Imaging in ankylosing spondylitis

Ther Adv Musculoskelet Dis. 2012 Aug; 4(4): 301–311.

Monitoring Editor: Gerolamo Bianchi

and

Mikkel Østergaard

Department of Rheumatology, Copenhagen University Hospital at Glostrup, Nordre Ringvej 57, DK-2600 Glostrup, Denmark

Robert G.W. Lambert

Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada

Mikkel Østergaard, Department of Rheumatology, Copenhagen University Hospital at Glostrup, Nordre Ringvej 57, DK-2600 Glostrup, Denmark;

Corresponding author.This article has been cited by other articles in PMC.

Abstract

Imaging is an integral part of the management of patients with ankylosing spondylitis and axial spondyloarthritis. Characteristic radiographic and/or magnetic resonance imaging (MRI) findings are key in the diagnosis. Radiography and MRI are also useful in monitoring the disease. Radiography is the conventional, albeit quite insensitive, gold standard method for assessment of structural damage in spine and sacroiliac joints, whereas MRI has gained a decisive role in monitoring disease activity in clinical trials and practice. MRI may also, if ongoing research demonstrates a sufficient reliability and sensitivity to change, become a new standard method for assessment of structural damage. Ultrasonography allows visualization of peripheral arthritis and enthesitis, but has no role in the assessment of axial manifestations. Computed tomography is a sensitive method for assessment of structural changes in the spine and sacroiliac joints, but its clinical utility is limited due to its use of ionizing radiation and lack of ability to assess the soft tissues. It is exciting that with continued dedicated research and the rapid technical development it is likely that even larger improvements in the use of imaging may occur in the decade to come, for the benefit of our patients.

Keywords: ankylosing spondylitis, computed tomography, imaging, magnetic resonance imaging, radiography, spondyloarthritis, ultrasonography, ultrasound

Introduction

Imaging in ankylosing spondylitis (AS) has been synonymous for decades with conventional radiography (CR). However, developments in computed tomography (CT), ultrasonography (US) and particularly magnetic resonance imaging (MRI) have dramatically increased the amount and scope of information obtainable by imaging. Imaging may be used for multiple reasons that include establishing or confirming the diagnosis, determining extent of disease in axial or peripheral joints and/or entheses, monitoring change in disease (e.g. activity and structural damage) for instance for assessment of therapeutic efficacy in trials, providing prognostic information or selecting patients for specific therapies. These entirely different contexts may favour different imaging approaches.

The present paper focuses on imaging of the spine and sacroiliac joints, i.e. the axial joints, in AS and other variants of axial spondyloarthritis (SpA). The reader is kindly referred to other review articles (e.g. Poggenborg et al. [2011]) for imaging aspects of peripheral involvement in SpA. This paper describes the virtues of CR and its current major importance in diagnosis and follow-up of AS, but also, by putting emphasis on MRI, stresses that AS management has entered a time of exciting and expanding therapeutic as well as imaging possibilities.

Conventional radiography

Technical aspects

The conventional radiograph is a two-dimensional summation image that is dependent on variable absorption of X-rays by different tissues for its inherent contrast. It has a very high spatial resolution that is rarely surpassed by other modalities but radiography only offers high contrast between a limited number of structures: bone (calcium), soft tissue and air. Fat is visible as a separate density but the distinction between soft tissue and fat is often subtle (except in mammography) and radiography cannot distinguish between the other soft tissues because cartilage, muscle, tendon, ligament, synovium and fluid all appear with the same density [Resnick, 2002]. These characteristics give the radiograph its inherent advantages and disadvantages. The conventional radiograph is relatively cheap, available worldwide and produces an image which is almost identical regardless of technical parameters or whether the image is analogue or digital.

CR shows skeletal structure very well, and because it is a summation image, it allows excellent overall assessment of skeletal trauma and alignment. The limited number of images produced facilitates rapid review and the high bone–soft tissue contrast often produces radiographic manifestations of disease in specific patterns that make the test particularly useful in daily clinical practice. The biggest disadvantage of radiography is its inherent lack of soft tissue contrast making it insensitive for the detection of soft tissue abnormalities.

Although CR uses ionizing radiation, radiography is regarded as relatively safe in older patients because of the long lag time for any negative effect to occur. However, spine and pelvis radiography doses need to be relatively high in order to penetrate the trunk and, in a younger population, MRI offers a safer and more informative alternative.

Ankylosing spondylitis

Sacroiliac joints

Erosion and ankylosis of the sacroiliac joints are the hallmarks of AS [Resnick, 2002; van der Linden et al. 1984]. Sacroiliitis is usually the first manifestation and is characteristically bilateral and symmetrical in AS [Berens, 1971; Resnick et al. 1977]. Early radiographic findings predominate on the iliac side of the cartilage compartment with erosion of subchondral bone causing loss of definition of the articular surfaces usually accompanied by variable degrees of adjacent osteoporosis and surrounding reactive sclerosis. Bone erosion may result in the radiographic observation of focal joint space widening () and, as the disease progresses, definition of the joint is completely lost with radiographic superimposition of erosion, sclerosis and new bone formation which fills in the erosions and the original cartilaginous ‘joint space’. The joint may disappear completely in late disease with ankylosis and remodelling of the bone (). The ligamentous compartment of the sacroiliac joint is frequently affected by bony erosion and entheseal proliferation although these may be hard to see radiographically [Berens, 1971; Resnick et al. 1977].

Radiographic findings in sacroiliac joints and spine in ankylosing spondylitis.

(A) Radiograph of the sacroiliac joints in a 23-year-old male demonstrates established ankylosing spondylitis. Bilateral erosions cause discrete foci of loss of subchondral bone and apparent joint space widening in some areas (arrows) and ill definition of the joint margin in other areas (arrowheads). Bilateral subchondral sclerosis is most prominent in the left ilium. (B)–(D) Radiographs of the spine in a 47-year-old male with widespread ankylosis. The cervical spine (B) exhibits extensive formation of vertical syndesmophytes that have bridged the anterior vertebral corners causing ankylosis. Some facet joints are fused, best appreciated at C2/3. The lumbar spine (C; enlargement of L1–L4 in D) shows similar ankylosis. Note the thick right L1/2 bridging (arrow) and compare this to the delicate vertical syndesmophytosis on the left at L3/4. The sacroiliac joints are completely fused with barely any remnant of joint visible.

Spine

The early radiographic manifestations of AS in the spine are most often due to enthesitis at the edges of the discovertebral joints [Berens, 1971]. Focal sclerosis (the ‘shiny corner’) and erosion (the ‘Romanus lesion’) develop at the attachment of the annulus fibrosis to the anterior corner of the vertebral endplate and are characteristic features of early AS [Hermann et al. 2005]. The anterior borders of vertebrae may appear straight or ‘squared’ due to periosteal proliferation of new bone filling in the normal concavity or erosion at the anterosuperior and anteroinferior vertebral margins. This observation is much easier to make in the lumbar spine where normal vertebrae are always concave anteriorly in comparison to the thoracic and cervical spine where the normal contour is much more variable and may be square or occasionally convex.

The hallmark of spinal disease in AS is the development of characteristic bony spurs: syndesmophytes (). These start as thin vertically oriented projections of bone that develop due to ossification within the outer fibres of the annulus fibrosus of the intervertebral disc. Syndesmophytes are radiographically visible on the anterior and lateral aspects of the spine starting from the corner of the vertebra.

Traditional literature indicates that all of the early signs of spinal involvement are most often visualized first near the thoracolumbar junction. While this may be true for radiography, MRI studies show a predilection for early involvement of the midthoracic spine. Both modalities would agree that the cervical spine is rarely affected first and spinal disease rarely occurs in the absence of significant SI joint involvement.

Progressive growth of syndesmophytes will bridge the intervertebral disc causing ankylosis () and extensive bone formation produces a smooth, undulating spinal contour: the ‘bamboo spine’. The syndesmophytes that characterize AS must be differentiated from other spinal and paraspinal bone formation. Degenerative bony spurring in spondylosis deformans arises several millimetres from the discovertebral junction, is typically triangular in shape and has a horizontally oriented segment of variable length at the point of origin. In diffuse idiopathic skeletal hyperostosis (DISH), bone formation in the anterior longitudinal ligament results in a flowing pattern of ossification that is usually thick and the sacroiliac joints are not involved.

Erosion of the vertebral endplate is common in later stages of AS and may be focal or diffuse. It is also seen when pseudarthrosis develops following a fracture in a previously ankylosed spine. Changes in the apophyseal joints are common and start with of ill-defined erosion and sclerosis but may be hard to see. Capsular ossification or intra-articular bony ankylosis frequently occurs in late disease. The ankylosed spine is very susceptible to fractures, which should always be suspected in case of unexplained pain exacerbations. Enthesitis at the interspinous and supraspinous ligamentous attachments is very common with bone formation causing whiskering and interspinous ankylosis.

Use in diagnosis, monitoring and prognostication

Diagnosis

While the modified New York Criteria are actually classification criteria, these criteria are the most commonly used criteria for the diagnosis of AS and are based on clinical features and radiographic sacroiliitis [van der Linden et al. 1984]. According to these criteria AS may be diagnosed if, in addition to one clinical criterion being present, grade 2 sacroiliitis (minimal sacroiliitis: loss of definition of the joint margins, minimal sclerosis, joint space narrowing and erosions) or higher occurs bilaterally, or grade 3 (moderate sacroiliitis: definite sclerosis on both sides of the joint, erosions, and loss of joint space) or grade 4 (complete bony ankylosis) occurs unilaterally [van der Linden et al. 1984]. Owing to the requirement for these radiographic structural changes, the duration of disease before diagnosis has been a median of 7–10 years [Feldtkeller et al. 2003]. The definitions of radiographic changes according to the New York Criteria are included in the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for SpA [Rudwaleit et al. 2009b], the European Spondyloarthritis Study Group (ESSG) criteria for spondyloarthritis [Dougados et al. 1991] and in the modified New York Criteria [van der Linden et al. 1984].

Monitoring

Radiography of the spine is not included in the classification criteria but may be useful to follow structural disease progression in patients with spinal involvement. The bone changes seen in patients with axial SpA develop slowly and are often not present in patients with early disease, and generally only minor changes can be observed in 1–2 years. Different scoring methods, all based on assessment of lateral views, have been developed to quantify changes in the spine of patients with AS: the Stoke AS Spine Score (SASSS), Bath AS Radiology Index (BASRI) and the modified Stoke AS Spine Score (mSASSS). A comparative study of the three methods concluded that all measures were reliable but mSASSS was more sensitive to change [Wanders et al. 2004]. These spine scores are primarily used in clinical research.

Prognostication

The amount of data documenting a prognostic value of CR findings is limited. However, low-grade (grade 1) sacroiliitis has been shown to have predictive value for the development of AS [Huerta-Sil et al. 2006], and the severity of radiographic damage has been documented to be related to subsequent radiographic damage progression [Maksymowych et al. 2010a; Poddubnyy et al. 2011].

Computed tomography

Technical aspects

Developments in computing and engineering have resulted in remarkable changes in the CT technology in the last decade. CT offers fast and reliable acquisition, high resolution and multiplanar capabilities that have enhanced its use in recent years, although the soft-tissue contrast is still limited.

Although CT image acquisition is restricted to the axial plane of imaging, the ability to acquire isotropic voxels has resulted in reliable and versatile multiplanar capabilities so that many CT scans of the body are now interpreted primarily from coronal or sagittal images in the same way as MRI. The data acquisition is so fast that patient motion is rarely a problem as CT scans are now routinely acquired in few seconds. In fact CT is often faster than taking multiple radiographs. Complex requirements for patient positioning in musculoskeletal CT are now substantially less important as the majority of studies can be reconstructed in orthogonal planes. Patient tolerance is excellent and, unlike MRI, there are no absolute contraindications to CT. Spatial resolution is high, usually higher than MRI, and contrast resolution between soft tissue and bone is unsurpassed by any other modality. However, despite all of the advantages listed above, the application of CT will remain somewhat limited, because the soft-tissue contrast is inferior to MRI and US and ionizing radiation is used. Radiation dose increases with the requirements for spatial detail and the depth of the body part, which is considerable for the sacroiliac joint and spine.

Ankylosing spondylitis/axial spondyloarthritis

CT allows visualization of the same pathological processes as CR (erosion, osteoporosis / sclerosis, and new bone formation/ankylosis) with the added benefit of multiplanar imaging free from superimposition of overlying structures.

In AS, the pathological processes start in bone marrow and at sites of entheses. However, CT has poor ability to detect soft-tissue change and is usually normal until structural damage is present. CT can detect osteoporosis or osteosclerosis quite well but these changes are very nonspecific. New bone formation is also well visualized in the form of syndesmophytes, ligamentous ossification and periarticular and intra-articular ankylosis, but the use for CT in this regard is limited. The primary value of CT in AS is its ability to detect and clearly define erosion of bone at any joint or enthesis, and for documenting fractures.

Use in diagnosis, monitoring and prognostication

Diagnosis

The diagnosis of AS is primarily based on the radiographic observation of bilateral moderate or unilateral severe sacroiliitis. When good quality radiographs of the sacroiliac joints are normal or radiographic changes meet diagnostic criteria, there is no role for CT. Early detection of AS is better investigated by MRI and if clearly defined structural damage is present on CR, then there is no additional diagnostic utility for CT. However, CT of the sacroiliac joints is much easier to interpret than radiography which is notoriously subject to poor observer reliability. When the radiographic findings are unclear, CT will usually resolve this uncertainty. Since CT shows bone erosion in exquisite detail, CT may also have a role to play in the further investigation of MRI equivocal findings. It should be noted that classification criteria for AS depend on radiographic findings and more recently MRI, but not CT specifically. In the spine, CT is useful in the diagnosis of complications of late disease such as spondylodiscitis or spinal fracture when patients may be unable to tolerate MRI due to pain or spinal deformity.

Monitoring disease activity and damage

CT has no useful role in monitoring disease activity or damage. CT cannot show active inflammation and the relatively high radiation dose of CT precludes its routine use for assessment of damage progression.

Prognostication

The prognostic value of CT findings of sacroiliitis require further investigation.

Ultrasonography

US is an evolving imaging technique increasingly used by the rheumatologist in daily clinical practice. Despite the fact that contrast-enhanced Doppler US has been reported to have a high negative predictive value for the detection of sacroiliitis [Klauser et al. 2005], the role of US in assessment of sacroiliac and spine involvement in AS and other types of axial SpA is minimal.

AS and other types of axial SpA frequently involve peripheral joints and entheses. US allows assessment of peripheral involvement in SpA. The reader is referred to other reviews (e.g. Gandjbakhch et al. [2011] and Poggenborg et al. [2011]) for further information on this.

Magnetic resonance imaging

Technical aspects

MRI provides multiplanar tomographic imaging with unprecedented soft-tissue contrast and allows assessment of all of the structures involved in musculoskeletal diseases. MRI is more sensitive than clinical examination and CR for the detection of inflammation and damage in inflammatory and degenerative rheumatological disorders. Disadvantages of MRI include longer examination times and higher costs and lower availability than radiography.

MRI involves no ionizing radiation or increased risk of malignancies, and adverse effects of the contrast agents are very rare. However, contrast agent use should be avoided in case of severely impaired renal function due to risk of nephrogenic systemic fibrosis.

T1-weighted (T1w) imaging sequences are favoured for the relatively short imaging times, good anatomical detail and the ability to visualize tissues with high perfusion and permeability, including the inflamed synovium, after intravenous contrast (paramagnetic gadolinium compounds; Gd) injection. Fat and Gd-enhanced tissues have a high signal intensity on T1w images. T2-weighted fat suppressed (T2wFS) and short tau inversion recovery (STIR) images depict water with a high signal intensity. These are well-suited for detection of oedematous tissue/fluid located in areas with fatty tissue, e.g. bone marrow oedema. Bone marrow abnormalities in both sacroiliac joints and spine are detected almost equally well with the STIR and contrast-enhanced T1w FS sequences in patients with SpA, so contrast injection is generally not needed [Baraliakos et al. 2005; Madsen et al. 2010]. T1w images are mandatory for evaluation of structural (sometimes referred to as chronic) changes, such as bone erosion, new bone formation and fat infiltrations.

The majority of MRI studies of the sacroiliac joint have used only one imaging plane (semicoronal, i.e. parallel with the axis of the sacral bone), usually T1W and T2wFS/STIR images. A supplementary T1w FS sequence may improve the evaluation of erosions [Madsen and Jurik, 2010a], and sequences designed for cartilage evaluation, e.g. 3D gradient echo sequences, may also be added [Puhakka et al. 2004]. To be maximally sensitive for changes in the ligamentous portion of the sacroiliac joints imaging in the semi-axial plane is required [Madsen and Jurik, 2010a]. This may therefore be recommended when MRI is used for diagnostic purposes, while it is probably not essential when used as an outcome measure in trials. While MRI for some indications (e.g. suspected disc herniation) should include axial images, MRI of the spine in SpA generally only involve sagittal images, but these should extend sufficiently lateral to include the frequently involved facet, costovertebral and costotransverse joints [Maksymowych et al. 2010b].

Ankylosing spondylitis/axial spondyloarthritis

MRI allows direct visualization of the abnormalities in peripheral and axial joints and entheses that occur in AS, psoriatic arthritis (PsA) and other forms of SpA.

MRI is, through its ability to detect inflammatory changes in bone and soft tissues, the most sensitive imaging modality for recognizing early spine and sacroiliac joint changes in AS. MRI findings indicating active disease in the sacroiliac joints (sacroiliitis) include juxta-articular bone marrow oedema and enhancement of the bone marrow and the joint space after contrast medium administration, while visible chronic changes include bone erosions, sclerosis, periarticular fatty tissue accumulation, bone spurs and ankylosis (). Typical lesions of the spine, which indicate active disease, are spondylitis, spondylodiscitis () and arthritis of the facet, costovertebral and costotransverse joints (). Structural changes, such as bone erosions, focal fat infiltration, bone spurs (syndesmophytes) and/or ankylosis (), frequently occur. Enthesitis is also common, and may affect the interspinal and supraspinal ligaments and the interosseous ligaments in the retro-articular space of the sacroiliac joints. Some patients also have disease manifestations in peripheral joints and entheses, and these can be visualized by MRI [Hermann and Bollow, 2004; Maksymowych and Landewe, 2006]. Definitions of key pathologies in axial SpA are provided in .

Early sacroiliitis on conventional radiography and MRI.

Radiograph (A) of the sacroiliac joints in a 28-year-old male reveals only subtle findings of possible erosion and minimal sclerosis. Short tau inversion recovery (STIR) MRI image (B) performed at the same time shows multiple bone marrow lesions, which appear as oedema (bright; arrows) involving the sacrum and ilium bilaterally, i.e. definite sacroiliitis was documented by MRI. The corresponding T1-weighted MRI image (C) shows some areas of diminished marrow fat signal corresponding to the intense oedema in the left upper quadrant. Some very subtle defects in the subchondral marrow in the lower quadrants, which likely represent tiny erosions (arrows), are also seen.

Inflammatory and fat lesions on MRI of the spine.

MRI of the lumbar and lower thoracic spine in 27-year-old male shows multiple tiny foci of infiltration of fat in the posterior corners of vertebral bodies on the T1-weighted sequence (A; arrows). On the short tau inversion recovery (STIR) sequence (B), these discs demonstrate no evidence of degeneration of the nucleus pulposis or tear of the annulus fibrosus, which is consistent with a postinflammatory cause of the marrow fat deposition rather than trauma or degenerative disc disease. Also note the solitary focus of inflammation on STIR imaging with increased signal at the anterosuperior corner of T10 (arrowhead). The appearance is typical for a corner inflammatory lesion (CIL) associated with spondyloarthritis (i.e. a triangular shaped lesion which may or may not (as in this case) be quite as bright in the extreme corner, with adjacent normal nucleus pulposus).

Bone marrow oedema in the transverse processes, costovertebral joints and manubriosternal joint.

MRI of the cervical and upper thoracic spine of a 29-year-old male patient scans were performed before (A–B and D–E) and 3 months after (C and F) initiation of anti-TNF therapy. Sagittal slices lateral to the spinal canal are shown.

(A)–(C) Sagittal slice through the pedicle and the lateral parts of the vertebrae, shows moderate bone oedema on the baseline STIR image (B) in the posterolateral aspects of all of the thoracic vertebral bodies, most pronounced at T4 and T5. The distribution is typical for inflammation on the vertebral side of the costovertebral joints. Also note inflammation in the manubriosternal joint anteriorly (arrow). Most foci of inflammation are still faintly visible after anti-TNF therapy (C), but are clearly less intense.

(D)–(F) Far lateral slice through the transverse processes and ribs. Intense bone marrow oedema is seen in the transverse processes of the upper thoracic spine (E; arrows), which resolves completely with treatment. This pattern of bone marrow oedema in the transverse processes, costovertebral joints and manubriosternal joint are pathognomonic of spondyloarthritis.

Progression of structural damage in the spine in ankylosing spondylitis, visualized by MRI.

T1-weighted MRIs of the thoracolumbar spine with a 3-year interval in a baseline (A) 23-year-old male with established ankylosing spondylitis. The follow-up MRI (B) demonstrates new anterior ankylosis at T9/10 with bridging anterior syndesmophytosis containing marrow fat signal. Note also several other findings indicating the progression of structural damage: the intervertebral disc at T10/11 is completely fused on the second scan; a new endplate defect has appeared at the inferior endplate of T9 with new fat infiltration; and the signal within the T8/9 disc has increased suggesting progression of disc ossification.

Table 1.

Use in diagnosis, monitoring and prognostication

Diagnosis

The introduction of MRI has resulted in a major improvement in the evaluation and management of patients with SpA. Diagnosis was previously dependent on the presence of bilateral moderate or unilateral severe radiographic sacroiliitis, as part of the modified New York criteria for AS [van der Linden et al. 1984]. This frequently delayed the diagnosis by 7–10 years [Feldtkeller et al. 2003]. Now, through the recent ASAS (ASsessment of SpondyloArthitis) classification criteria for axial SpA, MRI forms an integral part, as patients with active sacroiliitis on MRI plus one clinical feature (e.g. psoriasis, enthesitis or uveitis (see Rudwaleit et al. [2009b] for a complete list), should be classified as axial SpA [Rudwaleit et al. 2009b]. A consensus-based definition of the requirements to constitute active sacroiliitis, i.e. fulfil the MRI criterion of the ASAS criteria (‘a positive MRI’) has been defined: bone marrow oedema, located in ≥2 sites and/or in ≥2 slices [Rudwaleit et al. 2009a].

Recent data demonstrate that incorporating structural damage lesions (erosions) into the criteria, would improve the diagnostic utility of MRI [Weber et al. 2010a, 2010b]. However, ASAS in January 2011 decided to await further data before considering revision of the definition of a positive MRI in the axial SpA criteria.

Monitoring disease activity and damage

MRI can provide objective evidence of currently active inflammation in patients with SpA () [Hermann and Bollow, 2004; Maksymowych and Landewe, 2006]. Until the introduction of MRI, disease activity assessment was restricted to patient-reported outcomes, such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI), because disease activity could not be assessed in a sensitive manner by biochemical (mainly C-reactive protein [CRP]) or physical evaluation.

Several systems for assessment of disease activity in the sacroiliac joints and in the spine have been proposed (see a recent review by Østergaard et al. [2010] for details). Reproducible and responsive methods are available [Lukas et al. 2007]. The sensitivity to change and discriminatory ability of the three most used spine scoring systems (The Ankylosing Spondylitis spine Magnetic Resonance Imaging-activity [ASspiMRI-a] score, the Berlin modification of the ASspiMRI-a score and the Spondyloarthritis Research Consortium of Canada [SPARCC] scoring system) [Braun et al. 2003; Haibel et al. 2006; Maksymowych et al. 2005] have been demonstrated in clinical trials, and they have been tested against each other by the ASAS/OMERACT MRI in AS group [Lukas et al. 2007]. All methods were feasible, reliable, sensitive to change and discriminative. The SPARCC method had the highest sensitivity to change, as judged by Guyatt’s effect size, and the highest reliability as judged by the inter-reader intraclass correlation coefficient (ICC) [Lukas et al. 2007].

MRI is much less established for assessment of structural changes (often referred to as chronic changes) than inflammatory changes. Since MRI undoubtedly provides otherwise inaccessible information on inflammatory activity, just ‘equality’ of MRI with radiography concerning structural damage assessment is a step forward, because radiography, and the ensuing need for two examinations and exposure to ionizing radiation, could then be avoided. Scoring methods assess erosions, sclerosis, fat deposition and/or bone bridges separately or as global score [Braun et al. 2003; Madsen and Jurik, 2010b; Østergaard et al. 2009]. The validation of the methods for damage assessment is limited and their value is not yet clarified.

Prognostication

Several published spine studies have documented an association between the presence of bone marrow oedema at the anterior corners of the vertebrae on MRI and subsequent development of syndesmophytes on radiography after 2 years of follow up. Presence as opposed to absence of MRI anterior inflammation provides relative risks of 3–5 for a new anterior radiographic syndesmophyte at that level [Baraliakos et al. 2008; Maksymowych et al. 2009; Pedersen et al. 2011]. In two studies, the association was even more pronounced in those vertebral corners in which the inflammation had resolved following institution of anti-TNF therapy, possibly explained by tumour necrosis factor (TNF) in an active inflammatory lesion restricting new bone formation, whereas reduction of TNF by applying a TNF-antagonist allows tissue repair to manifest as new bone formation [Maksymowych et al. 2009; Pedersen et al. 2011]. A very recent study has demonstrated that fat infiltrations in vertebral corners increase the risk of subsequent radiographic syndesmophyte formation [Chiowchanwisawakit et al. 2011], bearing very interesting implications for fat infiltration (which can be easily recognized and reliably scored by MRI [Chiowchanwisawakit et al. 2009, 2011]), as a potentially valuable surrogate marker for new bone formation in AS. This, however, needs to be investigated in further longitudinal studies.

One study suggests that in early inflammatory back pain, severe sacroiliac MRI bone marrow oedema together with HLA-B27 positivity is a strong predictor of future AS, whereas mild or no sacroiliitis, irrespective of HLA-B27 status, was a predictor of not developing AS [Bennett et al. 2008]. Data on the value of MRI for predicting therapeutic response in SpA are very limited. A high spine MRI inflammation score and short disease duration have been reported as statistically significant predictors of clinical response (BASDAI improvement >50%) to anti-TNF therapy [Rudwaleit et al. 2008]. Further and larger studies are needed to clarify the role of MRI in the prediction of disease course and therapeutic response.

Conclusion

Imaging is an integral part of the management of patients with AS and axial SpA (). Characteristic radiographic and/or MRI findings are key in the diagnosis, and these modalities are also useful in monitoring the disease. CR is the conventional, albeit quite insensitive, gold standard method for assessment of structural damage in spine and sacroiliac joints, whereas MRI has developed a decisive role in monitoring disease activity in clinical trials and practice. MRI may also, if ongoing research demonstrates a sufficient reliability and sensitivity to change, become a new standard method for assessment of structural damage. It is exciting that with continued dedicated research and the rapid technical development it is likely that even larger improvements in the use of imaging may occur in the decade to come, for the benefit of our patients.

Table 2.

Practical use of imaging of axial joints in AS and axial SpA.

Footnotes

Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest statement: The authors declare no conflicts of interest in preparing this article.

Contributor Information

Mikkel Østergaard, Department of Rheumatology, Copenhagen University Hospital at Glostrup, Nordre Ringvej 57, DK-2600 Glostrup, Denmark.

Robert G.W. Lambert, Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada.

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Imaging in ankylosing spondylitis

Ther Adv Musculoskelet Dis. 2012 Aug; 4(4): 301–311.

Monitoring Editor: Gerolamo Bianchi

and

Mikkel Østergaard

Department of Rheumatology, Copenhagen University Hospital at Glostrup, Nordre Ringvej 57, DK-2600 Glostrup, Denmark

Robert G.W. Lambert

Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada

Mikkel Østergaard, Department of Rheumatology, Copenhagen University Hospital at Glostrup, Nordre Ringvej 57, DK-2600 Glostrup, Denmark;

Corresponding author.This article has been cited by other articles in PMC.

Abstract

Imaging is an integral part of the management of patients with ankylosing spondylitis and axial spondyloarthritis. Characteristic radiographic and/or magnetic resonance imaging (MRI) findings are key in the diagnosis. Radiography and MRI are also useful in monitoring the disease. Radiography is the conventional, albeit quite insensitive, gold standard method for assessment of structural damage in spine and sacroiliac joints, whereas MRI has gained a decisive role in monitoring disease activity in clinical trials and practice. MRI may also, if ongoing research demonstrates a sufficient reliability and sensitivity to change, become a new standard method for assessment of structural damage. Ultrasonography allows visualization of peripheral arthritis and enthesitis, but has no role in the assessment of axial manifestations. Computed tomography is a sensitive method for assessment of structural changes in the spine and sacroiliac joints, but its clinical utility is limited due to its use of ionizing radiation and lack of ability to assess the soft tissues. It is exciting that with continued dedicated research and the rapid technical development it is likely that even larger improvements in the use of imaging may occur in the decade to come, for the benefit of our patients.

Keywords: ankylosing spondylitis, computed tomography, imaging, magnetic resonance imaging, radiography, spondyloarthritis, ultrasonography, ultrasound

Introduction

Imaging in ankylosing spondylitis (AS) has been synonymous for decades with conventional radiography (CR). However, developments in computed tomography (CT), ultrasonography (US) and particularly magnetic resonance imaging (MRI) have dramatically increased the amount and scope of information obtainable by imaging. Imaging may be used for multiple reasons that include establishing or confirming the diagnosis, determining extent of disease in axial or peripheral joints and/or entheses, monitoring change in disease (e.g. activity and structural damage) for instance for assessment of therapeutic efficacy in trials, providing prognostic information or selecting patients for specific therapies. These entirely different contexts may favour different imaging approaches.

The present paper focuses on imaging of the spine and sacroiliac joints, i.e. the axial joints, in AS and other variants of axial spondyloarthritis (SpA). The reader is kindly referred to other review articles (e.g. Poggenborg et al. [2011]) for imaging aspects of peripheral involvement in SpA. This paper describes the virtues of CR and its current major importance in diagnosis and follow-up of AS, but also, by putting emphasis on MRI, stresses that AS management has entered a time of exciting and expanding therapeutic as well as imaging possibilities.

Conventional radiography

Technical aspects

The conventional radiograph is a two-dimensional summation image that is dependent on variable absorption of X-rays by different tissues for its inherent contrast. It has a very high spatial resolution that is rarely surpassed by other modalities but radiography only offers high contrast between a limited number of structures: bone (calcium), soft tissue and air. Fat is visible as a separate density but the distinction between soft tissue and fat is often subtle (except in mammography) and radiography cannot distinguish between the other soft tissues because cartilage, muscle, tendon, ligament, synovium and fluid all appear with the same density [Resnick, 2002]. These characteristics give the radiograph its inherent advantages and disadvantages. The conventional radiograph is relatively cheap, available worldwide and produces an image which is almost identical regardless of technical parameters or whether the image is analogue or digital.

CR shows skeletal structure very well, and because it is a summation image, it allows excellent overall assessment of skeletal trauma and alignment. The limited number of images produced facilitates rapid review and the high bone–soft tissue contrast often produces radiographic manifestations of disease in specific patterns that make the test particularly useful in daily clinical practice. The biggest disadvantage of radiography is its inherent lack of soft tissue contrast making it insensitive for the detection of soft tissue abnormalities.

Although CR uses ionizing radiation, radiography is regarded as relatively safe in older patients because of the long lag time for any negative effect to occur. However, spine and pelvis radiography doses need to be relatively high in order to penetrate the trunk and, in a younger population, MRI offers a safer and more informative alternative.

Ankylosing spondylitis

Sacroiliac joints

Erosion and ankylosis of the sacroiliac joints are the hallmarks of AS [Resnick, 2002; van der Linden et al. 1984]. Sacroiliitis is usually the first manifestation and is characteristically bilateral and symmetrical in AS [Berens, 1971; Resnick et al. 1977]. Early radiographic findings predominate on the iliac side of the cartilage compartment with erosion of subchondral bone causing loss of definition of the articular surfaces usually accompanied by variable degrees of adjacent osteoporosis and surrounding reactive sclerosis. Bone erosion may result in the radiographic observation of focal joint space widening () and, as the disease progresses, definition of the joint is completely lost with radiographic superimposition of erosion, sclerosis and new bone formation which fills in the erosions and the original cartilaginous ‘joint space’. The joint may disappear completely in late disease with ankylosis and remodelling of the bone (). The ligamentous compartment of the sacroiliac joint is frequently affected by bony erosion and entheseal proliferation although these may be hard to see radiographically [Berens, 1971; Resnick et al. 1977].

Radiographic findings in sacroiliac joints and spine in ankylosing spondylitis.

(A) Radiograph of the sacroiliac joints in a 23-year-old male demonstrates established ankylosing spondylitis. Bilateral erosions cause discrete foci of loss of subchondral bone and apparent joint space widening in some areas (arrows) and ill definition of the joint margin in other areas (arrowheads). Bilateral subchondral sclerosis is most prominent in the left ilium. (B)–(D) Radiographs of the spine in a 47-year-old male with widespread ankylosis. The cervical spine (B) exhibits extensive formation of vertical syndesmophytes that have bridged the anterior vertebral corners causing ankylosis. Some facet joints are fused, best appreciated at C2/3. The lumbar spine (C; enlargement of L1–L4 in D) shows similar ankylosis. Note the thick right L1/2 bridging (arrow) and compare this to the delicate vertical syndesmophytosis on the left at L3/4. The sacroiliac joints are completely fused with barely any remnant of joint visible.

Spine

The early radiographic manifestations of AS in the spine are most often due to enthesitis at the edges of the discovertebral joints [Berens, 1971]. Focal sclerosis (the ‘shiny corner’) and erosion (the ‘Romanus lesion’) develop at the attachment of the annulus fibrosis to the anterior corner of the vertebral endplate and are characteristic features of early AS [Hermann et al. 2005]. The anterior borders of vertebrae may appear straight or ‘squared’ due to periosteal proliferation of new bone filling in the normal concavity or erosion at the anterosuperior and anteroinferior vertebral margins. This observation is much easier to make in the lumbar spine where normal vertebrae are always concave anteriorly in comparison to the thoracic and cervical spine where the normal contour is much more variable and may be square or occasionally convex.

The hallmark of spinal disease in AS is the development of characteristic bony spurs: syndesmophytes (). These start as thin vertically oriented projections of bone that develop due to ossification within the outer fibres of the annulus fibrosus of the intervertebral disc. Syndesmophytes are radiographically visible on the anterior and lateral aspects of the spine starting from the corner of the vertebra.

Traditional literature indicates that all of the early signs of spinal involvement are most often visualized first near the thoracolumbar junction. While this may be true for radiography, MRI studies show a predilection for early involvement of the midthoracic spine. Both modalities would agree that the cervical spine is rarely affected first and spinal disease rarely occurs in the absence of significant SI joint involvement.

Progressive growth of syndesmophytes will bridge the intervertebral disc causing ankylosis () and extensive bone formation produces a smooth, undulating spinal contour: the ‘bamboo spine’. The syndesmophytes that characterize AS must be differentiated from other spinal and paraspinal bone formation. Degenerative bony spurring in spondylosis deformans arises several millimetres from the discovertebral junction, is typically triangular in shape and has a horizontally oriented segment of variable length at the point of origin. In diffuse idiopathic skeletal hyperostosis (DISH), bone formation in the anterior longitudinal ligament results in a flowing pattern of ossification that is usually thick and the sacroiliac joints are not involved.

Erosion of the vertebral endplate is common in later stages of AS and may be focal or diffuse. It is also seen when pseudarthrosis develops following a fracture in a previously ankylosed spine. Changes in the apophyseal joints are common and start with of ill-defined erosion and sclerosis but may be hard to see. Capsular ossification or intra-articular bony ankylosis frequently occurs in late disease. The ankylosed spine is very susceptible to fractures, which should always be suspected in case of unexplained pain exacerbations. Enthesitis at the interspinous and supraspinous ligamentous attachments is very common with bone formation causing whiskering and interspinous ankylosis.

Use in diagnosis, monitoring and prognostication

Diagnosis

While the modified New York Criteria are actually classification criteria, these criteria are the most commonly used criteria for the diagnosis of AS and are based on clinical features and radiographic sacroiliitis [van der Linden et al. 1984]. According to these criteria AS may be diagnosed if, in addition to one clinical criterion being present, grade 2 sacroiliitis (minimal sacroiliitis: loss of definition of the joint margins, minimal sclerosis, joint space narrowing and erosions) or higher occurs bilaterally, or grade 3 (moderate sacroiliitis: definite sclerosis on both sides of the joint, erosions, and loss of joint space) or grade 4 (complete bony ankylosis) occurs unilaterally [van der Linden et al. 1984]. Owing to the requirement for these radiographic structural changes, the duration of disease before diagnosis has been a median of 7–10 years [Feldtkeller et al. 2003]. The definitions of radiographic changes according to the New York Criteria are included in the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for SpA [Rudwaleit et al. 2009b], the European Spondyloarthritis Study Group (ESSG) criteria for spondyloarthritis [Dougados et al. 1991] and in the modified New York Criteria [van der Linden et al. 1984].

Monitoring

Radiography of the spine is not included in the classification criteria but may be useful to follow structural disease progression in patients with spinal involvement. The bone changes seen in patients with axial SpA develop slowly and are often not present in patients with early disease, and generally only minor changes can be observed in 1–2 years. Different scoring methods, all based on assessment of lateral views, have been developed to quantify changes in the spine of patients with AS: the Stoke AS Spine Score (SASSS), Bath AS Radiology Index (BASRI) and the modified Stoke AS Spine Score (mSASSS). A comparative study of the three methods concluded that all measures were reliable but mSASSS was more sensitive to change [Wanders et al. 2004]. These spine scores are primarily used in clinical research.

Prognostication

The amount of data documenting a prognostic value of CR findings is limited. However, low-grade (grade 1) sacroiliitis has been shown to have predictive value for the development of AS [Huerta-Sil et al. 2006], and the severity of radiographic damage has been documented to be related to subsequent radiographic damage progression [Maksymowych et al. 2010a; Poddubnyy et al. 2011].

Computed tomography

Technical aspects

Developments in computing and engineering have resulted in remarkable changes in the CT technology in the last decade. CT offers fast and reliable acquisition, high resolution and multiplanar capabilities that have enhanced its use in recent years, although the soft-tissue contrast is still limited.

Although CT image acquisition is restricted to the axial plane of imaging, the ability to acquire isotropic voxels has resulted in reliable and versatile multiplanar capabilities so that many CT scans of the body are now interpreted primarily from coronal or sagittal images in the same way as MRI. The data acquisition is so fast that patient motion is rarely a problem as CT scans are now routinely acquired in few seconds. In fact CT is often faster than taking multiple radiographs. Complex requirements for patient positioning in musculoskeletal CT are now substantially less important as the majority of studies can be reconstructed in orthogonal planes. Patient tolerance is excellent and, unlike MRI, there are no absolute contraindications to CT. Spatial resolution is high, usually higher than MRI, and contrast resolution between soft tissue and bone is unsurpassed by any other modality. However, despite all of the advantages listed above, the application of CT will remain somewhat limited, because the soft-tissue contrast is inferior to MRI and US and ionizing radiation is used. Radiation dose increases with the requirements for spatial detail and the depth of the body part, which is considerable for the sacroiliac joint and spine.

Ankylosing spondylitis/axial spondyloarthritis

CT allows visualization of the same pathological processes as CR (erosion, osteoporosis / sclerosis, and new bone formation/ankylosis) with the added benefit of multiplanar imaging free from superimposition of overlying structures.

In AS, the pathological processes start in bone marrow and at sites of entheses. However, CT has poor ability to detect soft-tissue change and is usually normal until structural damage is present. CT can detect osteoporosis or osteosclerosis quite well but these changes are very nonspecific. New bone formation is also well visualized in the form of syndesmophytes, ligamentous ossification and periarticular and intra-articular ankylosis, but the use for CT in this regard is limited. The primary value of CT in AS is its ability to detect and clearly define erosion of bone at any joint or enthesis, and for documenting fractures.

Use in diagnosis, monitoring and prognostication

Diagnosis

The diagnosis of AS is primarily based on the radiographic observation of bilateral moderate or unilateral severe sacroiliitis. When good quality radiographs of the sacroiliac joints are normal or radiographic changes meet diagnostic criteria, there is no role for CT. Early detection of AS is better investigated by MRI and if clearly defined structural damage is present on CR, then there is no additional diagnostic utility for CT. However, CT of the sacroiliac joints is much easier to interpret than radiography which is notoriously subject to poor observer reliability. When the radiographic findings are unclear, CT will usually resolve this uncertainty. Since CT shows bone erosion in exquisite detail, CT may also have a role to play in the further investigation of MRI equivocal findings. It should be noted that classification criteria for AS depend on radiographic findings and more recently MRI, but not CT specifically. In the spine, CT is useful in the diagnosis of complications of late disease such as spondylodiscitis or spinal fracture when patients may be unable to tolerate MRI due to pain or spinal deformity.

Monitoring disease activity and damage

CT has no useful role in monitoring disease activity or damage. CT cannot show active inflammation and the relatively high radiation dose of CT precludes its routine use for assessment of damage progression.

Prognostication

The prognostic value of CT findings of sacroiliitis require further investigation.

Ultrasonography

US is an evolving imaging technique increasingly used by the rheumatologist in daily clinical practice. Despite the fact that contrast-enhanced Doppler US has been reported to have a high negative predictive value for the detection of sacroiliitis [Klauser et al. 2005], the role of US in assessment of sacroiliac and spine involvement in AS and other types of axial SpA is minimal.

AS and other types of axial SpA frequently involve peripheral joints and entheses. US allows assessment of peripheral involvement in SpA. The reader is referred to other reviews (e.g. Gandjbakhch et al. [2011] and Poggenborg et al. [2011]) for further information on this.

Magnetic resonance imaging

Technical aspects

MRI provides multiplanar tomographic imaging with unprecedented soft-tissue contrast and allows assessment of all of the structures involved in musculoskeletal diseases. MRI is more sensitive than clinical examination and CR for the detection of inflammation and damage in inflammatory and degenerative rheumatological disorders. Disadvantages of MRI include longer examination times and higher costs and lower availability than radiography.

MRI involves no ionizing radiation or increased risk of malignancies, and adverse effects of the contrast agents are very rare. However, contrast agent use should be avoided in case of severely impaired renal function due to risk of nephrogenic systemic fibrosis.

T1-weighted (T1w) imaging sequences are favoured for the relatively short imaging times, good anatomical detail and the ability to visualize tissues with high perfusion and permeability, including the inflamed synovium, after intravenous contrast (paramagnetic gadolinium compounds; Gd) injection. Fat and Gd-enhanced tissues have a high signal intensity on T1w images. T2-weighted fat suppressed (T2wFS) and short tau inversion recovery (STIR) images depict water with a high signal intensity. These are well-suited for detection of oedematous tissue/fluid located in areas with fatty tissue, e.g. bone marrow oedema. Bone marrow abnormalities in both sacroiliac joints and spine are detected almost equally well with the STIR and contrast-enhanced T1w FS sequences in patients with SpA, so contrast injection is generally not needed [Baraliakos et al. 2005; Madsen et al. 2010]. T1w images are mandatory for evaluation of structural (sometimes referred to as chronic) changes, such as bone erosion, new bone formation and fat infiltrations.

The majority of MRI studies of the sacroiliac joint have used only one imaging plane (semicoronal, i.e. parallel with the axis of the sacral bone), usually T1W and T2wFS/STIR images. A supplementary T1w FS sequence may improve the evaluation of erosions [Madsen and Jurik, 2010a], and sequences designed for cartilage evaluation, e.g. 3D gradient echo sequences, may also be added [Puhakka et al. 2004]. To be maximally sensitive for changes in the ligamentous portion of the sacroiliac joints imaging in the semi-axial plane is required [Madsen and Jurik, 2010a]. This may therefore be recommended when MRI is used for diagnostic purposes, while it is probably not essential when used as an outcome measure in trials. While MRI for some indications (e.g. suspected disc herniation) should include axial images, MRI of the spine in SpA generally only involve sagittal images, but these should extend sufficiently lateral to include the frequently involved facet, costovertebral and costotransverse joints [Maksymowych et al. 2010b].

Ankylosing spondylitis/axial spondyloarthritis

MRI allows direct visualization of the abnormalities in peripheral and axial joints and entheses that occur in AS, psoriatic arthritis (PsA) and other forms of SpA.

MRI is, through its ability to detect inflammatory changes in bone and soft tissues, the most sensitive imaging modality for recognizing early spine and sacroiliac joint changes in AS. MRI findings indicating active disease in the sacroiliac joints (sacroiliitis) include juxta-articular bone marrow oedema and enhancement of the bone marrow and the joint space after contrast medium administration, while visible chronic changes include bone erosions, sclerosis, periarticular fatty tissue accumulation, bone spurs and ankylosis (). Typical lesions of the spine, which indicate active disease, are spondylitis, spondylodiscitis () and arthritis of the facet, costovertebral and costotransverse joints (). Structural changes, such as bone erosions, focal fat infiltration, bone spurs (syndesmophytes) and/or ankylosis (), frequently occur. Enthesitis is also common, and may affect the interspinal and supraspinal ligaments and the interosseous ligaments in the retro-articular space of the sacroiliac joints. Some patients also have disease manifestations in peripheral joints and entheses, and these can be visualized by MRI [Hermann and Bollow, 2004; Maksymowych and Landewe, 2006]. Definitions of key pathologies in axial SpA are provided in .

Early sacroiliitis on conventional radiography and MRI.

Radiograph (A) of the sacroiliac joints in a 28-year-old male reveals only subtle findings of possible erosion and minimal sclerosis. Short tau inversion recovery (STIR) MRI image (B) performed at the same time shows multiple bone marrow lesions, which appear as oedema (bright; arrows) involving the sacrum and ilium bilaterally, i.e. definite sacroiliitis was documented by MRI. The corresponding T1-weighted MRI image (C) shows some areas of diminished marrow fat signal corresponding to the intense oedema in the left upper quadrant. Some very subtle defects in the subchondral marrow in the lower quadrants, which likely represent tiny erosions (arrows), are also seen.

Inflammatory and fat lesions on MRI of the spine.

MRI of the lumbar and lower thoracic spine in 27-year-old male shows multiple tiny foci of infiltration of fat in the posterior corners of vertebral bodies on the T1-weighted sequence (A; arrows). On the short tau inversion recovery (STIR) sequence (B), these discs demonstrate no evidence of degeneration of the nucleus pulposis or tear of the annulus fibrosus, which is consistent with a postinflammatory cause of the marrow fat deposition rather than trauma or degenerative disc disease. Also note the solitary focus of inflammation on STIR imaging with increased signal at the anterosuperior corner of T10 (arrowhead). The appearance is typical for a corner inflammatory lesion (CIL) associated with spondyloarthritis (i.e. a triangular shaped lesion which may or may not (as in this case) be quite as bright in the extreme corner, with adjacent normal nucleus pulposus).

Bone marrow oedema in the transverse processes, costovertebral joints and manubriosternal joint.

MRI of the cervical and upper thoracic spine of a 29-year-old male patient scans were performed before (A–B and D–E) and 3 months after (C and F) initiation of anti-TNF therapy. Sagittal slices lateral to the spinal canal are shown.

(A)–(C) Sagittal slice through the pedicle and the lateral parts of the vertebrae, shows moderate bone oedema on the baseline STIR image (B) in the posterolateral aspects of all of the thoracic vertebral bodies, most pronounced at T4 and T5. The distribution is typical for inflammation on the vertebral side of the costovertebral joints. Also note inflammation in the manubriosternal joint anteriorly (arrow). Most foci of inflammation are still faintly visible after anti-TNF therapy (C), but are clearly less intense.

(D)–(F) Far lateral slice through the transverse processes and ribs. Intense bone marrow oedema is seen in the transverse processes of the upper thoracic spine (E; arrows), which resolves completely with treatment. This pattern of bone marrow oedema in the transverse processes, costovertebral joints and manubriosternal joint are pathognomonic of spondyloarthritis.

Progression of structural damage in the spine in ankylosing spondylitis, visualized by MRI.

T1-weighted MRIs of the thoracolumbar spine with a 3-year interval in a baseline (A) 23-year-old male with established ankylosing spondylitis. The follow-up MRI (B) demonstrates new anterior ankylosis at T9/10 with bridging anterior syndesmophytosis containing marrow fat signal. Note also several other findings indicating the progression of structural damage: the intervertebral disc at T10/11 is completely fused on the second scan; a new endplate defect has appeared at the inferior endplate of T9 with new fat infiltration; and the signal within the T8/9 disc has increased suggesting progression of disc ossification.

Table 1.

Use in diagnosis, monitoring and prognostication

Diagnosis

The introduction of MRI has resulted in a major improvement in the evaluation and management of patients with SpA. Diagnosis was previously dependent on the presence of bilateral moderate or unilateral severe radiographic sacroiliitis, as part of the modified New York criteria for AS [van der Linden et al. 1984]. This frequently delayed the diagnosis by 7–10 years [Feldtkeller et al. 2003]. Now, through the recent ASAS (ASsessment of SpondyloArthitis) classification criteria for axial SpA, MRI forms an integral part, as patients with active sacroiliitis on MRI plus one clinical feature (e.g. psoriasis, enthesitis or uveitis (see Rudwaleit et al. [2009b] for a complete list), should be classified as axial SpA [Rudwaleit et al. 2009b]. A consensus-based definition of the requirements to constitute active sacroiliitis, i.e. fulfil the MRI criterion of the ASAS criteria (‘a positive MRI’) has been defined: bone marrow oedema, located in ≥2 sites and/or in ≥2 slices [Rudwaleit et al. 2009a].

Recent data demonstrate that incorporating structural damage lesions (erosions) into the criteria, would improve the diagnostic utility of MRI [Weber et al. 2010a, 2010b]. However, ASAS in January 2011 decided to await further data before considering revision of the definition of a positive MRI in the axial SpA criteria.

Monitoring disease activity and damage

MRI can provide objective evidence of currently active inflammation in patients with SpA () [Hermann and Bollow, 2004; Maksymowych and Landewe, 2006]. Until the introduction of MRI, disease activity assessment was restricted to patient-reported outcomes, such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI), because disease activity could not be assessed in a sensitive manner by biochemical (mainly C-reactive protein [CRP]) or physical evaluation.

Several systems for assessment of disease activity in the sacroiliac joints and in the spine have been proposed (see a recent review by Østergaard et al. [2010] for details). Reproducible and responsive methods are available [Lukas et al. 2007]. The sensitivity to change and discriminatory ability of the three most used spine scoring systems (The Ankylosing Spondylitis spine Magnetic Resonance Imaging-activity [ASspiMRI-a] score, the Berlin modification of the ASspiMRI-a score and the Spondyloarthritis Research Consortium of Canada [SPARCC] scoring system) [Braun et al. 2003; Haibel et al. 2006; Maksymowych et al. 2005] have been demonstrated in clinical trials, and they have been tested against each other by the ASAS/OMERACT MRI in AS group [Lukas et al. 2007]. All methods were feasible, reliable, sensitive to change and discriminative. The SPARCC method had the highest sensitivity to change, as judged by Guyatt’s effect size, and the highest reliability as judged by the inter-reader intraclass correlation coefficient (ICC) [Lukas et al. 2007].

MRI is much less established for assessment of structural changes (often referred to as chronic changes) than inflammatory changes. Since MRI undoubtedly provides otherwise inaccessible information on inflammatory activity, just ‘equality’ of MRI with radiography concerning structural damage assessment is a step forward, because radiography, and the ensuing need for two examinations and exposure to ionizing radiation, could then be avoided. Scoring methods assess erosions, sclerosis, fat deposition and/or bone bridges separately or as global score [Braun et al. 2003; Madsen and Jurik, 2010b; Østergaard et al. 2009]. The validation of the methods for damage assessment is limited and their value is not yet clarified.

Prognostication

Several published spine studies have documented an association between the presence of bone marrow oedema at the anterior corners of the vertebrae on MRI and subsequent development of syndesmophytes on radiography after 2 years of follow up. Presence as opposed to absence of MRI anterior inflammation provides relative risks of 3–5 for a new anterior radiographic syndesmophyte at that level [Baraliakos et al. 2008; Maksymowych et al. 2009; Pedersen et al. 2011]. In two studies, the association was even more pronounced in those vertebral corners in which the inflammation had resolved following institution of anti-TNF therapy, possibly explained by tumour necrosis factor (TNF) in an active inflammatory lesion restricting new bone formation, whereas reduction of TNF by applying a TNF-antagonist allows tissue repair to manifest as new bone formation [Maksymowych et al. 2009; Pedersen et al. 2011]. A very recent study has demonstrated that fat infiltrations in vertebral corners increase the risk of subsequent radiographic syndesmophyte formation [Chiowchanwisawakit et al. 2011], bearing very interesting implications for fat infiltration (which can be easily recognized and reliably scored by MRI [Chiowchanwisawakit et al. 2009, 2011]), as a potentially valuable surrogate marker for new bone formation in AS. This, however, needs to be investigated in further longitudinal studies.

One study suggests that in early inflammatory back pain, severe sacroiliac MRI bone marrow oedema together with HLA-B27 positivity is a strong predictor of future AS, whereas mild or no sacroiliitis, irrespective of HLA-B27 status, was a predictor of not developing AS [Bennett et al. 2008]. Data on the value of MRI for predicting therapeutic response in SpA are very limited. A high spine MRI inflammation score and short disease duration have been reported as statistically significant predictors of clinical response (BASDAI improvement >50%) to anti-TNF therapy [Rudwaleit et al. 2008]. Further and larger studies are needed to clarify the role of MRI in the prediction of disease course and therapeutic response.

Conclusion

Imaging is an integral part of the management of patients with AS and axial SpA (). Characteristic radiographic and/or MRI findings are key in the diagnosis, and these modalities are also useful in monitoring the disease. CR is the conventional, albeit quite insensitive, gold standard method for assessment of structural damage in spine and sacroiliac joints, whereas MRI has developed a decisive role in monitoring disease activity in clinical trials and practice. MRI may also, if ongoing research demonstrates a sufficient reliability and sensitivity to change, become a new standard method for assessment of structural damage. It is exciting that with continued dedicated research and the rapid technical development it is likely that even larger improvements in the use of imaging may occur in the decade to come, for the benefit of our patients.

Table 2.

Practical use of imaging of axial joints in AS and axial SpA.

Footnotes

Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest statement: The authors declare no conflicts of interest in preparing this article.

Contributor Information

Mikkel Østergaard, Department of Rheumatology, Copenhagen University Hospital at Glostrup, Nordre Ringvej 57, DK-2600 Glostrup, Denmark.

Robert G.W. Lambert, Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada.

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Imaging in ankylosing spondylitis

Ther Adv Musculoskelet Dis. 2012 Aug; 4(4): 301–311.

Monitoring Editor: Gerolamo Bianchi

and

Mikkel Østergaard

Department of Rheumatology, Copenhagen University Hospital at Glostrup, Nordre Ringvej 57, DK-2600 Glostrup, Denmark

Robert G.W. Lambert

Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada

Mikkel Østergaard, Department of Rheumatology, Copenhagen University Hospital at Glostrup, Nordre Ringvej 57, DK-2600 Glostrup, Denmark;

Corresponding author.This article has been cited by other articles in PMC.

Abstract

Imaging is an integral part of the management of patients with ankylosing spondylitis and axial spondyloarthritis. Characteristic radiographic and/or magnetic resonance imaging (MRI) findings are key in the diagnosis. Radiography and MRI are also useful in monitoring the disease. Radiography is the conventional, albeit quite insensitive, gold standard method for assessment of structural damage in spine and sacroiliac joints, whereas MRI has gained a decisive role in monitoring disease activity in clinical trials and practice. MRI may also, if ongoing research demonstrates a sufficient reliability and sensitivity to change, become a new standard method for assessment of structural damage. Ultrasonography allows visualization of peripheral arthritis and enthesitis, but has no role in the assessment of axial manifestations. Computed tomography is a sensitive method for assessment of structural changes in the spine and sacroiliac joints, but its clinical utility is limited due to its use of ionizing radiation and lack of ability to assess the soft tissues. It is exciting that with continued dedicated research and the rapid technical development it is likely that even larger improvements in the use of imaging may occur in the decade to come, for the benefit of our patients.

Keywords: ankylosing spondylitis, computed tomography, imaging, magnetic resonance imaging, radiography, spondyloarthritis, ultrasonography, ultrasound

Introduction

Imaging in ankylosing spondylitis (AS) has been synonymous for decades with conventional radiography (CR). However, developments in computed tomography (CT), ultrasonography (US) and particularly magnetic resonance imaging (MRI) have dramatically increased the amount and scope of information obtainable by imaging. Imaging may be used for multiple reasons that include establishing or confirming the diagnosis, determining extent of disease in axial or peripheral joints and/or entheses, monitoring change in disease (e.g. activity and structural damage) for instance for assessment of therapeutic efficacy in trials, providing prognostic information or selecting patients for specific therapies. These entirely different contexts may favour different imaging approaches.

The present paper focuses on imaging of the spine and sacroiliac joints, i.e. the axial joints, in AS and other variants of axial spondyloarthritis (SpA). The reader is kindly referred to other review articles (e.g. Poggenborg et al. [2011]) for imaging aspects of peripheral involvement in SpA. This paper describes the virtues of CR and its current major importance in diagnosis and follow-up of AS, but also, by putting emphasis on MRI, stresses that AS management has entered a time of exciting and expanding therapeutic as well as imaging possibilities.

Conventional radiography

Technical aspects

The conventional radiograph is a two-dimensional summation image that is dependent on variable absorption of X-rays by different tissues for its inherent contrast. It has a very high spatial resolution that is rarely surpassed by other modalities but radiography only offers high contrast between a limited number of structures: bone (calcium), soft tissue and air. Fat is visible as a separate density but the distinction between soft tissue and fat is often subtle (except in mammography) and radiography cannot distinguish between the other soft tissues because cartilage, muscle, tendon, ligament, synovium and fluid all appear with the same density [Resnick, 2002]. These characteristics give the radiograph its inherent advantages and disadvantages. The conventional radiograph is relatively cheap, available worldwide and produces an image which is almost identical regardless of technical parameters or whether the image is analogue or digital.

CR shows skeletal structure very well, and because it is a summation image, it allows excellent overall assessment of skeletal trauma and alignment. The limited number of images produced facilitates rapid review and the high bone–soft tissue contrast often produces radiographic manifestations of disease in specific patterns that make the test particularly useful in daily clinical practice. The biggest disadvantage of radiography is its inherent lack of soft tissue contrast making it insensitive for the detection of soft tissue abnormalities.

Although CR uses ionizing radiation, radiography is regarded as relatively safe in older patients because of the long lag time for any negative effect to occur. However, spine and pelvis radiography doses need to be relatively high in order to penetrate the trunk and, in a younger population, MRI offers a safer and more informative alternative.

Ankylosing spondylitis

Sacroiliac joints

Erosion and ankylosis of the sacroiliac joints are the hallmarks of AS [Resnick, 2002; van der Linden et al. 1984]. Sacroiliitis is usually the first manifestation and is characteristically bilateral and symmetrical in AS [Berens, 1971; Resnick et al. 1977]. Early radiographic findings predominate on the iliac side of the cartilage compartment with erosion of subchondral bone causing loss of definition of the articular surfaces usually accompanied by variable degrees of adjacent osteoporosis and surrounding reactive sclerosis. Bone erosion may result in the radiographic observation of focal joint space widening () and, as the disease progresses, definition of the joint is completely lost with radiographic superimposition of erosion, sclerosis and new bone formation which fills in the erosions and the original cartilaginous ‘joint space’. The joint may disappear completely in late disease with ankylosis and remodelling of the bone (). The ligamentous compartment of the sacroiliac joint is frequently affected by bony erosion and entheseal proliferation although these may be hard to see radiographically [Berens, 1971; Resnick et al. 1977].

Radiographic findings in sacroiliac joints and spine in ankylosing spondylitis.

(A) Radiograph of the sacroiliac joints in a 23-year-old male demonstrates established ankylosing spondylitis. Bilateral erosions cause discrete foci of loss of subchondral bone and apparent joint space widening in some areas (arrows) and ill definition of the joint margin in other areas (arrowheads). Bilateral subchondral sclerosis is most prominent in the left ilium. (B)–(D) Radiographs of the spine in a 47-year-old male with widespread ankylosis. The cervical spine (B) exhibits extensive formation of vertical syndesmophytes that have bridged the anterior vertebral corners causing ankylosis. Some facet joints are fused, best appreciated at C2/3. The lumbar spine (C; enlargement of L1–L4 in D) shows similar ankylosis. Note the thick right L1/2 bridging (arrow) and compare this to the delicate vertical syndesmophytosis on the left at L3/4. The sacroiliac joints are completely fused with barely any remnant of joint visible.

Spine

The early radiographic manifestations of AS in the spine are most often due to enthesitis at the edges of the discovertebral joints [Berens, 1971]. Focal sclerosis (the ‘shiny corner’) and erosion (the ‘Romanus lesion’) develop at the attachment of the annulus fibrosis to the anterior corner of the vertebral endplate and are characteristic features of early AS [Hermann et al. 2005]. The anterior borders of vertebrae may appear straight or ‘squared’ due to periosteal proliferation of new bone filling in the normal concavity or erosion at the anterosuperior and anteroinferior vertebral margins. This observation is much easier to make in the lumbar spine where normal vertebrae are always concave anteriorly in comparison to the thoracic and cervical spine where the normal contour is much more variable and may be square or occasionally convex.

The hallmark of spinal disease in AS is the development of characteristic bony spurs: syndesmophytes (). These start as thin vertically oriented projections of bone that develop due to ossification within the outer fibres of the annulus fibrosus of the intervertebral disc. Syndesmophytes are radiographically visible on the anterior and lateral aspects of the spine starting from the corner of the vertebra.

Traditional literature indicates that all of the early signs of spinal involvement are most often visualized first near the thoracolumbar junction. While this may be true for radiography, MRI studies show a predilection for early involvement of the midthoracic spine. Both modalities would agree that the cervical spine is rarely affected first and spinal disease rarely occurs in the absence of significant SI joint involvement.

Progressive growth of syndesmophytes will bridge the intervertebral disc causing ankylosis () and extensive bone formation produces a smooth, undulating spinal contour: the ‘bamboo spine’. The syndesmophytes that characterize AS must be differentiated from other spinal and paraspinal bone formation. Degenerative bony spurring in spondylosis deformans arises several millimetres from the discovertebral junction, is typically triangular in shape and has a horizontally oriented segment of variable length at the point of origin. In diffuse idiopathic skeletal hyperostosis (DISH), bone formation in the anterior longitudinal ligament results in a flowing pattern of ossification that is usually thick and the sacroiliac joints are not involved.

Erosion of the vertebral endplate is common in later stages of AS and may be focal or diffuse. It is also seen when pseudarthrosis develops following a fracture in a previously ankylosed spine. Changes in the apophyseal joints are common and start with of ill-defined erosion and sclerosis but may be hard to see. Capsular ossification or intra-articular bony ankylosis frequently occurs in late disease. The ankylosed spine is very susceptible to fractures, which should always be suspected in case of unexplained pain exacerbations. Enthesitis at the interspinous and supraspinous ligamentous attachments is very common with bone formation causing whiskering and interspinous ankylosis.

Use in diagnosis, monitoring and prognostication

Diagnosis

While the modified New York Criteria are actually classification criteria, these criteria are the most commonly used criteria for the diagnosis of AS and are based on clinical features and radiographic sacroiliitis [van der Linden et al. 1984]. According to these criteria AS may be diagnosed if, in addition to one clinical criterion being present, grade 2 sacroiliitis (minimal sacroiliitis: loss of definition of the joint margins, minimal sclerosis, joint space narrowing and erosions) or higher occurs bilaterally, or grade 3 (moderate sacroiliitis: definite sclerosis on both sides of the joint, erosions, and loss of joint space) or grade 4 (complete bony ankylosis) occurs unilaterally [van der Linden et al. 1984]. Owing to the requirement for these radiographic structural changes, the duration of disease before diagnosis has been a median of 7–10 years [Feldtkeller et al. 2003]. The definitions of radiographic changes according to the New York Criteria are included in the Assessment of Spondyloarthritis International Society (ASAS) classification criteria for SpA [Rudwaleit et al. 2009b], the European Spondyloarthritis Study Group (ESSG) criteria for spondyloarthritis [Dougados et al. 1991] and in the modified New York Criteria [van der Linden et al. 1984].

Monitoring

Radiography of the spine is not included in the classification criteria but may be useful to follow structural disease progression in patients with spinal involvement. The bone changes seen in patients with axial SpA develop slowly and are often not present in patients with early disease, and generally only minor changes can be observed in 1–2 years. Different scoring methods, all based on assessment of lateral views, have been developed to quantify changes in the spine of patients with AS: the Stoke AS Spine Score (SASSS), Bath AS Radiology Index (BASRI) and the modified Stoke AS Spine Score (mSASSS). A comparative study of the three methods concluded that all measures were reliable but mSASSS was more sensitive to change [Wanders et al. 2004]. These spine scores are primarily used in clinical research.

Prognostication

The amount of data documenting a prognostic value of CR findings is limited. However, low-grade (grade 1) sacroiliitis has been shown to have predictive value for the development of AS [Huerta-Sil et al. 2006], and the severity of radiographic damage has been documented to be related to subsequent radiographic damage progression [Maksymowych et al. 2010a; Poddubnyy et al. 2011].

Computed tomography

Technical aspects

Developments in computing and engineering have resulted in remarkable changes in the CT technology in the last decade. CT offers fast and reliable acquisition, high resolution and multiplanar capabilities that have enhanced its use in recent years, although the soft-tissue contrast is still limited.

Although CT image acquisition is restricted to the axial plane of imaging, the ability to acquire isotropic voxels has resulted in reliable and versatile multiplanar capabilities so that many CT scans of the body are now interpreted primarily from coronal or sagittal images in the same way as MRI. The data acquisition is so fast that patient motion is rarely a problem as CT scans are now routinely acquired in few seconds. In fact CT is often faster than taking multiple radiographs. Complex requirements for patient positioning in musculoskeletal CT are now substantially less important as the majority of studies can be reconstructed in orthogonal planes. Patient tolerance is excellent and, unlike MRI, there are no absolute contraindications to CT. Spatial resolution is high, usually higher than MRI, and contrast resolution between soft tissue and bone is unsurpassed by any other modality. However, despite all of the advantages listed above, the application of CT will remain somewhat limited, because the soft-tissue contrast is inferior to MRI and US and ionizing radiation is used. Radiation dose increases with the requirements for spatial detail and the depth of the body part, which is considerable for the sacroiliac joint and spine.

Ankylosing spondylitis/axial spondyloarthritis

CT allows visualization of the same pathological processes as CR (erosion, osteoporosis / sclerosis, and new bone formation/ankylosis) with the added benefit of multiplanar imaging free from superimposition of overlying structures.

In AS, the pathological processes start in bone marrow and at sites of entheses. However, CT has poor ability to detect soft-tissue change and is usually normal until structural damage is present. CT can detect osteoporosis or osteosclerosis quite well but these changes are very nonspecific. New bone formation is also well visualized in the form of syndesmophytes, ligamentous ossification and periarticular and intra-articular ankylosis, but the use for CT in this regard is limited. The primary value of CT in AS is its ability to detect and clearly define erosion of bone at any joint or enthesis, and for documenting fractures.

Use in diagnosis, monitoring and prognostication

Diagnosis

The diagnosis of AS is primarily based on the radiographic observation of bilateral moderate or unilateral severe sacroiliitis. When good quality radiographs of the sacroiliac joints are normal or radiographic changes meet diagnostic criteria, there is no role for CT. Early detection of AS is better investigated by MRI and if clearly defined structural damage is present on CR, then there is no additional diagnostic utility for CT. However, CT of the sacroiliac joints is much easier to interpret than radiography which is notoriously subject to poor observer reliability. When the radiographic findings are unclear, CT will usually resolve this uncertainty. Since CT shows bone erosion in exquisite detail, CT may also have a role to play in the further investigation of MRI equivocal findings. It should be noted that classification criteria for AS depend on radiographic findings and more recently MRI, but not CT specifically. In the spine, CT is useful in the diagnosis of complications of late disease such as spondylodiscitis or spinal fracture when patients may be unable to tolerate MRI due to pain or spinal deformity.

Monitoring disease activity and damage

CT has no useful role in monitoring disease activity or damage. CT cannot show active inflammation and the relatively high radiation dose of CT precludes its routine use for assessment of damage progression.

Prognostication

The prognostic value of CT findings of sacroiliitis require further investigation.

Ultrasonography

US is an evolving imaging technique increasingly used by the rheumatologist in daily clinical practice. Despite the fact that contrast-enhanced Doppler US has been reported to have a high negative predictive value for the detection of sacroiliitis [Klauser et al. 2005], the role of US in assessment of sacroiliac and spine involvement in AS and other types of axial SpA is minimal.

AS and other types of axial SpA frequently involve peripheral joints and entheses. US allows assessment of peripheral involvement in SpA. The reader is referred to other reviews (e.g. Gandjbakhch et al. [2011] and Poggenborg et al. [2011]) for further information on this.

Magnetic resonance imaging

Technical aspects

MRI provides multiplanar tomographic imaging with unprecedented soft-tissue contrast and allows assessment of all of the structures involved in musculoskeletal diseases. MRI is more sensitive than clinical examination and CR for the detection of inflammation and damage in inflammatory and degenerative rheumatological disorders. Disadvantages of MRI include longer examination times and higher costs and lower availability than radiography.

MRI involves no ionizing radiation or increased risk of malignancies, and adverse effects of the contrast agents are very rare. However, contrast agent use should be avoided in case of severely impaired renal function due to risk of nephrogenic systemic fibrosis.

T1-weighted (T1w) imaging sequences are favoured for the relatively short imaging times, good anatomical detail and the ability to visualize tissues with high perfusion and permeability, including the inflamed synovium, after intravenous contrast (paramagnetic gadolinium compounds; Gd) injection. Fat and Gd-enhanced tissues have a high signal intensity on T1w images. T2-weighted fat suppressed (T2wFS) and short tau inversion recovery (STIR) images depict water with a high signal intensity. These are well-suited for detection of oedematous tissue/fluid located in areas with fatty tissue, e.g. bone marrow oedema. Bone marrow abnormalities in both sacroiliac joints and spine are detected almost equally well with the STIR and contrast-enhanced T1w FS sequences in patients with SpA, so contrast injection is generally not needed [Baraliakos et al. 2005; Madsen et al. 2010]. T1w images are mandatory for evaluation of structural (sometimes referred to as chronic) changes, such as bone erosion, new bone formation and fat infiltrations.

The majority of MRI studies of the sacroiliac joint have used only one imaging plane (semicoronal, i.e. parallel with the axis of the sacral bone), usually T1W and T2wFS/STIR images. A supplementary T1w FS sequence may improve the evaluation of erosions [Madsen and Jurik, 2010a], and sequences designed for cartilage evaluation, e.g. 3D gradient echo sequences, may also be added [Puhakka et al. 2004]. To be maximally sensitive for changes in the ligamentous portion of the sacroiliac joints imaging in the semi-axial plane is required [Madsen and Jurik, 2010a]. This may therefore be recommended when MRI is used for diagnostic purposes, while it is probably not essential when used as an outcome measure in trials. While MRI for some indications (e.g. suspected disc herniation) should include axial images, MRI of the spine in SpA generally only involve sagittal images, but these should extend sufficiently lateral to include the frequently involved facet, costovertebral and costotransverse joints [Maksymowych et al. 2010b].

Ankylosing spondylitis/axial spondyloarthritis

MRI allows direct visualization of the abnormalities in peripheral and axial joints and entheses that occur in AS, psoriatic arthritis (PsA) and other forms of SpA.

MRI is, through its ability to detect inflammatory changes in bone and soft tissues, the most sensitive imaging modality for recognizing early spine and sacroiliac joint changes in AS. MRI findings indicating active disease in the sacroiliac joints (sacroiliitis) include juxta-articular bone marrow oedema and enhancement of the bone marrow and the joint space after contrast medium administration, while visible chronic changes include bone erosions, sclerosis, periarticular fatty tissue accumulation, bone spurs and ankylosis (). Typical lesions of the spine, which indicate active disease, are spondylitis, spondylodiscitis () and arthritis of the facet, costovertebral and costotransverse joints (). Structural changes, such as bone erosions, focal fat infiltration, bone spurs (syndesmophytes) and/or ankylosis (), frequently occur. Enthesitis is also common, and may affect the interspinal and supraspinal ligaments and the interosseous ligaments in the retro-articular space of the sacroiliac joints. Some patients also have disease manifestations in peripheral joints and entheses, and these can be visualized by MRI [Hermann and Bollow, 2004; Maksymowych and Landewe, 2006]. Definitions of key pathologies in axial SpA are provided in .

Early sacroiliitis on conventional radiography and MRI.

Radiograph (A) of the sacroiliac joints in a 28-year-old male reveals only subtle findings of possible erosion and minimal sclerosis. Short tau inversion recovery (STIR) MRI image (B) performed at the same time shows multiple bone marrow lesions, which appear as oedema (bright; arrows) involving the sacrum and ilium bilaterally, i.e. definite sacroiliitis was documented by MRI. The corresponding T1-weighted MRI image (C) shows some areas of diminished marrow fat signal corresponding to the intense oedema in the left upper quadrant. Some very subtle defects in the subchondral marrow in the lower quadrants, which likely represent tiny erosions (arrows), are also seen.

Inflammatory and fat lesions on MRI of the spine.

MRI of the lumbar and lower thoracic spine in 27-year-old male shows multiple tiny foci of infiltration of fat in the posterior corners of vertebral bodies on the T1-weighted sequence (A; arrows). On the short tau inversion recovery (STIR) sequence (B), these discs demonstrate no evidence of degeneration of the nucleus pulposis or tear of the annulus fibrosus, which is consistent with a postinflammatory cause of the marrow fat deposition rather than trauma or degenerative disc disease. Also note the solitary focus of inflammation on STIR imaging with increased signal at the anterosuperior corner of T10 (arrowhead). The appearance is typical for a corner inflammatory lesion (CIL) associated with spondyloarthritis (i.e. a triangular shaped lesion which may or may not (as in this case) be quite as bright in the extreme corner, with adjacent normal nucleus pulposus).

Bone marrow oedema in the transverse processes, costovertebral joints and manubriosternal joint.

MRI of the cervical and upper thoracic spine of a 29-year-old male patient scans were performed before (A–B and D–E) and 3 months after (C and F) initiation of anti-TNF therapy. Sagittal slices lateral to the spinal canal are shown.

(A)–(C) Sagittal slice through the pedicle and the lateral parts of the vertebrae, shows moderate bone oedema on the baseline STIR image (B) in the posterolateral aspects of all of the thoracic vertebral bodies, most pronounced at T4 and T5. The distribution is typical for inflammation on the vertebral side of the costovertebral joints. Also note inflammation in the manubriosternal joint anteriorly (arrow). Most foci of inflammation are still faintly visible after anti-TNF therapy (C), but are clearly less intense.

(D)–(F) Far lateral slice through the transverse processes and ribs. Intense bone marrow oedema is seen in the transverse processes of the upper thoracic spine (E; arrows), which resolves completely with treatment. This pattern of bone marrow oedema in the transverse processes, costovertebral joints and manubriosternal joint are pathognomonic of spondyloarthritis.

Progression of structural damage in the spine in ankylosing spondylitis, visualized by MRI.

T1-weighted MRIs of the thoracolumbar spine with a 3-year interval in a baseline (A) 23-year-old male with established ankylosing spondylitis. The follow-up MRI (B) demonstrates new anterior ankylosis at T9/10 with bridging anterior syndesmophytosis containing marrow fat signal. Note also several other findings indicating the progression of structural damage: the intervertebral disc at T10/11 is completely fused on the second scan; a new endplate defect has appeared at the inferior endplate of T9 with new fat infiltration; and the signal within the T8/9 disc has increased suggesting progression of disc ossification.

Table 1.

Use in diagnosis, monitoring and prognostication

Diagnosis

The introduction of MRI has resulted in a major improvement in the evaluation and management of patients with SpA. Diagnosis was previously dependent on the presence of bilateral moderate or unilateral severe radiographic sacroiliitis, as part of the modified New York criteria for AS [van der Linden et al. 1984]. This frequently delayed the diagnosis by 7–10 years [Feldtkeller et al. 2003]. Now, through the recent ASAS (ASsessment of SpondyloArthitis) classification criteria for axial SpA, MRI forms an integral part, as patients with active sacroiliitis on MRI plus one clinical feature (e.g. psoriasis, enthesitis or uveitis (see Rudwaleit et al. [2009b] for a complete list), should be classified as axial SpA [Rudwaleit et al. 2009b]. A consensus-based definition of the requirements to constitute active sacroiliitis, i.e. fulfil the MRI criterion of the ASAS criteria (‘a positive MRI’) has been defined: bone marrow oedema, located in ≥2 sites and/or in ≥2 slices [Rudwaleit et al. 2009a].

Recent data demonstrate that incorporating structural damage lesions (erosions) into the criteria, would improve the diagnostic utility of MRI [Weber et al. 2010a, 2010b]. However, ASAS in January 2011 decided to await further data before considering revision of the definition of a positive MRI in the axial SpA criteria.

Monitoring disease activity and damage

MRI can provide objective evidence of currently active inflammation in patients with SpA () [Hermann and Bollow, 2004; Maksymowych and Landewe, 2006]. Until the introduction of MRI, disease activity assessment was restricted to patient-reported outcomes, such as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI), because disease activity could not be assessed in a sensitive manner by biochemical (mainly C-reactive protein [CRP]) or physical evaluation.

Several systems for assessment of disease activity in the sacroiliac joints and in the spine have been proposed (see a recent review by Østergaard et al. [2010] for details). Reproducible and responsive methods are available [Lukas et al. 2007]. The sensitivity to change and discriminatory ability of the three most used spine scoring systems (The Ankylosing Spondylitis spine Magnetic Resonance Imaging-activity [ASspiMRI-a] score, the Berlin modification of the ASspiMRI-a score and the Spondyloarthritis Research Consortium of Canada [SPARCC] scoring system) [Braun et al. 2003; Haibel et al. 2006; Maksymowych et al. 2005] have been demonstrated in clinical trials, and they have been tested against each other by the ASAS/OMERACT MRI in AS group [Lukas et al. 2007]. All methods were feasible, reliable, sensitive to change and discriminative. The SPARCC method had the highest sensitivity to change, as judged by Guyatt’s effect size, and the highest reliability as judged by the inter-reader intraclass correlation coefficient (ICC) [Lukas et al. 2007].

MRI is much less established for assessment of structural changes (often referred to as chronic changes) than inflammatory changes. Since MRI undoubtedly provides otherwise inaccessible information on inflammatory activity, just ‘equality’ of MRI with radiography concerning structural damage assessment is a step forward, because radiography, and the ensuing need for two examinations and exposure to ionizing radiation, could then be avoided. Scoring methods assess erosions, sclerosis, fat deposition and/or bone bridges separately or as global score [Braun et al. 2003; Madsen and Jurik, 2010b; Østergaard et al. 2009]. The validation of the methods for damage assessment is limited and their value is not yet clarified.

Prognostication

Several published spine studies have documented an association between the presence of bone marrow oedema at the anterior corners of the vertebrae on MRI and subsequent development of syndesmophytes on radiography after 2 years of follow up. Presence as opposed to absence of MRI anterior inflammation provides relative risks of 3–5 for a new anterior radiographic syndesmophyte at that level [Baraliakos et al. 2008; Maksymowych et al. 2009; Pedersen et al. 2011]. In two studies, the association was even more pronounced in those vertebral corners in which the inflammation had resolved following institution of anti-TNF therapy, possibly explained by tumour necrosis factor (TNF) in an active inflammatory lesion restricting new bone formation, whereas reduction of TNF by applying a TNF-antagonist allows tissue repair to manifest as new bone formation [Maksymowych et al. 2009; Pedersen et al. 2011]. A very recent study has demonstrated that fat infiltrations in vertebral corners increase the risk of subsequent radiographic syndesmophyte formation [Chiowchanwisawakit et al. 2011], bearing very interesting implications for fat infiltration (which can be easily recognized and reliably scored by MRI [Chiowchanwisawakit et al. 2009, 2011]), as a potentially valuable surrogate marker for new bone formation in AS. This, however, needs to be investigated in further longitudinal studies.

One study suggests that in early inflammatory back pain, severe sacroiliac MRI bone marrow oedema together with HLA-B27 positivity is a strong predictor of future AS, whereas mild or no sacroiliitis, irrespective of HLA-B27 status, was a predictor of not developing AS [Bennett et al. 2008]. Data on the value of MRI for predicting therapeutic response in SpA are very limited. A high spine MRI inflammation score and short disease duration have been reported as statistically significant predictors of clinical response (BASDAI improvement >50%) to anti-TNF therapy [Rudwaleit et al. 2008]. Further and larger studies are needed to clarify the role of MRI in the prediction of disease course and therapeutic response.

Conclusion

Imaging is an integral part of the management of patients with AS and axial SpA (). Characteristic radiographic and/or MRI findings are key in the diagnosis, and these modalities are also useful in monitoring the disease. CR is the conventional, albeit quite insensitive, gold standard method for assessment of structural damage in spine and sacroiliac joints, whereas MRI has developed a decisive role in monitoring disease activity in clinical trials and practice. MRI may also, if ongoing research demonstrates a sufficient reliability and sensitivity to change, become a new standard method for assessment of structural damage. It is exciting that with continued dedicated research and the rapid technical development it is likely that even larger improvements in the use of imaging may occur in the decade to come, for the benefit of our patients.

Table 2.

Practical use of imaging of axial joints in AS and axial SpA.

Footnotes

Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of interest statement: The authors declare no conflicts of interest in preparing this article.

Contributor Information

Mikkel Østergaard, Department of Rheumatology, Copenhagen University Hospital at Glostrup, Nordre Ringvej 57, DK-2600 Glostrup, Denmark.

Robert G.W. Lambert, Department of Radiology and Diagnostic Imaging, University of Alberta, Edmonton, AB, Canada.

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Ankylosing spondylitis x ray – wikidoc

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Overview

An x-ray may be helpful in the diagnosis of ankylosing spondylitis (AS). Findings on an x-ray suggestive of ankylosing spondylitis (AS) include erosion and ankylosis of the sacroiliac joints.

X Ray

Lateral Xray of neck showing complete fusion of anterior and posterior elements in ankylosing spondylitis, so called bamboo spine. Source: Case courtesy of A.Prof Frank Gaillard, From the case https://radiopaedia.org/cases/2912″>rID: 2912

Ankylosing spondylitis DAGGER SPINE

X-ray Ap view of spine showing fusion of the spinous processes, so called dagger sign in AS Case courtesy of A.Prof Frank Gaillard, From the case https://radiopaedia.org/cases/3382″>rID: 3382

References

1. ↑ Jang JH, Ward MM, Rucker AN, Reveille JD, Davis JC, Weisman MH, Learch TJ (January 2011). “Ankylosing spondylitis: patterns of radiographic involvement–a re-examination of accepted principles in a cohort of 769 patients”. Radiology. 258 (1): 192–8. doi:10.1148/radiol.10100426. PMC 3009382. PMID 20971774.
2. ↑ Poddubnyy D, Brandt H, Vahldiek J, Spiller I, Song IH, Rudwaleit M, Sieper J (December 2012). “The frequency of non-radiographic axial spondyloarthritis in relation to symptom duration in patients referred because of chronic back pain: results from the Berlin early spondyloarthritis clinic”. Ann. Rheum. Dis. 71 (12): 1998–2001. doi:10.1136/annrheumdis-2012-201945. PMID 22915622.
3. ↑ Ostergaard M, Lambert RG (August 2012). “Imaging in ankylosing spondylitis”. Ther Adv Musculoskelet Dis. 4 (4): 301–11. doi:10.1177/1759720X11436240. PMC 3403247. PMID 22859929.
4. ↑ Baraliakos X, Braun J (January 2010). “Hip involvement in ankylosing spondylitis: what is the verdict?”. Rheumatology (Oxford). 49 (1): 3–4. doi:10.1093/rheumatology/kep298. PMID 19755506.

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Diagnosis | Stanford Health Care

Your doctor will use your medical history, a physical exam, and an X-ray to diagnose AS.

By asking questions about your medical history, your doctor can evaluate your symptoms. Most people with AS have back pain with four or all of the following characteristics: 

• Pain starts before the age of about 35
• It starts and gets worse gradually 
• It lasts for at least 3 months 
• The pain is linked with morning stiffness that usually lasts for more than 1 hour 
• The pain improves with exercise

The clearest sign of the disease is a change in the sacroiliac joints at the base of the low back. This change can take up to a few years to show up on an X-ray. 

Your doctor will want to know if you have any family members who have AS or a related joint disease. Many people with AS have a family member with the same condition. The doctor may also ask if you’ve had ongoing diarrhea, belly pain, multiple infections of the cervix (in women) or urethra (more common in men), psoriasis, or inflammation of the eye chamber (uveitis). These could be clues to having a condition other than AS. 

You will have a physical exam to see how stiff your back is and whether you can expand your chest normally. Your doctor will also look for tender areas, especially over the points of the spine, the pelvis, the areas where your ribs join your breastbone, and your heels. You may have chest pain and stiffness. 

Tests related to ankylosing spondylitis include: 

• X-rays of the spine and pelvis. These tests can check for bone changes (bony erosions, fusion, or calcification of the spine and sacroiliac joints). Certain changes in the sacroiliac joint confirm the diagnosis of AS. But those changes can take several years to develop enough to show on an X-ray.
• Magnetic resonance imaging (MRI) and computed tomography (CT) scan are more sensitive than X-ray. If no changes to the sacroiliac joints show on the X-ray but your doctor still suspects AS, an MRI or CT scan may allow an earlier diagnosis.
• Ultrasound is being studied as a way to diagnose ankylosing spondylitis earlier. 
• Blood tests may include: 
• C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), also called “sed rate,” to look for inflammation
• Rheumatoid factor or antinuclear antibody test (ANA) to look for other types of arthritis or illness 
• A genetic test may help show if you have a gene (HLA-B27) often linked with AS. Many people who have the HLA-B27 gene won’t get AS. So, having this test won’t confirm that you have the condition. But the test results can be helpful if your symptoms and physical exam haven’t pointed to a clear diagnosis

Imaging of Musculoskeletal Disorders – Spondyloarthropathy

Key features

• Sacroiliitis
• Romanus lesions
• Syndesmophytes
• Ankylosis
• Ankylosing spondylitis has characteristic radiological features in a symmetric distribution
• The other spondyloarthropathies have similar features but are usually more asymmetric

The seronegative spondyloarthropathies most commonly affect the sacroiliac joints and the spine (seronegative = negative for rheumatoid factor and other autoimmune antibodies).

Ankylosing spondylitis is the most common seronegative spondyloarthropathy. It has characteristic radiological features. Similar radiological features may be seen in patients with other spondyloarthopathies such as psoriatic arthritis, reactive arthritis (formerly known as ‘Reiter’s disease’), or enteropathic spondyloarthropathy (spondyloarthropathy in patients with inflammatory bowel disease). Ankylosing spondylitis tends to be symmetrical whereas the other spondyloarthropathies tend to be more asymmetric.

All these diseases are characterised by inflammation of the entheses; the point at which ligaments and tendons connect to bone. The axial skeleton is most commonly affected, but the small and large joints of the appendicular skeleton may also be affected.

Sacroiliitis

Ankylosing spondylitis most commonly affects the sacroiliac joints first. Early changes of sacroiliitis (inflammation of the sacroiliac joints) are not visible on plain X-rays and so MRI is frequently employed in the early diagnosis of seronegative spondyloarthropathies.

Sacroiliitis – MRI

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Sacroiliitis – MRI

• Asterisks = Iliac bones
• These MRI images show decreased fat signal (T1 image) and increased fluid signal (STIR image) due to bone oedema adjacent to the sacroiliac joints bilaterally
• These are typical features of an active sacroiliitis
• MRI evidence of sacroiliitis supports the diagnosis of ankylosing spondylitis if this diagnosis is suspected clinically
• The plain X-rays were completely normal in this patient

Sacroiliitis – X-ray

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Sacroiliitis – X-ray

• Normal sacroiliac joints shown for comparison
• As sacroiliitis progresses the sacroiliac joints may widen and the articular surfaces become sclerotic

Sacroiliitis – Chronic

Chronic sacroiliitis due to a spondyloarthropathy can eventually lead to ankylosis (fusion) of the sacroiliac joints.

Sacroiliac joint fusion – X-ray

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Sacroiliac joint fusion – X-ray

• Normal sacroiliac joints shown for comparison
• On the lower image the sacroiliac joints are not visible due to ankylosis (joint fusion)

Spondyloarthropathy of the spine

‘Romanus lesions’ – which correspond to enthesitis at the insertion points of the longitudinal spinal ligaments – are the earliest sign of spondyloarthropathy affecting the spine. They can be detected with MRI much earlier than with X-ray.

On MRI Romanus lesions manifest as foci of bone oedema at the corners of the vertebral bodies. Over time the overlying cortical bone surface becomes sclerotic and so are visible as ‘shiny corners’ on plain X-ray images.

Romanus lesions

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Romanus lesions

• A T2 weighted (water sensitive) MRI image is shown next to the plain X-ray
• The plain X-ray shows sclerosis at the corners of two vertebral bodies
• These ‘shiny corners’ are chronic Romanus lesions – they are not clearly visible on the MRI as sclerosis appears black on all types of MRI images
• The MRI image shows multiple small foci of high signal (fluid) in the bone marrow of the adjacent vertebral body corners (arrowheads)
• This fluid represents bone marrow oedema caused by enthesitis at the point of insertion of the longitudinal spinal ligaments
• Several other foci of bone oedema seen at the corners of other vertebral body corners are due to developing Romanus lesions which are not yet visible on the plain X-ray

Ankylosis

Ankylosis (fusion of bones at a joint) is a late manifestation of ankylosing spondylitis.

Chronic inflammation at the entheses of the spine – the point of attachment of the ligaments of the spine on the vertebral bodies – results in formation of syndesmophytes. These have a different appearance from that of osteophytes seen in osteoarthritis; syndesmophytes form a smooth layer of calcification, whereas osteophytes are sharp bone spurs which stick out from their point of origin.

Syndesmophytes are sometimes referred to as ‘flowing’ as they flow smoothly across the surface of the vertebral bodies affected.

Ankylosis – Bamboo spine

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Ankylosis – Bamboo spine

• Normal C-spine shown for comparison
• Flowing syndesmophytes are seen fusing the cervical spine vertebral bodies anteriorly leading to the classic ‘bamboo spine’ sign – the fused spine resembles bamboo
• In this patient the facet joints of the spine have also fused

Large and small joint involvement

Large and small joints may also be involved in patients with seronegative spondyloarthropathies.

Psoriatic arthritis – hip involvement

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Psoriatic arthritis – hip involvement

• This young patient (25 years old) with psoriatic arthritis has severe narrowing of the hip joint space with large osteophytes and sub-cortical cysts
• The appearances are identical to changes seen in osteoarthritis, but onset is typically at a younger age and progression tends to be more rapid

Psoriatic arthritis – pencil-in-cup deformity

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Psoriatic arthritis – pencil-in-cup deformity

• Severe erosions may be seen in joints of the fingers and toes such that joints can be destroyed resulting in severe deformity
• The severe joint erosion in this patient’s finger progressed over a period of 4 years – erosion is seen in both the middle phalanx (MP) and the distal phalanx (DP) of the finger
• The middle phalanx is narrowed, like a pencil, and the distal phalanx is eroded centrally, like a cup, hence ‘pencil-in-cup’ deformity
• Note: Similar erosion may occur in a septic arthritis but progresses more rapidly

(PDF) Bamboo spine – X-ray findings of ankylosing spondylitis revisited

SAJR September 2012 Vol. 16 No. 3 111

Ankylosing spondylitis (AS) is one of the sero-negative spondylo-

arthropathies.

1

This group of arthritides is characterised by specific

skeletal imaging findings and, biochemically, by the absence of

rheumatoid factor or nodules, and the presence of the HLA-B27 gene.

These spondylo-arthropathies can be divided into 5 major groups: (i)

ankylosing spondylitis, (ii) reactive arthritis/Reiter’s syndrome, (iii)

arthritis associated with inflammatory bowel disease, (iv) psoriatic

arthritis and (v) undifferentiated spondylo-arthropathy.

1

AS is a debilitating disease, affecting mostly white men, with a

male:female ratio of about 6:1 within the age group 15 – 35 years of age.

Early lumbar axial ankylosis and spinal involvement is more marked

in male patients than female, with early radiographic signs of hip

involvement.

2-4

Classic joint involvement includes: bilateral sacro-iliac, thoraco-

lumbar and lumbo-sacral joints (early) and cervical spine (late).

5

The

peripheral skeleton is involved in 10 – 20% of cases, with apical fibrosis

of the lung parenchyma reported in only 1% of AS patients.

6

Additional

cardiac manifestations, such as aortic valve and root abnormalities, and

with conduction and rhythm abnormalities, have also been reported in

2 – 10% of patients.

6

Genetic susceptibility has been mentioned as a causative factor, with

96% of patients testing positive for the HLA-B27 gene.

1

Associated

diseases include: ulcerative colitis, iritis and aortic insufficiency.

Prognosis depends on age at first presentation, as well as the radiological

grade, as defined by either the Bath Ankylosing Spondylitis Radiology

Index (BASRI) – for cervical and lumbar spine and hips – or the

Modified New York Criteria for the Extent of Sacro-iliitis, with lumbar

and bilateral sacro-iliac joint involvement being marked in the early

years of the disease.

6

Pathology and imaging characteris-

tics

In this pictorial essay, we focus on the characteristic axial skeleton

imaging findings of AS, as it presents on conventional X-ray:

1

• florid anterior spondylitis (Romanus lesions)

• florid diskitis (Andersson lesions)

Ankylosing spondylitis is a debilitating disease that is one of the sero-

negative spondylarthropathies, affecting more males than females in

the proportion of about 6:1 in the age group 15 – 35 years of age. Early

radiographic findings include bilateral sacro-iliitis and early axial

(lower lumbar spine) ankylosis. Typical X-ray findings are florid

spondylitis (Romanus lesions), florid diskitis (Andersson lesions),

early axial ankylosis, enthesitis, syndesmophytes and insufficiency

fractures. Typical radiological abnormalities are pointed out on

conventional X-rays and reviewed for early diagnosis and prompt

treatment of patients at risk.

S Afr J Rad 2012;16(3):111-113. DOI:10.7196/SAJR.684

Bamboo spine – X-ray findings of ankylosing

spondylitis revisited

Antoinette Reinders, MB ChB

Matthys J van Wyk, MB ChB, FCRad Diag (SA)

Department of Diagnostic and Interventional Radiology, University of the Free State, Bloemfontein

Corresponding author: A Reinders ([email protected])

Fig 1. Lateral lumbar spine view. Note the ‘squaring’ of the lumbar vertebrae

(open arrowhead), together with the central radio-dense region in the vertebral

endplate of the 5th lumbar vertebra, superiorly (white arrowhead). This is

known as an Andersson lesion.

Sulfasalazine for ankylosing spondylitis (ankylosing spondylitis)

We reviewed the effect of sulfasalazine in people with ankylosing spondylitis. After searching for all relevant studies up to November 2013, we found 11 studies involving 895 people. Our results are summarized below.

A review found that in people with ankylosing spondylitis:

– Compared to simulated tablets (placebo), sulfasalazine probably has little or no difference in pain, disease activity, physical function, spinal mobility, and in global patient and physician assessment;

– Spinal injury visible on radiographs or on MRI (magnetic resonance imaging) has not been evaluated and therefore it is not known whether sulfasalazine slows down the injury.

– had side effects such as upset stomach, skin reactions / rashes and mouth ulcers;

– More people stopped taking sulfasalazine due to side effects than those who took the fake pill. and

– There is insufficient evidence to be sure of the benefits and harms of sulfasalazine for ankylosing spondylitis, and more research is needed.

What is ankylosing spondylitis and what is sulfasalazine?

Ankylosing spondylitis is a type of arthritis that usually occurs in the joints and ligaments of the spine. It can also affect the shoulders, hips, or other joints. Pain, stiffness, and restriction of movement in the back and other affected joints occur.

Main results of this review

Pain

– People who took sulfasalazine rated their pain 3 bars lower on a 0-100 scale after 3-36 months than those who took placebo (3% absolute improvement).

– People who took sulfasalazine rated their pain as 47 on a 0-100 scale after 3-36 months.

– People who took a placebo rated their pain 50 on a scale of 0 to 100 after 3-36 months.

Ankylosing spondylitis activity index (IASAS; BASDAI)

This outcome was not measured in these studies.

Index of function (functional disorders) in ankylosing spondylitis (IFAS; BASFI)

This outcome was not measured in these studies.

Metrological index of ankylosing spondylitis (MIAS; BASMI)

This outcome was not measured in these studies.

X-ray progression

This outcome was not measured in these studies.

Total number of dropouts due to adverse events

– 23 more people who took sulfasalazine dropped out due to adverse events than those who took placebo.

– 13 out of 100 people taking sulfasalazine dropped out due to adverse events.

– 9 out of 100 people who took fake pills (placebo) dropped out due to adverse events.

Serious adverse (unwanted) events

Only one person in 469 stopped taking sulfasalazine due to serious adverse events.

Identification of the gene for histocompatibility HLA-B27.Determination of the predisposition to the development of spondyloarthropathies (including ankylosing spondylitis

Identification of a genetic predisposition to spondyloarthritis, during which the HLA-B27 allele is determined using the polymerase chain reaction.

Russian synonyms

Identification of allele 27 of locus B of the main human histocompatibility complex, HLA-B 27 antigen.

English synonyms

Ankylosing spondylitis Histocompatibility Antigen, Ankylosing spondylitis Human Leukocyte Antigen.

Research method

Polymerase chain reaction (PCR).

Which biomaterial can be used for research?

Venous blood.

How to properly prepare for the study?

Do not smoke for 30 minutes prior to examination.

General information about the study

Spondyloarthritis is a group of inflammatory diseases of the axial skeleton with a pronounced genetic orientation.These include ankylosing spondylitis (ankylosing spondylitis), reactive arthritis (Reiter’s syndrome), psoriatic arthropathy and some other diseases. Most patients with spondyloarthritis are carriers of a particular allele of the B locus of the main human histocompatibility complex – HLA-B27. For screening, diagnosis, and prognosis of spondyloarthritis, a genetic study (typing) is performed to detect the presence or absence of the HLA-B27 allele.

About 8% of people are carriers of the HLA-B27 allele (HLA-B27-positive, in the literature you can also find the expression “carriers of the HLA-B27 antigen”).The prevalence of ankylosing spondylitis in HLA-B27-positive people is 1.3%. It occurs in 15-20% of HLA-B27-positive patients with a blood relative with ankylosing spondyloarthritis, which corresponds to a 16-fold increase in the risk of this disease in the presence of a burdened history. A positive HLA-B27 typing result increases the risk of developing any disease from the spondyloarthritis group by 20 times. Therefore, HLA-B27 typing can be used to assess the risk of developing spondyloarthritis.

In the differential diagnosis of articular syndrome, the presence of HLA-B27 is a characteristic feature of spondyloarthritis: this allele is present in 90-95% of patients with ankylosing spondyloarthritis, in 60-90% with reactive arthritis, in 50% with psoriatic arthropathy and 80-90% – with juvenile ankylosing spondylitis. The presence of HLA-B27 in patients with other diseases with joint damage (gout, rheumatoid arthritis, septic arthritis) does not exceed 7-8%. Typing HLA-B27 is especially useful when the diagnosis of the disease cannot be formulated on the basis of basic diagnostic criteria.

Typing HLA-B27 is of greatest importance in the diagnosis of early ankylosing spondylitis. In most cases, it takes 5-10 years between the first signs of the disease and the final diagnosis. This is due to the fact that the main diagnostic criterion is the X-ray signs of sacroiliitis, which develops only after several years of the inflammatory process in the sacroiliac joints. Patients with complaints of back pain without radiological signs of sacroiliitis do not actually get into the field of vision of a rheumatologist.Finding HLA-B27 in such a situation may be sufficient reason for referral to a specialist with a narrow profile. Typing is indicated when examining a patient with inflammatory pain in the back in the absence of radiological signs of sacroiliitis or when examining a patient with asymmetric oligoarthritis.

The presence of HLA-B27 is associated with an increased risk of extra-articular manifestations of ankylosing spondylitis. Of greatest importance are the associations of the HLA-B27 allele and acute anterior uveitis, aortic valve insufficiency, acute leukemia, IgA nephropathy, and psoriasis.HLA-B27-positive patients are more at risk for tuberculosis and malaria. On the other hand, the presence of HLA-B27 also plays a certain “protective” role: some viral infections (influenza, herpesvirus type 2, infectious mononucleosis, hepatitis C and HIV) are milder in carriers of HLA-B27.

It should be noted that there are other, both hereditary and acquired, risk factors for the development of spondyloarthritis. The absence of HLA-B27 does not contradict the diagnosis of ankylosing spondylitis, in which case it is classified as HLA-B27-negative and develops at a later age than HLA-B27-positive spondyloarthritis.

In addition, typing of HLA-B27 is carried out when making a prognosis of complications of rheumatoid arthritis. The presence of HLA-B27 is associated with a three-fold increased risk of atlanto-axial subluxation.

What is the research used for?

• For differential diagnosis of articular syndrome (seronegative spondyloarthritis, rheumatoid and septic arthritis, gout and others).
• For the screening, diagnosis and prognosis of ankylosing spondylitis.
• To assess the risk of developing atlanto-axial subluxation in rheumatoid arthritis.

When is the study scheduled?

• With articular syndrome: asymmetric oligoarthritis, especially in combination with pain in the lumbar region of the back of an inflammatory nature (morning stiffness for more than 1 hour, improvement with exercise, worsening at night) and signs of enthesitis.
• With a burdened hereditary history of ankylosing spondylitis.
• For rheumatoid arthritis.

What do the results mean?

Reference values: negative.

Positive result:

• occurs in 90-95% of patients with ankylosing spondyloarthritis and juvenile ankylosing spondyloarthritis,
• in 60-90% of patients with reactive arthritis,
• in 50% with psoriatic arthropathy,
• in 7-8% of people in the European population.

Negative result:

• is observed in 92-93% of people in the European population,
• in 10% of patients with ankylosing spondyloarthritis (HLA-B27-negative spondyloarthritis).

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Clinical Trial of Spondyloarthropathy: Methotrexate – Clinical Trial Registry

The established classification criteria for ankylosing spondylitis (BS) are based on radiological combination with no clinical symptoms below Grade 2 bilateral or Grade 3 unilateral It usually takes several years to obtain a specific x-ray.sacroiliitis to develop. The diagnosis of AS may be delayed up to 10 years after the onset of symptoms if the diagnosis is based on radiographic findings.

A group of leading experts in the field of spondyloarthropathies proposed in 2004 the term “axial spondyloarthritis” as an attempt to close the 5-10 year gap between the first symptoms and the diagnosis of AS (Rudwaleit et al. Ann Rheum Dis 2004; 63: 535-43). Using the proposed approach, early diagnosis of AS (or axial spondyloarthritis) can be performed using a high degree of confidence when there are at least two to three signs of spondyloarthritis (clinical findings, laboratory studies, or skeletal images).Magnetic resonance imaging (MRI) of the sacroiliac joints is proving to be a particularly useful tool in the diagnosis of early AS. Early diagnosis and treatment is likely to prevent structural damage and lead to improved functional outcomes.

Treatment of AS mainly consisted of non-steroidal anti-inflammatory drugs (NSAIDs). Most disease-modifying antirheumatic drugs are ineffective for axial manifestations. Sulfasalazine has some efficacy for peripheral symptoms.Tumor necrosis factor (TNF) alpha blocking drugs infliximab and etanercept are effective in both axial and peripheral manifestations of the disease. The consensus is that the onset of anti-TNF alpha therapy requires a definitive diagnosis of AS based on radiographic findings. sacroiliitis.

It is well known that oral methotrexate is effective and safe in the treatment of rheumatoid arthritis and psoriatic arthritis. However, there are no studies to prove its usefulness in the treatment of AS.To date, there have been three small randomized and controlled studies on this issue. No clarifications have been made on this issue. The dose of methotrexate used in these studies was low, only 7.5 to 10 mg per week. One of these studies has shown the benefit of active treatment group. There was no statistically significant benefit of methotrexate in the other two cases. research.

The aim of this study is to evaluate the efficacy of oral methotrexate in adults.with active axial spondyloarthritis. Subjects will be randomly assigned to Placebo or Methotrexate Treatment Groups. All subjects in the active treatment group receive at least 15 mg per week of oral methotrexate. For the reduction of mucous membranes, gastrointestinal tract and hematologic side effects of low doses of methotrexate. All subjects also received 5 mg of folic acid per week. A stable dose of NSAIDs is allowed during the study. The duration of the double-blind treatment period is 24 weeks.

Treatment efficacy is assessed by the reduction of signs and symptoms of axial spondyloarthritis at 12 and 24 weeks. If the primary outcome ASAS20 (AS score in the Response Criteria for Ankylosing Spondylitis, patient improvement of at least 20% of symptoms) is not observed at 12 weeks, the dose of methotrexate or the corresponding placebo can be increased to 20 mg per week for weeks 12 through 24.

Clinical history of anterior uveitis and its frequency during the study are also recorded.An ophthalmic examination is done at baseline and at 24 weeks.

Selected patients will have an MRI of the sacroiliac joints also at 24 weeks to evaluate changes in active inflammatory lesions detected by MRI.

An expanded radiological progression study is also planned. X-ray changes in the sacroiliac bone of the joints and lumbosacral spine will be assessed at baseline and after 3 and 5 years.

DIAGNOSTIC MARKERS OF RHEUMATOLOGICAL DISEASE – “InfoMedPharmDialogue”

Often, patients have an increased level of antibodies to antistreptolysin O, which are secreted by beta-hemolytic streptococcus group A. patients for consultation with a rheumatologist is impractical.

The second block of examinations, which should be performed in patients with suspected rheumatological diseases, are tests to identify additional markers of inflammation: ferritin, calprotectin, procalcitonin and D-dimer.And the focus has traditionally been on ferritin.

Ferritin reflects the level of iron deposition and at the same time serves as an indicator of the acute phase of inflammation. As mentioned above, an increase of more than 10 times in combination with leukocytosis is a characteristic sign of Still’s disease. It may also indicate the risk of macrophage activation syndrome in Still’s disease and SLE. It should be borne in mind that an increase in ferritin is a nonspecific marker of inflammation and can occur not only with CTD (for example, infectious diseases, incl.h. COVID-19).

An increase in procalcitonin (> 0.5 ng / ml) should also make one think about the infectious process.

The growth of creatinine phosphokinase in combination with a slight increase in transaminases and lactate dehydrogenase (ALT and AST) indicates the breakdown of longitudinal-transverse muscle fibers, which occurs, for example, in inflammatory myopathies, dermatopolymyositis.

Cholestasis syndrome, which can occur in rheumatologic patients, includes elevations in alkaline phosphatase and gamma-glutamyltransferase, cholesterol and direct bilirubin.It can occur while taking corticosteroids, as well as in the framework of autoimmune liver diseases.

D-dimer is primarily an indicator of thromboembolic events, but also a nonspecific marker that can increase against the background of infectious diseases, in persons of the older age group, in cancer and inflammatory processes.

Urinary syndrome – a complex of various changes in the composition of urinary sediment, serves as a very important indicator for the diagnosis of rheumatological diseases.However, it always requires the exclusion of a bacterial infection and an assessment of the degree of kidney involvement in the inflammatory process.

For this purpose, it is necessary to analyze two syndromes – nephrotic and nephritic. Nephrotic syndrome, which is characterized by proteinuria> 3.5 g / day, gravitationally distributing edema, can be detected in patients with SLE and vasculitis, as well as in amyloidosis and paraneoplastic nephritis. At the same time, erythrocyturia is not observed in patients. But micro- and macrohematuria appear in nephritic syndrome, which is also accompanied by proteinuria and the development of acute renal failure.This symptom complex is characteristic of lupus nephritis, ANCA-associated nephritis and vasculitis.

90,000 Bechterew’s disease (ankylosing spondylitis) – symptoms, treatment, diagnosis

Ankylosing spondylitis refers to systemic inflammatory diseases in which the spine is predominantly affected. The pathological process proceeding in the spine gradually leads to the fusion of individual vertebrae with each other (ankylosis), which results in the development of limiting the mobility of the spine.At the same time, ossification of the ligaments surrounding the spine occurs, and as a result, the spine loses its mobility to one degree or another.

The disease was first described by the Russian neurologist V. M. Bekhterev, which was fixed in the name. Mostly young men are ill (3-6 times more often than women). The peak incidence occurs in the age range of 25-35 years. It is believed that people over 45-50 years old get sick extremely rarely.

Causes of ankylosing spondylitis

The cause of this disease is unknown, but the hereditary factor is not denied (i.e.n. the gene for histocompatibility HLA-B27 is found in 90% of patients, although the presence of the gene does not mean that you will develop ankylosing spondylitis).

Symptoms of ankylosing spondylitis

Usually, the disease begins with the onset of gradual back pain, which eventually spreads to other parts of the spine. Pain can occur sporadically, but more often it is persistent and only temporarily decreases after taking medication. The nature of the pain has the following features:

• Pain worse at rest, especially in the second half of the night or in the morning;
• are accompanied by stiffness;
• decrease or disappear completely after exercise;
• are quickly stopped by taking non-steroidal anti-inflammatory drugs.

Posture is gradually changing: strengthening or straightening the physiological curves of the spine, the development of the so-called “supplicant” or “proud” posture, limitation of the mobility of the spine, respiratory excursion of the chest.

Patients with ankylosing spondylitis often develop lesions of other organs besides the spine: joints (arthritis, usually of the lower extremities, sternoclavicular joints) enthesitis (pain and inflammation at the attachment points of tendons), tenosynovitis (inflammation of the tendons), eyes (uveitis, iridocyclitis ).

Diagnostics

Laboratory tests: complete blood count (accelerated ESR), increased C-reactive protein. HLA-B27 study.

Instrumental methods. The most significant test for the diagnosis of ankylosing spondylitis is sacroiliitis (inflammation of the sacroiliac joints). Sacroiliitis is detected by radiography or magnetic resonance imaging (in the early stages).

Treatment of ankylosing spondylitis

It is carried out in several stages, therefore it requires an integrated approach and the availability of the necessary equipment in the medical center for diagnostics and rehabilitation programs.First of all, after confirming the diagnosis, the specialist will select means for relieving pain and stopping the inflammatory process. After a thorough analysis of the current state, it will be necessary to develop a program to restore the mobility of the spine and maintain it in a stable state.

To restore the mobility of the spine is a difficult task that requires not only high professionalism of the team of specialists, but also a responsible attitude of the patient – the treatment will take more than one month.Required:

• intra-articular and paravertebral administration of drugs;
• an individually designed regular exercise program;
• acupuncture, massage;
• and for severe, advanced forms – surgery (replacement of the joint with an artificial one, endoprosthetics).

It is difficult to collect all possible means for diagnostics and treatment under the guidance of proven and experienced specialists within one medical center, but we succeeded, so our patients receive all the necessary assistance in one place.

In the rheumatology center of the Federal Research Center of the Federal Medical and Biological Agency, much attention is paid to the professionalism of its employees: these are regular refresher courses and support for scientific research with subsequent publications; and inviting Russian and foreign colleagues to exchange experience. All modern methods of treatment are available to our patients, diagnostics is carried out using high-precision equipment, and specialists have successful experience in treating even advanced stages of ankylosing spondylitis. But of course, you should not delay making an appointment for a consultation with a doctor: the sooner people come to us with complaints of pain in the spine, the more favorable the prognosis of treatment and recovery with a confirmed diagnosis.

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With ankylosing spondylitis, a higher level of inflammation is observed than with radiologically unconfirmed axial spondylitis

Ankylosing spondylitis (AS) and radiologically unconfirmed axial spondyloarthritis are forms of axial sponliditis (SpA). It is characterized by chronic inflammatory arthritis of the spine and sacroiliac joints with minor differences in diagnosis.These differences include structural changes in the sacroiliac joints and the spine, which are observed only in patients with AS.

According to a recent study, patients with AS have a higher level of inflammation and a higher proportion of male patients compared with patients with radiologically unconfirmed axial SpA. The ratio of other factors, such as disease activity, physical activity and health status, is comparable.

To determine the differences between these groups, the scientists performed a study involving 100 consecutive patients with axial spondylitis who had not previously received tumor necrosis factor (TNF) antagonists. A comparison was made between the data of these patients. The analysis of the data looked at factors such as patient-reported outcomes, the level and type of inflammation, and structural changes. These indicators were measured using certain diagnostic methods, such as analysis of inflammation by the level of C-reactive protein (CRP), inflammation of the spine according to MRI and structural changes according to a conventional X-ray.

In 56 out of 100 patients, AS was diagnosed, and in the rest – radiologically unconfirmed axial SpA. CRP levels and disease activity index (DAS) were higher in patients with AS than in patients with radiologically unconfirmed axial SpA. In addition, the foci of inflammation according to MRI were also observed only in patients with AS. In addition, AS was more pronounced in men than in women.

In general, it can be assumed that patients with radiologically unconfirmed axial SpA should not be classified as patients with radiologically unconfirmed AS, but rather as a dead-end subgroup of SpA with symptoms very similar to those of advanced AS.This form of the disease was more pronounced in women, with a higher level of functioning and less structural damage. Nevertheless, the data obtained confirmed the feasibility of including patients with radiologically unconfirmed axial SpA in the new recommendations when using antibodies to TNF, since the adverse consequences of the disease were largely comparable in patients with radiologically unconfirmed axial SpA and AS at a late stage.