Rheumatology

Ankylosing spondylitis:
Vera Golder
Lionel Schachna
an update
Background Spondyloarthritis (SpA) encompasses a group of rheumatic
Ankylosing spondylitis (AS) affects one in 200 individuals and disorders that share clinical, genetic and radiographic
is usually diagnosed many years after onset of symptoms. features and includes psoriatic arthritis, reactive arthritis
Chronic back pain is common and recognition of early disease and arthritis of inflammatory bowel disease. These
requires clinical experience and a high index of suspicion. disorders affect 2–3% of the population and are twice as
Further, inflammatory markers are not invariably elevated and common as rheumatoid arthritis. As they often cause long-
radiographic changes are often late findings. term disability, early recognition is important.
Objective
The objective of this review is to address AS and the recently This review will focus on ankylosing spondylitis (AS) and the recently
defined disorder of non-radiographic axial spondyloarthritis. defined disorder of non-radiographic axial SpA.1 These conditions
The latter is a common early presentation of AS, before the occur in one in 200 individuals but most general practitioners have
development of radiographic sacroiliitis, and will evolve into never identified a new case of AS, suggesting the need for a higher
typical AS in 50% of patients. index of suspicion in primary care.
Discussion
MRI may be particularly useful in evaluating early disease, Clinical features
although chronic changes of sacroiliitis are better seen on
Back pain
plain X-rays. Nonsteroidal anti-inflammatory drugs (NSAIDs)
are first-line therapy and recent studies suggest that regular Approximately 5% of chronic lower back pain is attributable to SpA.
use among patients with AS slows radiographic progression.
The presence of inflammatory back pain (IBP), the archetypal feature
Tumour necrosis inhibitor therapy has strikingly improved
of AS, increases the likelihood of SpA to approximately 14%.2 Table 1
quality of life for the more than two-thirds of AS patients with
shows the differentiating features of inflammatory and mechanical
an inadequate response to NSAIDs.
back pain. Two very specific features of IBP are alternating buttock
Keywords pain and awakening only in the second half of the night with spinal
rheumatology; ankylosing spondylitis; spondyloarthritis; pain or stiffness. Clinicians can only assess the activity of IBP by
therapeutics subjective symptoms: fatigue, spinal pain, and severity and duration
of morning stiffness. Identification of IBP should prompt more detailed
evaluation and consideration of a multimodality treatment approach.2

Table 1. Characteristics of inflammatory and

mechanical back pain
Inflammatory Mechanical
Age at <40 years old Any age
symptom onset
Onset Insidious, persists Variable
for >3 months
Activity Improves with Improves with
exercise rest
Morning Moderate, persists Mild, short-lived
stiffness for >45 minutes
Inflammatory Elevated in Normal
markers 50–70%

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Reduced spinal mobility Juvenile SpA
The most common measures of spinal mobility are listed below. It is important to be aware of juvenile SpA and 50% of cases will
• Modified Schober’s test (Figure 1 ): serial measures are valuable in evolve into typical AS. Asymmetric oligoarthritis, often associated
assessing progression of spinal restriction; may be abnormal with with severe midfoot pain (tarsitis), is a common presentation. HLA-
disc disease and degenerative lumbar disease. B27, tarsitis and hip involvement are predictors of the persistence of
• Lumbar side flexion: the best measure of overall spinal restriction disease as AS into adulthood.
and disease activity.
• Occiput-to-wall distance: should be zero in normal people. Investigations
Chest expansion (at the fourth intercostal space): abnormal (<5 cm) in Imaging
only a minority of patients during the first few years of disease
It is important to note that in early disease, spinal mobility may be X-ray
normal. A single anteroposterior pelvis X-ray (rather than dedicated sacroiliac
joint views) should be adequate to assess the sacroiliac joints. AS
Extra-axial features is defined by IBP and at least bilateral grade 2 or unilateral grade 3
Peripheral arthritis occurs in all variants of SpA. Up to 50% of AS changes (Figure 2 ).4
patients develop asymmetric oligoarthritis (≤4 joints), often targeting The radiographic findings represent reparative changes in response
the lower limb joints. Enthesitis or inflammation at insertions of to earlier acute inflammation. As such, the appearance of radiographic
tendons, ligaments and joint capsules into bone can present as abnormalities is typically delayed. In the spine, there is progression
Achilles tendinitis, plantar fasciitis and intercostal enthesitis, which from reactive sclerosis (‘shiny corner’ or Romanus lesion), squaring
causes chest wall pain. Dactylitis (‘sausage digit’) is diffuse swelling and erosions at the edge of the vertebral bodies to syndesmophyte
of a finger or toe caused by tenosynovitis of the digital flexor tendon, formation and bony bridging (Figure 3 ). The classic ‘bamboo spine’ is
and is more common in psoriatic and reactive arthritis. characteristic of advanced AS.

Extra-articular features Magnetic resonance imaging (MRI)

Uniocular anterior uveitis occurs in about 40% of patients and MRI is often considered when X-rays are normal but there is a clinical
typically presents as acute painful red eye, with blurred vision suspicion of SpA. MRI may be particularly helpful in early disease,
and photophobia. In suspected first episodes of anterior uveitis, although it can be normal even in active SpA and the chronic changes
ophthalmology review for slit-lamp examination is mandatory. of sacroiliitis are better seen on plain X-rays. Fat-suppressed short
First-line treatment is a combination of corticosteroid and mydriatic T1 inversion recovery (STIR) sequences demonstrate marrow oedema
eye drops. About 60% of AS patients have mucosal inflammation at the sacroiliac joints and/or vertebral corners. Marrow oedema is
on colonoscopy, while symptomatic inflammatory bowel disease associated with later development of bony sclerosis or fusion, either of
occurs in 10% of patients. Osteopenia and osteoporosis commonly the sacroiliac joints or spine.5
occur, particularly in long-standing persistently active disease, and
Ultrasonography
the risk of vertebral fracture is increased approximately sevenfold.
Importantly, bone densitometry in the spine may be spuriously Ultrasonography can be useful in detecting enthesitis, such as
elevated by the syndesmophytes of AS. Patients with AS are at risk Achilles tendonitis. Its role in the detection of sacroiliitis remains to
of developing apical pulmonary fibrosis (up to 15%) and aortic valve be determined as this modality is largely operator-dependent. There
incompetence (up to 10%). These features usually develop late in the are, however, some suggestions that colour Doppler ultrasound may be
disease and are often asymptomatic. used to diagnose early sacroiliitis and to monitor response to therapy.

A) Patient standing erect. Mark

an imaginary line connecting
both posterior superior iliac
spines (close to the dimples of
Venus).
B) A mark is placed 10 cm above.
C) The patient bends forward
maximally, measure the
difference between the two
marks. Report the increase (in
A B C cm to the nearest 0.1 cm). The
Figure 1. Spinal Mobility – Modified Schober best of two tries is recorded.
Reproduced with permission from ASAS handbook, Ann Rheum Dis 2009; 68 (Suppl II)

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 FOCUS Ankylosing spondylitis: an update

Grade 1 Grade 2

Grade 3 Grade 4

Figure 2. Radiographic grading of sacroiliac joints. Grade 1: Suspicious changes, not definitive. Grade 2: Small localised
areas of erosions or sclerosis; normal joint space width. Grade 3: Definite changes of erosions, sclerosis, narrowing or partial
fusion. Grade 4: Complete fusion

Laboratory tests longer among women, who comprise one third of AS patients, perhaps
Acute phase reactants such as erythrocyte sedimentation rate (ESR) and related to a misconception that AS is rare among women.
C-reactive protein are useful markers of inflammation but are elevated in Features of SpA are important to identify early at presentation and
only 50–70% of AS patients. They are more likely to be elevated in patients include alternating buttock pain, asymmetric peripheral arthritis, heel
with concurrent peripheral arthritis and inflammatory bowel disease. pain, uveitis, positive family history and good response to non-steroidal
anti-inflammatory drugs (NSAIDs). The presence of one or two of these
The role of HLA-B27 and other genes features increases the likelihood of SpA to 35–70%, and three or more
The association of HLA-B27 with AS is well established and occurs features increases the likelihood to 80–95%.3
in 85–90% of patients. HLA-B27 is seen in 5–15% of the general
population, with some variability associated with ethnic background, Non-radiographic axial SpA
but only 5% of HLA-B27 positive people develop AS. As such, HLA-B27 Even in the modern era of MRI, X-ray changes at the sacroiliac joints
in the patient with clinical features of SpA can support the diagnosis must be present in order to establish a diagnosis of AS. The delay
but has no role as a general screening test for spinal pain. from symptom onset to X-ray changes, however, can be 10 years
or more. Many but not all patients with early presentations have
Delay in diagnosis active sacroiliitis on MRI scan. If MRI abnormalities are identified,
The delay between onset of symptoms and physician diagnosis of AS is a diagnosis of non-radiographic axial SpA can be established if at
5–7 years on average.6 Chronic back pain is common and recognition of least one clinical feature of SpA is present. If the MRI is normal, then
early disease requires clinical experience and a high index of suspicion. HLA-B27 and two or more SpA features are required. The Assessment
Further, inflammatory markers are not invariably elevated and of SpondyloArthritis International Society (ASAS) has developed and
radiographic changes are often a late finding. The delay in diagnosis is validated these classification criteria (Figure 4).7

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 Ankylosing spondylitis: an update FOCUS

Although patients with non-radiographic axial SpA patients have and NSAIDs, but not for non-radiographic axial SpA. As such, X-ray
fewer intense inflammatory changes on MRI and have lower levels changes of sacroiliitis are required. Randomised controlled trials,
of inflammatory markers, they have similar levels of disease activity however, suggest better clinical responses in early non-radiographic
and pain as those with established AS. Therefore patients with non- disease.
radiographic axial SpA warrant early evaluation and treatment. For IBP, all TNF inhibitors have similar efficacy and the choice
of agent is often determined by extra-articular features and patient
Predictors of outcome preference. Approximately 94% of AS patients commenced on
Several factors associated with poor prognosis are identified in AS, treatment with a TNF inhibitor at Austin Health in Melbourne remain
most importantly juvenile-onset and hip arthritis. Other factors include on long-term treatment (personal communication). To date, there is
persistent active disease, cigarette smoking, inadequate response to little evidence to suggest slowing of spinal fusion with TNF blockers.
NSAIDs and baseline spinal radiographic changes.
Other DMARDs
Management Traditional DMARDs such as methotrexate and sulfasalazine have little
Symptom management effect in spinal disease, but can be useful for an associated peripheral
arthritis. Other biologic agents available for rheumatoid arthritis in
Education and exercise Australia have not been effective in AS.
As with any chronic condition, patient education and support is vital in
the management of AS. Patient disease and medication information, Assessment and monitoring
as well as access to support groups, can be found on the Arthritis In concert with the treating rheumatologist, the general practitioner
Australia website (www.arthritisaustralia.com.au). A tailored exercise has an important part to play in monitoring of AS patients. The goal of
and stretching program is recommended for AS patients and there are AS treatment in 2013 should be to achieve a state of minimal morning
several useful online resources (eg. www.nass.co.uk/exercise) and stiffness and gel phenomenon, stable measures of spinal mobility
mobile apps (eg. iAnkSpond). and optimal functional status. A significant change in any of these

NSAIDs
NSAIDs are first-line therapy for symptomatic AS patients. Recent Chronic back pain
(>3 months) with age of
studies suggest that regular NSAID use in AS slows radiographic
onset <45 years
progression more than on-demand use.8 An individualised assessment
of risk of long-term NSAID use should be made in consultation with the
rheumatologist before long-term daily NSAID use is recommended. Sacroiliitis on
OR HLA-27 positive
imaging (MRI or
Tumour necrosis factor (TNF) inhibitors plus at least 2 other
X-ray) plus at least
SpA features
TNF inhibitor therapy has strikingly improved the quality of life for 1 other SpA feature
the more than two thirds of AS patients with an inadequate response
to NSAIDs.9 These agents are listed on the Pharmaceutical Benefits SpA features:
Scheme (PBS) for active AS not adequately responsive to exercise • inflammatory back pain
• arthritis
• enthesitis
• uveitis
• dactylitis
• psoriasis
• IBD
• good response to NSAIDS
• family history of SpA
• HLA-B27
• elevated CRP

Figure 4. ASAS classification criteria for axial

spondyloarthritis.7 These classification criteria have a
sensitivity of 83% and specificity of 84% for detecting
Figure 3. Lumbar spine changes in AS. A) Shiny corners all axial SpA. (IBD = inflammatory bowel disease,
and erosions. B) Early syndesmophytes C) Spinal fusion CRP = C-reactive protein, NSAID = non-steroidal anti-
or ankylosis inflammatory drug)

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 FOCUS Ankylosing spondylitis: an update

parameters should prompt semi-urgent review by a rheumatologist. drugs reduce radiographic progression in patients with ankylosing spondy-
litis: a randomized clinical trial. Arthritis Rheum 2005;52:1756–65.
General practitioners should familiarise themselves with the risks of 9. van der Heijde D, Sieper J, Maksymowych WP, et al. 2010 Update of the
TNF inhibitors, particularly infection. Among Australian patients, risk international ASAS recommendations for the use of anti-TNF agents in
patients with axial spondyloarthritis. Ann Rheum Dis 2011;70:905–08.
of melanoma and other skin cancers is important to recognise. Before
major surgery, TNF inhibitors are generally withheld for 1–2 half-
lives. The treating rheumatologist should be notified of any possible
complications of treatment, to consider whether to withhold or cease
treatment.

Key points
• Inflammatory back pain can be identified only by a targeted medical
history.
• In early disease, spinal mobility may be normal.
• Identification of IBP should prompt more detailed evaluation and
consideration of a multimodality treatment approach.
• The diagnosis of AS is established by IBP and the presence of
definite X-ray changes of sacroiliitis.
• Non-radiographic axial SpA, with or without MRI changes, is often
an early presentation of AS.
• Patient education and a tailored exercise routine are essential
aspects of management.
• NSAIDs are first-line therapy in SpA.
• TNF inhibitors are indicated in AS patients with inadequate
response to exercise and NSAIDs.
• Regular review of IBP symptoms and spinal mobility is important to
determine the effectiveness of treatment.

Authors
Vera Golder MBBS, Advanced Trainee in Rheumatology, Austin Health,
Melbourne, VIC. vera.golder@gmail.com
Lionel Schachna MBBS, FRACP, PhD, Consultant Rheumatologist,
Austin Spondylitis Clinic, Austin Health, Melbourne, VIC

Competing interests: None.

Provenance and peer review: Commissioned; externally peer reviewed.

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