RA Flashcards
What is Rheumatoid Arthritis?
- Autoimmune, systemic inflammatory disease that typically affects small joints
- Chronic, persistent synovial inflammation leads to destruction of articular cartilage and bone (synovial membrane is what surrounds the joint).
- Causes decline in joint function and progressive disability
- Between 0.5-1% of adults have condition, relatively common disease (Smolen et al., 2016)
Reduced life expectancy
What are the clinical featurs of RA?
- The most common feature is a symmetrical polyarthritis (same type of the joint on both left and right of the body) with pain and swelling affecting the small joints of the hands and feet
- Patients with RA can experience morning stiffness in and around the affected joints which improves with activity
- Systemic features: increased incidence of atherosclerosis and vasculitis (inflammation of the blood vessels – affects the cardiovascular system) (same type of inflammation on left and right of the body)
What would lab results show?
- increased level of acute phase reactants (e.g. C reactive protein (CRP)
- increased level of erythrocyte sedimentation rate (ESR)) (going down much faster – well known marker for increased inflammation)
- presence of autoantibodies such as RF and ACPA
What are the Symptoms of RA?
• Swelling, tenderness pain, warm when touch joint
What are the Risk Factors of RA?
- Gender: Female gender (3:1 – 3 times more likely than men, perhaps hormonal involvement)
- Genetic predispositions: There are strong associations between HLA-DR4 and HLA-DR1 and RA, which may be familial or non-familial (sporadic).
- Heritability 53% - 68% - genes play a big role
- HLA peptide binding grove - “Shared epitope”
- The protein tyrosine phosphatase 22 gene (PTPN22)
CTLA4 – negative regulator, STAT4,IL-6, NF-Kb, PAD enzymes – involved in regulating the immune function
- Age - increases with age (60+).
- Environmental risk factors
- Smoking
- Infection
- Microbes: P.gingivalis – bacteria in the gums – periodontitis. This bacterium carries the enzymes which generate auto antibodies
- Dust/silica exposure
- Diet
- Hormonal
What are the antibodies in RA?
• Rheumatoid factors (RFs) are autoantibodies that recognize the Fc portion of immunoglobulin G molecules
RFs have numerous causes in addition to RA and therefore have limited specificity for RA
What are the autoantibodies associated with RA?
Autoantibodies to citrullinated protein/peptide antigens (ACPAs)
PAD enzymes in the presence of Ca can convert Arginine into Citrulline
The anticyclic citrullinated peptide (anti-CCP) assay broadly detects antibodies against citrullinated proteins (ACPAs) and has high specificity and excellent sensitivity in RA
Anti-CCP/ACPAs precede the onset of clinical RA and are associated with more severe disease, making them useful as diagnostic and prognostic tools
How many points of the ACR/EULAR criteria does someone need to be diagnosed as having RA?
Need 4/7 to be diagnosed
- Morningstiffness
- Arthritis of 3 or more joints
- Arthritis of hand joints
- Symmetric arthritis
- Rheumatoid arthritis
- Serum Rheumatoid factor
- Radiographic changes
Describe the pathogenesis of RA
- Macrophages produce loads of pro-inflammatory cytokines
- Neutrophils become activated
- No control – cause uncontrollability and then damage of the joint. Leads to new cell epitopes which will be presented to the cells
- Lymph node: has antigen presenting cells such as dendritic cells which will present newly self-modified proteins to the t cells. Interaction Is between MHC molecule and T cell. T cell activated and immune response activated
- B cells become activate and proliferate and produce autoantibodies against cytrillinated proteins.
- Synovial fibroblasts – they become activate and start to proliferate. They invade the joint towards the cartilage. They produce matrix degrading enzyme which causes cartilage breakdown.
What is the DAS28 score?
Shows you the level of disease activity
Clinician will:
- Count the number of swollen joints (out of the 28)
- Count the number of tender joints (out of the 28)
- Take blood to measure the erythrocyte sedimentation rate (ESR) or C reactive protein (CRP)
Ask patient to make a ‘global assessment of health’ (indicated by marking a 10 cm line between very good and very bad)
Results are then fed into a mathematical formula to produce the overall disease activity score
• DAS28 > 5.1 - active disease
• DAS28 < 3.2 - low disease activity
• DAS < 2.6 – remission
When is the window of opportunity to treat RA?
3 MONTHS (First onset of clinical symptoms)
What is the first line treatment for RA?
Methotrexate
What are the conventional synthetic DMARDs?
methotrexate, sulfasalazine, leflunomide and hydroxychloroquine
What are the Targeted synthetic DMARDs (tsDMARD?
tofacitinib (Janus kinase signalling molecule inhibitor)
Describe the pharmacological treatment pathway of RA.
- Monotherapy with csDMARD - MTX, Sulfasalazine, leflunomaide - within 3 months
Alternative: Hydroxychloroquine - Short term bridging with glucocorticoid
- Offer additional csDMARD if disease not improving despite increase in dose.
- Inadequate control with csDMARD. Try bDMARD - TNFa inhibitor
- Inadquate response -> Rituximab with MTX
Symptom control with NSAID and PPI (Offer lowest dose).
