 92100, France. E-mail address: [email protected]
Rheum Dis Clin N Am - (2016) -–http://dx.doi.org/10.1016/j.rdc.2016.07.012 0889-857X/16/ª 2016 Elsevier Inc. All rights reserved.
rheumatic.theclinics.com
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Fig. 1. Why imaging in spondyloarthritis?
the “inflammatory” involvement.8 In this context, Niepel and associates9 were the first to use the term “enthesitis” for describing the inflammatory symptoms commonly observed at the calcaneal insertion of the Achilles tendon in patients with ankylosing spondylitis. The pivotal role of enthesitis as common characteristic lesion of the SpA complex was suggested for the first time by John Ball.7 In his famous “Heberden Horation,” Ball pointed out that the persistent inflammation of the entheses (ie, “enthesitis”) is the distinctive pathologic feature of ankylosing spondylitis, whereas the characteristic feature of rheumatoid arthritis (RA) is the persistent inflammation of the synovial membrane (ie, “synovitis”).7 Recent knowledge regarding the function, anatomy, and physiology of the enthesis in human and animal models led to improvements in our understanding of the entheseal pathology in the course of many rheumatic diseases, especially SpA.10,11
ANATOMY, FUNCTION, AND HISTOPATHOLOGY OF ENTHESITIS
Although anatomic studies are difficult to perform, because the entheses represent areas where hard and soft tissues meet, 2 types of enthesis are usually described: fibrous and fibrocartilageous. In the fibrous entheses the collagen fibers of the tendons or ligaments attach directly to the bone, whereas in fibrocartilaginous entheses 4 transitional zones are observed4–6: (1) collagen zone, directly derived from the tendon (or ligament, capsule, tendon, aponeurosis, or annulus) structure, (2) noncalcified fibrocartilaginous zone, (3) tidemark-calcified fibrocartilaginous zone, and (4) subchondral bone zone. The entheses are vascularized primarily by the vessels coming from the bone marrow, and partially by the vessels of the peritenon (eg, in the fibrocartilaginous entheses). Blood vessels are present predominantly at the junction between the uncalcified and calcified fibrocartilaginous zones.6,12,13 Few histopathologic studies have been performed on the entheses of ankylosing spondylitis patients, and most of them were performed on material obtained during joint replacement; some of them (especially in late 1960s) using biopsies from painful entheseal sites.7
Ultrasonography and MRI in Detecting Enthesitis
The histologic hallmark of the “enthesitis” seems to be the coexistence of lesions of different durations at the same site, with erosions, microscopic inflammatory foci at the tendon/ligament insertion, and areas of bone repair.7,14 The enthesis was primarily viewed as a site of metabolic activity, notably during growth.15 In a second time the role of the enthesis as biomechanical site has played a major role. In contrast with other skeletal locations, the enthesis is a site of repetitive biomechanical forces.15 Clinical observations, supported by animal model experiences, suggest that mechanical stress may trigger the development of an enthesitis, by stimulating an inflammatory cascade with cytokine production, which affects not only the bony attachment interface and the enthesis itself, but also the surrounding tissues, such as the bursa, fat pad, and synovium.16–18 In the early phases of this process, the predominant pattern seems to be the destruction of the fibrocartilage, with neovascularization and infiltration of inflammatory cell predominantly at the sites where synovium, subchondral bone, and bone marrow are close. This results in an articular inflammatory response in the adjacent synovial tissue, driving the concept of the synovio–entheseal complex.19–21 Secondarily, the adjacent bone reacts with formation of enthesophytes and spurs.22 IMAGING AND ENTHESITIS
Historically, the radiographic features of enthesitis have played a pivotal role in defining the enthesitis lesions in SpA. Enthesitis was defined mainly by the abnormalities observed at the bone insertion such as osteopenia, bone cortex irregularity, erosions, entheseal soft tissue calcifications, and new bone formation (Fig. 2).23–26 However, entheseal bone changes appear late and are also common in mechanical disorders and in crystal related pathology. Aging is also associated with an increased prevalence of asymptomatic radiographic changes.23–26 In the past, before the extensive use of MRI and US, the only technique able to study inflammatory changes of articular and periarticular structures was bone scintigraphy, revealing diffuse increase in bone and articular uptake in active SpA patients. However, the poor spatial resolution of this technique, the lack of specificity, and the relative radiation hampered its extensive use.27,28
Fig. 2. Conventional radiography of the calcaneus. The radiograph shows a lateral view of a calcaneus of a patient with spondyloarthritis. Arrows show the spurs at the cortical insertion of the Achilles tendon and plantar fascia.
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MRI AND ENTHESITIS
MRI is currently considered the best imaging modality to identify early axial involvement (spine and sacroiliac joints) in patients with SpA, when conventional radiography is still normal.29 Although MRI methods have faced a rapid evolution over the past years, the imaging technique itself has not completely changed. Conventional T1-weighted sequences and short T1 inversion recovery images are regarded as the methods of choice to depict structural and inflammatory lesions, respectively. The use of MRI for evaluating peripheral entheses has permitted to demonstrate elegantly the link between enthesitis and synovitis.30,31 The use of fat-suppressed, fat-saturated, and water-sensitive MRI sequences has shown that the extraarticular inflammation quite often observed represents enthesitis. In fact, the typical appearance of peripheral enthesitis on MRI includes soft tissue inflammatory changes and perientheseal bone marrow edema (Fig. 3). However, with the actual MRI equipment, the depiction of enthesitis is limited in case of absence of concomitant bone edema. In structures with low water accumulation, such as at the bone attachment, the visualization of lesions is quite difficult owing to the low signal on conventional MRI. To improve the visualization of early inflammatory changes several techniques and sequences used in other fields (such as neuroimaging) are now being tested for potential use in SpA.32 WHOLE BODY MRI
Another limitation of the conventional MRI is the fact that only 1 site at time can be examined. To permit the simultaneous assessment of the entire spine (including the sacroiliac joints) and of peripheral structures (including the peripheral entheses) Whole body MRI has now been applied (Fig. 4). The simultaneous evaluation is possible by the concurrent use of several coils scanning the entire body within 30 to 40 minutes without patient repositioning. The visualization of inflammatory changes in the spine has a spatial resolution similar to the standard MR examinations33–35; however, the quality and reproducibility of the detection of the peripheral involvement, especially
Fig. 3. MRI of calcaneus. The 2 panels show the presence of enthesitis (as a focal thickening with high signal in the medial aspect of the plantar fascia (arrow of panel A), and also at the enthesis attachment on to calcaneus (arrow of panel B). Presence of edema and erosive changes in the subcortical bone marrow (A); and also edema in the surrounding soft tissue of the plantar fascia, close to the insertion and in the body of the fascia (B).
Ultrasonography and MRI in Detecting Enthesitis
Fig. 4. Whole body MRI. Example of normal aspect.
of peripheral enthesitis and of synovitis of small joints, is not completely adequate. Whole body MRI may be useful in the initial evaluation of disease activity as well as for follow-up evaluation and in clinical trials. High-resolution MRI
High-resolution MRI using gradient echo sequences with fat saturation produce images with hyperintense depiction of cartilage whereas surrounding bone is depicted hypointense, thus allowing detailed analysis of erosions and, when applied, to small joints a greater visualization of the entheses insertion.36,37 Diffusion-weighted MRI
Diffusion-weighted MRI is based on the tissue-dependent signal attenuation caused by incoherent thermal motion of water molecules. Mobility of water molecules is driven by thermal agitation and depends greatly on its cellular environment. This technique might potentially permit to detect early inflammatory changes especially in the bone.38,39
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MRI AND ULTRASONOGRAPHY IN THE EVALUATION OF PERIPHERAL ENTHESITIS: WHICH MODALITIES?
Table 1 delineates the advantages and limitations of US and MRI. Although MRI should be consider the reference choice for the assessment of the axial involvement, the use of MRI for the evaluation of peripheral enthesitis is actually limited by its cost, availability, and accuracy.31 Moreover, there are not available scoring systems at the moment. Therefore, US should be considered the method of choice both in clinical practice and in the research setting.40,41 Ultrasound and Enthesitis
The extensive description of US involvement of entheses in SpA patients was made for the first time by Lehtinen and colleagues42 in 1994 and then by Balint and colleagues43 in 2002. These authors described in grey scale the US abnormalities of lower limb enthesitis of SpA, revealing the high frequency of asymptomatic findings. Grey scale enthesitis is characterized by the loss of normal fibrillar echogenicity of tendon insertion with an increase of the thickness insertion, or by intralesional focal changes of tendon insertion, such as calcific deposits, fibrous scares aspect, 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. Thus grey scale US permits to depict both signs of acute and chronic inflammation of enthesis as well as structural damage. Since then, discordant data have been published about the capability of grey scale US alone to differentiate between enthesis involvement in SpA and in other pathologies.44,45 This discordance is related to several factors: the absence in some of these studies of a clear definition of enthesis involvement (most of these data regarded also the tendon and bursa involvement)45; the difficulty to clearly define inflammatory changes by using only grey scale. The main appearance of inflammation in grey scale is edema, which is characterized by the loss of normal echostructure (ie, hypoechogenicity), associated or not to the increase of the thickness of tendon insertion, which is very difficult to quantify. The use of power Doppler for visualizing abnormal vascularization and hyperemia has made possible to overcome this lack of specificity.46 The landmark of an enthesitis detected on US in SpA patients when compared with Table 1 Strengths and weakness of ultrasound and MRI Ultrasound Strengths
Weaknesses
Real-time and dynamic Unable to image imaging within bone
MRI Strengths
Weaknesses
Ability to image bone
Limited to 1 body region
Potential for motion More complete artifact and assessment of whole contraindications joint (all articular (eg, pacemaker) surfaces)
Immediately accessible; complements the physical examination
Specialist training not always available
Relatively easy to examine multiple body regions
Limited accessibility of Quantitative some structures measurement of (acoustic window) synovium
Time and patient tolerance
Portability
Interobserver variability and training needs
Cost
Better reproducibility
Ultrasonography and MRI in Detecting Enthesitis
controls (RA patients and mechanical spinal disease patients) is the presence of abnormal vascularization at enthesis insertion, allowing the differentiation between SpA involvement and other mechanical or metabolic involvements.47 US has indeed proven to be a highly useful and sensitive tool in the evaluation of enthesitis by improving the ability of the clinical examination to detect enthesitis.48,49 Several studies have also demonstrated the prognostic value of the detection of enthesitis for an early diagnosis of SpA.50–52 In particular, the most recent prospective cohort study conducted in patients with symptoms suggestive of SpA50 has shown that vascularization at cortical bone detected by PDUS was the only independent contributor to a diagnosis of SpA made 2 years later, and that PDUS vascularized enthesis combined with Amor’s criteria53 was highly effective in making an early diagnosis of SpA in the absence of other clinical, imaging and biological findings. US is also useful for evaluating disease activity and to monitor response to treatment,54,55 although this aspect has been explored in few studies until now. Despite promising results, the use of power Doppler US for the management of SpA has remained less often evaluated than in RA.56 This discrepancy is probably owing to the perception that US, especially for detecting enthesitis, remains an operatordependent technique owing to the greater difficulty of assessing vascular blood flow with Doppler in the entheses than in the synovium.57 The latter difference can be explained by a greater abundance of vessels in the inflamed synovium, than in enthesitis.10–14 In addition, Doppler artifacts are frequently produced at the enthesis attachment owing the close proximity of the cortical bone, which is a highly reflecting surface,58,59 and only few studies are available comparing histology evidence of inflammation and signs of enthesitis assessed by US.60 A study comparing the grey scale US signs of enthesitis and the histologic sample taken in the same place, showed that the hypoechoic area detected by US corresponds with macrophage infiltration, increased vascularity, and edema.60 Three competences are critically needed to optimize the evaluation of enthesitis by grey scale and Doppler US: (i) a specific knowledge of the anatomy of each enthesis (in particular the localization of normal nutrition vessels), (ii) the capacity to distinguish very slow vascular flow (which is the hallmark of the inflammatory process in the enthesis) from artifacts, on power Doppler,57 and (iii) the US machine used as the characteristics of the Doppler modality vary according to the US device used.61 Normal Ultrasound Aspect of Peripheral Enthesis
Under normal conditions, the 4 zones of fibrocartilageous enthesis are not visible or are only just visible owing to the small thickness of the fibrocartilage and to the quality and resolution of US equipment (Fig. 5). Thus, the normal US aspect of the enthesis is difficult to distinguish from the US aspect of the body of tendon or ligament and it appears as a normal continuity of the tendon/ligament into the bone. Ultrasound Definition of Enthesitis
The OMERACT (Outcome Measures in Rheumatology) US task force proposed 10 years ago, preliminary US definitions for elementary pathologic findings, at the joint level, including enthesopathy.62 At that time, it was decided to define enthesopathy instead of enthesitis to include both mechanical and inflammatory pathologies. In this definition, both acute and chronic inflammatory aspects in grey scale (ie, loss of normal echostructure, increased of the thickness, focal calcic deposits) as well as Doppler signal are combined with findings of structural damage (ie, enthesophytes, bony erosions). This combination is helpful for defining the presence or absence of
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Fig. 5. Normal enthesis by ultrasonography (US). (A) Normal US appearance of the insertion of the quadriceps tendon in a longitudinal scan. The rectangle shows the area of the enthesis. (B) Drawing of the enthesis and the surrounding structures (tendon, bone, bursa). Rectangle shows the enthesis.
enthesitis, but probably not for responsiveness and for differential diagnosis between diseases (SpA vs RA vs mechanical or metabolic entheseal involvement).44,45 Ultrasound Definition of Elementary Lesions of Enthesitis
Recently, the same OMERACT US group has tried to standardize the definition of each elementary component participating to the enthesitis definition.63 They first decided to consider enthesitis as an involvement of the anatomic enthesis, which is different from the involvement of bursa and body of tendon (see Fig. 5). Bursa and tendon can be involved in SpA inflammatory process, but should be evaluated as different structures and not included in the definition of US-detected enthesitis (Fig. 6). In grey scale, enthesitis can be characterized by the following elementary lesions that should be detected within 2 mm from the bone surface: Hypoechogenicity of the insertion of tendon/ligament/capsule into the bone, which can be defined as a lack of the homogeneous echotexture pattern, with loss of the tightly packed echogenic lines after correcting anisotropy artifact (Fig. 7). Increased of thickness of tendon/ligament/capsule insertion into the bone, as compared with the body of tendon/ligament/capsule, with or without blurring of the tendon/ligament/capsule margins.
Fig. 6. Ultrasound (US) aspect of the enthesitis of the Achilles tendon in grey scale and power Doppler. Longitudinal US scan of the Achilles tendon insertion. The elementary components present are entheseal hypoechogenicity (H), erosion of the calcaneus (E), and deep retrocalcaneal bursitis (B). The presence of power Doppler signal inside the bursa (B) and the entheseal erosions (E).
Ultrasonography and MRI in Detecting Enthesitis
Fig. 7. Ultrasound (US) aspect of the enthesitis of the Achilles tendon in grey scale. Longitudinal US scan of the Achilles tendon insertion. The elementary components present are entheseal hypoechogenicity (H), calcifications (C), and enthesophytes (E).
Calcifications or fibrous scares detected at the tendon/ligament/capsule insertion into the bone, defined as hyperechoic foci consistent with calcic deposits, with or without acoustic shadow, seen in 2 perpendicular planes (see Fig. 7). Enthesophytes, defined as a step up of bony prominence at the end of the normal bone contour seen in 2 perpendicular planes, with or without acoustic shadow (see Fig. 7). Erosions, defined as a cortical breakage with a step down contour defect, seen in 2 perpendicular planes, at enthesis insertion (Fig. 8A). Cortical irregularities, defined as a loss of the normal regular bone contour, without any clear sign of enthesophyte and/or erosion. These grey scale abnormalities can be associated with Doppler signal in case of inflammation (Fig. 8 B, C). For defining enthesitis instead of enthesopathy, the presence of Doppler signal should be detected at the cortical enthesis insertion, and should be differentiated from reflecting surface artifact or nutrition vessel signal. Doppler signal can be present even in absence of cortical irregularities, erosions, or enthesophytes. The latter explanation is important because it has been shown, in histologic studies, that normal aged entheses may have bone microdamage at enthesis associated with microscopic vascular changes, which are likely involved in the repair response.10–13 Vascular changes are also present adjacent to enthesophytes in the normal aged enthesis.13 Until now, no studies have demonstrated the possibility to detect a normal vascularization of enthesis by using US in a healthy normal subject, even when the Doppler signal is enhanced by using medium US contrast agents.11 Recently, a study has shown the capability of contrast enhanced US to confirm the presence of an enthesitis in case of doubtful Doppler signal, confirming therefore the importance of Doppler for evaluating enthesitis.64 Inflammation and structural damage can coexist. Table 2 summarizes the structural and inflammatory findings that can be detected on US. Grey Scale and Doppler Modalities: Which Is the Best for Studying Enthesitis?
The quality of machine and probe used for entheses examination is very important. All peripheral entheses are very superficial structures, localized directly under the skin and subcutaneous tissue. Thus, a linear high-frequency probe (ideally >14 MHz) is necessary for accurate visualization of the enthesis structure. The Doppler used
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Fig. 8. Ultrasound (US) aspect of the enthesitis of the Achilles tendon in grey scale and power Doppler. (A) Longitudinal US scan of the Achilles tendon insertion. The elementary component present is the entheseal erosion of calcaneus (E). Corresponding images with Doppler enhancement (longitudinal B) and transverse (C).
should have the same characteristics of resolution and be adapted to superficial structures and to slow blood flows. Higher Doppler frequency gives a more detailed image of the vessels but at the expense of penetration. Thus, frequency, Doppler gain, pulse repetition frequency, and wall filter settings are key issues. Among the different Doppler modalities, power Doppler often has most of those prerequisites. Its theoretic advantage over color Doppler is sensitivity. Disregarding the direction of flow and disregarding velocity the power (energy) of the many different frequency shifts inside a cell are added to form the power signal. Therefore, it is almost angle independent and without aliasing. The optimum frequency may vary from machine to machine and must therefore be found in practice and not in theory.62
Table 2 Structural and inflammatory findings detected by ultrasound Component
Inflammation
Damage
Enthesitis
Insertion thickening Hypoechogenicity Vascularity
Entheseal erosion New bone growth-periosteal/ enthesophyte
Ultrasonography and MRI in Detecting Enthesitis
Box 1 Published ultrasound scoring systems at the enthesis and patient levels US scoring systems GS only Glasgow Enthesitis Scoring System (enthesis 1 patient level) 43 - Balint and colleagues Spanish Enthesitis Index (enthesis level) 65 - Alcalde and colleagues GS and Doppler D’Agostino Scoring System (enthesis 1 patient level) 47,50 - D’Agostino and colleagues Madrid Sonographic Enthesitis Index (enthesis 1 patient level) 49,51 - De Miguel and colleagues
How to Score Enthesitis Involvement by Ultrasound?
The scoring systems can either be qualitative, semiquantitative, or quantitative and can be developed at patient level or at enthesis level. Box 1 shows the published US scoring systems. Scoring systems are relevant for monitoring changes. The first and still commonly accepted US scoring system on enthesitis, the Glasgow Enthesitis Scoring System (GUESS), was developed by Balint and colleagues43 in 2002. GUESS was designed to assess 5 entheses of the lower limb and only gray scale findings were included. Its application for therapy monitoring was not able to detect any differences when used to assess sulphasalazine treatment, which might simply indicate ineffective therapy.44 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 damage47,50; (b) the Spanish Enthesitis Index, developed as a global (ie, patient-level) scoring system and uses grey scale abnormalities only.65 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 includes involvement of the bursa.49,51 The MASEI is a global enthesitis index and the GUESS and D’Agostino scoring systems are the scoring systems at enthesis level. There remains a need to reach a consensus on the best system to use. SUMMARY
Grey scale US combined with power Doppler should be considered as a gold standard for the imaging evaluation of peripheral enthesitis in SpA, because MRI should be considered the gold standard for the evaluation of the axial involvement. However, further validation is still needed as both US and MRI are evolving techniques. Inflammation at the enthesis is likely modulated by multiple factors. A better understanding of the enthesis disease combined with the new advances in imaging will permit to understand better the role of enthesitis in the pathogenesis of SpA. Research agenda Development of MRI scoring system for peripheral enthesitis. Comparing US and MRI findings of activity and damage. Test the responsiveness to change of US and MRI lesions.
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ACKNOWLEDGMENTS
The authors acknowledge Rene Poggenborg, MD, PhD, for his contribution with the MRI and whole body MRI images. REFERENCES
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38. Gaspersic N, Sersa I, Jevtic V, et al. Monitoring ankylosing spondylitis therapy by dynamic contrast-enhanced and diffusion weighted magnetic resonance imaging. Skeletal Radiol 2008;37:123–31. 39. Gezmis E, Donmez FY, Agildere M. Diagnosis of early sacroiliitis in seronegative spondyloarthropathies by DWI and correlation of clinical and laboratory findings with ADC values. Eur J Radiol 2013;82:2316–21. 40. D’Agostino MA. Ultrasound imaging in spondyloarthropathies. Best Pract Res Clin Rheumatol 2010;24:693–700. 41. D’Agostino MA. Role of ultrasound in the diagnostic work-up of spondyloarthritis. Curr Opin Rheumatol 2012;24:375–9. 42. Lehtinen A, Taavitsainen M, Leirisalo-Repo M. Sonographic analysis of enthesopathy in the lower extremities of patients with spondylarthropathy. Clin Exp Rheumatol 1994;12:143–8. 43. Balint PV, Kane D, Wilson H, et al. Ultrasonography of entheseal insertions in the lower limb in spondyloarthropathy. Ann Rheum Dis 2002;61:905–10. 44. Genc H, Duyur Cakit B, Nacir B, et al. The effects of sulfasalazine treatment on enthesal abnormalities of inflammatory rheumatic diseases. Clin Rheumatol 2007;26:1104–10. 45. Feydy A, Lavie-Brion MC, Gossec L, et al. Comparative study of MRI and power Doppler ultrasonography of the heel in patients with spondyloarthritis with and without heel pain and in controls. Ann Rheum Dis 2012;71:498–503. 46. Newman JS, Adler RS. Power Doppler sonography: applications in musculoskeletal imaging. Semin Musculoskelet Radiol 1998;2:331–40. 47. D’Agostino MA, Said-Nahal R, Hacquard-Bouder C, et al. Assessment of peripheral enthesitis in the spondylarthropathies by ultrasonography combined with power Doppler: a cross-sectional study. Arthritis Rheum 2003;48:523–33. 48. Kiris A, Kaya A, Ozgocmen S, et al. Assessment of enthesitis in ankylosing spondylitis by power Doppler ultrasonography. Skeletal Radiol 2006;35:522–8. 49. De Miguel E, Cobo T, Munoz-Fernandez S, et al. Validity of enthesis ultrasound assessment in spondylarthropathy. Ann Rheum Dis 2008;68(2):169–74. 50. D’Agostino MA, Aegerter P, Bechara K, et al. How to diagnose spondyloarthritis early? Accuracy of peripheral enthesitis detection by power Doppler ultrasonography. Ann Rheum Dis 2011;70:1433–40. 51. De Miguel E, Munoz-Fernandez S, Castillo C, et al. Diagnostic accuracy of enthesis ultrasound in the diagnosis of early spondyloarthritis. Ann Rheum Dis 2011;70: 434–9. 52. Ruta S, Gutierrez M, Pena C, et al. Prevalence of subclinical enthesopathy in patients with spondyloarthropathy: an ultrasound study. J Clin Rheumatol 2011;17: 18–22. 53. Amor B, Dougados M, Mijiyawa M. Criteria for the classification of spondylarthropathies. Rev Rheum Mal Osteoartic 1990;57:85–9. 54. Naredo E, Batlle-Gualda E, Garcia-Vivar ML, et al. Power Doppler ultrasonography assessment of entheses in spondyloarthropathies: response to therapy of entheseal abnormalities. J Rheumatol 2010;37:2110–7. 55. D’Agostino MA, Breban M, Said-Nahal R, et al. Refractory inflammatory heel pain in spondylarthropathy: a significant response to infliximab documented by ultrasound [letter]. Arthritis Rheum 2002;46:840–1. 56. Gandjbakhch F, Terslev L, Joshua F, et al. Ultrasound in the evaluation of enthesitis: status and perspectives. Arthritis Res Ther 2011;13:R188.
Ultrasonography and MRI in Detecting Enthesitis
57. D’Agostino MA, Aegerter P, Jousse-Joulin S, et al. How to evaluate and improve the reliability of power Doppler ultrasonography for assessing enthesitis in spondylarthritis. Arthritis Rheum 2009;61:61–9. 58. Torp-Pedersen ST, Terslev L. Settings and artefacts relevant in colour/power Doppler ultrasound in rheumatology. Ann Rheum Dis 2008;67:143–9. 59. Balint PV, Mandl P, Kane D. “All that glistens is not gold”–separating artefacts from true Doppler signals in rheumatological ultrasound. Ann Rheum Dis 2008; 67:141–2. 60. McGonagle D, Marzo-Ortega H, O’Connor P, et al. Histological assessment of the early enthesitis lesion in spondyloarthropathy. Ann Rheum Dis 2002;61:534–7. 61. Torp-Pedersen S, Christensen R, Szkudlarek M, et al. Power and color Doppler ultrasound settings for inflammatory flow: impact on scoring of disease activity in patients with rheumatoid arthritis. Arthritis Rheumatol 2015;67:386–95. 62. Wakefield RJ, Balint PV, Szkudlarek M, et al. Musculoskeletal ultrasound including definitions for ultrasonographic pathology. J Rheumatol 2005;32:2485–7. 63. Terslev L, Naredo E, Iagnocco A, et al. Defining enthesitis in spondyloarthritis by ultrasound: results of a Delphi process and of a reliability reading exercise. Arthritis Care Res (Hoboken) 2014;66:741–8. 64. Mouterde G, Aegerter P, Correas JM, et al. Value of contrast-enhanced ultrasonography for the detection and quantification of enthesitis vascularization in patients with spondyloarthritis. Arthritis Care Res (Hoboken) 2014;66:131–8. 65. Alcalde M, Acebes JC, Cruz M, et al. A sonographic enthesitic index of lower limbs is a valuable tool in the assessment of ankylosing spondylitis. Ann Rheum Dis 2007;66:1015–9.
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MD, PhD
a,b,
*, Lene Terslev,
MD, PhD
c
KEYWORDS Ultrasonography Enthesitis Spondyloarthritis MRI KEY POINTS Power Doppler ultrasonography (PDUS) and MRI have changed the management of spondyloarthritis (SpA). MRI and PDUS are key imaging modalities for evaluating disease activity at entheseal level. Recent advancement in MRI, as whole body MRI, may have potential in early diagnosis and better understanding of SpA; further testing and validation are warranted.
INTRODUCTION
Over the last 40 years, the concept of spondylarthritis (SpA) has evolved thanks to the introduction of new drugs and an earlier detection of the disease, owing to the introduction of new imaging techniques such as MRI and ultrasound imaging (US; Fig. 1). The latter have permitted to visualize what is considered the landmark lesion: the enthesitis.1–3 Understanding of the imaging findings of enthesitis hinges on the knowledge of the relevant joint anatomy.3–7 ENTHESIS, ENTHESOPATHY, AND ENTHESITIS
The term enthesis refers to the anatomic interface, or bony attachment, of tendons, ligaments, fascia, muscles, and joint capsules. The involvement of the entheses in any pathologic process, whatever the origin (ie, metabolic, inflammatory, traumatic or degenerative), is usually defined as “enthesopathy,” whereas “enthesitis” defines a
Rheumatology Department, APHP, Hoˆpital Ambroise Pare´, 9 avenue Charles, de Gaulle, Boulogne-Billancourt 92100, France; b INSERM U1173, Laboratoire d’Excellence INFLAMEX, UFR Simone Veil, 2 Avenue de la Source de la Bie`vre, Montigny-le-Bretonneux, VersaillesSaint-Quentin University, Saint-Quentin en Yvelines 78180, France; c Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Rigshospitalet, Blegdamsvej 9, University of Copenhagen, 2100 Copenhagen, Denmark * Corresponding author. Rheumatology Department, APHP, Hoˆpital Ambroise Pare´, 9 avenue Charles de Gaulle, Boulogne-Billancourt 92100, France. E-mail address: [email protected]
Rheum Dis Clin N Am - (2016) -–http://dx.doi.org/10.1016/j.rdc.2016.07.012 0889-857X/16/ª 2016 Elsevier Inc. All rights reserved.
rheumatic.theclinics.com
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Fig. 1. Why imaging in spondyloarthritis?
the “inflammatory” involvement.8 In this context, Niepel and associates9 were the first to use the term “enthesitis” for describing the inflammatory symptoms commonly observed at the calcaneal insertion of the Achilles tendon in patients with ankylosing spondylitis. The pivotal role of enthesitis as common characteristic lesion of the SpA complex was suggested for the first time by John Ball.7 In his famous “Heberden Horation,” Ball pointed out that the persistent inflammation of the entheses (ie, “enthesitis”) is the distinctive pathologic feature of ankylosing spondylitis, whereas the characteristic feature of rheumatoid arthritis (RA) is the persistent inflammation of the synovial membrane (ie, “synovitis”).7 Recent knowledge regarding the function, anatomy, and physiology of the enthesis in human and animal models led to improvements in our understanding of the entheseal pathology in the course of many rheumatic diseases, especially SpA.10,11
ANATOMY, FUNCTION, AND HISTOPATHOLOGY OF ENTHESITIS
Although anatomic studies are difficult to perform, because the entheses represent areas where hard and soft tissues meet, 2 types of enthesis are usually described: fibrous and fibrocartilageous. In the fibrous entheses the collagen fibers of the tendons or ligaments attach directly to the bone, whereas in fibrocartilaginous entheses 4 transitional zones are observed4–6: (1) collagen zone, directly derived from the tendon (or ligament, capsule, tendon, aponeurosis, or annulus) structure, (2) noncalcified fibrocartilaginous zone, (3) tidemark-calcified fibrocartilaginous zone, and (4) subchondral bone zone. The entheses are vascularized primarily by the vessels coming from the bone marrow, and partially by the vessels of the peritenon (eg, in the fibrocartilaginous entheses). Blood vessels are present predominantly at the junction between the uncalcified and calcified fibrocartilaginous zones.6,12,13 Few histopathologic studies have been performed on the entheses of ankylosing spondylitis patients, and most of them were performed on material obtained during joint replacement; some of them (especially in late 1960s) using biopsies from painful entheseal sites.7
Ultrasonography and MRI in Detecting Enthesitis
The histologic hallmark of the “enthesitis” seems to be the coexistence of lesions of different durations at the same site, with erosions, microscopic inflammatory foci at the tendon/ligament insertion, and areas of bone repair.7,14 The enthesis was primarily viewed as a site of metabolic activity, notably during growth.15 In a second time the role of the enthesis as biomechanical site has played a major role. In contrast with other skeletal locations, the enthesis is a site of repetitive biomechanical forces.15 Clinical observations, supported by animal model experiences, suggest that mechanical stress may trigger the development of an enthesitis, by stimulating an inflammatory cascade with cytokine production, which affects not only the bony attachment interface and the enthesis itself, but also the surrounding tissues, such as the bursa, fat pad, and synovium.16–18 In the early phases of this process, the predominant pattern seems to be the destruction of the fibrocartilage, with neovascularization and infiltration of inflammatory cell predominantly at the sites where synovium, subchondral bone, and bone marrow are close. This results in an articular inflammatory response in the adjacent synovial tissue, driving the concept of the synovio–entheseal complex.19–21 Secondarily, the adjacent bone reacts with formation of enthesophytes and spurs.22 IMAGING AND ENTHESITIS
Historically, the radiographic features of enthesitis have played a pivotal role in defining the enthesitis lesions in SpA. Enthesitis was defined mainly by the abnormalities observed at the bone insertion such as osteopenia, bone cortex irregularity, erosions, entheseal soft tissue calcifications, and new bone formation (Fig. 2).23–26 However, entheseal bone changes appear late and are also common in mechanical disorders and in crystal related pathology. Aging is also associated with an increased prevalence of asymptomatic radiographic changes.23–26 In the past, before the extensive use of MRI and US, the only technique able to study inflammatory changes of articular and periarticular structures was bone scintigraphy, revealing diffuse increase in bone and articular uptake in active SpA patients. However, the poor spatial resolution of this technique, the lack of specificity, and the relative radiation hampered its extensive use.27,28
Fig. 2. Conventional radiography of the calcaneus. The radiograph shows a lateral view of a calcaneus of a patient with spondyloarthritis. Arrows show the spurs at the cortical insertion of the Achilles tendon and plantar fascia.
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MRI AND ENTHESITIS
MRI is currently considered the best imaging modality to identify early axial involvement (spine and sacroiliac joints) in patients with SpA, when conventional radiography is still normal.29 Although MRI methods have faced a rapid evolution over the past years, the imaging technique itself has not completely changed. Conventional T1-weighted sequences and short T1 inversion recovery images are regarded as the methods of choice to depict structural and inflammatory lesions, respectively. The use of MRI for evaluating peripheral entheses has permitted to demonstrate elegantly the link between enthesitis and synovitis.30,31 The use of fat-suppressed, fat-saturated, and water-sensitive MRI sequences has shown that the extraarticular inflammation quite often observed represents enthesitis. In fact, the typical appearance of peripheral enthesitis on MRI includes soft tissue inflammatory changes and perientheseal bone marrow edema (Fig. 3). However, with the actual MRI equipment, the depiction of enthesitis is limited in case of absence of concomitant bone edema. In structures with low water accumulation, such as at the bone attachment, the visualization of lesions is quite difficult owing to the low signal on conventional MRI. To improve the visualization of early inflammatory changes several techniques and sequences used in other fields (such as neuroimaging) are now being tested for potential use in SpA.32 WHOLE BODY MRI
Another limitation of the conventional MRI is the fact that only 1 site at time can be examined. To permit the simultaneous assessment of the entire spine (including the sacroiliac joints) and of peripheral structures (including the peripheral entheses) Whole body MRI has now been applied (Fig. 4). The simultaneous evaluation is possible by the concurrent use of several coils scanning the entire body within 30 to 40 minutes without patient repositioning. The visualization of inflammatory changes in the spine has a spatial resolution similar to the standard MR examinations33–35; however, the quality and reproducibility of the detection of the peripheral involvement, especially
Fig. 3. MRI of calcaneus. The 2 panels show the presence of enthesitis (as a focal thickening with high signal in the medial aspect of the plantar fascia (arrow of panel A), and also at the enthesis attachment on to calcaneus (arrow of panel B). Presence of edema and erosive changes in the subcortical bone marrow (A); and also edema in the surrounding soft tissue of the plantar fascia, close to the insertion and in the body of the fascia (B).
Ultrasonography and MRI in Detecting Enthesitis
Fig. 4. Whole body MRI. Example of normal aspect.
of peripheral enthesitis and of synovitis of small joints, is not completely adequate. Whole body MRI may be useful in the initial evaluation of disease activity as well as for follow-up evaluation and in clinical trials. High-resolution MRI
High-resolution MRI using gradient echo sequences with fat saturation produce images with hyperintense depiction of cartilage whereas surrounding bone is depicted hypointense, thus allowing detailed analysis of erosions and, when applied, to small joints a greater visualization of the entheses insertion.36,37 Diffusion-weighted MRI
Diffusion-weighted MRI is based on the tissue-dependent signal attenuation caused by incoherent thermal motion of water molecules. Mobility of water molecules is driven by thermal agitation and depends greatly on its cellular environment. This technique might potentially permit to detect early inflammatory changes especially in the bone.38,39
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MRI AND ULTRASONOGRAPHY IN THE EVALUATION OF PERIPHERAL ENTHESITIS: WHICH MODALITIES?
Table 1 delineates the advantages and limitations of US and MRI. Although MRI should be consider the reference choice for the assessment of the axial involvement, the use of MRI for the evaluation of peripheral enthesitis is actually limited by its cost, availability, and accuracy.31 Moreover, there are not available scoring systems at the moment. Therefore, US should be considered the method of choice both in clinical practice and in the research setting.40,41 Ultrasound and Enthesitis
The extensive description of US involvement of entheses in SpA patients was made for the first time by Lehtinen and colleagues42 in 1994 and then by Balint and colleagues43 in 2002. These authors described in grey scale the US abnormalities of lower limb enthesitis of SpA, revealing the high frequency of asymptomatic findings. Grey scale enthesitis is characterized by the loss of normal fibrillar echogenicity of tendon insertion with an increase of the thickness insertion, or by intralesional focal changes of tendon insertion, such as calcific deposits, fibrous scares aspect, 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. Thus grey scale US permits to depict both signs of acute and chronic inflammation of enthesis as well as structural damage. Since then, discordant data have been published about the capability of grey scale US alone to differentiate between enthesis involvement in SpA and in other pathologies.44,45 This discordance is related to several factors: the absence in some of these studies of a clear definition of enthesis involvement (most of these data regarded also the tendon and bursa involvement)45; the difficulty to clearly define inflammatory changes by using only grey scale. The main appearance of inflammation in grey scale is edema, which is characterized by the loss of normal echostructure (ie, hypoechogenicity), associated or not to the increase of the thickness of tendon insertion, which is very difficult to quantify. The use of power Doppler for visualizing abnormal vascularization and hyperemia has made possible to overcome this lack of specificity.46 The landmark of an enthesitis detected on US in SpA patients when compared with Table 1 Strengths and weakness of ultrasound and MRI Ultrasound Strengths
Weaknesses
Real-time and dynamic Unable to image imaging within bone
MRI Strengths
Weaknesses
Ability to image bone
Limited to 1 body region
Potential for motion More complete artifact and assessment of whole contraindications joint (all articular (eg, pacemaker) surfaces)
Immediately accessible; complements the physical examination
Specialist training not always available
Relatively easy to examine multiple body regions
Limited accessibility of Quantitative some structures measurement of (acoustic window) synovium
Time and patient tolerance
Portability
Interobserver variability and training needs
Cost
Better reproducibility
Ultrasonography and MRI in Detecting Enthesitis
controls (RA patients and mechanical spinal disease patients) is the presence of abnormal vascularization at enthesis insertion, allowing the differentiation between SpA involvement and other mechanical or metabolic involvements.47 US has indeed proven to be a highly useful and sensitive tool in the evaluation of enthesitis by improving the ability of the clinical examination to detect enthesitis.48,49 Several studies have also demonstrated the prognostic value of the detection of enthesitis for an early diagnosis of SpA.50–52 In particular, the most recent prospective cohort study conducted in patients with symptoms suggestive of SpA50 has shown that vascularization at cortical bone detected by PDUS was the only independent contributor to a diagnosis of SpA made 2 years later, and that PDUS vascularized enthesis combined with Amor’s criteria53 was highly effective in making an early diagnosis of SpA in the absence of other clinical, imaging and biological findings. US is also useful for evaluating disease activity and to monitor response to treatment,54,55 although this aspect has been explored in few studies until now. Despite promising results, the use of power Doppler US for the management of SpA has remained less often evaluated than in RA.56 This discrepancy is probably owing to the perception that US, especially for detecting enthesitis, remains an operatordependent technique owing to the greater difficulty of assessing vascular blood flow with Doppler in the entheses than in the synovium.57 The latter difference can be explained by a greater abundance of vessels in the inflamed synovium, than in enthesitis.10–14 In addition, Doppler artifacts are frequently produced at the enthesis attachment owing the close proximity of the cortical bone, which is a highly reflecting surface,58,59 and only few studies are available comparing histology evidence of inflammation and signs of enthesitis assessed by US.60 A study comparing the grey scale US signs of enthesitis and the histologic sample taken in the same place, showed that the hypoechoic area detected by US corresponds with macrophage infiltration, increased vascularity, and edema.60 Three competences are critically needed to optimize the evaluation of enthesitis by grey scale and Doppler US: (i) a specific knowledge of the anatomy of each enthesis (in particular the localization of normal nutrition vessels), (ii) the capacity to distinguish very slow vascular flow (which is the hallmark of the inflammatory process in the enthesis) from artifacts, on power Doppler,57 and (iii) the US machine used as the characteristics of the Doppler modality vary according to the US device used.61 Normal Ultrasound Aspect of Peripheral Enthesis
Under normal conditions, the 4 zones of fibrocartilageous enthesis are not visible or are only just visible owing to the small thickness of the fibrocartilage and to the quality and resolution of US equipment (Fig. 5). Thus, the normal US aspect of the enthesis is difficult to distinguish from the US aspect of the body of tendon or ligament and it appears as a normal continuity of the tendon/ligament into the bone. Ultrasound Definition of Enthesitis
The OMERACT (Outcome Measures in Rheumatology) US task force proposed 10 years ago, preliminary US definitions for elementary pathologic findings, at the joint level, including enthesopathy.62 At that time, it was decided to define enthesopathy instead of enthesitis to include both mechanical and inflammatory pathologies. In this definition, both acute and chronic inflammatory aspects in grey scale (ie, loss of normal echostructure, increased of the thickness, focal calcic deposits) as well as Doppler signal are combined with findings of structural damage (ie, enthesophytes, bony erosions). This combination is helpful for defining the presence or absence of
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Fig. 5. Normal enthesis by ultrasonography (US). (A) Normal US appearance of the insertion of the quadriceps tendon in a longitudinal scan. The rectangle shows the area of the enthesis. (B) Drawing of the enthesis and the surrounding structures (tendon, bone, bursa). Rectangle shows the enthesis.
enthesitis, but probably not for responsiveness and for differential diagnosis between diseases (SpA vs RA vs mechanical or metabolic entheseal involvement).44,45 Ultrasound Definition of Elementary Lesions of Enthesitis
Recently, the same OMERACT US group has tried to standardize the definition of each elementary component participating to the enthesitis definition.63 They first decided to consider enthesitis as an involvement of the anatomic enthesis, which is different from the involvement of bursa and body of tendon (see Fig. 5). Bursa and tendon can be involved in SpA inflammatory process, but should be evaluated as different structures and not included in the definition of US-detected enthesitis (Fig. 6). In grey scale, enthesitis can be characterized by the following elementary lesions that should be detected within 2 mm from the bone surface: Hypoechogenicity of the insertion of tendon/ligament/capsule into the bone, which can be defined as a lack of the homogeneous echotexture pattern, with loss of the tightly packed echogenic lines after correcting anisotropy artifact (Fig. 7). Increased of thickness of tendon/ligament/capsule insertion into the bone, as compared with the body of tendon/ligament/capsule, with or without blurring of the tendon/ligament/capsule margins.
Fig. 6. Ultrasound (US) aspect of the enthesitis of the Achilles tendon in grey scale and power Doppler. Longitudinal US scan of the Achilles tendon insertion. The elementary components present are entheseal hypoechogenicity (H), erosion of the calcaneus (E), and deep retrocalcaneal bursitis (B). The presence of power Doppler signal inside the bursa (B) and the entheseal erosions (E).
Ultrasonography and MRI in Detecting Enthesitis
Fig. 7. Ultrasound (US) aspect of the enthesitis of the Achilles tendon in grey scale. Longitudinal US scan of the Achilles tendon insertion. The elementary components present are entheseal hypoechogenicity (H), calcifications (C), and enthesophytes (E).
Calcifications or fibrous scares detected at the tendon/ligament/capsule insertion into the bone, defined as hyperechoic foci consistent with calcic deposits, with or without acoustic shadow, seen in 2 perpendicular planes (see Fig. 7). Enthesophytes, defined as a step up of bony prominence at the end of the normal bone contour seen in 2 perpendicular planes, with or without acoustic shadow (see Fig. 7). Erosions, defined as a cortical breakage with a step down contour defect, seen in 2 perpendicular planes, at enthesis insertion (Fig. 8A). Cortical irregularities, defined as a loss of the normal regular bone contour, without any clear sign of enthesophyte and/or erosion. These grey scale abnormalities can be associated with Doppler signal in case of inflammation (Fig. 8 B, C). For defining enthesitis instead of enthesopathy, the presence of Doppler signal should be detected at the cortical enthesis insertion, and should be differentiated from reflecting surface artifact or nutrition vessel signal. Doppler signal can be present even in absence of cortical irregularities, erosions, or enthesophytes. The latter explanation is important because it has been shown, in histologic studies, that normal aged entheses may have bone microdamage at enthesis associated with microscopic vascular changes, which are likely involved in the repair response.10–13 Vascular changes are also present adjacent to enthesophytes in the normal aged enthesis.13 Until now, no studies have demonstrated the possibility to detect a normal vascularization of enthesis by using US in a healthy normal subject, even when the Doppler signal is enhanced by using medium US contrast agents.11 Recently, a study has shown the capability of contrast enhanced US to confirm the presence of an enthesitis in case of doubtful Doppler signal, confirming therefore the importance of Doppler for evaluating enthesitis.64 Inflammation and structural damage can coexist. Table 2 summarizes the structural and inflammatory findings that can be detected on US. Grey Scale and Doppler Modalities: Which Is the Best for Studying Enthesitis?
The quality of machine and probe used for entheses examination is very important. All peripheral entheses are very superficial structures, localized directly under the skin and subcutaneous tissue. Thus, a linear high-frequency probe (ideally >14 MHz) is necessary for accurate visualization of the enthesis structure. The Doppler used
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Fig. 8. Ultrasound (US) aspect of the enthesitis of the Achilles tendon in grey scale and power Doppler. (A) Longitudinal US scan of the Achilles tendon insertion. The elementary component present is the entheseal erosion of calcaneus (E). Corresponding images with Doppler enhancement (longitudinal B) and transverse (C).
should have the same characteristics of resolution and be adapted to superficial structures and to slow blood flows. Higher Doppler frequency gives a more detailed image of the vessels but at the expense of penetration. Thus, frequency, Doppler gain, pulse repetition frequency, and wall filter settings are key issues. Among the different Doppler modalities, power Doppler often has most of those prerequisites. Its theoretic advantage over color Doppler is sensitivity. Disregarding the direction of flow and disregarding velocity the power (energy) of the many different frequency shifts inside a cell are added to form the power signal. Therefore, it is almost angle independent and without aliasing. The optimum frequency may vary from machine to machine and must therefore be found in practice and not in theory.62
Table 2 Structural and inflammatory findings detected by ultrasound Component
Inflammation
Damage
Enthesitis
Insertion thickening Hypoechogenicity Vascularity
Entheseal erosion New bone growth-periosteal/ enthesophyte
Ultrasonography and MRI in Detecting Enthesitis
Box 1 Published ultrasound scoring systems at the enthesis and patient levels US scoring systems GS only Glasgow Enthesitis Scoring System (enthesis 1 patient level) 43 - Balint and colleagues Spanish Enthesitis Index (enthesis level) 65 - Alcalde and colleagues GS and Doppler D’Agostino Scoring System (enthesis 1 patient level) 47,50 - D’Agostino and colleagues Madrid Sonographic Enthesitis Index (enthesis 1 patient level) 49,51 - De Miguel and colleagues
How to Score Enthesitis Involvement by Ultrasound?
The scoring systems can either be qualitative, semiquantitative, or quantitative and can be developed at patient level or at enthesis level. Box 1 shows the published US scoring systems. Scoring systems are relevant for monitoring changes. The first and still commonly accepted US scoring system on enthesitis, the Glasgow Enthesitis Scoring System (GUESS), was developed by Balint and colleagues43 in 2002. GUESS was designed to assess 5 entheses of the lower limb and only gray scale findings were included. Its application for therapy monitoring was not able to detect any differences when used to assess sulphasalazine treatment, which might simply indicate ineffective therapy.44 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 damage47,50; (b) the Spanish Enthesitis Index, developed as a global (ie, patient-level) scoring system and uses grey scale abnormalities only.65 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 includes involvement of the bursa.49,51 The MASEI is a global enthesitis index and the GUESS and D’Agostino scoring systems are the scoring systems at enthesis level. There remains a need to reach a consensus on the best system to use. SUMMARY
Grey scale US combined with power Doppler should be considered as a gold standard for the imaging evaluation of peripheral enthesitis in SpA, because MRI should be considered the gold standard for the evaluation of the axial involvement. However, further validation is still needed as both US and MRI are evolving techniques. Inflammation at the enthesis is likely modulated by multiple factors. A better understanding of the enthesis disease combined with the new advances in imaging will permit to understand better the role of enthesitis in the pathogenesis of SpA. Research agenda Development of MRI scoring system for peripheral enthesitis. Comparing US and MRI findings of activity and damage. Test the responsiveness to change of US and MRI lesions.
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ACKNOWLEDGMENTS
The authors acknowledge Rene Poggenborg, MD, PhD, for his contribution with the MRI and whole body MRI images. REFERENCES
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