Rheumatoid Arthritis (RA)
Overview
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by symmetrical
inflammatory polyarthritis, primarily affecting the small joints of the hands and feet. Over time,
persistent inflammation leads to joint destruction, deformity, and functional disability, significantly
impairing quality of life.
These notes are structured for medical, nursing, and health science students, using clear headings,
concise explanations, and exam‑relevant detail.
Definition
Rheumatoid arthritis is a chronic autoimmune disease in which the immune system mistakenly attacks
synovial joints, resulting in inflammation, cartilage destruction, bone erosion, and extra‑articular
manifestations.
Etiology
The exact cause of RA is unknown. It is considered a multifactorial disease involving genetic susceptibility,
environmental triggers, and immune dysregulation.
1. Genetic Factors
• Strong association with HLA‑DR4 and HLA‑DR1 alleles (Class II MHC)
• Increased risk among first‑degree relatives
2. Environmental Factors
• Cigarette smoking (strongest known risk factor)
• Infections: Epstein‑Barr virus, Porphyromonas gingivalis
• Pollution and occupational exposures (e.g., silica)
3. Immune System Dysregulation
• Loss of immune tolerance to self‑antigens
• Activation of B cells and T cells
• Production of autoantibodies:
• Rheumatoid Factor (RF)
• Anti‑cyclic citrullinated peptide antibodies (anti‑CCP)
• Cytokine release (TNF‑α, IL‑1, IL‑6) causes synovial inflammation, pannus formation, and joint
destruction
1
, Pathophysiology
An environmental trigger (e.g., smoking or infection) initiates an autoimmune response in genetically
predisposed individuals, leading to chronic synovial inflammation.
Phases of Disease Development
Phase I: Interaction between genetic and environmental risk factors
Phase II: Production of RF and anti‑CCP antibodies
Phase III: Arthralgia and joint stiffness
Phase IV: Early arthritis (1–2 joints) - Intermittent form: Palindromic rheumatism
Phase V: Established rheumatoid arthritis
RA may also present with extra‑articular manifestations affecting the skin, lungs, heart, eyes, and blood
vessels.
Pathoanatomy of RA
Key pathological events include: - Antigen–antibody reactions - Microvascular proliferation and obstruction -
Synovial pannus formation with intimal hyperplasia - Cartilage destruction and bone erosion - Joint
subluxation and ankylosis - Tenosynovitis and tendon rupture
Risk Factors
• Age: Risk increases with advancing age
• Sex: More common in females
• Genetics
• Environmental exposure
• Smoking
• Infections (e.g., EBV, hepatitis C)
• Psychological stress and childhood trauma
Clinical Presentation
Early/Systemic Features
• Fever
• Malaise
• Fatigue
• Arthralgia
2
Overview
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by symmetrical
inflammatory polyarthritis, primarily affecting the small joints of the hands and feet. Over time,
persistent inflammation leads to joint destruction, deformity, and functional disability, significantly
impairing quality of life.
These notes are structured for medical, nursing, and health science students, using clear headings,
concise explanations, and exam‑relevant detail.
Definition
Rheumatoid arthritis is a chronic autoimmune disease in which the immune system mistakenly attacks
synovial joints, resulting in inflammation, cartilage destruction, bone erosion, and extra‑articular
manifestations.
Etiology
The exact cause of RA is unknown. It is considered a multifactorial disease involving genetic susceptibility,
environmental triggers, and immune dysregulation.
1. Genetic Factors
• Strong association with HLA‑DR4 and HLA‑DR1 alleles (Class II MHC)
• Increased risk among first‑degree relatives
2. Environmental Factors
• Cigarette smoking (strongest known risk factor)
• Infections: Epstein‑Barr virus, Porphyromonas gingivalis
• Pollution and occupational exposures (e.g., silica)
3. Immune System Dysregulation
• Loss of immune tolerance to self‑antigens
• Activation of B cells and T cells
• Production of autoantibodies:
• Rheumatoid Factor (RF)
• Anti‑cyclic citrullinated peptide antibodies (anti‑CCP)
• Cytokine release (TNF‑α, IL‑1, IL‑6) causes synovial inflammation, pannus formation, and joint
destruction
1
, Pathophysiology
An environmental trigger (e.g., smoking or infection) initiates an autoimmune response in genetically
predisposed individuals, leading to chronic synovial inflammation.
Phases of Disease Development
Phase I: Interaction between genetic and environmental risk factors
Phase II: Production of RF and anti‑CCP antibodies
Phase III: Arthralgia and joint stiffness
Phase IV: Early arthritis (1–2 joints) - Intermittent form: Palindromic rheumatism
Phase V: Established rheumatoid arthritis
RA may also present with extra‑articular manifestations affecting the skin, lungs, heart, eyes, and blood
vessels.
Pathoanatomy of RA
Key pathological events include: - Antigen–antibody reactions - Microvascular proliferation and obstruction -
Synovial pannus formation with intimal hyperplasia - Cartilage destruction and bone erosion - Joint
subluxation and ankylosis - Tenosynovitis and tendon rupture
Risk Factors
• Age: Risk increases with advancing age
• Sex: More common in females
• Genetics
• Environmental exposure
• Smoking
• Infections (e.g., EBV, hepatitis C)
• Psychological stress and childhood trauma
Clinical Presentation
Early/Systemic Features
• Fever
• Malaise
• Fatigue
• Arthralgia
2
