Rheumatoid Arthritis
Goals
General Approach to Arthritis Rheumatoid Arthritis
Diagnostic Criteria Pathophysiology Therapeutic Approach Disease Severity and Course
Approach to Arthritis
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)
Number of Joints Affected Inflammatory vs. Non-Inflammatory
Number of Joints 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
Inflammatory: i.e. RA
Inflammatory vs. Non-i.e. Non-Inflammatory: Osteoarthritis Generalized AM stiffness InflammatoryAM stiffness > 30 min Localized
Resolves with movement Classic signs of inflammation < 30 min
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
Rheumatoid Arthritis
RA
Systemic inflammatory autoimmune disorder ~1% of population Onset: 52 years
40-70 years of age <60 - 3-5:1 female predominance
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
Pathophysiology
Immunology
Macrophages:
Produce cytokines Cytokines (TNF-) cause systemic features Release chemokines recruit PMNs into synovial fluid/membrane
TH-1 cells:
Mediate disease processes Activate B cells
B cells:
Release cytokines Plasma cells that produce Ab
TNF- & IL-1:
Proliferation of T cells Activation of B cells Initiates proinflammatory/jointdamaging processes
Osteoclasts:
Bone erosion Juxta-articular & Systemic osteoporosis
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
Bottom Line
Proliferation Destruction of joints Disability
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
Clinical Presentation
Gradual onset Stiffness & Swelling Intermittent or Migratory involvement Extraarticular manifestations Myalgia, fatigue, low-grade fever, wt loss, depression
Stiffness & Swelling
Pain with pressure to joint Pain with movement of joint Swelling due to hypertrophy Effusion Heat Redness
Physical Exam
Decreased grip strength Boxing glove edema Carpal tunnel Ulnar deviation Boutonniere/Swan neck deformities Extensor tendon rupture
Extraarticular Involvement
Anemia Rheumatoid nodules Pleuropericarditis Neuropathy Episcleritis, Scleritis Splenomegaly Sjogrens Vasculitis
Differential
Seronegative polyarthritis Psoriatic arthritis Crystal-induced
Tophaceous gout Pseudogout
Erosive inflammatory OA Reiters Enteropathic arthritis SLE Paraneoplastic syndrome
Diagnostic Criteria
Diagnostic Criteria
Symmetric peripheral polyarthritis AM Stiffness >1 hour Rheumatoid nodules Laboratory features Radiographic bone erosions
3 or more Joints for >6 weeks
Small Joints
Hands & Feet Peripheral to Proximal
Symmetric Peripheral Polyarthritis
MCP and PIP Joints
SPARES DIP
MTP & Plantar subluxation Leads to Deformity & Destruction of Joints
Erosion of cartilage and bone
Stiffness
AM or after Prolonged Inactivity Bilateral In/Around Joints > 1 hours
Reflects severe joint inflammation
Better with movement Present >6 weeks
Rheumatoid Nodules
Extensor surfaces
elbows
Very Specific Only occur in ~30% Late in Disease
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
Rheumatoid Factor
IgM against IgG IgM+ pts: more severe disease & poorer outcome Non-specific
SLE, Sjgren's, Sarcoidosis, Chronic infections
Anti-CCP
IgG against synovial membrane peptides damaged via inflammation
Value in IgM-RF negative
Sensitivity (65%) & Specificity (95%)
Predictive of Erosive Disease
Disease severity Radiologic progression Poor functional outcomes
Other Lab Abnormalities
AOCD Thrombocytosis Leukocytosis ANA
30-40%
Inflammatory synovial fluid Hypoalbuminemia
Radiology
Evaluate disease activity & joint damage Bony decalcification Baseline AP views Initiation of DMARDs
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
Disease Severity
Mild Disease
Arthralgias >3 inflamed joints Mild functional limitation Minimally elevated ESR & CRP No erosions/cartilage loss No extraarticular disease i.e. anemia
Moderate Disease
6-20 Inflamed joints Moderate functional limitation Elevated ESR/CRP Radiographic evidence of inflammation No extraarticular disease
Severe Disease
>20 persistently inflamed joints Rapid decline in functional capacity Radiographic evidence of rapid progession of bony erosions & loss of cartilage Extraarticular disease:
AOCD, Hypoalbuminemia
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
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 = Decreased atherosclerosis/morbidity
Lipid screening & treatment Control of obesity, Hyperhomocystinemia, DM, HTN ASA
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
Staging
Early
<3 months
Established/Persistent
6-12 months
End-stage
Significant joint destruction Functional disability
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
Treatment Strategies
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
Pharmacologic Therapy
Analgesics NSAIDs Glucocorticoids SAARD/DMARD Anticytokine therapy
Analgesics
Topical Capsaicin Diclofenac Oral Tylenol Opiods
NSAIDs
Pros:
Analgesic, Antipyretic, Antiinflammatory
Cons:
Dont alter disease progression Ineffective in Erosive disease
GI/Ulcers Hepatotoxicity Nephrotoxicity AIN Bleeding antiplatelet Rash Aseptic meningitis
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
Disease modification
SAARD slow acting antirheumatic drugs DMARD disease modifying antirheumatic drugs
Methotrexate
Dihydrofolate reductase inhibitor
Well tolerated, Mono/Combo Onset: 6-12 weeks
Nausea Mucosal ulcerations Fatigue & Flu-like symptoms BM Toxicity Hepatotoxicity Treat with Folic acid, 1 mg/d
Metabolism: Liver Clearance: Kidneys
Monitoring:
Baseline:CXR, PFTs, HIV, HBV/HCV CBC, LFTs Q4-8 weeks Caution with CRI
Leflunomide
Derm - rash, alopecia Diarrhea BM toxicity Hepatotoxicity
Inhibits dihydrooratate dehydrogenase Dec. activated T-cells Onset: rapid Efficacy: 6 weeks
Monitoring:
CBC, LFTs
Azathioprine
Corticosteroid-sparing Monitoring:
CBC Q1-2 months AST/ALT
Infection BM Toxicity Hepatitis Malignancy
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 with acrolein Oral more toxic than IV
Anticytokine therapy
Anti-TNF alpha agents
Etanercept Infliximab Adalimumab IL-1 receptor antagonist (Anakinra)
TNF-a Inhibitors
Anti-inflammatory Block TNF- (proinflammatory cytokine) Etanercept, Adalimumab (SQ), Infliximab (IV)
Very expensive: > $15,000/patient
Injection site reaction Infection Reactivated TB Infliximab
infusion reaction
Combo therapy with MTX
Pancytopenia Autoantibody/SLE-like Exacerbate CHF Malignancy lymphoma
More aggressive approach Combo therapy Adjunctive therapy: TNF- antagonist
Disease Course
Long Remission
10%
Intermittent Disease
15-30%
Progressive Disease
Summary
Approach to Arthritis
Number of Joints Affected Inflammatory vs. Non-Inflammatory
Rheumatoid Arthritis
Diagnostic Criteria Pathophysiology Therapeutic Approach Disease Severity and Course
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