03.rheumatoid arthritis
TRANSCRIPT
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Introduction
Clinical features
Laboratory features
Extra-articular features
Management considerations and paradigmsPrognosis
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RA - Definition
Chronic systemic inflammatory disorder
Unknown etiology
Symmetrical joints
Synovium affected
Bone, cartilage, ligamentsDeformity
Extra-articular manifestations
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RA - Definition
Clinical diagnosis
Cymmetric polyarthritis of small jointssubacute
acute
Rheumatoid factor positivityErosive disease
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RA - Epidemiology
Worldwide distribution
All races
Female > male 3:1
Usual age of onset 20-40 years though individuals
of any age group may be affected
Genetic associationsHLA-DR4, DR1
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Rheumatoid factor
series of antibodies that recognize the Fc portion
of an IgG molecule
any serotype
most IgM
many conditions associated with RF positivity -
chronic inflammation
70% RA positive at onset, overall 85% in first twoyears
associated with more severe disease, extra-
articular manifestations, mortality
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Etiology
Probable background genetic susceptibility(multiple genes/risk factors involved)
Concordance rates 15-30% identical twins
2.5-3.0 times more prevalent inWomen>Men
Family history
Female Sex
Specific genes: HLA-DR4
Specific region in HLA DRB1 gene
confers increased risk of RA and severity
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Case Presentation:
55 YOF complains of months of bilateral handpain. She describes progressive morningstiffness lasting 3 hours with wrist, MCP, andPIP pain and swelling. She has also noted some
discomfort and perhaps swelling in her wrists,shoulders, knees, and toes.
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Rheumatoid Arthritis
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Rheumatoid nodule
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Case Presentation:
Physical exam is notable for swelling,
tenderness, and warmth in the elbows,
wrists, MCPs, PIPs, knees, and MTPs withnon-tender soft tissue nodules over the
olecronon.
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Laboratory abnormalities
anemia of chronic disease
thrombocytosis in active disease
ESR
CRP
X rays of joints
Rheumatoid factor
ACPA
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RA: Erosion Progression
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Rheumatoid arthritis- late stage
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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, cervical cord
compression
Hematologic
Feltys syndrome, large granular lymphocyte
syndrome, lymphomas
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Extra-articular manifestations
Pulmonary
pleuritis, nodules, interstitial lung disease,
bronchiolitis obliterans, arteritis, effusions
Others
Sjogrens syndrome, amyloidosis
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Feltys syndrome
classic triad
RA, splenomegaly, leukopenia
generally a neutropenia (
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D.Dx of a positive RF
normal - 1-4%, 10-25% over age 70
systemic autoimmune diseases
infections
malignancy
chronic liver diseasepulmonary diseases
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ANA in RA
25% RA are positive for ANA
other serologies usually negative
? more severe disease (RA) with worse
prognosis
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Anti-Citrullinated Peptide
Antibodies (ACPA)Rheumatoid factor (RF) has low specificity
for RA
ACPA more specific than RF for RA
CCP is commercially available test
Sensitivity similar to RF (~60-80%)More specific for RA (~96%)
Predicts poor prognosis
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RA - differential diagnosis
Common diseases
Spondyloarthropathies
rheumatic fever
CTDs
viral infections
fibromyalgia
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RA - differential diagnosis
Uncommon
hypothyroidism
SBE
sarcoidosis
lyme disease
amyloidHIV
malignancies/paraneoplastic syndromes
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Problems with old ACR Criteria
Work best in longstanding RA
But DMARDs work best in early RA and the goal is
to prevent development of damage
Need criteria addressing earlier diagnosis given thebenefits of early treatment
Need to include ACPA (CCP)
Balance with need for use in low resource settingswhere CCP not available
Goal of new criteria: predict who should be treated
with DMARDs
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New ACR/EULAR Proposed Criteria
Initial screen: 1+ swollen joints (if no, not RA)
Better explained by other dz? (if yes, not RA) Typical RA erosion on X-ray? (if yes, RA)
Next step:
Pattern of joint involvement (more points for more joints
and small joints)
Serology (RF and/or CCP, negative, low, high)
Duration (
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ACR Guidelines for Management
Summarize evidence for DMARDs and
biologics in different settings
Incorporate the following in treatmentdecisions
Disease duration (24 mo)
Disease activity (low, moderate, high) Features of poor prognosis
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Measurement of Disease Activity: DAS28 as
Example
DAS28 = 0.56 * sqrt(tender28) + 0.28 *
sqrt(swollen28) + 0.70 * ln(ESR) + 0.014
* GHIncludes:
Tender joint count
Swollen joint count
ESR (or CRP in different version)
GH: Patient global disease activity assessment
Categorized as low, moderate, or high
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Poor Prognostic Factors in
RA
Presence of RF and/or CCP antibodiesRadiographic erosions
Functional limitation
Extraarticular disease
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RA - Management
Non-pharmacologic
rest
fatigue, splinting
pain relief
heat, cold, ultrasound, paraffin, massage
physical therapyoccupational therapy
Patient education
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RA - Management
Pharmacologic
analgesics
NSAIDs - full dose
corticosteroids
prednisone at low dose - bridge, burst
intra-articular steroids
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Disease modifying agents
every patient should be considered for at
least one modifying agent
limitations
may not prevent damage
may not have lasting effect
may not be tolerated due to toxicity
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DMARDs
hydroxychloroquine
mild non-erosive disease
combinations
200 mg bid
eye exams
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DMARDs
Sulfasalazine
1 gm bid - tid
CBC, LFTs
onset 1 - 2 months
Methotrexate
most commonly used drug
fast acting (4-6 weeks)
po, SQ - weekly
FBC, LFTs
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DMARDs
IM Gold
slow onset (3-6 months)
weekly then monthly injections
CBC, UA before each injection
Oral Gold
less effective
slow acting (4-6 months)
daily
CBC, UA
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DMARDs
Azathioprine
100-200 mg daily
CBC, LFTs
?malignancy potential
onset 2 - 3 months
D-Penicillamine
daily
slow onset (3-6 months)
CBC, UA
autoimmune phenomenon
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DMARDs
CyclosporinA
daily
BP, UA
Cyclophosphamide
refractory cases
CBC
Chlorambucil
CBC
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New Therapies for RA
Enbrel
Soluble tumor necrosis factor fusion protein
Arava
Leflunomide
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Chimeric A2 (cA2) Monoclonal Antibody
Mouse(binding site for TNF-a)
Human (IgG1)
Chimeric (mouse/human) IgG1
monoclonal antibody
Binds to TNF-a with high
affinity and specificity
Knight, et al.Mol Immunol. 1993.
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Response to therapy
AM stiffness, total number swollen, tender
joints, (S1T2W+)
perception of pain
perception of overall response
health assessment measurement
ESR, CRP levels
physicians assessment
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Criteria for Remission (ACR)
no fatigue
morning stiffness for 15 minutes or less
no joint pain
no joint tenderness or pain on motion
no soft tissue swelling in joints or tendon sheath
ESR
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RA - long term prognosis
RA shortens survival and produces disability
1/3 leave work force in five years
aggressive DMARD TX can reduce disability by30% in 10-20 years