1. 1 IN THE NAME OF GOD

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

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5. 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

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

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

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

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

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11. 11 ANTIGEN Genetic Background MACROPHAGE

12. 12 DR MACROPHAGE IL -1 CD80/86

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

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

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

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

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

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

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

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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

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

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

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

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

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

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

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

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

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

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

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

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

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

37. Vasculitis Uncommon Renal vasculitis is rare 37

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

39. Pleuropulmonary ILD Pulmonary nodules 39

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

41. Cardiovascular Most common cause of death Inflammatory markers 41

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

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

44. 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

45. Osteoporosis Inflammation Glucocorticoid 45

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

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

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

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

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

52. Radiography 52

53. Patholog Pannus: - Invades bone-cartilage 53

54. Clinical course Persistent but fluctuating disease activity Early aggressive treatment 54

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

56. 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

57. 57 2010 ACR-EULAR criteria for classification of RA Joint involvement: Score - 1 large joint 0 - 2-10 large joint 1 - 1-3 small joint 2 - 4-10 small joint 3 - > 10 joint (at least small joint) 5

58. 58 2010 ACR-EULAR criteria for classification of RA Serology: Score - Negative RF or Anti-CCP 0 - Low positive (< 3 times) 2 - High (> 3 times) 3

59. 59 2010 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

60. Treatment NSAIDs Glucocorticoid DMARDs Biologic 60

61. 61 YAZD-GHALAH THANKS FOR YOUR ATTENTION