Rheumatoid Arthritis Systemic chronic inflammatory disease Mainly affects synovial joints

1. Rheumatoid Arthritis Systemic chronic inflammatory disease Mainly affects synovial joints Variable expression Prevalence about 3% Worldwide distribution Female:male ratio 3:1 Peak age of onset: 25-50 years

2. Rheumatoid Arthritis • Unknown etiology • Genetics • Environmental • Possible infectious component • Autoimmune disorder

3. THE PATHOLOGY OF RA • Serositis 1. Synovitis Joints Tendon sheaths Bursae • Nodules • Vasculitis

5. RA Is Characterised by Synovitis and Joint Destruction NORMAL RA Inflamed synovial membrane Synovial membrane • Major cell types: • T lymphocytes • macrophages Pannus Cartilage • Minor cell types: • fibroblasts • plasma cells • endothelium • dendritic cells Synovial fluid • Major cell type: • neutrophils Capsule Cartilage thinning Adapted from Feldmann M, et al. Annu Rev Immunol. 1996;14:397-440.

6. Numerous Cellular Interactions Drive the RA Process Immune complexes Bacterial products IL-1, TNF-, etc Rheumatoid factors B cell IL-1 Soluble factors and direct cell–cell contact T cell HLA -DR Antigen- presenting cells Macrophage B cell or macrophage IL-1 and TNF- Synoviocytes Chondrocytes Pannus Articular cartilage Production of collagenase and otherneutral proteases Arend W. Semin Arthritis Rheum. 2001;30(suppl 2):1-6.

7. IL-1 and TNF- Have a Number of Overlapping Proinflammatory Effects Proinflammatory effects of IL-1 Proinflammatory effects of TNF- COX-2PGE2NOAdhesion moleculesChemokinesCollagenasesIL-6 TNF-Osteoclast activation Angiogenic factors IL-1 cell death COX-2 = cyclo-oxygenase type 2; PGE2 = prostaglandin-E2; NO = nitric oxide

8. IL-1 Plays a Pivotal Role in the Inflammatory and Destructive Processes of RA IL-1 Activates monocytes/macrophages Induces fibroblast proliferation Activates chondrocytes Activates osteoclasts Inflammation Synovial pannus formation Cartilage breakdown Bone resorption

9. Signs and Symptoms • Joint inflammation • Tender, warm swollen joints • Symmetrical pattern • Pain and stiffness • Symptoms in other parts of the body • Nodules • Anemia • Fatigue, occasional fever, malaise

10. JOINT INVOLVEMENT ON PRESENTATION OF RA Polyarticular 75% Monoarticular 25% Small joints Knee 50% of hands and feet 60% Large joints 30% Shoulder } Wrist } Large and Hip } 50% Small joints 10% Ankle } Elbow }

11. Articular features seen in the Rheumatoid Hand WRIST:PIPs: Synovitis Synovitis Prominent ulnar styloid Fixed flexion or extension Subluxation and collapse of deformities carpus (Swan neck or boutonniere Radial deviation deformity) MCPs: THUMBS: Synovitis Synovitis Ulnar deviation ‘Z’ deformity Subluxation

15. Joint Destruction

17. Extra-articular manifestations • General • fever, lymphadenopathy, weight loss, fatigue • Dermatologic • palmar erythema, nodules, vasculitis • Ocular • episcleritis/scleritis, scleromalacia perforans, choroid and retinal nodules

18. Extra-articular manifestations • Cardiac • pericarditis, myocarditis, coronary vasculitis, nodules on valves • Neuromuscular • entrapment neuropathy, peripheral neuropathy, mononeuritis multiplex • Hematologic • Felty’s syndrome, large granular lymphocyte syndrome, lymphomas

19. Extra-articular manifestations • Pulmonary • pleuritis, nodules, interstitial lung disease, bronchiolitis obliterans, arteritis, effusions • Others • Sjogren’s syndrome, amyloidosis

26. Investigations: • Hematology : CBC , ESR • Biochemistry : LFT , Renal profile • Serology : RF , Anti-CCP • Radiography : Joints , Spines ,Chest

28. Treatment Goals • Relieve pain • Reduce inflammation • Prevent/slow joint damage • Improve functioning and quality of life

29. Treatment Approaches • Lifestyle modifications • Rest • Physical and occupational therapy • Medications • Surgery

31. Rationale for the Early Treatment of R.A. • •Erosions develop early in the disease course • •Destruction is irreversible • •Disease activity is strongly associated with joint destruction later in the disease course • •Early treatment can slow down radiographic progress • •Disease activity must be suppressed maximally in its early stages to prevent destruction and preserve function

32. Drug Treatments • Nonsteroidal anti-inflammatory drugs (NSAIDs) • Disease-modifying antirheumatic drugs (DMARDs) • Biologic response modifiers • Corticosteroids

33. Traditional NSAIDs Aspirin Ibuprofen Ketoprofen Naproxen COX-2 Inhibitors Celecoxib Rofecoxib Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

34. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) • To relieve pain and inflammation • Use in combination with a DMARD • Gastrointestinal side effects

35. Hydroxychloroquine Sulfasalazine Methotrexate Leflunomide Gold Azathioprine Disease-Modifying Antirheumatic Drugs (DMARDs)

36. Disease-Modifying Antirheumatic Drugs (DMARDs) • Control symptoms • No immediate analgesic effects • Can delay progression of the disease (prevent/slow joint and cartilage damage and destruction) • Effects generally not seen until a few weeks to months

37. DMARDs • hydroxychloroquine • mild non-erosive disease • combinations • 200 mg bid • eye exams

38. DMARDs • Sulfasalazine • 1 gm bid - tid • CBC, LFTs • onset 1 - 2 months • Methotrexate • most commonly used drug • fast acting (4-6 weeks) • po, SQ - weekly • CBC, LFTs

39. DMARDs • IM Gold • slow onset (3-6 months) • weekly then monthly injections • CBC, UA before each injection • Oral Gold • less effective • slow acting (4-6 months) • daily • CBC, UA

40. Biologic Response Modifiers • Etanercept • Infliximab • Anakinra

41. Biologic Response Modifiers • Etanercept and infliximab target tumor necrosis factor alpha (TNF-) • Anakinra targets interleukin-1 receptor

42. OSTEOARTHRITIS

45. MULTIFACTORAL ETIOLOGY OF OA ● Joint instability ● Age ● Hormonal factors ● Trauma ● Altered biochemistry ● Inflammation ● Genetic predisposition ● ? Others

46. SYMPTOMS AND SIGNS OF OA • Pain – worse on use of joint • Stiffness – mild after immobility • Loss of movement • Pain on movement/restricted range • Tenderness (articular or periarticular) • Bony swelling • Soft tissue swelling • Joint crepitus

47. RADIOLOGICAL FEATURES OF OA • Narrowing of joint space • Osteophytosis • Altered bone contour • Bone sclerosis and cysts • Periarticular calcification • Soft-tissue swelling