Rheumatoid Arthritis Flashcards
What are the functions of the synovium?
- Maintenance of intact tissue surface
- Lubrication of cartilage
- Control of synovial fluid volume and composition
- Nutrition of chondrocytes within joints
What is the definition of rheumatoid arthritis?
A chronic symmetric polyarticular inflammatory joint disease, which primarily affects the small joints of the hands and feet
Describe the characteristics of rheumatoid synovitisis
- Inflammatory cell infiltration
- Synoviocyte proliferation
- Neoangiogenesis
- Synovial fluid contains neutrophils
- Causes bone and cartilage destruction
Describe the role of autoimmunity in rheumatoid arthritis
- Can be present several years before clinical arthritis
- Autoantibodies (e.g. RFs and anti-citrullinated protein antibodies) - associated with RA
- These either recognise joint antigens (e.g. Type 2 collagen) or systemic antigens (e.g. glucose phosphate isomerase)
- The autoantibodies can then contribute to inflammation through several mechanisms (including activation of complement)
Which antibodies are found in seropositive RA and how can they be detected?
- Rheumatoid factor
- Anti-citrullinated protein antibody (ACPA)
- Anti-CCP assays recognised citrullinated self-proteins
- Patients with ACPA+ disease have a less favourable prognosis
Which genes play a role in RA?
HLA-DRB1, PTPN22, CTLA4 and c-REL
List the environmental factors which are associated with RA
- Smoking and bronchial stress
- Infectious agents: viruses, E. coli, mycoplasma, peridontal disease and microbiome
- Repeated insults in a genetically susceptible individual
What is the role of neoangiogenesis and how is it mediated?
- It provides nutrients to the hyperplastic synovium
- Hypoxic conditions and angiogenic factors (IL-8 and VEGF) enhance blood vessel proliferation in the synovium
- Microvascular endothelia in the synovium express adhesion molecules that guide circulating cells into the joint
How are cartilage and bone destruction caused in RA?
- Proteases (e.g. metalloproteinases and aggrecanases) are produced by FLS in the intimal lining
- Synovial lining cells, especially FLS, can attach to and invade the cartilage
- Bone destruction is mediated by osteoclasts that are activated under the influence of RANKL
List the systemic consequences of RA
- Vasculitis, nodules scleritis and amyloidosis (due to uncontrolled chronic inflammation)
- CVS Disease: altered lipid metabolism, increased endothelial activation etc.
- Fatigue and reduced cognitive function
- Anaemia of chronic disease
- Lungs: interstitial lung disease and fibrosis
- Sarcopoenia
- Osteoporosis
- Secondary Sjogren’s syndrome
List the therapeutic categories for RA therapeutics
- NSAIDs
- Disease modifying anti rheumatic drugs (DMARD)
- Biologics
- Corticosteroids
What are disease modifying anti rheumatic drugs (DMARDs)?
-Structurally unrelated, typically small molecule drugs which have been demonstrated to have slow onset effect on disease activity and retard disease progression
Name the DMARDs currently in use
- Methotrexate
- Sulfalazine
- Hydroxychloroquine
- Leflunomide
Why is methotrexate useful in the treatment of RA?
- Effective, well tolerated and cheap
- Can be used in combination
- People will stay on it
What are biologics DMARDs and why are they used?
- Large complex proteins which need to be given parenterally
- They work rapidly and are generally well tolerated (although they do have toxicities)
