Title: Rheumatoid Arthritis
1Rheumatoid Arthritis
- Dr. Andy Thompson
- Assistant Professor of Medicine
- Division of Rheumatology
- University of Western Ontario
2Objectives
- Gain a basic understanding of Rheumatoid
Arthritis - Understand the presentation of Rheumatoid
Arthritis (Inflammatory Arthritis) - Understand the current treatment paradigm and
medications used
3Disclaimer
- The following case is real but the characters are
fictional
4This is Shari
5Shari is 40
Married to Scott
6They have 3 boys
7Shari works as a teller at CIBC
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9Case 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)
10Case 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.
11Case 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.
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13Case 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
14Case Presentation
- She asks you What is going on with me?
15Differential Diagnosis
- INFLAMMATORY POLYARTHRITIS
- Infection
- Rheumatoid Arthritis
- Seronegative Arthritis (Psoriatic)
- Connective Tissue Disease (SLE etc)
- Associated with another Systemic Disease
16Working 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)
17Who 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
18How 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
19How does RA start?
- Initially, most patients notice stiffness of the
joints which seems more pronounced in the morning - Some fatigue
- Some pain
20What 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!
21Small Joints of the Hand
22What Joints are affected?
23How are the Joints Affected
- Joints are usually
- Swollen
- Warm
- NOT RED (might be a bit purple)
24NO REDNESS!
25Morning 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?
26Morning Stiffness
- Inflammatory fluid increases in and around the
joint - As patients get moving the fluid gets resorbed
- Stiffness can occur after rest gelling
27Constitutional 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.
28Functional 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
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30Rheumatoid 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
31Doesnt just affect the joints
- EXTRA-ARTICULAR
- MANIFESTATIONS
32Xerophthalmia (Dry Eyes)
33Xerostomia (Dry Mouth)
34Raynauds Phenomenon
35Carpal Tunnel Syndrome
36Pleural Effusion
37Rheumatoid Nodules
38Rheumatoid Nodules
39Rheumatoid Vasculitis
40Extra-Articular Manifestations
- Sicca Features Xerostomia Xerophthalmia
- Raynauds Phenomenon
- Neuropathy Carpal Tunnel Syndrome
- Rheumatoid Nodules
- Pleural Effusions
- Rheumatoid Vasculitis
41Tests, Tests, Tests
- INVESTIGATING A PATIENT WITH SUSPECTED RA
42Back to Shari
43SUMMARY
- 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.
44INFLAMMATION
- 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)
45ORGAN 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
46ANTIBODIES
- Rheumatoid Factor
- Anti-Nuclear Antibody
47Rheumatoid 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
48Rheumatoid 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
49Rheumatoid 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
50Pearls 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
52Periarticular OsteopeniaJoint Space
NarrowingErosionsMal-Alignment
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54 55Rheumatoid Synovium
- A Non-Suppurative (no pus) inflammatory
infiltrate in the synovium - Due to the aggregation of lymphocytes and plasma
cells
56Rheumatoid Synovium
57PRINCIPLES OF TREATMENT
58The Big Bang
90 of the joints involved in RA are affected
within the first year SO TREAT IT EARLY
59Disability in Early RA
- Inflammation
- Swollen
- Stiff
- Sore
- Warm
- Fatigue
- Potentially Reversible
60Disability 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!
61A 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?
62Clinical 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.
63Why 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
64Why is Early Treatment Important?
- EARLY Treatment has Long-Term Beneficial Effects
- WINDOW OF OPPORTUNITY
- Delay of 4 months can have long-term effects
65Disability in Late RA (Too Late)
- Damage
- Bones
- Cartilage
- Ligaments and other structures
- Fatigue
- Not Reversible
66Induce Remission
Maintain Remission
67The Good Ship RA
Non-Pharmacologic
NSAIDs COXIBs
Dont Let the Ship Sail TREAT EARLY AGGRESSIVELY
Steroids
DMARDs Biologics
68DMARDs
- 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
69DMARDs
- Reduce swelling Inflammation
- Improve Pain
- Improve Function
- Have been shown to reduce radiographic
progression (erosions)
70DMARDs
- Methotrexate
- Sulfasalazine
- Hydroxychloroquine (Plaquenil)
- Leflunomide (Arava)
- Gold
- Azathioprine (Imuran)
71Combining 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
72Lotto 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
73You Might Get Lucky
74You Might Not
75Lets Buy 3 Tickets!
76Combination therapy (using 2 to 3) DMARDs at a
time works better than using a single DMARD
77Common DMARD Combinations
- Triple Therapy
- Methotrexate, Sulfasalazine, Hydroxychloroquine
- Double Therapy
- Methotrexate Leflunomide
- Methotrexate Sulfasalazine
- Methotrexate Hydroxychloroquine
- Methotrexate Gold
- Sulfasalazine Plaquenil
78Shari
- 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
79Shari
- Change DMARDs Add leflunomide
- Biologic Therapy
80BIOLOGIC THERAPY
81Tumour 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)
82TNF Receptor
How Does TNF Exert Its Effect?
Any Cell
Trans-Membrane Bound TNF
Soluble TNF
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84TNF Receptor
How Are the Effects of TNF Naturally Balanced?
Any Cell
Trans-Membrane Bound TNF
Soluble Receptor
Soluble TNF
85Strategies for Reducing Effects of TNF
Monoclonal Antibody (Infliximab Adalimumab)
Trans-Membrane Bound TNF
Macrophage
Soluble TNF
86Infliximab (Remicade) Adalimumab (Humira)
- Chimeric (murine human) monoclonal antibody
directed against TNF-a
87Strategies for Reducing Effects of TNF
Soluble Receptor Decoy (Etanercept)
Trans-Membrane Bound TNF
Macrophage
Soluble TNF
88Etanercept (Enbrel)
- 2 soluble p75receptors attached to the Fc portion
of the IgG molecule
89Biologics
- 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
90Side Effects
- Infection
- Common (Bacterial)
- Opportunistic (Tb, Histo)
- Demyelinating Disorders
- Malignancy
- Worsening CHF
- Blood Counts
91Do 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
92Do they work?
93SUMMARY
- Rheumatoid Arthritis is a chronic potentially
debilitating illness - Early treatment can have a PROFOUND effect on
this disease
94Its UP TO YOU
95TO BECOME A RHEUMATOLOGIST
96OR TO GET THEM TO US