The Assessment of SpondyloArthritis International Society (ASAS) has developed the concept of axial spondyloarthritis (SpA) in 2009. The symptoms and burden of disease of nonradiographic axial SpA and Ankylosing Spondylitis (AS) are similar and both can affect multiple organs and systems. Assessment and monitoring in SpA are, therefore, crucial. Different instruments have been developed for assessing and monitoring the wide variety of presentations in SpA. Generally, disease monitoring of patients can include patient reported outcome, clinical findings, laboratory tests, imaging, and disease activity composite scores.
Spondyloarthritis (SpA) is an umbrella term consisting of a group of inflammatory diseases involving both the joints and the entheses. Its prototype is ankylosing spondylitis (AS).
Other included diseases are psoriatic arthritis, inflammatory bowel disease related SpA, undifferentiated SpA, and reactive arthritis.
The modified New York Criteria in 1984 requires the presence of both clinical criteria and radiologic sacroiliitis to diagnose AS. However, it was found that radiologic sacroiliitis was a late finding in the disease course of many patients. Patients can have the classical clinical pattern but with normal radiographs. Magnetic resonance imaging (MRI) shows signs of inflammation earlier than structural changes demonstrated on radiographs. Therefore, the Assessment of SpondyloArthritis international Society (ASAS) developed the concept of axial SpA for earlier diagnosis. Nowadays, it is important for earlier diagnosis1 particularly with the introduction of vast biologics, which can retard radiologic progression, and for patients who have poor prognostic factor such as smoker,2 human leukocyte antigen (HLA) B27 positivity,3 male,3 and elevated C-reactive protein (CRP). The term “axial SpA” comprises the spectrum of patients with radiographic sacroiliitis (AS or radiographic axial SpA) and without radiographic sacroiliitis (nonradiographic axial SpA).
SpA is a systemic disease giving rise to various signs and symptoms. Disease monitoring should, hence, include a wide variety of instruments. Generally, disease monitoring of patients should include patient-reported outcome, clinical findings, laboratory tests, imaging, and disease activity composite scores.
1 Patient reported outcome
Similar to other rheumatologic diseases, patient-reported outcomes play a major part of the assessment of the disease.
1.1 Physical Function
Physical function in axial SpA is measured most commonly by the Bath Ankylosing Spondylitis Functional Index (BASFI).4 It comprises 10 questions, in which 8 of them refer to functional anatomy and the remaining 2 refer to the ability to cope with daily living. Questions are rated on numerical rating scale (NRS) or on a 10-cm visual analog scale (VAS). The BASFI score is calculated on the average of these 10 questions. The BASFI score has been well validated by comparing with instruments measuring similar constructs.5
1.2 Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been the preferred tool for disease activity assessment in patients with SpA since its development. It is easy to administer and interpret. It involves six items based on levels of back pain, fatigue, peripheral joint pain and swelling, localized tenderness, and the duration and severity of morning stiffness.
Patients report on a numeric response scale of 0–10 or by 0- to 10-cm VAS while duration of morning stiffness is anchored by a time scale of 0–2 or more hours. BASDAI is an entirely patient-generated index and does not include any objective measurements.
1.3 Spinal Stiffness, pain and fatigue
Symptoms of spinal stiffness, pain, and fatigue are reported by patients based on an NRS or alternatively on a 10-cm VAS.
2 Clinical Findings
The most common presentation for patients with SpA is axial stiffness, affecting their mobility and daily living. Enthesitis and peripheral arthritis are also not uncommon. Detailed physical examination during each visit is crucial for the overview assessment for patients with SpA.
2.1 Spinal Mobility
For spinal mobility, ASAS has recommended to assess chest expansion, modified Schober’s test, occiput-to-wall distance, cervical rotation, and lateral spinal flexion. The Bath Ankylosing Spondylitis Metrology Index (BASMI) is an alternative instrument that includes the modified Schober’s test, cervical rotation, tragus-to-wall distance, lateral spinal flexion, and intermalleolar distance. In the original instrument BASMI called BASMI-2, each continuous assessment was converted into a nominal score of 0, 1, or 2. The second version BASMI10 was developed, in which the individual assessment was scored between 0 and 10. The linear version, BASMI10, was developed subsequently and was found to be more sensitive to changes.6 It is calculated by having each continuous assessment converted into a linear scale using equations. The final BASMI10 score is the mean of the five linear scores ranging from 0 to 10.
2.2 Peripheral Arthritis and Enthesitis
It is common for patients with axial SpA to have peripheral joint involvement. Tender and swollen joints can be assessed using the 44-joint count.
Enthesitis is a characteristic feature of axial SpA. Different instruments have been developed for assessment. The first known instrument is the Mander enthesitis index (MEI).7 Patients’ response to pain following local pressure to 66 entheseal sites are scored on a scale of 0–3, with 0 = no pain, 1 = mild tenderness, 2 = moderate tenderness, or 3 = tenderness that is severe enough to withdraw. However, the MEI based on the 66 sites is time consuming and not feasible. Other instruments including the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES),8 which is based on 13 entheseal sites scored on a dichotomous basis, are a much simpler method. These focus mainly on the most commonly affected entheseal sites, which are the bilateral first and seventh costochondral joints, the anterior and posterior superior iliac spines, the iliac crests, the fifth lumbar spinous process, and the insertion of the Achilles tendon into the calcaneus. In 2009, the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index9 was developed and validated according to the essential criteria of the Outcome Measures in Rheumatology (OMERACT) filter: truth, discrimination, and feasibility. It focuses on 16 sites: bilateral greater trochanter, bilateral quadriceps tendon insertion into the patella, bilateral patellar ligament insertion into the tibial tuberosity and patella, bilateral Achilles tendon insertion, bilateral plantar fascia insertion, bilateral medial and lateral epicondyles, and bilateral supraspinatus insertion into the greater tuberosity of humerus.
3 Laboratory Tests
Laboratory abnormalities for SpA are usually nonspecific and do not correlate well with the disease activity. Not every patient with SpA may have elevated CRP and erythrocyte sedimentation rate (ESR). One study compared the levels of CRP and ESR in patients with recent onset of inflammatory back pain of less than 2 years who met the classification criteria for axial SpA with patients who were diagnosed to have mechanical back pain. It was found that the levels of the acute phase reactants were not statistically different between the 2 groups.10 However, CRP may have a role in screening for axial-joint and inflammation11 and also an independent predictor of bone ankylosis.12
The HLA-B27 genetic marker has been the most commonly used biomarker for diagnosing SpA. The prevalence of HLA-B27 in Chinese patients with AS is about 95%.13 Patients who have family members with SpA who are HLA-B*27 positive have a 5- to 16-fold increase in the risk of developing AS if they are also HLA-B27 positive.14 However, 5% of the general population with HLA-B27 positivity will develop SpA.15 Therefore, HLA-B*27 cannot be used as a screening test. Patients with HLA-B27 may be associated with an earlier onset of inflammatory back pain and axial inflammation and radiographic damage of the SI joint.
4.1 Conventional radiography
The hallmark of AS is erosion and ankylosis of the sacroiliac joints. Early radiographic changes usually predominate on the iliac side of the SI joint with erosion of subchondral bone, resulting in loss of definition of articular surfaces with surrounding reactive sclerosis. Bone erosion will result in radiographic focal joint space widening. Ultimately, new bone formation fills in the erosions and the joint space, leading to fusion and ankylosis of the SI joints. The New York Criteria16 has classified the severity of sacroiliac joint changes into 5 stages: Stage 0 with normal findings of the SI joints; Stage 1 with suspicious changes such as blurring of the joint margin; Stage 2 with minimal areas of erosions or sclerosis without alteration in the joint width; Stage 3 with erosion, sclerosis, widening, narrowing, or partial fusion of the SI joints; and Stage 4 with complete ankylosis of the joints.
The earliest radiographic change in the spine is most commonly due to enthesitis at the disco-vertebral joint edges. Focal sclerosis (Shiny corners) and erosions (Romanus lesion) develop over the anterior corner of the vertebral endplates. The anterior borders may appear “squared” as new bone from periosteal proliferation fill in the normal concavity over the vertebral margins. As time goes by, bony spurs called syndesmophytes start to develop over these areas because of ossification within the annulus fibrosus of the intervertebral disc. With progressive growth of syndesmophytes, ankylosis and bridging of the intervertebral disc occur, producing the characteristic “bamboo spine” contour. Plain radiography is the tool for detecting structural changes.
Different scoring methods have been developed to assess and quantify the radiographic changes in the spine: the Stoke Ankylosing Spondylitis Spine Score (SASSS), Bath AS Radiology Index (BASRI) and the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). A comparative study has shown that all methods were reliable yet mSASSS has shown the best reliability and sensitivity to changes.17 The mSASSS is a composite index characterizing radiographic changes in the cervical and lumbar spine. In the lateral X-rays of the cervical and lumbar spines, a total of 24 sites are scored, that is, the anterior corners of the vertebrae from the lower border of C2 to the upper border of T1 and from the lower border of T12 to the upper border of S1. Each corner will be scored from 0 to 3: 0 being normal; 1 for the presence of erosion, sclerosis, or squaring of the anterior corner; 2 for the presence of syndesmophytes; and 3 for the presence of complete bridging. The total mSASSS score is calculated by the sum of the individual scores at each vertebral level. More recently, a new scoring system, the Radiographic Ankylosing Spondylitis Spinal Spore (RASSS), has been developed, which includes four lower thoracic vertebrae as it was hypothesized that most radiographic progression is found in this area. The scoring method is similar to that of mSASSS. However, it was found that the contribution of the thoracic vertebrae is negligible and the additional scoring efforts were not justified.18 The mSASSS is still the most commonly used scoring method for the spine in SpA.
4.2 Magnetic Resonance Imaging (MRI)
Plain conventional radiographs detect structural changes in the spine and SI joints that may not be apparent in the early course of the disease, resulting in a delay of diagnosis with around 7–10 years.19 MRI is more sensitive to inflammation and has a role in detecting disease activity. It has the capability to reveal early diagnosis that could not be detected on plain radiographs. It also involves no ionizing radiation but the cost is higher and less readily available than radiography.
T1-weighted (T1W) imaging sequence allows good visualization of anatomical structures, detection of chronic structural changes, and fatty changes. With the injection of intravenous contrast, inflamed tissue such as the synovium will be visualized as hyperintense signals. T2-weighted fat suppressed (T2wFS) and short tau inversion recovery (STIR) are the methods used for detecting the active inflammation even without the need of contrast injection. Water is depicted as hyperintense signals, and hence, active bone marrow edema will be detected as hyperintense lesions. Sacroiliitis on MRI has been defined as one of the two imaging criteria in the ASAS classification criteria for axial SpA. Active sacroiliitis is denied as the presence of active inflammatory signal on at least two consecutive MRI slices; if there is more than one signal on a single slice, then one slice may be sufficient for diagnosis.
Several instruments have been developed for the assessment of MRI changes in the SI joints and spine. The three most commonly used scoring systems are the Ankylosing Spondylitis spine Magnetic Resonance Imaging activity (ASspiMRI-a) score, the Berlin modification of the ASspiMRI-a score, and the SPARCC scoring system. The SPARCC method has been shown to have the highest sensitivity to change and the highest reliability.20
The SPARCC MRI spinal inflammation index is based on a disco-vertebral unit (DVU), which is the region between two imaginary lines drawn through the middle of two adjacent vertebras. Six of the most severely affected DVUs will be selected for scoring. For each detected lesion, three consecutive sagittal slices will be assessed in order to evaluate the extent of inflammation in three dimensions. The presence of an increased MRI STIR signal in the four quadrants of the DVU will be scored on a dichotomous basis, with 1 being the presence of signal and 0 being the absence of signal. For signals that exhibit comparable intensity to cerebrospinal fluid, an additional score for “intensity” will be given. For signals that occupy a continuous depth of ≥1 cm extending from the endplate, additional score for “depth” will be given. The SPARCC spinal score will be the sum of the scores from these six slices.
The SPARCC scoring method for the SI joints also relies on the increase in STIR signal in the joint, which is suggestive of bone marrow edema. Six coronal slices of the SI joint with the greatest signal intensity will be selected. Each SI joint is divided into four quadrants. The presence of increased signal is scored on a dichotomous basis. An additional score for “intensity,” if the signal intensity is comparable to the perisacral veins and an additional score for “depth,” is given if the lesion extends for a depth of at least 1 cm from the articular surface. The total SPARCC SI joint score will be the sum of the scores from these six slices.
However, MRI cannot be used as the gold standard for diagnosis of SpA because of its limitation in specificity and sensitivity. Several studies have shown that a sizable proportion of non-SpA patients who have mechanical back pain may also present with bone marrow edema in the SI joints. A reported prevalence of 27% in healthy individuals and patients with mechanical back pain were noted.21 Also, bone marrow edema in vertebral corners was noted in 26% of healthy controls.22 MRI lesions in patients with SpA may also fluctuate from time to time. Studies have shown that sensitivity of MRI in detecting suspected early SpA was at best 50%.23 Contextual interpretation of structural damage depicted by T1W images with active inflammatory lesions depicted by STIR sequence may improve and increase the diagnostic utility of MRI.24
5 Disease Activity Composite Scores
Similar to other rheumatologic diseases, it is crucial for the development of a disease activity composite index that can encompass the wide range of presentations and measures in SpA. The well-known BASDAI, which is an entirely patient-reported index mentioned earlier, and the latest Ankylosing Spondylitis Disease Activity Index (ASDAS) are the most commonly used indices for disease activity measurement.
Ankylosing Spondylitis Disease Activity Index (ASDAS) Given that BASDAI is a subjective score that may be affected by many other factors resulting in back pain in patients with SpA such as the co-existence of fibromyalgia, ASAS developed a new index for measuring the disease activity in patients with AS in 2009.25
ASDAS combines both patient-reported outcomes and objective parameters. It encompasses five disease activity variables including back pain, duration of morning stiffness, patient global assessment of disease activity, pain, and swelling in peripheral joints and either ESR or CRP. The ASAS has selected the ASDAS-CRP as the preferred version and the ASDAS-ESR as the alternative version. ASDAS has shown to be longitudinally associated with radiographic progression in AS. The effect of disease activity on radiographic progression is stronger in the early phase of disease.26
It has been shown that ASDAS correlated better with patient and physicians’ level of disease activity.27 Also, it has been shown to have a longitudinal relationship with the radiographic progression in the spine, whereas such relationship has not been proven for BASDAI alone.18
ASAS has formally validated the cutoff levels for disease activity states: an ASDAS value below 1.3 is considered low disease activity, between 1.3 and 2.1 as moderate disease activity, between 2.1 and 3.5 as high disease activity, and above 3.5 as very high disease activity.28
ASAS has defined response criteria based on the ASDAS score. The ASDAS improvement criteria states that a change in the score of at least 1.1 units signifies “clinically important improvement” and a change of at least 2 units suggests “major improvement.” A value below 1.3 units is considered “inactive disease.”
SpA is a “systemic disease” with a wide variety of presentations. Many instruments have been developed to assess the disease in different aspects. Assessing the disease in the aspect of patient-reported outcomes, clinical findings, laboratory tests, imaging, and disease activity composite scores can help one to better understand the disease, to aid earlier diagnosis, to initiate appropriate treatment at an appropriate time, and to monitor the disease course.
Chung HY Lau CS Wu KP Wong WS Mok MY. Comparison of performance of the Assessment of SpondyloArthritis International Society the European Spondyloarthropathy Study Group and the modified New York criteria in a cohort of Chinese patients with spondyloarthritis. Clin Rheumatol. 2011 Jul; 30(7): 947-53.
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Chung HY, Lau CS, Wu KP, Wong WS, Mok MY. Comparison of performance of the Assessment of SpondyloArthritis International Society, the European Spondyloarthropathy Study Group and the modified New York criteria in a cohort of Chinese patients with spondyloarthritis. Clin Rheumatol. 2011 Jul; 30(7): 947-53.)| false 10.1007/s10067-011-1693-6
Chung HY Machado P van der Heijde D D’Agostino MA Dougados M. Smokers in early axial spondyloarthritis have earlier disease onset more disease activity inflammation and damage and poorer function and health-related quality of life: results from the DESIR cohort. Ann Rheum Dis. 2012 Jun;71(6):809-16.
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Chung HY, Machado P, van der Heijde D, D’Agostino MA, Dougados M. Smokers in early axial spondyloarthritis have earlier disease onset, more disease activity, inflammation and damage, and poorer function and health-related quality of life: results from the DESIR cohort. Ann Rheum Dis. 2012 Jun;71(6):809-16.)| false 10.1136/annrheumdis-2011-200180
Chung HY Machado P van der Heijde D D’Agostino MA Dougados M. HLA-B27 positive patients differ from HLA-B27 negative patients in clinical presentation and imaging: results from the DESIR cohort of patients with recent onset axial spondyloarthritis. Ann Rheum Dis. 2011 Nov;70(11):1930-6.
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Chung HY, Machado P, van der Heijde D, D’Agostino MA, Dougados M. HLA-B27 positive patients differ from HLA-B27 negative patients in clinical presentation and imaging: results from the DESIR cohort of patients with recent onset axial spondyloarthritis. Ann Rheum Dis. 2011 Nov;70(11):1930-6.)| false 10.1136/ard.2011.152975
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van der Heijde, D., Deodhar, A., Inman, R. D., Braun, J., Hsu, B. and Mack, M. (2012), Comparison of three methods for calculating the Bath Ankylosing Spondylitis Metrology Index in a randomized placebo‐controlled study. Arthritis Care Res, 64: 1919-1922)| false 10.1002/acr.21771
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Maksymowych WP Mallon C Morrow S Shojania K Olszynski WP Wong RL Sampalis J Conner-Spady B. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009 Jun;68(6):948-53.
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Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, Sampalis J, Conner-Spady B. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009 Jun;68(6):948-53.)| false 10.1136/ard.2007.084244
Turina MC Yeremenko N van Gaalen F van Oosterhout M Berg IJ Ramonda R Lebre CM Landewé R Baeten D. Serum inflammatory biomarkers fail to identify early axial spondyloarthritis: results from the SpondyloArthritis Caught Early (SPACE) cohort. RMD Open. 2017 Jan 11;3(1):e000319.
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Turina MC, Yeremenko N, van Gaalen F, van Oosterhout M, Berg IJ, Ramonda R, Lebre CM, Landewé R, Baeten D. Serum inflammatory biomarkers fail to identify early axial spondyloarthritis: results from the SpondyloArthritis Caught Early (SPACE) cohort. RMD Open. 2017 Jan 11;3(1):e000319.)| false 10.1136/rmdopen-2016-000319
Tsang HHL Chung HY. The Discriminative Values of the Bath Ankylosing Spondylitis Disease Activity Index Ankylosing Spondylitis Disease Activity Score C-Reactive Protein and Erythrocyte Sedimentation Rate in Spondyloarthritis-Related Axial Arthritis. J Clin Rheumatol. 2017 Aug;23(5):267-272.
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Tsang HHL, Chung HY. The Discriminative Values of the Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Disease Activity Score, C-Reactive Protein, and Erythrocyte Sedimentation Rate in Spondyloarthritis-Related Axial Arthritis. J Clin Rheumatol. 2017 Aug;23(5):267-272.)| false 10.1097/RHU.0000000000000522
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Ramiro, Sofia & Tubergen, Astrid & Stolwijk, Carmen &Landewé, Robert & Van den Bosch, Filip & Dougados, Maxime & van der Heijde, Desiree. (2013). Scoring radiographic progression in ankylosing spondylitis: Should we use the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) or the Radiographic Ankylosing Spondylitis Spinal Score (RASSS)?. Arthritis research & therapy. 15. R14. 10.1186/ar4144.)| false 23327723
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Marzo-Ortega H, McGonagle D, O’Connor P, Hensor EM, Bennett AN, Green MJ, Emery P. Baseline and 1-year magnetic resonance imaging of the sacroiliac joint and lumbar spine in very early inflammatory back pain. Relationship between symptoms, HLA-B27 and disease extent and persistence. Ann Rheum Dis. 2009. Nov;68(11):1721-7.)| false 10.1136/ard.2008.097931
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Weber U, Hodler J, Kubik RA, Rufibach K, Lambert RG, Kissling RO, Pfirrmann, CW, Maksymowych WP. Sensitivity and specificity of spinal inflammatory lesions assessed by whole-body magnetic resonance imaging in patients with ankylosing spondylitis or recent-onset inflammatory back pain. Arthritis Rheum. 2009 Jul 15;61(7):900-8.)| false 10.1002/art.24507
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Weber U, Lambert RG, Østergaard M, Hodler J, Pedersen SJ, Maksymowych WP. The diagnostic utility of magnetic resonance imaging in spondylarthritis: an international multicenter evaluation of one hundred eighty-seven subjects. Arthritis Rheum. 2010 Oct;62(10):3048-58.)| false 10.1002/art.27571
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Ramiro S, van der Heijde D, van Tubergen A, et al Higher disease activity leads to more structural damage in the spine in ankylosing spondylitis: 12-year longitudinal data from the OASIS cohort. Annals of the Rheumatic Diseases 2014;73:1455-1461.)| false 24812292 10.1136/annrheumdis-2014-205178
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