Rheumatoid Arthritis Flashcards
Define Rheumatoid Arthritis
Chronic autoimmune disease characterised by pain, stiffness and SYMMETIRCAL SYNOVITIS (inflammation of synovial membrane) of synovial (diarthrodial) joints
When is the stiffness in the joints particularly bad in CHRONIC rheumatoid arthritis and what can make it better?
In the morning
It gets better with exercise
What causes the Rheumatoid nodules?
Rheumatoid factor produces immune complexes that can go anywhere. Nodules=immune complexes surrounded by macrophages (see below)
Nodules are formed via a Central area of fibrinoid necrosis (a type of necrosis) surrounded by histiocytes (type of issue macrophage) and peripheral layer of connective tissue
What type of antibody is the rheumatoid factor?
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 toRheumatoid 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
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 when left untreated
Swan-neck deformity Hyperextension of PIP Hyperflexion of DIP Boutonniere deformity (button-like) Hyperflexion at PIP
What is the term given to fingers that are completely swollen, notjust around the joints?
Dactylitis – this can’t be explained by Rheumatoid Arthritis because it is not just the joints that are inflame
Describe the appearance of extensor tenosynovitis.
There will be swelling of the Tenosynovium(synovial sheath surrounding tendons of extensor muscles of hand)
around the extensor tendon.
When the fingers are extended, the swelling will move showing that the inflammation is around the tendon and not the joint
Other that joints and around tendons, where else can synovium become inflamed?
Bursae –> Bursitis
bursas are lined with synovial membrane
What are sub-cutaneous nodules?
Central area of fibrinoid necrosis surrounded by histiocytes and a peripheral layer of connective tissue
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 (deamination because you are removing an amine group when converting arginine to citrulline)
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. ( more inflammation=more inflamamtory cells eg neutrophils= more PAD enzymes)
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.
Fever, weight loss, malaise (feel ill) and lethargy (tired). These are driven by cytokines and hence anti cytokine therapies eg anti TNF will also make patients feel better
Subcutaneous nodules (rheumatoid nodules)
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 (osteopenia is loss of bone minerals and protein but not as bad as osteoporosis ie BTEC osteoporosis)
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
Gold
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
