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Rheumatology Research CenterRheumatology Research Center
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CHARACTERISTICSCHARACTERISTICS
• Peripheral Arthritis: Asymmetric, Lower Limb
• Tendency to Sacroiliitis (X-Ray)
• Absence: RF, RA Nodes, Extra-articular Features
• Familial Aggregation
• HLA-B27
• Peripheral Arthritis: Asymmetric, Lower Limb
• Tendency to Sacroiliitis (X-Ray)
• Absence: RF, RA Nodes, Extra-articular Features
• Familial Aggregation
• HLA-B27
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CLASSIFICATIONCLASSIFICATION
• Ankylosing Spondylitis
• Reiter’s Syndrome
• Arthropathy of Inflammatory Bowel Dis.
• Psoriatic Arthritis
• Undifferentiated SPA
• Juvenile AS
• Ankylosing Spondylitis
• Reiter’s Syndrome
• Arthropathy of Inflammatory Bowel Dis.
• Psoriatic Arthritis
• Undifferentiated SPA
• Juvenile AS
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Rheumatology Research CenterRheumatology Research Center
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GENERAL PATTERNGENERAL PATTERN
• Young Male
• Articular Manifestations– SI Joints– Spine– Peripheral Joints: Rhyzomelic
• Extra-Articular Manifestations– Uveitis– Aortitis
• HLA-B27
• Young Male
• Articular Manifestations– SI Joints– Spine– Peripheral Joints: Rhyzomelic
• Extra-Articular Manifestations– Uveitis– Aortitis
• HLA-B27
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HISTORYHISTORY
• Brodie 1850• 31 year old man, Ankylosed Spine, Uveitis
• Strumpell 1884• 2 patients, Ankylosed Spine, Hip Joints
• Pierre Marie 1889
• Von Bechterew 1893
• X-Ray: SI joints 1930
• Brodie 1850• 31 year old man, Ankylosed Spine, Uveitis
• Strumpell 1884• 2 patients, Ankylosed Spine, Hip Joints
• Pierre Marie 1889
• Von Bechterew 1893
• X-Ray: SI joints 1930
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EPIDEMIOLOGYEPIDEMIOLOGY• Prevalence
– 0.5 to 2 / 1000
– 10 to 20 / 1000 of B27
– 100 to 300 / 1000 of B27 + Family Background
• Incidence– 7.3 / 100,000 / Year
• Racial Distribution– B27 Related
– White, African American, African, Japanese
• Prevalence – 0.5 to 2 / 1000
– 10 to 20 / 1000 of B27
– 100 to 300 / 1000 of B27 + Family Background
• Incidence– 7.3 / 100,000 / Year
• Racial Distribution– B27 Related
– White, African American, African, Japanese
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ETIOLOGYETIOLOGY• Unknown
• Strong Association with B27: Hypothesis
– In Susceptible Individuals
Immune Response
Genetically Determined
To Environmental Factors
• Unknown
• Strong Association with B27: Hypothesis
– In Susceptible Individuals
Immune Response
Genetically Determined
To Environmental Factors
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HLA-B27HLA-B27
• B*2705, B*2704, B*2702 Association
• B*2706, B*2709 Preventive
• HLA-B27 in General Population 2-10%
• HLA-B27 in AS 90%
– Iran (RRC) 55% - 60%
• AS in HLA-B27 1-2%
• AS in First Degree Relatives 10-30%
• B*2705, B*2704, B*2702 Association
• B*2706, B*2709 Preventive
• HLA-B27 in General Population 2-10%
• HLA-B27 in AS 90%
– Iran (RRC) 55% - 60%
• AS in HLA-B27 1-2%
• AS in First Degree Relatives 10-30%
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FAMILIAL BACKGROUNDFAMILIAL BACKGROUND
• Siblings 10%
• Twins
– Monozygotic 63%
– Dizygotic 12.5%
– Dizygotic + B27 23%
• Other Genetic Factors
• Siblings 10%
• Twins
– Monozygotic 63%
– Dizygotic 12.5%
– Dizygotic + B27 23%
• Other Genetic Factors
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OTHER GENETIC FACTORSOTHER GENETIC FACTORS
• HLA-B60 3-6 fold increase
• Other Genetic Factors
– Other HLA
• B7-Creg, B38, B39, DR1, DR8
– Non-HLA
• Chromosome 16 (Crohn), 17 (Psoriasis)
• HLA-B60 3-6 fold increase
• Other Genetic Factors
– Other HLA
• B7-Creg, B38, B39, DR1, DR8
– Non-HLA
• Chromosome 16 (Crohn), 17 (Psoriasis)
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ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS
• Shigella Flexneri
– Reactive to Anti-B27 Antibody
• Yersinia Enterocolittica
– Reactive to Anti-B27 Antibody
• Escherishia Coli
– IgA Antibody in AS Patients
• Klebsiella Pneumoniae
• Shigella Flexneri
– Reactive to Anti-B27 Antibody
• Yersinia Enterocolittica
– Reactive to Anti-B27 Antibody
• Escherishia Coli
– IgA Antibody in AS Patients
• Klebsiella Pneumoniae
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KLEBSIELLA PneumoniaeKLEBSIELLA Pneumoniae• IgA & IgG Antibodies in AS
– ELISA
• Antigen Resembling B27
– Nitrogenase Enzyme
• Cross-Reacting Antibodies
– Anti-B27 Antibody
• Bind to B27 positive Cells
• Disease Manifestations
• IgA & IgG Antibodies in AS
– ELISA
• Antigen Resembling B27
– Nitrogenase Enzyme
• Cross-Reacting Antibodies
– Anti-B27 Antibody
• Bind to B27 positive Cells
• Disease Manifestations
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SCENARIOSCENARIO
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INFECTIOUS DISSEMINATIONINFECTIOUS DISSEMINATIONMICRO-ORGANISM
(Intra Cellular)MICRO-ORGANISM
(Intra Cellular)
APC – B27APC – B27
T-Cell (CD8+)T-Cell (CD8+)
IMMUNE RESPONSEIMMUNE RESPONSE
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MOLECULAR MIMICRYMOLECULAR MIMICRY
ANTIBODY(anti B27)
ANTIBODY(anti B27)
B27 CellsB27 Cells
T-Cell (CD8+)T-Cell (CD8+)
IMMUNE REACTIONIMMUNE REACTION
MICRO-ORGANISM(Peptide Mimicking B27)MICRO-ORGANISM(Peptide Mimicking B27)
APC APC
T-Cell (CD4+)T-Cell (CD4+)
B-CellB-Cell
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AUTO-REACTIVE T CELLSAUTO-REACTIVE T CELLS
HLA-B27(Intra Thymus)
HLA-B27(Intra Thymus)
Autoreactive CD8+ T-CellAutoreactive CD8+ T-Cell
MICRO-ORGANISM(Intra Cellular)
MICRO-ORGANISM(Intra Cellular)
APC – B27APC – B27
T-Cell (CD8+)T-Cell (CD8+)
IMMUNE RESPONSEIMMUNE RESPONSE
Periphery
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GENERAL PATTERNGENERAL PATTERN• Articular Manifestations
– Central• SI Joints• Lumbar Spine• Dorsal Spine• Cervical Spine
– Peripheral
• Extra-Articular Manifestations– Enthesitis– Eye– Aorta– Kidney
• Articular Manifestations– Central
• SI Joints• Lumbar Spine• Dorsal Spine• Cervical Spine
– Peripheral
• Extra-Articular Manifestations– Enthesitis– Eye– Aorta– Kidney
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PAIN & STIFFNESSPAIN & STIFFNESS
• INFLAMMATORY
– Morning
– > 1 hour
• NOCTURNAL
– Second half
– Awaken
– Walk
• INFLAMMATORY
– Morning
– > 1 hour
• NOCTURNAL
– Second half
– Awaken
– Walk
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SACROILIITISSACROILIITIS• Bilateral Pelvic Pain
– Buttock
– Referral Pain
• Physical Exam– Direct Pressure
– Direct Mobilization
– Indirect Mobilization
• Evolution– Bony Ankylosis
• Bilateral Pelvic Pain – Buttock
– Referral Pain
• Physical Exam– Direct Pressure
– Direct Mobilization
– Indirect Mobilization
• Evolution– Bony Ankylosis
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LUMBAR SPINELUMBAR SPINE
• Low Back Pain– Referral Pain
– Sciatica Irradiation
• Physical Exam– Limitation
– Shober Test
• Progression– Loss of Lordosis
– Ankylosis
• Low Back Pain– Referral Pain
– Sciatica Irradiation
• Physical Exam– Limitation
– Shober Test
• Progression– Loss of Lordosis
– Ankylosis
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DORSAL SPINEDORSAL SPINE
• Back Pain– Chondro-costal Pain
– Intercostal Irradiation
• Physical Exam– Limitation
– Chest Expansion
• Progression– kyphosis
– Ankylosis
• Back Pain– Chondro-costal Pain
– Intercostal Irradiation
• Physical Exam– Limitation
– Chest Expansion
• Progression– kyphosis
– Ankylosis
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CERVICAL SPINECERVICAL SPINE
• Neck Pain
– Referral Pain
– Cervico-Brachial Irradiation
• Physical Exam
– Limitation
• Progression
– Loss of Lordosis, kyphosis
– Ankylosis
• Neck Pain
– Referral Pain
– Cervico-Brachial Irradiation
• Physical Exam
– Limitation
• Progression
– Loss of Lordosis, kyphosis
– Ankylosis
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SPINE DEFORMITYSPINE DEFORMITY
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PERIPHERAL JOINTSPERIPHERAL JOINTS
• Rhyzomelic Joints
– Hip
– Shoulder
• Talalgia
• Large and Medium Joints
• Small Joints
– Sterno-Clavicular
– Temporo-Mendibular
• Rhyzomelic Joints
– Hip
– Shoulder
• Talalgia
• Large and Medium Joints
• Small Joints
– Sterno-Clavicular
– Temporo-Mendibular
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EXTRA-ARTICULAREXTRA-ARTICULAR
• Eye Involvement
• Cardiovascular Manifestations
• Pulmonary Disease
• Neurological Manifestations
• Renal Manifestations
• Bowel Disease
• Eye Involvement
• Cardiovascular Manifestations
• Pulmonary Disease
• Neurological Manifestations
• Renal Manifestations
• Bowel Disease
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EYE LESIONS (Ant. Uveitis)EYE LESIONS (Ant. Uveitis)
• 25%, Unilateral, Acute Onset, B27 Related
• Clinical Manifestations– Pain
– Increased Lacrymation
– Photophobia
– Blurred Vision
• Exam– Discolored Iris
– Small Pupil
• Progression Self Subsiding
• 25%, Unilateral, Acute Onset, B27 Related
• Clinical Manifestations– Pain
– Increased Lacrymation
– Photophobia
– Blurred Vision
• Exam– Discolored Iris
– Small Pupil
• Progression Self Subsiding
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CARDIAC MANIFESTATIONSCARDIAC MANIFESTATIONS
• Aortic Valve Incompetence
• Ascending Aortitis
• Cardiac Conduction Abnormality
• Cardiomegaly
• Pericarditis
• Aortic Valve Incompetence
• Ascending Aortitis
• Cardiac Conduction Abnormality
• Cardiomegaly
• Pericarditis
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PULMONARYPULMONARY
• Rare, very late onset (20 y)
• Fibrosis of Upper lobes
– Cough
– Dyspnea
– Hemoptysis
• X-ray Linear or Patchy Opacities
• Rare, very late onset (20 y)
• Fibrosis of Upper lobes
– Cough
– Dyspnea
– Hemoptysis
• X-ray Linear or Patchy Opacities
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NEUROLOGICALNEUROLOGICAL
• Quadriplegia– Atlantoaxial Subluxation
– Cervical Fracture Dislocation
• Paraplegia– Cervical or Dorsal Fracture
• Coda Equina– Spontaneous
– Fracture
• Quadriplegia– Atlantoaxial Subluxation
– Cervical Fracture Dislocation
• Paraplegia– Cervical or Dorsal Fracture
• Coda Equina– Spontaneous
– Fracture
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RENAL INVOLVEMENYRENAL INVOLVEMENY
• IgA Nephropathy
• Amyloidosis
• IgA Nephropathy
• Amyloidosis
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BOWEL DISEASEBOWEL DISEASE
• Enteric Mucosal Inflammation
– Terminal Ileum
– Colon
– Asymptomatic
• Enteric Mucosal Inflammation
– Terminal Ileum
– Colon
– Asymptomatic
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LAB TESTSLAB TESTS
• Inflammatory
– ESR
– CRP
• HLA-B27
– 90% (Iran 55%, RRC Studies)
• Urinalysis
– Proteinuria
• Inflammatory
– ESR
– CRP
• HLA-B27
– 90% (Iran 55%, RRC Studies)
• Urinalysis
– Proteinuria
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X-RAYX-RAY
• SI Joints
• Spine
• Peripheral Joints
– Hip
– Others
• SI Joints
• Spine
• Peripheral Joints
– Hip
– Others
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SACROILIAC JOINTSACROILIAC JOINT
• Pseudo-Widening
• Blurred Borders
• Irregularity (Post Stamp Serration)
• Bony Sclerosis
• Progression
– Bony Ankylosis
• Pseudo-Widening
• Blurred Borders
• Irregularity (Post Stamp Serration)
• Bony Sclerosis
• Progression
– Bony Ankylosis
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SACROILIITISSACROILIITIS
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SACROILIITISSACROILIITIS
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SACROILIITISSACROILIITIS
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SACROILIITISSACROILIITIS
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SACROILIITISSACROILIITIS
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SACROILIITISSACROILIITIS
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SACROILIITISSACROILIITIS
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SACROILIITISSACROILIITIS
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SPINESPINE
• Syndesmophyte
• Squaring (Romanus)
• Ligament Ossification
• Spondylodiscitis
• Syndesmophyte
• Squaring (Romanus)
• Ligament Ossification
• Spondylodiscitis
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SYNDESMOPHYTESYNDESMOPHYTE
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SYNDESMOPHYTESYNDESMOPHYTE
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SYNDESMOPHYTESYNDESMOPHYTE
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BAMBOO SPINEBAMBOO SPINE
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PATHOPHYSIOLOGYPATHOPHYSIOLOGY
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DISCAL OSSIFICATIONDISCAL OSSIFICATION
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ROMANUSROMANUS
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ROMANUSROMANUS
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SPONDYLO-DISCITISSPONDYLO-DISCITIS
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LIGAMENT OSSIFICATIONLIGAMENT OSSIFICATION
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PERIPHERAL JOINTSPERIPHERAL JOINTS
• Hip
– Erosive Arthritis
– Non Erosive Bony Ankylosis
• Others
• Hip
– Erosive Arthritis
– Non Erosive Bony Ankylosis
• Others
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COXITISCOXITIS
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COXITISCOXITIS
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COXITISCOXITIS
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COXITISCOXITIS
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COXITISCOXITIS
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SHOULDERSHOULDER
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CALCANEITISCALCANEITIS
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CALCANEITISCALCANEITIS
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CALCANEITISCALCANEITIS
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NSAIDNSAID
• Full Dose
– COX1: Indomethacin 150 mg/24h
– COX2: Celecoxib (Cobix*) 600 mg/24h
• Adjust To Need
• Full Dose
– COX1: Indomethacin 150 mg/24h
– COX2: Celecoxib (Cobix*) 600 mg/24h
• Adjust To Need
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DMARDDMARD
• Sulphasalazine 2 to 3 g/24 h
• Methotrexate 7.5 to 15 mg/week
• Prednisolone 5-10 mg/daily
• Anti TNF
– Etanercept 25mg 2/weekly SC
– Infliximab 5mg/kg week 0-2-6-12-18 IV
• Sulphasalazine 2 to 3 g/24 h
• Methotrexate 7.5 to 15 mg/week
• Prednisolone 5-10 mg/daily
• Anti TNF
– Etanercept 25mg 2/weekly SC
– Infliximab 5mg/kg week 0-2-6-12-18 IV
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