Back pain in ankylosing spondylitis (AS) is usually referred to as inflammatory back pain (IBP). IBP is the key clinical symptom of AS, but it can also be present in other spondylarthritides in which there is axial involvement (1–5). Since IBP has certain characteristic features, obtaining the clinical history has been proposed as a screening test to identify patients with AS among those who have chronic back pain (6, 7). However, the value of such a screening test has been questioned (8). Indeed, the clinical history has been considered to be of low to moderate value at best (9, 10). Given the low (∼5%) prevalence of AS and its early, preradiographic stages among patients with chronic back pain (11), a powerful test for IBP as the leading symptom in AS would be of great help not only for screening (12), but also for diagnostic evaluation of patients with back pain (13, 14).
The first precise clinical description of IBP dates back to the report by Hart and colleagues in 1949 (15). In the patients described in that report, the pain was located in one or both buttocks, also occasionally in the mid-lumbar region, and was accompanied by stiffness. Hart et al wrote, “A frequent feature of the pain and stiffness was the aggravation caused by immobility. Waking in the morning stiff and in pain, the patient gradually became more supple during the day, feeling at his best from the afternoon until bedtime. One patient noted that by frequent exercise, his condition was kept in check, but confinement to bed for any cause made him worse. Another woke himself up [every 2 hours] throughout the night to exercise his spine as otherwise, he suffered unduly in the morning.” Those investigators also noted that a few patients were exceptional, in that rest appeared to ease the pain. In some patients, heavy exertion or strain acted as an aggravator (15). The description by Hart nicely illustrates the typical features of IBP, but even at the outset, it indicates that these features do not apply to all patients.
The first set of criteria for IBP was proposed in 1977 by Calin et al (6). The criteria, which were derived from a study of 42 AS patients and 24 patients with back pain of other origin, consist of 5 features: 1) insidious onset, 2) age at onset <40 years, 3) duration of back pain ≥3 months, 4) associated with morning stiffness, and 5) improve with exercise. IBP was considered to be present if at least 4 of the 5 features were fulfilled (sensitivity 95%; specificity 76% [in patients with mechanical low back pain]) (6). The modified New York criteria for AS, which were published in 1984 (16), incorporated aspects of the findings by Calin et al and defined the back pain associated with AS as “low back pain and stiffness for more than 3 months, which improves with exercise, but is not relieved by rest.” Subsequent studies found the specificity of Calin's screening test to be about 75% (17, 18) and the sensitivity to be only about 23% (17) and 38% (16), respectively. The disappointingly low sensitivity led to new proposals for IBP criteria, such as “getting out of bed at night” as a single item, which had a sensitivity of 65% and a specificity of 79% in one study (17).
The recent broadening of treatment options for AS, from physical therapy plus nonsteroidal antiinflammatory drug (NSAID) treatment only to tumor necrosis factor (TNF) blockers as additional highly efficacious agents (19), has raised interest in the correct and early diagnosis of AS. The aim of this study was to evaluate again in an exploratory study the individual features of IBP and to compose various combinations of features and compare them with each other. Since AS is a differential diagnosis in patients with chronic back pain, whereas acute back pain often is nonspecific in nature and subsides without intervention within 3 months in 90% of patients (20, 21), and since ∼95% of all AS patients develop back pain before the age of 40–45 years (4, 22, 23), we decided to focus on patients younger than 50 years who had chronic back pain.
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- PATIENTS AND METHODS
The identification of patients with suspected AS among the many patients with chronic low back pain is of relevance in clinical practice (12, 20, 21). The typical features of IBP associated with AS, such as morning stiffness or improvement in back pain with exercise, have been known for some time (15), but there are only a few systematic studies that have sought to establish criteria for IBP. Furthermore, the results of those earlier studies were discordant (6, 16, 17), which may be partly related to the small numbers of either study patients (17) or controls (6). Moreover, parameters such as awakening because of back pain during the night were assessed in some studies (17, 28) but not in others (6, 29). These shortcomings motivated us to explore again the clinical history features of IBP in a large cohort of patients with AS and MLBP.
The frequencies of a variety of IBP features differed significantly between AS and MLBP patients. Of note, logistic regression analysis demonstrated the independent contribution of several of these features to the association with IBP. However, none of the parameters we tested had both a sufficiently high sensitivity and a sufficiently high specificity to be used as a single discriminating test. On the other hand, none of the single parameters or combinations of parameters of the clinical history were useful in ruling out AS. The highest sensitivity was found for improvement with exercise, since this was reported by 78.2% of AS patients. However, improvement with exercise was also reported by ∼50% of patients with MLBP, indicating a poor specificity of this item. Our creation of the conditional feature of improvement with exercise but not with rest clearly resulted in a better discrimination between patients and controls (55.4% versus 21.4%), but at the cost of sensitivity.
In the study by Calin et al (6) as well as in other studies (16, 28, 29), the duration of morning stiffness in AS was not defined. To our knowledge, Gran (17) was the only investigator who assessed the duration of morning stiffness and found that a duration of >30 minutes was relevant in AS (sensitivity 64% and specificity 58%). In our study, we also found morning stiffness of >30 minutes' duration to differentiate well between AS and MLBP patients, thereby confirming the finding by Gran (17).
Likewise, there has been no consistent definition of insidious onset of back pain. While Calin et al (6) distinguished only sudden onset from slow onset, Gran (17) differentiated between acute (within 1 week), subacute (within 1 month), and insidious (within >1 month) onset. Møller et al (28) differentiated sudden onset (minutes to hours) from onset of a few days to weeks and from insidious onset, but did not give a time period for the latter. While in the study by Møller et al, an insidious onset of back pain was reported by ∼73% of AS patients, in the study by Gran (17), insidious onset did not differentiate between AS patients and controls. Interestingly, in our study, about the same percentage of AS patients reported a very acute onset of back pain (within 1 hour; 23.7%) as reported a very slow onset (within 1 year; 24.7%). Therefore, if one considers “insidious” as representing the onset of back pain within 1 year, this indeed discriminated between AS and MLBP patients, but would apply to only one-fourth of the AS patients. If one considers “insidious” as representing the onset of back pain within a period of more than 1 week, this did not differentiate between AS patients (42.3%) and MLBP patients (33.3%) in our study.
Since none of the single parameters of IBP sufficiently distinguished AS patients from MLBP patients, we generated various sets of IBP parameters. We mainly considered the parameters that were significantly different between the 2 groups. A well-balanced tradeoff between sensitivity and specificity was found for several combinations, such as sets 9b, 7b, 8a, 10a, and 8i, all of which showed a range of sensitivity and specificity between 70% and 80%. Somewhat surprisingly, none of these candidate sets performed outstandingly better than the others. Whatever the combination of parameters tested, the sensitivity and specificity generally did not exceed 70–80% each, indicating a substantial overlap of the clinical history of AS patients and patients with MLBP. Among the candidate sets, criteria set 8a, which consisted of the 4 parameters of morning stiffness of >30 minutes' duration, improvement in back pain with exercise but not with rest, awakening because of back pain during the second half of the night only, and alternating buttock pain (at least 2 of 4 positive), evolved to us as an interesting candidate set of criteria for the classification of IBP. Set 8a also performed somewhat better than the Calin criteria, which had both a lower sensitivity and a lower specificity. As an alternative to set 8a, set 7b, which consisted of the 3 parameters of morning stiffness of >30 minutes' duration, improvement in back pain with exercise but not with rest, and age at onset of back pain <30 years (2 of 3 positive), would also be a good option because of its ease of application and its acceptable test properties, making it another interesting candidate set of criteria.
Whereas for classification purposes, a dichotomous approach (criterion fulfilled: yes/no) is generally applied, making a diagnosis in an individual patient requires more flexibility. In this regard, a multilevel approach to the application of IBP criteria may be conceivable. For example, if 3–4 parameters of set 8a were present in a patient, the positive LR would be 12.4, which represents a substantial diagnostic gain (27): assuming a 5% prevalence of AS and other spondylarthritides with predominantly axial involvement (11), the resulting posttest probability of ∼40% would make AS likely, and the primary care physician may choose to immediately refer the patient to a rheumatologist. If, in contrast, none of the 4 parameters of set 8a are present in a patient, the positive LR would be 0.25, and the resulting posttest probability of ∼1.3% would render AS very unlikely. The presence of just 2 parameters (positive LR 2.3) renders the diagnosis of AS a little bit more likely (posttest probability 11%), whereas the presence of only 1 parameter renders the disease less likely (posttest probability 2.5%).
Although the multilevel application of the criteria may seem complicated at first glance, this very much reflects clinical decision-making by experts in everyday practice (the more parameters present, the more likely the diagnosis). In fact, a multilevel application of the clinical history criteria for IBP helps to resolve the discrepancy between the consideration by many experts that the clinical history is indeed a useful diagnostic test in the individual patient and the rather poor performance of established criteria for IBP if applied at certain cutoff levels (criterion fulfilled: yes/no) that are aimed at being balanced between sensitivity and specificity.
The new candidate criteria for IBP proposed herein arose from studying a cohort of patients with definite diagnoses and established and longstanding disease who received medical care at secondary and tertiary centers. This implies several limitations, however. First, patients were selected for this study nonsystematically (“convenience sample”). Further, the examiner who took the clinical history was not effectively blinded to the diagnosis. To reduce this potential bias, a structured questionnaire was applied in the same way to every patient. Recall bias in patients with longstanding disease could also have influenced the results. Thus, the findings of this exploratory study need to be prospectively validated in another study. In such a validation study, primary care physicians might be invited to refer to rheumatologists all young adults who have chronic back pain and who are suspected of having AS, but in whom there is no clear diagnosis. AS might be suspected because of clinical manifestations that include features of IBP, a family history of AS, or the presence of HLA–B27. In all consecutively referred patients, features of IBP should be assessed and documented prior to making the diagnosis, ideally by an independent and blinded examiner (27, 30, 31).
In this study, the frequencies of HLA–B27 and of elevated levels of acute-phase reactants were also assessed, and tests for spinal mobility were performed. As expected, there were significant differences between AS and MLBP patients. Of interest, the frequency of HLA–B27 among MLBP patients was within the range of the background frequency in the general population (2), thus demonstrating the lack of association between HLA–B27 and MLBP. When the parameters of clinical history of IBP (set 8a; at least 2 of 4 parameters positive), HLA–B27 positivity, and elevated CRP level were combined, the presence of at least 2 of these 3 parameters was found in 80.1% of the AS patients but in only 6.3% of the MLBP patients. This confirms the use of these parameters, in particular, HLA–B27, as additional helpful diagnostic tests for AS, as was recently proposed (14). In established and longstanding AS, spinal mobility is frequently restricted; this was also the case in our study. Of note, in this cohort of AS patients with a mean duration of back pain of 12.9 years, the test for lateral spinal flexion was far more specific for AS than was the test for anterior spinal flexion (Schober's test), which is not consistent with the findings of a previous study (17). The diagnostic value of the tests for spinal mobility in early disease, however, is unknown.
Interestingly, during their overall course of disease, the AS patients changed doctors more often than did the patients with MLBP: the mean number of doctors visited by AS patients was 5.3, compared with 3.5 doctors visited by MLBP patients. Visits to 5 or more different doctors were reported by 56.4% of AS patients, but only by 21.8% of MLBP patients. Unfortunately, we cannot deduce from our data whether this was done mainly in search of a diagnosis or in search of relief from back pain.
In summary, in this exploratory study, we defined new candidate criteria for the clinical history of IBP in a large cohort of patients. Detailed emphasis was placed on several features of the clinical history, and numerous combinations of parameters were compared. For diagnostic purposes, a multilevel approach to the application of IBP criteria is conceivable. We have proposed a new set of IBP criteria that appears to be superior to existing sets, but this needs to be validated in a prospective study.