MSK; Lecture 4, 5 and 6 - Pathogenesis of AI disease, Rheumatoid Arthritis and Osteoarthritis/Reactive arthritis Flashcards
What is rheumatoid arthritis?
Chronic joint inflammation that can result in joint damage (permanent) -> synovium is inflammed; associated with autoantibodies
Which autoantibodies are associated with rheumatoid arthritis?
Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP)
What is ankylosing spondylitis?
Chronic spinal inflammation that can result in spinal fusion and deformity -> chronic back pain from enthesis (site of inflammation - junction between intervertebral disc and vertebrae); no autoantibodies.
What are seronegative spondyloarthropathies?
Ankylosing spondylitis; reiters syndrome and reactive arthritis. Arthritis associated with psoriasis (psoriatic arthritis)/GI inflammation (IBS - enteropathic synovitis)
What are the signs of the patient with ankylosing spondylitis?
Excessive thoracic kyphosis; no lordosis in lumbar spine and hyperextension of neck -> spine moves as a block
What is SLE?
Chronic tissue inflammation in presence of Ab direted against self-Ag; multi-site inflammation, particularly joints, skin and kidneys -> excessive immune complexes which deposit in tissues, but have low complement levels Associated with autoAb
Which autoAb is SLE associated with?
Antinuclear Ab and anti-double stranded DNA ab
What are the different connective tissue diseases?
Systemic lupus erythematosus Inflammatory muscle disease: polymyositis, dermatomyositis Systemic sclerosis Sjogren’s syndrome A mixture of the above: ‘Overlap syndromes’
Which HLA molecules are associated with rheumatoid arthritis, SLE and ankylosing spondylitis?
RA = HLA-DR4 (class II) SLE = HLA-DR3 (class II) AS = HLA-B27 (class I)
What is the importance of the MHC being class I or II?
- Presents ag to T-cells.
- Pathogenesis of HLA-associated disease -> due to a peptide antigen (exogenous or self) that is able to bind to HLA molecule and trigger disease (‘arthritogenic antigen’)
What are the overall autoantibodies used in rheumatology (RA, SLE, osteoarthritis, reactive arthritis, gout, AS, systemic vasculitis)?
What are the autoantibodies in diffuse/limited systemic sclerosis, dermato-polymitosis, sjogren’s syndrome, mixed connective tissue disease?
What are the autoantibodies of SLE?
NB: antinuclear antibodies do not enter the nucleus/cell; the nuclear antigens are presented by the cell via HLA receptor (e.g.)
What are antinuclear antibodies reacting to?
If ANA is positive the clinical laboratory will perform further tests to determine which type of ANA it is – typically these include screening for: Anti-Ro Anti-La Anti-centromere Anti-Sm Anti-RNP Anti-ds-DNA antibodies Anti-Scl-70 Cytoplasmic antibodies include: Anti-tRNA synthetase antibodies Anti-ribosomal P antibodies
How is the disease activity of SLE worked out?
Sick lupus patients have low complement levels and high levels of anti-ds-DNA Ab, which cycles
What are the cytokines used in rheumatology and what are their effects?
TNF-a is very beneficial as it is the main inflammatory mediator, so by inhibiting it helps greatly reduce the inflammation
How does TNF-a act in rheumatoid arthritis?
TNF-a is very beneficial as it is the main inflammatory mediator, so by inhibiting it helps greatly reduce the inflammation -> reduces cartilage damage and joint inflammation
What other cytokine inhibitors are present in clinic for rheumatoid conditions?
IL-6 and IL-1 blockade are now available in clinic; can also deplete B cells in rheumatoid arthritis by parenteral admin of Ab against CD20
How is RANKL used in rheumatology?
How can B cells inhibitors be used to treat SLE?
How are prostaglandins used in rheumatology?
See them as anti-iinflammatory and analgesic -> don’t modify joint destruction, just manages the pain not stopping the disease
What is rheumatoid arthritis?
Chronic AI disease characterised by pain, joint stiffness and SYMMETRICAL synovitis of synovial joints (needs to be on both sides of body)
What are the environmental/genetic components of rheumatoid arthritis?
What are the commonest affected joints in rheumatoid arthritis?
MCP, Proximal interphalangeal joints, wrists, knees, ankles, MTP
What are the types of joint damage and destruction that occurs in rheumatoid arthritis?
Swan-neck deformity and boutonniere deformity
What are the types of synovitis that can appear and where?
What are sub-cutaneous nodules that can present in rheumatoid arthritis?
Histiocytes surrounded by connective tissue
What is the importance of Ab to citrullinated protein antigens?
What is the pathology of rheumatoid arthritis?
Peri-osteus inflammation; articular cartilage is lost
What are the features of the synovial joint?
Synovium, synovial fluid and articular cartilage (type II collagen - bONE has type I
How is synovial fluid abnormal in rheumatoid arthritis?
How is TNF-a important in rheumatoid arthritis and how can we use this for treatment?
Dominant detrimental role of TNFα in rheumatoid arthritis validated by the therapeutic success of TNFα inhibition in this condition. TNFα inhibition is achieved through parenteral administration (most commonly sub-cutaneous injection) of antibodies or fusion proteins
What are the biological therapies for rheumatoid arthritis?
What are the treatment goals and general treatments for rheumatoid arthritis?
Methotrexate is the main drug given to patients. Think of side effect profiles for long standing treatment
What are DMARDS?
What are the negatives of biological therapy for rheumatoid arthritis?
What is reactive arthritis?
How can you differentiate the musculoskeletal symptoms of reactive arthritis from enthesitis and spondylitis?
Can present as monoarthritis
What are the extra-articular features of reactive arthritis?
NB: reiter’s syndrome is the same thing as reactive arthritis
What is the difference between rheumatoid and reactive arthritis?
K. blennorhagicum (psoriasis-like rash in feet). NB: NO Ab in reactive
*What is osteoarthritis?
Chronic slowly progressive disorder due to failure of articular cartilage that typically affecting joints of the hand (especially those involved in pinch grip), spine and weight-bearing joints (hips and knees)
Which joints are affected in osteoarthritis?
Joints of hand -> DIP, PIP and CMC (not MCP); spine and weight bearing joints of lower limbs -> hip, knees and MTP
What are some physical features of osteoarthritis?
x
What features can osteoarthritis be associated with?
x
What are the radiographic features of osteoarthritis?
Joint space narrowing Subchondral bony sclerosis Osteophytes Subchondral cysts
What is the pathology for osteoarthritis?
Defective and irreversible articular cartilage an damage to underlying bone -> develops due to excessive loading on joints and/or abnormal joint components
What are proteoglycans?
Aggrecan is the major proteoglycan in articular cartilage Hyaluronic acid is the only non-sulphated GAG and is major component of synovial fluid where it has an important role in maintaining synovial fluid viscosity
How do you manage osteoarthritis?
Mainly to improve pain management, not real treatment
What is Belimumab?
Recombinant fully human IgG1 mAb against BLYS -> inhibits activity of BAFF resulting in impaired B cell survival and reduced B cell numbers
What is rheumatoid factor?
What are the extra-articular features of rheumatoid arthritis?
What are the radiographic abnormalities of rheumatoid arthritis at different progressions?
x
How do you diagnose reactive arthritis?
What is the difference between septic vs reactive arthritis?
How do you treat reactive arthritis?
What are the radiographic changes in rheumatoid arthritis vs osteoarthritis?
How is the articular cartilage different in osteoarthritis?
What are the cartilage and bone changes in osteoarthritis?
How do you treat osteoarthritis?
