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IN THE NAME OF GOD

IN THE NAME OF GOD. Rheumatoid Arthritis. Rheumatoid Arthritis. A chronic multisystem disease Characteristic feature: Persistent inflammatory synovitis Peripheral joints Symmetric Cartilage damage and bone erosions . Destruction. Epidemiology and Genetics. Epidemiology.

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IN THE NAME OF GOD

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  1. IN THE NAME OF GOD

  2. Rheumatoid Arthritis

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

  4. Epidemiology and Genetics

  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

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

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

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

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

  10. Etiology

  11. Genetic Background ANTIGEN MACROPHAGE

  12. DR CD80/86 IL -1 MACROPHAGE

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

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

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

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

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

  18. ONSET

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

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

  21. ARTICULAR SIGNS & SYMPTOMS

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

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

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

  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

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

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

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

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

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

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

  32. EXTRAARTICULAR MANIFESTATION

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

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

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

  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

  37. Vasculitis • Uncommon • Renal vasculitis is rare

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

  39. Pleuropulmonary • ILD • Pulmonary nodules

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

  41. Cardiovascular • Most common cause of death • Inflammatory markers

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

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

  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

  45. Osteoporosis • Inflammation • Glucocorticoid

  46. LABORATORY

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

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

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

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

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