Abstract
Spinal pain or back pain is a very common symptom that can have many reasons. The most studied location is low back pain, and it is considered to be nonspecific in the majority of cases. Only a small proportion of patients have axial inflammation as the major cause of their back complaints with chronic inflammatory back pain (IBP) as the most prominent clinical feature of spondyloarthritis (SpA). The recognition of IBP and patients with axial spondyloarthritis (axSpA) is challenging in primary care, and it is important to further facilitate the early diagnosis of SpA. Proposals for improving the referral of patients with a possible diagnosis of axSpA include clinical parameters, human leukocyte antigen (HLA) B27, and imaging parameters.
Imaging is crucial for the visualization, objective validation, and understanding of back pain. Numerous diseases such as degenerative disk disease, degenerative changes in the intervertebral (facet) joints and the associated ligaments, spinal instability, herniation of the intervertebral disk, and spinal stenosis have to be differentiated in interpreting imaging of the spine. The sacroiliac joints and the spine are of major importance for the diagnosis and classification of axSpA. Conventional radiographs and magnetic resonance imaging (MRI) are the most important imaging technologies for visualization of structural changes such as syndesmophytes and axial inflammation such as sacroiliitis and spondylitis.
The pathogenesis of axSpA is largely genetically determined. HLA B27 has the strongest contribution to the total genetic burden, but other major contributors such as endoplasmic reticulum aminopeptidase (ERAP)-1 and interleukin (IL)-23R have also been identified.
Introduction
Spinal pain or back pain is a very common symptom that can have many reasons.
The most studied location is low back pain, which was recently shown to be a major issue worldwide, with the highest prevalence among female individuals and those aged 40–80 years. The mean standard error of the mean (SEM) point prevalence was estimated to be 11.9 ± 2.0%, and the 1-month prevalence was estimated to be 23.2 ± 2.9% .
Mostly low back pain is considered to be nonspecific . Some of the most frequent causes identified include muscle tension and spasm, for example, in patients with fibromyalgia, all kinds of degeneration including disk hernia, lumbar stenosis, and osteoarthritis, and fractures, mostly in patients with osteoporosis. Only a small proportion of patients have axial inflammation as the major cause of their back complaints – many of which are identified as chronic or inflammatory back pain (IBP) . This article concentrates mainly on this relatively small patient group.
The term “axial spondyloarthritis” (axSpA) covers both patients who already have radiographic changes in the sacroiliac joints (radiographic sacroiliitis) and patients who do not have such changes. Patients in the former group are diagnosed as ankylosing spondylitis (AS), while those in the latter are now classified as non-radiographic axSpA (nr-axSpA) . The main clinical symptoms of patients with axSpA are pain and stiffness of the back , and the most characteristic symptom of axSpA is IBP . Other symptoms and manifestations are listed in Table 1 . The most relevant items and findings are part of the Assessment of SpondyloArthritis International Society (ASAS) classification criteria ( Fig. 1 ).
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The majority of patients with axSpA develop structural changes in the axial skeleton at some point in time , and 20–30% of patients with axSpA develop structural changes in the sacroiliac joints in the first 2 years of disease . Thereafter, the rate of development of structural changes has been reported to be about 12% within 2 years . New bone formation in the spine (syndesmophytes, ankylosis) will occur in the majority of patients, usually at later time points . Several parameters have been identified as prognostic markers for radiographic progression in AS ( Table 2 ).
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Inflammatory back pain
The most prominent clinical feature of spondyloarthritis (SpA) is chronic IBP . Patients with IBP complain about morning stiffness (about >30-min duration), insidious onset of back pain, awakening because of back pain during the second half of the night, and alternating buttock pain. Many patients report that the level of pain improves by movement rather than by resting. Patients are relatively young at onset (<45 years). IBP is characterized as a chronic back pain with >3-month duration. However, none of the single parameters mentioned earlier differentiate reliable IBP from other causes of back pain. Various attempts have been made to define a set of IBD variables criteria to serve as a screening test to identify patients with SpA. The definitions of IBP used in these criteria sets are variable, and views on the clinical usefulness, sensitivity, and specificity of the items are contradictory ( Table 3 ). The sensitivity of IBP for a diagnosis of axial SpA has been shown to be no greater than 70%. However, there is no general agreement about the exact definition of IBP.
| Calin A et al.: first historical definition | Rudwaleit M et al.: Based on study data | Sieper J et al.: Based on expert consensus | |
|---|---|---|---|
| Age | <40 years | <45 years | ≤40 years (odds ratio (OR): 9.9) |
| Duration | ≥3 months | ≥3 months | |
| Onset | Insidious | insidious (OR: 12.7) | |
| Clinical features | Morning stiffness | Morning stiffness > 30 min | |
| Response to interventions | Improvement by movement | Improvement by movement (OR: 23.1) | |
| No improvement by rest | No improvement by rest (OR: 7.7) | ||
| Alternating buttock pain | |||
| Wakening up in the second half of the night | Night pain (OR: 20.4) | ||
| # Sensitivity | If 4/5 criteria: 90% | If 2/4 criteria: 70% | If 4/5 criteria: 80% |
| + Specificity | If 4/5 criteria: 52% | If 2/4 criteria: 81% | If 4/5 criteria: 72% |
However, it is fair to say that there is some evidence that IBP is a rather characteristic feature of axSpA, and the following items have been shown to be relevant in that regard:
- •
Duration of >3 months
- •
Age at onset– <45 years (or younger)
- •
Localized at the lower back
- •
Insidious mode of onset
- •
Inflammatory symptom of morning stiffness for >30 min
- •
Time of –wakening up in the 2nd half of the night
- •
Response to intervention, that is, improvement by movement, not by rest
- •
Excellent improvement shown due to use of nonsteroidal anti-inflammatory drugs (NSAIDs)–
Because the items of IBP alone have limited value in the classification of patients with axSpA, chronic back pain instead of IBP has become the first-line criterion in the ASAS classification criteria for axial SpA ( Fig. 1 ).
As back pain is such a common symptom of patients presenting to general practitioners (GPs) and orthopedic surgeons, the recognition of IBP and patients with axSpA is important not just for rheumatologists. However, the diagnostic value of the IBP criteria sets have been evaluated in centers specialized in care for patients with rheumatic diseases. Because the perception of IBP in GP care is weak, it can be hypothesized that the diagnostic value of the IBP criteria sets in GP care is probably even much lower . Furthermore, the performance of IBP criteria sets differ between GPs and rheumatologist offices because the pretest probability of axial SpA is relatively low in primary care.
Recognition of SpA features in patients presenting with back pain in GP care is important to further facilitate the early diagnosis of SpA. There is still a 5–10-year delay between the occurrence of first symptoms and making a diagnosis of AS . Earlier diagnosis is not only important to introduce effective treatment but also to avoid unnecessary diagnostic and therapeutic procedures.
Proposals for improving the referral of patients with a possible diagnosis of axSpA have been developed, and others have just been tested in controlled trials . These can be subdivided into basically four different approaches: (1) only clinical variables, limited items; (2) only clinical variables, more items; (3) addition of human leukocyte antigen (HLA) B27; and (4) addition of imaging.
As our experience with imaging in primary care is that too many X-rays and magnetic resonance imaging (MRI) scans are performed, most of which are inappropriate, we tend to discourage GPs from ordering imaging but rather ask simple questions and possibly order a laboratory test for HLA B27 ( see below ).
When one concentrates on clinical items in our study, we found that the five best discriminating criteria were as follows:
- 1.
Age at onset <35 years
- 2.
Wakening up in the second half of the night
- 3.
Alternating buttock pain
- 4.
Improvement by movement, and not by rest
- 5.
Improvement by NSAIDs within 48 h
If > 3 criteria are fulfilled, the sensitivity is close to 80% and the specificity close to 50% ( Fig. 2 ).
The sensitivities and specificities for ≥4 criteria were 47.8% and 86.1%, for ≥3 criteria 78.8% and 46.4%, and ≥2 criteria 96.5% and 17.0%, respectively.
Based on all the studies performed, it appears that (i) chronic back pain lasting >3 months (ii) and which has started before the age of 45 years effectively aid in preselection of patients as potential candidates for a diagnosis of axSpA .
The central role of HLA B27 in referral programs has recently been confirmed . The use of HLA B27 and all combinations of clinical items as well as in a two-step strategy ( Fig. 3 ) is recommended. The role of HLA B27 is discussed in detail subsequently.
Inflammatory back pain
The most prominent clinical feature of spondyloarthritis (SpA) is chronic IBP . Patients with IBP complain about morning stiffness (about >30-min duration), insidious onset of back pain, awakening because of back pain during the second half of the night, and alternating buttock pain. Many patients report that the level of pain improves by movement rather than by resting. Patients are relatively young at onset (<45 years). IBP is characterized as a chronic back pain with >3-month duration. However, none of the single parameters mentioned earlier differentiate reliable IBP from other causes of back pain. Various attempts have been made to define a set of IBD variables criteria to serve as a screening test to identify patients with SpA. The definitions of IBP used in these criteria sets are variable, and views on the clinical usefulness, sensitivity, and specificity of the items are contradictory ( Table 3 ). The sensitivity of IBP for a diagnosis of axial SpA has been shown to be no greater than 70%. However, there is no general agreement about the exact definition of IBP.
| Calin A et al.: first historical definition | Rudwaleit M et al.: Based on study data | Sieper J et al.: Based on expert consensus | |
|---|---|---|---|
| Age | <40 years | <45 years | ≤40 years (odds ratio (OR): 9.9) |
| Duration | ≥3 months | ≥3 months | |
| Onset | Insidious | insidious (OR: 12.7) | |
| Clinical features | Morning stiffness | Morning stiffness > 30 min | |
| Response to interventions | Improvement by movement | Improvement by movement (OR: 23.1) | |
| No improvement by rest | No improvement by rest (OR: 7.7) | ||
| Alternating buttock pain | |||
| Wakening up in the second half of the night | Night pain (OR: 20.4) | ||
| # Sensitivity | If 4/5 criteria: 90% | If 2/4 criteria: 70% | If 4/5 criteria: 80% |
| + Specificity | If 4/5 criteria: 52% | If 2/4 criteria: 81% | If 4/5 criteria: 72% |
However, it is fair to say that there is some evidence that IBP is a rather characteristic feature of axSpA, and the following items have been shown to be relevant in that regard:
- •
Duration of >3 months
- •
Age at onset– <45 years (or younger)
- •
Localized at the lower back
- •
Insidious mode of onset
- •
Inflammatory symptom of morning stiffness for >30 min
- •
Time of –wakening up in the 2nd half of the night
- •
Response to intervention, that is, improvement by movement, not by rest
- •
Excellent improvement shown due to use of nonsteroidal anti-inflammatory drugs (NSAIDs)–
Because the items of IBP alone have limited value in the classification of patients with axSpA, chronic back pain instead of IBP has become the first-line criterion in the ASAS classification criteria for axial SpA ( Fig. 1 ).
As back pain is such a common symptom of patients presenting to general practitioners (GPs) and orthopedic surgeons, the recognition of IBP and patients with axSpA is important not just for rheumatologists. However, the diagnostic value of the IBP criteria sets have been evaluated in centers specialized in care for patients with rheumatic diseases. Because the perception of IBP in GP care is weak, it can be hypothesized that the diagnostic value of the IBP criteria sets in GP care is probably even much lower . Furthermore, the performance of IBP criteria sets differ between GPs and rheumatologist offices because the pretest probability of axial SpA is relatively low in primary care.
Recognition of SpA features in patients presenting with back pain in GP care is important to further facilitate the early diagnosis of SpA. There is still a 5–10-year delay between the occurrence of first symptoms and making a diagnosis of AS . Earlier diagnosis is not only important to introduce effective treatment but also to avoid unnecessary diagnostic and therapeutic procedures.
Proposals for improving the referral of patients with a possible diagnosis of axSpA have been developed, and others have just been tested in controlled trials . These can be subdivided into basically four different approaches: (1) only clinical variables, limited items; (2) only clinical variables, more items; (3) addition of human leukocyte antigen (HLA) B27; and (4) addition of imaging.
As our experience with imaging in primary care is that too many X-rays and magnetic resonance imaging (MRI) scans are performed, most of which are inappropriate, we tend to discourage GPs from ordering imaging but rather ask simple questions and possibly order a laboratory test for HLA B27 ( see below ).
When one concentrates on clinical items in our study, we found that the five best discriminating criteria were as follows:
- 1.
Age at onset <35 years
- 2.
Wakening up in the second half of the night
- 3.
Alternating buttock pain
- 4.
Improvement by movement, and not by rest
- 5.
Improvement by NSAIDs within 48 h
If > 3 criteria are fulfilled, the sensitivity is close to 80% and the specificity close to 50% ( Fig. 2 ).
