In the name of God the merciful the compassionate

In the name of God the merciful the compassionate

Ankylosing Spondylitis

Iraj Salehi Abari salehiabari@sina.tums.ac.ir

Iraj Salehi-Abari 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 Amir Alam Hosp.

Iraj Salehi-Abari Amir Alam Hosp.

Previous names: Marrie Strumble disease Bechtereve disease
Iraj Salehi-Abari Previous names: Marrie Strumble disease Bechtereve disease Amir Alam Hosp.

Name in nowadays: Ankylosing Spondylitis Ankylos: Bony bridging
Iraj Salehi-Abari Name in nowadays: Ankylosing Spondylitis Ankylos: Bony bridging Spondylos: Vertebra Amir Alam Hosp.

Names in future: Spondylo-sacroiliitis Rheumatoid Spondylitis
Iraj Salehi-Abari Names in future: Spondylo-sacroiliitis Rheumatoid Spondylitis Amir Alam Hosp.

Iraj Salehi-Abari 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 Amir Alam Hosp.

Historic names of SpA: Seronegative Rheumatism Spondyloarthropathies
Iraj Salehi-Abari Historic names of SpA: Seronegative Rheumatism Spondyloarthropathies SEA syndrome: Spondylitis, Enthesitis, Arthritis BASE syndrome: B27, Arthritis, Sacroiliitis, Enthesitis SpondyloArthritis Amir Alam Hosp.

SpA family members: Ankylosing Spondylitis (AS)
Iraj Salehi-Abari SpA family members: Ankylosing Spondylitis (AS) Reactive arthritis (ReA): Reiter’s Synd.) Psoriatic Arthritis (PsA) Enteropathic Arthritis (IBDrA) Juvenile Spodyloarthropathy (JSpA) Undifferentiated SpA (USpA) Amir Alam Hosp.

Sacroiliitis: History: Buttock pain
Iraj Salehi-Abari Sacroiliitis: History: Buttock pain Ph. Exam: Positive Sacral push test Pelvic X-Ray: Sclerosis Erosion Narrowing Ankylosis Bilateral: AS Unilateral: other SpA Amir Alam Hosp.

Iraj Salehi-Abari Enthesitis: The Enthesis is the region of attachment of tendons and ligaments to bone Enthesitis: Inflammation of Enthesis Achille tendinitis, Plantar fasciitis, Costochondritis, … Amir Alam Hosp.

SpA-Iraj Salehi-Abari

Epidemiology-I: Chronic LBP is a common symptom
Iraj Salehi-Abari Epidemiology-I: Chronic LBP is a common symptom 5% of chronic LBP is inflammatory Prevalence of Axial SpA: 1% Amir Alam Hosp.

Epidemiology-II: Young adults Peak age of onset: 20-30 years
Iraj Salehi-Abari Epidemiology-II: Young adults Peak age of onset: years Prevalence of AS: % AS in (+)HLA-B27 population: 5-6% Amir Alam Hosp.

Epidemiology-III: M/F ratio: (+)FH of AS  5.6–16 fold increases AS
Iraj Salehi-Abari 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% Amir Alam Hosp.

Attention please: Rate of AS is increased by: Hx of chronic LBP: X 10
Iraj Salehi-Abari 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 Amir Alam Hosp.

Definite inflammatory LBP:
Iraj Salehi-Abari 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) Amir Alam Hosp.

Probable inflammatory LBP type I*:
Iraj Salehi-Abari 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) * [Defined by Iraj Salehi-Abari, Rheumatol Int, 2012] Amir Alam Hosp.

Probable inflammatory LBP type II*:
Iraj Salehi-Abari 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) * [Defined by Iraj Salehi-Abari, Rheumatol Int, 2012] Amir Alam Hosp.

Epidemiology in Iran*:
Iraj Salehi-Abari Epidemiology in Iran*: Mean age at diagnosis: 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 Amir Alam Hosp.

Clinical Features: Axial joint involvement;
Iraj Salehi-Abari Clinical Features: Axial joint involvement; Spondylitis and Sacroiliitis Peripheral joint involvement: Root joints (Hip, Shoulder), other Enthesitis: Plantar fasciitis, Achille tendinitis Extra-articular involvement Amir Alam Hosp.

Initial presentation:
Iraj Salehi-Abari Initial presentation: History: Inflammatory LBP Buttock pain Heel pain Back pain Cervical pain Articular pain (Shoulder, Hip, Knee, Ankle) Chest pain Amir Alam Hosp.

Initial presentation:
Iraj Salehi-Abari 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, … Amir Alam Hosp.

Initial presentation*:
Iraj Salehi-Abari Initial presentation*: History: A male (75%) with age of years Definite inflammatory LBP: #65% Probable inflammatory LBP: 25% Buttock pain (+) Family history (FH) of AS #10% *Iraj Salehi-Abari, Early diagnosis of AS, Rheumatol Int. 2012, table 3 Amir Alam Hosp.

Iraj Salehi-Abari Initial presentation*: A Positive FH: In first-degree relatives: Increases the risk of AS by folds In second-degree relatives: Increases the risk of AS by folds *Iraj Salehi-Abari, Early diagnosis of AS, Rheumatol Int. 2012, table 3 Amir Alam Hosp.

Iraj Salehi-Abari 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, Early diagnosis of AS, Rheumatol Int. 2012, table 3 Amir Alam Hosp.

Axial involvement: Sacroiliitis: Spondylitis: Buttock pain
Iraj Salehi-Abari Axial involvement: Sacroiliitis: Buttock pain Sacral push test Spondylitis: Inflammatory LBP Back pain Neck pain Spinal limitation of motion Limited chest expansion Amir Alam Hosp.

Spinal limitation of motion:
Iraj Salehi-Abari 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 Amir Alam Hosp.

Enthesitis: Inflammation of Enthesis Chest and spinal enthesitis
Iraj Salehi-Abari Enthesitis: Inflammation of Enthesis Chest and spinal enthesitis Extraspinal enthesitis Amir Alam Hosp.

Chest and spinal enthesitis:
Iraj Salehi-Abari Chest and spinal enthesitis: Costosternal Costovertebral Spinous processes Paraspinal Iliac crests Ischial tuberosities Sternoclavicular Manubriosternal Amir Alam Hosp.

Extraspinal enthesitis:
Iraj Salehi-Abari Extraspinal enthesitis: Heels: Achilles tendonitis Plantar fasciitis Shoulder tendonitis Greater Trochanters Tibial tubercles, Others Differentiated with FMS by dramatic response to NSAIDs Amir Alam Hosp.

Peripheral arthritis:
Iraj Salehi-Abari Peripheral arthritis: Limb arthritis Upper limb joints Lower limb joint Root joint: Hip & shoulder Extra-limb arthritis TMJ arthritis Sternoclavicular arthritis Amir Alam Hosp.

Iraj Salehi-Abari Peripheral arthritis: Root joints arthritis: 25-35% Other joints: 30% Early hip arthritis: worse prognosis Amir Alam Hosp.

Iraj Salehi-Abari 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 Amir Alam Hosp.

Imaging and Sacroiliitis:
Iraj Salehi-Abari 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 Amir Alam Hosp.

Radiological Sacroiliitis:
Iraj Salehi-Abari 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 Amir Alam Hosp.

Radiological Sacroiliitis:
Iraj Salehi-Abari Radiological Sacroiliitis: In AS: Bilateral sacroiliitis is more common than Unilateral Symmetric sacroiliitis is a Hallmark feature In other SpA: Unilateral or Asymmetric sacroiliitis is a compatible feature Amir Alam Hosp.

Imaging and spondylitis:
Iraj Salehi-Abari 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 Amir Alam Hosp.

Iraj Salehi-Abari 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 Amir Alam Hosp.

Iraj Salehi-Abari Imaging and spondylitis: Later X-ray findings: Syndesmophytes Ankylosis of the facet joints Calcification of the anterior longitudinal ligament Bamboo spine Amir Alam Hosp.

Iraj Salehi-Abari Imaging and spondylitis: Other X-ray findings: C1-C2 subluxation: documented by MRI Spondylodiscitis Fracture Amir Alam Hosp.

Initiation & propagation of axial findings in Plain X-ray:
Iraj Salehi-Abari Initiation & propagation of axial findings in Plain X-ray: Symmetric Sacroiliitis Symmetric Lumbar syndesmophytes Ascending toward thoracic and Cervical spine 4. Bamboo spine Amir Alam Hosp.

Extra-Articular (Systemic) features:
Iraj Salehi-Abari 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 Amir Alam Hosp.

Iraj Salehi-Abari Extra-Articular (Systemic) features: Renal: IgA nephropathy NSAIDs nephropathy Amyloidosis Urinary stones Amir Alam Hosp.

Iraj Salehi-Abari Extra-Articular (Systemic) features: Heart: Aortic regurgitation (AR) due to Aortitis Heart block (CHB) Lungs: Apical pulmonary fibrosis Amir Alam Hosp.

Iraj Salehi-Abari Extra-Articular (Systemic) features: Bowel: Subclinical Ileo-colitis: 50% 5-10% of AS have IBD 5-10% of IBD have AS Amir Alam Hosp.

Iraj Salehi-Abari Extra-Articular (Systemic) features: Nervous system: Cervical myelopathy Atlantoaxial subluxation Fractures of C5-C6 Spinal canal stenosis Cauda equina syndrome Amir Alam Hosp.

Juvenile AS: Peripheral arthritis: Enthesitis: Axial arthritis:
Iraj Salehi-Abari Juvenile AS: Peripheral arthritis: usually predominate Enthesitis: Usually predominate Axial arthritis: Late adolescence 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
Iraj Salehi-Abari 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 ? Amir Alam Hosp.

AS in women: Subclinical: Spinal ankylosis: less frequent
Iraj Salehi-Abari AS in women: Subclinical: Mild and slowly progressive Spinal ankylosis: less frequent Cervical ankylosis: more frequent Peripheral arthritis: more frequent Amir Alam Hosp.

AS in women: Some of AS are missed And some of AS are mistaken with:
Iraj Salehi-Abari 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 Amir Alam Hosp.

AS in pregnancy: Improved: 1/3 Unchanged: 1/3 Deteriorated: 1/3
Iraj Salehi-Abari 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 Amir Alam Hosp.

Pregnancy in AS: No infertility No abortion No stillbirth
Iraj Salehi-Abari Pregnancy in AS: No infertility No abortion No stillbirth No premature labour C-Section > normal delivery Epidural anesthesia will be ignored Normal newborn Amir Alam Hosp.

Host susceptibility to AS:
Iraj Salehi-Abari Host susceptibility to AS: AS occurs worldwide roughly in proportion to the prevalence of HLA-B27 In general population: prevalence of % 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 Amir Alam Hosp.

Other Genes for AS: ERAP1 IL-23R TNFSF15 TNFSF1A STAT3 ANTXR2 IL-1R2
Iraj Salehi-Abari Other Genes for AS: ERAP1 IL-23R TNFSF15 TNFSF1A STAT3 ANTXR2 IL-1R2 Amir Alam Hosp.

Patient’s posture: Forward stoop of the neck
Iraj Salehi-Abari 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 Amir Alam Hosp.

Disease progression can be estimated by:
Iraj Salehi-Abari Disease progression can be estimated by: Loss of height Limitation of chest expansion Spinal flexion Occiput –to-wall distance Amir Alam Hosp.

Spinal fracture: Most serious complication of spine
Iraj Salehi-Abari Spinal fracture: Most serious complication of spine Lower cervical spine (C5-C6): Most common Displaced  myelopayhy > 10% lifetime risk of fracture Thoracolumbar: Pseudoarthrosis Amir Alam Hosp.

Laboratory test: No diagnostic test HLA-B27 positivity
Iraj Salehi-Abari Laboratory test: No diagnostic test HLA-B27 positivity Elevated ESR/CRP Mild Anemia Elevated ALK. Ph. Elevated serum IgA Amir Alam Hosp.

HLA-B27 positivity: 10-fold increase in chance of AS In USA:
Iraj Salehi-Abari 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] Amir Alam Hosp.

HLA-B27 positivity: AS associated alleles:
Iraj Salehi-Abari HLA-B27 positivity: AS associated alleles: HLA-B*2704 HLA-B*2705 Alleles not associated with AS: HLA-B*2706 HLA-B*2709 Amir Alam Hosp.

Iraj Salehi-Abari 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 expansion Radiological criteria: Sacroiliitis grade > 2 bilaterally Sacroiliitis grade 3-4 unilaterally Amir Alam Hosp.

MNYC Criteria for Ankylosing Spondylitis:
Iraj Salehi-Abari 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 Amir Alam Hosp.

MNYC criteria is low sensitive and moderately specific because:
Iraj Salehi-Abari 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 Amir Alam Hosp.

MNYC criteria is low sensitive and moderately specific because:
Iraj Salehi-Abari 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 Amir Alam Hosp.

ASAS* classification criteria for Axial SpA:
Iraj Salehi-Abari 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 Amir Alam Hosp.

ASAS classification criteria for Axial SpA:
Iraj Salehi-Abari 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 hours, 9. FH of SpA, 10. Elevated CRP Amir Alam Hosp.

“…. Criteria” for early diagnosis of AS:
Iraj Salehi-Abari “…. 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. Amir Alam Hosp.

Iraj Salehi-Abari “…. Criteria” for early diagnosis of AS: Clinical criteria: Up to 8 P. Inflammatory LBP: Up to 2 p. Definite P. Probable P. Positive family history of AS Up to 2 P. First-degree P. Second-degree P. Lumbar LOM in all directions P. Positive sacral push test P. Enthesitis &/or arthritis P. Amir Alam Hosp.

Iraj Salehi-Abari “…. Criteria” for early diagnosis of AS: Imaging criteria: Up to 3 P. AP X-ray or MRI of pelvis: Unilateral sacroiliitis (grade >2) P. Bilateral sacroiliitis (grade > 2) P. Whole body bone scan (WBS): Enthesitis &/or arthritis P. Spondylitis P. Sacroiliitis P. HLA-B27 positivity (+1) Amir Alam Hosp.

Iraj Salehi-Abari “…. Criteria” for early diagnosis of AS: Clinical criteria points Imaging criteria points HLA-B27 positivity point Amir Alam Hosp.

AS is the diagnosis if there are:
Iraj Salehi-Abari 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. Amir Alam Hosp.

“Amir alam Hospital” approach towards diagnosis of AS:
Iraj Salehi-Abari “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) Amir Alam Hosp.

Iraj Salehi-Abari “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. Amir Alam Hosp.

Iraj Salehi-Abari “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 Amir Alam Hosp.

“Iran criteria” versus “MNYC criteria” for diagnosis of AS:
Iraj Salehi-Abari “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% Amir Alam Hosp.

“Iran criteria” versus “MNYC criteria” for diagnosis of AS:
Iraj Salehi-Abari “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 Amir Alam Hosp.

Iraj Salehi-Abari 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 Amir Alam Hosp.

Differential diagnosis:
Iraj Salehi-Abari 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 Amir Alam Hosp.

Iraj Salehi-Abari 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 Amir Alam Hosp.

Pathogenesis: Inflammation: New bone formation:
Iraj Salehi-Abari 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: Amir Alam Hosp.

Iraj Salehi-Abari 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) Amir Alam Hosp.

Pathogenesis: New bone formation: Endochondral Two major pathways:
Iraj Salehi-Abari Pathogenesis: New bone formation: Endochondral Two major pathways: Bone morphogenic proteins (BMP) Wingless (Wnt) family of proteins Amir Alam Hosp.

Pathogenesis: Wnt pathway: Modulated by PGE2
Iraj Salehi-Abari 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 Amir Alam Hosp.

Treatment: Pharmacologic Non-pharmacologic NSAIDs Non-Biologic DMARDs:
Iraj Salehi-Abari 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 Amir Alam Hosp.

Iraj Salehi-Abari 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 Amir Alam Hosp.

Treatment: NSAIDs inhibite COX  decrease PG:
Iraj Salehi-Abari Treatment: NSAIDs inhibite COX  decrease PG: Arrest inflammation and bone erosions Arrest new bone formation via decreasing of PGE2 Amir Alam Hosp.

Surgery: Total joint replacement; Wedge osteotomy:
Iraj Salehi-Abari Surgery: Total joint replacement; Advanced Hip arthritis Wedge osteotomy: Severe spine deformities Fusion of Atlantoaxial joint: C1-C2 subluxation Amir Alam Hosp.

Mortality: X 1.5 Older, higher ESR, more peripheral arthritis
Iraj Salehi-Abari Mortality: X 1.5 Older, higher ESR, more peripheral arthritis Causes of death: Secondary amyloidosis Cardiovascular Accidents Suicide Amir Alam Hosp.

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