J. H. Stone (ed.), A Clinician's Pearls and Myths in Rheumatology,
DOI:10.1007/978-1-84800-934-9_7, © Springer Science + Business Media B.V. 2009

57

Myth:

AS is a rare disease.

Reality: AS, the most common subtype of spondyloarthritis,
has a prevalence in the range of 0.3–0.5% (Braun and Sieper
2007). The group of spondyloarthritides as a whole has a
prevalence that is approximately as high as that of rheumatoid
arthritis (RA) (Saraux et al. 2005). The prevalence of spondy-
loarthritis among patients who present to general practitioners

with chronic back pain that has persisted for more than 3
months is on the order of 5% (Underwood and Dawes 1995).

Myth:

AS is a benign disease with a relatively good prognosis.

Reality: An oft-quoted study that examined military veterans
with AS is partly responsible for this myth (Carette et al.,
1983). However, that study was characterized by a high loss
to follow-up. Contrary to this Myth as stated, many patients
who were tracked for a long period developed severe func-
tional restrictions. Other studies indicate that at least one
third of patients with AS have severe courses characterized
by signifi cant pain and disability (Zink et al. 2000). These
morbidities have substantial implications for family life and
occupation (Ward et al. 2008).

Myth:

Only males get AS.

Reality: Older textbooks of rheumatology reported the male
predominance in AS to be as high as 16:1. However, a more
accurate estimation of the male:female ratio is on the order of
2:1. Besides numbers, some true differences do appear between
male and female patients with AS. For example, male patients
are more likely to have syndesmophytes and bony ankylosis
than females with the disease (Rudwaleit et al. 2009a).

Myth:

Infl ammatory back pain is such a highly specifi c symp-

tom that it is nearly diagnostic of AS or some form of spondy-
loarthritis.

Reality: Infl ammatory back pain is a hallmark of AS.
However, it is present in only about 70% of patients with
established disease. In addition, up to 30% of patients with
back pain due to other causes also report symptoms compat-
ible with an infl ammatory etiology. Thus, additional history
that supplements symptoms compatible with infl ammatory
back pain is required to make the diagnosis. Such additional
information might include a good response to NSAIDs, posi-
tivity for HLA-B27, an elevated C-reactive protein, other
features of spondyloarthritis such as uveitis, psoriasis, and
colitis, and compatible fi ndings on imaging studies of the
sacroiliac joints. New criteria for infl ammatory back pain
(Rudwaleit et al. 2006) and axial SpA (Rudwaleit et al.
2009b, c) have been proposed recently.

Ankylosing Spondylitis

Juergen Braun and David Tak Yan Yu

7

7.1 Overview of Ankylosing Spondylitis

Ankylosing spondylitis (AS) is the prototypical form

›

of the spondyloarthritides, a group of disorders that
involves infl ammation of the sacroiliac joints, spine,
joints, and entheses, as well as extraspinal lesions of
the eye, bowel, and heart.
Human leukocyte antigen (HLA) B27 is a strong

›

genetic risk factor for AS. However, this gene is nei-
ther necessary nor suffi cient to cause the disease. Other
recently recognized genes are also involved in the
pathophysiology of this condition.
The principal musculoskeletal lesions of AS are sacro-

›

iliitis, spondylitis, synovitis, and enthesitis. Enthesitis
consists of infl ammation at the site of tendinous inser-
tions into bone.
Sacroiliitis causes infl ammatory back pain often local-

›

ized to the buttocks that can be uni- or bilateral and
typically alternates between the left and right side.
Spondylitis begins characteristically in the lumbosacral

›

region and proceeds cephalad.
The most common extraspinal joints involved are the

›

hips, knees, ankles, and metatarsophalangeal joints. The
pattern of arthritis is typically an asymmetric oligoarthri-
tis that involves the large joints of the lower extremities.
Acute anterior uveitis usually occurs in one eye at a

›

time, although either eye can be involved in any given
episode. Patients usually present with a red, painful,
photophobic eye.

58

J. Braun and D. T. Y. Yu

Myth:

All patients with AS are HLA-B27 positive.

Reality: Although HLA-B27 is clearly the strongest genetic
factor involved in the pathogenesis of AS, it is neither neces-
sary nor suffi cient to cause the disease. The risk contributed
by HLA B27 is about 50% of the total risk attributed to
genes. Other genetic factors such as the IL-23 receptor and
ERAP-1 have been discovered recently (Wellcome Trust
Nature Genetics 2007). Environmental factors may also play
a role, albeit a less important one. Firmly linked environmen-
tal factors have been identifi ed for only a subgroup of SpA,
namely, patients with reactive arthritis (see Chap. 9).

The relative frequency of HLA-B27 varies across differ-

ent populations. More than 40 HLA-B27 subtypes exist. At
least two subtypes are not associated with AS. These are
HLA-B2706 found in Thailand (Lopez-Larrea et al. 2002)
and HLA-B2709 found in Sardinia. In Western countries, it
is generally not useful to determine HLA B27 subtypes.
Caucasians usually carry the HLA B2705 subtype, which is
known to be associated with the disease. A substantial num-
ber of patients who have clinical features compatible with
AS, but who lack HLA-B27 actually have psoriasis or infl am-
matory bowel disease.

Myth:

HLA-B27 is not useful for the diagnosis of AS.

Reality: In certain populations, including the Caucasians of
North America and Western Europe and most of the popula-
tions in China and India, HLA-B27 is present in at least 90%
of patients with AS but among less than 10% of the general
population.

The utility of HLA-B27 in diagnosing AS and SpA is

because, in a patient who presents with lower back pain of
greater than 3 months’ duration, the likelihood of an SpA
increases tenfold if HLA-B27 is present (Braun et al. 1998).
In general, the pretest probability of having the disease mat-
ters. The higher the suspicion of AS before the test, the
greater the posttest probability of a positive result (

Fig. 7.1

)

(Brown 2007). However, its contribution to clinical diagno-
sis is greatest in early disease, the time at which patients
often do not have defi nitive radiographic signs. Accordingly,
a negative test for HLA-B27 largely decreases the likelihood
for AS and SpA.

Thus, if HLA-B27 genotyping is used in an appropriate

clinical circumstance, a positive result contributes signifi -
cantly to the diagnostic evaluation. Therefore, HLA B27
testing has become an important item in the new classifi ca-
tion criteria for axial SpA (Rudwaleit et al. in press (b)).

Myth:

All patients with AS have elevated C-reactive protein

(CRP) levels.

Reality: This unfortunate but widely espoused myth frequently
leads to diagnostic delays. Only one half of all patients with
AS have elevated CRP levels (Spoorenberg et al. 1999).
However, among the sizeable subset of patients who have

elevated CRP levels at baseline, these levels usually fall
dramatically once TNF inhibition is begun (Braun et al. 2002).

A low CRP level does not necessarily predict that the

patient will respond poorly to TNF inhibition. If suffi cient
doses of NSAIDs do not lead to an adequate clinical response,
a trial of a TNF inhibitor is indicated.

Myth:

Measurement of CRP levels is the only way to assess

disease activity in AS.

Reality: The clinical standard to assess disease activity in AS
is the BASDAI (see below). The items “pain” and “morning
stiffness” are considered especially relevant in this regard.
However, magnetic resonance imaging (MRI) has emerged
as an important tool that has the capacity to localize spinal
infl ammation rather exactly (

Fig. 7.2

) (Braun 2002). MRI is

also useful in quantifying the extent of spondylitis before
and after anti-TNF therapy (Braun 2006a).

Myth:

Function in AS is mainly determined by ankylosis.

Reality: As shown in a recent study (Landewé 2009), disease
activity and structural damage both contribute independently
to functional decline in patients with AS. This information is
highly relevant for determining patients’ prognosis for func-
tional recovery and informs management decisions.

Pearl:

Remember to exclude infl ammatory bowel disease in

a patient with AS/SpA.

Comment: The clinical features of AS overlap substantially
with those of infl ammatory bowel disease. Patients with

Fig. 7.1

The relationship between pretest probability to posttest prob-

ability for HLA-B27 determinations (Reproduced from Brown 2007,
with permission from Wiley-Blackwell)

100

90

80

70

60

50

40

30

20

10

0

0

50

Prior disease probability

Post-test probability

100

7 Ankylosing

Spondylitis

59

symptoms such as elevated stool frequency and unexplained
abdominal pain should undergo endoscopy. A low threshold
for endoscopy should also be maintained in patients who are
HLA-B27 negative. This is because, among patients with
infl ammatory bowel disease who have symptoms of SpA,
only approximately 50% are HLA-B27 positive. This con-
trasts with the situation with AS, a population of patients in
whom the great majority are HLA-B27 positive.

A reorientation of the diagnosis to infl ammatory bowel

disease alters the entire therapeutic strategy for a patient with
joint symptoms. TNF blockers such as infl iximab and adali-
mumab are also approved for Crohn’s disease, but additional
therapeutic measures may also be important.

Myth:

Because all patients with AS have sacroiliitis, the

diagnosis is generally quite straightforward.

Reality: The 1984 New York classifi cation criteria for AS
(van der Linden et al. 1984) are useful for the purpose of
classifi cation and diagnosis in patients with long-standing
disease, but not in patients with early disease. This is
because the sensitivity of structural changes within the
sacroiliac joints is high among patients with established
disease, but low (approximately 20%) in patients with
early SpA.

New criteria under development for the diagnosis of AS

include HLA-B27 positivity and fi ndings on MRI studies.
These new criteria are likely to resolve most issues related to
an early diagnosis of axial SpA. Importantly, several param-
eters are required in order for the diagnosis to be classifi ed as
secure (

Table 7.1

) (Rudwaleit et al. b, c).

In the discipline of rheumatology, criteria sets seldom

obviate the need for astute clinical judgement.

Myth:

The radiographic pattern of sacroiliac changes is

clinically relevant because it helps differentiate among the
different forms of spondyloarthritis.

Reality: Structural changes in the sacroiliac joints occur in
approximately 95% of patients with AS. In contrast, only
about 30% of patients with psoriatic SpA and an even smaller
percentage of those with reactive arthritis develop sacroilii-
tis. Thus, AS is much more prevalent than other forms of
axial SpA.

Whereas the sacroiliitis in AS is typically bilateral (at

least in advanced stages of disease), sacroiliac joint infl am-
mation in PsA and ReA is often unilateral and asymmetric
(Muche et al. 2003). However, the full clinical picture and an
accurate determination of symptoms and signs of infl amma-
tion in all joints (and skin, eyes, and gastrointestinal tract) is
crucial. In the early diagnosis of sacroiliitis, MRI is clearly
the study of choice.

Fig. 7.2

Patient with AS,

spondylitis, and structural
changes (a) chronic structural
changes (b) active lesions

a

b

Table 7.1

Preliminary criteria for the diagnosis of ankylosing spondylitis

In patients with

≥

3 months

back pain and age at onset
< 45 years

Sacroiliitis on

imaging plus

≥

1 SpA feature

OR

OR

SpA features

−

IBP

−

arthritis

−

enthesitis heel

−

uveitis

−

dactylitis

−

psoriasis

−

Crohn’s/colitis

−

good response to NSAIDs

−

family history for SpA

−

HLA-B27

−

elevated CRP

≥

1 SpA features

−

Uveitis

−

psoriasis

−

Crohn’s/colitis

−

Preceding infection

−

HLA-B27

≥

2 SpA features

−

Arthritis

−

enthesitis

−

Dactylitis

−

amily history for SpA

−

Sacroiliitis on imaging

HLA-B27 plus

≥

2 other SpA

features

ASAS classification criteria for SpA

In patients with peripheral
symptoms ONLY

Arthritis or enthesitis or

dactylitis plus

60

J. Braun and D. T. Y. Yu

A patient with cutaneous psoriasis and defi nite structural

changes in the sacroiliac joints is usually diagnosed more
appropriately as AS associated with psoriasis. Structural
changes in the sacroiliac joints of patients with reactive
arthritis are relatively rare.

Pearl and

Myth:

The nature of syndesmophytes differs across

the subtypes of spondyloarthritis.

Comment: The syndesmophytes of AS are usually symmet-
ric, delicate, and vertical— at least in about 90% of the
patients (

Fig. 7.3

). In contrast, the syndesmophytes of

patients with psoriasis are often bulky, asymmetric, and tend
to protrude laterally before progressing vertically.

Although this fi ne point is correct from the standpoint of

diagnosis, it makes little difference now in most circumstances
with regard to treatment. Regardless of the radiologic appear-
ance of their syndesmophytes, the back pain symptoms of
patients with AS, psoriatic arthritis, or infl ammatory bowel
disease all respond well to TNF inhibitors.

Myth:

Syndesmophytes are distinguished easily from the osteo-

phytes associated with degenerative arthritis of the spine.

Reality: Advanced cases of AS are diffi cult to distinguish
from diffuse idiopathic skeletal hyperostosis (DISH). One
study of patients with AS, who had a mean disease duration
of approximately 12 years, indicated that more than 10% of
all spinal osteophytes detected had the radiologic appearance
of degenerative osteophytes. The cutoff used in that study
was a 45° growth angle (Baraliakos et al. 2007b).

There are two potential causes of diffi culty in parsing the

etiology of syndesmophytes. First, patients with AS may
develop degenerative spinal changes secondary to those
induced by infl ammation. Second, not all syndesmophytes
follow the same rules, and they may have a less than classic
appearance. There is evidence that the detection of syndesmo-
phytes by MRI is diffi cult (Braun 2002). Radiography remains
the gold standard for syndesmophyte characterization.

Pearl:

Remember to consider DISH before diagnosing

advanced AS.

Comment: Many patients with late-stage AS are recognizable
easily by their posture. They have a forward stooping of the
neck, a high dorsal kyphosis, a rounding of the shoulders,
loss of the normal lumbar lordosis, wasting of the buttocks
muscles, fl attening of the chest, and ballooning of the abdo-
men (Olivieri et al. 2007). Before rendering the diagnosis of
AS on this posture alone, however, clinicians should consider
an alternative diagnosis that can cause the identical postural
changes: diffuse idiopathic skeletal hyperostosis, commonly
known as DISH or Forestier’s disease (Mader 2008).

Physical examination maneuvers alone cannot distinguish

DISH from AS. The range of motion in the cervical and lum-
bar spines can be limited to similar extents in these two con-
ditions. In addition, patients with DISH have similar decreases
in their chest expansions and in the ranges of motion at the
shoulders and hips. Patients with DISH may complain of spi-
nal pain, but their history of back pain starts usually later than
in AS, and the initial localization is different.

Patients with both DISH and AS develop bony bridges

between their vertebral bodies. The key to differentiating
these disorders is that these bony bridges have different
radiologic appearances:

DISH leads to ossifi cation of the anterior longitudinal lig-

•

ament of the spine. These changes are frequently described
as “exuberant” or “fl owing” mantles along the anterior and
anterolateral aspects of the vertebrae (

Fig. 7.4

).

In AS, the bony bridges between the vertebrae are vertical

•

and much more slender, involving the outer margin of the
annulus fi brosus (see

Fig. 7.3

).

The other radiological feature that distinguishes AS from
DISH, sometimes more reliably, is the presence of erosions
within the sacroiliac joints of patients with AS. Sacroiliac
joint erosions are present invariably among patients with AS
who have signifi cant radiological involvement of the spine.

Fig. 7.3

Lateral view of the cervical spine in a patient with ankylosing

spondylitis. Note the slender and vertical characters of the bony briges
between the anterior aspects of the vertebrae (Figure courtesy of
Dr. Thomas Learch, Cedar Sinai Medical Center, Los Angeles)

7 Ankylosing

Spondylitis

61

Sacroiliac joint erosions tend to occur fi rst on the iliac side of
the joint.

Sacroiliac joint erosions do not occur in DISH, but the

sacroiliac joints are obscured in some patients by sacroiliac
capsular bridging. In such cases, computed tomography may
be required to differentiate AS from DISH. However, this is
a largely academic question that has usually no therapeutic
consequences.

HLA-B27 is present in a subtantially higher percentage of

patients with AS compared with patients with DISH. However,
the coexistence of not only HLA-B27 positivity and DISH but
also AS and DISH has been reported (Maertens et al. 1992).

Myth:

AS is caused by Klebsiella or some other species of

bacteria.

Reality: The concept that bacterial infections in the urogeni-
tal tract, gastrointestinal tract, and other sites can trigger a
noninfectious infl ammatory arthritis stems from the strong
association that exists between certain pathogens and reac-
tive arthritis (Chapter 9). Reactive arthritis shares some fea-
tures with other SpA.

The hypothesis that Klebsiella infections cause some

cases of AS was put forth in the 1970s and 1980s on the basis
of two arguments:

The potential for molecular mimicry between Klebsiella

•

species and HLA B27
The reportedly high prevalence of antiKlebsiella antibod-

•

ies in AS.

The functional relevance of the molecular similarity between
Klebsiella species and HLA B27 has never been proven. In
addition, the serologic fi ndings are probably attributable to
silent gut infl ammation, possibly enhanced by NSAID use,
rather than a true pathogenetic mechanism.

Putative links between AS and Chlamydia species or other

bacteria that can cause clinically inapparent infl ammation
within the urogenital tract have been proposed, but the data
for such associations are not convincing. Extensive poly-
merase chain reaction studies have provided evidence for
small amounts of bacterial DNA in the joints of patients with
reactive arthritis but not of those with AS (Braun et al. 2007a,
b). However, it is altogether much more probable that the cel-
lular immune reaction to bacterial antigens is of greater
pathophysiological importance than the presence of bacte-
ria—especially since they have also been detected in the joints
of healthy individuals.

Although several interesting ideas have been followed, the

pathogenesis of AS has still not been fully elucidated. The
genetic contribution seems to be rather dominant, explaining
at least 80% of the pathogenesis.

Myth:

AS is diffi cult to treat.

Reality: This was true–painfully true–until the era of TNF
inhibitors (Braun 2002). Assuming that patients have access to
appropriate anti-TNF regimens, most respond very well to this
intervention. Of note, there is some evidence that these agents
work even better in SpA than in RA (Heiberg et al. 2008).

NSAIDs remain the standard fi rst-line therapy for AS

(Zochling et al. 2006). TNF inhibition, on the other hand, is
the standard of care for patients who have persistently high
disease activity despite optimal NSAID regimens. In contrast to
the situation with RA, in which methotrexate remains the cor-
nerstone of therapy even if a biologic agent is employed simul-
taneously (see Chap. 1), methotrexate and other synthetic
DMARDs have extremely limited roles in the treatment of AS.

Pearl:

Doses of NSAIDs must be optimized.

Comment: NSAIDs should be employed in at the highest
approved dose when treating AS. NSAIDs with longer half
lives may be more effective than those with shorter half lives,
particularly in providing pain relief through the night. If a
particular, NSAID has not demonstrated suffi cient therapeu-
tic effect within 1 week, another NSAID should be prescribed
(Song et al. 2008).

Fig. 7.4

Lateral view of the cervical spine in a patient with DISH. Note

the exuberant appearance of the ossifi cation along the anterior margins
of the vertebrae (Figure courtesy of Dr. Thomas Learch, Cedar Sinai
Medical Center, Los Angeles)

62

J. Braun and D. T. Y. Yu

The potential for gastrointestinal, renal, and cardiovascu-

lar adverse effects must always be considered when using
NSAIDs and weighed against the possible adverse effects of
TNF inhibitors.

Pearl:

Elevated acute phase reactants in a patient with AS do

not imply that glucocorticoids will be an effective treatment.

Comment: The systemic use of glucocorticoids is not recom-
mended in AS, in contrast to RA. Clinical experience in AS
indicates that only high doses of glucocorticoids (too high) are
effective for the spinal disease in AS, and even then only in
some patients. Greater effi cacy of glucocorticoids may be
anticipated for patients with a predominantly peripheral
arthritis, but even this has not been tested adequately. The clini-
cal judgement of AS experts is that comparable doses of gluco-
corticoids are far less likely to be effective in AS than in RA.

Pearl:

Injectable glucocorticoid preparations are effective in

patients with isolated sacroiliitis, monoarthritis or oligoar-
thritis of peripheral joints, or enthesitis.

Comment: Although oral glucocorticoids are generally inef-
fective in AS, clinical anecdotes suggest that intraarticular
injections provide clinical relief for up to 9 months in many
patients. Computed tomography-guided injections may be
necessary for the sacroiliac joints, especially if sacroiliitis is
the predominant clinical problem (Braun et al. 1996).

Pearl:

Methotrexate defi nitely does not work for axial disease.

Comment: Although methotrexate has been used for this indi-
cation for a long time, there is no evidence (not even a hint)
that this agent is effective for the spinal infl ammation of AS
(Haibel et al. 2007). There is also no evidence that the addi-
tion of methotrexate to a TNF inhibitor regimen potentiates
the effect of the biologic agent (Breban et al. 2008). In theory,
methotrexate might prevent the formation of human antichi-
meric antibodies in patients treated with infl iximab, but this
has not been demonstrated to be relevant in patients with AS.

Pearl:

Consider sulfasalazine in patients with relatively mild

disease, but don’t hesitate to prescribe anti-TNF therapy in
patients with persistently active disease.

Comment: Some studies indicate a limited effect of sulfasala-
zine for patients with active peripheral and axial disease,
especially in early stages (Braun 2006b). However, this does
not imply that sulfasalazine must be prescribed before resort-
ing to an anti-TNF agent. Patients with persistently active
disease should receive a TNF inhibitor early in their disease
course (Zochling et al. 2006).

Myth:

TNF blockers are useful only in patients with AS before

their spines become fused.

Reality: Most of the phase III studies on the use of TNF block-
ers have not included patients with total ankylosis of the spine.

A prevalent myth holds that as the spine becomes ankylosed,
the degree of infl ammation also subsides, such that patients’
symptoms become much less responsive to antiinfl ammatory
therapies. The response of the patient whose spine is shown

Fig. 7.5

to infl iximab repudiates this myth strongly.

The only phase III TNF blocker study that included some

patients with AS with complete spinal ankylosis (n = 11) was
a multicenter trial involving 315 patients that compared adal-
imumab with placebo (Van der Heijde et al. 2006). Among
these patients, three of the six who were treated with adali-
mumab demonstrated signifi cant clinical responses. In con-
trast, none of the fi ve patients who received placebo were
responders. Hence, TNF blockers can be considered even in
patients with very late stages of the AS, especially if NSAIDs
and other analgesics are poorly tolerated or not effi cacious.

This is in agreement with immunohistological studies

showing that even at a late stage of ankylosis, signifi cant
infl ammatory changes still exist in the spine (Appel 2006;
Neidhart et al. 2008).

Myth:

TNF blockers can arrest the progression of AS.

Reality: The reverse side of the myth discussed earlier is the
misconception that TNF inhibitors should be used early in
patients with AS, even those with mild disease, because they
will arrest the progression of structural damage. One of the
major problems in trying to test this hypothesis is that AS
progresses at a slower rate compared with that of RA. At
least 2 years are required in AS to detect signifi cant radio-
logic changes using the best available scoring system, the
mSASSS. In this era, it is not ethical to put patients on pla-
cebo for a period that long.

Fig. 7.5

A patient with severe ankylosis of the spine from long-standing,

untreated ankylosing spondylitis. The patient had a serum C-reactive
protein level of 62.4 mg/dL (normal < 8.0 mg/dL) and an erythrocyte
sedimentation rate of 132 mm/h (normal < 20 mm/h). He responded
dramatically to infl iximab, with pronounced symptom relief and a swift
normalization of his acute phase reactants

7 Ankylosing

Spondylitis

63

Because of this limitation, radiological progression in

patients on TNF blockers can be compared only with base-
line observations of the same cohort or alternately to data of
cohorts collected before use of biologics. Using either method
of comparison, neither infl iximab nor etanercept has shown
signifi cant effects on radiological progression (Baraliakos
et al. 2007a; Van der Heijde et al. 2008). This is not surpris-
ing, because the process of bone remodeling responsible for
ankylosis may be partly independent of that of infl ammation
(Baraliakos et al. 2008). Etanercept, which suppresses the
symptoms of AS effectively, does not suppress ankylosis in
an animal model of enthesitis (Lories et al. 2007). The opti-
mal approach to suppressing bone remodeling is a major cur-
rent focus of AS research.

Myth:

The concomitant use of methotrexate enhances the

utility of TNF blockers in patients with AS.

Reality: In a randomized trial, patients with AS received
either the combination of infl iximab and methotrexate or inf-
liximab and placebo (Breban et al. 2008). No additional
effect of MTX was found. In another study, there was no
synergistic effect of methotrexate plus a TNF inhibitor on
MRI progression of disease (Li et al. 2008).

Not all patients with AS respond dramatically to their fi rst

TNF inhibitor. In practice, if a patient with AS responds
poorly to one TNF blocker, it is probably more useful to
switch to another TNF blocker than to add methotrexate
(Coates et al. 2008).

Pearl:

Remind the patient regularly that physiotherapy and

exercise are as important as the use of medications designed
to inhibit infl ammation.

Comment: Patients (and clinicians) sometimes place too
much faith on the pharmacological side of therapy. Regular
physiotherapy and exercise are also critical features of the
therapy for patients with AS. These measures improve and
maintain muscle strength over time and contribute to the
preservation of proper posture.

Pearl:

Talk to the patient about the increased cardiovascular

risk associated with systemic infl ammatory disorders and
explain the detrimental effects of smoking on the disease.

Comment: Patients with AS have an increased cardiovascu-
lar risk because of the chronic infl ammation. Moreover,
smoking is a risk factor for poor clinical outcomes. Patients
should understand the importance of pursuing healthful
lifestyles and modifying risk factors for cardiovascular
disease.

Pearl:

Check bone mineral density in time and measure it at

the right location.

Comment: Approximately half of all patients with AS have
abnormal bone mineral density levels. The risk of pathologic

fractures among patients with AS is increased several fold
compared with healthy controls. The treatment of osteopenia
and osteoporosis has not been studied in AS, but reasonable
approaches to this problem include calcium (1,500 mg of
elemental calcium per day) and vitamin D, as well as bispho-
sphonates if appropriate. Some data indicate that bisphos-
phonates have a favorable effect on other disease outcomes
(Maksymowych et al. 2002).

Bone mineral density measurements at the lumbar spine

in patients with syndesmophytes are not useful because the
measurements will be falsely high (Karberg et al. 2005).

Pearl:

Talk to the patient with a physically demanding job

about the future of his employment.

Comment: A physically demanding profession is associated
with a poor AS outcome in terms of both structural and func-
tional damage (Ward et al. 2008). Patients with AS should be
advised of the potential wisdom of selecting different types
of work if their current occupations bring signifi cant physi-
cal demands.

Pearl:

Systematic assessments of disease activity are crucial

to the longitudinal management of AS.

Comment: Standardized and validated assessments are
increasingly the standard of care for the management of
patients with RA. Similarly, measuring the degree of disease
activity is also crucial to the management of AS. It helps
physicians to decide on what particular therapies to initiate.
Once a therapy is initiated, disease activity assessment is
required to monitor response. However, assessing disease
activity in AS is more diffi cult than that in RA because of
several factors: there are very few if any swollen joints to
count; the correlation with acute phase reactants is often
poor; and radiographic changes are comparatively slow.

Partly because of our ignorance on the factors that cause

the symptoms and disability of AS, the instruments we use to
measure disease activity are rather artifi cial and not based on
the pathophysiology of the disease. For drug trials and for
consideration of TNF blocker treatment, a frequently recom-
mended method is the Bath AS Disease Activity Index
(BASDAI) (Garrett et al. 1994). The BASDAI is available at

http://www.basdai.com/

and is illustrated in

Table 7.2

.

For patients with established AS, the BASDAI scores are

rather stable when studied over a period as long as 5 years
(Robertson and Davis 2004). BASDAI scores have been used
to assist in making decisions about whether or not TNF
inhibitors should be employed in a patient with AS. A
BASDAI score >4.0 has been felt to justify TNF inhibitor
use (Braun et al. 2005; Henderson and Davis 2006). Most
clinical trials of TNF blockers in AS have used this cutoff as
one of the entry criteria.

An obvious drawback of the BASDAI is that the parame-

ters are dependent entirely upon subjective patient-based

64

J. Braun and D. T. Y. Yu

evaluations. Alternative strategies for measuring disease
activity in AS have been proposed (Spoorenberg et al. 2005;
Dougados et al. 2008; Maksymowych et al. 2007).

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•

How would you describe the overall level of fatigue/tiredness you

have experienced?

•

How would you describe the overall level of AS neck, back or hip

pain you have had?

•

How would you describe the overall level of pain/swelling in

joints other than neck, back or hips you have had?

•

How would you describe the overall level of discomfort you have

had from any areas tender to touch or pressure?

•

How would you describe the overall level of morning stiffness

you have had from the time you wake up?

•

How long does your morning stiffness last from the time you

wake up? The scale of the duration of morning stiffness ranges
from the minimum score of 0 h to the maximum score of 2 or
more hours.

Table 7.2

Calculating the Bath Ankylosing Spondylitis Disease

Activity Index (BASDAI)

Calculating the mean BASDAI score:

Patients are requested to provide a score for six questions regarding
their conditions in the preceding week. The scoring can be accom-
plished either on a visual analogue scale or in a numerical scale ranging
from 0 to 10.

Because questions fi ve and six both address the symptom of morning
stiffness, their scores are averaged and then added to the sum of the
other four questions. The total of these fi ve items are then divided by 5
to derive the mean BASDAI score.

7 Ankylosing

Spondylitis

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