Rheumatoid Arthritis
What is arthritis?
The word “arthritis” means “joint inflammation” and it is an umbrella term referring to more than 100 different medical conditions.
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All of these conditions affect the musculoskeletal system and specifically the joints. The cause of RA is not completely understood.
Rheumatoid Arthritis (RA) is an autoimmune disorder affecting approximately 1% of the population. Approximately 75% of people with RA are women, with an onset peak between 20 and 45 years of age – but can occur in children, teenagers, and older adults.
RA is a chronic inflammatory disease that can result in joint destruction, disability, deformity, and even premature death. It is a leading cause of disability, and more than 50% of people with RA completely stop working within 10 years of disease onset. In RA, the body’s immune system attacks the joint and surrounding structures.White blood cells enter the synovial space of the joint and activate the immune system, contributing to the destruction of cartilage, bone, and other tissues.
How is RA diagnosed?
Currently, the diagnosis of RA relies heavily on clinical parameters established by the American College of Rheumatology (ACR). These criteria are relatively insensitive. Disease progression may be significant before a diagnosis is made. There is no “gold standard” for diagnosing RA.
Many different laboratory tests are ordered when a physician is trying to diagnose (or rule out) RA. They include:
- Rheumatoid factor (RF) – a marker for autoimmune activity
- Erythrocyte sedimentation rate (ESR) – a marker for inflammation
- C-reactive protein (CRP) – a marker for inflammation
- Liver enzyme levels
- Complete blood cell count (CBC), urinalysis, creatinine, and electrolyte levels
None of these tests are very specific for RA, but used together provide clinical information to be used in the diagnosis.
Current challenges in diagnosis and treatment of RA
RF testing is considered especially important in the diagnosis of RA (included in major guidelines).
RF is present in about 80% of patients with established RA (i.e., good sensitivity).
However …
- RF is present in 10 – 15% of healthy individuals
- RF is present in other inflammatory diseases
- A negative RF test does not definitively rule out RA (e.g., early disease, possible remission phase, etc.)
Disease outcome can vary from mild symptoms to severe, systemic disease and joint destruction. The main goals in managing RA are to prevent or control joint damage, prevent loss of function, decrease pain.
| Progression of hand RA | ||
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| Year 1 | Year 6 | Year 8 |
| Adapted from (09/21/2006): www.cco.caltech.edu/~sciwrite/journal03/A-L2/Jacobi.html | ||
Early detection allows early, aggressive treatment
What is Anti-CCP and what is its potential role in the diagnosis and management of RA?
Anti-CCP is the name given to a family of auto-antibodies directed against citrulline-containing proteins. These antibodies are also known by other names, such as APF (anti-perinuclear factor), AFA (anti-filaggrin autoantibodies), AKA (‘anti-keratin’ autoantibodies).
What is citrulline?
Citrulline is a “non-standard” amino acid. Amino acids are the “building blocks” of proteins in the body. 20 “standard” amino acids used by the body to make proteins. Citrulline is made by the modification of the standard amino acid arginine, and several proteins are known to contain citrulline. Many patients with RA develop an immune response against proteins containing citrulline.
Adapted from: Vossenar ER Clin Applied Imm Rev 2004;4:239-262
What is anti-CCP-1? Anti-CCP-2?
Anti-CCP 1*
* (Anti-CCP 1 assays are no longer available – when reading papers, be careful to notice what version of anti-CCP assay was used) |
Anti-CCP 2
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| Adapted from: Vossenar ER Clin Applied Imm Rev 2004;4:239-262 | |
A good disease marker should be sensitive and highly specific for the disease, detectable very early in the disease, useful for predicting disease outcome.
European League Against Rheumatism (EULAR) Recommendations
In every patient presenting with early arthritis to the rheumatologist, the following factors predicting persistent and erosive disease should be measured by:
- Number of tender and swollen joints
- ESR or CRP
- Levels of rheumatoid factor and anti-CCP antibodies
- Radiographic erosions
Summary
Rheumatoid arthritis (RA) is a common autoimmune disorder that can cause joint destruction and deformity. RA is a leading cause of disability around the world. Currently, diagnosis of RA relies heavily on clinical symptoms. Disease progression may be significant before a diagnosis is made. Early diagnosis and treatment of RA is critical to minimize joint destruction.
