Rheumatoid Arthritis

1

• Rheumatoid Arthritis
• Systemic chronic inflammatory disease
• Mainly affects synovial joints
• Variable expression
• Prevalence about 3
• Worldwide distribution
• Femalemale ratio 31
• 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

4
(No Transcript)
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.
199614397-440.
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 cellcell 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. 200130(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
Activates chondrocytes
Induces fibroblast proliferation
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

12
(No Transcript)
13
(No Transcript)
14
(No Transcript)
15
Joint Destruction
16
(No Transcript)
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
• Feltys syndrome, large granular lymphocyte
  syndrome, lymphomas

19
Extra-articular manifestations

• Pulmonary
• pleuritis, nodules, interstitial lung disease,
  bronchiolitis obliterans, arteritis, effusions
• Others
• Sjogrens syndrome, amyloidosis

20
(No Transcript)
21
(No Transcript)
22
(No Transcript)
23
(No Transcript)
24
(No Transcript)
25
(No Transcript)
26
Investigations

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

27
(No Transcript)
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

30
(No Transcript)
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)

• COX-2 Inhibitors
• Celecoxib
• Rofecoxib

• Traditional NSAIDs
• Aspirin
• Ibuprofen
• Ketoprofen
• Naproxen

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
• 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
43
(No Transcript)
44
(No Transcript)
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

48
(No Transcript)
49
(No Transcript)
50
(No Transcript)
51
(No Transcript)
52
(No Transcript)
53
MANAGEMENT OF OSTEOARTHTITIS

• Confirm diagnosis
• Initial Therapy
• Pysiotherapy
• Wt loss
• Local therapy
• Paracetamol

54
MANAGEMENT OF OSTEOARTHTITIScont

• Second-line approach
• NSAIDS
• Intra-articular therapy
  steroids,hyalurinate
• Opioids
• ?glucosamines
• Arthroscopy
• Surgery

55
(No Transcript)