Rheumatoid Arthritis Pathophysiology
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Questions and Answers

Which type of T-cells release inflammatory mediators that stimulate other inflammatory cells leading to tissue injury in RA?

  • Dendritic cells
  • CD4+ T-cells (correct)
  • CD8+ T-cells
  • Natural Killer cells

    • Which cytokine is secreted by macrophages and stimulates resident synovial cells to secrete proteases that destroy hyaline cartilage in RA?

  • IL-17
  • IL-1 (correct)
  • TNF
  • INF-γ

    • What is the function of RANKL expressed on activated T cells in RA?

  • Regulates synovial cell activation
  • Stimulates bone resorption (correct)
  • Inhibits bone resorption
  • Stimulates bone formation

    • What is the significance of the presence of anti-CCP antibodies in RA?

    <p>Indicates autoimmune response</p> Signup and view all the answers

    What is the function of IgM and IgA auto-antibodies that bind IgG Fc region in RA?

    <p>Forms immune complexes</p> Signup and view all the answers

    What is citrulline?

    <p>Not mentioned in the content</p> Signup and view all the answers

    What is the significance of the presence of germinal centers with secondary follicles and plasma cells in RA?

    <p>Indicates autoimmune response</p> Signup and view all the answers

    What is the typical duration of morning stiffness in rheumatoid arthritis?

    <p>More than 1 hour</p> Signup and view all the answers

    Which of the following is NOT a cytokine involved in the pathophysiology of RA?

    <p>EBV</p> Signup and view all the answers

    Which of the following is a characteristic wrist finding in rheumatoid arthritis?

    <p>All of the above</p> Signup and view all the answers

    What is the approximate number of children affected by juvenile idiopathic arthritis in the US?

    <p>30,000 - 50,000</p> Signup and view all the answers

    What is a common feature of systemic arthritis in juvenile idiopathic arthritis?

    <p>High spiking fevers</p> Signup and view all the answers

    What is the typical joint distribution in juvenile idiopathic arthritis?

    <p>Large joints are affected more often than small joints</p> Signup and view all the answers

    What is a complication of long-term use of anti-inflammatory drugs in rheumatoid arthritis?

    <p>GI bleeding</p> Signup and view all the answers

    What is the prognosis of juvenile idiopathic arthritis?

    <p>Only 10% tend to progress to severely disabling disease</p> Signup and view all the answers

    What is a characteristic feature of oligoarthritis in juvenile idiopathic arthritis?

    <p>Arthritis affecting four or fewer joints</p> Signup and view all the answers

    What is the primary characteristic of pannus formation in rheumatoid arthritis?

    <p>Transformation of smooth surface to one covered by villous, finger-like projections</p> Signup and view all the answers

    Which of the following cells are NOT typically found in the inflammatory infiltrate in rheumatoid arthritis?

    <p>Neutrophils</p> Signup and view all the answers

    What is the consequence of osteoclastic activity in subchondral bone in rheumatoid arthritis?

    <p>Bony erosion around the joint</p> Signup and view all the answers

    What is the typical distribution of joint involvement in rheumatoid arthritis?

    <p>Symmetrical distribution</p> Signup and view all the answers

    Which of the following joints are typically affected in rheumatoid arthritis?

    <p>MCP, PIP, MTP, wrist, and ankle</p> Signup and view all the answers

    What is the consequence of ankylosis in rheumatoid arthritis?

    <p>Decreased range of motion</p> Signup and view all the answers

    What is the typical course of joint damage in rheumatoid arthritis?

    <p>Greatest joint damage occurs in the first 4-5 years</p> Signup and view all the answers

    What is the characteristic of joint damage in rheumatoid arthritis?

    <p>Destruction of cartilage, bone, joint capsules, tendons, and ligaments</p> Signup and view all the answers

    What is the typical age of onset for asymmetric juvenile idiopathic arthritis?

    <p>Younger than 6 years</p> Signup and view all the answers

    Which type of juvenile idiopathic arthritis is commonly associated with iridocyclitis and a positive ANA?

    <p>Asymmetric juvenile idiopathic arthritis</p> Signup and view all the answers

    What is the characteristic of rheumatoid-factor positive polyarthritis?

    <p>Similar to adult RA, usually found in teenage girls</p> Signup and view all the answers

    What is the characteristic of enthesitis-related arthropathy?

    <p>Primarily found in younger males</p> Signup and view all the answers

    What is the hallmark of osteoarthritis?

    <p>Articular cartilage degeneration</p> Signup and view all the answers

    What percentage of the population have some radiological evidence of osteoarthritis by age 65?

    <p>80-90%</p> Signup and view all the answers

    What is a risk factor for osteoarthritis?

    <p>Lower estrogen levels</p> Signup and view all the answers

    What is the characteristic of secondary osteoarthritis?

    <p>Occurs in younger populations secondary to joint deformity</p> Signup and view all the answers

    What is the primary reason for rapid joint destruction in infectious arthritis?

    <p>Limited regenerative capacity of cartilage</p> Signup and view all the answers

    Which of the following is a risk factor for suppurative infectious arthritis?

    <p>Individuals with deficiencies in complement factors C5-C9</p> Signup and view all the answers

    What is the primary mode of bacterial infection in suppurative infectious arthritis?

    <p>Hematogenous spread from distant sites</p> Signup and view all the answers

    Which of the following organisms is commonly associated with suppurative infectious arthritis?

    <p>N. gonorrhea</p> Signup and view all the answers

    What is the typical clinical presentation of suppurative infectious arthritis?

    <p>Sudden development of an acutely painful, swollen joint with limited range of motion</p> Signup and view all the answers

    What is a common complication of suppurative infectious arthritis?

    <p>Long-term joint pain</p> Signup and view all the answers

    What is the primary cause of mycobacterial infectious arthritis?

    <p>M. tuberculosis</p> Signup and view all the answers

    What is the mortality rate associated with Staph aureus septic arthritis?

    <p>50%</p> Signup and view all the answers

    What is the characteristic of juvenile idiopathic arthritis that develops at an early age and is commonly associated with iridocyclitis and a positive ANA?

    <p>Asymmetric arthritis</p> Signup and view all the answers

    What is the characteristic of rheumatoid-factor positive polyarthritis?

    <p>Similar to adult RA, usually found in teenage girls</p> Signup and view all the answers

    What is the characteristic of enthesitis-related arthropathy?

    <p>Primarily found in younger males, HLA-B27 positive</p> Signup and view all the answers

    What is the primary characteristic of osteoarthritis?

    <p>Characterized by articular cartilage degeneration</p> Signup and view all the answers

    What percentage of the population have some radiological evidence of osteoarthritis by age 65?

    <p>80-90%</p> Signup and view all the answers

    What is a risk factor for osteoarthritis?

    <p>Genetics</p> Signup and view all the answers

    What is the characteristic of secondary osteoarthritis?

    <p>Occurs in younger populations secondary to joint deformity, prior injury, or underlying systemic disease</p> Signup and view all the answers

    What is the hallmark of osteoarthritis?

    <p>Articular cartilage degeneration</p> Signup and view all the answers

    What is the primary reason for rapid joint destruction in infectious arthritis?

    <p>Limited regenerative capacity of cartilage</p> Signup and view all the answers

    What is a characteristic feature of infectious arthritis caused by Borrelia burgdorferi?

    <p>Migratory arthritis lasting weeks to months</p> Signup and view all the answers

    Which of the following is a risk factor for suppurative infectious arthritis?

    <p>Individuals with deficiencies in complement factors C5-C9</p> Signup and view all the answers

    What is a common feature of viral infectious arthritis?

    <p>Acute to subacute arthritis</p> Signup and view all the answers

    What is the primary mode of bacterial infection in suppurative infectious arthritis?

    <p>Hematogenous spread</p> Signup and view all the answers

    Which joints are commonly affected in Lyme arthritis?

    <p>Knees, shoulders, elbows, and ankles</p> Signup and view all the answers

    Which of the following organisms is commonly associated with suppurative infectious arthritis?

    <p>N. gonorrhea</p> Signup and view all the answers

    What is a common cause of infectious arthritis?

    <p>All of the above</p> Signup and view all the answers

    What is the typical clinical presentation of suppurative infectious arthritis?

    <p>Sudden development of an acutely painful, swollen joint with limited range of motion</p> Signup and view all the answers

    What is a common complication of suppurative infectious arthritis?

    <p>All of the above</p> Signup and view all the answers

    What is a characteristic of joint symptoms in infectious arthritis?

    <p>Intermittent pain in multiple joints</p> Signup and view all the answers

    What is the primary cause of mycobacterial infectious arthritis?

    <p>M. tuberculosis</p> Signup and view all the answers

    What is a common complication of suppurative infectious arthritis?

    <p>Rapid joint destruction</p> Signup and view all the answers

    What is the mortality rate associated with Staph aureus septic arthritis?

    <p>50%</p> Signup and view all the answers

    What is the role of HLA-DR4 allele in the pathogenesis of rheumatoid arthritis?

    <p>It presents an epitope of a citrullinated protein to T-cells.</p> Signup and view all the answers

    What is the process by which a microbial antigen resembles a self-antigen, leading to autoimmune response?

    <p>Molecular mimicry</p> Signup and view all the answers

    What type of cells are activated by Th17 and Th1 cytokines in rheumatoid arthritis?

    <p>Macrophages</p> Signup and view all the answers

    What is the characteristic morphologic feature within the joint in rheumatoid arthritis?

    <p>Formation of a pannus</p> Signup and view all the answers

    What is the role of citrullination in rheumatoid arthritis?

    <p>It is involved in the conversion of arginine to citrulline within proteins.</p> Signup and view all the answers

    What is the result of prominent angiogenesis in the synovium during pannus formation?

    <p>Increased blood flow to the joint</p> Signup and view all the answers

    Which type of cells are typically found in the inflammatory infiltrate in rheumatoid arthritis?

    <p>All of the above</p> Signup and view all the answers

    Which joints are most commonly affected in rheumatoid arthritis?

    <p>Small joints of the hands and feet</p> Signup and view all the answers

    What is the consequence of osteoclastic activity in subchondral bone in rheumatoid arthritis?

    <p>Bone erosion and osteopenia</p> Signup and view all the answers

    What is the consequence of environmental factors such as smoking in rheumatoid arthritis?

    <p>It promotes the citrullination of self-proteins.</p> Signup and view all the answers

    What is the role of macrophages in the joints of patients with rheumatoid arthritis?

    <p>They secrete pro-inflammatory cytokines and contribute to pannus formation.</p> Signup and view all the answers

    What is the typical distribution of joint involvement in rheumatoid arthritis?

    <p>Symmetrical, affecting small and large joints</p> Signup and view all the answers

    What is the characteristic of joint damage in rheumatoid arthritis?

    <p>Irreversible and affecting multiple joint tissues</p> Signup and view all the answers

    What is the consequence of ankylosis in rheumatoid arthritis?

    <p>Decreased range of motion</p> Signup and view all the answers

    What is the typical course of joint damage in rheumatoid arthritis?

    <p>Gradual and relentless over the first 4-5 years</p> Signup and view all the answers

    What is the characteristic of joint involvement in rheumatoid arthritis?

    <p>Warm, tender, and swollen joints that progress to instability and deformity</p> Signup and view all the answers

    Study Notes

    Rheumatoid Arthritis (RA) - Pathophysiology

    • CD4+ T-cells release inflammatory mediators that stimulate other inflammatory cells, leading to tissue injury
    • Key cytokines involved:
      • INF-γ (secreted by cells, activates macrophages and resident synovial cells)
      • IL-17 (from cells, recruits neutrophils and monocytes)
      • TNF and IL-1 (from macrophages, stimulates resident synovial cells to secrete proteases that destroy hyaline cartilage)
      • RANKL (expressed on activated T cells, stimulates bone resorption)

    RA - Pathophysiology Continued

    • Joint synovium contains germinal centers with secondary follicles and plasma cells that secrete autoantibodies
      • Anti-CCP (anti-citrullinated peptide) detected in serum in up to 70% of patients with RA
      • IgM and IgA auto-antibodies that bind IgG Fc region (rheumatoid factor) detected in serum in up to 80% of patients with RA

    RA - Joint Morphology

    • Pannus formation:
      • Joint synovium becomes edematous and thickened
      • Hyperplasia and proliferation result in transformation from smooth surface to one covered by villous, finger-like projections
      • Prominent angiogenesis in the synovium
      • Inflammatory cells infiltrate the pannus (CD4+ T helper cells, B cells, plasma cells, dendritic cells, and macrophages)
      • Fibrinopurulent exudate is deposited on synovial and joint surfaces
      • Osteoclastic activity in subchondral bone causes bony erosion around the joint

    RA - Joint Destruction

    • Ankylosis:
      • Pannus forms a "bridge" between apposing bones, forming a fibrous ankylosis
      • Eventual ossification results in a bony ankylosis that "fuses" bones across a joint
    • Joint damage encompasses:
      • Destruction of cartilage
      • Destruction of bone next to the joint
      • Damage to joint capsules, tendons, and ligaments
      • Ankylosis (decreased range of motion)

    Juvenile Idiopathic Arthritis (JIA)

    • Heterogeneous group of disorders
    • Occur prior to age 16 years and persist for at least 6 weeks
    • Idiopathic – no clearly described etiology
    • Shares some pathogenic features with RA
    • Associated with HLA and PTPN22 gene variants
    • 30,000 – 50,000 children affected in the US

    Osteoarthritis (OA)

    • Characterized by articular cartilage degeneration resulting in structural and functional synovial joint failure
    • Can be primary or secondary
    • Epidemiology:
      • Very common: 80-90% of the population have some radiological evidence of osteoarthritis by age 65
      • 50% are significantly affected by osteoarthritis by age 65
    • Risk factors include:
      • Age, genetics
      • Trauma, repetitive use, obesity, other orthopedic disease
      • Reproductive hormones

    Infectious Arthritis

    • Suppurative:
      • Bacterial infection entering joints from distant sites via hematogenous spread
      • Risk factors: deficiencies in complement factors C5-C9, immunodeficiencies, joint trauma, chronic arthritis, and IV drug use
      • Organisms: N.gonorrhea, Chlamydia, Staphylococcus, Streptococcus, H.influenzae, E.coli, Salmonella
    • Mycobacterial:
      • Chronic progressive monoarticular infections caused by M.tuberculosis
      • Occurs primarily in adults as a complication of adjacent osteomyelitis or disseminated from visceral site of infection

    Rheumatoid Arthritis (RA)

    • Citrullination of proteins can occur within joints, converting arginine amino acids to citrulline
    • Proteins that can undergo citrullination include fibrinogen, type II collagen, alpha-enolase, and vimentin
    • HLA-DR4 allele is associated with anti-citrulline antibody, and environmental factors like smoking may promote citrullination of self-proteins

    Pathogenesis of RA

    • Molecular mimicry occurs when a microbial antigen resembles a self-antigen, leading to activation of CD4+ cells that recognize self
    • This process is thought to be important in the pathophysiology of autoimmune and hypersensitivity disorders, including RA

    Joint Morphology in RA

    • RA commonly affects the small joints of the hands and feet, particularly the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints
    • Characteristic morphologic features within the joint include formation of a pannus, which is a mass of edematous synovium, inflammatory cells, granulation tissue, and fibroblast growth causing articular cartilage erosion

    Pannus Formation

    • Joint synovium becomes edematous and thickened, with hyperplasia and proliferation resulting in transformation from a smooth surface to one covered by villous, finger-like projections into the joint
    • Prominent angiogenesis occurs in the synovium
    • Inflammatory cells, including CD4+ T helper cells, B cells, plasma cells, dendritic cells, and macrophages, infiltrate the pannus
    • Fibrinopurulent exudate is deposited on synovial and joint surfaces

    Joint Destruction in RA

    • Ankylosis can occur, resulting in a "bridge" of fibrous tissue across the joint that limits range of motion
    • Joint damage includes destruction of cartilage, bone, and joint capsules, tendons, and ligaments
    • Greatest joint damage occurs in the first 4-5 years, with the younger the age of onset, often the more severe the course of disease

    Osteoarthritis (OA)

    • Characterized by articular cartilage degeneration, resulting in structural and functional synovial joint failure
    • Can be primary or secondary, with primary OA occurring without an apparent initiating cause and secondary OA occurring due to joint deformity, prior injury, or underlying systemic disease

    Epidemiology of OA

    • Most common joint disease, with 80-90% of the population having some radiological evidence of OA by age 65
    • About 5% of cases occur in younger patients, often due to secondary OA

    Etiology of OA

    • Risk factors include age, genetics, trauma, repetitive use, obesity, and other orthopedic disease
    • Reproductive hormones, particularly estrogen, may also play a role

    Infectious Arthritis

    • Suppurative arthritis occurs when bacteria enter the joint from distant sites via hematogenous spread
    • Risk factors include deficiencies in complement factors, immunodeficiencies, joint trauma, chronic arthritis, and IV drug use
    • Organisms that can cause infectious arthritis include N. gonorrhea, Chlamydia, Staphylococcus, Streptococcus, H. influenzae, E. coli, and Salmonella

    Clinical Features of Infectious Arthritis

    • Sudden development of an acutely painful, swollen joint with limited range of motion
    • Fever and leukocytosis
    • Joint aspiration reveals purulent fluid and identification of the infectious organism

    Complications and Prognosis of Infectious Arthritis

    • Up to 50% of patients can have long-term joint pain after the infection resolves, even with quick recognition and treatment
    • Since it is often associated with sepsis, it can also be associated with severe outcomes, including mortality

    Mycobacterial Arthritis

    • Chronic progressive monoarticular infections caused by M. tuberculosis
    • Occurs primarily in adults as a complication of adjacent osteomyelitis or disseminated from visceral site of infection
    • Insidious onset of increasing joint pain, with the hip, knee, and ankle joints commonly affected

    Lyme Arthritis

    • Caused by the spirochete Borrelia burgdorferi
    • If untreated, up to 80% of patients will develop a migratory arthritis lasting weeks to months
    • Joint pain is periodic, oligoarticular, and can affect the knees, shoulders, elbows, and ankles

    Viral Arthritis

    • Can occur with a variety of viral infections, including alphavirus, parovirus B19, rubella, Epstein-Barr, and Hepatitis B & C
    • Clinical features include acute to subacute arthritis
    • Joint symptoms can be caused by the virus itself or an autoimmune reaction triggered by the infection

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    Description

    Understand the pathophysiology of Rheumatoid Arthritis, including the role of CD4+ T-cells, inflammatory mediators, and key cytokines involved in tissue injury.

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