Rheumatoid Arthritis Flashcards
Define Rheumatoid Arthritis
Chronic autoimmune disease characterised by pain, stiffness and SYMMETIRCAL SYNOVITIS of synovial (diarthrial) joints
When is the stiffness in the joints particularly bad in rheumatoid arthritis and what can make it better?
In the morning
It gets better with exercise
What is a relatively common extra-articular manifestation of rheumatoid arthritis?
Rheumatoid nodules
What causes the extra-articular manifestations of Rheumatoid arthritis?
Rheumatoid factor produces immune complexes that can go anywhere
What type of antibody is the rheumatoid factor and where does t bind?
IgM antibody that binds to the Fc portion of IgG
Is rheumatoid arthritis more common in males or females?
More common in females (3:1)
What is the important genetic component that predisposes to Rheumatoid Arthritis?
The genetic component comes down to a specific set of amino acids within the beta chain of the DR molecule (amino acids 70-74 of the DR Beta1-chain)
This set of amino acids is conserved among all HLA subtypes that are associated with rheumatoid arthritis – it is called the shared epitope. HLA-DR4
What important environmental factor can affect the susceptibility and severity of Rheumatoid Arthritis?
Smoking
State some joints that are commonly affected in Rheumatoid Arthritis.
Metacarpophalangeal joint (MCP) Proximal interphalangeal joint (PIP) Wrists Knees Ankles Metatarsophalangeal joint (MTP)
Name and describe two deformities that are indicative of Rheumatoid Arthritis.
Swan-neck deformity Hyperextension of PIP Hyperflexion of DIP Boutonniere deformity (button-like) Hyperflexion at PIP
Other that joints and around tendons, where else can synovium become inflamed?
Bursae –> Bursitis
Why are rheumatoid nodules an important clinical finding?
Patients with rheumatoid nodules are always rheumatoid factor positive
Where are rheumatoid nodules commonly seen?
Along the ulnar border
What proportion of cases of Rheumatoid Arthritis is rheumatoid factor negative?
1/3
Name another autoantibody that is very specific for Rheumatoid Arthritis.
Anti-cyclic citrullinated peptide antibody
Which enzymes are responsible for the citrullination of peptides?
Peptidyl arginine deaminases (PADs
Why do citrullinated peptide antigens develop in rheumatoid arthritis?
PADs are present in high concentrations in neutrophils and monocytes so there is increased citrullination of autologous peptides in inflamed synovium
Citrulline binds much better than arginine to the shared epitope (specific peptide sequence that is conserved in all MHC molecules that are associated with Rheumatoid Arthritis)
So Anti-CCP antibodies are more likely to develop in individuals with citrullinated autoantigens and those that have the shared epitope
State some rare extra-articular manifestations of Rheumatoid Arthritis.
Vasculitis
Episcleritis
What is the name given to the thickened, chronically inflamed synovial tissue in Rheumatoid Arthritis?
Pannus
How thick is the normal synovial membrane?
It is normally almost a single cell lining
Which cells are responsible for producing synovial fluid?
Synovial fibroblasts
NOTE: macrophages are also found within the lining
Why is synovial fluid viscous?
It contains hyaluronic acid
What type of collagen is present in articular cartilage?
Type 2 collagen
What is the main proteoglycan in articular cartilage?
Aggrecan
What three main things are responsible for the synovium becoming a proliferated mass (pannus)?
Neovascularisation Lymphangiogenesis Inflammatory cell recruitment: Activated T and B cells Plasma cells Mast cells Activated macrophages
What are the three main cytokines involved in rheumatoid arthritis?
IL-1
IL-6
TNF-alpha
What is the dominant cytokine and which cells produce it?
TNF-alpha
Produced by activated macrophages
What class of drugs are commonly used in Rheumatoid Arthritis to modify the natural history of the disease?
Disease-modifying anti-rheumatic drugs (DMARDs)
Describe the onset of action of DMARDs.
Slow onset and complex action
Give some examples of DMARDs.
Methotrexate
Sulphasalazine
What are the shortcomings of DMARDs?
They have significant adverse effects and require regular blood test monitoring
Ant TNF antibodies
Infliximab
What is the main treatment goal for Rheumatoid Arthritis with DMARDs?
Prevent joint damage and reduce synovial inflammation
What is citrulination
conversion of arginine to citruline (not one of standard 20 amino acids) - a post translational modification
What are the major risks with biological therapy?
EXPENSIVE
All biological therapies are associated with an increase infection risk
TNF-alpha inhibition is associated with increased susceptibility to mycobacterial infections (TUBERCULOSIS)
