Title: Rheumatoid Arthritis * * * * 7 * * * * * * * * * * * * * *
1Rheumatoid Arthritis
2Acknowledgements
- Dr. Andrew Thompson, rheumatologist at SJHC and
developer of the UWO rheumatology medical school
program
3Objectives
- Gain a basic understanding of Rheumatoid
Arthritis - Understand the presentation of Rheumatoid
Arthritis (Inflammatory Arthritis) - Understand the current treatment paradigm and
medications used
4Case Presentation
- 43 yo woman, has been healthy apart from
- C-Section for
- Mild depression
- Her current medications are
- Sertraline 100 mg per day (depression)
- Naproxen 500 mg twice a day (recent joint pain)
5Case Presentation
- 4 months ago developed pain in the left knee with
some mild swelling. - The episode lasted a few days and then went away.
6Case Presentation
- About a week later the right knee began to swell
and become sore - 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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8Case Presentation
- 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
9Differential Diagnosis
- INFLAMMATORY POLYARTHRITIS
- Infection
- Rheumatoid Arthritis
- Seronegative Arthritis (Psoriatic)
- Connective Tissue Disease (SLE etc)
- Associated with another Systemic Disease
10Who 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
11How 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
12How does RA start?
- Initially, most patients notice stiffness of the
joints which seems more pronounced in the morning - Some fatigue
- Some pain
13What 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!
14Small Joints of the Hand
15What Joints are affected?
16How are the Joints Affected
- Joints are usually
- Swollen
- Warm
- NOT RED (might be a bit purple)
17NO REDNESS!
18Morning 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?
19Morning Stiffness
- Inflammatory fluid increases in and around the
joint - As patients get moving the fluid gets resorbed
- Stiffness can occur after rest gelling
20Constitutional 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.
21Functional 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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23Rheumatoid 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
24Doesnt just affect the joints
- EXTRA-ARTICULAR
- MANIFESTATIONS
25Xerophthalmia (Dry Eyes)
26Xerostomia (Dry Mouth)
27Raynauds Phenomenon
28Carpal Tunnel Syndrome
29Pleural Effusion
30Rheumatoid Nodules
31Rheumatoid Nodules
32Rheumatoid Vasculitis
33Extra-Articular Manifestations
- Sicca Features Xerostomia Xerophthalmia
- Raynauds Phenomenon
- Neuropathy Carpal Tunnel Syndrome
- Rheumatoid Nodules
- Pleural Effusions
- Rheumatoid Vasculitis
34Tests, Tests, Tests
- INVESTIGATING A PATIENT WITH SUSPECTED RA
35CASE 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.
36INFLAMMATION
- 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)
37ORGAN 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
38ANTIBODIES
- Rheumatoid Factor
- Anti-Nuclear Antibody
39Rheumatoid 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
40Rheumatoid 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
41Rheumatoid 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
42Pearls 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
43- RADIOGRAPHIC
- FINDINGS IN RA
44Periarticular OsteopeniaJoint Space
NarrowingErosionsMal-Alignment
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46 47Rheumatoid Synovium
- A non-suppurative (no pus) inflammatory
infiltrate in the synovium - Due to the aggregation of lymphocytes and plasma
cells
48Rheumatoid Synovium
49PRINCIPLES OF TREATMENT
50The Big Bang
90 of the joints involved in RA are affected
within the first year SO TREAT IT EARLY
51Disability in Early RA
- Inflammation
- Swollen
- Stiff
- Sore
- Warm
- Fatigue
- Potentially Reversible
52Disability 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!
53A 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?
54Clinical 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.
55Why 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
56Why is Early Treatment Important?
- EARLY Treatment has Long-Term Beneficial Effects
- WINDOW OF OPPORTUNITY
- Delay of 4 months can have long-term effects
57Disability in Late RA (Too Late)
- Damage
- Bones
- Cartilage
- Ligaments and other structures
- Fatigue
- Not Reversible
58Induce Remission
Maintain Remission
59DMARDs
- Disease Modifying Anti-Rheumatic Drugs
- Reduce swelling inflammation
- Improve pain
- Improve function
- Have been shown to reduce radiographic
progression (erosions)
60DMARDs
- Methotrexate
- Sulfasalazine
- Hydroxychloroquine (Plaquenil)
- Leflunomide (Arava)
- Gold
- Azathioprine (Imuran)
61Combining 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
62Combination therapy (using 2 to 3) DMARDs at a
time works better than using a single DMARD
63Common DMARD Combinations
- Triple Therapy
- Methotrexate, Sulfasalazine, Hydroxychloroquine
- Double Therapy
- Methotrexate Leflunomide
- Methotrexate Sulfasalazine
- Methotrexate Hydroxychloroquine
- Methotrexate Gold
- Sulfasalazine Plaquenil
64Case Study
- 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
65Case Study
- Change DMARDs Add leflunomide
- Biologic Therapy
66BIOLOGIC THERAPY
67Tumour 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)
68TNF Receptor
How Does TNF Exert Its Effect?
Any Cell
Trans-Membrane Bound TNF
Soluble TNF
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70TNF Receptor
How Are the Effects of TNF Naturally Balanced?
Any Cell
Trans-Membrane Bound TNF
Soluble Receptor
Soluble TNF
71Strategies for Reducing Effects of TNF
Monoclonal Antibody (Infliximab Adalimumab)
Trans-Membrane Bound TNF
Macrophage
Soluble TNF
72Infliximab (Remicade) Adalimumab (Humira)
- Chimeric (murine human) monoclonal antibody
directed against TNF-a
73Strategies for Reducing Effects of TNF
Soluble Receptor Decoy (Etanercept)
Trans-Membrane Bound TNF
Macrophage
Soluble TNF
74Etanercept (Enbrel)
- 2 soluble p75receptors attached to the Fc portion
of the IgG molecule
75Biologics
- 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)
- Monoclonal Antibody to CD-20
- Rituximab (Rituxan)
76Side Effects
- Infection
- Common (Bacterial)
- Opportunistic (Tb, Histo)
- Demyelinating Disorders
- Malignancy
- Worsening CHF
- Blood Counts
77Do 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
78SUMMARY
- Rheumatoid Arthritis is a chronic potentially
debilitating illness - Early treatment can have a PROFOUND effect on
this disease - Treatment is multidisciplinary