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Research Review By Dr. Brynne Stainsby©


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Date Posted:

May 2017

Study Title:

Ankylosing Spondylitis and Axial Spondyloarthritis


Taurog JD, Chhabra A & Colbert RA

Author's Affiliations:

Rheumatic Diseases Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; Musculoskeletal Imaging Division, Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Pediatric Translational Research Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.

Publication Information:

New England Journal of Medicine 2016; 374: 2563-2574.

Background Information:

Although low back pain (LBP) is a common cause of pain and disability, rarely is a specific cause or cure identified. One specific cause of chronic LBP is ankylosing spondylitis (AS), an inflammatory disorder which may lead to pain, loss of range of motion and even eventual vertebral fusion. AS is now considered a subset of axial spondyloarthritis, a broader and more prevalent diagnostic entity, the overall estimated prevalence of which is 0.9-1.4% of the adult population (which, for comparison, is similar to the prevalence rheumatoid arthritis) (1). Historically, diagnosis was based on pain, stiffness, and loss of lumbar (and thoracic) range of motion (ROM) in the context of sacroiliitis observed on imaging (3). In 1973, the association of HLA-B27 was identified (4). The current classification system allows for the broader diagnosis of axial spondyloarthritis to be made without radiographic sacroiliitis if it is detected on MRI, or when there is a positive HLA-B27 result in combination with clinical symptoms.

While axial spondyloarthritis is typically diagnosed and treated by rheumatologists, the prolonged and often deleterious diagnostic delay in the majority of cases requires non-rheumatologist clinicians to have an understanding of etiology and presentation of this condition (2). This narrative review aimed to enhance awareness and understanding of axial spondyloarthritis and ankylosing spondylitis, and the relationship between the two, to facilitate prompt and accurate diagnosis and initiation of proper treatment.


Diagnosis of Axial Spondyloarthritis & Ankylosing Spondylitis:

Inflammatory Back Pain:

The nature and pattern of back pain, along with the age of the patient are important in recognizing axial spondyloarthritis clinically. Inflammatory back pain is the most typical symptom, and the list below outlines common presentations. The presence of two or more of the following features should raise the index of suspicion for inflammatory back pain:
  • Initial onset less than 45 years of age
  • Pain duration > 3 months
  • Pain of insidious onset
  • Morning stiffness lasting longer than 30 minutes
  • Improvement with exercise
  • No improvement (or worsening) with rest
  • Night pain (causing waking), especially during the second half of sleep duration
  • Alternating buttock pain
Ankylosing Spondylitis:

The modified New York criteria were originally found to be very specific in the diagnosis of ankylosing spondylitis (AS), however, insensitive in the diagnosis of early stage disease due to their emphasis on observable, radiographic changes to the SI joints. For contemporary clinicians, screening for inflammatory back pain (as recommended above) likely provides greater clinical utility. The (newer) modified New York criteria require the following for diagnosis of AS:
  • Detection of advanced sacroiliitis on plain films, with any one of the following:
    1. Inflammatory back pain
    2. Limitation of lumbar ROM
    3. Restricted chest expansion
Axial Spondyloarthritis:

In 2009, the Assessment of SpondyloArthritis International Society (ASAS) (5, 6) created classification criteria to encompass both non-radiographic spondyloarthritis (patients with symptoms similar to AS, but without advanced sacroiliitis on plain film) and AS. These authors found that if a patient had not progressed from non-radiographic spondyloarthritis to AS within a decade, it was unlikely to occur. It was also noted that females were more likely to present with non-radiographic spondyloarthritis, and these patients also presented with lower levels of inflammatory markers. These criteria for diagnosis of axial spondyloarthritis are as follows:
  • Back pain for 3 or more months consecutively before the age of 45
  • Sacroiliitis confirmed on MRI or plain film
  • At least one clinical or laboratory finding
Current & Classic Classifications of Spondyloarthritis:

Current Classifications:
  • Axial spondyloarthritis: 1) with radiographic sacroiliitis; or 2) without sacroiliitis (but with sacroiliitis on MRI OR positive HLA-B27 plus clinical criteria)
  • Peripheral spondyloarthritis: 1) with psoriasis; 2) with inflammatory bowel disease (Crohn’s or ulcerative colitis); 3) with preceding infection; or 4) without psoriasis or IBD or preceding infection
Classic Classifications:
  • Ankylosing Spondylitis
  • Reactive arthritis (infection-associated arthritis)
  • Psoriatic spondyloarthritis (predominantly axial or peripheral)
  • Enteropathic spondyloarthritis (associated with inflammatory bowel disease)
  • Juvenile-onset spondyloarthritis (enthesis-related juvenile idiopathic arthritis)
  • Undifferentiated spondyloarthritis
Outcome Measures:
  • Subjective/self-report questionnaires:
    1. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
    2. Bath Ankylosing Spondylitis Functional Index (BASFI)
  • Spinal mobility and radiographic damage:
    1. Bath Ankylosing Spondylitis Metrology Index (BASMI)
    2. Ankylosing Spondylitis Disease Activity Score (ASDAS)
Associated Clinical Manifestations of Axial Spondyloarthritis:
  • Peripheral arthritis, enthesitis or dactylitis (up to half of AS patients)
  • Acute anterior uveitis (30-40% in AS patients)
  • Psoriasis (> 10% of AS patients)
  • Inflammatory bowel disease (5-10% of AS patients)
  • Osteoporosis

Treatment of axial spondyloarthritis (including AS) should focus on reducing symptoms, maintaining spinal mobility, reducing functional limitations and maintaining the ability to work and perform activities of daily living, along with decreasing the complications of disease. The most commonly accepted treatment options include:
  • Active exercise programs to maintain posture and ROM.
  • NSAIDs (including COX2 inhibitors), with doses adjusted according to severity of symptoms.
  • Tumour Necrosis Factor (TNF) inhibitors (particularly if patients are young, have short disease duration, high baseline inflammatory markers and low disability levels).
EDITOR’S NOTE: there is a distinct lack of evidence regarding the efficacy of manual therapy (including spinal mobilization and manipulation) for the treatment of inflammatory back pain. In my experience, this type of treatment can be very beneficial for some patients, yet may not help, or even exacerbate symptoms, for others. The decision to include manual therapy for these patients should include a trial of care with close monitoring of symptoms in order to reach the best management decision for an individual patient.

Clinical Application & Conclusions:

This review paper emphasized the importance of a high index of suspicion when treating patients with chronic LBP, particularly those less than 45 years of age with greater than three months of symptoms. In these patients, clinicians should assess for the presence of symptoms indicative of inflammatory back pain. Although not overtly expected to diagnose AS, non-rheumatological clinicians should evaluate patients and make appropriate referrals in order to prevent the delay in diagnosis that many of these patients unfortunately experience.

It is important to note that plain film radiography may be inadequate for the diagnosis of axial spondyloarthritis (including AS) in the early stage of the disease. It may be appropriate to acquire MRI, laboratory tests (particularly HLA-B27) in the context of clinical symptoms.

Study Methods:

This was a narrative literature review including review and discussion of existing evidence and clinical practice guidelines. As such, no specific methods were outlined.

Study Strengths / Weaknesses:

  • This paper provided a helpful overview of the role of clinical assessment, imaging and laboratory testing in the diagnosis of AS.
  • The importance of a high index of suspicion in the management of patients with chronic LBP was appropriately highlighted.
  • The clinical features of inflammatory LBP were clearly outlined.
  • The primary limitation of this study is that is a narrative review. As such, there is a lack of described methodology. Though it provided a brief summary of the literature, without an understanding of the research question, search strategy or appraisal methods used, the results must be interpreted with a degree of caution.
  • There was little comment or discussion relating to sample sizes, characteristics or strengths and weaknesses of the included studies.
  • We must consider the potential high risk of bias associated with conditions for which pharmaceuticals are considered first line treatment approaches. The authors may not have covered the treatment literature comprehensively, but as mentioned, there is a dearth of manual therapy literature to draw upon at this time.

Additional References:

  1. Reveille JD, Witter JP, Weisman MH. Prevalence of axial spondylarthritis in the United States: estimates from a cross-sectional survey. Arthritis Care Res 2012; 64: 905-10.
  2. van Hoeven L, Luime J, Han H, et al. Identifying axial spondyloarthritis in Dutch primary care patients, ages 20-45 years, with chronic low back pain. Arthritis Care Res 2014; 66: 446-53.
  3. van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum 1984; 27: 361-8.
  4. Feldtkeller E, Khan MA, van der Heijde D, et al. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol Int 2003; 23: 61-6.
  5. Rudwaleit M, van der Heijde D, Landew. R, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): Validation and final selection. Ann Rheum Dis 2009; 68: 777-83.
  6. Rudwaleit M, van der Heijde D, Landew R, et al. The Assessment of SpondyloArthritis international Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011; 70: 25-31.

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