Rheumatoid Arthritis Overview

Rheumatoid Arthritis Lecture Notes

• Rheumatoid arthritis (RA) is a chronic autoimmune disease.
• It causes inflammation and destruction of joints.
• Synovial joints (often hands, wrists, and feet) are primarily affected.
• RA is a systemic condition and cannot be cured.

Objectives

• Define RA with key terms
• Explain RA pathogenesis and the immune response.
• Identify potential drug targets for RA treatment.
• Describe RA drug treatments.
• Define disease-modifying antirheumatic drugs (DMARDs) and explain their mechanisms.

What is Rheumatoid Arthritis?

• Common chronic autoimmune disease.
• Causes inflammation and joint destruction (arthropathy).
• Synovial joints (primarily hands, wrists, and feet) are targeted by the disease.
• RA is a systemic condition.
• It cannot be cured.

Normal Joint Structure

• Articular cartilage acts as a shock absorber.
• Facilitates friction-free joint movement.
• Synovial membrane secretes synovial fluid.
• Synovial fluid nourishes cartilage and cushions the bones.
• Synovial membrane is not innervated.

Pathophysiology of RA

• Articular symptoms are common in RA
• Non-articular components can also occur (systemic).

Articular Symptoms of RA

• Painful, warm, and swollen joints
• Three or more involved joints
• Stiffness for >30 minutes in the morning

Joints Commonly Involved in RA

• Hands and feet (MCP, PIP, MTP joints—90%)
• Knees, ankles, and wrists (80%)
• Shoulders (60%)
• Elbows (50%)
• Acromioclavicular and sternoclavicular joints (30%)

Other Joints in RA

• Cervical spine - instability can impinge on the spinal cord.
• Thoracolumbar, sacroiliac, and distal interphalangeal joints (DIPs) are not typically involved.

Stages of RA

• Early stage - involves joint swelling and pain
• Late stage - characterized by joint deformity (boutonniere and swan-neck deformities)

Non-articular Features of RA

• Rheumatoid nodules (firm tissue bumps on the arms)
• Inflammation in other organ systems (Eyes, Lungs, Heart)
• Blood dyscrasias (anemia)
• Symptoms like fatigue, fever, and tiredness.

Impact of RA

• Age of onset typically younger (40-50 years), but older (70) is possible.
• ~ 1% of the UK population is affected.
• 12,000 patients under 16 years of age are also affected.
• Significant NHS and UK economic costs; approximately £560 million and £3.8-4.75 billion respectively annually. (NICE guidelines)
• Poor prognosis, ~33% risk of severe disability and 3-18 years shortened life expectancy on average.

Pathophysiology of RA (detailed view with diagram)

• Normal joint structure and inflamed joint structure are visually presented
• Illustrates synovial membrane hyperplastic changes and the involvement of various cells (neutrophils, plasma cells, B cells, T cells).
• Diagram shows initial and advanced RA pathologies.

Untreated RA Causes Joint Damage

• Untreated inflammation leads to significant joint damage as highlighted in the visual progression of damaged joints over time.

Signalling Pathways in RA

• Pathway involving cytokines (e.g., IL-1, TNF-α, IL-6) and cell types (macrophages, T cells, osteoclasts).
• Pathway explains important inflammatory cytokines implicated in RA.
• Pathway provides insight into the link between inflammation, cartilage/bone erosion and the progression of RA.

Auto-antibodies in RA

• Activation of B cells and production of autoantibodies like rheumatoid factor (RF).
• Presence of RF doesn't always indicate RA (can be normal in some).
• Anti-citrullinated protein antibodies (anti-CCP) are significant in RA diagnosis due to high specificity (90%).

Causes of RA

• Genetic predisposition (first-degree relatives at higher risk).
• Environmental factors (smoking, hormones, infection, geography, diet)

Diagnosis of RA

• Physical exam and blood tests (FBC, CRP, ESR/RF, anti-CCP).
• Imaging techniques (X-ray and MRI).

Drug Therapy for RA

• Immunosuppressants (methotrexate)
• Anti-TNF agents
• Glucocorticoids
• DMARDs. (sulfasalazine, penicillamine, gold compounds, chloroquine).

This quiz covers key concepts related to rheumatoid arthritis, including its definition, pathogenesis, and treatment options. Participants will explore the systemic nature of the disease and understand the significance of disease-modifying antirheumatic drugs. Prepare to deepen your knowledge of this chronic autoimmune condition.