ANKYLOSING

SPONDILITIS
DR.dr. BLONDINA MARPAUNG, Sp.PD-KR
Rheumatology Division of Internal Medicine
Department

DEFINITION

Chronic, progressive immunemediated inflammatory

disorder that results in
ankylosis of the vertebral
column and sacroiliac joints1

The spine and sacroiliac joints

are the common affected sites1
Chronic spinal inflammation
(spondylitis) can lead to
fusion of vertebrae
(ankylosis)1

Ankylosing Spondylitis

Bamboo Spine
Repeated process of healing and
bone formation leads to formation
of syndesmophytes
bone bridges

ACR Slide Collection on the Rheumatic Diseases; 3 rd edition. 1994.

EPIDEMIOLOGY

The incidence of AS may be

underestimated due to unreported cases1
HLA-B27 gene is associated with AS6
Age of onset typically between 15 and 35
years1,2,3
2-3 times more frequent in men than in
women6

The Spondylitis Association of America. Available at: www.spondylitis.org. Accessed December

2,2004. 61(suppl 3);iii818. 6Khan MA. Ann Intern Med. 2002;136:896907.
1

EPIDEMIOLOGY

The prevalence varies depending upon

the ethnic group and the prevalence of
HLA-B27.
Spondyloarthropathy is common in
Eskimos and Inuit persons HLA B 27
is seen in 25% to 40%
Rare in Japanese persons who have a
very low <1% prevalence of HLA B 27

AS and HLA-B27
Disease

AS
Reactive arthritis (ReA)
Juvenile spondyloarthropathy

Approximate
Prevalence of HLA-B27
(%)
90
40-80
70

Enteropathic spondyloarthropathy

35-75

Psoriatic arthritis

40-50

Undifferentiated spondyloarthropathy

70

Acute anterior uveitis

50

Aortic incompetence with heart block

80

Khan MA. Ann Intern Med 2002;136(12):896-907

Percentage of Patients (%)

Age at Onset Distribution of AS and

Rheumatoid Arthritis (RA)
RA

AS

Economically active individuals

with a major impact on their ability
to work1
Barkham N et al. Rheumatology 2005;44:1277-1281

CLINICAL MANIFESTATIONS
Axial manifestations:

Chronic low back pain

With or without buttock pain

Inflammatory characteristics:
Occurs at night (second part)
Sleep disturbance
Morning stiffness

Limited lumbar motion

Onset before age of 40 years

CLINICAL MANIFESTATIONS
Peripheral manifestations
Enthesitis

50% patients with

enthesitis1

Peripheral arthritis

Up to 58% patients
ever had arthritis1

Dactylitis

Much smaller number

of patients2

Cruyssen BV et al. Ann Rheum Dis 2007;66:1072-1077

2
Sidiropoulos PI et al. Rheumatology 2008;47:355-361

Why are Dactylitis and Enthesitis Important?

Likelihood of erosions is higher

for digits with dactylitis than
those without1

The first abnormality to appear in swollen

joints associated with
spondyloarthropathies is an enthesitis2

Brockbank. Ann Rheum Dis 2005;62:188-90;

2
McGonagle et al. The Lancet 1998;352.

Extra-skeletal Signs and Symptoms

Other common symptoms seen during the early stages of disease
include:

Anorexia

Malaise
Low grade fever
Weight loss
Fatigue
Fatigue is a frequent complaint of
patients with AS1

Missaoui B. et al. Ann Readapt Med Phys 2006;49:305-8, 389-391

Linden VD et al. Chapter 10. In: Firestein, Budd, Harris, McInnes, Ruddy and Sergent, eds. Kelleys
Textbook of Rheumatology: Spondyloarthropathies. 8th ed. Saunders Elsevier;2009:p.1176
1

Extra-articular Manifestations (EAM)

EAM

Anterior uveitis

Cardiac
abnormalities

Prevalence in AS
Patients (%)

Anterior uveitis

30-50

IBD

5-10

Subclinical inflammation of the gut

25-49

Cardiac abnormalities
Conduction disturbances
Aortic insufficiency

1-33
1-10

Psoriasis

10-20

Renal abnormalities

10-35

Lung abnormalities
Airways disease
Interstitial abnormalities
Emphysema

40-88
82
47-65
9-35

Bone abnormalities
Osteoporosis
Osteopenia

11-18
39-59

Terminal ileitis

Elewaut D & Matucci MC. Rheumatology 2009;48:1029-1035

Characteristic Pathologic Features

Chronic inflammation in:
Axial structures (sacroiliac joint, spine, anterior chest wall,

shoulder and hip)

Possibly large peripheral joints, mainly at the lower limbs

(oligoarthritis)
Entheses (enthesitis) sites of bony insertion of ligaments

and tendons

Bone formation particularly in the axial joints

Inflammation

Structural damage

Disease activity

Syndesmophytes formation

Sieper J. Arthritis Res Ther 2009;11:208

Elewaut D & Matucci MC. Rheumatology 2009;48:1029-1035

AS can occur in individuals

in various places of the
body.

The major places of

incidence with AS include:
- sacroiliac joints
- apophyseal joints
- costoveterbral joints
- the intervertebral disc
articulations

In as many as 33% of cases

of AS, individuals have been
known to have unilateral
symptoms of peripheral
joints

DIAGNOSIS

DIAGNOSIS

X-rays of the spine and pelvis to check for

bone changes (bony erosions, fusion, or
calcification of the spine and sacroiliac
joints). Certain changes in the sacroiliac
joint confirm the diagnosis of ankylosing
spondylitis, but those changes can take
several years to develop enough to show
on X-ray. MRI and ultrasound are both
being studied as ways to diagnose
ankylosing spondylitis earlier.

Ankylosing Spondylitis: X-Ray

Changes

DIAGNOSIS

A genetic test (through a blood test), which

may be done to determine the presence of
a particular gene (HLA-B27) that is often
associated with ankylosing spondylitis. This
test will not confirm whether you have
ankylosing spondylitis. However, if you
have the HLA-B27 gene, you could pass it
along to your children. This would increase
the chances they could get ankylosing
spondylitis or one of the other
spondyloarthropathies.

DIAGNOSIS

You will have a physical exam to see

how stiff your back is and whether you
can expand your chest normally. Your
doctor will also look for tender areas,
especially over the points of the spine,
the pelvis, the areas where your ribs join
your breastbone, and your heels.

PHYSICAL
DIAGNOSTIC

PHYSICAL
DIAGNOSTIC

Treatment

Medical
NSAIDs
DMARDs
TNF blockers

Surgical

NSAIDs

A quick effect on pain, morning stiffness

and functional disability is usually seen
after initiation of NSAIDs
Although short term efficacy is observed,
long term efficacy was not established.
A recent study demonstrated that
continuous use of NSAIDs reduced
radiographic progression of disease

DMARDs

In contrast to R.A few studies have been performed

on the treatment of patients with AS with disease
modifying anti-rheumatic drugs, and none of which
have proved clearly effective in axial disease
SLZ may be beneficial in the treatment of the
peripheral arthritis associated AS
MTX/ARAVA studies have shown success of these
drugs in the treatment of psoriatic arthritis, but
there is no data to suggest any impact on axial
disease in AS
Oral CS or SI joint injections have not proven to be
effective

TNF blockers

The new TNF blockers have been

proven highly effective in improving the
spinal and extra spinal manifestations of
SpA

Infliximab

Braun, Lancet 2002 359; 1187-93

German multicenter placebo controlled trial of 70 pts with active
AS
Txed with infliximab 5mg/kg at wks 0,2,6 and observed until week
12
53 % had regression of disease activity of at least 50% of
fatigue, spinal pain, morning stiffness, enthesial pain and joint pain
One year open extension F/U 5mg/kg q 6weeks f/U for 54 weeks
the same magnitude of improvement was sustained
Significant adverse effects
Systemic TB (1)
Poly arthritis with high ANA (3) and skin lupus (1)
Mild luekopenia (1)
Increased LFT (1)
Infusion reactions (2)

Infliximab

Makysmowych, J Rheumatol 2002;29:959

Prospective observational inception cohort of
pts with NSAIDs refractory AS- 21pts
Infliximab 3mg/kg at 0,2,6 wks and Q 2m
At 14 wks significant improvement in BASDAI
and BASFAI, maintained at one year
AE- Septic OM (1), Severe hypersensitivity (1)
5 pts ANA +ve at base line no change with
Tx

Infliximab

Optimal dose
5mg/kg every 6 weeks

OR
3mg/kg every 8 weeks
( limited data )

Etanercept

Gorman JD. NEJM 2002, 346: 1349

Randomized double blind placebo controlled 4
month study with 6 month open label extension
40 pts with AS tx with etanercept 25mg SQ 2/wk
Primary end point 20% improvement in
morning stiffness, spinal pain, swollen joint
count, global assessment of disease activity
and function
Etanercept group 80% achieved primary end
point and results seen as early as one month

Etanercept - cont

AE
Self limited injection site reactions
2 neuro events in one pt tinnitus and
increase muscle fasciculation ( increase from
a pre-existing condition )
No change in ANA
Infection rate similar to placebo
Measures which did not improve
- modified schobers index
- Occiput to wall measurement
- Fatigue severity scale

Indications for Surgical treatment

Unstable injuries
Presence of neurological
deficits
Painful spinal deformity
Functionally/cosmetically
unacceptable deformitis
Minimally invasive

techniques of corrective
osteotomy

PROGNOSIS

5-7 yr lapse prior to diagnosis

Most damage occurs first 10 yrs of disease
Factors predictive of more severe disease
Onset < 16yrs
Hip arthritis / Oligoarthritis
Poor response to NSAIDs
Sausage like digits
Limitation of lumbarspine
ESR > 30

THANK YOU

THANK YOU