Rheumatoid Arthritis

Question 1

RA

Answer 1

• inflammatory chronic disease
• systemic
• progressive
• heterogenous
• complex

Question 2

Symptoms

Answer 2

More prevalent in women than men
- pain
- swelling
- tenderness
- morning stiffness
- symmetrical

Question 3

Pathophysiology

Answer 3

1. Initiation and Autoimmune Response:
   Genetic and Environmental Triggers: RA is influenced by genetic predispositions (e.g., HLA-DR4 and HLA-DR1 alleles) and environmental factors like smoking and infections, which may trigger an abnormal immune response.
   Autoantibodies Production: The immune system mistakenly identifies components of the body as foreign, leading to the production of autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs).
   Citrullination: Inflammatory processes lead to the modification of proteins through citrullination, altering their structure and making them appear foreign to the immune system.
2. Synovial Inflammation (Synovitis):
   Inflammatory Cell Infiltration: The synovial membrane becomes infiltrated with T cells, B cells, macrophages, and dendritic cells, leading to the secretion of pro-inflammatory cytokines (e.g., TNF-α, IL-1, IL-6).
   Cytokine Storm: These cytokines promote a cycle of chronic inflammation and further recruitment of immune cells, amplifying the immune response.
   Angiogenesis: New blood vessels form within the synovium, supplying oxygen and nutrients to the growing mass of inflammatory tissue.
3. Formation of Pannus:
   Pannus Development: The chronic inflammation leads to the formation of pannus, an abnormal layer of fibrovascular or granulation tissue.
   Aggressive Tissue Growth: The pannus invades and erodes adjacent cartilage and bone due to the activity of osteoclasts activated by cytokines like RANKL.
   Joint Destruction: This erosion damages the joint structure, leading to the loss of cartilage and bone, causing pain, deformity, and impaired function.
4. Chronic Joint and Systemic Effects:
   Destruction of Joint Structures: Continued inflammation and pannus formation result in joint stiffness, swelling, and deformity.
   Systemic Manifestations: RA is a systemic disease, so it can involve other organs, leading to complications such as rheumatoid nodules, vasculitis, lung disease, and an increased risk of cardiovascular disease.
   Fatigue and Anemia: Chronic inflammation can result in systemic effects such as fatigue and anemia of chronic disease due to the ongoing production of inflammatory cytokines.
5. Progression and Remission:
   Flare-ups and Remissions: RA often follows a pattern of flares and remissions, where periods of increased symptoms alternate with times of reduced activity.
   Joint Deformities: Over time, without effective treatment, permanent joint deformities and disability can develop.
   Summary of Key Pathological Features:
   Immune dysregulation: T cells, B cells, and cytokines play critical roles.
   Chronic inflammation: Synovitis leading to pannus formation.
   Joint destruction: Cartilage and bone erosion.
   Systemic impact: Beyond joints, RA affects other organ systems.
   Treatment of RA focuses on reducing inflammation, slowing disease progression, and managing symptoms through disease-modifying antirheumatic drugs (DMARDs), biologics targeting specific immune mediators, and anti-inflammatory agents.

Question 4

Early RA

Answer 4

• mild swelling of the metacarpophalangeal joints and proximal interphalangeal joints

Question 5

Established RA

Answer 5

• deformities including subluxation at the metacarpophalangeal joints, deformities of several fingers and a deformity of the thumb

Question 6

Extraarticular symptoms

Answer 6

• general sense of being unwell
• fibromyalgia
• rheumatoid nodules
• rheumatoid vasculitis
• rheumatoid lung disease
• CVD

Question 7

Diagnosis

Answer 7

• clinical history
• blood tests
• x-rays/ MRI

Question 8

Risk Factors

Answer 8

• sex
• genetic background
• infections
• epigenetics
• smoking
• dust inhalation
• microbiota
  -obesity
• mortality