Transcript Rheumatoid Arthritis

Rheumatoid Arthritis
DOM MR Week of 9/8/2008
Rozina Mithani
www.powerpointpresentationon.blogspot.com
Goals
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General Approach to Arthritis
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Rheumatoid Arthritis
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Diagnostic Criteria
Pathophysiology
Therapeutic Approach
Disease Severity and Course
Rheumatoid Arthritis:
Definition
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Progressive, systemic, inflammatory
disorder
Unknown etiology
Characterized by
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Symmetric synovitis
Joint erosions
Multisystem extra-articular manifestations
Epidemiology of Rheumatoid
Arthritis
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Approximately 1% of the total adult
population is affected by RA
40% to 60% with advanced (functional
class IV) RA will:
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Survive 5 years or less following diagnosis
Die 10-15 years earlier than expected
Approach to
Arthritis
Joint Pain
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most common symptom
Pain (arthralgia) vs. Inflammation
Inflammation:
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(arthritis)
heat, redness, pain, swelling, loss of function
inflammatory arthritis (RA, SLE) vs. pain syndrome
(fibromyalgia)
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Number of Joints Affected
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Inflammatory vs. Non-Inflammatory
Number of Joints Affected
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Monoarticular
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Crystal-induced
Infection
Reactive Arthritis
Hemarthrosis
OA: joint effusions
Autoimmune disease
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Psoriasis, IBD, AS,
Behçet's
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Oligo/Polyarticular
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Monoarticular causes
RA
SLE
Viral infection
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B19
Acute Serum Sickness
Untreated Crystal-induced
Vasculidities
Inflammatory vs. Non-Inflammatory
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Inflammatory: i.e. RA
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Generalized AM
stiffness
> 30 min
Resolves with
movement
Classic signs of
inflammation
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Non-Inflammatory:
i.e. Osteoarthritis
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Localized AM stiffness
< 30 min
Arthrocentesis
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Confirm diagnoses
Differentiate between inflammatory & noninflammatory
Therapeutic/Adjunct to Antibiotics
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Labs:
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cell count w/diff
crystal analysis
Gram stain & Culture
WBC >2000/µL indicates inflammatory arthritis
Arthroscopy
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Evaluate ligamentous & cartilaginous integrity
Biopsy
Infectioun: aspirate thick or loculated fluid
Rheumatoid
Arthritis
RA
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Systemic inflammatory autoimmune disorder
~1% of population
Onset: 52 years
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40-70 years of age
<60 - 3-5:1 female predominance
Genetics
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Increased incidence among Pima &
Chippewa Native American tribes (5%)
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Genetic & Environmental
HLA-DRB1*0401 & HLA-DRB1*0404
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Increased risk
Increased joint damage
Increased joint surgery
Pathophysiology
Immunology
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Macrophages:
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Produce cytokines
Cytokines (TNF-α) cause
systemic features
Release chemokines  recruit
PMNs into synovial
fluid/membrane
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TH-1 cells:
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B cells:
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TNF-α & IL-1:
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Proliferation of T cells
Activation of B cells
Initiates proinflammatory/jointdamaging processes
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Mediate disease processes
Activate B cells
Release cytokines
Plasma cells that produce Ab
Osteoclasts:
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Bone erosion
Juxta-articular & Systemic
osteoporosis
Pathophysiology
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Swelling of Synovial lining
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Rapid division/growth of cells = Pannus
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Angiogenesis
Synovial thickening/hyperplasia
Inflammatory vascularized tissue
Generation of Metalloproteinases
Cytokine release
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Infiltration of leukocytes
Change in cell-surface adhesion molecules & cytokines
Destruction of bone & cartilage
Bottom Line
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Proliferation
Destruction of joints
Disability
Disease Trigger
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Subclinical vs. Viral trigger
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Lab manifestations up to 10 yrs before clinical
RF & anti-CCP (anti–cyclic citrullinated peptide) Ab
Increased CRP subclinical inflammatory disease
ADLs:
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> 50% of pts stop working w/i 5-10 years of disease onset
~ 80% disabled to some degree > 20 years
Life expectancy: decreased by 3-18 years
Clinical Presentation
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Gradual onset
Stiffness & Swelling
Intermittent or Migratory involvement
Extraarticular manifestations
Myalgia, fatigue, low-grade fever, wt
loss, depression
Stiffness & Swelling
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Pain with pressure to joint
Pain with movement of joint
Swelling due to hypertrophy
Effusion
Heat
Redness
Physical Exam
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Decreased grip strength
Boxing glove edema
Carpal tunnel
Ulnar deviation
Boutonniere/Swan neck deformities
Extensor tendon rupture
Extraarticular Involvement
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Anemia
Rheumatoid nodules
Pleuropericarditis
Neuropathy
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Episcleritis, Scleritis
Splenomegaly
Sjogren’s
Vasculitis
Differential
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Seronegative polyarthritis  Erosive inflammatory OA
Psoriatic arthritis
 Reiter’s
Crystal-induced
 Enteropathic arthritis
 Tophaceous gout
 SLE
 Pseudogout
 Paraneoplastic syndrome
Diagnostic
Criteria
Diagnostic Criteria
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Symmetric peripheral polyarthritis
AM Stiffness >1 hour
Rheumatoid nodules
Laboratory features
Radiographic bone erosions
Symmetric Peripheral Polyarthritis
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3 or more Joints for >6 weeks
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Small Joints
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Hands & Feet
Peripheral to Proximal
MCP and PIP Joints
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SPARES DIP
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MTP & Plantar subluxation
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Leads to Deformity & Destruction of Joints
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Erosion of cartilage and bone
Stiffness
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AM or after Prolonged Inactivity
Bilateral
In/Around Joints
> 1 hours
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Reflects severe joint inflammation
Better with movement
Present >6 weeks
Rheumatoid Nodules
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Extensor surfaces
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elbows
Very Specific
Only occur in ~30%
Late in Disease
Laboratory Features
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RF
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Anti-Cyclic Citrulline Peptide (anti-CCP)
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70-80% of pts
Overlap with HCV/Cryoglobulinemia
Rare overlap with HCV
Acute Phase reactants
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ESR, CRP  monitoring disease activity
Rheumatoid Factor
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IgM against IgG
IgM+ pts: more severe disease & poorer outcome
Non-specific
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SLE, Sjögren's, Sarcoidosis, Chronic infections
Anti-CCP
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IgG against synovial membrane peptides damaged via
inflammation
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Value in IgM-RF negative
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Sensitivity (65%) & Specificity (95%)
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Predictive of Erosive Disease
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Disease severity
Radiologic progression
Poor functional outcomes
Other Lab Abnormalities
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AOCD
Thrombocytosis
Leukocytosis
ANA
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30-40%
Inflammatory synovial fluid
Hypoalbuminemia
Radiology
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Evaluate disease activity & joint damage
Bony decalcification
Baseline AP views
Initiation of DMARDs
Radiological Studies
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Plain Films
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Bilateral hands & feet
Only 25% of lesions
Less expensive
Through bone cortex around joint margins
Color Doppler U/S & MRI
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Early signs of damage i.e. Erosions
Bone Edema - even with normal findings on radiography
Disease
Severity
Mild Disease
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Arthralgias
>3 inflamed joints
Mild functional limitation
Minimally elevated ESR & CRP
No erosions/cartilage loss
No extraarticular disease i.e. anemia
Moderate Disease
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6-20 Inflamed joints
Moderate functional limitation
Elevated ESR/CRP
Radiographic evidence of inflammation
No extraarticular disease
Severe Disease
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>20 persistently inflamed joints
Rapid decline in functional capacity
Radiographic evidence of rapid progession
of bony erosions & loss of cartilage
Extraarticular disease:
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AOCD, Hypoalbuminemia
Prognostic Features
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RF & Anti-CCP antibodies
Early development of multiple inflamed joints
and joint erosions
Severe functional limitation
Female
HLA epitope presence
Lower socioeconomic status & Less education
Persistent joint inflammation for >12 weeks
CV Disease
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Leading cause of death ~50%
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2x more likely to develop MI
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chronic, inflammatory vascular burden  premature atherosclerosis
MTX: elevated homocysteine levels
Control inflammatory process = Decreased
atherosclerosis/morbidity
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Lipid screening & treatment
Control of obesity, Hyperhomocystinemia, DM, HTN
ASA
Other diseases
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70% more likely to have a stroke
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70% higher risk for developing infection
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Likely 2/2 treatment
44x more likely to develop NHL
Staging
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Early
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Established/Persistent
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<3 months
6-12 months
End-stage
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Significant joint destruction
Functional disability
Management
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Early and aggressive disease control
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Rheumatologist Referral
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Early/Undiagnosed: NSAIDs, short course Corticosteroids
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Late/Uncontrolled: DMARD therapy
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depends on the presence or absence of joint damage, functional
limitation, presence of predictive factors for poorer prognosis
Goals
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achieve NED & inflammation
no treatment to resolve erosions once they occur
Treatment
Strategies
Therapy
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Non-Pharmacologic:
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Referral to PT/OT
Evaluate ADLs
Assistive devices/splints
Weight loss
Smoking cessation
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Pharmacologic:
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Anti-inflammatory
Interrupt progression
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Development of erosions
Joint space narrowing
Pharmacologic Therapy
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Analgesics
NSAIDs
Glucocorticoids
SAARD/DMARD
Anticytokine therapy
Analgesics
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Topical
 Capsaicin
 Diclofenac
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Oral
 Tylenol
 Opiods
NSAIDs
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Pros:
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Analgesic, Antipyretic, Antiinflammatory
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Cons:
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Don’t alter disease progression
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Ineffective in Erosive disease
GI/Ulcers
Hepatotoxicity
Nephrotoxicity
AIN
Bleeding – antiplatelet
Rash
Aseptic meningitis
Corticosteroids
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Decrease cytokines
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Slow Joint Inflammation
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Insomnia
Emotional lability
Fluid retention
Weight gain
HTN
Hyperglycemia
Osteoporosis
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Bisphosphonates: >5mg/d for >3months
Cataracts
Avascular necrosis
Myopathy
Psychosis
Disease modification
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SAARD – slow acting antirheumatic drugs
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DMARD – disease modifying antirheumatic drugs
Methotrexate
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Dihydrofolate reductase
inhibitor
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Well tolerated, Mono/Combo
Onset: 6-12 weeks
Metabolism: Liver
Clearance: Kidneys
Monitoring:
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Baseline:CXR, PFTs, HIV,
HBV/HCV
CBC, LFTs Q4-8 weeks
Caution with CRI
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Nausea
Mucosal ulcerations
Fatigue & Flu-like symptoms
BM Toxicity
Hepatotoxicity
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Treat with Folic acid, 1 mg/d
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Leflunomide
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Inhibits dihydrooratate
dehydrogenase
 Dec. activated T-cells
 Onset: rapid
Efficacy: ≤6 weeks
Monitoring:
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CBC, LFTs
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Derm - rash, alopecia
Diarrhea
BM toxicity
Hepatotoxicity
Azathioprine
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Corticosteroid-sparing
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Monitoring:
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CBC Q1-2 months
AST/ALT
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Infection
BM Toxicity
Hepatitis
Malignancy
Cyclophosphamide
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Alkylating agent
Monitoring:
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CBC, UA monthly
Yearly UA +/- Cytology
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Alopecia
Nausea
Infection
BM suppression  pancytopenia
Infertility – pretreat women with
Leuprolide
Renal: hemorrhagic cystitis,
bladder malignancy – treat with
acrolein
Oral more toxic than IV
Anticytokine therapy
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Anti-TNF alpha agents
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Etanercept
Infliximab
Adalimumab
IL-1 receptor antagonist (Anakinra)
TNF-a Inhibitors
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Anti-inflammatory
Block TNF-α
(proinflammatory cytokine)
Etanercept, Adalimumab
(SQ), Infliximab (IV)
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Very expensive:
> $15,000/patient
Combo therapy with MTX
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Injection site reaction
Infection
Reactivated TB
Infliximab
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infusion reaction
Pancytopenia
Autoantibody/SLE-like
Exacerbate CHF
Malignancy – lymphoma
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More aggressive approach
Combo therapy
Adjunctive therapy: TNF-α antagonist
Disease Course
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Long Remission
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Intermittent Disease
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10%
15-30%
Progressive Disease
Summary
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Approach to Arthritis
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Number of Joints Affected
Inflammatory vs. Non-Inflammatory
Rheumatoid Arthritis
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Diagnostic Criteria
Pathophysiology
Therapeutic Approach
Disease Severity and Course
Questions?