1 IN THE NAME OF GOD

2

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

4

Epidemiology Most common form of chronic inflammatory arthritis Prevalence :~1% (range 0.3–2.1%) women: 3 times more often than men Throughout world; all races 5

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

Genetics First-degree relative 2-10 times Concordant in monozygotic twins 15–20% 7

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

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

10

11 ANTIGEN Genetic Background MACROPHAGE

12 DR MACROPHAGE IL -1 CD80/86

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

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

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

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

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 β-HSD1 11 β-HSD2 Arth Rheum 2005 Abnormal receptor Abnormal postreceptor ADENOSIN

18

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

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

21

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

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

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

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

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

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

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

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

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

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

32

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

Rheumatoid nodule In 20–30% On areas subjected to mechanical pressure Elsewhere 34

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

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

Vasculitis Uncommon Renal vasculitis is rare 37

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

Pleuropulmonary ILD Pulmonary nodules 39

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

Cardiovascular Most common cause of death Inflammatory markers 41

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

Eye <1% Long-standing disease and nodules Episcleritis, scleritis 15–20% of patients Sjögren's syndrome 43

Felty’s syndrome Consists of: - Splenomegaly - Neutropenia Leukopenia is selective neutropenia (PMN <1500 cells/L) Late stage of sever RA High titers of RF, nodules 44

Osteoporosis Inflammation Glucocorticoid 45

46

Laboratory RF autoantibodies reactive with Fc portion of IgG 2/3 of patients No specific 5% of healthy Rheumatic & infectiuse 47

Laboratory Predictive value: low <1/3 of patients with a positive test for RF have RA Not useful as screening Prognostic 48

Laboratory Anti-CCP: - Sensitivity: 70% - Specificity: 90% - Prognostic - 1.5% of population 49

Laboratory Normochromic, normocytic anemia Anemia and thrombocytosis disease activity ESR & CRP Synovial fluid: WBC 50

Radiography Early: soft tissue swelling Juxtaarticular osteopenia Loss of articular cartilage Bone erosions 51

Radiography 52

Patholog Pannus: - Invades bone-cartilage 53

Clinical course Persistent but fluctuating disease activity Early aggressive treatment 54

Diagnosis No pathognomonic finding in: Clinic Paraclinic Almost exclusively on: History Physical examination 55

Diagnosis Typical picture: - Bilateral symmetric polyarthritis - Small and large joints - Upper and lower extremities - Sparing of the axial skeleton except cervical spine Constitutional features Morning stiffness Nodules RF & AntiCCP Radiography 56

ACR-EULAR criteria for classification of RA Joint involvement: Score - 1 large joint large joint small joint small joint 3 - > 10 joint (at least small joint) 5

ACR-EULAR criteria for classification of RA Serology: Score - Negative RF or Anti-CCP 0 - Low positive (< 3 times) 2 - High (> 3 times) 3

ACR-EULAR criteria for classification of RA Acute Phase reactants: Score - ERS/CRP NL 0 - Abnormal 1 Duration - <6 weeks 0 - ≥6 weeks 1 Definite RA ≥6

Treatment NSAIDs Glucocorticoid DMARDs Biologic 60

61 YAZD-GHALAH THANKS FOR YOUR ATTENTION