Rheumatoid Arthritis Flashcards
RHEUMATOID ARTHRITIS is….
CHRONIC AUTOIMMUNE DISEASE CHARACTERISED BY PAIN, STIFFNESS AND SYMMETRICAL SYNOVITIS (INFLAMMATION OF THE SYNOVIAL MEMBRANE) OF SYNOVIAL (DIARTHRODIAL) JOINTS
Why can’t RA cause back pain
the back has no synovia
3 key features of RA?
CHRONIC ARTHRITIS
EXTRA-ARTICULAR DISEASE CAN OCCUR
RHEUMATOID ‘FACTOR’ MAY BE DETECTED IN THE BLOOD
Examples of synovial joints?
- Metacarpophalangeal joints (MCP)
- Proximal interphalangeal joints (PIP)
- Wrists
- Knees
- Anles
- Metatarsophalangeal joints (MTP)
Key features of chronic arthritis in RA? (5)
- Polyarthritis- swelling of the small joints of the hand and wrists s common
- Symmetrical
- Early morning stiffness around joints
- May lead to joint damage and destruction- ‘joint erosions’ or radiographs
o Patients tend to feel ‘unwell’ as it’s a systemic illness
What is rheumatoid factor?
- IgM autoantibody against IgG
What is extra-articular disease and how do these occur?
- Rheumatoid nodules - subcutaneous swelling that occur in certain places which are related to rheumatoid factor and immune complexes that form
- Others rare e.g. vasculitis, episcleritis
o This is because of rheumatoid factor (autoantibody) forming immune complexes, which can go anywhere
RA is more common in males or females?
Females
what is a shared epitope
specific set of amino acids is conserved among all HLA subtypes that are associated with RA
Important environmental factor in RA?
Smoking
What does synovitis to cause damage
Synovitis causes joint damage by damaging articular cartilage
What is the Swan-neck Deformity
o Hyperextension at the PIP
o Hyperflexion at the DIP
What is the Boutonniere Deformity
o Hyperflexion at the PIP
o Boutonniere means ‘button-like’
What deformity is:
o Hyperflexion at the PIP
Boutonniere Deformity
What deformity is:
o Hyperextension at the PIP
o Hyperflexion at the DIP
Swan-neck Deformity
3 sites of pathology of the synovium kn RA?
- Synovial joints
- Tenosynovium surrounding tnedons
- Bursa
What is SUB-CUTANEOUS NODULES? Incidence?
- Central area of fibrinoid necrosis surrounded by histocytes and peripheral layer of connective tissue
- Occur in 30% of patients
Rheumatoid factor is fundamentally what and most commonly how does this manifest?
- Antibodies that recognise the Fc portion of IgG as their target antigen
- Typically, IgM antibodies i.e. IgM anti-IgG antibody
What antibodies are highly specific for RA?
ANTIBODIES TO cyclic CITRULLINATED PROTEIN ANTIGENS (ACPA) (ACCP antibodies)
What is the tenosynovium
wraps around tendons to allow them to move freely
if rheumatoid nodules are present, then the patient is always XX positive
rheumatoid factor
Why is the fact that its IgM producing autoantibodies key to producing nodules
Because its a pentameric Ig
Citrullination of peptides is mediated by enzymes termed….
- PEPTIDYL ARGININE DEIMINASES
Where are peptides citrullinated
Frequently in areas of inflammation
Why do multiple HLA serotypes predispose to RA?
Because they all contain the shared epitope, the shared 67aa long chain in their antigen binding group
HLA serotypes associated with RA? (4)
HLA-DR1, HLA-DR6, HLA-DR10 as well as the HLA-DR4.
Common extraarticular features of RA? (2)
- Fever, weight loss
- Subcutaneous nodules
Uncommon extraarticular features of RA? (6)
- Vasculitis
- Ocular inflammation e.g. episcleritis
- Neuropathies
- Amyloidosis
- Lung disease- nodules, fibrosis, pleuritic
- Felty’s syndrome- triad of splenomegaly, leukopenia and RA
RADIOGRAPHIC ABNORMALITIES IN EARLY RA?
Juxta-articular osteopenia
RADIOGRAPHIC ABNORMALITIES IN LATE RA?
Joint erosions at margins of the joint
RADIOGRAPHIC ABNORMALITIES IN LATEST RA?
Joint deformity and destruction
Thickness of the synovium?
1-3 cells deep
Main molecule in the synovium lining?
Type 1 collagen
What produces synovial fluid
Fibroblasts
What cells are within the synovial lining? (2)
Macrophages and fibroblasts
What molecule is in synovial fluid? What is thickness of the synovial fluid?
Hyaluronic acid
Viscous
What is the articular cartilage made of?
T2 collagen
Aggrecan (proteoglycan)
What is a pannus
proliferated mass of tissue
What is the pathogenesis of RA? (2, 1st can be split into 3)
Synovial membrane is abnormal
The synovium becomes a proliferated mass of tissue (PANNUS) due to:
- Neovascularisation
- Lymphangiogenesis
- Inflammatory cells e.g. activated T and B cells, plasma cells, mast cells and activated macrophages
Recruitment, activation and effector functions of these cells is controlled by a cytokine network- there are more pro-inflammatory cytokines than anti-inflammatory (cytokine imbalance)
• The key cytokines involved in RA are…
o TNFalpha, IL-1, IL-6
• TNF-alpha is mainly produced by….
activated macrophages
Best form of antibody treatment for RA patients? another 3?
Anti-TNFalpha
Anti IL6 is next best then Anti IL1
B cells in RA can also be depleted by parenteral (IV) administration of an AB against a B cell surface antigen- CD20.
2 approaches in managing RA?
MDT approach
Medication
Drugs that are used to treat RA? (4)
Disease modifying anti-rheumatic drugs (DMARDs)
Biological therapies
glucocorticoids
DMARD THERAPY aims to achieve what (2)
- Reducing synovial inflammation
2. Slowing/preventing structural joint damage e.g. bone erosions
Onset of DMARDs?
Slow onset of action e.g. weeks
Example of DMARD?
- METHOTREXATE or
JANUS KINASE INHIBITORS
4 biologic therapies for RA?
INHIBITION OF TNF-ALPHA (ANTI-TNF)
B CELL DEPLETION
3. MODULATION OF T CELL CO-STIMULATION
4. INHIBITION OF IL-6
Anti-TNFalpha antibody name?
infliximab
Downside to biological therapy? (2)
ll expensive so in England their use follows NICE guidelines
Side-effects for all include increased infection risk
