SPONDYLOARTHROPATHIES
Axial spondyloarthritis
Charles Raine
Andrew Keat
Abstract
In Europe and the USA, axial spondyloarthritis (AxSpA) affects approx-
imately 1% of the general population. The term encompasses a wide
spectrum of disease from modest sacroiliac inflammation only detect-
able by magnetic resonance imaging (MRI) to devastating disease with
bony ankylosis. With characteristic X-ray changes, the term ‘anky-
losing spondylitis0 (AS) is used. AS affects men three times more
often than women, but AxSpA without X-ray changes affects men
and women equally. Symptoms usually begin in the third decade of
life with inflammatory back pain. The key pathological element is
enthesitis, although the main diagnostic feature is sacroiliitis. Approx-
imately one-third of patients develop peripheral lesions including oli-
goarthritis, heel enthesitis, iritis, inflammatory bowel disease and
psoriasis. Vertebral osteoporosis is not uncommon, and cardiovascu-
lar disease and renal impairment can complicate severe AS. The diag-
nosis of AxSpA can be made on the basis of imaging or on clinical
features alone. The cause(s) of AxSpA remain unknown, but genetic
factors, including HLA-B27 and the interleukin (IL)-23 receptor, confer
susceptibility; and a link with gut inflammation and microbiota is sus-
pected. Treatment includes regular exercises and non-steroidal anti-
inflammatory drugs; tumour necrosis factor (TNF) and IL-17 inhibitor
drugs provide dramatic improvements in symptoms, function and
quality of life.
Keywords Ankylosing spondylitis; axial spondyloarthritis; biologic
therapy; diagnostic criteria; enthesitis; MRCP; treatment
Introduction
Axial spondyloarthritis (AxSpA) is an aseptic inflammatory
condition primarily affecting entheses and synovial joints in the
spine, producing pain, fatigue and progressive spinal stiffness.
Involvement of extraspinal sites is also common and can be
especially disabling.
It is now recognized that AxSpA occupies a spectrum. Many
patients have inflammation at the sacroiliac joints or elsewhere
in the spine that is detectable by magnetic resonance imaging
(MRI), but approximately half of these will develop radiographic
sacroiliac joint and/or spinal changes. When radiographic
changes at the sacroiliac joints are present, the term ‘ankylosing
spondylitis’ (AS) is used. It is a life-long condition of adults that
substantially impairs quality of life and work capacity, and can
shorten life.
Charles Raine BM BCh MRCP Specialist Registrar, Department of
Rheumatology, Northwick Park Hospital, Harrow, UK. Competing
interests: none declared.
Andrew Keat MD FRCP Consultant Rheumatologist, Department of
Rheumatology, Northwick Park Hospital, Harrow, UK.Competing
interests: none declared.
MEDICINE 46:4
Key points
C The spectrum of axial spondyloarthritis, ranging from non-
radiographic disease to severe ankylosing spondylitis, is
now well recognized
C Enthesitis and osteitis, both of which are demonstrable on
MRI, are the key pathological lesions representing active dis-
ease. Emerging evidence supports early recognition and
treatment to improve long-term outcomes
C MRI scanning, using selected fat-suppressed (STIR) and T1
sequences offers the best objective guide to early diagnosis
C A variety of patient- and physician-reported disease activity
scoring systems exist and should be used regularly to monitor
progress and response to treatment; these include the Anky-
losing Spondylitis Disease Activity Score, which provides
useful gradations of disease activity
C Genome-wide association studies have identified multiple
genetic loci, notably ERAP1 and IL23R, that contribute to the
development of ankylosing spondylitis in addition to HLA-B27
C Mechanisms of pathogenesis probably include roles for the
gut microbiota and local mucosal immunity, a novel popula-
tion of interleukin (IL)-23-dependent T cells resident in
entheses, HLA-B27 metabolism, and the IL-23eIL-17 axis
C Tumour necrosis factor-inhibitor drugs are the mainstay of
treatment of severe AS. IL-17 inhibition with secukinumab is
equally effective, and new drugs, including both biologic
agents and oral ‘small molecules’, are currently in clinical trials
AxSpA is a member of the spondyloarthritis (SpA) family,
whose members share similar clinico-pathological features and
genetic predisposition, notably an association with the HLA-B27
and other genes. Other members of this group are psoriatic
arthritis, reactive arthritis and enteropathic arthritis. Undiffer-
entiated forms of SpA also occur in both children and adults,
although involvement of the spine tends not to occur until the
late teenage years. The prevalence of AxSpA varies in different
populations, according to the background prevalence of HLA-
B27, being higher in some circumpolar regions and lower in
some black African populations. The prevalence of AxSpA in the
USA has been defined as 1.0e1.4%, and that of AS 0.52e0.55%.1
Clinical features
AxSpA usually begins in the late teens or 20s, typically present-
ing with inflammatory back pain (Table 1).2 Back pain and
stiffness are usually worse after inactivity and can awaken the
sufferer from sleep. Symptoms improve with movement, so ex-
ercise is usually helpful. Sacroiliitis often causes buttock pain
that can radiate down the back or front of either or both thighs
but not below the knee. Typically, symptoms affect one side for a
period of weeks or months and then subside, only to be followed
231 Ó 2018 Published by Elsevier Ltd.
 SPONDYLOARTHROPATHIES
Inflammatory spinal pain2
ASAS definition e spinal pain ‡3 months plus:
C Onset <40 years of age
C Insidious onset
C Improvement with exercise
C No improvement with rest
C Pain at night (with improvement on getting up)
The criteria are fulfilled if four or five parameters are met.
Table 1
by similar symptoms on the other side. This is known as alter-
nating buttock pain. In up to one-third of patients, the peripheral
skeleton is affected.
Extra-articular sites, including the entheses and eyes, can also
be involved; both can precede the spinal symptoms. Chest wall
pain is also common, resulting from either costochondritis or
referred pain from the thoracic spine. Fatigue is often a disabling
symptom.
Male predominance is the rule when radiographic changes are
present (ratio of 3:1), but in non-radiographic AxSpA (nrAxSpA),
the sex ratio is equal. Morbidity in nrAxSpA is similar to that in
established AS.
Poor quality of life and socioeconomic consequences are criti-
cally important. In AxSpA, reduced work capacity is associated
with both personal and societal costs, and many sufferers have
substantial difficulties with personal relationships and recreation.3
Musculoskeletal features
Enthesitis: the key pathological lesion of AxSpA is enthesitis.
Entheses are complex and variable structures at the junction
between ligaments, joint capsules or tendons and bone. In the
spine, entheses are affected at the attachment of joint capsules
around facet joints and sacroiliac joints, at the discovertebral
junctions and at the attachments of the interspinous ligaments.
Initially, inflammatory entheseal lesions may be detectable by
MRI e although this is not always of sufficient sensitivity e as
areas with a high water signal on fat-suppressed sequences
(e.g.short tau inversion recovery (STIR)). Later, radiographs may
show areas of decalcification (‘erosions’) that subsequently give
place to new bone formation. Ultrasound scanning is increas-
ingly used to identify peripheral entheseal lesions. Ossification of
entheseal lesions leads to the process of ankylosis.
Peripheral enthesitis is a characteristic feature of AxSpA. Most
commonly, the heel is involved. Achilles tendon enthesitis oc-
curs at the point of attachment, in marked contrast to the
thickening and pain higher up the tendon that is seen in athletes.
Enthesitis is often associated with formation of an Achilles
tendon bursa, seen best from behind with the patient standing.
Involvement of the plantar fascia is also characteristic, with
troublesome pain and the formation of a fluffy bony spur on X-
ray. These changes can be impossible to distinguish from
degenerative plantar fasciitis. Evaluation of the entheseal lesions
can be performed using the Maastricht Ankylosing Spondylitis
Enthesis Score (MASES) or the Leeds Enthesitis Index (LEI).
Dactylitis, usually affecting a single toe (‘sausage toe’), results
from multiple entheseal lesions, often with associated synovitis,
MEDICINE 46:4
and is highly suggestive of SpA (see Jacques and McGonagle in
Further reading).
Sacroiliitis: this is often the cause of the presenting symptoms of
buttock and/or thigh pain. It must be distinguished from me-
chanical pain referred to the same areas from the lumbosacral
spine. Clinical signs are unreliable, and the diagnosis is best
made by MRI; however, the sensitivity of MRI is limited by the
relatively dynamic bone marrow changes, and distinction from
degenerative change can be difficult. Typical appearances are of
juxta-articular bone marrow oedema best seen on a STIR (or
similar) sequence, with later fatty change also seen on T1 se-
quences. Diagnostic appearances are defined and well illustrated
in the Assessment of SpondyloArthritis International Society
(ASAS) handbook.3
Radiographic changes of sacroiliitis are graded as 0e4, but
such changes take several months or years to become diagnostic.
MRI scanning may allow detection of pre-radiographic change
and hence facilitate early diagnosis.
Spinal lesions: radiographic changes occur late, but are highly
specific, whereas MRI changes may be detected earlier but are
less specific. Inflammatory lesions at the corners of vertebral
bodies are characteristic; these appear as bone oedema or fatty
change on MRI and as sclerotic ‘shiny corners’ on X-ray. In older
adults, such changes of osteitis are relatively non-specific,
although osteitis at the pedicle is strongly linked with AxSpA.
Osteitis can occur around the facet joints and vertebral spines.
Such changes can lead to new bone formation that is eventually
visible on radiographs as syndesmophytes or bony obscuration
of the facet and sacroiliac joints.3 Spinal deformity with pro-
nounced thoracolumbar kyphosis is not unusual among those
severely affected, and the flexed posture can be aggravated by
hip involvement. Deformity often leads to personal isolation as
well as practical difficulties.
Peripheral arthritis: up to 30% of patients with AxSpA also
develop peripheral arthritis. This is usually asymmetrical oli-
goarthritis affecting the hip, knee and metatarsophalangeal
joints, in contrast to the symmetrical changes in rheumatoid
disease. Synovitis is histologically non-specific, but MRI may
demonstrate extensive entheseal lesions within the joint area.
Extra-articular manifestations
The SpA family of conditions is characterized not only by the
clustering of spinal and peripheral skeletal lesions but also by the
co-occurrence of acute anterior uveitis (AAU; iritis), inflamma-
tory bowel disease (IBD) and cutaneous and mucosal psoriasis.
The link with these lesions is probably explained by common
genetic factors.
Uveitis: AAU occurs in around 30% of people with AxSpA at
some stage but is usually asynchronous with the clinical activity
of other lesions. In unselected patients presenting with AAU, up
to 50% have or develop other features of SpA. AAU is typically
unilateral, causing pain, redness of the eye and photophobia.
Onset is acute and, unless treatment is rapid, blindness can
ensue. Prompt treatment normally leads to full resolution. In
most instances, topical corticosteroid treatment is effective but in
232 Ó 2018 Published by Elsevier Ltd.
 SPONDYLOARTHROPATHIES
cases of refractory uveitis associated with SpA, treatment with
tumour necrosis factor (TNF)-blocking agents can be successful.
Dryness of the eyes in AS is also not uncommon and can cause
minor irritation.
Inflammatory bowel disease: axial or peripheral SpA occurs in
5e15% of people with ulcerative colitis or Crohn’s disease.
Conversely, up to 60% of people with AS have subclinical IBD
detectable by ileocolonoscopy; however, the significance of
subclinical disease in this respect is not clear. Overt IBD can be
exacerbated by non-steroidal anti-inflammatory drugs (NSAIDs)
used to treat AxSpA.
Psoriasis: when AxSpA and psoriasis concur, the term ‘psoriatic
spondylitis’ is usually used. In psoriatic spondylitis, spinal
involvement is typically asymmetrical, often with prominent,
non-marginal syndesmophytes. Sacroiliitis can be unilateral.
Psoriatic lesions are commonly associated with each of the SpAs,
ranging from typical extensor plaque psoriasis to pustular pso-
riasis on the soles, and mucosal psoriasis affecting the mouth and
genitalia.
Co-morbidities
Cardiovascular disease: in up to 1% of patients with long-
standing AS, aortic valve incompetence occurs as a result of
aortitis of the ascending aorta. Cardiac conduction abnormalities
occur in about 5% of patients, and left ventricular dysfunction
has also been described. Active inflammation, high blood pres-
sure, smoking and NSAID consumption can all contribute to an
elevated cardiovascular morbidity in this population. However, it
is likely that most individuals with AxSpA have a normal life
expectancy.
Respiratory disease: rarely, chest wall rigidity is associated with
apical pulmonary fibrosis. More commonly, patients experience
breathlessness on exertion as a result of costovertebral joint
fusion. Sleep apnoea has been described in a few patients.
Renal disease: renal impairment is described in around 10e35%
of patients with AS and may be linked to long-term use of
NSAIDs. Immunoglobulin A nephropathy and amyloidosis have
also been described in individuals with long-standing active AS.
Osteoporosis: axial osteoporosis occurs in around 25% of pa-
tients with AS, with vertebral fractures in 10%.4 Thus, acute
spinal pain in established AS should suggest a diagnosis of spinal
fracture. Treatment with TNF inhibitors prevents or reduces the
severity of osteoporosis.
Aetiology
AxSpA is likely to result from the interaction between environ-
mental and genetic factors. Although no clear mechanism has yet
emerged, different strands of evidence point to a role for intes-
tinal dysbiosis and changes in gut mucosa. Similarly, some evi-
dence suggests that biomechanical stresses can also contribute,
although much work remains to be done.
In contrast, evidence for genetic factors is abundant. Among
white individuals with AS, 95% carry the major
MEDICINE 46:4
histocompatibility complex (MHC) gene HLA-B27, although this
occurs in only 8% of most white populations. In such pop-
ulations, only approximately 2% of HLA-B27 carriers develop
AS, so testing for HLA-B27 is not routinely useful in diagnosing
AS unless there is a high index of suspicion.
However, MHC genes account for considerably <50% of the
genetic susceptibility. Recent genome-wide association studies
have identified significant associations with the endoplasmic
reticulum aminopeptidase1 (ERAP-1, also called ARTS-1) and
interleukin (IL)-23 receptor genes. ERAP-1, which has the second
strongest association with AS, is involved in the processing of
peptides by MHC class I molecules. AS is associated with the
same single-nucleotide polymorphisms of the IL-23 receptor as
those linked to psoriasis and IBD. Other loci elsewhere in the
genome are likely to contribute to susceptibility to AS; some,
including the killer cell immunoglobulin-like receptor (KIR)
genes, may protect against the development of AS or modulate
disease expression.
Current hypotheses of mechanisms by which HLA-B27 leads
to AxSpA involve evidence that HLA-B27 misfolds intracellularly,
leading to the production of IL-23. This has recently been com-
plemented by the finding of a population of T cells resident in
entheses that promote inflammation characteristic of spondy-
loarthritis in response to IL-23 (see Lories and McInnes, and
Hanson and Brown, in Further reading).
Diagnosis
AxSpA encompasses a spectrum of disease from subclinical dis-
ease with limited imaging evidence seen only on MRI scanning
(nrAxSpA) to severe, disabling AS with major morbidity, spinal
deformity and extensive radiographic changes. The presence of
radiographic sacroiliitis is a key feature of the modified New York
criteria for AS (Table 2).5 The ASAS classification criteria
describe the whole spectrum of AxSpA, with evidence of sac-
roiliitis being based on either radiographic or MRI evidence
(Table 3);3 this set of criteria also allows classification on a
purely clinical basis.
Diagnosis is often delayed for up to 10 years, especially in
women, because of difficulties in recognizing inflammatory
Diagnostic criteria for AS5
Modified New York criteria
Clinical criteria:
C Low back pain and stiffness for >3 months that improves with
exercise but is not relieved by rest
C Limitation of motion of the lumbar spine in the sagittal and
frontal planes
C Limitation of chest expansion relative to normal values correlated
for age and sex
Radiological criterion:
C Sacroiliitis grade 2 bilaterally or grade 3e4 unilaterally
Definite AS if the radiological criterion is associated with at least one clinical
criterion.
Table 2
233 Ó 2018 Published by Elsevier Ltd.
 SPONDYLOARTHROPATHIES
ASAS criteria for AxSpA3
In patients with >3 months’ back pain and age at onset <45 years:
Sacroiliitis on imaginga plus 1 SpA featureb
b a
SpA features
C Inflammatory back pain
C Arthritis
C Enthesitis (heel)
C Uveitis
C Dactylitis
C Psoriasis
C Crohn’s/colitis
C Good response to NSAIDs
C Family history of SpA
C HLA-B27
C Elevated CRP concentration
CRP, C-reactive protein.
Table 3
spinal pain, the relatively low incidence of AxSpA among other
causes of back pain, and the long interval between the onset of
symptoms and the appearance of diagnostic radiographic
changes. During this period, irreversible changes frequently
occur, and potential opportunities for treatment can be lost (see
Isdale et al. in Further reading).
Clinical assessment
AxSpA has been very difficult to assess in terms of inflammatory
intensity, impact of disease and skeletal progression. This is prin-
cipally because visualization and quantitation of inflammatory le-
sions are difficult, symptoms are to some extent non-specific, and
radiographic signs of progression are slow to develop. Moreover,
changing levels of acute-phase reactants correlate poorly with spi-
nal disease and can be influenced by co-morbidities.
Numerous measures have been introduced for assessing disease
activity, function, metrology, quality of life and disease progres-
sion.3 These are immensely important in planning and evaluating
treatment, although most suffer from the drawback of subjectivity.
The most widely used measures are summarized below.
Disease activity is most usually measured by the Bath Anky-
losing Spondylitis Disease Activity Index (BASDAI). This is a self-
completed questionnaire relating to symptoms of fatigue, axial
pain, peripheral pain, enthesopathy and stiffness, scored on vi-
sual analogue scales (VASs). The Ankylosing Spondylitis Disease
Activity Score (ASDAS) is a calculation based on some elements
of this, combined with patient global assessment and the addi-
tion of a measure of either serum C-reactive protein or erythro-
cyte sedimentation rate (ESR). An online calculator is available
on the ASAS website. Scoring systems for enthesitis are available
but instruments for the specific evaluation of peripheral SpA are
lacking, so measures used in rheumatoid arthritis and PsA are
usually used.
Graded response scores for the evaluation of axial disease have
also been devised for clinical studies by the ASAS Working
MEDICINE 46:4
Or HLA-B27 plus 2 other SpA featuresb
Sacroiliitis on imaging
C Active (acute) inflammation on MRI highly
suggestive of sacroiliitis associated with
SpA
C Definite radiographic sacroiliitis according
to modified New York criteria
Group. Thus, combined responses in the four domains of patient
global assessment, pain, function and inflammation, are graded
as ASAS 20, ASAS 40 and ASAS 70 scores.
Objective measures of spinal inflammation have been developed
by several groups, notably the Berlin, Leeds, Spondyloarthritis
Research Consortium of Canada (SPARCC) and Danish groups. In
addition, quantitative measures of MRI inflammatory lesions are in
development. These are all cumbersome in clinical practice and
lack optimum sensitivity but are valuable in clinical studies.
Function is most commonly measured using the Bath Ankylosing
Spondylitis Functional Index (BASFI). This records ease of un-
dertaking 10 day-to-day activities on VASs.
Metrology is most commonly assessed using the numerical Bath
Ankylosing Spondylitis Metrology Index (BASMI), which is a
composite measure of spinal movements.
Health-related quality of life and utility in AxSpA/AS can be
measured by a number of generic instruments. SF-36 question-
naire profiles patients’ general health status within four physical
and four mental health domains. The Ankylosing Spondylitis
Quality of Life (ASQoL) questionnaire provides simple scores on
18 questions and is easy to use in clinical settings. The five-
dimension EuroQol (EQ-5D) allows the derivation of a health
utility score from which quality-adjusted life-years can be
calculated.
Spinal disease progression is usually assessed in research
studies using the modified Stoke Ankylosing Spondylitis Spine
Score (mSASSS). This is a measure of anterior syndesmophyte
formation in the cervical and lumbosacral spine. It is convenient
to score, requiring only lateral radiographs of the cervical and
lumbosacral spine and is sensitive to change; however, it does
not take into account changes in the posterior spine or thoracic
segment.
234 Ó 2018 Published by Elsevier Ltd.
 SPONDYLOARTHROPATHIES
Treatment
The treatment of AxSpA should be regarded as the sum of
treatments of the individual lesions. Hence, treatment of pe-
ripheral arthritis and enthesitis follows approaches used in other
peripheral arthritides and iritis, psoriasis and IBD require specific
regimens, as in individuals without AS.
Treatment of spinal disease is aimed at reducing pain and
stiffness and increasing well-being and function. The prevention
of bony progression remains an important aim, although it re-
mains uncertain whether any current treatment modality can
achieve this. The key to maintaining comfort and spinal mobility
is regular exercise. Intermittent physiotherapy can be necessary
to correct or minimize deformity and restriction of spinal
mobility, as well as to maintain motivation; regular sporting
activities are also highly desirable and remain so throughout life.
The reduction of pain and stiffness and the ability to exercise
are usually best achieved by regular treatment with NSAIDs. Both
non-selective cyclo-oxygenase inhibitors, such as diclofenac and
naproxen, and selective cyclo-oxygenase-2 inhibitors, such as
etoricoxib and celecoxib, can be helpful. Regular NSAID medica-
tion should be accompanied by use of a proton pump inhibitor in
individuals aged >65 years. The risk of enhanced cardiovascular
and renal disease with regular NSAID use should also be borne in
mind in treatment-planning; pre-existing risk factors should be
controlled to minimize risk. Regular NSAID usage can help to slow
ankylosis, although on-demand treatment may be better tolerated.
Smoking cessation is an important part of management as
smoking is associated with both higher disease activity and faster
radiographic progression. Disease-modifying anti-rheumatoid
drugs, such as sulfasalazine, methotrexate and leflunomide,
exert little or no effect on spinal disease but can be helpful in the
treatment of peripheral joints and entheseal disease.
Treatment with biologic agents is a well-established approach
for patients in whom NSAIDs have produced insufficient symp-
tomatic benefit. TNF inhibitors, adalimumab, etanercept, goli-
mumab, certolizumab and infliximab have been shown
substantially to reduce symptoms and improve function and
quality of life. The recent introduction of biosimilar versions of
some of these agents offers the ability to achieve the same efficacy
at lower cost. TNF inhibitors have been shown to be beneficial in
peripheral as well as axial disease and may antagonize the
development of osteoporosis in AS patients. However, in contrast
to their effects in rheumatoid arthritis, evidence of reduction of
bony progression is so far weak. This aspect of treatment is being
further explored with earlier treatment regimens.
Non-TNF-blocking biologic agents are also important in this
respect, as it is now clear that both IL-23 and IL-17 play a crucial
role in AxSpA. The IL-23 and IL-12 blocker ustekinumab has been
shown to be effective for treatment of both axial and peripheral
SpA; although it is approved for treatment of psoriatic arthritis,
benefits in AxSpA are modest, so it is not widely available for this
purpose. Investigation of other IL-23 blockers continues. Antago-
nism of IL-17 has, however, been shown to be highly effective,
comparable to TNF inhibitors, and secukinumab is approved for
treatment of AxSpA, psoriatic arthritis and psoriasis. Other bi-
ologics, including anakinra, rituximab, tocilizumab and abatacept,
appear to have little or no effect on axial disease.
MEDICINE 46:4
Biologic treatment is regulated in many countries by national
guidelines. In the UK, guidance has been published by the Na-
tional Institute for Health and Care Excellence (NICE - technology
appraisals 143, 233, 383 and 407). Guidance on the management
of AxSpA has been published by the British Society for Rheu-
matology (see Hamilton et al. in Further reading).
The search for small molecule treatments for AxSpA, which
can be administered orally, is well advanced. However, neither
apremilast, a phosphodiesterase type 4 inhibitor that is effective
in psoriatic arthritis, nor tofacitinib, a Janus kinase (JAK) in-
hibitor effective in the treatment of rheumatoid arthritis, has
shown sufficient efficacy in AxSpA.
For patients whose quality of life is significantly compromised
by advanced spinal deformity, surgical correction through
osteotomy remains an important therapeutic consideration. Hip
and knee arthritis also necessitates surgery in a substantial mi-
nority, with heterotopic ossification commonly leading to
recurrent joint restriction and surgical revision.
Outcomes
There are few reliable predictors of outcome for people devel-
oping AxSpA, although it is clear that severe early disease, hip
involvement, male sex and elevated acute-phase markers bode ill
for future function. In patients with early disease, it is likely that
the presence of syndesmophytes at baseline, elevated acute-
phase markers and smoking status predict spinal radiographic
progression. It is not clear how often disease becomes quiescent
(‘burns out’): although this is sometimes described; apparent
quiescence often reflects tolerance of long-term symptoms by
patients and low-grade persistent chronic disease.
For many patients, work disability provides a measure of
functional impairment and an indicator of social and personal
morbidity. Hence maintenance of normal work status remains a
key outcome of treatment. Spinal deformity is becoming less
common, although it is still a blight for around 5% of hospital
attenders with AS.
Most people with AS live a normal lifespan. However, for
those with severe disease, premature death can result from car-
diovascular disease or renal impairment. Complications of skel-
etal surgery, trauma to a rigid spine and amyloidosis make a
small additional contribution to excess mortality. Cardiovascular
risk management, as recommended by European League Against
Rheumatism guidelines, might help to reduce the increased
atherosclerotic risk in patients with SpA in the future. A
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FURTHER READING
Hamilton L, Barkham N, Bhalla A, et al. BSR and BHPR Standards,
Guidelines and Audit Working Group.BSR and BHPR guideline for
the treatment of axialspondyloarthritis (including ankylosing
TEST YOURSELF
To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the
end of the issue or online here.
Question 1
A 24-year-old woman presented with a 6-month history of low
back and buttock pain radiating to the left posterior thigh. She
was an active sportswoman but there was no history of injury.
She had developed marked fatigue with pronounced stiffness in
the morning and after inactivity. At age 18, she had an episode of
iritis (anterior uveitis).
Clinical examination showed no abnormal signs.
Which of the below would best confirm the most likely
diagnosis at this stage?
A Assessment of response to non-steroidal anti-inflammatory
agent treatment (NSAIDs)
B Bath Ankylosing Spondylitis Metrology Index (BASMI)
score conducted by a specialist physiotherapist
C Blood tests for inflammatory markers
D Magnetic resonance imaging of the whole spine including
the sacroiliac joints
E X-ray of the sacroiliac joints
Question 2
A 29-year-old man with ankylosing spondylitis had been given
anti-tumour necrosis factor (TNF) treatment with golimumab for
the previous 12 months. He reported a significant reduction in
pain and stiffness since commencing the medication and no
longer needed to use regular non-steroidal anti-inflammatory
drugs (NSAIDs). His Bath Ankylosing Spondylitis Disease Ac-
tivity Index (BASDAI) and visual analogue scale spinal pain score
had fallen from 6.8 to 5.0, respectively (pre-treatment), to 3.2
MEDICINE 46:4
spondylitis) with biologics. Rheumatology (Oxford) 2017; 56:
313e6.
Hanson A, Brown MA. Genetics and the causes of ankylosing spon-
dylitis. Rheum Dis Clin N Am 2017; 43: 401e14.
Isdale A, Keat A, Barkham N, et al. Expanding the spectrum of in-
flammatory spinal disease: AS it was, as it is now. Rheumatology
(Oxford) 2013; 52: 2103e5.
Jacques P, McGonagle D. The role of mechanical stress in the path-
ogenesis of spondyloarthritis and how to combat it. Best Pract Res
Clin Rheumatol 2014; 28: 703e10.
Lories RJ, McInnes IB. Primed for inflammation: enthesis-resident T
cells. Nat Med 2012; 18: 1018e9.
and 1, respectively. However, on assessment by the specialist
physiotherapist, his Bath Ankylosing Spondylitis Metrology
Index (BASMI) score was found to have risen since the initiation
of effective treatment.
What is the most appropriate action at this point?
A Continue current management
B Restart regular NSAIDs
C Refer for formal physiotherapy
D Switch to secukinumab
E Switch to an alternative anti-TNF agent
Question 3
A 68-year-old man presented with a 2-week history of severe
pain in the lower thoracic spine with no preceding trauma. He
had long-standing ankylosing spondylitis, generally well-
controlled in recent years with self-directed exercise and occa-
sional NSAIDs (co-prescribed with a proton pump inhibitor)
during flares.
On clinical examination, there was intense pain on thoracic
rotation and exquisite tenderness at the T12 vertebra.
What is the next most appropriate action?
A Arrange a spinal X-ray
B Prescribe full-dose NSAID therapy
C Plan urgent biologic treatment
D Refer to physiotherapy
E Refer to a spinal surgeon
236 Ó 2018 Published by Elsevier Ltd.