Rheumatoid Arthritis

 

RA is a chronic, inflammatory, systemic disease of unkown etiology characteriezed by a symmetric arthrolpathy and variable symptoms outside the joints.

 

 

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

 

 

Signs, Symptoms, and Diagnosis

  • History
  • Physical Exam
  • Lab Investigations

History

 

 

 

Physical Exam

Lab Investigations

 

Anti-CCP is a new, sensitive test.

Inflammatory process distinguished from degenerative osteoarthritis in a number of ways,

 

Hours of morning stiffness

many joints often involved, with symmetry

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.

 

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.

 

X-ray

pan carpal disease can result in subluxation of all bones in the joint.

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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

macrophages/type A synoviocytes

 

 

 

 

 

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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. (LOE = 1a)

Reference
Donahue KE, Gartlehner G, Jonas DE, et al. Systematic review: Comparative effectiveness and harms of disease-modifying medications for rheumatoid arthritis. Ann Intern Med 2008;148(2):124-134

Study design: Systematic review

Funding: Government

Allocation: N/A

Setting: Various (meta-analysis)

Synopsis
Despite an RA prevalence of 2 million patients in the United States alone, comparative studies that evaluate the relative benefit of different DMARDs as initial therapy or different combinations are scant. The researchers conducting this systematic review identified controlled trials and prospective cohort studies by searching 4 databases, including the Cochrane Library. Two researchers independently selected studies for inclusion and the results were abstracted and then validated by a third researcher. They relied on meta-analyses if already available but did not otherwise combine the data. The research included the synthetic DMARDs leflunomide, methotrexate, and sulfasalazine, and also the uber-expensive biologic antitumor necrosis factor (anti-TNF) agents adalimumab, etanercept, and infliximab. Most studies were of relatively short duration and enrolled highly selected populations. Here are their results (with extrapolation across studies when no direct comparisons exist): Single drug treatment: - Overall data of low to moderate quality did not identify a major difference among the synthetic DMARDs, though leflunomide may offer a slight benefit over sulfasalazine. Rates of adverse effects and discontinuation rates were similar among the 3 drugs. - Current research shows no difference among the anti-TNF agents and there is insufficient study of relative harms to draw any conclusions. As a group, the anti-TNF agents seem to produce better response than anakinra. - The anti-TNF agents show no benefit over methotrexate with regard to clinical outcomes, though they may be more likely to prevent radiographic progression in patients with early RA (number needed to treat = 8). Combination therapy: - Starting with combination therapy with combination synthetic DMARDs offers greater benefits than single drug or step-up therapy. - Adding prednisone to 1, 2, or 3 synthetic DMARDS improves clinical response rates and slows progression as compared with single drug therapy. - Adding methotrexate to anti-TNF therapy improves clinical response, functional capacity, and quality of life as compared with either methotrexate alone or anti-TNF treatment alone..The effect is not the same when sulfasalazine is added to anti-TNF treatment. - Adding anakinra to etanercept offers no additional benefit. Combination anti-TNF agents increase adverse effects.

 

 Biologic Agents

etanercept

infliximab

 

 

 

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Consequences and Course

Mortality rates in people with RA are higher, though people die of the same types of events.

 

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The Patient

 

 

 

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Health Care Team

 

What's the difference between a rheumatologist and an urologist? In rheumatology, morning stiffness is a bad thing.

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Community Involvement

 

 

 

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References