Rheumatoid Arthritis
What is arthritis?
The word “arthritis” means “joint inflammation.” It is an umbrella term referring to more than 100 different medical conditions.
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These conditions affect the musculoskeletal system, specifically the joints. The cause of Rheumatoid Arthritis (RA) is not completely understood.
RA is an autoimmune disorder that affects approximately 1% of the population. About 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 characterized by chronic joint inflammation that can result in joint destruction and long-term disability.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?
There is no “gold standard” for diagnosing RA. Currently, the diagnosis of RA relies heavily on clinical parameters established by the American College of Rheumatology (ACR). The ACR criteria for diagnosing RA were last updated in 1987. These criteria are relatively insensitive, particularly in the earlier stages of the disease. Disease progression may be significant even before a diagnosis is made.
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
These tests are not specific for RA; but used together provide clinical information as an aid in the diagnosis of RA.
Current challenges in diagnosis and treatment of RA
RF testing is considered especially important in the diagnosis of RA, and is included in major guidelines. RF is present in about 80% of patients with established RA
However …
- RF is present in 10 – 15% of healthy individuals
- RF can be present in other inflammatory diseases
- A negative RF test does not definitively rule out RA (e.g., early disease, possible remission phase, etc.)
- Only 50% of RA patients are RF positive in the first 6 months of illness
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, and decrease pain.
| Progression of hand RA | ||
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| Year 1 | Year 6 | Year 8 |
Early detection allows early, aggressive treatment
Early detection and treatment are critical to improved outcomes.
What is Anti-CCP?
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), and AKA (‘anti-keratin’ autoantibodies).
Citrulline is a “non-standard” amino acid. There are 20 “standard” amino acids used by the body to make proteins. Arginine, a standard amino acid, is converted into citrulline by several enzymes that are present in the synovium of inflamed joints in RA patients. Many patients with RA develop an immune response against these proteins containing citrulline.
Adapted from: Vossenar ER Clin Applied Imm Rev 2004;4:239-262
What the potential role of Anti-CCP in the Diagnosis and Management of RA?
The American College of Rheumatology (ACR) last updated the classification criteria for diagnosing RA in 1987. Anti-CCP was not available when the criteria were last updated. In early RA, many patients exhibit mild, nonspecific symptoms and may not meet the ACR criteria. Using Anti-CCP may aid in the diagnosis of RA.
A recent study by Liao et al, evaluated the 1987 ACR guidelines. The authors concluded that adding anti-CCP as a diagnostic criterion and removing rheumatoid nodules and radiographic changes from the criteria improved sensitivity regardless of symptom duration. More importantly, adding anti-CCP testing greatly improved sensitivity in patients with symptoms < 6 months (25% with 1987 criteria vs. 63% with proposed study criteria).
Adapted from: Liao et al Ann Rheum Dis2008;67;1557-1561
European League Against Rheumatism (EULAR) Recommendations
EULAR recommends including anti-CCP in the detection and evaluation of RA. 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
A study evaluating the cost effectiveness of adding anti-CCP testing to the ACR criteria concluded, “Taken together, anti-CCP is likely to be a very cost effective or even cost saving diagnostic complement in early diagnosis of RA for patients with undifferentiated arthritis (UA). This is especially true when considering indirect costs.” Indirect costs were based on diminished productivity as a result of job loss due to disability.
Adapted from: Konnopka et al Ann-Rheum-Dis; 67: 1399-405.
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 are critical to minimize joint destruction.