Rheumatoid Arthritis

Rheumatoid Arthritis
Rheumatoid arthritis is an autoimmune disease in which
the normal immune response is directed against an
individual's own tissue, including the joints, tendons,
and bones, resulting in inflammation and destruction of
these tissues.

Epidemiology
Age of onset typically between 20 and 45 years but over
25% cases start over 60 years old
Female to male ratio is nearly 3:1
Annual incidence: 36 cases per 100,000 women

Pathophysiology

Clinic manifestation
ARTICULAR - Classic
Insidious onset of symmetric polyarthritis, particularly
MCPs, MTPs, PIPs, wrists
Morning stiffness lasting more than one hour
Constitutional symptoms such as fatigue common

ARTICULAR Less common

Acute polyarthritis with prominent myalgias and
constitutional symptoms
Palindromic rheumatism one or several joints acutely
involved for hours to few days with symptom free
intervals lasting days to months
Persistent monoarthritis as herald of disease

Confirmation of Synovitis
Synovitis needs to be confirmed by reliable examiner
since it is essential requirement for diagnosis
If synovitis is equivocal on exam
*May need to follow patient
*Occasionally imaging techniques such
as MRI helpful

EXTRAARTICULAR
-Constitutional
-Nodules
-Sjogren syndrome
-Pulmonary
-Cardiac
-Vasculitis
-Hematologic
-Lymphoma

Diagnosis Criteria

Clinically Useful Biologic Markers

Rheumatoid factor
Anti-CCP antibody
ESR / CRP

Rheumatoid Factor(s)
Found in 75-80% of RA patients
Positivity lower at onset but peaks by 6-12 months
High levels associated with more aggressive disease
Nonspecific can occur in chronic infections (such as
HCV) and other autoimmune disease

Anti-Cyclic Citrullinated Peptide (CCP)

Antibodies
Found in 50-75% of RA patients
May precede clinical symptoms
Confers increased risk of progressive disease
More specific than RF

Testing for both RF and anti-CCP antibodies

Sensitivity
RF

Specificity

73%

Anti-CCP
Both positive

82%
56%
48%

90%
96%

Remember: higher the specificity, higher the positive predictive

value (more likely to have disease)

Acute Phase Reactants ESR/CRP

Not specific, but fairly sensitive
Elevation of both: stronger indication of radiographic
progression
Correlate with disease activity and used in various
metrics to follow disease activity

THERAPY
1. Relief of signs and symptoms.
2. Improvement in patient reported outcomes
3. Inhibition of structural damage
These 3 interrelated aims best achieved by rapid and
sustained suppression of disease to remission or low
disease activity with DMARDs.

NON PHARMALOGICAL THERAPY

Education about the disease and therapy
Exercise Artritis
Cod liver oil suplement
Cold/hot therapy to reduce pain

Consult for surgery if there is:

Severe pain (related to extensive joint destruction)
Limitation of movement or function
Tendon rupture

PHARMACOLOGICAL THERAPY
NSAIDs
Glucocorticoids : prednisone 10 mg/d
DMARDs
- Methotrexate 10-25 mg/w
- Leflunomide 10-20 mg/d
- Sulfasalazine 500mg 2x1 1000-1500mg 2x1
- Hydroxychloroquine 200-400 mg/d
Biologic DMARDs
- TNF-alpha inhibitor: Infliximab, Etanercept, Adalimumab, Golimumab,
- Abatacept
- Anakinta
- Rituximab
- Toclizumab

Certolizumab

basic evaluation should be performed

before DMARDs Therapy
Examination
DMARD

CBC

Liver
transaminase

Creatinin
serum

Hepatitis B
and C

Ophthalmolo
gy

Non-Biologic
Hydroxychloroq
uine

Leflunomide

Methotrexate

Minocycline

Sulfasalazine

Biologic
All biologic
agent

Measures of Disease Activity

A metric utilizing several parameters to assess activity
Used to initially stage disease
Can evaluate response to therapy adequate (tight) or
not
Can be used to define remisson

Assessment of Disease Activity in Early

RA
Semi Quantitative
Mild
# joints

ModerateSevere
< 6 6-20

> 20

Extraarticular No No Common
Erosions No +/- ++
RF/CCP+ +/- +

++

ESR/CRP +/- +

++

Quantitative
DAS 28

2.4-3.6 3.7-5.5 > 5.5

Treatment of Mild Disease in Early RA

NSAIDS and traditional DMARDs may suffice
*hydroxychloroquine
(HCQ)
*sulfasalazine
(SSA)
*methotrexate
(MTX)
*leflunomide
(LEF)
*doxycycline
Combination of traditional DMARDS sometimes used
Corticosteroids not at all or sparingly

Treatment of Moderate/Severe Early RA

Goal: Remission of low disease activity
A. MTX (or LEF) monotherapy for 8-12 week trial
B. Inadequate responders to A: MTX + anti-TNF
C. Inadequate responders to B: TNF switching or
MTX + other traditional DMARDs or
MTX + newer biologic agent
tocilizumab (Actemra)
rituximab (Rituxin)
abatacept (Orencia)
NSAIDS and Corticosteroids adjunctive

Role of Corticosteroids in Early

RA
If patient systemically ill or experiencing rapid decline in
function, prednisone 10 mg/daily
Once patient responds sufficiently, dose should be
tapered to 5 mg/day or less
Intraarticular route very effective and may bypass
systemic use
Also consider protection for osteoporosis if prednisone
used at >5 mg/day for greater than 3 months

Safety Issues - NSAIDS

Toxicity increases with dose escalation regardless of
agent
Gastroprotection in patients with risk factors for
gastropathy age > 65, past history of ulcer

Safety Issues - Methotrexate

Hepatotoxicity
Pulmonary toxicity
Bone marrow suppression
Teratogenecity
Although not nephrotoxic lower doses with reduced
renal function

Potential Safety Issues with TNF

Inhibitors
Target Related (general immunomodulatory / TNF Specific)
Infectious / serious infections
Opportunistic infections (eg, TB)
Malignancies (lymphoma, skin, etc)
Demyelinating conditions
Hematologic abnormalities
Congestive heart failure
Autoantibodies (>40% het ANA+, 10% anti-DNA; ACL also seen: however, few other autoantibodies,
and lupus-like syndromes rare)
Hepatotoxicity
Skin reactions / psoriasis

Agent related
Administration reaction
Immunogenicity

Tuberculosis & TNF Antagonists

Latent TB (LTBI): +PPD/-Sxs/-CXR
All TNF inhibitor Rx patients should be evaluated for LTBI with a
tuberculin skin test prior to initiation
Obtain CXR? Not routinely advocated in USA. Do:
*If PPD positive
*If signs/Sxs present
*Recent known TB contact
If latent TB (no signs/Sxs): initiate INH prior to or with TNF
inhibitor therapy
If active TB infection, treat 4 drugs, delay initiation of TNF
inhibitor therapy

Prevention While on TNFi

General precautions
*General infection control
*Manage comorbidities (alcohol and smoking cessation, DM
control, minimize steroid dose)

2006 ACIP Guidelines on Immunizations

*Influenza vaccine every year
*Pneumococcal vaccine
*Meningococcal, Hepatitis B where exposure is likely
*Avoid live-attenuated vaccines (oral polio*, MMR, varicella,
shingles)

Conclusions
Early diagnosis important, which leads to
Early treatment, aggressive if necessary, which leads to

Better outcomes
Communication important between PCP and
rheumatologist

THANK YOU