Rheumatoid Arthritis (RA)

Question 1

Rheumatoid Arthritis (RA)
Etiology and Pathophysiology

Answer 1

Chronic, systemic autoimmune disease
• Inflammation of connective tissue in diarthrodial (synovial) joints
• Periods of remission and exacerbation
• Extraarticular manifestations
• Autoimmune etiology: Genetics and environmental triggers

Question 2

Etiology and Pathophysiology

Answer 2

Antigen triggers formation of abnormal immunoglobulin G (IgG)
• Autoantibodies develop against the abnormal IgG: Rheumatoid
factor (RF)
• Rheumatoid factor combines with IgG immune complexes →
deposit on synovial membranes or cartilage in joints →
activates complement → inflammatory response
• Neutrophils → proteolytic enzymes → damage cartilage and
thicken synovial lining

Question 3

Etiology and Pathophysiology continued…

Answer 3

T helper cells (CD4) activated → stimulate monocytes,
macrophages, and synovial fibroblasts → secrete
proinflammatory cytokines
• Interleukin-1 (IL-1)
• Interleukin-6 (IL-6)
• Tumor necrosis factor (TNF)
• Genetic link
• Higher incidence in identical twins
• HLA-DR4 and HLA-DR1 antigens
• Smoking increases risk in patients genetically predisposed

Question 4

Etiology and Pathophysiology

Answer 4

Stage I: Early
• Stage II: Moderate
• Stage III: Severe
• Stage IV: Terminal

Question 5

Clinical Manifestations

Answer 5

Onset typically insidious
• Fatigue, anorexia, weight loss, generalized stiffness
• May report history of precipitating event
• Infection, stress, exertion, childbirth, surgery
• Specific articular involvement: Pain, stiffness, limitation of
motion, and signs of inflammation
• Symptoms occur symmetrically
• Most often affects small joints. Larger joints and cervical spine
may be involved

Question 6

Diagnostic Studies

Answer 6

Laboratory studies
• Rheumatoid factor (RF)
• Erythrocyte sedimentation rate (ESR)
• C-reactive protein (CRP)
• Antinuclear antibody (ANA)
• Anti-citrullinated protein antibody (ACPA)
• Synovial fluid analysis
• X-rays of involved joints
• Bone scan