Definition and Causes:

DEFINITION:

A disease due to chronic inflammation of unknown cause, that affects joints resulting in deformities and functional limitations if not adequately controlled. It can also produce inflammation in other parts of the body and may involve organs such as skin, lungs, heart, and eyes.

CAUSES:

• Rheumatoid arthritis (RA) is an autoimmune condition, in which the body’s immune system begins “attacking” the body itself. There are many different types of autoimmune diseases. In RA the immune system “attacks” the lubricating membrane of joints
• The precise cause is unknown, but there are various factors which may contribute and include:
  • Environmental factors: e.g. smoking
  • Infections: Certain viruses may be involved in causing RA, but is still under research
  • Hormonal factors: Estrogens may have some role to play since females are affected 3 times more than males
  • Genes: Having certain genes may make a person more susceptible to RA, but is still being investigated by researchers
  • Immunological factors: Certain immune cells in our body may be “turned-on” to attack the joints by producing destructive antibodies (called auto-anti-antibodies)

Symptoms:

• Patients may experience gradual onset, with slow progression of the disease
• Symptoms may start from small joints (wrist, hand, feet), but can affect any joint of the body, plus it can also affect other parts/organs such as lungs, heart, and eyes, etc.
• The following signs and symptoms are common:
  • Joint pain
  • Muscle pain
  • Swelling
  • Stiffness
  • Limited joint function
  • Redness around joint
  • Trouble walking
  • Difficulty using hands

No one can predict what symptoms an individual will present with and how severely they will be affected.

Usually, it is recommended that once diagnosed, do not delay the treatment. Disease-Modifying Antirheumatic Drugs referred to as DMARDs, has been proven to halt the progression of the disease and should be initiated early in the disease course.

Investigations and Treatment:

INVESTIGATION:

• It is a combination of history, physical examination, blood tests, and x-rays which enables the doctor to diagnose rheumatoid arthritis
• Several visits are initially required to diagnose the disease

Physical examination:

• Inspection of joints for:
  • Inflammation (warmth and redness of the affected joint)
  • Tenderness
  • Swelling
  • Deformities
  • Firm bumps (nodules) under the skin
  • To determine which joints are involved (small or large)

Blood tests:

• Erythrocyte sedimentation rate (ESR): It is a measure of how fast red blood cells fall to the bottom of a test tube. Assess the extent of inflammation within the body
• C-reactive proteins (CRP): Another method of measuring the degree of inflammation
• Antinuclear antibody (ANA): Frequently found in people with RA
• Rheumatoid Factor (RF): Antibody found in 80% of patients with RA. (Rheumatoid patients in whom RF cannot be found are referred to as seronegative RA)
• Anti-cyclic citrullinated peptide antibody (ACCP): Also found frequently in RA patients

Note: While the above tests may assist with the diagnosis of RA, these tests can also be abnormal in other autoimmune diseases and inflammatory conditions so only these blood tests alone are not sufficient for diagnosis of RA. The diagnosis of RA is based on a combination of clinical presentation, physical examination, blood tests, x-rays, and other imaging techniques.

Imaging:

Various imaging techniques used in arthritis are as follows:

1. X-Rays:

• X-rays can show bone/joint erosions typical seen in RA
• Joint X-rays can also be helpful in monitoring joint damage and disease progression over time

2. Bone scanning:

• A procedure using a small amount of a radioactive substance, used to identify inflamed joints

3. MRI: Used to show joint damage

• An MRI (or magnetic resonance imaging) scan is a radiology technique that uses magnet, radio waves, and a computer to produce images of body structures
• The MRI scanner is a large tube surrounded by a giant circular magnet
• The patient is placed on a moveable bed that is inserted into the magnet
• The image and resolution produced by MRI are quite detailed and can detect tiny changes of structures within the body. For some procedures, contrast agents, such as gadolinium, are used to increase the accuracy of the images

Synovial joint analysis

A needle is inserted into an affected joint, and a small amount of fluid (called synovial fluid) is removed. The fluid is then sent to be analyzed for infection, inflammation (auto-immune disorders), and other chemicals such as uric acid crystals.

TREATMENT:

Treatment objective would be to help:

• Relieve signs and symptoms
• Slow down the disease progression
• Improve patient quality of life
• Achieve a remission or low disease activity

Treatment involves:

1. Use of medication
2. Non-medical strategies
3. Surgical interventions

Medications:

• Patients are treated based on their symptoms. Undiagnosed individuals with possible RA, should be seen as soon as possible by a rheumatologist, or other healthcare professional trained or experienced in RA, for definitive diagnosis and treatment
• Treatment approach has undergone major changes over the past years:
• Nonsteroidal anti-inflammatory (NSAIDs) – see below
  • NSAIDs (e.g. ibuprofen, naproxen, etc.) are only beneficial for relief of symptoms
  • NSAIDs have no effect on disease progression

1. Analgesic – Nonsteroidal anti-inflammatory drugs (NSAIDs):

• Recommended for relief of symptomatic pain and inflammation (if present)
• No longer used as the sole first-line agent for RA
• There are many different types of NSAIDs which act in different ways (i.e. different mechanisms of action)
• Some examples of NSAIDs are shown below. Note that NSAIDs are separated into different groups based on the way they work on the disease

2. Analgesic (non-NSAID)

• Tylenol (acetaminophen)

3. Disease-modifying antirheumatic drugs (DMARDs):

DMARDs are usually started immediately for patients with active disease.

• Active RA patients require frequent monitoring (every 1-3 months)
• Patients with well-controlled disease may be monitored less frequently
• DMARD therapy usually adjusted every 3-6 months, to achieve treatment goals

Types of DMARDs:

Two main types: Non-Biologic DMARDs and Biologic DMARDs

I. Non-Biologic DMARDs:

• Usually chosen as initial therapy due to the rapid onset of action and less toxicity (side effects)
• Examples include:

• Methotrexate (MTX):
  • Most preferred of all the DMARDs
  • Most patients treated with MTX exhibit clinical and radiological improvement, a change in therapy should be considered in patients with radiographic progression despite the adequate clinical response

Note: Some type of steroids called glucocorticoids (e.g. prednisone) may be used for flare-ups while initiating or waiting for DMARDs to take effect. Lowest possible effective steroid dose for a shorter period is suggested.

• Combination therapy with DMARDs may be used if:
  • Moderate to high disease activity in newly diagnosed patients
  • Poor or weak response to a single drug
  • Methotrexate is often used as an “anchor” agent

II. Biological DMARDs:

These drugs work on different areas of the immune system to help suppress immune activity. The reduced immune activity slows down the attack on the joints thereby reducing inflammation, joint damage, and disease progression.

The immune system is very complex and involves interaction between 2 types of white blood cells (T cells and B cells), and the chemicals/molecules that they make (e.g. Interleukin). These drugs are designed to deplete or reduce some types of immune cells OR inhibit or oppose (antagonize) the action of these cells or their chemical activity.

Sometimes patients may require to switch to biological agents. This is often recommended if:

• At least 2 non-biological DMARDs (including MTX), have failed to control disease activity with a single drug or combination therapy after 3 months of achieving the required target dose.
• Some examples of these DMARDs and where they may work in the immune system is shown below:

NOTE: While there are potential side effects from using these medications, there are also the effects of untreated RA – which include disease progression with increasing pain and joint damage leading to decreased mobility and overall poor quality of life. Consequently, the treating physician will assess the side effects risks versus the benefits in controlling symptoms and improving quality of life (risk versus benefit ratio), before recommending treatment. If the patient has other medical conditions or using other medications, these are taken into account when prescribing medications. The patient is advised to take note of and report potential side effects to the treating physician.

Non-Pharmacological Interventions:

Supportive measures

• Nutrition
• Rest
• Physical measures
  • Joint splinting
  • Orthopedic or athletic shoes
  • Exercises
  • Heat and cold therapy
  • Paraffin baths
  • Massage

Surgical interventions:

• Tendon reconstruction, joint fusion, and joint replacement are potential treatment modalities to prevent disability in advanced RA

Follow-up recommendations:

• The treating physician may recommend regular follow up visits to discuss i.e. any improvement, worsening or side effects of medications, such as prolonged steroid use (e.g. prednisone) could lead to osteoporosis, diabetes, and hypertension. Regular screening for these conditions may include blood work (for blood sugar) as well as bone density assessments
• The physician will evaluate any change in health, as well as the patient’s adherence to the treatment. He will require knowing if the patient has received any additional prescription by any other source, or use of herbal medication, etc.

Prognosis

The following factors suggest that the treatment might be challenging with the likelihood of poor outcome:

• Early or advanced age at disease onset
• Persistent moderate to severe disease
• Multiple joints affected
• Blood work showing the presence of antibodies called: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACCP) antibody
• X-ray evidence of early advanced joint disease with or without symptoms

50% of patients may have difficulty with continuing on with their primary job within 10 years of onset.

Risk Factors and Prevention:

Risk Factor Management:

• Obesity
• Inactive lifestyle
• Family history of disease
• Age – more common in individuals over 65
• Joint trauma
• Diet – certain food types are felt to help reduce the disease burden. These include foods rich in anti-oxidants, oils (omega 3 and 6), may be helpful for some. Folic acid supplementation is important for those patients using methotrexate

To reduce the risk of arthritis individual should:

• Maintain a healthy weight
• Exercise regularly
• Take appropriate measures to minimize sport injury
• Ensure diet contains necessary vitamins and minerals (e.g. folate, omega3, and calcium)

Outcome:

• Most cases of arthritis are incurable and are treated to minimize the impact on everyday life in an effort to improve the quality of life
• Chronic cases will require lifelong treatment