1. Rheumatoid arthritis & Gout 1

2.  (RA) is an autoimmune disease that causes chronic inflammation of the joints & can also cause inflammation of the tissue around the joints.  Inflammatory arthritis  Peak incidence in 3rd to 4th decades( عقود ) of life  3-5 times higher preponderance(( يكثر in females than males 2

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4.  Exact mechanism is not known  1) Autoantibody-Rheumatoid factor(R.F.) : R.f. is Anti-IgG  2)other autoantibodies:  Antinuclear factor(ANF)  Antibodies to Collagen type-2 class  Antibodies to cytoskeleton 4

5.  3) Activation of cell-mediated immunity which is observed by numerous inflammatory cells  4)Trigger events :-  Local/systemic infection  It includes some infectius agents such as Epstein-Barr Virus(EBV) cytomegalovirus(CMV) rubella 5

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7. Longitudinal Course of RA Reproduced with permission from McInnes IB, et al. Nat Rev Immunol. 2007;7(6):429- 442. CCP, cyclic citrullinated peptide; CTLA4, cytotoxic T-lymphocyte antigen 4; GP39, cartilage glycoprotein 39; PADI4, peptidyl arginine deiminase, type IV; PTPN22, protein tyrosine phosphatase, non- receptor type 22. 7

9.  Tender, warm, swollen joints  Joints inflammation often affect wrist & finger joints  Also affect other joints including neck,shoulder,elbow,hips,knees,ankles,feet  Fatigue,occasional fever,sense of not feeling well  Pain & stiffness after morning wake up or after a long rest 9

10. By imaging:  X-ray  MRI  Ultra sound By Blood tests: a)Inflammatory markers:  ESR(erythrocytes sedimentation rate)  C reactive protein(CRP)  ANA(anti-nuclear antibody) b)Rheumatoid factor: c)Anti-ccp antibodies : it in 99% gives +ve result d)Anti-MCV assay(anti-Mutated citrullinated Vimentin) 10

11.  There is no cure for RA,there is some treatments which can modify the disease process. GOAL for Treatments : 1. Relieve pain 2. Reduce inflammation 3. slow down or stop joint damage 11

12. 1)medication 2)surgery 3)lifestyle 1)medication:  Classification: 1.Anti-inflammatory-analgesic drugs 2.Anti-inflammatory drugs without direct analgesic action 3.Disease Modifying Antirheumatic Drugs(DMRDs) 4.immunosuppressants 5.TNF-alpha blockers 6.Interleukin-1 blockers 12

13. ANTIINFLAMMATORY-ANALGESIC DRUGS Eg.aspirin,indomethacin,ibuprofen,naproxen, piroxicam,nabumetone,diclofenac,celecoxib M.O.A: It inhibit pg,& chemicals that are responsible for pain and swelling 13

14.  Ibuprofen-: Individuals should not use ibuprofen for more than 10 days for the treatment of pain or more than 3 days for the treatment of a fever unless directed by a physician  Celecoxib:  The lowest effective dose should be used for each patient GLUCOCORTICOIDS-:They are used when disease  Is not responding NSAIDs.  Have serious side effect incase of high doses  Eg.prednisolone:- 14

15.  Eg.  Methotrexate  Hydroxychloroquine  Sulfasalazine  Gold salts 15

16. METHOTREXATE:  It is antimetabolite drug M.O.A:-  It inhibit dihydro folate  Reductase enzyme. 16

17.  It is antimalerial drug. 17 Sulfasalazine is used to treat rheumatoid arthritis in combination with anti- inflammatory medications. Sulfasalazine is generally well tolerated. 17  Eg.  Gold thioglucose(SOLGANAL)  Gold thiomalate (MYOCHRYSINE)  Auranofin (RIDAURA)

18. 18 Hip replacement Knee replacement SYNOVECTOMY

20.  It is metabolic disorder characterized by hyperuricaemia  Normal plasma=1-5 mg/dl  Stages of gout:- 1.asymptomatic hyperuricaemia 2.acute gouty arthritis 3.intercritical period 4.chronic tophaceous stage 20

21.  Types :-  1)metabolic-10% cases  Over production of uric acid  2)renal- 90% cases  Reduced renal excretion of uric acid  Causes:-  1)genetic(absence of hypoxanthine)  2)medication:-  3)lifestyle 21

22. Drugs that causes hyperuricaemia :  Alcohol  Thiazide  Cytotoxic drugs  Amiloride  Isoretinoin  Ethambutol  Cyclophosphamide 22

23.  Acute attack:  Over hours frequently nocturnal  Excruciating pain  Swelling, redness and tenderness  Podagra  May effect knees, wrist, elbow, and rarely SI and hips  Chronic:  Destructive tophacous  Much greater chance if untreated  nodules 23

24. DIAGNOSIS:- 1. X-ray 2. Synovial fluid test:- 3. Blood test:-  Normal level:1-5mg/dl  Above 7 in males  Above 6 in females indicate hyperuricaemia.  W.B.C.,ESR is increased in gout without infection. 24

25.  Uric acid is end product of purine metabolism  Monosodium urate has low water solubility  When conc. Of MSU is above 7mg/dl,their solubility is decreased due to saturation and it form crystal. 25

26. Goal of treatment:-  Relieve pain  Reduce inflammation  Terminate acute attack  Prevent recurrent attack  Prevent complications associated with chronic deposition of urate crysals in tissues. 26

27. Classification of drugs no cure alone)  1)NSAIDs  2)colchicine  3)corticosteroids  4)uricosuric drugs  5)xanthine oxidase inhibitor NSAIDs:-  Indomethacin  Naproxen  Piroxicam  diclofenac 27

28. COLCHICINE:-  It is an alkaloid from colchicum autumnale.  It is antimitotic drug. MOA-  it inhibit release of Glycoprotein & subsequent Events.  It inhibit granulocyte Migration into inflamed joints. 28

29. CORTICOSTEROIDS:-  Eg.prednisolone  They are rarely used.they are used in case of patient which is contraindicate to NSAIDs.  they produce rapid response like colchicine.but it is contraindicated to patients with renal failure. 29

30. PROBENECID:-  It is uricosuric drug.  MOA-  It is act by inhibiting reabsorption of uric acid.so,excretion of uric acid is increased. XANTHIN OXIDASE INHIBITOR:-  Eg.allopurinol.  It is hypoxanthine analogue.  MOA:-  It is act by inhibiting Xanthine oxidase which is required for synthesis of uric acid. 30

32.  OA is a group of diseases and mechanical abnormalities entailing degradation of joints, including articular cartilage and the subchondral bone next to it  OA is derived from the Greek word ‘ostoe’, meaning ‘of the bone’, ‘arthro’, meaning ‘joint’, and ‘itis’, meaning inflammation

33.  Osteoarthritis is the most common type of arthritis.  The prevalence increases with age  80% of people over 60 years will have some radiological evidence of it, although only 60% of those will show symptoms.

43. Primary Osteoarthritis Most Common Thought to be result of Aging Decreased ability to withstand stress Ligaments supporting joints weaken

44. Obesity Trauma Surgery Abnormal jointsGoutDiabetes Hormone disorders Causes

45. To Relieve pain Increase motion Improve strength