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