Ankylosing Spondylitis

1. Guided By
Mr.P.Raut
Presented By
Gayatri R.Kachh

2.  Introduction of A.S.
 Epidemiology of A.S
 Characteristics Pathological Features
of A.S.
 Symptoms of A.S.
 Structural Damage in A.S.
 Causes of A.S.
 HLA-B27
 Pathogenesis of HLA-B27
 Diagnosis of A.S.
 Treatment of A.S.
 Humira Pen Therapy(Adalimumab)
for A.S.
 Quality of Life
 Conclusion
 References

3.  Ankylosing Spondylitis is a Rheumatic disease of
unknown cause that primarily affects the back
bone or spine.
 The name is derived from the Greek words
‘Ankylos” meaning fusion and “Spondylos”
meaning vertebra. “Itis” denotes inflammation
of the body part. The name therefore describes
the inflammatory process in the spinal joints
 It is considered to be one of a group of diseases
called the Spondylo-Arthropathies
 AS is a chronic, progressive immune-mediated
inflammatory disorder that results in ankylosis
of the vertebral column and sacroiliac joints
 Also referred to as the Bekhterev-Strumpell
syndrome after the first doctor to actually study
the disease. Aka Strumpell-Marie(or Marie-
Strumpell) disease after his wife, the first
officially noted case study

4.  First documented AS case was reported in
1691
 Unknown cause
 First signs of Ankylosing Spondylitis were
unearthed in the skeletal remains of a 5000
year old Egyptian mummy
 The incidence of AS may be underestimated
due to unreported cases
 HLA-B27 gene is associated with AS
 Age of onset typically between 15 and 35
years
 2-3 times more frequent in men than in
women
 More common in whites than in nonwhites

5. 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)
 Bone formation particularly in the axial joints
 Serronegative
 Presence of HLA-B27

6. 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
Other common symptoms seen during the early stages of disease include:
Anorexia
Malaise
Low grade fever
Weight loss
Fatigue

7.  Most striking feature of AS =
New bone formation in the
spine with:
• Spinal syndesmophytes
• Ankylosis
 Both can be seen on
conventional radiography
 Bamboo Spine: Repeated
process of healing and bone
formation leads to the
formation of Syndesmophytes
i.e. “Bone Bridges”

8. The exact cause of ankylosing spondylitis is unknown, but
genes are thought to play a part. The tendency for
developing ankylosing spondylitis is believed to be
genetically inherited, and the majority (nearly 90%) of
patients with ankylosing spondylitis is born with the HLA-
B27 gene.
The HLA-B27 gene appears only to increase the tendency of
developing ankylosing spondylitis
One can likely to get AS if you have a history of it in your
family.
Studies show that almost nine out of ten people with AS have
the gene called HLA-B27.
Researchers currently think that exposure to certain
environmental triggers can lead to the development of AS in
people with the gene. But these triggers are unknown.

9.  Human leukocyte antigens (HLAs) are
proteins that help the body's immune
system tell the difference between its own
cells and foreign, harmful substances.
 The human leukocyte antigen (HLA) is
not a single antigen, but is rather a group
of proteins that are located on the surface
of White Blood Cells (WBCs).
 The HLA is the human version of a
complex that is known as the major
histocompatibility complex.
 A variation of the HLA-B gene
called HLA-B27 increases the risk of
developing ankylosing spondylitis.
 Mechanism of HLA-B27 action in AS
patients may still involve peptide
handling (the canonical function of HLA-
B27 as a MHC class I molecule).

10.  HLA-B27 is the strongest associated gene
in AS. Recent Genome Wide Association
Studies (GWAS) have implicated several
other genes associated with AS thus
affirming the complex, oligogenic nature
of the disease
 HLA-B27 consists of a heavy chain having
three a domains, which non-covalently
binds short peptides and β2-microglobulin
(β2M)
 Although the HLA-B27 has remained a
center of extensive research, the
mechanism whereby HLA-B27 confers
susceptibility to AS is not well defined.
Current hypotheses regarding the
pathogenesis of AS have sought to
incorporate HLA B27 into mechanistic
models.

11. MRI
X-Ray
CT-Scan
Several Lab test are also
performed such as measuring the
concentration of CRP and ESR in
the blood samples of A.S. Patients.
There is no direct test to diagnose
AS

12.  There is not yet a cure for AS. However, there are
effective treatment options that can relieve pain and
improve your condition
 The general approach is a conservative treatment plan
that includes: medication, physical therapy, and
exercise
Drugs like. Local steroid injection
To single inflamed joints, entheses, bursae
Beware of weight bearing enthesis
Not more than 3 injections a yr
NSAIDs
Spinal stiffness, pain
Persistent synovitis or enthesopathy
Caution in elderly, peptic ulcer
COX II inhibitors
Oral or systemic steroids
Short courses for intolerable symptoms
Uveitis
May result in osteoporosis
Precipitate heart failure
 DMARDS & TNF Blocker(Anti-TNF)
These are some most frequently used drugs in A.S.
Condition

13.  Right Posture, Swimming, Daily workouts are some of the physical
therapies.
 In severe cases of AS, surgery can be an option in the form of joint
replacements, particularly in the knees and hips
Daily Workouts Surgery

14.  HUMIRA (adalimumab) is a recombinant
human IgG1 monoclonal antibody specific
for human tumor necrosis factor (TNF).
HUMIRA is a medicine called a Tumor
Necrosis Factor (TNF) blocker.
 Adalimumab is produced by recombinant
DNA technology in a mammalian cell
expression system and is purified by a
process that includes specific viral
inactivation and removal steps. It consists of
1330 amino acids and has a molecular
weight of approximately 148 kilodaltons.
 Adalimumab binds specifically to TNF-
alpha and blocks its interaction with the
p55 and p75 cell surface TNF receptors.

15. AS=23.7 years
90.2
83.1
62.4
54.1
0
20
40
60
80
100
Stiffness Pain Fatigue Poor
SleepN=175
PercentageofPatients(%)
 Bad Quality
Pain
Sleep problems
Fatigue
Loss of mobility and
dependency
Loss of social life
 Effect employability
 Higher rate of mortality

16.  Ankylosing spondylitis has been a challenging disorder with few
therapeutic options. In previous studies, patients receiving traditional
therapies such as NSAIDs and DMARDs have received only mild to
moderate benefit. Importantly, no intervention has been shown to alter
progressive loss of spinal mobility.
 The need for new alternatives for treating these patients is substantial.
The pathogenesis of AS is poorly understood. HLA-B27 stands as the
earliest and most robust genetic marker associated with a rheumatic
disease
 Researchers are currently exploring the pathogenic role of inflammatory
cellular infiltrates, including various cytokines such as TNFα
 Use TNF inhibitor like Adalimumab(Humira). However, these treatments
are of limited benefit. Emerging biological therapies target the
inflammatory processes underlying AS, and thus, may favourably alter
the disease process while providing relief of symptoms.

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