1. Rheumatoid Arthritis(RA) Dr. Gehan Mohamed

2. Learning objectives: At the end of this lecture the student should be able to : understand definition,genetic predisposition of RA. Discuss pathophysiology, clinical features of RA. Identify Diagnostic Criteria,Laboratory Features and bad prognostic Features of Rheumatoid Arthritis.

3. RA Systemic inflammatory autoimmune disorder Age incidence : 40-70 years of age

4. Genetics Patients which have HLA-DRB have Increased risk for : RA development. Increased joint damage Increased joint need for surgery

5. Pathophysiology

6. Role of Immunolog in RA Macrophages: Produce cytokines Cytokines (TNF-α) cause systemic features Release chemokines  recruit PMNs into synovial fluid/membrane TNF-α & IL-1: Proliferation of T cells Activation of B cells Initiates proinflammatory/joint- damaging processes TH-1 cells: Mediate disease processes Activate B cells B cells: Release cytokines Plasma cells that produce Ab Osteoclasts induce: Bone erosion Juxta-articular & Systemic osteoporosis

7. Pathophysiology Swelling of Synovial lining Angiogenesis Pannus formation in form of : Synovial thickening/hyperplasia Inflammatory vascularized tissue Generation of Metalloproteinases Cytokine release Infiltration of leukocytes Change in cell-surface adhesion molecules & cytokines Destruction of bone & cartilage

8. Sequence of events : Proliferation of synovial membrane cells with inflammatory cell infiltrate Destruction of joints Disability

9. Diagnosis: 1- clinical criteria 2- investigations

10. 1- Diagnostic Criteria Symmetric peripheral polyarthritis Morning Stiffness >1 hour Extraarticular manifestations Rheumatoid nodules

11. Symmetric Peripheral Polyarthritis 3 or more Joints for >6 weeks Intermittent or Migratory involvement Small Joints Hands & Feet Peripheral to Proximal Leads to Deformity & Destruction of Joints Erosion of cartilage and bone

12. Stiffness Morning or after Prolonged Inactivity Bilateral > 1 hours Reflects severe joint inflammation Better with movement Pain with pressure to joint Pain with movement of joint Swelling due to hypertrophy of synovium Effusion Hottness Redness

13. Physical Exam Decreased grip strength Carpal tunnel syndrome(condition characterized by pain and numbing or tingling sensations in the hand and caused by compression of a nerve in the carpal tunnel at the wrist. Ulnar deviation Boutonniere/Swan neck deformities Extensor tendon rupture

15. Extraarticular Involvement Myalgia, fatigue, low- grade fever, weight loss, depression. Anemia Rheumatoid nodules Pleuropericarditis Neuropathy Scleritis Splenomegaly Vasculitis

16. Rheumatoid Nodules Extensor surfaces elbows Very Specific Only occur in ~30% Late in Disease

17. Investigations

18. Arthrocentesis Confirm diagnoses Differentiate between inflammatory & noninflammatory Labs: White blood cell count if WBC >2000/µL indicates inflammatory arthritis Gram stain & Culture Arthroscopy Evaluate ligamentous & cartilaginous integrity Biopsy Infection: aspirate thick

19. Rheumatoid arthritis : showing inflammatory cell infiltrate in the synovium

20. Laboratory Features Rhumatoid Factor 70-80% of pts. - Lab manifestations up to 10 years before clinical - IgM or IgG - If IgM+ve : more severe disease & poorer outcome. Overlap with Hepatitis C Virus. Acute Phase reactants ESR, CRP  monitoring disease activity

21. Radiology Evaluate disease activity & joint damage Bony decalcification

22. Radiological Studies Plain Films Bilateral hands & feet Color Doppler U/S & MRI Early signs of damage i.e. Erosions Bone Edema - even with normal findings on radiography

25. Disease Severity

26. Arthralgias >3 inflamed joints Mild functional limitation Minimally elevated ESR & CRP No erosions/cartilage loss No extraarticular disease Mild Disease

27. Moderate Disease 6-20 Inflamed joints Moderate functional limitation Elevated ESR/CRP Radiographic evidence of inflammation No extraarticular disease

28. Severe Disease >20 persistently inflamed joints Rapid decline in functional capacity Radiographic evidence of rapid progession of bony erosions & loss of cartilage Extraarticular disease

29. bad prognostic Features RF +ve Early development of multiple inflamed joints and joint erosions Severe functional limitation Female HLA epitope presence Lower socioeconomic status & Less education Persistent joint inflammation for >12 weeks

30. Differential diagnosis of arthritis Seronegative polyarthritis Psoriatic arthritis Osteoarthritis SLE Paraneoplastic syndrome Crystal-induced arthritis Tophaceous gout Pseudogout