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Rheumatoid Arthritis — Pathophysiology, Manifestations, Diagnosis, and Management (Summary from lecture)

Pathophysiology of Rheumatoid Arthritis

  • Rheumatoid arthritis (RA) is an autoimmune disease, unlike osteoarthritis which is primarily wear-and-tear degeneration. The immune system fails to distinguish self from non-self, leading to antibodies attacking joint cells.
  • Key consequence: inflammation inside the joint with standard inflammatory signs (heat, redness, swelling, pain).
  • Autoimmune and immune system involvement:
    • Formation of rheumatoid factors and immunoglobulins; involvement of both innate and adaptive immune responses.
    • B cells and T cells participate; autoantibodies include rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA).
    • Immune complexes form and contribute to inflammation within the joint.
    • Cytokines, macrophages, mast cells, and neutrophils migrate to the joint and amplify inflammation; angiogenesis (new blood vessel formation) occurs in the joint.
  • Disease course:
    • RA is characterized by periods of remission (symptoms settle or disappear) and exacerbations (flare-ups) where inflammation and pain worsen.
    • Remission does not mean the disease is cured; it can flare up again.
  • Systemic nature and symmetry:
    • RA is a systemic disease, often bilateral (e.g., both hands) rather than unilateral.
    • It can affect other organs beyond the joints (heart, kidneys, lungs, skin, etc.).
  • Joint pathology specifics:
    • Inflammation within the joint leads to recruitment of inflammatory cells and formation of pannus (abnormal granulation tissue) in the joint space.
    • Pannus formation is driven by synovial hyperplasia and immune cell invasion; it invades and damages articular cartilage and subchondral bone.
    • This process is distinct from the cartilage degeneration seen in osteoarthritis.
  • Cellular and molecular players:
    • Synovial lining cells proliferate (synovial hyperplasia) and fibroblast-like synoviocytes contribute to pannus formation.
    • Osteoclasts (RANKL-mediated) and osteoblasts regulate bone resorption and formation, contributing to bone erosion and potential deformities.
    • Macrophages, mast cells, neutrophils, and other immune cells secrete cytokines and enzymes that propagate inflammation and tissue damage.
    • RANKL (receptor activator of nuclear factor kappa-Β ligand) links to osteoclast activity; osteoclasts resorb bone, osteoblasts lay down new bone; imbalance favors erosion.
  • Synovial membrane and joint space changes:
    • Synovial membrane (synovial sites) becomes inflamed and proliferates; synovial fibroblast-like cells drive hyperplasia and pannus formation.
    • The pannus tissue forms within the joint space, containing inflammatory cells and enzymes that degrade cartilage and bone.
    • In RA, excessive pannus and inflammatory mediators lead to joint destruction, instability, and possible ankylosis (joint fusion) and deformity.
  • Flow of pathophysiology (conceptual):
    • B cells produce autoantibodies (RF, ACPA) → immune complexes form → T cells and cytokines activate macrophages/mast cells/neutrophils → synovitis with pannus formation → synovial hyperplasia and extracellular matrix tissue invade cartilage/bone → enzymes and mediators damage cartilage and bone → joint deformity and potential ankylosis • cycle can vary in timing and degree depending on disease stage and flare status.
  • Diagrammatic emphasis (described): inflammation of the synovial membrane leads to increased synovial fluid and proliferation of synovial cells, producing pannus tissue containing inflammatory cells; pannus and inflammatory mediators destroy articular cartilage and underlying bone, potentially causing fixation and deformity.
  • Genetic and molecular influences:
    • Genetics plays a significant role; HLA-DRB1 alleles are linked to RA susceptibility.
    • The interaction of B cells, T cells, RF, and ACPA contributes to immune complex formation and disease progression.
    • The balance of osteoclast and osteoblast activity (via RANKL) influences bone erosion versus formation.
  • Notable nuances:
    • The degree to which each pathway contributes to exacerbation varies with time and disease stage; there is not a strictly linear sequence of events.
    • Exacerbations are associated with increased synovitis, synovial hyperplasia, enhanced pannus formation, and more granulation tissue and fibrosis, leading to enzyme release, cartilage damage, joint instability, and potential ankylosis.

Clinical manifestations (overview)

  • RA is a systemic autoimmune disease; manifestations are both musculoskeletal and systemic.
  • Musculoskeletal (joints):
    • Commonly affected joints include small joints of the hands and feet, wrists, knees, and elbows; involvement tends to be symmetrical (bilateral).
    • Inflammation causes pain, heat, redness, swelling, and loss of function in affected joints.
    • Morning stiffness and reduced ROM are typical; stiffness lasts longer than an hour, especially after inactivity.
    • Notable deformities arise from chronic inflammation and pannus formation (e.g., joint deformity when pannus causes destruction), and ankylosis can occur leading to immobility.
  • Systemic manifestations:
    • Can affect lungs, heart, kidneys, and skin; systemic symptoms include fatigue and generalized aching.
    • Sleep disturbance and fatigue contribute to reduced daily functioning and can contribute to depression.
    • Mental health impact and reduced ability to perform daily tasks (e.g., buttoning a shirt, brushing hair) are common.
    • Lymphadenopathy and other systemic signs may occur.
  • Visual and imaging correlates referenced in teaching materials include a pannus-containing joint and deformities associated with chronic RA; note that these are illustrative and part of broader clinical assessment.

Diagnosis and diagnostic criteria (key points)

  • Core features used in assessment:
    • Inflammation of multiple joints with prolonged morning stiffness (>1 hour).
    • Symmetric joint involvement (often more than one joint on both sides).
    • A combination of clinical, laboratory, and imaging findings support diagnosis.
  • Laboratory tests:
    • Rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) levels are commonly checked.
    • RF and ACPA are associated with disease and help in establishing the diagnosis when combined with clinical features.
  • Diagnostic criteria (summary from teaching materials):
    • Diagnosis typically requires four or more of the following seven criteria, with the patient showing involvement of three or more joints and stiffness lasting longer than 60 minutes. In the provided content, the exact seven criteria are referenced but not enumerated; four of seven criteria are needed for confirmation, in addition to clinical joint involvement and stiffness duration. The key points include:
    • Stiffness lasting > 60 minutes
    • Involvement of multiple joints (at least three)
    • Four or more of a set of seven criteria (as listed in the source material)
    • Positive RF and/or ACPA (serologic markers)
  • Practical approach:
    • Diagnosis is supported by clinical presentation (symmetrical polyarthritis, morning stiffness), serology (RF/ACPA), and clinical imaging as part of a comprehensive assessment.

Management and practical considerations

  • Lifestyle and psychosocial factors:
    • Regular physical activity and exercise can help maintain function and mood.
    • Smoking cessation is important; diet modification can have supportive benefits.
    • Social engagement and outdoor activity can improve mental health and coping with chronic pain.
    • Depression is a possible consequence of chronic pain and reduced function, so mental health support is important.
  • Pharmacologic and medical management (summarized from lecture):
    • There are several medications that can help RA; specifics are to be covered in a separate lecture.
    • A general management plan typically includes addressing inflammation, pain, and functional status while aiming to minimize autoimmune activity and prevent joint damage.
  • Practical implications for daily living:
    • RA can severely affect ability to perform daily tasks (e.g., buttoning a shirt, brushing hair, knitting) due to hand joint involvement and stiffness.
    • Joint protection and occupational therapy strategies can help maintain independence.

Additional notes on interpretation and study tips

  • Remember the hallmark of RA is autoimmune-driven, bilateral, systemic inflammatory involvement with potential for joint destruction and deformity.
  • The pannus is the key RA-specific pathologic feature driving cartilage and bone destruction; it is a major therapeutic target in many treatment strategies.
  • The balance between osteoclast and osteoblast activity (via RANKL signaling) contributes to bone erosions and deformations; understanding this helps explain radiographic changes and long-term joint outcomes.
  • The knowledge of RF and ACPA helps distinguish RA from other arthritides and supports prognosis and disease monitoring.
  • When studying, focus on how immunologic components (B cells, T cells, RF, ACPA, cytokines) translate into synovial pathology (hyperplasia, pannus), which then leads to clinical symptoms and potential systemic effects.

ext{RA diagnosis if } (J \,\ge\, 3) \ \, S > 60 \text{ minutes} \ \text{and} \ 4 \,\le\, k \,\le\, 7, \text{ where } k \text{ are the seven criteria}

ext{RANKL} \involves \,\text{osteoclast activity} \Rightarrow \text{bone erosion}

End of notes