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Rheumatoid Arthritis
• Objectives:
By the end of this lecture student should be able to:
• Recognize which patient is likely to have RA
• Know the different modes of presentation of RA
• Develop a plan of investigation and management of RA
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Rheumatoid Arthritis
Systemic chronic inflammatory disease
Mainly affects synovial joints
• Variable modes of presentation
• Prevalence about 3%
• Worldwide distribution
• Female:male ratio 3:1
• Peak age of onset: 25-50 years
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Rheumatoid Arthritis
• Unknown etiology
– Genetics
– Environmental
– Possible infectious component
• Autoimmune disorder
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RA Is Characterised by Synovitis and Joint Destruction
NORMAL RA
Synovial membrane
Cartilage
CapsuleSynovialfluid
Inflamed synovial
membrane
Pannus
Major cell types:• T lymphocytes• macrophages
Minor cell types:• fibroblasts• plasma cells• endothelium• dendritic cells
Major cell type:• neutrophils
Adapted from Feldmann M, et al. Annu Rev Immunol. 1996;14:397-440.
Cartilage thinning
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Numerous Cellular Interactions Drive the RA Process
B cell
T cell
Antigen-presenting
cells
B cell ormacrophage
Synoviocytes
Pannus
Articularcartilage
Production of collagenase and otherneutral proteases
IL-1 andTNF- Chondrocytes
Rheumatoidfactors
Soluble factors and direct cell–cell contact
Immune complexesBacterial productsIL-1, TNF-, etc
Macrophage
IL-1
Arend W. Semin Arthritis Rheum. 2001;30(suppl 2):1-6.
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IL-1 and TNF- Have a Number of
Overlapping Proinflammatory Effects
COX-2 = cyclo-oxygenase type 2; PGE2 = prostaglandin-E2; NO = nitric oxide
COX-2
PGE2
NO
Adhesion molecules
Chemokines
Collagenases
IL-6
Proinflammatory
effects of IL-1Proinflammatory
effects of TNF-
TNF-
Osteoclast
activation
Angiogenic
factors
IL-1
cell death
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Activates
monocytes/
macrophages
Activates
chondrocytes Induces fibroblast
proliferation
Activates
osteoclasts
Inflammation Synovial pannus
formation
Cartilage
breakdown Bone
resorption
IL-1
IL-1 Plays a Pivotal Role in the Inflammatory and Destructive Processes of RA
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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
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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 }
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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
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Joint Destruction
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Extra-articular manifestations
• General
– fever, lymphadenopathy, weight loss, fatigue
• Dermatologic
– palmar erythema, nodules, vasculitis
• Ocular
– episcleritis/scleritis, scleromalacia perforans,
choroid and retinal nodules
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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
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Extra-articular manifestations
• Pulmonary
– pleuritis, nodules, interstitial lung disease,
bronchiolitis obliterans, arteritis, effusions
• Others
– Sjogren’s syndrome, amyloidosis
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Investigations:
• Hematology : CBC , ESR
• Biochemistry : LFT , Renal profile
• Serology : RF , Anti-CCP
• Radiography : Joints , Spines ,Chest
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The 2010 ACR / EULAR classification criteria for rheumatoid arthritis
Target population (Who should be tested?): Patients who
1) have at least 1 joint with definite clinical synovitis (swelling)
2) with the synovitis not better explained by another disease
Add A–D; a score of 6/10 is needed to classify patient as having definite RA
A. Joint involvement
1 large joint. 0
2-10 large joints 1
1-3 small joints (with or without involvement of large joints) 2
4-10 small joints (with or without involvement of large joints) 3
3-10 joints (at least 1 small joint) 5
B. Serology (at least 1 test result is needed for classification)
Negative RF and negative ACPA 0
Low-positive RF or low-positive ACPA 2
High-positive RF or high-positive ACPA 3
C. Acute-phase reactants (1 test result is needed for classification)
Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
D. Duration of symptoms
6 weeks 0
>6 weeks 1
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Treatment Goals
• Relieve pain
• Reduce inflammation
• Prevent/slow joint damage
• Improve functioning and quality of life
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Treatment Approaches
• Lifestyle modifications
• Rest
• Physical and occupational therapy
• Medications
• Surgery
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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
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Drug Treatments
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Disease-modifying antirheumatic drugs (DMARDs)
• Biologic response modifiers
• Corticosteroids
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Nonsteroidal Anti-Inflammatory Drugs
(NSAIDs)
Traditional NSAIDs
• Diclofenac
• Ibuprofen
• Ketoprofen
• Naproxen
COX-2 Inhibitors
• Celecoxib
• Etericoxib
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Nonsteroidal Anti-Inflammatory
Drugs (NSAIDs)
• To relieve pain and inflammation
• Use in combination with a DMARD
• Gastrointestinal side effects
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Disease-Modifying Antirheumatic
Drugs (DMARDs)
• Hydroxychloroquine (eye exam)
• )• Sulfasalazine (CBC, LFTs)
• Methotrexate (CBC, LFTs)
• Leflunomide (CBC, LFTs)
• Azathioprine (CBC, LFTs)
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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
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Biologic Response Modifiers
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Biologic Response Modifiers
• TNF Inhib: etanercept,infliximab,Adalimumab
• IL6 receptor inhib: tocilizumab
• T Cell costimulation modulator: abatacept
• Anti- CD20: Rituximab
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Physiotherapy
• Effective in maintaining the range of
motion
• Strengthening of muscles
• Prevent contractures
• Prevent deformities
• Maintain activities of daily living
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Occupational Therapy
• Education of patients in the use of daily
living activities
• Prevention of joint contractures and
deformities
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THANK YOU