1. Management of Rheumatoid Arthritis

2. 2

3. 3 1. Morning stiffness Morning stiffness in and around the joints, lasting at least 1 hour before maximal improvement at any time inthe disease course. 2. Arthritis in at least three joint Areas* Soft tissue swelling or fluid observed by a physician, with swelling at current examination or deformity and a documented history of swelling. Arthritis of hands 3. Arthritis of hands Swelling of wrist, MCP, or PIP with swelling at current examination or deformity and a documented history of swelling. 4. Symmetric arthritis Simultaneous involvement of the same joint areas (defined in 2) on both sides of the body (bilateral involvement of PIPs, MCPs, or MTPs is acceptable without absolute symmetry) with swelling at current examination or deformity and a documented history of swelling. 5. Rheumatoid nodules nodules Over bony prominences or extensor surfaces, or in peri- articular regions 6.Rheumatoid factor factor Detected by a method positive in less than 5% normal controls at current examination or documented to have been positive in the past by any assay method. 7. Radiographic changes changes Typical of RA on posteroanterior hand and wrist radiographs which must include erosions or unequivocal bony decalcification localized to or most marked adjacent to the involved joints (osteoarthritis changesalone do not qualify). *Note: At least four criteria must be fulfilled for classification as RA.

4. 4 Autoimmune/Genetic factors?

5. 5 Other factors  Silica Dust Exposure  Increased risk for RA in smokers  Infections?-  Infections?-(EBV)  Dietary Factors- ? red meat ? intake of fruit and oily fish may protect against RA (Mediterranean diet)  ?Interactions between genes and environment and stochastic factor contributions

6. 6 Other nutrient factors  Lower intakes of fruit and vegetables (high consumption of the antioxidants cryptoxanthin and zeaxanthin) increased the risk of inflammatory polyarthritis  Lower intakes of vitamin C, fruit and vegetables (high consumption of the antioxidants cryptoxanthin and zeaxanthin) increased the risk of inflammatory polyarthritis

7. 7 Articular and Peri-articular Manifestations  Duration of signs and symptoms at more than 3 months was the strongest predictor of RA  Slow, insidious disease onset (70%)   Intermediate onset (20%)   Sudden acute onset (10%)  Complain of pain, stiffness, and swelling of their peripheral joints

8. 8 Clinical Findings  Examination of the joints reveals tenderness to palpation, synovial thickening, joint effusion, redness and warmth  May show decreased range of motion, ankylosis, and subluxation  Upper limb (50%) multiple joints affected (30%) hand only (25%)

9. 9 Clinical Findings   Symmetrical joints involvement (85%)   Joints most commonly affected are-   The proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the hands and wrists, followed by   The metatarsophalangeal (MTP) joints of the feet, ankles, and shoulders.

10. 10  Radiograph of the left hand. Soft tissue swelling is present around the MCP joints and wrist with diffuse narrowing of MCP, PIP, and radiocarpal joint spaces.  Erosions are seen at the first CMC joint and distal ulna.  Periarticular osteopenia surrounds all of the articulations.

11. 11  Radiograph of the left wrist reveals soft-tissue swelling with narrowing about the radial carpal joint associated with early reactive sclerosis involving the radial articular surface.  There is widening of the distal radial–ulnar joint and cysts are present within the carpal navicular and distal ulna.

12. 12   An MRI of the left wrist of the same patient multiple bony erosions in the ulna, lunate, triquetrum, and distal radius.   Complete loss of articular cartilage is with slight ulnar shift   Exuberant synovial proliferation with inflamed synovium is seen to enter the large erosion within the distal ulna, illustrating the extensive synovitis that is missed on conventional radiography

13. 13   Diffuse swelling of the hand with polyarthritis of the MCPs, PIPs, and wrists seen in remitting seronegative symmetric synovitis with pitting edema

14. 14

15. 15 Extra-Articular Manifestations  Rheumatoid Nodules  Anemia of chronic disease, lymphadenopathy  Vasculitis- sensorimotor neuropathy, nail-fold infarcts, leg ulcers, purpura, and digital gangrene

16. 16 Treatment of Early Arthritis  Nonsteroidal Anti-Inflammatory Drugs-  Nonsteroidal Anti-Inflammatory Drugs- do not alter the course of the arthritis and its outcome  Glucocorticoids-  Disease-Modifying Antirheumatic Drugs  Methotrexate- favorable risk–benefit ratio, is (as in established RA) regarded to be the drug of first choice   hydroxychloroquine or sulfasalazine

17. 17 QOL assessment ● Mobility ● Self-care ● Usual activities ● Pain/discomfort ● Anxiety/depression

18. 18 Specific drugs: Methotrexate  Anti folic acid-  Anti folic acid- inhibition of proliferation of cells responsible for synovial inflammation   Decreases markers of inflammation, including the erythrocyte sedimentation rate and c-reactive protein (CRP)   Adverse Effects-low-dose weekly-7.5 to 10 mg   anorexia, nausea, vomiting, and diarrhea(10%)   Hematologic-leukopenia (3%)   ? cirrhosis and liver failure (1/1000)   acute interstitial pneumonitis

19. 19 “MTX is currently considered a first-line agent in the treatment of RA, and the “anchor drug” for combination therapy with other DMARDs and biologic agents. It has become the standard of care and the most widely used drug in the treatment of RA.”

20. 20 Leflunomide   A second choice DMARD to be used after methotrexate   has a long half-life (2 wks)   dose:20 mg daily   lefl unomide, sulfasalazine, and methotrexate reduced radiologic progression

21. 21 Other Drugs  Antimalarials  Sulfasalazine  Tetracyclines  Gold Salts  D-penicillamine  Azathioprine  Cyclosporine