Rheumatoid Arthritis Flashcards
What is the normal composition of the synovium/synovial membrane?
Two layers with two kinds of cells-macrophages and fibroblasts. Beneath this is the sub-synovium which is made from loose connective tissue.
What is the pathology of RA?
Inflamed synovium with hyperplasia. The synovium shows increased angiogenesis, cellular hyperplasia, influx of inflammatory cells (neutrophils, B cells, T cells and macrophages), changes in the expression of cell surface adhesion molecules, and many cytokines. This leads to eventual destruction of all parts of the involved joint.
What is the definition of RA?
Rheumatoid arthritis is a chronic symmetric polyarticular inflammatory joint disease, which primarily affects the small joints of the hands and feet
What are the antibodies generated in RA?
Rheumatoid factor
Anti-citrullinated protein antibody (ACPA)
Diagnostic anti-CCP assays recognise citrullinated self-proteins
α-enolase, keratin, fibrinogen, fibronectin, collagen, vimentin
What are the genes associated with RA?
PTPN22
HLA-DRB1
What are environmental factors that can affect RA?
Smoking and bronchial stress (exposure to silica)
Infectious agents have been associated with RA
-Viruses (EBV, CMV)
-E. Coli
-Mycoplasma
-Periodontal disease (Porphyromonas gingivalis)
-Microbiome (gut microbes)
What is citrullination and what is its role in RA?
Citrullination is the conversion of the amino acid arginine in a protein into the amino acid citrulline and these proteins are attacked by the body.
What are the systemic effects of RA?
Vasculitis, nodules, scleritis, amyloidosis are secondary to uncontrolled chronic inflammation Cardiovascular disease -Altered lipid metabolism -Elevated acute-phase reactants -Increased endothelial activation Fatigue and reduced cognitive function (secondary fibromyalgia) Dysregulation of the HPA axis Liver -Elevated acute-phase response -Anaemia of chronic disease (IL-6 increases hepatocyte production of hepcidin, an iron-regulatory hormone) Lungs -Interstitial lung disease -Fibrosis Muscles (sarcopoenia) Bone (osteoporosis) Secondary Sjogren’s syndrome
What is the usual age of onset for RA?
4th or 5th decade but can present at any age above 16
What are the signs and symptoms of RA?
Joint pain Joint swelling Stiffness particularly in the morning Immobility Poor function Rheumatoid Nodules Systemic Symptoms-anaemia, fatigue and weight loss Tenderness Limitation of Movement Redness Heat
What investigations should be done in RA?
FBC CRP ESR Rheumatoid Factor Anti CCP antibody ANCP antibody X-ray Ultrasound
How can RA be assessed and monitored?
DAS28
DAS<2.4 represents clinical remission
DAS>5.1 represents eligibility for biologic therapy
What things are taken into account in DAS28?
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 you (the patient) to make a ‘global assessment of health' (indicated by marking a 10 cm line between very good and very bad).
What are the four categories of treatment for RA?
Non steroidal anti inflammatory drugs (NSAID)
Disease Modifying anti Rheumatic drugs (DMARD)
Biologics
Corticosteroids
Name four DMARDs
Methotrexate
Sulfasalazine
Hydroxychloroquine
Leflunomide
