Rheumatoid arthritis Flashcards
What is rheumatoid arthritis?
Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of synovial membrane) of synovial joints
What is a key identifying feature of arthritis?
It is symmetrical
How do patients with rheumatoid arthritis tend to present?
Pain and swelling in both hands/wrists/knees- stiffness in and around joints which is particularly bad in the morning is normal
How does the stiffness in rheumatoid arthritis change with exercise?
It gets better
Why do you need to that and modify the natural history of the disease?
The inflammation damages the joints (joint erosions on radiographs)
What does extra-articular disease that can occur with rheumatoid arthritis consist of?
Rheumatoid nodules
Others are rare e.g. vasculitis, episcleritis- Rheumatoid factor forms immune complexes which can go anywhere
Where can rheumatoid factor be detected?
In the blood
Why is rheumatoid factor sometimes called rheumatoid antibody?
It is an IgM autoantibody against |gG
What is the gender distribution of rheumatoid arthritis like?
More common in females- 3 times more
What is the most common cause of cause?
Chronic synovitis
What genetic component is very strongly linked to rheumatoid arthritis (shared epitope)?
A specific set of amino acids within the beta chain of the DR molecule which is conceived among all HLA subtypes associated with rheumatoid arthritis- referred to as the shared epitope
What lifestyle factor increases susceptibility and severity of the disease?
Smoking
What joints are most commonly affected in rheumatoid arthritis?
Metacarpophalangeal joint Proximal interphalangeal joint Wrists Knees Ankles Metatarsophalangeal joint
What is the swan neck deformity?
Hyperextension at PIP
Hyperflexion at FIP
What is boutonniere deformity?
Hyperflexion at PIP
Synovitis has damaged joints and the tendons are pulling an abnormal joint which causes “button deformity”
What is dactylitis?
Whole digit is swollen
If a patient presented with several fully swollen fingers how do you know this isn’t rheumatoid?
Not just the joints that are swollen
What does tenosynovium do?
Wraps around tendons to allow them to move freely
What are bursas?
Pockets of fluid that are found on the surface of the joints- can get inflamed causing bursitis
What are subcutaneous nodules?
Rheumatoid factor produces immune complexes that can deposit in any tissue and they have a tendency to deposit in subcutaneous tissue and cause extra-articular manifestations
Where are rheumatoid nodules commonly seen?
Along ulnar border of forearm
What is rheumatoid factor?
IgM antibody that recognises and binds to Fc portion of |gG as their target antigen
Why isn’t Fc portion of IgG used as diagnostic test?
1/3 of rheumatoid arthritis is rheumatoid factor negative
Antibodies against what are highly specific for rheumatoid arthritis?
Citrullinated peptides
What is citrullination of peptides mediated by?
Enzymes called peptidyl arginine deaminase (PADs)
Why do citrullinated peptide antigens develop in rheumatoid arthritis?
PADs are present in high concentrations in neutrophils and monocytes and consequently there is increased citrullination of autologous peptides in inflamed synovium
What extra-articular features are common in rheumatoid arthritis?
Fever
Weight loss
Subcutaneous nodules
(Others are vasculitis, ocular inflammation, neuropathies, amyloidosis and lung disease)
What are the three common extra-articular features caused by?
Abnormal cytokine response
In the early stages, what radiographic abnormalities are there?
Juxta-articular osteopenia (less dense around joints)
In later stages, what radiographic abnormalities are there?
Joint erosions at margins of joint
Joint deformity and destruction
What happens to synovial membrane in rheumatoid arthritis?
It becomes thickened and chronically inflamed and will cause joint swelling
What is pannus?
Synovial tissue that is chronically inflamed
What happens after synovial tissue is inflamed?
It starts to eat away at adjacent bone starting with small area of bone which isn’t covered by articular cartilage- periarticular erosions are seen first
What is the cellular structure of synovium like?
It is almost a single cell lining and there are macrophages and fibroblasts (which produce synovial fluid) within synovial lining
Why is synovial fluid viscous?
It contains a lot of hyaluronic acid
What is articular cartilage made up of?
Type 2 collagen- main proteoglycan is aggrecan
Why does the synovium become a proliferated mass of tissue (panes)?
Neovascularisation- formation of new blood vessels
Lymphangiogenesis- formation of new lymphatics
What cells will there be a lot of within the joint?
Inflammatory: Activated B and T cells Plasma cells Mast cells Activated macrophages
How is there a cytokine imbalance?
Excess of pro-inflammatory cytokines
What are the key cytokines involved?
IL-1
IL-6
TNF-alpha
What does pleiotropic mean?
When one gene influences two or more seemingly unrelated phenotypic traits. Consequently a mutation in a pleiotropic gene may have an effect on some or all traits simultaneously
What is the aim of treatment for rheumatoid arthritis?
Prevent joint damage
What are DMARDS?
Disease-modifying anti-rheumatic drugs
Dont cure but may induce remission and prevent joint damage- reduces inflammation in synovium
What examples of DMARDs are there?
Methotrexate (commonly used) Sulphasalazine (commonly used) Hydroxychloroquine (commonly used) Leflunomide (uncommon) Gold (rarely used now)
What is the problem with DMARDs?
All have significant adverse effects so require regular blood test monitoring during therapy
What is the problem with biological therapy?
Drugs are very expensive
Increased infection
What is TNF alpha inhibition associated with?
TNF alpha inhibition is associated with increased susceptibility to mycobacterial infection (in, particular, tuberculosis)- all patents need to be screened for TB
What is B cell depletion therapy associated with?
Hepatitis B reactivation so need to screen all patients for hep B before treatment
Also associated with JC virus infection and progressive multifocal leukoencephalopathy
