RHEUMATOID ARTHRITIS:
OVERVIEW
AND
NEW INFORMATION
Pamela E. Prete MD, FACP, FACR
Section Chief, Rheumatology
Professor of Medicine, Emeritus
THIS CASE
36 female complains of fatigue, has right 3rd mcp
And left 2nd PIP joint swelling for 5 months, BUT
no am stiffness and minimal response to NSAIDS.
 PE shows no other joint involvement, no RA
nodules.
 X-rays show no erosions or JSN.

Pamela E. Prete MD
LABORATORY RESULTS
Dr Prete does a full clinical musculoskeletal exam and
orders a bunch of tests
But the Results are NOT back yet…So Does she have
this disease Rheumatoid arthritis ---whatever that is
Pamela E. Prete MD
Hemoglobin is 12.1
WBC 4500
Platelets 550,000 ( normal ?)
ESR 46mm/hour
C- reactive protein 12 ( normal < 5)
RF is 1:80
RHEUMATOID
ARTHRITIS
- DEFINITION
Pamela E. Prete MD
A prototypic chronic systemic auto-inflammatory
disease with features of autoimmunity
 Of undetermined etiology involving primarily the
synovial membranes and articular structures
 With pain, stiffness, and swelling of joints,
leading to deformity and ankylosis (fused joints)
 With significant extra-articular manifestations
related to the widespread systemic auto inflammation.

RHEUMATOID ARTHRITIS – THE MOST COMMON
AUTOINFLAMMATORY/AUTOIMMUNE DISEASE





1% population or 3 per
10,000
3:1 female to male
Highest in 3rd and 4th
decades
Two peaks incidence
Morbid/mortal disease
Description dates to the
17th century -A New
World Disease
Pamela E. Prete MD

RHEUMATOID ARTHRITIS
Affects the peripheral
joints in a symmetric
pattern.
 Extra-articular
involvement of organs
such as the skin,
heart, lungs, and eyes
can be significant.
 Constitutional
symptoms, including
Fatigue, malaise, and
morning stiffness

Pamela E. Prete MD
FIRST AND FOREMOST -
INFLAMMATORY
ARTHRITIS SYMMETRIC
Pamela E. Prete MD
MORNING STIFFNESS…



Not just AM but after
any long period of rest
Must elicit correctly
Our case patient did
not have it,…..
Pamela E. Prete MD

Needs to be >1 hour
- FEET TOO
“BUNIONS”
WITH COCKUP TOES AND
Feet are involved 90%
 MTP’s
 ( Although patients
get Hallux valgus –
the 1st MTP is spared
in RA)
--

Pamela E. Prete MD
WHAT IS MOST CHARACTERISTIC OF RA? - PATHOPHYSIOLOGY OF RA SYNOVITIS
Normal Diarthrodial JOINT
Pamela E. Prete MD
RA SYNOVITIS- PANNUS
T lymphocytes, CD 4 helper
cells, macrophages
Pamela E. Prete MD
NORMAL SYNOVIAL LINING
Pamela E. Prete MD
Pamela E. Prete MD
Pamela E. Prete MD
SYNOVIAL PANNUS
Pamela E. Prete MD
SYNOVITIS CAUSES THE
EROSIONS AND JUXTA –
ARTICULAR OSTEOPENIA
Pamela E. Prete MD
MUSCULOSKELETAL ULTRASOUNDDETECTS SUBCLINICAL INFLAMMATION
Pamela E. Prete MD
RHEUMATOID ARTHRITIS – AN AUTOINFLAMMATORY DISEASE WITH AUTOIMMUNE
FEATURES- AUTOANTIBODIES

ANA positive in 20%
Screening test
Rheumatoid Factor
 New RA autoantibody


Anti Cyclic
Citrullinated Peptide
(anti CCP)
Pamela E. Prete MD

RHEUMATOID FACTOR
IS AN
1.
3.
4.
5.
6.
A human antibody
against Fc portion
human Ig
Usually IgM directed
against IgG (but any
combo has been noted)
Binds Complement
Not diagnostic of RA
Does NOT follow
disease activity
Seen in any disease
with polyclonal b cell
activation
Pamela E. Prete MD
2.
AUTOANTIBODY
NEW
AUTOANTIBODY
ANTI CCP
What is a citrullinated
exchange of the charged arginine for
peptide?
the non charged citrulline
Pamela E. Prete MD
1. Newest autoantibody
found in RA patients
2. Highly specific for RA
but not sensitive
3. Associated with
“shared epitope”
3. RA disease- CVD,
more joint destruction
WHAT IS THE EVIDENCE FOR GENETIC
FACTORS IN RHEUMATOID ARTHRITIS?



But only certain alleles
of HLA DR4
All RA associated alleles
“share” an amino acid
sequence, located HLA
DRB1 gene
In all populations,
RA susceptibility is in
the “shared epitope”
Pamela E. Prete MD

1970’s association with
HLA DR4
THE IMMUNE CASCADE IN RA
Dendritic
T
Co-stimulation
required
TNF
alpha
Pamela E. Prete MD
macrophage
TNF
IL-1
IL-6
Co-stimulation
required
B
Anti-CCP
Rheumatoid
factors
WHAT DO WE KNOW ABOUT THE ETIOLOGY
OF RHEUMATOID ARTHRITIS?
Genetic “shared epitope” 67-74 HLA DRB1
 Autoreactive Polyclonal B cells
 Autoantibodies RF and Anti CCP
 Complement cascade activated
 Immune complexes are formed
 Production of certain cell products the activate
inflammation and destruction - CYTOKINES

Pamela E. Prete MD
Interleukin 1
 Tumor necrosis factor
 Interleukin 6

RHEUMATOID ARTHRITIS – SYSTEMIC
AUTOIMMUNE / AUTO INFLAMMATORY DISEASE-
By causing…
1. Synovitis
2. Serositis
3. Nodules
4. Vasculitis
5. Autoantibodies
Pamela E. Prete MD
How dose RA affect
all these organ
systems ?
RA SYSTEMIC DISEASE—SICCA
SYNDROME –DRY EYE AND MOUTH
Major cause of
Secondary Sjogren’s
disease
 Defined as sicca with
Lymphocytic
infiltration of the
lacrimal gland

Pamela E. Prete MD
KERATOCONJUNCTIVITIS SICCA (KCS)
DRY EYE WITH THINNING OF THE SCLERA
Pamela E. Prete MD
SCLEROMALACIA- THINNING OF SCLERA

Pamela E. Prete MD
Blue choroid coming through
thinned sclera
Scleromalacia
perforans - rare
historic note only
RHEUMATOID LUNG - MOST SERIOUS VISCERAL
ORGAN AFFECTED BY RHEUMATOID ARTHRITIS

Rheumatoid nodules
Pamela E. Prete MD
**LUNG
 Most common small
bilateral pleural
effusions
 Cause of lung fibrosis
 Pulmonary vasculitis
 Caplan’s syndrome
CAPLAN’S SYNDROME
First reported in coal
miners with RA
 RA nodules
 If solitary must biopsy
 RA patients have
nodules elsewhere
 Can also result as an
abnormal rxn to
methotrexate
(methotrexate
nodulosis)

Pamela E. Prete MD
SUMMARY OF RHEUMATOID LUNG

Pleura ---------------Pleuritis, pleural effusions

Air way------------- Cricoarytenoid arthritis, bronchiolitis



Parenchyma---------Pneumonitis, BOOP, LIP, nodules,
lung fibrosis
Pulmonary
vessels---- -----------Vasculitis
Lymphoid tissue----Lymphoid hyperplasia or lymphoma
RA treatment induced
Lung --------------------------Methotrexate fibrosis, infection
reactivation of TB
Pamela E. Prete MD

RHEUMATOID ARTHRITIS






Rare presentation
Rheumatoid factor,
present in 93%
Subcutaneous nodules
were present in 47%.
left-sided chest pain most
common symptom
pericardial friction rub
Cardiomegaly,,
accompanied by pleural
effusion
pericardial fluid



low sugar concentration
elevated lactic
dehydrogenase
low complement
Pamela E. Prete MD

PERICARDITIS
NEUROLOGIC
Entrapment Carpal
Wrist Synovitis in RA
tunnel
C1 C2 subluxation
synovial involvement of the
ligament over the odontoid
Pamela E. Prete MD
RHEUMATOID NODULES?
Occur over extensor
tendons
 Elbow most common
 Firm nodule -0.3-1cm
 Occur with disease
activity
 Can occur anywhere
 Have a characteristic
pathology

Pamela E. Prete MD
NODULES
Pamela E. Prete MD
RA NODULE -PATHOGNOMONIC
PATHOLOGY
 Central necrosis
 Palisading histiocytes
 Fibrotic capsule

ULTRASOUND

Hypoechoic
homogeneous mass
with anechoic center
Pamela E. Prete MD

RHEUMATOID VASCULITIS - A THING OF THE
PAST BECAUSE OF THE TARGETED THERAPIES

Digital infarcts

Small vessel Vasculitis

Result in Lung
hemorrhage or GI
bleeding
Pamela E. Prete MD

warning sign of small
vessel vasculitis in RA
or impending digital
gangrene
WHAT IS NEW IN RA
The pathophysiology and new genetic
information has led to specific targeted
immunotherapy and the use of the new
BIOLOGICS. AND the discovery that Rheumatoid
arthritis has multiple subclasses based on the
responses to the targeted therapies.
BUT WE NEED TO START THERAPY EARLIER
AT THE MOLECULAR LEVEL –HOW CAN WE DO
THAT?
Pamela E. Prete MD
AND WHY
HAS IT BEEN A GREAT DECADE
FOR RHEUMATOID ARTHRITIS?
THE “OLD” AMERICAN COLLEGE OF
RHEUMATOLOGY (ACR) CRITERIA FOR THE
DIAGNOSIS OF
RHEUMATOID ARTHRITIS 7
1.
3.
4.
5.
6.
7.
Pamela E. Prete MD
2.
Morning stiffness
Arthritis of 3 or more joint areas, observed by a
physician.
Arthritis of hand and wrist joints
Symmetric arthritis
Rheumatoid nodule
Serum Rheumatoid Factor
Radiographic changes hand and wrist
radiographs--erosions or juxta-articular
osteopenia
NEW ACR EULAR CRITERIA FOR RA
4 DOMAINS
1. Domain: Joint involvement – max 5points

2. Domain: Serology -max 3points

3. Domain: Duration of synovitis- max 1point

4. Domain: Acute phase reactants -max 1point

YOU NEED 6 points for a DEFINITE RA
DIAGNOSIS
Pamela E. Prete MD

DOMAIN: JOINT INVOLVEMENT





Note: Patients receive the highest
point level they fulfill within each
domain. For example, a patient with
five small joints involved and four
large joints involved scores 3 points.
Pamela E. Prete MD

– 1 medium-large joint
(0 points)
– 2-10 medium-large joints
(1 point)
– 1-3 small joints
(2 points)
– 4-10 small joints
(3 points)
– More than 10 small joints
(5 points)
DOMAIN: SEROLOGY -MAX 3POINTS
What is CCP?

Pamela E. Prete MD

-No RF or anti-CCP)
(0 points)
– One positive at low titer,
< 3x normal
(2 points)
– One positive at high titer,
> 3x normal
(3 points)
DOMAIN: DURATION OF SYNOVITIS- MAX
1POINT
<
Pamela E. Prete MD
6 weeks
(0 points)
 >6 weeks or longer
(1 point)
DOMAIN: ACUTE PHASE REACTANTS
Neither (CRP) nor (ESR)
is abnormal
(0 points)
 –Abnormal CRP or
abnormal ESR
(1 point)

Pamela E. Prete MD
SUMMARY OF THE NEW RA CRITERIA
Pamela E. Prete MD
WORK UP FOR RA INCLUDES

Specific history and physical
Serologies

CBC and Differential, ESR, C Reactive protein, ANA,
Rheumatoid factor and Anti CCP
On the spot imaging with musculoskeletal
ultrasound –newest modality for Rheumatologists
 Joint tap- Synovial fluid – inflammatory- low
glucose
 Other Imaging


X-rays- hands, feet , MRI early erosions, Bone scan
Pamela E. Prete MD

Fam hx, msk exam, ROS
TREATMENT
BEFORE THE
BIOLOGICS
NSAIDs for stiffness
 Corticosteroids for inflammation and to suppress
the autoimmunity
 Disease Modifying Anti rheumatic Drugs
(DMARDs)

Pamela E. Prete MD
Drug of choice -Methotrexate 7.5-25mg weekly
 But also Cyclosporine, Azathioprine,
cyclophosphamide

MONOCLONAL ANTIBODIES AND RA

Tumor Necrosis (alpha) Inhibitors 5 FDA approved








Rituximab (rituxan) anti CD20 B cells
Abatacept anti Costimulation blocking CD80/86
CD28
Anakinra (Kineret) anti IL 1 receptor DOES NOT
WORK
Tocilizumab (Actemra) anti IL 6
Pamela E. Prete MD

Infliximab ( Remicaid ) an infusion
Etanercept ( Enbrel) against soluble TNF receptors
Adalimunab (Humira) against soluble and
membrane
bound TNF receptors
Certolizumab (Cimza) pegylated
Golimumab (Simponi)
Pamela E. Prete MD
THESE
TARGETED THERAPIES HAVE
CHANGED THE COURSE OF RA…







Pamela E. Prete MD

No deformities
No synovectomies
No splinting
No small vessel
vasculitis
Resolution of nodules
Less RA lung
Less Mortality from
CVD
Decreased incidence of
Non Hodgkin’s
Lymphoma
RHEUMATOID ARTHRITIS SUMMARY


Eyes, lungs, heart, lymph glands
There the unknown antigen trigger
 Genetic predisposition-- HLA DR4 and “Shared”
epitope located on HLA DRB1
 Autoantibodies

rheumatoid factor and new anti cyclic citrullinated
peptides- define subclasses of RA
 Have pathogenic and prognostic significance


Involves the Adaptive and Innate Immune
system
Pamela E. Prete MD
Auto-inflammatory disease ( with autoimmune
features) resulting in symmetric joint
destruction, systemic disease
RHEUMATOID ARTHRITIS SUMMARY
Multiple effector cells release cellular products
cytokines, in synovial proliferation resulting in
joint and multiple organ destruction
 Immune complexes and complement are active
 Multiple theories have been proposed to explain
the findings
 Suppression of the auto reactivity improves
Rheumatoid arthritis

Pamela E. Prete MD
RHEUMATOID ARTHRITIS SUMMARY
But Targeted therapies have changed the course
of Rheumatoid arthritis
 Information from Targeted therapy suggest T
cell or IL 1 suppression not helpful once the
disease is apparent
 Varied responses to the Targeted therapies
indicate Rheumatoid arthritis is not one disease
and autoimmune processes overlap between
autoimmune diseases

Pamela E. Prete MD
ATTENTION
If questions or help with a patient
page Dr Prete or email pamela.prete@va.gov
Pamela E. Prete MD
THANK YOU FOR YOUR KIND
Pamela E. Prete MD
Pamela E. Prete MD
Pamela E. Prete MD
Pamela E. Prete MD
Pamela E. Prete MD
Pamela E. Prete MD
Definitions
JOINT DISTRIBUTION (0-5)
0
2-10 large joints
1
1-3 small joints (large joints not counted)
2
4-10 small joints (large joints not counted)
3
>10 joints (at least one small joint)
5
Definition of “JOINT INVOLVEMENT”
- Any swollen or tender joint (excluding DIP
of hand and feet, 1st MTP, 1st CMC)
SEROLOGY (0-3)
Negative RF AND negative ACPA
0
Low positive RF OR low positive ACPA
2
High positive RF OR high positive ACPA
3
SYMPTOM DURATION (0-1)
<6 weeks
0
≥6 weeks
1
ACUTE PHASE REACTANTS (0-1)
Normal CRP AND normal ESR
0
Abnormal CRP OR abnormal ESR
1
≥6 = definite
RA
- Additional evidence from MRI / US
may be used for confirmation of the
clinical findings
Pamela E. Prete MD
1 large joint
Definitions
JOINT DISTRIBUTION (0-5)
0
2-10 large joints
1
1-3 small joints (large joints not counted)
2
4-10 small joints (large joints not counted)
3
>10 joints (at least one small joint)
5
Definition of “SMALL JOINT”
Negative RF AND negative ACPA
0
MCP, PIP, MTP 2-5, thumb IP, wrist
Low positive RF OR low positive ACPA
2
High positive RF OR high positive ACPA
3
SEROLOGY (0-3)
SYMPTOM DURATION (0-1)
<6 weeks
0
≥6 weeks
1
ACUTE PHASE REACTANTS (0-1)
Normal CRP AND normal ESR
0
Abnormal CRP OR abnormal ESR
1
≥6 = definite
RA
NOT: DIP, 1st CMC, 1st MTP
Pamela E. Prete MD
1 large joint
Definitions
JOINT DISTRIBUTION (0-5)
0
2-10 large joints
1
1-3 small joints (large joints not counted)
2
4-10 small joints (large joints not counted)
3
>10 joints (at least one small joint)
5
SEROLOGY (0-3)
Negative RF AND negative ACPA
0
Low positive RF OR low positive ACPA
2
High positive RF OR high positive ACPA
3
SYMPTOM DURATION (0-1)
<6 weeks
0
≥6 weeks
1
ACUTE PHASE REACTANTS (0-1)
Normal CRP AND normal ESR
0
Abnormal CRP OR abnormal ESR
1
≥6 = definite
RA
Definition of “LARGE JOINT”
Shoulder, elbow, hip, knee, ankles
Pamela E. Prete MD
1 large joint
Definitions
JOINT DISTRIBUTION (0-5)
0
2-10 large joints
1
1-3 small joints (large joints not counted)
2
4-10 small joints (large joints not counted)
3
>10 joints (at least one small joint)
5
SEROLOGY (0-3)
Negative RF AND negative ACPA
0
Low positive RF OR low positive ACPA
2
High positive RF OR high positive ACPA
3
SYMPTOM DURATION (0-1)
<6 weeks
0
≥6 weeks
1
ACUTE PHASE REACTANTS (0-1)
Normal CRP AND normal ESR
0
Abnormal CRP OR abnormal ESR
1
≥6 = definite
RA
Definition of “>10 JOINTS”
- At least one small joint
- Additional joints include:
temporomandibular,
sternoclavicular,
acromioclavicular, and
others (reasonably expected in RA)
Pamela E. Prete MD
1 large joint
Definitions
JOINT DISTRIBUTION (0-5)
0
2-10 large joints
1
1-3 small joints (large joints not counted)
2
4-10 small joints (large joints not counted)
3
>10 joints (at least one small joint)
5
SEROLOGY (0-3)
Negative RF AND negative ACPA
0
Low positive RF OR low positive ACPA
2
High positive RF OR high positive ACPA
3
SYMPTOM DURATION (0-1)
<6 weeks
0
≥6 weeks
1
ACUTE PHASE REACTANTS (0-1)
Normal CRP AND normal ESR
0
Abnormal CRP OR abnormal ESR
1
≥6 = definite
RA
Definition of “SEROLOGY”
Pamela E. Prete MD
1 large joint
Negative: ≤ULN (for the respective lab)
Low positive: >ULN but ≤3xULN
High positive: >3xULN
Definitions
JOINT DISTRIBUTION (0-5)
0
2-10 large joints
1
1-3 small joints (large joints not counted)
2
4-10 small joints (large joints not counted)
3
>10 joints (at least one small joint)
5
SEROLOGY (0-3)
Negative RF AND negative ACPA
0
Low positive RF OR low positive ACPA
2
High positive RF OR high positive ACPA
3
SYMPTOM DURATION (0-1)
<6 weeks
0
≥6 weeks
1
ACUTE PHASE REACTANTS (0-1)
Normal CRP AND normal ESR
0
Abnormal CRP OR abnormal ESR
1
≥6 = definite
RA
Definition of “SYMPTOM DURATION”
Refers to the patient’s self-report on the maximum
duration of signs and symptoms of any joint that is
clinically involved at the time of assessment.
Pamela E. Prete MD
1 large joint
NEW RA CRITERIA

Patients are definitively diagnosed with RA if they score 6 or more points according to the
following criteria


















Note: Patients receive the highest point level they fulfill within each domain. For example, a
patient with five small joints involved and four large joints involved scores 3 points.
Pamela E. Prete MD

1. Domain: Joint involvement
– 1 medium-large joint
(0 points)
– 2-10 medium-large joints
(1 point)
– 1-3 small joints
(2 points)
– 4-10 small joints
(3 points)
– More than 10 small joints
(5 points)
2. Domain: Serology
– No rheumatoid factor (RF) or anti–citrullinated protein antibody (anti-CCP)
(0 points)
– One of these two tests is positive at low titer, less than three times the upper limit of normal
(2 points)
– One test is positive at high titer, more than three times the upper limit of normal
(3 points)
3. Domain: Duration of synovitis
– Less than 6 weeks
(0 points)
– 6 weeks or longer
(1 point)
4. Domain: Acute phase reactants
– Neither C-reactive protein (CRP) nor erythrocyte sedimentation rate (ESR) is abnormal
(0 points)
– Abnormal CRP or abnormal ESR
(1 point)
4 DOMAINS
1.Domain: Joint involvement – max 5points

2. Domain: Serology -max 3points


3. Domain: Duration of synovitis- max
1point
4. Domain: Acute phase reactants -max
1point
Pamela E. Prete MD

DOMAIN: JOINT INVOLVEMENT





Note: Patients receive the highest
point level they fulfill within each
domain. For example, a patient
with five small joints involved and
four large joints involved scores 3
points.
Pamela E. Prete MD

– 1 medium-large joint
(0 points)
– 2-10 medium-large joints
(1 point)
– 1-3 small joints
(2 points)
– 4-10 small joints
(3 points)
– More than 10 small joints
(5 points)
DOMAIN: SEROLOGY -MAX 3POINTS
(0 points)
(2 points)

One positive at high titer, > 3x normal (3 points)
Pamela E. Prete MD

No RF or anti-CCP)
One positive at low titer, < 3x normal

DOMAIN: DURATION OF SYNOVITIS- MAX1POINT
• < 6 weeks
• >6 weeks or longer
(0 points)
(1 point)
DOMAIN: ACUTE PHASE REACTANTS
Neither (CRP) nor
(ESR) is abnormal
(0 points)
 –Abnormal CRP or
abnormal ESR
(1 point)

Pamela E. Prete MD
LABORATORY RESULTS





Anti CCP 52 units/mL
(normal is < 16units/mL)

RF mildly increased 1:80

ESR -64 mm/hr

Urinalysis Normal
Anti DD DNA abs, SSA,
SSB, RNP, Smith all
negative!
Does she have RA?


Under the old Criteria NO!
Under the NEW –you bet!
Pamela E. Prete MD

CBC mild anemia
Serum iron normal
Serum ferritin normal
ANA 1:40
3 ACR CRITERIA ARE PRESENT
SYMMETRIC, 3 OR MORE JOINTS, AND
INVOLVEMENT OF HAND AND WRIST
Pamela E. Prete MD
RADIOGRAPHIC CHANGES
On Hand and Wrist
x-rays
 Juxta-articular
osteopenia
 Frank erosions
 Not cysts, not
osteoarthritis changes

Pamela E. Prete MD
SYNOVIAL CAVITY


>10-50 thousand wbc’s
 Low glucose
 Low complement


Pamela E. Prete MD

Synovial Cavity
Normally only a
"potential" space with 12ml of highly viscous
fluid few cells.
In RA, large collections
of fluid ("effusions")
occur
RA synovial fluid is
highly inflammatory
Pamela E. Prete MD
Pamela E. Prete MD
Pamela E. Prete MD
RA IMMUNE CASCADE
Pamela E. Prete MD
Pamela E. Prete MD
WHY ARE ACPA
IMPORTANT IN
RA?
Pamela E. Prete MD
Pamela E. Prete MD
RA – AUTO-INFLAMMATORY, WASTING
DISEASE IF UNTREATED
Pamela E. Prete MD
RHEUMATOID ARTHRITIS – JOINT DAMAGE
Pamela E. Prete MD
REMEMBER THIS CASE…


Family history reveals an Aunt with
Rheumatoid arthritis
Social history reveals she is a 2 pack a day
smoker, married with two children No IVD,
Medications - Tylenol 4 per day
Pamela E. Prete MD

You are in Arthritis Clinic and Dr Prete asks you
to see a 29 YO female with fatigue and early
morning stiffness that lasts all day. She states
her hands have swelled and ached for the past 2
months.
ETIOLOGY
Worldwide, 3 cases per 10,000 population
 Prevalent in some Native American groups (56%) and much less prevalent in others (e.g., black
persons from the Caribbean region).
 First-degree relatives of individuals with RA are
at an increased risk (2- to 3-fold) of the disease.
 Disease concordance in monozygotic twins is
only15-20%
 Because the worldwide frequency of RA is
relatively constant, a ubiquitous infectious agent
has been postulated to play an etiologic role.

Pamela E. Prete MD
ARTHRITIS?
Definite swelling
 MCP’s, PIP’s

But was it observed by a
Provider >6 weeks?
Pamela E. Prete MD
So our patient has
 1. 3 or more joints
 2. Involvement of the
hands and wrist
 3. Symmetric

Fatigue
stiffness
PIP and MCP involvement
… She has an inflammatory arthritis but is it RA?
Pamela E. Prete MD
WHAT ABOUT OUR PATIENT?
Rheumatoid Arthritis?
ARE we sure of the diagnosis?
Does the diagnosis fulfill ACR criteria?
…Does it matter?
Pamela E. Prete MD
WHAT IS THE DIAGNOSIS?…
SO WHAT ABOUT OUR PATIENT ?

She had
morning stiffness
 3 or more joints inflamed at the same time
 Hand involvement
 Symmetric arthritis

She did not have
No Rheumatoid nodules
 No hand x-ray changes
 We don’t know about RF…


She has 4 of the 7 ACR criteria so it is most likely
she has rheumatoid arthritis just on CLINICAL
EXAMINATION alone!
Pamela E. Prete MD

EULAR CRITERIA FOR RA-- NEW
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Pamela E. Prete MD
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score 6 or more points according to the following
criteria, four domains:
Domain: Joint involvement
– 1 medium-large joint (0 points)
– 2-10 medium-large joints (1 point)
– 1-3 small joints (2 points)
– 4-10 small joints (3 points)
– More than 10 small joints (5 points)
Note: Patients receive the highest point level they
fulfill within each domain. For example, a patient
with five small joints involved and four large joints
involved scores 3 points
Domain: Serology
 – Not positive for either rheumatoid factor or
anti–citrullinated protein antibody (0 points)
 – At least one of these two tests are positive at
low titer, defined as more than the upper limit of
normal but not higher than three times the upper
limit of normal (2 points)
 – At least one test is positive at high titer,
defined as more than three times the upper limit
of normal (3 points)
.
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Pamela E. Prete MD
REMEMBER YOU NEED 6 POINTS
Domain: Duration of synovitis
 – Less than 6 weeks (0 points)
 – 6 weeks or longer (1 point)
 Domain: Acute phase reactants
 – Neither C-reactive protein nor erythrocyte
sedimentation rate is abnormal (0 points)
 – Abnormal CRP or abnormal ESR (1 point)

Pamela E. Prete MD
Pamela E. Prete MD
Unknown but here are the data
we know
Pamela E. Prete MD
WHAT CAUSES RHEUMATOID
ARTHRITIS …
Pamela E. Prete MD
Associated with the
shared epitope
RA-associated HLADR4 molecules (DR4)
can bind and present
citrullinated peptides
much more efficiently
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Pamela E. Prete MD
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the shared epitope of the HLA-DR4/DR1 cluster is present in up to
90% of patients
Synovial cell hyperplasia and endothelial cell activation are early
events in the pathologic process that progresses to uncontrolled
inflammation and consequent cartilage and bone destruction.
CD4 T cells, mononuclear phagocytes, fibroblasts, osteoclasts, and
neutrophils play major cellular roles in the pathophysiology of RA,
while B lymphocytes produce autoantibodies (i.e., rheumatoid factors
[RFs]).
Abnormal production of numerous cytokines, chemokines, and other
inflammatory mediators (e.g., tumor necrosis factor alpha [TNFalpha], interleukin (IL)–1, IL-6, transforming growth factor beta, IL8, fibroblast growth factor, platelet-derived growth factor) has been
demonstrated in patients with RA. Ultimately, inflammation and
exuberant proliferation of synovium (i.e., pannus) leads to destruction
of various tissues, including cartilage, bone, tendons, ligaments, and
blood vessels. Although the articular structures are the primary sites
involved by RA, other tissues are also affected.
Pamela E. Prete MD
Pamela E. Prete MD
Pamela E. Prete MD
RHEUMATOID FACTOR
Pamela E. Prete MD
1. 80% of all RA patients
2. High titer (quantity)
3. Found in serum but also Joint, pleural or
pericardial fluids
4. By itself-not diagnostic
5. Found in other diseases with polyclonal
stimulation of B Cells
Aging
Hepatitis C
Chronic infections
Lymphomas
Other AI diseases – highest in Sjogren’s
DESTRUCTIVE NATURE OF
RHEUMATOID ARTHRITIS AND
ITS SYSTEMIC FEATURES…
We need to know it’s
pathophysiology
Pamela E. Prete MD
TO EXPLAIN THE EROSIVE,
PANNUS- JOINT DESTRUCTION
Pamela E. Prete MD
GENETIC FACTORS IN RHEUMATOID
ARTHRITIS

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In all populations RA
susceptibility is
conferred by the
shared epitope
Pamela E. Prete MD

Risk of RA is 2-3 if you
have a relative with RA
Only certain alleles of
HLA DR4 confer
susceptibility
Susceptibility – located
at 67-74 amino acids on
HLA DRB1 gene
All RA associated alleles
“share” an amino acid
sequence – the shared
epitope

Pamela E. Prete MD
Pamela E. Prete MD
Pamela E. Prete MD
WHY THE JOINTS?
Pamela E. Prete MD
Pamela E. Prete MD
RHEUMATOID ARTHRITIS - JOINT
SYNOVIAL CAVITY
EROSIONS JOINT
DESTRUCTION
Pamela E. Prete MD
THE NEW TREATMENT PARADIGM
Higher dose steroids
for flares or extraarticular disease
Occupational therapy
Intraarticular steroids
Physical therapy
Patient
education
Simple
analgesic
Pamela E. Prete MD
Orthopedic surgery