New tools for diagnosing spondyloarthropathy

Joint Bone Spine 77 (2010) 108–114

Review

New tools for diagnosing spondyloarthropathy Samira Rostom ∗ , Maxime Dougados , Laure Gossec UPRES-EA 4058, département de rhumatologie B, faculté de médecine, hôpital Cochin, AP–HP, université Paris-Descartes, 27, rue du Faubourg-St-Jacques, 75014 Paris, France

a r t i c l e

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Article history: Accepted 13 July 2009 Available online 12 February 2010 Keywords: Spondylarthropathies Ankylosing spondylitis Early diagnosis Diagnosis Criteria Classification Criteria

a b s t r a c t Ankylosing spondylitis (AS) in its established and early forms accounts for more than 5% of all cases of chronic low back pain. Attention has focused recently on decreasing the time from symptom onset to the diagnosis of AS, which currently ranges from five to 10 years. An earlier diagnosis would lead to improved management, in particular thanks to the recent introduction and continuing development of biotherapies, such as TNF␣ antagonists, and new imaging techniques, including Doppler ultrasonography and magnetic resonance imaging have proved capable of detecting early signs of AS. Biotherapies not only improve the symptoms, but may also slow or halt the progression of the inflammatory lesions before the development of radiographic changes. Current criteria for AS (New York, Amor, and ESSG) are classification criteria that provide useful diagnostic orientation in clinical practice but have inadequate sensitivity for the diagnosis of recent-onset AS. Several groups have been working on means of improving the early diagnosis of AS. An algorithm for the early diagnosis of axial AS developed by Rudwaleit et al. needs to be confirmed by prospective studies. The Assessment of SpondyloArthritis international Society (ASAS) has just issued new diagnostic criteria for AS that performed well in a large cohort of patients with recent-onset low back pain. © 2010 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie.

1. Introduction Ankylosing spondylitis (AS) is among the most common inflammatory joint diseases, with a prevalence of 0.2% to 1.2% in Caucasian European populations [1]. In France, the estimated prevalence of AS is 0.34% [2]. AS is one of the spondyloarthropathies (SpAs), a family of diseases that also includes reactive arthritis, chronic inflammatory bowel disease with arthropathy, psoriatic arthritis, and undifferentiated spondyloarthropathy [3]. AS and undifferentiated SpA are the most common SpAs [4–6]. All SpAs can progress to AS. The diagnosis of AS is often made late, the interval from symptom onset to the diagnosis being five to 11 years in several studies [7,8]. Several factors explain this long time to diagnosis. First, the radiographic changes that constitute a major diagnostic criterion develop late in the course of the disease. Second, the presenting symptoms lack specificity; thus, low back pain is the most common presenting symptom. Third, many physicians have inadequate knowledge about AS and underestimate the prevalence of the disease [3,9]. Finally, the criteria used to diagnose AS may lack sensitivity at the early stages of the disease.

∗ Corresponding author. E-mail address: [email protected] (S. Rostom).

The last few years have witnessed considerable progress in the diagnosis and treatment of SpAs. Tools are now available for establishing the diagnosis at an early stage, when appropriate treatment may be able to control the inflammatory process, limit the functional impairments, and improve quality of life. The main advances are the use of magnetic resonance imaging (MRI) to assess the sacroiliac joints and spine, the use of Doppler ultrasonography, and the administration of TNF␣ antagonists to treat SpAs. TNF␣ antagonists not only control the inflammatory process, but also reverse the inflammatory lesions before the development of radiographic changes, even at the stage of undifferentiated SpA. In patients with established SpA, TNF␣ antagonists can lessen the inflammation, but their ability to slow the progression of the structural damage is a matter of considerable debate, as studies suggest uncoupling of inflammation, bone loss, and ossification. Therefore, the early detection and treatment of SpAs is crucial. A new diagnostic approach based on symptoms, laboratory test results, and imaging study findings has been developed to improve the early diagnosis of SpAs [10]. The objective of this paper was to discuss available tools for diagnosing SpAs, based on an extensive literature review. We will discuss existing classification criteria, evaluations of the new Berlin diagnostic criteria and of the criteria issued very recently by the Assessment of SpondyloArthritis international Society (ASAS), and the main parameters that can assist in the early diagnosis of SpAs.

1297-319X/$ – see front matter © 2010 Published by Elsevier Masson SAS on behalf of the Société Française de Rhumatologie. doi:10.1016/j.jbspin.2009.12.005

S. Rostom et al. / Joint Bone Spine 77 (2010) 108–114 Table 1 Amor’s classification criteria for spondyloarthropathy (1990) [11]. Clinical symptoms or past history Clinical symptoms Lumbar or dorsal pain at night or morning stiffness in the lumbar or dorsal region Asymmetric oligoarthritis Buttock pain, unspecified Alternating buttock pain Sausage digit Heel pain or other enthesopathy Iritis Nongonococcal urethritis or cervicitis within 1 month before the onset of arthritis Acute diarrhea within 1 month before the onset of arthritis Past or current psoriasis and/or balanitis Radiographic findings Sacroiliitis (bilateral grade >2 or unilateral grade 3) Genetic background Presence of HLA B27 and/or family history of ankylosing spondylitis, reactive arthritis, psoriasis, uveitis, or chronic inflammatory bowel disease Response to treatment Clear-cut improvement within 48 h after NSAID intake or rapid relapse of the pain (within 48 h) after NSAID discontinuation

Points

Table 2 European Spondylarthropathy Study Group (ESSG) classification criteria for spondyloarthropathy (1991) [12]. Inflammatory spinal pain

Past or present pain in the lumbar, thoracic, or cervical spine having at least four of the characteristics listed below Onset before 45 years of age Insidious onset Improved by exercise Accompanied with morning stiffness Of at least 3 months’ duration

Synovitis

Asymmetric or predominantly affecting the lower limbs, past or current

Family history

Presence in first- or second-degree relatives of at least one of the conditions listed below: Ankylosing spondylitis Psoriasis Anterior uveitis Reactive arthritis Inflammatory bowel disease

Psoriasis

Past or current psoriasis diagnosed by a physician

Inflammatory bowel disease

Past or current Crohn’s disease or ulcerative colitis diagnosed by a physician and confirmed by imaging studies or endoscopy

Urethritis, cervicitis, or acute diarrhea within 1 months before the onset of arthritis

Episode of diarrhea or of nongonococcal urethritis or cervicitis within the month preceding the onset of arthritis

Alternating buttock pain

Past or current buttock pain alternating between the right and left sides

Enthesopathy

Past or current spontaneous pain or tenderness to palpation at the site of insertion of the Achilles tendon or plantar fascia

Sacroiliitis

Bilateral grade 2 to 4 or unilateral grade 3 or 4 sacroiliitis; the grades are defined as follows: 0, normal; 1, possible; 2, minimal; 3, moderate; and 4, ankylosis

1 2 1 2 2 2 2 1 1 2 3 2 2

2

A patient is considered to have SpA if the total number of points is 6 or more.

2. Existing criteria 2.1. The concept of spondyloarthropathy and spondyloarthritis The spondyloarthropathies constitute a heterogeneous group of diseases that includes AS, arthritis related to chronic inflammatory bowel disease (Crohn’s disease and ulcerative colitis), psoriatic arthritis, reactive arthritis, and SAPHO, as well as juvenile-onset SpA and undifferentiated SpA [1]. Patients who have SpA with inflammatory back pain usually progress to AS. Two examples of classification criteria for SpAs are Amor’s criteria [11] and the criteria developed by the European Spondylarthropathy Study Group (ESSG) [12] (Tables 1 and 2). Amor’s criteria are a list of signs, none of which must be present to classify the disease as SpA. Instead, a patient with any of the signs should be examined for the presence of other signs. Some signs contribute 1 point and others 2 points, and a score of 6 or more classifies the patient as having SpA. With the ESSG criteria, in contrast, inflammatory low back pain and/or peripheral arthritis are required. Patients having at least one major criterion and one minor criterion are classified as having SpA. The name AS reflects the most striking feature of the disease, which is ankylosis of the spine. However, this feature takes several years to develop. The modified New York criteria can be used to classify AS patients based on sacroiliac joint involvement. According to the modified New York criteria, radiological bilateral sacroiliitis grade 2 or higher or radiological unilateral sacroiliitis grade 3 or 4 classifies the patient as having definite AS (Table 3) [13]. At present, the term “spondyloarthritis” is being increasingly used [14], as some patients with AS have no ankylosis and often no radiographic sacroiliitis despite clinical axial symptoms and MRI evidence of inflammation of the sacroiliac joints and spine. Thus, spondyloarthritis is SpA with axial involvement but with or without radiographic sacroiliitis and/or syndesmophytes. Recently, a new approach has been developed by several groups to improve the early diagnosis of SpA based on a combination of symptoms, laboratory test results, and imaging study findings. Establishing the diagnosis of SpA at an early stage is a major challenge for clinicians today. Recent-onset SpA shares similarities with spondyloarthritis, as there are no radiographic changes and the use

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A diagnosis of spondyloarthropathy is given in patients who have at least one major criterion and one minor criterion Major criteria Inflammatory back pain Synovitis that is asymmetric or that predominates in the lower limbs Minor criteria Family history of spondyloarthropathy Psoriasis Urethritis, cervicitis, or acute diarrhea within 1 month before arthritis onset Chronic inflammatory bowel disease Alternating buttock pain Enthesopathy Radiographic sacroiliitis, bilateral grade ≥ 2or unilateral grade ≥ 3

Table 3 Modified New York classification criteria for ankylosing spondylitis (1984) [13]. Clinical criteria Low back pain: present for more than 3 months, improved by exercise and not relieved by rest Limitation of lumbar spine motion in the sagittal and frontal planes Limitation of chest expansion relative to normal values for age and sex Radiographic criteria Bilateral sacroiliitis grade 2 or higher or unilateral sacroiliitis grade 3 or 4 Definite AS: radiographic criterion plus at least one clinical criterion Probable AS: all three clinical criteria or only the radiographic criterion

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of TNF␣ antagonists may be effective in improving disease activity, function, and MRI signs of inflammation. 2.2. Classification criteria versus diagnostic criteria 2.2.1. Classification criteria Diagnostic criteria are designed to assist clinicians in establishing a diagnosis under the conditions of their everyday practice. Classification criteria, in contrast, ensure the optimal differentiation of a specific rheumatic disease from another group of diseases for purposes of clinical or epidemiological research. Importantly, most of the criteria initially developed for the classification of rheumatic diseases (for clinical research) are widely used as diagnostic criteria. Examples include the American College of Rheumatology criteria for rheumatoid arthritis and the abovementioned criteria for SpA. The study design, patient selection, and reference standard used to develop diagnostic criteria differ from those used for classification criteria [15]. The reference standard may be either a previously validated tool or the opinion of experts (used for the ESSG criteria) [15]. The classification criteria for AS are the modified New York criteria, which are also used for diagnostic purposes. Clearly, these criteria cannot ensure the diagnosis of early-stage AS, minimalsymptom AS, or borderline AS (e.g., inflammatory low back and buttock pain, inflammatory heel pain without radiographic sacroiliitis). There is a need for a diagnostic tool that can provide the diagnosis before the development of radiographic sacroiliitis, which may require several years. The two classification criteria sets for SpAs, namely, Amor’s criteria and the ESSG criteria, are useful for diagnosing SpAs. These criteria are broader than the modified New York criteria. However, they are intended for purposes of classification and may lack sensitivity for establishing the early diagnosis of SpA. Since their development, they have been studied in other populations and found to be valid. In a multicenter cross-sectional study done in France, both criteria sets showed satisfactory values for sensitivity, specificity, positive predictive value, and negative predictive value [16]. Clinicians can use either set, since the performance characteristics are similar overall [16], although Amor’s criteria perform somewhat better.

Fig. 1. Decision tree developed in 2004 by Rudwaleit et al. [10] for diagnosing axial spondyloarthropathy (SpA) in patients with chronic low back pain of more than three months’ duration. The diagnosis of axial SpA is considered definite when the probability is greater than 90% and probable when the probability is 80–90%. SpA: spondyloarthropathy; NSAID, nonsteroidal antiinflammatory drug; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein.

Table 4 ASAS criteria for axial spondyloarthropathy [17]. Back pain ≥ 3 months and age < 45 years ET Sacroiliitis by MRI or radiography* + 1 other feature Features of axial SpA Inflammatory back pain

Arthritis

2.2.2. Diagnostic criteria 2.2.2.1. The Berlin criteria. The Berlin criteria were developed recently by Rudwaleit et al. [10] (Fig. 1) to assist clinicians in diagnosing axial SpA at an early stage. The goal is to diagnose spondyloarthritis or axial SpA in patients with inflammatory low back pain of more than three months’ duration. In this criteria set, the clinical features are considered routinely and the laboratory features (HLA-B27) and imaging study findings (MRI of the sacroiliac joints) when needed. Each time a feature is added to the algorithm, the probability of axial SpA is estimated. A probability of 90% or more indicates definite axial SpA and a probability of 80% to 89% probable axial SpA. The starting point is inflammatory low back pain without radiographic abnormalities, and the presence of at least three additional clinical features establishes the diagnosis of SpA. If fewer than three other clinical features are present, HLA-B27 testing and, if needed, MRI of the sacroiliac joints should be performed. An interesting characteristic of this approach is that the diagnostic properties of each criterion are used to develop the algorithm. The diagnosis of recent-onset axial SpA can be established in patients who have clinical features without radiographic changes but with MRI evidence of inflammatory lesions. 2.2.2.2. The ASAS criteria. The ASAS has just issued a new set of diagnostic criteria for axial SpA [17] that does not require the presence of radiographic sacroiliitis (Table 4). In a patient younger than

Enthesitis

Uveitis Dactylitis Psoriasis Crohn’s disease/ulcerative colitis Good response to NSAIDs

Family history for SpA

HLA-B27 Elevated CRP

OR

HLA B27 + 2 other features

4 of the 5 following characteristics Age < 40 years Insidious onset Improvement with exercise No improvement with rest Pain at night Past or present active synovitis diagnosed by a physician Pain spontaneously or upon palpation of the Achilles tendon insertion site or plantar fascia Past or present anterior uveitis diagnosed by a physician Past or present active dactylitis diagnosed by a physician Past or present active psoriasis diagnosed by a physician Past or present, diagnosed by a physician 24–48 h after the initiation of full-dose NSAID therapy, the pain is gone or much better First- or second-degree relative with any of the following: SpA, psoriasis, acute uveitis, reactive arthritis, chronic inflammatory bowel disease Presence of B27 CRP above the upper limit of the normal range, in the absence of another cause of CRP elevation

*Sacroiliitis (X- rays or MRI): Definite radiographic sacroiliitis (grade 2 bilaterally or grade 3-4 unilaterally; according to modified New York criteria 1984) Or - active (acute) inflammation of sacroiliac joints on MRI, highly suggestive of sacroiliitis associated with spondyloarthritis.

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45 years of age who has inflammatory low back pain of more than three months’ duration, a diagnosis of axial SpA can be given, based on either imaging study evidence of sacroiliitis plus at least one other feature of SpA or presence of HLA B27 plus at least two other features of SpA [17]. The features of SpA are listed in Table 4. Sacroiliitis is defined in this criteria set as MRI evidence of sacroiliac joint inflammation or radiographic evidence of sacroiliitis meeting modified New York criteria (82% sensitivity and 84% specificity compared to expert opinion). As they emerge, new criteria will be incorporated into existing criteria sets. Therefore, we will now discuss the contribution of several clinical, laboratory and imaging findings to the diagnosis of recent-onset SpA. Findings that contribute to the diagnosis of recent-onset spondyloarthropathy. 2.3. Clinical findings Clinical findings are of considerable interest as they are inexpensive to obtain and can be used by all clinicians. 2.3.1. Low back pain Chronic inflammatory low back pain is considered the most common presenting symptom of SpA. This symptom is particularly suggestive when present for longer than three months in a patient who is younger than 50 years of age [10,18,19] (Table 4). The probability of SpA is only 5% in patients with low back pain compared to 14% in those with chronic inflammatory low back pain before 50 years of age [8]. Four characteristics of the pain should be assessed [10,20–23]: • morning stiffness for more than 30 minutes, which suggests inflammatory low back pain related to SpA rather than nonspecific low back pain [18,23]; • improvement with exercise but not with rest; • pain causing the patient to awake during the second half of the night; • concomitant presence of alternating buttock pain (Table 5). 2.3.2. Other clinical findings Clinical findings such as a good response to NSAIDs and the presence of buttock pain are useful because they are more common among patients with SpA than among controls [17]. A good to excellent response to full-dose NSAID therapy within 48 hours has 75% sensitivity for SpA [18,22,23]. This criterion should be tested with three different classes of NSAIDs. Other findings that are helpful for the early diagnosis of SpA are a family history of SpA, enthesitis, dactylitis, uveitis, and asymmetric peripheral oligoarthritis. 2.4. Laboratory test findings Two features may be useful, namely the presence of systemic inflammation as assessed using the erythrocyte sedimentation rate (ESR) or serum C-reactive protein (CRP) level and the HLA27 type. 2.4.1. ESR or CRP Laboratory evidence of systemic inflammation is inconsistent in SpA. The estimated sensitivity of ESR/CRP is 38% to 45% in patients with isolated spondyloarthritis and 50% at best in those with recent-onset SpA [10]. In addition, in one study, the laboratory signs of inflammation correlated poorly with the clinical disease activity parameters [24], although these results were challenged recently [25].

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2.4.2. HLA B27 The HLA B27 status is extremely relevant to the early diagnosis of SpA. In the population at large, 5% to 10% of individuals are HLA B27positive [10], versus 80% to 95% of patients with AS and 70% of those with undifferentiated SpA [26]. HLA B27 testing alone is unhelpful in chronic low back pain patients, as the post-test probability in this population is 30% at best. Other clinical and imaging features should be used also [12,27–29]. 3. Contribution of magnetic resonance imaging to the early diagnosis of spondyloarthropathy MRI is a valuable tool for the early diagnosis of axial SpA as it can detect early evidence of inflammation, as well as structural damage to the sacroiliac joints and spine. The introduction of MRI as a diagnostic investigation for SpA is a major advance. We will discuss the many studies assessing the contribution of MRI to the diagnosis of SpA. 3.1. Sequences Four MRI sequences are used: T1 to assess chronic structural damage, T2, a fat suppression sequence such as STIR (Short Tau Inversion Recovery), and T1 after gadolinium injection. STIR and postgadolinium T1 sequences are effective in detecting evidence of acute inflammation [30,31]. Intravenous gadolinium injection is not useful for the diagnosis of SpA in everyday practice. The definite diagnosis of sacroiliitis by MRI requires the presence of unequivocal inflammation on both sides of the joint. 3.2. MRI of the sacroiliac joints MRI is sensitive for detecting bone marrow edema and infraradiographic erosions [32,33]. Postgadolinium enhancement of T1 images and high signal on STIR images correlate with the inflammatory cell infiltrate [34]. Several scores have been developed to quantify the sacroiliac inflammation in patients enrolled in clinical trials. The latest is the MRI index developed by the Spondylarthritis Research Consortium of Canada (SPARCC) [35]. A study done by the ASAS working group and based on the OMERACT filter found no evidence that one score was superior over the others [36]. The definite diagnosis of sacroiliitis by MRI requires the presence of unequivocal inflammation on both sides of the joint. 3.3. MRI of the spine Active inflammation can be detected by MRI at various spinal sites including the intervertebral disk, vertebras, interbody ligament entheses, facet joints, and costovertebral joints. Active facet joint inflammation by MRI correlates with the degree of histological inflammation [37]. Several MRI scores for spinal lesions have been developed. Among them, the most widely used is the ASspiMRI [38], which provides an activity score and a chronicity score. The activity score measures the edema (0 to 3 points) and erosions (4 to 6 points) at each vertebral unit from C2 to S1. The chronicity score measures the structural damage based on the presence of erosions, sclerosis, squaring, syndesmophytes, and vertebral fusion. The recently developed SPARCC MRI [39] score for evaluating spinal inflammation has been reported to compare favorably with the ASspiMRI. 3.4. MRI at other sites MRI is a good tool for the early diagnosis of active peripheral enthesitis [40]. A recently developed whole-body MRI technique

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Table 5 Definitions of inflammatory low back pain. Calin et al. [18]

Modified New York [13]

Rudwaleit et al. [10]

Onset < 40 years of age Insidious onset Duration ≥ 3 months With morning stiffness Improves with exercise Inflammatory low back pain if the patient meets at least 4 of the 5 criteria Sensitivity 38% Specificity 100%

Pain and stiffness of the lumbar spine Duration ≥ 3 months Improves with exercise but not with rest

Morning stiffness > 30 minutes Improves with exercise but not with rest Pain causing arousals in the second half of the night With alternating buttock pain

Sensitivity and specificity unknown

Inflammatory low back pain if the patient meets at least 2 of the 4 criteria Sensitivity 70.3% Specificity 81.2%

is effective in detecting enthesitis at most sites in patients with recent-onset SpA [41].

[10,42,43]. Furthermore, combining MRI of the sacroiliac joints and spine provides more information than MRI of either site alone.

3.5. Diagnostic contribution of MRI

3.7. Limitations of MRI

MRI is a useful diagnostic tool because it has good specificity (88% to 98.5%). However, MRI may have limited sensitivity for detecting low-grade inflammation (32%–50%) [20,21,38,41–43]. In a cohort of 350 patients with chronic low back pain, MRI of the sacroiliac joints was 88% sensitive for infraradiographic SpA and 87.5% sensitive for SpA with radiographic sacroiliitis [21]. MRI evidence of spinal inflammation had 41% and 50% sensitivity for these two conditions, respectively. MRI had good specificity, showing inflammation in only 1.5% of patients not classified as having SpA. In a study of 81 patients [44] with axial or peripheral manifestations suggesting recent-onset SpA (including 39 finally classified as having SpA), combined MRI imaging of the sacroiliac joints and spine was 44% sensitive and 95.6% specific for SpA. Conflicting data have been published. Among 34 patients with inflammatory low back pain of 19 months’ duration on average, 32 (95%) had MRI evidence of inflammation or structural damage of the sacroiliac joints [45]. In a cohort of 68 patients with inflammatory low back pain of less than 2 years’ duration, of whom 84% who met ESSG criteria for SpA (including 20.6% who met modified New York criteria), MRI of the sacroiliac joints was 32% sensitive for diagnosing SpA [20]. In a study presented at the 2008 ACR meeting [46], inflammation of the sacroiliac joints was visible in about 75% of patients (in whom SpA was diagnosed by an expert), compared to only 46% for inflammation of the spine. However, about 5% to 10% of patients had inflammatory lesions at the spine but not at the sacroiliac joints [46]. MRI of the spine is not entirely specific. Thus, nearly 20% of healthy individuals may have isolated inflammation of the vertebral corners (Romanus lesions) according to an abstract presented at the 2008 ACR meeting [47].

As mentioned above, the diagnostic usefulness of MRI in clinical practice is unclear, as sensitivity is limited. Thus, some patients with active disease remain difficult to identify [38]. This shortcoming may stem from the use of suboptimal MRI techniques. For instance, an MRI study in 38 patients with active AS found thoracic spinal abnormalities in 74% of cases, but the thoracic spine is not routinely evaluated in patients with suspected SpA [50]. Others reported a high rate of costovertebral joint involvement that was best detected on axial and lateral sections [43]. Discrepancies across study results may be related in part to differences in the criteria used to define a positive MRI scan. No studies have evaluated the diagnostic performance of MRI for diagnosing SpA in patients who are HLA B27-negative and who fail to meet criteria for inflammatory low back pain. Most of the studies in which MRI contributed to the diagnosis of recent-onset SpA were conducted in HLA B27-positive patients who had chronic inflammatory low back pain [37,38].

3.6. Changes in MRI over time In a prospective study of 40 patients with inflammatory back pain of less than two years’ duration at baseline and a mean followup of 7.7 years, 23 (58%) patients were HLA B27-positive and 39 (98%) met ESSG criteria for SpA [48]. Sacroiliitis was a feature in 33 (83%) patients, and six (12%) patients met modified New York criteria for AS at baseline. The results showed that severe sacroiliitis by MRI in an HLAB27-positive patient strongly predicted progression to AS (likelihood ratio, 8.0; specificity, 92%), whereas mild or absent sacroiliitis, regardless of HLA B27 status, predicted absence of progression to AS (38% specificity). At the spine, syndesmophytes visible on radiographs taken two years after study inclusion developed preferentially at previous sites of MRI inflammation [49]. In sum, negative MRI findings do not rule out SpA, the probability of recent-onset SpA in a patient with inflammatory low back pain is ten times higher when MRI shows inflammatory lesions

4. Contribution of ultrasonography to the diagnosis of spondyloarthropathy Ultrasonography, an imaging technique that is widely used to diagnose rheumatoid arthritis, can also assist in the diagnosis of SpA. 4.1. Enthesitis Ultrasonography is a simple and inexpensive investigation that is more sensitive than the physical examination for diagnosing enthesitis related to SpA. In a cross-sectional study of 164 patients with SpA and 64 controls with other conditions, ultrasound findings consistent with enthesitis were found at one or more sites in 161 (98%) SpA patients and the most common sites of involvement were the Achilles tendon and plantar fascia [51]. Of the 1131 sites of enthesitis in the SpA patients, 916 (81%) exhibited vascularization by power Doppler, always at the site of cortical bone insertion, compared to none of the controls. The same group studied the usefulness of ultrasonography in a prospective study of 124 patients with a suspicion of SpA based on any of the following: inflammatory back pain, arthritis, enthesitis/dactylitis, uveitis and presence of HLA B27, or family history of SpA [52]. A diagnosis of definite SpA was made in 81 patients. Ultrasonography was 87% sensitive and 90% specific for SpA. In another study, ultrasonography findings at the Achilles tendon were compared in 20 patients who had recent-onset SpA meeting ESSG criteria, with Achilles tendon enthesitis, and in 10 healthy controls [53]. In the recent-onset SpA patients, bone erosions were found at the proximal insertion or superior tuberosity (11/20 patients, P < 0.001 versus distal

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Table 6 Recommendations for imaging studies in patients with spondyloarthropathy – 2006 Meeting of Rheumatology Experts [58].

The diagnosis of ankylosing spondylitis requires standard radiographs of the pelvis (anteroposterior view) and lumbar spine (anteroposterior and lateral views including the thoracolumbar junction) When standard radiographs conclusively demonstrate bilateral sacroiliitis, further imaging studies are not necessary for establishing the diagnosis of ankylosing spondylitis When radiographs are normal or doubtful in a patient with a clinical suspicion of ankylosing spondylitis, diagnostic MRI of the sacroiliac joints is recommended MRI of the spine can contribute to the diagnosis of ankylosing spondylitis in patients who have inflammatory back pain with nonsuggestive radiographs of the pelvis and spine To evaluate entheseal involvement in patients with a clinical suspicion of ankylosing spondylitis, radiographs may be useful and, if needed, Doppler ultrasonography or MRI may deserve to be performed, or radionuclide scanning when multiple entheses are involved Given the current state of knowledge, imaging methods other than standard radiography are not useful to predict the functional or structural outcome of ankylosing spondylitis Given the current state of knowledge, imaging is not appropriate for the routine follow-up of patients with ankylosing spondylitis. Instead, additional imaging should be performed as dictated by the clinical course Given the current state of knowledge, imaging is not recommended for evaluating treatment responses in patients with ankylosing spondylitis

enthesis), whereas spurs were seen almost exclusively at the distal enthesis (eight of 10 patients, P < 0.0001), suggesting uncoupling of bone erosion and bone formation. Among the 10 controls, none had erosions and eight had small spurs located at the distal enthesis. 4.2. Ultrasonography of the sacroiliac joints Two recent studies have provided data on the performance of color Doppler ultrasonography for detecting inflammation of the sacroiliac joints and spine [54,55]. These data need to be confirmed by further studies. 5. Contribution of scintigraphy of the sacroiliac joints Two recent systematic reviews suggest that scintigraphy of the sacroiliac joints may be of limited usefulness for the early diagnosis of sacroiliitis; sensitivity was 51.8% and specificity 78.3% compared to a group of controls with mechanical low back pain [56,57]. 6. Contribution of standard radiographs Standard radiographs to look for sacroiliitis or syndesmophytes contribute little to the diagnosis of recent-onset SpA, as structural damage does not develop until several years after symptom onset. 7. Implications for clinical practice Although the existing criteria sets (Amor, ESSG) are intended for purposes of classification, they assist in the diagnosis of SpA. However, they may lack sensitivity for the diagnosis of recent-onset SpA. The Berlin algorithm is interesting but does not identify patients in whom extraspinal lesions inaugurate the disease. Furthermore, the Berlin algorithm has not been extensively validated. In a recent study of 68 patients with inflammatory low back pain of less than two years’ duration, HLA B27 testing and MRI scanning of the sacroiliac joints contributed little to the diagnosis [20], and the Berlin criteria performed less well than the ESSG and Amor criteria. The new ASAS criteria are extremely promising. They have been tested in a vast international cohort and found to be 82% sensitive and 84% specific versus the opinion of an expert. In contrast

Level of evidence

Grade of recommendation

Agreement among experts (%)

2b

D

92.8

-

D

90.1

2a

B

98.7

3

C

98.6

2b/3

D

81.7

2b

D

94.4

2a

C

95.1

1b/2b

C

97.1

to Amor’s criteria, whose performance is similar, the ASAS criteria cannot identify patients with SpA who do not have inflammatory low back pain (Table 1). In practice, as none of the available criteria sets is ideal, a careful history should be taken to look for suggestive signs in the patient or family, a trial of NSAID therapy should be performed (with three NSAIDs belonging to three different classes, each taken in the full dose for at least three days), and a thorough physical examination should be performed. Presence of the HLA B27 antigen strongly supports the diagnosis of SpA in patients with clinical or imaging study features. In patients without such features, in contrast, the HLA B27 status does not contribute to the diagnosis. If the clinical features do not immediately establish the diagnosis, an anterior posterior radiograph of the pelvis is useful to look for sacroiliitis. When this investigation fails to show sacroiliitis, we recommend MRI of the sacroiliac joints and thoracolumbar spine to look for inflammation, in keeping with recent recommendations (Table 6) [58]. Doppler ultrasonography can also contribute to the diagnosis of enthesitis and peripheral synovitis. In some patients, however, only the test of time can confirm the diagnosis of SpA. The clinical usefulness of suggested diagnostic criteria needs to be assessed in vast prospective cohorts such as the DESIR cohort established under the aegis of the French Society for Rheumatology. These cohorts will provide a means of validating prognostic criteria and or developing tools for monitoring the treatment response. They should be used to validate criteria specifically designed to establish the diagnosis of recent-onset SpA. Finally, vast prospective cohorts will prove useful for evaluating the efficacy of various treatments at the stage of undifferentiated SpA. Conflict of interest The authors have no conflict of interest to declare. References [1] Sieper J, Rudwaleit M, Khan MA, Braun J. Concepts and epidemiology of spondyloarthritis. Best Pract Res Clin Rheumatol 2006;20:401–17. [2] Saraux A, Guillemin F, Guggenbuhl P, et al. Prevalence of spondyloarthropathies in France: 2001. Ann Rheum Dis 2005;64(10):1431–5. [3] Khan MA. Update on spondyloarthropathies. Ann Intern Med 2002;136:896–907. [4] Braun J, Bollow M, Remlinger G, et al. Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum 1998;41:58–67.

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