Transcript HLA-B27

Rheumatology Research Center
CHARACTERISTICS
• Peripheral Arthritis: Asymmetric, Lower Limb
• Tendency to Sacroiliitis (X-Ray)
• Absence: RF, RA Nodes, Extra-articular Features
• Familial Aggregation
• HLA-B27
CLASSIFICATION
• Ankylosing Spondylitis
• Reiter’s Syndrome
• Arthropathy of Inflammatory Bowel Dis.
• Psoriatic Arthritis
• Undifferentiated SPA
• Juvenile AS
Rheumatology Research Center
GENERAL PATTERN
• Young Male
• Articular Manifestations
– SI Joints
– Spine
– Peripheral Joints: Rhyzomelic
• Extra-Articular Manifestations
– Uveitis
– Aortitis
• HLA-B27
HISTORY
• 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
EPIDEMIOLOGY
• 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
ETIOLOGY
• Unknown
• Strong Association with B27: Hypothesis
– In Susceptible Individuals
Immune Response
Genetically
Determined
To Environmental Factors
HLA-B27
• B*2705, B*2704, B*2702
• B*2706, B*2709
Association
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%
FAMILIAL BACKGROUND
• Siblings
10%
• Twins
– Monozygotic
63%
– Dizygotic
12.5%
– Dizygotic + B27
23%
• Other Genetic Factors
OTHER 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)
ENVIRONMENTAL FACTORS
• Shigella Flexneri
– Reactive to Anti-B27 Antibody
• Yersinia Enterocolittica
– Reactive to Anti-B27 Antibody
• Escherishia Coli
– IgA Antibody in AS Patients
• Klebsiella Pneumoniae
KLEBSIELLA 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
SCENARIO
INFECTIOUS DISSEMINATION
MICRO-ORGANISM
(Intra Cellular)
APC – B27
T-Cell (CD8+)
IMMUNE RESPONSE
MOLECULAR MIMICRY
MICRO-ORGANISM
IMMUNE REACTION
(Peptide Mimicking B27)
T-Cell (CD8+)
APC
B27 Cells
T-Cell (CD4+)
ANTIBODY
B-Cell
(anti B27)
AUTO-REACTIVE T CELLS
HLA-B27
(Intra Thymus)
MICRO-ORGANISM
(Intra Cellular)
APC – B27
Autoreactive CD8+ T-Cell
Periphery
T-Cell (CD8+)
IMMUNE RESPONSE
GENERAL PATTERN
• Articular Manifestations
– Central
•
•
•
•
SI Joints
Lumbar Spine
Dorsal Spine
Cervical Spine
– Peripheral
• Extra-Articular Manifestations
–
–
–
–
Enthesitis
Eye
Aorta
Kidney
PAIN & STIFFNESS
• INFLAMMATORY
– Morning
– > 1 hour
• NOCTURNAL
– Second half
– Awaken
– Walk
SACROILIITIS
• Bilateral Pelvic Pain
– Buttock
– Referral Pain
• Physical Exam
– Direct Pressure
– Direct Mobilization
– Indirect Mobilization
• Evolution
– Bony Ankylosis
LUMBAR SPINE
• Low Back Pain
– Referral Pain
– Sciatica Irradiation
• Physical Exam
– Limitation
– Shober Test
• Progression
– Loss of Lordosis
– Ankylosis
DORSAL SPINE
• Back Pain
– Chondro-costal Pain
– Intercostal Irradiation
• Physical Exam
– Limitation
– Chest Expansion
• Progression
– kyphosis
– Ankylosis
CERVICAL SPINE
• Neck Pain
– Referral Pain
– Cervico-Brachial Irradiation
• Physical Exam
– Limitation
• Progression
– Loss of Lordosis, kyphosis
– Ankylosis
SPINE DEFORMITY
PERIPHERAL JOINTS
• Rhyzomelic Joints
– Hip
– Shoulder
• Talalgia
• Large and Medium Joints
• Small Joints
– Sterno-Clavicular
– Temporo-Mendibular
EXTRA-ARTICULAR
• Eye Involvement
• Cardiovascular Manifestations
• Pulmonary Disease
• Neurological Manifestations
• Renal Manifestations
• Bowel Disease
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
CARDIAC MANIFESTATIONS
• Aortic Valve Incompetence
• Ascending Aortitis
• Cardiac Conduction Abnormality
• Cardiomegaly
• Pericarditis
PULMONARY
• Rare, very late onset (20 y)
• Fibrosis of Upper lobes
– Cough
– Dyspnea
– Hemoptysis
• X-ray
Linear or Patchy Opacities
NEUROLOGICAL
• Quadriplegia
– Atlantoaxial Subluxation
– Cervical Fracture  Dislocation
• Paraplegia
– Cervical or Dorsal Fracture
• Coda Equina
– Spontaneous
– Fracture
RENAL INVOLVEMENY
• IgA Nephropathy
• Amyloidosis
BOWEL DISEASE
• Enteric Mucosal Inflammation
– Terminal Ileum
– Colon
– Asymptomatic
LAB TESTS
• Inflammatory
– ESR
– CRP
• HLA-B27
– 90%
(Iran 55%, RRC Studies)
• Urinalysis
– Proteinuria
X-RAY
• SI Joints
• Spine
• Peripheral Joints
– Hip
– Others
SACROILIAC JOINT
• Pseudo-Widening
• Blurred Borders
• Irregularity (Post Stamp Serration)
• Bony Sclerosis
• Progression
– Bony Ankylosis
SACROILIITIS
SACROILIITIS
SACROILIITIS
SACROILIITIS
SACROILIITIS
SACROILIITIS
SACROILIITIS
SACROILIITIS
SPINE
• Syndesmophyte
• Squaring (Romanus)
• Ligament Ossification
• Spondylodiscitis
SYNDESMOPHYTE
SYNDESMOPHYTE
SYNDESMOPHYTE
BAMBOO SPINE
PATHOPHYSIOLOGY
DISCAL OSSIFICATION
ROMANUS
ROMANUS
SPONDYLO-DISCITIS
LIGAMENT OSSIFICATION
PERIPHERAL JOINTS
• Hip
– Erosive Arthritis
– Non Erosive Bony Ankylosis
• Others
COXITIS
COXITIS
COXITIS
COXITIS
COXITIS
SHOULDER
CALCANEITIS
CALCANEITIS
CALCANEITIS
NSAID
• Full Dose
– COX1: Indomethacin
150 mg/24h
– COX2: Celecoxib (Cobix*)
600 mg/24h
• Adjust To Need
DMARD
• Sulphasalazine
• Methotrexate
2 to 3 g/24 h
7.5 to 15 mg/week
• Prednisolone
5-10 mg/daily
• Anti TNF
– Etanercept
25mg
2/weekly
– Infliximab
5mg/kg
week 0-2-6-12-18 IV
SC