rheumatoid arthritis Flashcards
epidemiology
0.3-1.5% of the population and 1% of the UK
aetiology
- ages of 25-50 - 2-3:1 (F: M) - genetics with no racial or geographical significance
genetic factors in RA
- HLA (human leukocyte antigen - 15-20% concordance in twins
environmental factors in RA
- tobacco smoke, air pollution, mineral oil, female hormones, streoptoccocous
pathophysiology of RA
systemic, chronic autoimmune disease affecting the synovial joints, lungs, heart and eyes
what are the 4 phases of RA
- initiator phase 2. inflammation stage 3. self-perpetuating phase 4. destruction phase
what happens in the initiator phase
Event unknown, antigen presenting cells and citrillination of proteins - now seen as non-self
what happens in the inflammation stage
Self-antigens are presented causing clonal expansion of T/B cells insufficiently controlled by Tregs
what happens in the self perpetuating stage
Inflammatory damage in synovium causes self-antigens previously unseen by the immune system to be exposed
what happens in the destruction phase
Synovial fibroblasts and osteoclasts activated by cytokines (TNF, IL6)
cells involved in synovial inflammation
b cells, autoantibodies, t cells, mmps
role of b cells in synovial inflammation
produce autoantibodies, which can activate compliment and bind to activated macrophages in synovium, perpetuates inflammation
role of t cells in synovial inflammation
potentially activate monocytes, macrophages and synovial fibroblasts which produce TNFα, IL-1 and IL-6
role of autoantibodies in synovial inflammation
rheumatoid factor (RF) (directed against Fc fragment of IgG) and anti-citrullinated peptides (anti- CCP) are directed against antigens commonly present outside of the joint.
role of mmps in synovial inflammation
degrade the cartilage
role of IL6
iron redistribution in liver
Effects of excess TNF/RANKL
low bone mineral density/fractures
role of TBFa/IL6/1
low stress tolerance, depression
role of TNFa/IL6
free fatty acid adipocytes
What can compliment immune complexes/IL6/TNFa cause
atherogenesis, MI, stroke
signs/symptoms
varies and often insidious - fever, malaise, weakness, weight loss, fatigue, nodules, synovitis (symmetrical)
co-morbidities
Increases CV, infection, respiratory, osteoporosis, malignancy, depression risk - Worse when treatment is delayed
diagnosis
- Erythrocyte sedimentation rate (ESR): quicker sedimentation means more inflammation * C-reactive protein (CRP): more inflammation means more inflammation * Rheumatoid factor (RF): not specific but indicative severe disease * Antinuclear antibody (ANA): uncommon (40%) indicative of severe disease * Anti-cyclic peptide (anti-CCP): more RA specific, not present in everyone ○ ANA and anti-CCP = 0 positive * Anaemia * Radiology - On examination * Limitation of movement and tenderness on palpation
aims of treatment
- To minimise pain and swelling - Prevent deformity - Maintain quality of life and control extra articular manifestations
