Rheumatoid Arthritis Flashcards
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 common extra-articular manifestations of Rheumatoid Arthritis.
Rheumatoid nodules Fever Weight loss
State some rare extra-articular manifestations of Rheumatoid Arthritis.
Vasculitis Episcleritis Neuropathies Amyloidosis Lung disease (nodules, fibrosis, pleuritis) Felty’s syndrome (triad of splenomegaly, leukopenia and rheumatoid arthritis)
What is an early radiographic abnormality in Rheumatoid Arthritis?
Juxta-articular osteopenia
What are some later radiographic abnormalities in Rheumatoid Arthritis?
Joint erosion and, subsequently, joint destruction and deformity
What is the name given to the thickened, chronically inflamed synovial tissue in Rheumatoid Arthritis?
Pannus
Which area of bone tends to be eroded first in Rheumatoid Arthritis?
Bare area of bone – this is within the synovial membrane but is not covered by articular cartilage (periarticular erosion)
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 this disease process?
IL-1 IL-6 TNF-alpha
What is the dominant cytokine and which cells produce it?
TNF-alpha Produced by activated macrophages
What is the main treatment goal for Rheumatoid Arthritis?
Prevent joint damage
What class of drugs are commonly used in Rheumatoid Arthritis to modify the natural history of the disease?
Disease-modifying anti-rheumatic drugs (DMARDs)
When are glucocorticoids used and why are they not used long term?
They are used in the short-term to control, for example, exacerbation of the disease They are not used long-term because of their large side effect profile
Describe the onset of action of DMARDs.
Slow onset and complex action
Give some examples of DMARDs.
Methotrexate Sulphasalazine Hydroxychloroquine Leflunomide Gold Penicillamine
What are the shortcomings of DMARDs?
They have significant adverse effects and require regular blood test monitoring
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) So all patients must be screened for TB before starting treatment B cell depletion is associated with HEPATITIS B activation so patients need to be screened for this as well B cell depletion is also associated with JC virus infection and progressive multifocal leukoencephalopathy (PML) – RARE
