Arthritis Flashcards
What is rheumatoid arthritis?
An autoimmune disorder primary affecting joints resulting in warm, swollen, painful joints
Symptoms typically worse after rest- morning stiffness in and around joints
Affects multiple joints
What is the main kind of inflammation in rheumatoid arthritis?
Synovial inflammation Includes: - synovial joints - Tenosynovium surrounding tendons - Bursa Synovial membrane is abnormal in rheumatoid arthritis
What occurs to the synovium in rheumatoid arthritis?
Synovium becomes a proliferated mass of tissue due to:
Neovascularisation
Lymphangiogenesis
Inflammatory cells: activated B and T cells, plasma cells, mast cells, activated macrophages
What is the role of cytokine in rheumatoid arthritis?
There is a cytokine imbalance between pro-inflammatory and anti-inflammatory cytokines (cytokine imbalance)
The cytokine TNF- alpha is the dominant pro-inflammatory cytokine in rheumatoid synovium.
What are the roles of TNF- alpha?
Osteoclast activation
Chondrocyte activation (cartilage destruction)
Angiogenesis
Leukocyte accumulation
Endothelial cell activation (upregulation of E-selectin and VCAM-1)
Chemokine release (RANTES, MCP-1, IL8, SDF-1)
Pro-inflammatory cytokine release (IL1, IL6, IL23, GM-CSF)
Hepcidin induction
PGE2 production
How can we treat rheumatoid arthritis?
TNF-alpha inhibition- can be done through injecting antibodies or fusion proteins
What 2 antibodies are found in rheumatoid arthritis?
Rheumatoid factor
Antibodies to citrullinated protein antigens (ACPA)
What are rheumatoid factor antibodies?
Antibodies recognise the Fc portion of IgG as their target antigen
Typically IgM antibodies
They form complexes which trigger inflammation
What are antibodies to citrullinated protein antigens?
Antibodies to citrullinated peptides are highly specific for rheumatoid arthritis
E.g. Anti- cyclic citrullinated peptide antibody (anti-CCP antibody)
Cirtrullination of peptides is mediated by enzymes termed peptidyl arginine deiminases
What are symptoms of rheumatoid arthritis?
Chronic arthritis:
- polyarthritis- swelling of small joints of hands and wrists common
- symmetrical
- may lead to joint damage and destruction
Extra-articular disease:
- rheumatoid nodules
- fever
- weight loss
Subcutaneous nodules
What causes subcutaneous nodules?
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Associated with: rheumatoid factor, extra- articular manifestations, severe disease
What drugs can we use to treat rheumatoid arthritis?
Disease modifying anti-rheumatic drugs (DMARDs)
1st line treatment is methotrexate (folate antagonist) in combination with hydroxychloroquine or sulfasalazine
2nd line treatment is biological therapies inc. Janus kinase inhibitors: Tofacitinib and Baricitinib
Glucocorticoid therapy- avoid long term use
Multi- diciplinary approach e.g. physiotherapy, occupational therapy, surgery etc.
What biological treatments can we use for rheumatoid arthritis?
These are proteins that specifically target a protein such inflammatory cytokines e.g:
- Inhibition of TNF-alpha- antibodies (infliximab), fusion proteins (etanercept)
- B cell depletion- Rituximab (antibody against B cell antigen CD20)
- Mediation of T cell co-stimulation- Abatacept
- Inhibition of IL-6 signalling- Tocilizumab (RoActemra) and Sarilumab (Kevzara)- both antibodies against IL6 receptor
What is septic arthritis?
Bacterial infection of synovial joint (usually caused by spread from blood)
Its a medical emergency and needs to be treated immediately
Usually 1 joint is affected (monoarthritis)
What are risk factors and symptoms of septic arthritis?
Risk factors: Immunosupressed, pre-existing joint damage, IV drug use
Symptoms: Acute pain, red, hot, swelling of joint
How is septic arthritis diagnosed and what are common organisms that cause it?
Joint aspiration. Send sample for gram stain and culture
Common organisms: s. aures, streptococci, gonococcus (usually affects multiple joints and less likely to cause joint destruction)
How is septic arthritis treated?
Surgical washout and IV antibiotics