Dr. Jon Chan Disclosures: Given talks and provided training lectures for: Abbvie, Amgen, Celgene, Janssen, Eli Lilly, Novartis, Mylan, UCB, Canadian Spondylitis Association, and Canadian Rheumatology Association. Participated in advisory boards for: Abbvie, Amgen, Celgene, Janssen, Eli Lilly, Novartis, Gilead, Roche, Sandoz, UCB, Fresenius Kabi, and Merck. Received grants from clinical trials with Janssen, Novartis, Abbvie, and UCB. Mitigating potential bias: Only published trial data is presented. Only recommendations consistent with published guidelines or guidelines in the works (SPARCC, ACR/SPARTAN, and EULAR/ASAS) are presented. Recommendations are consistent with current practice patterns. The article does not cover the topic of treatment but rather diagnosis.
Dr. Neda Amiri Disclosures: Received financial payments from Abbvie, Amgen, Fresenius Kabi, Janssen, Lily, Novartis, Pfizer, UCB. Member of advisory boards for Abbvie, Amgen, Fresenius Kabi, Janssen, Lily, Novartis, Pfizer, UCB. Received funding for grants from UCB. Mitigating potential bias: Only published trial data is presented. Recommendations are consistent with published guidelines. Recommendations are consistent with current practice patterns.
What care gaps or frequently asked questions I have noticed
Low back pain is a common complaint encountered in the general practitioner’s office. In fact, about two-thirds of adults suffer from low back pain at some point in their life, and it is second to only upper respiratory problems as a reason for visits to a physician (1). Axial spondyloarthritis is an autoimmune disease that results in inflammation in the spine. A number of therapies exist for this condition and early therapy may prevent progressive spinal fusion. Given the sheer prevalence of low back pain, identifying patients with axial spondyloarthritis can be challenging.
Inflammatory back pain (IBP) is associated strongly with, but not diagnostic of, axial spondyloarthritis.
We will review the following commonly encountered topics:
- Key features in recognizing and distinguishing inflammatory back pain from mechanical etiologies
- Extra-articular manifestations to screen for
- Imaging — what modalities to use
- If and when autoimmune serology is required as part of work-up
Data that answers these topics
Inflammatory back pain characteristics
Many IBP criteria have been proposed over the years, including Calin (1977), Berlin (2006), and Assessment of SpondyloArthritis International Society (ASAS) (2009).
The ASAS criteria (2) were developed at a consensus conference with spondyloarthritis experts. Fulfillment of at least 4/5 features has an associated sensitivity of 77.0% and specificity of 91.7%. The criteria are listed as follows (in descending order of highest associated odds ratios (OR)):
- Improvement with exercise (OR 23.1)
- Pain at night (with improvement upon getting up) (OR 20.4)
- Insidious onset (OR 12.7)
- Age at onset <40 years (OR 9.9)
- No improvement with rest (OR 7.7)
Other features of inflammatory back pain not listed as part of these criteria are good response to non-steroidal anti-inflammatory drugs (NSAIDs) and alternating buttock pain. It should also be noted that morning stiffness is non-specific and does not help in distinguishing inflammatory back pain.
Extra-articular manifestations to screen for
IBP is associated with multiple different rheumatologic conditions, namely seronegative spondylarthritis (SpA). They may often share similar extra-axial manifestations that are important to recognize for prognostic and treatment purposes.
- Ocular — anterior uveitis (25-30%). This presents with acute pain, loss of vision and redness in one eye that usually subsides spontaneously or with local corticosteroid therapy after several weeks. Other ocular manifestations include posterior uveitis, scleritis, episcleritis. (3)
- Gastrointestinal — IBD (5-10% of patients with SpA will develop IBD; conversely, 10% of patients with IBD develop SpA). Microscopic colitis (identified during biopsies with endoscopy) is described in 60% of patients with SpA, though the clinical significance is unclear. (4)
- Dermatologic — psoriasis (10-25%). Conversely, about 30% of patients with psoriasis may develop psoriatic arthritis. (5)
- Peripheral arthritis — inflammatory arthritis (30%) often involving large joints of the lower limbs in an asymmetric, oligoarticular pattern. (6)
- Peripheral peri-articular structures — enthesitis (typical structures include the Achilles tendons, plantar fascia, costosternal junctions, tibial tubercles) (7), dactylitis, and tenosynovitis.
- Cardiac — aortic valve involvement (1-10%), most commonly regurgitation. Involvement of AV node (conduction disturbance), LV dysfunction, and risk of atherosclerotic events also increased (2x compared to age-matched controls). (8)
- Pulmonary — apical pulmonary fibrosis (and bullous disease), extra-thoracic chest wall restriction. (9)
The prevalence of IBP among adults aged 20-69 in the US is 5-6% (10). In contrast, the prevalence of SpA is estimated to range from 0.4-1.3% (11). Predictors of progression (12) to SpA include history of uveitis (HR 5.0), male sex (HR 2.7) and family history (HR 3.2).
In addition, it is always important to screen for red flags of back pain including constitutional symptoms, history of malignancy, bladder or bowel dysfunction, saddle anesthesia, progressive neurologic deficits, and intravenous drug use. These can be associated with malignancy, cauda equina syndrome, or infectious etiologies.
The previous 1984 modified New York criteria for the diagnosis of ankylosing spondylitis required presence of advanced sacroiliitis on pelvic X-ray (13). Although the criteria are quite specific and perform well in patients with established disease, they are often insensitive for diagnosis at early stages of disease. There is an average delay of 7 years from onset of first clinical symptoms to final diagnosis of AS (14).
The 2009 ASAS classification criteria for axial SpA comprises both an imaging and clinical arm, and highlight the role of MRI in diagnosing early disease (2).
It should be noted that inflammation in spondyloarthritis almost invariably begins in the sacroiliac joints (SIJ) (15), and imaging of the SIJ should always be the initial location imaged if axial SpA is suspected.
Conventional radiography (CR) of the SIJ is still widely accepted as first-line imaging modality as it is inexpensive and easy to access (16). In select patients (i.e., young patients and those with short symptom duration, repeated radiation exposure, and women of child-bearing age), MRI may be considered as a reasonable first-line alternative if there is high clinical suspicion. If the diagnosis of axial SpA cannot be established based on clinical features and conventional radiography, and the diagnosis is still suspected, MRI of the SIJ with a fluid sensitive sequence is recommended to assess for sacroiliitis. On MRI, both active inflammatory lesions (bone marrow edema) and structural lesions (bone erosion, new bone formation, sclerosis, and fat infiltration) may be visualised (14).
Traditional CT imaging has been shown to be superior to conventional radiography for detection of SIJ structural lesions (17). However, it is not routinely recommended in the diagnosis of axial SpA as it is not able to detect bone marrow edema and is associated with a significant amount of radiation. Low-dose CT protocols have been developed that use the same amount of radiation as a pelvic X-ray, and dual energy CT (DECT) can be used to detect bone marrow edema (18). The exact role of these imaging techniques has not been defined but in our view, they may be used in situations where patients are unable to undergo MRI whether due to access, cost, or contraindication. Finally, bone scans should not be ordered as they have poor sensitivity and specificity in detecting sacroiliitis (19).
If advanced imaging such as CT or MRI is being considered, it is reasonable to involve a rheumatologist for facilitation of the tests and interpretation of the findings in the clinical context.
It is also important to keep in mind that a mild degree of bone marrow edema in the SIJs can be nonspecific and other conditions such as sacroiliac joint infection, fracture, or malignancy should be considered.
Role of serologic investigations
We do not recommend antinuclear antibody (ANA) and rheumatoid factor (RF) testing in back pain, as sacroiliitis is not a feature of rheumatoid arthritis or connective tissue disease.
HLA-B27 is an MHC class I antigen that is strongly associated with SpA. Its frequency, while dependent on ethnic variations, is approximately 10% among the general population. More than 75-90% of patients with AS are HLA-B27 positive. The risk of developing AS in HLA-B27 positive individuals can be 5-7% (20). HLA-B27 positivity has an associated likelihood ratio (LR) of +9.0 for axial SpA (21). Despite the high positive LR of the HLA-B27 test, the post-test probability of AS in a patient with chronic low back pain is still only 30% (22), given that back pain is such a common complaint in the general population. A positive test should therefore be interpreted with caution.
Finally, acute phase reactants are often used to assess for active inflammation in axial SpA. C-reactive protein (CRP), rather than ESR, is favoured, and is included as a measure on various ankylosing spondylitis disease activity scores (e.g. ASDAS-CRP). While the prevalence of CRP elevation varies depending on the presence of imaging findings of spondyloarthritis, in general only about 30% of patients will have a modestly elevated CRP in the 5-15mg/L range (23) so a normal CRP does not rule out the condition.
NSAIDs are first-line therapy in management of axial spondyloarthritis. We recommend initiation (if no contraindications) if IBP is clinically suspected and while awaiting workup. Discussion and monitoring of side effects should include gastrointestinal toxicity, renal injury, cardiovascular events, and avoidance in pregnancy (24).
80% of patients with AS who are treated with NSAIDs report at least good improvement in their symptoms, in contrast to only 15% of patients with mechanical back pain (25). Thus NSAIDs are not only useful in management, but can also be helpful in diagnostic differentiation. Various NSAIDs have been shown in RCTs to demonstrate similar efficacy (26–28). Commonly used regimens at maximum daily doses include Naproxen 500mg BID, Celecoxib 200mg BID, Ibuprofen 800mg TID. One study comparing etoricoxib to naproxen found etoricoxib had superior response (29), though it is unfortunately not available in Canada.
Full dose NSAIDs should be used consistently for at least 2–4 weeks to determine if there is a response. Further discussion on NSAIDs and advanced therapeutics (e.g. TNF, IL-17 and JAK inhibitors) will be reviewed in detail in a follow-up article.
What we recommend
- Detailed history and clinical evaluation are key in differentiating inflammatory back pain from mechanical etiology (ASAS criteria: improvement with exercise, pain at night, insidious onset, age at onset <40 years, no improvement with rest). In addition, back pain red flags should always be assessed.
- Screen for extra-axial manifestations that may increase likelihood of spondyloarthritis. A young patient with chronic low back pain and any one of uveitis, psoriasis, ulcerative colitis, or Crohn’s disease is at increased risk of AS.
- First-line imaging for inflammatory back pain is SI joint X-rays. However, they may often be normal in early disease. If normal and clinical suspicion is still high, MRI SI joints with a fluid-sensitive sequence should be pursued.
- Autoimmune serology (ANA, RF, anti-CCP) is not recommended in the work-up of low back pain. CRP can be useful to assess for active inflammation in suspected spondyloarthritis but is only 30% sensitive.
- HLA-B27 is strongly associated with spondyloarthritis. There is no consensus for when this test should be ordered but, in our opinion, it should be considered in young patients with moderate/severe chronic low back pain especially if there are inflammatory features on history.
- First-line management with full dose NSAIDs can be trialled (if no contraindications) while awaiting diagnostic workup for IBP. Various NSAID regimens have been shown to have similar efficacy.
- Deyo RA, Weinstein J. Low Back Pain. N Engl J Med. 2001;344(5):363-70. DOI: 10.1056/NEJM200102013440508. (Request with CPSBC or view with UBC)
- Rudwaleit M, Landewé R, Van Der Heijde D, Listing J, Brandt J, Braun J, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): Classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis. 2009;68(6):770-6. DOI: 10.1136/ard.2009.108233. (View)
- Bacchiega ABS, Balbi GGM, Ochtrop MLG, de Andrade FA, Levy RA, Baraliakos X. Ocular involvement in patients with spondyloarthritis. Rheumatology (United Kingdom). 2017;56(12):2060-2067. DOI: 10.1093/rheumatology/kex057. (View)
- Mielants H, Veys EM, Cuvelier C, De Vos MD. Ileocolonoscopic findings in seronegative spondylarthropathies. Br J Rheumatol. 1988;27 Suppl 2:95-105. DOI: 10.1093/rheumatology/XXVII.suppl_2.95. (Request with CPSBC or view with UBC)
- Busse K, Liao W. Which Psoriasis Patients Develop Psoriatic Arthritis? Psoriasis Forum. 2010; 16(4):17-25. DOI: 10.1177/247553031016a00403. (View)
- Van Der Horst Bruinsma IE, Nurmohamed MT. Management and evaluation of extra-articular manifestations in spondyloarthritis. Ther Adv Musculoskelet Dis 2012;4(6):413-22. DOI: 10.1177/ 1759720X12458372. (View)
- McGonagle D, Benjamin M. Entheses, enthesitis and enthesopathy. Arthritis Research UK. 2009;4:1–6. (Link not available)
- O’Neill TW, Bresnihan B. The heart in ankylosing spondylitis. Ann Rheum Dis. 1992; 51(6):705-6. DOI: 10.1136/ard.51.6.705. (View)
- Kanathur N, Lee-Chiong T. Pulmonary Manifestations of Ankylosing Spondylitis. Clin Chest Med. 2010;31(3):547-54. DOI: 10.1016/j.ccm.2010.05.002. (View with CPSBC or UBC)
- Weisman MH, Witter JP, Reveille JD. The prevalence of inflammatory back pain: Population-based estimates from the US National Health and Nutrition Examination Survey. Ann Rheum Dis 2013;72(3):369-73. DOI: 10.1136/annrheumdis-2012-201403. (View)
- Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008;58(1):26-3. DOI: 10.1002/art.23176. (View)
- Wang R, Crowson CS, Wright K, Ward MM. Clinical Evolution in Patients With New-Onset Inflammatory Back Pain: A Population-Based Cohort Study. Arthritis Rheumatol. 2018;70(7):1049-1055. DOI:g doi:10.1002/art.40460. (View)
- Van Der Linden S, Valkenburg HA, Cats A. Evaluation of Diagnostic Criteria for Ankylosing Spondylitis. Arthritis Rheum. 1984;27(4):361-8. DOI: 10.1002/art.1780270401. (View)
- Khmelinskii N, Regel A, Baraliakos X. The role of imaging in diagnosing axial spondyloarthritis. Front Med. 2018;5:106. DOI: 10.3389/fmed.2018.00106. (View)
- Bollow M, Hermann KGA, Biedermann T, Sieper J, Schöntube M, Braun J. Very early spondyloarthritis: Where the inflammation in the sacroiliac joints starts. Ann Rheum Dis. 2005;64(11):1644-6. DOI: 10.1136/ard.2004.034967. (View)
- Mandl P, Navarro-Compán V, Terslev L, Aegerter P, Van Der Heijde D, D’Agostino MA, et al. EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice. Ann Rheum Dis. 2015;74(7):1327-39. DOI: 10.1136/ annrheumdis-2014-206971. (View)
- Fam AG, Rubenstein JD, Chin‐Sang H, Leung FYK. Computed tomography in the diagnosis of early ankylosing spondylitis. Arthritis Rheum. 1985;28(8):930-7. DOI:10.1002/art.1780280813. (View)
- Wu H, Zhang G, Shi L, Li X, Chen M, Huang X, et al. Axial spondyloarthritis: Dual-energy virtual noncalcium CT in the detection of bone marrow edema in the sacroiliac joints. Radiology. 2019;290(1):157-164. DOI:10.1148/radiol.2018181168. (View)
- Song IH, Carrasco-Fernández J, Rudwaleit M, Sieper J. The diagnostic value of scintigraphy in assessing sacroiliitis in ankylosing spondylitis: A systematic literature research. Ann Rheum Dis. 2008;67(11):1535-40. DOI: 10.1136/ard.2007.083089. (Request with CPSBC or view with UBC)
- Sharip A, Kunz J. Understanding the pathogenesis of spondyloarthritis. Biomolecules. 2020;10(10):1461. DOI: 10.3390/biom10101461. (View)
- Rudwaleit M, Van Der Heijde D, Khan MA, Braun J, Sieper J. How to diagnose axial spondyloarthritis early. Ann Rheum Dis. 2004; 63(5):535-43. DOI: 10.1136/ard.2003.011247. (View)
- Brown MA. Human leucocyte antigen-B27 and ankylosing spondylitis. Intern Med J. 2007;37(11):739-40. DOI:10.1111/j.1445-5994.2007.01491.x. (Request with CPSBC or view with UBC)
- Van Tubergen A. The changing clinical picture and epidemiology of spondyloarthritis. Nat Rev Rheumatol. 2015;11(2):110-8. DOI: 10.1038/nrrheum.2014.181. (Request with CPSBC or view with UBC)
- Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: An update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci 2013;16(5):821-47. (View)
- Amor B, Dougados M, Listrat V, Menkes CJ, Roux H, Benhamou C, et al. Are classification criteria for spondylarthropathy useful as diagnostic criteria? Rev Rhum Engl Ed 1995 Jan;62(1):10-5. (Request with CPSBC)
- Sieper J, Klopsch T, Richter M, Kapelle A, Rudwaleit M, Schwank S, et al. Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: Results of a 12-week randomised, double-blind, controlled study. Ann Rheum Dis 2008 Mar;67(3):323-9. (View)
- Barkhuizen A, Steinfeld S, Robbins J, West C, Coombs J, Zwillich S. Celecoxib is efficacious and well tolerated in treating signs and symptoms of ankylosing spondylitis. J Rheumatol 2006 Sep ;33(9) :1805-12. (Request with CPSBC)
- Luis F, Alcazar V, De Buergo MA, Lenza HR, Fruitös EM. Aceclofenac Is As Safe and Effective as tenoxicam in the treatment of ankylosing spondylitis: A 3 month multicenter comparative trial. J Rheumatol 1996 Jul;23(7):1194-9. (Request with CPSBC)
- Van Der Heijde D, Baraf HSB, Ramos-Remus C, Calin A, Weaver AL, Schiff M, et al. Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: Results of a fifty-two-week, randomized, controlled study. Arthritis Rheum 2005 Apr;52(4):1205-15. (View)