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IN THE NAME OF GOD

Explore the comprehensive overview of Rheumatoid Arthritis, covering epidemiology, genetic factors, symptoms, and various manifestations. Learn about the diagnostic and laboratory aspects of this chronic inflammatory disease affecting multiple systems.

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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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