in the name of god the merciful the compassionate
TRANSCRIPT
In the name of God
the merciful
the compassionate
Ankylosing
Spondylitis
Definition:
Ankylosing Spondylitis (AS) is a
chronic inflammatory disease of the
axial skeleton manifested by
inflammatory LBP and progressive
stiffness of the spine accompanied
by enthesitis and/or arthritis
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Previous names:
• Marrie Strumble disease
• Bechtereve disease
Iraj Salehi-Abari
Amir Alam Hosp.
Name in nowadays:
Ankylosing Spondylitis
• Ankylos: Bony bridging
• Spondylos: Vertebra
Iraj Salehi-Abari
Amir Alam Hosp.
Names in future:
• Spondylo-sacroiliitis
• Rheumatoid Spondylitis
Iraj Salehi-Abari
Amir Alam Hosp.
Introduction:
AS is the prototype member of the Spondyloarthritis (SpA) family of disorders
SpA are characterized by:• Spondylitis• Sacroiliitis• Enthesitis• Arthritis• HLA-B27 positivity• Usually RF negativity
Iraj Salehi-Abari
Amir Alam Hosp.
Historic names of SpA:
• Seronegative Rheumatism• Spondyloarthropathies• SEA syndrome:– Spondylitis, Enthesitis, Arthritis
• BASE syndrome:– B27, Arthritis, Sacroiliitis, Enthesitis
• SpondyloArthritis
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
SpA family members:
• Ankylosing Spondylitis (AS)
• Reactive arthritis (ReA): Reiter’s Synd.)
• Psoriatic Arthritis (PsA)
• Enteropathic Arthritis (IBDrA)
• Juvenile Spodyloarthropathy (JSpA)
• Undifferentiated SpA (USpA)
Iraj Salehi-Abari
Amir Alam Hosp.
Sacroiliitis:• History: Buttock pain
• Ph. Exam: Positive Sacral push test
• Pelvic X-Ray:
– Sclerosis
– Erosion
– Narrowing
– Ankylosis
• Bilateral: AS
• Unilateral: other SpA
Iraj Salehi-Abari
Amir Alam Hosp.
Enthesitis:
• The Enthesis is the region of
attachment of tendons and
ligaments to bone
• Enthesitis: Inflammation of Enthesis
• Achille tendinitis, Plantar fasciitis,
Costochondritis, …
Iraj Salehi-Abari
Amir Alam Hosp.
SpA-Iraj Salehi-Abari
SpA-Iraj Salehi-Abari
SpA-Iraj Salehi-Abari
Epidemiology-I:
• Chronic LBP is a common symptom
• 5% of chronic LBP is inflammatory
• Prevalence of Axial SpA: 1%
Iraj Salehi-Abari
Amir Alam Hosp.
Epidemiology-II:
• Young adults
• Peak age of onset: 20-30 years
• Prevalence of AS: 0.2-1.4%
• AS in (+)HLA-B27 population: 5-6%
Iraj Salehi-Abari
Amir Alam Hosp.
Epidemiology-III:
• M/F ratio: –Many years ago: > 3/1
– A few years ago; 3/1 t0 2/1
– Nowadays: #1/1
• (+)FH of AS 5.6–16 fold increases AS
• FH and HLA-B27 both positivity:– AS rate of 10-30%
Iraj Salehi-Abari
Amir Alam Hosp.
Attention please:
Rate of AS is increased by:
• Hx of chronic LBP: X 10
• Positive FH of AS: X 10
• Positive HLA-B27: X 10
Iraj Salehi-Abari
Amir Alam Hosp.
Definite inflammatory LBP:
LBP lasting for > 3 months and at least 4 out of 5 below parameters:
• Age at onset < 40 years• Insidious onset• Improvement with exercise• No improvement with rest• Pain at night (with improvement
upon getting up)
Iraj Salehi-Abari
Amir Alam Hosp.
Probable inflammatory LBP type I*:
LBP lasting for < 3 months and at least 4 out of 5 below parameters:
• Age at onset < 40 years• Insidious onset• Improvement with exercise• No improvement with rest• Pain at night (with improvement
upon getting up)
Iraj Salehi-Abari
Amir Alam Hosp.
* [Defined by Iraj Salehi-Abari, Rheumatol Int, 2012]
Probable inflammatory LBP type II*:
LBP lasting for > 3 months and 2–3 out of 5 below parameters:
• Age at onset < 40 years• Insidious onset• Improvement with exercise• No improvement with rest• Pain at night (with improvement
upon getting up)
Iraj Salehi-Abari
Amir Alam Hosp.
* [Defined by Iraj Salehi-Abari, Rheumatol Int, 2012]
Epidemiology in Iran*:• Mean age at diagnosis: 35+10 years• Male; 75%, Female: 25%• Definite inflammatory LBP: #65%• Probable inflammatory LBP: 25%• Positive family history of AS:– First-degree relatives: 8.5%– Second-degree relatives: 1%
• HLA-B27 positivity in Iranian AS: 45%
*Iraj Salehi-Abari, Early diagnosis of AS, Rheumatol Int. 2012, table 3
Iraj Salehi-Abari
Amir Alam Hosp.
Clinical Features:• Axial joint involvement;– Spondylitis and Sacroiliitis
• Peripheral joint involvement:– Root joints (Hip, Shoulder), other
• Enthesitis:– Plantar fasciitis, Achille tendinitis
• Extra-articular involvement
Iraj Salehi-Abari
Amir Alam Hosp.
Initial presentation:History:• Inflammatory LBP• Buttock pain• Heel pain• Back pain • Cervical pain• Articular pain (Shoulder, Hip, Knee,
Ankle)• Chest pain
Iraj Salehi-Abari
Amir Alam Hosp.
Initial presentation:Physical examination:• Spondylitis:– Axial tenderness– Limitation of motion in all directions
• Sacroiliitis:– Positive Sacral push test
• Enthesitis:– Plantar fasciitis, Achille tendinitis, …
• Arthritis:– Shoulder, Hip, Knee, Ankle, …
Iraj Salehi-Abari
Amir Alam Hosp.
Initial presentation*:
History:
• A male (75%) with age of 35 + 10 years
• Definite inflammatory LBP: #65%
• Probable inflammatory LBP: 25%
• Buttock pain
• (+) Family history (FH) of AS #10%
Iraj Salehi-Abari
Amir Alam Hosp.
*Iraj Salehi-Abari, Early diagnosis of AS, Rheumatol Int. 2012,
table 3
Initial presentation*:
A Positive FH:
• In first-degree relatives:
– Increases the risk of AS by 75-94 folds
• In second-degree relatives:
– Increases the risk of AS by 20-25 folds
Iraj Salehi-Abari
Amir Alam Hosp.
*Iraj Salehi-Abari, Early diagnosis of AS, Rheumatol Int. 2012,
table 3
Initial presentation*:Physical examination:• Lumbar LOM in all direction: 75%• Positive sacral push test: > 20%• Enthesitis: #30%• Arthritis: 40%• Limited chest expansion: < 2%• No systemic manifestations
Iraj Salehi-Abari
Amir Alam Hosp.
*Iraj Salehi-Abari, Early diagnosis of AS, Rheumatol Int. 2012, table 3
Axial involvement:• Sacroiliitis:– Buttock pain– Sacral push test
• Spondylitis:– Inflammatory LBP– Back pain– Neck pain– Spinal limitation of motion– Limited chest expansion
Iraj Salehi-Abari
Amir Alam Hosp.
Spinal limitation of motion:
• Schober sign: 10 cm above S1 (5. 1-
2)
• Ott sign: 30 cm below C7 (2-4, 1-2)
• Fingertips-to-floor distance test
• Occiput to wall test
• Chest expansion test
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Enthesitis:
Inflammation of Enthesis
• Chest and spinal enthesitis
• Extraspinal enthesitis
Iraj Salehi-Abari
Amir Alam Hosp.
Chest and spinal enthesitis:
• Costosternal
• Costovertebral
• Spinous processes
• Paraspinal
• Iliac crests
• Ischial tuberosities
• Sternoclavicular
• Manubriosternal
Iraj Salehi-Abari
Amir Alam Hosp.
Extraspinal enthesitis:
• Heels:– Achilles tendonitis
– Plantar fasciitis
• Shoulder tendonitis
• Greater Trochanters
• Tibial tubercles, Others
• Differentiated with FMS by dramatic response to NSAIDs
Iraj Salehi-Abari
Amir Alam Hosp.
Peripheral arthritis:
• Limb arthritis– Upper limb joints– Lower limb joint– Root joint: Hip & shoulder
• Extra-limb arthritis– TMJ arthritis– Sternoclavicular arthritis
Iraj Salehi-Abari
Amir Alam Hosp.
Peripheral arthritis:
• Root joints arthritis: 25-35%
• Other joints: 30%
• Early hip arthritis: worse prognosis
Iraj Salehi-Abari
Amir Alam Hosp.
Peripheral arthritis:
• Asymmetric > symmetric arthritis• Lower limb > upper limb• Large > small• Acute > chronic• Non-erosive non-deforming >
erosive-destructive • Mono > oligo > polyarthritis• It is in opposite point of RA
Iraj Salehi-Abari
Amir Alam Hosp.
Imaging and Sacroiliitis:
• Standard AP plain X-ray of the pelvis:
It may show sacroiliitis with a delay
of 8-10 years
• MRI of the pelvis; the most sensitive
• Whole Body Bone Scan (WBS) or
Scintigraphy of Bones
Iraj Salehi-Abari
Amir Alam Hosp.
Radiological Sacroiliitis:
• Grade 0: Normal SI joints• Grade 1: Suspicious changes of SI
joints• Grade 2: Minimal erosions or
sclerosis of SI joints without altration in the joint width
• Grade 3: Moderate to significant erosions, sclerosis, Widening, narrowing, or Partial ankylosis of SI joints
• Grade 4: Total ankylosis of SI joints
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Radiological Sacroiliitis:
In AS: • Bilateral sacroiliitis is more common
than Unilateral• Symmetric sacroiliitis is a Hallmark
featureIn other SpA:• Unilateral or Asymmetric sacroiliitis is
a compatible feature
Iraj Salehi-Abari
Amir Alam Hosp.
Imaging and spondylitis:
• MRI of the spine may show bone marrow edema of the vertebrae before there are changes on plain radiographs
• But only Plain X-ray is recommended for early diagnosis of spondylitis
• Why?: because, 95% of AS patients will also have bone marrow edema in the SI joints early in the course of their disease
• So, MRI is recommended for sacroiliitis
Iraj Salehi-Abari
Amir Alam Hosp.
Imaging and spondylitis:
Plain X-ray of spine:
• “Squaring” of the vertebral bodies is an
early finding due to AS in lateral view
• So, we recommend a lateral view of lumbar
spine in early AS
• “Barreling”,“Romanus” sign & “Shiny corner”
sign are other early findings in lateral view
Iraj Salehi-Abari
Amir Alam Hosp.
Imaging and spondylitis:
Later X-ray findings:
• Syndesmophytes
• Ankylosis of the facet joints
• Calcification of the anterior longitudinal
ligament
• Bamboo spine
Iraj Salehi-Abari
Amir Alam Hosp.
Imaging and spondylitis:
Other X-ray findings:
• C1-C2 subluxation:
– documented by MRI
• Spondylodiscitis
• Fracture
Iraj Salehi-Abari
Amir Alam Hosp.
Initiation & propagation of axial findings in Plain X-ray:
1. Symmetric Sacroiliitis
2. Symmetric Lumbar syndesmophytes
3. Ascending toward
• thoracic and
• Cervical spine
4. Bamboo spine
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Extra-Articular (Systemic) features:
Usually no initial presentation Eyes:• Acute anterior asymmetric uveitis (AAAU)• The most common systemic feature• It occurs in 25-40% of cases of AS• About 50% of cases with AAAU have SpA• No correlation with articular activity and
severity• Cataracts and glaucoma
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Extra-Articular (Systemic) features:
Renal:
• IgA nephropathy
• NSAIDs nephropathy
• Amyloidosis
• Urinary stones
Iraj Salehi-Abari
Amir Alam Hosp.
Extra-Articular (Systemic) features:
Heart:
• Aortic regurgitation (AR) due to Aortitis
• Heart block (CHB)
Lungs:
• Apical pulmonary fibrosis
Iraj Salehi-Abari
Amir Alam Hosp.
Extra-Articular (Systemic) features:
Bowel:
• Subclinical Ileo-colitis: 50%
• 5-10% of AS have IBD
• 5-10% of IBD have AS
Iraj Salehi-Abari
Amir Alam Hosp.
Extra-Articular (Systemic) features:
• Nervous system:
– Cervical myelopathy
• Atlantoaxial subluxation
• Fractures of C5-C6
– Spinal canal stenosis
– Cauda equina syndrome
Iraj Salehi-Abari
Amir Alam Hosp.
Juvenile AS:
• Peripheral arthritis:– usually predominate
• Enthesitis:– Usually predominate
• Axial arthritis: – Late adolescence
Iraj Salehi-Abari
Amir Alam Hosp.
Late onset AS:
• About 5% of AS
• Begin after Age of 40
Iraj Salehi-Abari
Amir Alam Hosp.
AS in women:
• In far past: man’s disease: M/F > 5-
10/1
• In near past: M/F = 2-3/1
• Nowadays: M/F = 1/1 ?
Iraj Salehi-Abari
Amir Alam Hosp.
AS in women:• Subclinical:
–Mild and slowly progressive
• Spinal ankylosis: less frequent
• Cervical ankylosis: more frequent
• Peripheral arthritis: more frequent
Iraj Salehi-Abari
Amir Alam Hosp.
AS in women:• Some of AS are missed
• And some of AS are mistaken with:
– RA
– FMS
• So it is suggested to us that M/F ratio
is more
Iraj Salehi-Abari
Amir Alam Hosp.
AS in pregnancy:• Improved: 1/3
• Unchanged: 1/3
• Deteriorated: 1/3
• 20% OF female AS initiate in pregnancy
• 60% flare up after delivery: 4-12 wk
• Uveitis : improved in pregnancy and recured
after delivery
Iraj Salehi-Abari
Amir Alam Hosp.
Pregnancy in AS:• No infertility
• No abortion
• No stillbirth
• No premature labour
• C-Section > normal delivery
• Epidural anesthesia will be ignored
• Normal newborn
Iraj Salehi-Abari
Amir Alam Hosp.
Host susceptibility to AS:• AS occurs worldwide roughly in proportion to the
prevalence of HLA-B27• In general population: prevalence of 0.2-1.4%• In adults inheriting HLA-B27: prevalence of 5-6%• In HLA-B27(+) adult with positive FH (1rt-d) of AS: 10-
30%• Concordance rate in identical twins: 65%• HLA-B27 positivity in AS:
– IN American white AS: 90%– In American black AS: 45%– In Iranian AS: 45%
• HLA-B27 positivity in general population of USA : 7%• So susceptibility to AS is largely determined by HLA-B27
Iraj Salehi-Abari
Amir Alam Hosp.
Other Genes for AS:• ERAP1• IL-23R• TNFSF15• TNFSF1A• STAT3• ANTXR2• IL-1R2
Iraj Salehi-Abari
Amir Alam Hosp.
Patient’s posture:• Forward stoop of the neck• Obliterated lumbar lordosis• Buttock atrophy• Accentuated thoracic kyphosis• Flexion contractures at the hips• Compensated by flexion at the
knees
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Disease progression can be estimated by:
• Loss of height
• Limitation of chest expansion
• Spinal flexion
• Occiput –to-wall distance
Iraj Salehi-Abari
Amir Alam Hosp.
Spinal fracture:
• Most serious complication of spine
• Lower cervical spine (C5-C6):
– Most common
– Displaced myelopayhy
• > 10% lifetime risk of fracture
• Thoracolumbar: Pseudoarthrosis
Iraj Salehi-Abari
Amir Alam Hosp.
Laboratory test:
• No diagnostic test
• HLA-B27 positivity
• Elevated ESR/CRP
• Mild Anemia
• Elevated ALK. Ph.
• Elevated serum IgA
Iraj Salehi-Abari
Amir Alam Hosp.
HLA-B27 positivity:
• 10-fold increase in chance of AS
• In USA:
– In North American whites: 7%
– In white AS: 90%
– In black AS: 45%
• In Iranian AS: 45% [ Iraj Salehi-Abari, Rheumatol Int,
2012]
Iraj Salehi-Abari
Amir Alam Hosp.
HLA-B27 positivity:
• AS associated alleles:
– HLA-B*2704
– HLA-B*2705
• Alleles not associated with AS:
– HLA-B*2706
– HLA-B*2709
Iraj Salehi-Abari
Amir Alam Hosp.
1984 Modified New York Classification (MNYC) Criteria for Ankylosing Spondylitis:Clinical criteria:• LBP and stiffness for > 3 months that
improves with exercise but is not relieved by rest
• Lumbar LOM (sagittal & frontal)• Limitation of chest expansionRadiological criteria:• Sacroiliitis grade > 2 bilaterally• Sacroiliitis grade 3-4 unilaterally
Iraj Salehi-Abari
Amir Alam Hosp.
MNYC Criteria for Ankylosing Spondylitis:
A patient is regarded as having
definite AS if he or she fulfills at least
one radiological criteria plus at least
one clinical criteria
• It is Moderately specific and
• It has a low degree of sensitivity
Iraj Salehi-Abari
Amir Alam Hosp.
MNYC criteria is low sensitive and moderately specific because:
• Radiologic changes in pelvis X-ray
appear with at least 8 years delay in
most cases and MRI is not used for
detecting Sacroiliitis
• Limited chest expansion is an
uncommon and delayed finding
Iraj Salehi-Abari
Amir Alam Hosp.
MNYC criteria is low sensitive and moderately specific because:
• Inflammatory LBP is a leading symptom
with sensitivity of 75% and it is typical
in about 70-80% of patients with LBP
• It is not included FH of AS
• It is not included Enthesitis
• It is not included HLA-B27 positivity
Iraj Salehi-Abari
Amir Alam Hosp.
ASAS* classification criteria for Axial SpA:
• It is for all Axial SpA
• Step I (Entry criteria): LBP for > 3 months in
an age of onset of < 45 years
• Step II: HLA-B27 positivity or Sacroiliitis on
imaging
*Assessment of SpondyloArthritis International Society
Iraj Salehi-Abari
Amir Alam Hosp.
ASAS classification criteria for Axial SpA:
• Step III:– HLA-B27 positivity with at least 2 features
of SpA or– Sacroiliitis with at least one feature of SpA
• SpA features: 1. Inflammatory LBP, 2. Arthritis, 3. Heel enthesitis, 4. Uveitis, 5. Dactylitis, 6. Psoriasis, 7. IBD, 8. Good response to NSAIDs within 24-48 hours, 9. FH of SpA, 10. Elevated CRP
Iraj Salehi-Abari
Amir Alam Hosp.
“…. Criteria” for early diagnosis of AS:
Entry criteria:
• No other prominent diagnosis such
as other SpA (ReA, PsA, IBDrA) and
Brucellosis is proposed according to
the patient’s Hx. and Ph. Exam.
Iraj Salehi-Abari
Amir Alam Hosp.
“…. Criteria” for early diagnosis of AS:Clinical criteria: Up to 8 P.• Inflammatory LBP: Up to 2 p. – Definite 2 P.– Probable 1 P.
• Positive family history of AS Up to 2 P.– First-degree 2 P.– Second-degree 1 P.
• Lumbar LOM in all directions 2 P. • Positive sacral push test 1 P.• Enthesitis &/or arthritis 1 P.
Iraj Salehi-Abari
Amir Alam Hosp.
“…. Criteria” for early diagnosis of AS:Imaging criteria: Up to 3 P.• AP X-ray or MRI of pelvis:– Unilateral sacroiliitis (grade >2) 2 P.– Bilateral sacroiliitis (grade > 2) 3 P.
• Whole body bone scan (WBS):– Enthesitis &/or arthritis 1 P.
– Spondylitis 1 P.– Sacroiliitis 2 P.
• HLA-B27 positivity (+1)
Iraj Salehi-Abari
Amir Alam Hosp.
“…. Criteria” for early diagnosis of AS:
• Clinical criteria 8 points
• Imaging criteria 3 points
• HLA-B27 positivity +1 point
Iraj Salehi-Abari
Amir Alam Hosp.
AS is the diagnosis if there are:
• Six clinical points or
• Five clinical and imaging points
or
• If HLA-B27 is positive:
– Five clinical points or
– Four clinical and imaging points.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
AS is the diagnosis if there are:
• Six clinical points or
• Five clinical and imaging points
or
• If HLA-B27 is positive:
– Five clinical points or
– Four clinical and imaging points.
Iraj Salehi-Abari
Amir Alam Hosp.
“Amir alam Hospital” approach towards diagnosis of AS:
• Step I: Hx. and Ph. Exam. by
Rheumatologist
• Step II: AP X-ray of pelvis and HLA-B27
• Step III: MRI of pelvis
• Step IV: Whole body bone scan (WBS)
Iraj Salehi-Abari
Amir Alam Hosp.
“Amir alam Hospital” approach towards diagnosis of AS:
• The physician must go through the
steps one by one and if …. criteria for
AS are not yet satisfied in each step,
go through the next.
Iraj Salehi-Abari
Amir Alam Hosp.
“Amir alam Hospital” approach towards diagnosis of AS:
• However, if the patients fulfil the criteria in
the first step, we suggest the
investigations be necessarily continued by
the second step as in routine practice, a
pelvic X-ray and HLA-B27 testing are
beneficial for documentation and
prognosis of AS patients
Iraj Salehi-Abari
Amir Alam Hosp.
“Iran criteria” versus “MNYC criteria” for diagnosis of AS:
• Sensitivity of Iran criteria is 100% from the initial presentation of disease
• Sensitivity of New York criteria:– Two years after initial presentation:
48.4%– Five years after initial presentation:
74.2%– Ten years after initial presentation: 80% – After 10 years: 92.1%–Mean sensitivity: 74.2%
Iraj Salehi-Abari
Amir Alam Hosp.
“Iran criteria” versus “MNYC criteria” for diagnosis of AS:
• Specificity of Iran criteria is more
than New York criteria?
• Iran criteria is a diagnostic criteria
for AS but New York criteria has
been made for classification of AS
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Conclusion:
Iran criteria for AS is a highly
sensitive instrument to detect AS in
its early and late, clinical and
subclinical, radiographic and pre-
radiographic stages as well as
atypical forms
Iraj Salehi-Abari
Amir Alam Hosp.
Differential diagnosis:• Spondylosis: NormaL SI joint, Osteophyte• DISH: Diffuse Idiopathic Skeletal Hyperostosis– “Flowing wax”– Normal SI joint– Normal facet joint– Normal intervertebral disk spaces
• Ochronosis; Wafer like calcification• Axial Brucellosis: – Lumbar spondylodiscitis– “Parrot beak” bony bridging– Unilateral sacroiliitis
Iraj Salehi-Abari
Amir Alam Hosp.
Pathology of AS:
• In AS major pathological feature is “Enthesitis”, but in RA is “Synovitis”
• “Uncoupled” bone erosion (Inflammatory) and new bone formation processes occur in entheses:– Ankylosis of SI joints– Syndesmophytes, Bamboo spine– Ischial wiskering
Iraj Salehi-Abari
Amir Alam Hosp.
Pathogenesis:
Genetic susceptibility: 90% of the risk of developing AS is heritable
Immune-mediated events or Osteoimmunology (no autoimmunity)
• Inflammation:– TNF-a, IL-17, …– Bacterial trigger??
• New bone formation:
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Pathogenesis:
Genome-wide association studies
(GWAS) have demonstrated an
association between AS and a
region of the chromosome
encompassing the genes LTBR
(Lymphotoxin beta receptor) and
TNFRSF1A (Tumor necrosis factor
receptor 1)
Iraj Salehi-Abari
Amir Alam Hosp.
Pathogenesis:
New bone formation:
• Endochondral
• Two major pathways:
– Bone morphogenic proteins (BMP)
–Wingless (Wnt) family of proteins
Iraj Salehi-Abari
Amir Alam Hosp.
Pathogenesis:
Wnt pathway:
• Modulated by PGE2
• Suppressed by noggin, sclerostin & DKK-1
• PGE2 and defective gene of promoting
synthesis of DKK-1 play a central role in
new bone formation in AS
Iraj Salehi-Abari
Amir Alam Hosp.
Treatment:
• Pharmacologic– NSAIDs– Non-Biologic DMARDs:
• Sulfasalazine, MTX, Arava, for peripheral arthritis
– Biologic Anti TNF-a agents– Glucocorticoids
• Non-pharmacologic– Life style & health recommendation– Exercise– Surgery
Iraj Salehi-Abari
Amir Alam Hosp.
Treatment:
• Biologic anti TNF-a agents suppress the
symptoms of AS, as well as the acute
phase response. Hence, there is no doubt
that TNF-a is a critical mediator of
inflammation in AS. However, these TNF-a
inhibitors do not arrest the progression of
bone erosions or syndesmophyte
formation
Iraj Salehi-Abari
Amir Alam Hosp.
Treatment:
NSAIDs inhibite COX decrease PG:
• Arrest inflammation and bone
erosions
• Arrest new bone formation via
decreasing of PGE2
Iraj Salehi-Abari
Amir Alam Hosp.
Surgery:
• Total joint replacement;
– Advanced Hip arthritis
• Wedge osteotomy:
– Severe spine deformities
• Fusion of Atlantoaxial joint:
– C1-C2 subluxation
Iraj Salehi-Abari
Amir Alam Hosp.
Mortality:
• X 1.5• Older, higher ESR, more peripheral
arthritis• Causes of death:
1. Secondary amyloidosis2. Cardiovascular3. Accidents4. Suicide
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.
Iraj Salehi-Abari
Amir Alam Hosp.