Rheumatoid Arthritis
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Introduction
RA is a chronic, inflammatory, systemic disease of unkown etiology characteriezed by a symmetric arthrolpathy and variable symptoms outside the joints.
What's the difference between a rheumatologist and an urologist? In rheumatology, morning stiffness is a bad thing.
The Case of...
a simple case introducing clincial presentation and calling for a differential diagnosis to get students thinking.
Causes and Risk Factors
Prevalence between 0.3-2%
prevalence 2.5x higher in women
RA can occur at any age, but peak is between 30-60
worldwide distribution All races affected
some native populations have prevalence as high as 5-6%
family history: first degree relative gives 16x increase in risk
Pathophysiology
Host susceptibility, likley in interaction with environmental factors, leads to an immune response and chronic inflammation.
Synovium is critical in disease initiation and progression. Synovium in RA undergoes massive tissue proliferation, with high cellularity. The intima undergoes hyperplasia and becomes 5-6 cells thick, while the sub-intima becomes filled with lymphopid cell aggregates. These cells are nearly immuno-competent, with B, T, plasma, and antigen presenting cells.
These cells can directly invade adjacent tissues, including cartilage and bone, resulting in radiographic erosiions, as well as mkae circulating factors: cytokines, prostaglandins, MMPs, etc
Cytokines include:
T-Cells
- IL-2
- IL-3
- TNF-alpha
macrophages/type A synoviocytes
- Il-1
- IL-6
- IL-8
- TNF-alpha
pan carpal disease can result in subluxation of all bones in the joint.
Signs and Symptoms
Inflammatory process distinguished from degenerative osteoarthritis in a number of ways.
- history
- physical exam
History
Hours of morning stiffness
many joints often involved, with symmetry
Physical Exam
swelling and warmth in joint
reheumatoid nodules which are squishy, rather than hard like in OA
Boutenierre's and swan-neck deformities can occur over the years.
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
Approximately 75% of people with RA have a positive RF, though in early disease, the RF can be negative. High levels tend to suggest aggressive disease
Antibodies to cyclic citrillated peptides - proteins that contain citrulline are the target of an autoantibody that is highly specific (up to 97%)for RA. Sensitivities are 50-70%. They can be elevated in early disease when RF is still negative. Antibodies are detected via ELISA.
Anti-CCP is a new, sensitive test.
Diagnostic Imaging
X-ray
Differential Diagnosis
Treatments
Goals of treatment include slowing progression, treating pain, and preserving function.
RA options: MTX still first-line
Clinical question
Which disease-modifying antirheumatic drugs are more effective and safer for rheumatoid arthritis?
Bottom line
Research guiding the choice of disease-modifying antirheumatic drugs
(DMARDs) for the treatment of rheumatoid arthritis (RA) is incomplete,
and current recommendations are generally made on the basis of
short-term studies and extrapolated studies rather than on the evidence
from any head-to-head comparisons. There is no clear advantage of the
dramatically more expensive new drugs over methotrexate regarding
benefit or adverse effects, though they may offer a benefit when
combination therapy is needed. Specific conclusions regarding
individual and combination treatments are listed in the synopsis below.
Biologic Agents
etanercept
infliximab
Consequences and Course
Mortality rates in people with RA are higher, though people die of the same types of events.
Resources and References
Topic Development
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