rheumatoid arthritis. goals general approach to arthritis rheumatoid arthritis diagnostic criteria...
TRANSCRIPT
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,
Behçet's
Oligo/Polyarticular Monoarticular causes RA SLE Viral infection
B19 Acute Serum Sickness Untreated Crystal-
induced Vasculidities
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
Arthrocentesis
Confirm diagnoses Differentiate between inflammatory & noninflammatory Therapeutic/Adjunct to Antibiotics Labs:
cell count w/diff crystal analysis Gram stain & Culture WBC >2000/µL indicates inflammatory arthritis
Arthroscopy Evaluate ligamentous & cartilaginous integrity Biopsy Infectioun: aspirate thick or loculated fluid
RheumatoidArthritis
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-α) cause
systemic features Release chemokines
recruit PMNs into synovial fluid/membrane
TNF-α & 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
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 (anti–cyclic 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 Sjogren’s Vasculitis
Differential
Seronegative polyarthritis
Psoriatic arthritis Crystal-induced
Tophaceous gout Pseudogout
Erosive inflammatory OA
Reiter’s Enteropathic arthritis SLE Paraneoplastic
syndrome
DiagnosticCriteria
Diagnostic Criteria
Symmetric peripheral polyarthritis AM Stiffness >1 hour Rheumatoid nodules Laboratory features Radiographic bone erosions
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 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, Sjögren'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
DiseaseSeverity
Arthralgias >3 inflamed joints Mild functional limitation Minimally elevated ESR & CRP No erosions/cartilage loss No extraarticular disease i.e. anemia
Mild Disease
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
TreatmentStrategies
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,
Anti-inflammatory
Cons: Don’t 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
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
Leflunomide
Inhibits dihydrooratate dehydrogenase Dec. activated T-
cells Onset: rapid
Efficacy: ≤6 weeks
Monitoring: CBC, LFTs
Derm - rash, alopecia Diarrhea BM toxicity Hepatotoxicity
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-α
(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
More aggressive approach Combo therapy Adjunctive therapy: TNF-α
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
Questions?