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: years

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

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

5. Inflamed synovial membrane
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:

6. Numerous Cellular Interactions Drive the RA Process
Rheumatoid
factors
Immune complexes
Bacterial products
IL-1, TNF-, etc
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 other neutral 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
Activates monocytes/ macrophages
Induces fibroblast
proliferation
Activates
chondrocytes
Activates osteoclasts
Inflammation
Synovial pannus formation
Cartilage breakdown
Bone resorption

9. Signs and Symptoms Joint inflammation Pain and stiffness
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 % Monoarticular %
Small joints Knee %
of hands and feet %
Large joints % Shoulder }
Wrist }
Large and Hip } %
Small joints % 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:
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. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Traditional NSAIDs
Aspirin
Ibuprofen
Ketoprofen
Naproxen
COX-2 Inhibitors
Celecoxib
Rofecoxib

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

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

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

39. DMARDs IM Gold Oral 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 36

41. Biologic Response Modifiers
Etanercept and infliximab target tumor necrosis factor alpha (TNF-)
Anakinra targets interleukin-1 receptor 36

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

53. MANAGEMENT OF OSTEOARTHTITIS
Confirm diagnosis
Initial Therapy :
Pysiotherapy
Wt loss
Local therapy
Paracetamol

54. MANAGEMENT OF OSTEOARTHTITIS cont
Second-line approach:
NSAIDS
Intra-articular therapy: steroids,hyalurinate
Opioids
?glucosamines
Arthroscopy
Surgery