Slide 1

1 IN THE NAME OF GOD

Slide 2

2

Slide 3

Rheumatoid Arthritis A chronic multisystem disease Characteristic feature: Persistent inflammatory synovitis Peripheral joints Symmetric Cartilage damage and bone erosions Destruction 3

Slide 4

4

Slide 5

Epidemiology Most common form of chronic inflammatory arthritis Prevalence :~1% (range 0.32.1%) women: 3 times more often than men Throughout world; all races 5

Slide 6

Epidemiology Onset: 4 and 5 decades of life Incidence between 25 and 50 y 6

Slide 7

Genetics First-degree relative 2-10 times Concordant in monozygotic twins 1520% 7

Slide 8

Genetics Major genetic risk factors class II HLA HLA-DR4 (DR1*0401) and related alleles 8

Slide 9

Environmental factors Climate and urbanization Incidence and severity of RA Smoking : Relative Risk: 1.5-3.5 Severe RA with antibodies to CCP 9

Slide 10

10

Slide 11

11 ANTIGEN Genetic Background MACROPHAGE

Slide 12

12 DR MACROPHAGE IL -1 CD80/86

Slide 13

13 ANTIGEN DR MACROPHAGET-CELL CD4+ IL -1 CD80/86 CD 28

Slide 14

14 Genetic Background IL- 1 ANTIGEN MACROPHAGE T CELL IL 2 B Cell ANTIBODY

Slide 15

15 AUTOIMMUNE REACTION Genetic Background IL- 1 ANTIGEN MACROPHAGE T CELL IL 2 B Cell IMMUNE COMPLEX ANTIBODY

Slide 16

16 AUTOIMMUNE REACTION Genetic Background IL- 1 ANTIGEN MACROPHAGE T CELL IL 2 B Cell ANTIBODY IMMUNECOMPLEX COMPLEMENT TARGET INFLAMMATION

Slide 17

17 HYPOTHALAMUS PITUITARY GLAND ADRENAL CORTISOL IL-1, IL-6, TNF DHEA BRAIN STEM ESTROGEN AUTONOM SYNOVITIS RA: Plasma cortisol Nature 2007 Cortisol Cortisone 11 -HSD1 11 -HSD2 Arth Rheum 2005 Abnormal receptor Abnormal postreceptor ADENOSIN

Slide 18

18

Slide 19

Onset In 2/3 of patients begins with: - Fatigue, anorexia, generalized weakness This prodrome may persist for weeks or months 19

Slide 20

Onset Specific symptoms appear gradually - Especially: hands, wrists, knees, feet - Symmetric 1/3 of patients Initially one or a few joints 20

Slide 21

21

Slide 22

Articular Most common manifestation: - Pain An almost invariable feature: - Morning stiffness of >1-h Constitutional symptoms: - Weakness, easy fatigability, anorexia, and weight loss 22

Slide 23

Articular Synovial inflammation causes: Swelling Tenderness Limitation of motion Warmth 23

Slide 24

Articular Initially, impairment in physical function is caused by: - Pain and inflammation Later: - Fibrous or bony ankylosis 24

Slide 25

Articular Symmetric Certain specific joints: - Wrist joints - MCP, PIP - Synovitis of the elbow Flexion contractures - Knee - Forefoot, ankles, and subtalar - Hip & shoulder DIP: rare Not affect lumbar and thoracic spine 25

Slide 26

Articular Synovial joints of C1-C2: - On occasion - Atlantoaxial subluxation - Pain in the occiput - Rarely: compression of the cord 26

Slide 27

Articular Characteristic joint changes: Hand: - "Z" deformity Radial deviation at wrist Ulnar deviation digits 27

Slide 28

Articular Characteristic joint changes: Hand: - Swan-neck deformity PIP hyperextension DIP Flexion 28

Slide 29

Articular Characteristic joint changes: Hand: - Boutonnire deformity PIP flexion DIP extension 29

Slide 30

Articular Characteristic joint changes: Hand: - Thumb Hyperextension of the first IP Flexion of the first MCP 30

Slide 31

Articular Characteristic joint changes: Foot: - Hallux valgus - Eversion at hindfoot - Plantar subluxation of the metatarsal heads - Widening of the forefoot - Lateral deviation and dorsal subluxation of the toes 31

Slide 32

32

Slide 33

Extraarticular Manifestation RA is a systemic disease 40% of patients As a rule: occur in high titers of RF or antiCCP 33

Slide 34

Rheumatoid nodule In 2030% On areas subjected to mechanical pressure Elsewhere 34

Slide 35

Rheumatoid nodule Common locations: Olecranon bursa, proximal ulna, Achilles tendon, occiput 35

Slide 36

Vasculitis Severe RA and high titers of RF Can affect nearly any organ Polyneuropathy and mononeuritis multiplex Cutaneous ulceration and dermal necrosis Digital gangrene Visceral infarction 36

Slide 37

Vasculitis Uncommon Renal vasculitis is rare 37

Slide 38

Pleuropulmonary Pleuritis: - Most common pulmonary manifestation - Autopsy Common - Symptomatic Infrequent 38

Slide 39

Pleuropulmonary ILD Pulmonary nodules 39

Slide 40

Cardiovascular Pericarditis: - Asymptomatic - 50% in autopsy Congestive heart failure IHD 40

Slide 41

Cardiovascular Most common cause of death Inflammatory markers 41

Slide 42

Nervous system Central nervous system Spare Vasculitis Peripheral neuropathy Atlantoaxial subluxation Nerve entrapment 42

Slide 43

Eye