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Rheumatoid Arthritis

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Title: Rheumatoid Arthritis


1
Rheumatoid Arthritis
  • Dr. Andy Thompson
  • Assistant Professor of Medicine
  • Division of Rheumatology
  • University of Western Ontario

2
Objectives
  • Gain a basic understanding of Rheumatoid
    Arthritis
  • Understand the presentation of Rheumatoid
    Arthritis (Inflammatory Arthritis)
  • Understand the current treatment paradigm and
    medications used

3
Disclaimer
  • The following case is real but the characters are
    fictional

4
This is Shari
5
Shari is 40
Married to Scott
6
They have 3 boys
7
Shari works as a teller at CIBC
8
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9
Case Presentation
  • Shari has been healthy apart from
  • C-Section for the birth of David (12 years ago)
  • Mild depression with a mild exacerbation in the
    post-partum period (with David)
  • Her current medications are
  • Sertraline 100 mg per day (depression)
  • Naproxen 500 mg twice a day (recent joint pain)
  • Shari has No Known Drug Allergies (NKDA)

10
Case Presentation
  • 4 months ago Shari developed pain in the left
    knee with some mild swelling. The episode lasted
    a few days and then went away.
  • She didnt think much of it as she had a similar
    episode after the birth of David that lasted a
    week or so and went away.

11
Case Presentation
  • About a week later the right knee began to swell
    and become sore
  • She hobbled around on this knee for a week and
    then both wrists began to swell and become sore.
    She also noticed some soreness in her feet.
  • About two weeks later her hands started to
    stiffen up and she couldnt get her rings on.

12
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13
Case Presentation
  • Shari explains that she feels stiff when she
    wakes up in the morning and this stiffness lasts
    for at least 3 hours
  • She has no energy and has missed the last week of
    work
  • Her sleep is difficult because she is
    uncomfortable
  • She isnt running because it hurts too much

14
Case Presentation
  • She asks you What is going on with me?

15
Differential Diagnosis
  • INFLAMMATORY POLYARTHRITIS
  • Infection
  • Rheumatoid Arthritis
  • Seronegative Arthritis (Psoriatic)
  • Connective Tissue Disease (SLE etc)
  • Associated with another Systemic Disease

16
Working Diagnosis
  • Nothing else on history or physical examination
    to suggest a connective tissue disorder (youll
    learn about these in another lecture)
  • Nothing else to suggest a seronegative
    spondyloarthritis (again, another lecture)
  • Dx Rheumatoid Arthritis (for the sake of this
    lecture)

17
Who gets RA?
  • ANYONE CAN GET RA
  • From babies to the very old
  • Common Age to Start 20s to 50s
  • Sex Females more common than males 31

18
How does RA start?
  • RA usually starts off slowly (insidious) over
    weeks to months and progresses (70)
  • It can come on overnight (acute) but this is rare
    (10)
  • It can come on over a few weeks (subacute 20)
  • Palindromic Presentation
  • RACECAR, RADAR, MOM, DAD

19
How does RA start?
  • Initially, most patients notice stiffness of the
    joints which seems more pronounced in the morning
  • Some fatigue
  • Some pain

20
What Joints are affected?
  • RA usually begins as an oligoarticular process
    (lt5 joints) and progresses to polyarticular
    involvmement
  • Has a predilection for the small joints of the
    hands and feet!

21
Small Joints of the Hand
22
What Joints are affected?
23
How are the Joints Affected
  • Joints are usually
  • Swollen
  • Warm
  • NOT RED (might be a bit purple)

24
NO REDNESS!
25
Morning Stiffness
  • Prominent Feature
  • Greater than 60 minutes of morning stiffness
    (Patients minimize)
  • Some patients have difficulty answering the
    question because they are stiff all day
  • How long does it take until you are the best you
    are going to be?

26
Morning Stiffness
  • Inflammatory fluid increases in and around the
    joint
  • As patients get moving the fluid gets resorbed
  • Stiffness can occur after rest gelling

27
Constitutional Features
  • Fever Unusual
  • Weight Loss Can be seen with severe
    polyarticular disease (again not common)
  • Anorexia Unusual
  • Fatigue VERY COMMON
  • Sleep Disturbance VERY COMMON
  • Musculoskeletal Reasons
  • Neurologic Reasons Carpal Tunnel
  • Psychological Reasons Worry about illness,
    finances, job, family etc.

28
Functional Status
  • In the Rheumatology Clinic we use a Health
    Assessment Questionnaire (HAQ)
  • Dressing, Bathing, Grooming
  • Cooking, Cleaning, Shopping
  • Mobility Walking and Standing
  • Working
  • Social Activities Sports
  • Rank the Functional Status (IMPORTANT)
  • Mild, Moderate, or Severe

29
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30
Rheumatoid Arthritis is
  • Usually insidious in onset
  • Adds joints over time
  • Has a predilection for the small joints of the
    hands and feet
  • Joints become warm and swollen but not red
  • Morning stiffness is greater than 1 hour
  • Patients are often tired and dont sleep properly
  • Can result in significant disability very quickly

31
Doesnt just affect the joints
  • EXTRA-ARTICULAR
  • MANIFESTATIONS

32
Xerophthalmia (Dry Eyes)
33
Xerostomia (Dry Mouth)
34
Raynauds Phenomenon
35
Carpal Tunnel Syndrome
36
Pleural Effusion
37
Rheumatoid Nodules
38
Rheumatoid Nodules
39
Rheumatoid Vasculitis
40
Extra-Articular Manifestations
  • Sicca Features Xerostomia Xerophthalmia
  • Raynauds Phenomenon
  • Neuropathy Carpal Tunnel Syndrome
  • Rheumatoid Nodules
  • Pleural Effusions
  • Rheumatoid Vasculitis

41
Tests, Tests, Tests
  • INVESTIGATING A PATIENT WITH SUSPECTED RA

42
Back to Shari
43
SUMMARY
  • Has a 4 month history of an inflammatory
    polyarthritis
  • Nothing else on History or Physical Examination
    to suggest an associated connective tissue
    disorder or seronegative spondyloarthropathy.

44
INFLAMMATION
  • Complete Blood Count (CBC)
  • Hemoglobin May be anemic (normocytic)
  • WBC Should be normal
  • Platelets May be normal to elevated
  • Erythrocyte Sedimentation Rate (ESR)
  • C-Reactive Protein (CRP)

45
ORGAN FUNCTION
  • TO MAKE SURE MEDS WILL BE SAFE
  • Renal Function
  • Creatinine Urinalysis
  • Liver Enzymes
  • AST, ALT, ALP, ALB
  • Hepatitis B C Testing
  • Consider baseline Chest X-Ray

46
ANTIBODIES
  • Rheumatoid Factor
  • Anti-Nuclear Antibody

47
Rheumatoid Factor
IgG Molecule Fc Portion
Autoantibodies (IgM) directed against the Fc
Fragment of IgG An Antibody to an Antibody Their
Role in RA is not understood
IgM Molecule
Antigen Binding Groove
48
Rheumatoid Factor
  • Non- Rheumatic Disease
  • Normal Aging
  • Infection
  • Hepatitis B C
  • SBE
  • Tb
  • HIV
  • Sarcoidosis
  • Idiopathic Pulmonary Fibrosis
  • Rheumatic Disease
  • Sjogrens syndrome
  • Rheumatoid Arthritis
  • SLE
  • MCTD
  • Myositis
  • Cryoglobulinemia

49
Rheumatoid Factor (RF)
  • Question What Percentage of New Onset RA will
    have a positive RF?
  • Answer 30-50
  • Question What Percentage of Established RA will
    have a positive RF?
  • Answer 70-85
  • NOT USEFUL FOR DIAGNOSIS OF RA

50
Pearls about RF in RA
  • Asymptomatic people with a positive RF are
    unlikely to go on to develop RA
  • The higher the value the greater the likelihood
    of rheumatic disease
  • USEFUL for PROGNOSIS
  • Patients who are RF ve are more likely to have
    aggressive disesase
  • NOT USEFUL to FOLLOW TITRES
  • Not predictive of flare
  • Not predictive of improvement

51
  • RADIOGRAPHIC
  • FINDINGS IN RA

52
Periarticular OsteopeniaJoint Space
NarrowingErosionsMal-Alignment
53
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54
  • SYNOVIAL
  • FINDINGS IN RA

55
Rheumatoid Synovium
  • A Non-Suppurative (no pus) inflammatory
    infiltrate in the synovium
  • Due to the aggregation of lymphocytes and plasma
    cells

56
Rheumatoid Synovium
57
PRINCIPLES OF TREATMENT
58
The Big Bang
90 of the joints involved in RA are affected
within the first year SO TREAT IT EARLY
59
Disability in Early RA
  • Inflammation
  • Swollen
  • Stiff
  • Sore
  • Warm
  • Fatigue
  • Potentially Reversible

60
Disability in RA
  • Most of the disability in RA is a result of the
    INITIAL burden of disease
  • People get disabled because of
  • Inadequate control
  • Lack of response
  • Compliance
  • GOAL Control the Disease Early On!

61
A Fire in the Joints
If theres a fire in the kitchen do you wait
until it spreads to the living room or do you try
and put it out?
62
Clinical Course of RA
Severity of Arthritis
Years
Type 1 Self-limited5 to 20 Type 2
Minimally progressive5 to 20Type 3
Progressive60 to 90
Pincus. Rheum Dis Clin North Am. 199521619.
63
Why is Early Treatment Important?
  • Joint Damage Occurs EARLY
  • 93 of patients with less than 2 years of disease
    have radiographic abnormalities
  • Rate of radiographic progression is higher in the
    first 2 years of disease
  • Disability Occurs EARLY
  • 50 out of work at 10 years
  • Increased MORTALITY
  • With Severe Disease

64
Why is Early Treatment Important?
  • EARLY Treatment has Long-Term Beneficial Effects
  • WINDOW OF OPPORTUNITY
  • Delay of 4 months can have long-term effects

65
Disability in Late RA (Too Late)
  • Damage
  • Bones
  • Cartilage
  • Ligaments and other structures
  • Fatigue
  • Not Reversible

66
Induce Remission
Maintain Remission
67
The Good Ship RA
Non-Pharmacologic
NSAIDs COXIBs
Dont Let the Ship Sail TREAT EARLY AGGRESSIVELY
Steroids
DMARDs Biologics
68
DMARDs
  • Disease Modifying Anti-Rheumatic Drugs
  • All patients with RA SHOULD BE TAKING A DMARD
  • Pardon? All patients with RA SHOULD BE TAKING A
    DMARD
  • One more time All patients with RA SHOULD BE
    TAKING A DMARD

69
DMARDs
  • Reduce swelling Inflammation
  • Improve Pain
  • Improve Function
  • Have been shown to reduce radiographic
    progression (erosions)

70
DMARDs
  • Methotrexate
  • Sulfasalazine
  • Hydroxychloroquine (Plaquenil)
  • Leflunomide (Arava)
  • Gold
  • Azathioprine (Imuran)

71
Combining DMARDs
  • DMARDs all work slightly differently
  • Never truly know how a patient will respond to an
    individual DMARD
  • Most clinicians now agree that combinations of
    DMARDs are more effective than single agents
  • This is now supported by some research

72
Lotto 649
  • Odds of Winning 1 in 13,983,816
  • Only way to improve your odds is to buy more
    tickets
  • Buy 3 tickets and odds are now 3 in 13,983,816
  • Thank fully Arthritis isnt as difficult to treat
    as it is to win the lottery but the principles
    are similar the big gamble

73
You Might Get Lucky
74
You Might Not
75
Lets Buy 3 Tickets!
76
Combination therapy (using 2 to 3) DMARDs at a
time works better than using a single DMARD
77
Common DMARD Combinations
  • Triple Therapy
  • Methotrexate, Sulfasalazine, Hydroxychloroquine
  • Double Therapy
  • Methotrexate Leflunomide
  • Methotrexate Sulfasalazine
  • Methotrexate Hydroxychloroquine
  • Methotrexate Gold
  • Sulfasalazine Plaquenil

78
Shari
  • Began therapy with Methotrexate, Sulfasalazine,
    Plaquenil
  • Initially responded well and took them for 4
    months
  • On a friends advice, stopped all DMARDs in
    favour of natural therapy
  • Natural therapy was a dismal failure
  • Triple therapy re-instituted difficulty
    obtaining adequate control

79
Shari
  • Change DMARDs Add leflunomide
  • Biologic Therapy

80
BIOLOGIC THERAPY
81
Tumour Necrosis Factor (TNF)
  • TNF is a potent inflammatory cytokine
  • TNF is produced mainly by macrophages and
    monocytes
  • TNF is a major contributor to the inflammatory
    and destructive changes that occur in RA
  • Blockade of TNF results in a reduction in a
    number of other pro-inflammatory cytokines (IL-1,
    IL-6, IL-8)

82
TNF Receptor
How Does TNF Exert Its Effect?
Any Cell
Trans-Membrane Bound TNF
Soluble TNF
83
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84
TNF Receptor
How Are the Effects of TNF Naturally Balanced?
Any Cell
Trans-Membrane Bound TNF
Soluble Receptor
Soluble TNF
85
Strategies for Reducing Effects of TNF
Monoclonal Antibody (Infliximab Adalimumab)
Trans-Membrane Bound TNF
Macrophage
Soluble TNF
86
Infliximab (Remicade) Adalimumab (Humira)
  • Chimeric (murine human) monoclonal antibody
    directed against TNF-a

87
Strategies for Reducing Effects of TNF
Soluble Receptor Decoy (Etanercept)
Trans-Membrane Bound TNF
Macrophage
Soluble TNF
88
Etanercept (Enbrel)
  • 2 soluble p75receptors attached to the Fc portion
    of the IgG molecule

89
Biologics
  • Monoclonal Antibodies to TNF
  • Infliximab (Remicade)
  • Adalimumab (Humira)
  • Soluble Receptor Decoy for TNF
  • Etanercept (Enbrel)
  • Receptor Antagonist to IL-1
  • Anakinra (Kineret) (rarely used)
  • Monoclonal Antibody to prevent T-Cell Signaling
  • Abatacept (Orencia) NEW
  • Monoclonal Antibody to CD-20
  • Rituximab (Rituxan) NEW

90
Side Effects
  • Infection
  • Common (Bacterial)
  • Opportunistic (Tb, Histo)
  • Demyelinating Disorders
  • Malignancy
  • Worsening CHF
  • Blood Counts

91
Do they work?
  • Resounding YES!
  • Outcome measured by ACR20
  • 20 reduction in swollen tender joints
  • Plus 20 reduction in at least 3 of the
    following
  • Patient VAS pain
  • Physician global VAS
  • Patient global VAS
  • HAQ
  • ESR or CRP

92
Do they work?
93
SUMMARY
  • Rheumatoid Arthritis is a chronic potentially
    debilitating illness
  • Early treatment can have a PROFOUND effect on
    this disease

94
Its UP TO YOU
95
TO BECOME A RHEUMATOLOGIST
96
OR TO GET THEM TO US
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