Rheumatoid Arthritis Flashcards
Define Rheumatoid Arthritis
Chronic AI disease characterised by pain, stiffness + SYMMETIRCAL SYNOVITIS of synovial (diarthrial) joints
What is a relatively common extra-articular manifestation of rheumatoid arthritis?
Rheumatoid nodules
What causes the extra-articular manifestations? What are 2 rarer extra-articular manifestations?
Rheumatoid factor produces immune complexes that can go anywhere
Vasculitis
Episcleritis
What type of antibody is the rheumatoid factor?
IgM autoantibody 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?
Specific set of AA’s (70-74) within the beta chain of the HLA-DR binding groove
This set of AA’s is conserved among all HLA subtypes that are associated with RA = the shared epitope
What important environmental factor can affect the susceptibility and severity of Rheumatoid Arthritis?
Smoking
State 6 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
Describe the appearance of extensor tenosynovitis.
Swelling around the extensor tendon that is inflamed
When the fingers are extended, the swelling will move showing the inflammation is around the tendon + not the joint
Other than joints and around tendons, where else can synovium become inflamed?
Bursae –> Bursitis
What are sub-cutaneous nodules?
Central area of fibrinoid necrosis surrounded by histiocytes + 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 of the forearm
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 + monocytes so there is increased citrullination of autologous peptides in inflamed synovium
Citrulline binds much better than arginine to the shared epitope
Anti-CCP antibodies are more likely to develop in individuals with citrullinated autoantigens (e.g. smokers)+ those that have the shared epitope
State 3 common extra-articular manifestations of Rheumatoid Arthritis.
Subcutaneous nodules
Fever
Weight loss
State 6 rare extra-articular manifestations of Rheumatoid Arthritis.
Vasculitis
Episcleritis (ocular inflammation)
Neuropathies
Amyloidosis
Lung disease (nodules, fibrosis, pleuritis)
Felty’s syndrome (triad of splenomegaly, leukopenia + RA)
What is an early radiographic abnormality in Rheumatoid Arthritis?
Juxta-articular osteopenia
What are some later radiographic abnormalities in Rheumatoid Arthritis?
Joint erosion at margins of joint
Subsequent joint destruction + 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: within the synovial membrane but is not covered by articular cartilage (periarticular erosion)
How thick is the normal synovial membrane?
~ single cell lining
Which cells are responsible for producing synovial fluid?
Synovial fibroblasts (Synoviocytes) Macrophage like cells 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 + 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 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?
Used in the short-term to control, e.g. control flare of disease
Not used long-term because of their large side effect profile
Describe the onset of action of DMARDs.
Slow onset + complex action
Give 3 examples of DMARDs.
Methotrexate
Sulphasalazine
Hydroxychloroquine
What are the shortcomings of DMARDs?
All have significant adverse effects + require regular blood test monitoring
What are 5 major risks with biological therapy?
Expensive
All associated with an increase infection risk
TNF-alpha inhibition is associated with increased susceptibility to mycobacterial infections:
TUBERCULOSIS- patients must be screened for TB before starting treatment)
B cell depletion is associated with HEPATITIS B reactivation so patients need to be screened for this
B cell depletion is also associated with JC virus infection + progressive multifocal leukoencephalopathy (PML), RARE
List 4 key features of rheumatoid arthritis
Chronic
Polyarthritis
Symmetrical
Early morning stiffness in + around joints
Describe the character of the swellings in rheumatoid arthritis
Soft on palpation
List 4 examples of biological therapy for rheumatoid arthritis
Inhibition of tumour necrosis factor alpha (TNF alpha)
B cell depletion
Modulation of T cell co-stimulation
Inhibition of IL6
