5: Rheumatoid Arthritis Flashcards
What is rheumatoid arthritis?
Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of the synovial membrane) of synovial (diarthrodial) joints
What are the key signs and symptoms of rheumatoid arthritis?
Chronic athritis
- Polyarthritis (>5) - swelling of the small joints of the hand and wrists is common
- Symmetrical
- Early morning stiffness in and around joints (long time, several hours (not resolved in 30 min as in osteoathritis)
- May lead to joint damage and destruction - ‘joint erosions’ on radiographs
Other features
- Rheumatoid nodules
- •Others rare e.g. vasculitis, episcleritis
Summarise the epidemiology of rheumatoid athritis
- 1% of population, common cause for disabilities in young patients
- women 3x more likely
Which role do genetics and environment palay in the development of rheumatoid arthritis?
- Genetic
- there is an important genetic component, predisposition
- HCA-DR gene variants –> Type 2 HDL –> CD4-positive T-cells
- Environment
- Smoking increases risk
What are the joints most commonly affected by Rheumatoid arthritis?
- Metacarpophalangeal joints (MCP)
- Proximal interphalangeal joints (PIP)
- normally sparing of DIP
- Wrists
- Knees
- Ankles
- Metatarsophalangeal joints (MTP)
–> Early manifestation in Hands and feet
How would you describe the athritis seen in rheumatoid arthritis?
Sympettrical polyarthritis
What is a swan-neck deformity?
What is it associated with?
Swan-neck deformity affecting the ring finger – there is hyper-extension at the PIP joint and hyper-flexion at the DIP joint
–> Can be commonly seen in rheumatoid arthritis
Which kind of joints are usually inflammed in rheumatoid arthritis?
Synovial joints
–> it is an inflammation of the synovial membrane
including
- bursa and
- Tenosynovium surrounding tendons
What is the Boutonnière deformity?
Boutonnière (‘button-like’) deformity affecting little finger – there is hyper-flexion at the PIP joint
How does the swelling around the joints feel on examination in rheumatoid arthritis?
It feels soft (in contrast to hard, ossefied in osteoarthritis)
What are Rheumatoid nodules in rheumatoid arthritis?
What are they associated with?
Sub-cutaneous nudules with
- Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
- 30% of patients
- often associated with severer disease outcome
What is the Rheumatoid Factor?
Antibodies that is associated with Rheumatoid arthritis:
- Antibodies that recognize the Fc portion of IgG as their target antigen
- typically IgM antibodies i.e. IgM anti-IgG antibody !
- •Positive in 70% at disease onset and further 10-15% become positive over the first 2 years of diagnosis
What are ACPA?
What do they indicate and why?
Antibodies to citrullinated protein antigens (ACPA)
- highly specific for rheumatoid arthritis
There is a citrullination (Argnin is converted into Citrulline) of proteins, mediated by Peptidyl arginine deiminases (PADs)
- PADs are high in Monocytes/Neutorphils –> increase in citrullination in inflammed joints
- Higher Citrullination in Rheumatoid arthritis
- immune response against citrullin triggered (influcenced by genetic predisposition + smoking)
Explain the involvement of the “shared epiptope” in Rheumatic Arthitis
- It is a speicial sequence on the HLA-DA antigen-binding groove
- makes it more likely to develop antibodies against citrullated proteins –> higher chance of development of RA
What are the common Extra-articular features of rheumatoid arthritis?
- •Fever, weight loss
- •Subcutaneous nodules
Name other exapmples of extra-articular features in Rhematoid Arthritis
- vasculitis
- Ocular inflammation e.g. episcleritis
- Neuropathies
- Amyloidosis
- Lung disease – nodules, fibrosis, pleuritis
- Felty’s syndrome – triad of splenomegaly, leukopenia and rheumatoid arthritis
What are the radiological findings in Rheumatoid Arthritis?
- Early
- Juxta-articular osteopenia
- •Later
- Joint erosions at margins of the joint
- •Later still
- Joint deformity and destruction
–> Airm is to prevent any changes to occur!
What are the 4 pathological joint based features in rheumatoid arthritis?
- Synovitis
- Bone erosion
- Pannus (connective tissue growth)
- Cartilage degradation + joint space narrowing
Explain the pathogenesis of rheumatoid arthritis
The synovial membrane is abnormal due to
- becomes a proliferateive mase (pannus)
- neovascularisation
- lymphangiogenesis
- inflammatory cells:
- •activated B and T cells
- •plasma cells
- •mast cells
- •activated macrophages
- Controlled by cytokines
- there is an excess of pro-inflammatory vs. anti-inflammatory cytokines (‘cytokine imbalance’)
What is the role of TNF-alpha in rheumtoid arthritis?
It is the predominant cytokine
- pro-inflammatory
- Causing:
- further recruitement of lympho/leukocytes and pro-inflammatory mediators
Explain the biological treatment of rheumatoid arthritis
Often Treated by antibodies to reduce inflammatory response
Biological treatments
- TFN-alpha inhibitors –> decrease inflammation in joint (it is the main pro-inflammatory cytokine in joint) –> antibodies
- Now: also other cytokine blockers (anti IL-6/ anti-IL-11
- Rituximab –> anti: B-cell CD20
- Modulaiton of T cell co-stimmulation
- Abatacept
What is the overall management plan for rheumatoid arthritis?
- Multidisciplinary
- Physiotherapy, occupational therapy etc.
- Medication
- •disease- modifying anti-rheumatic drugs - ‘DMARDs’
- controll the disease process, steroid sparing, are started early in management
- Glucocorticoid therapy
- avoid long-term but can be used for acute treatment
- Biological therapies
- •disease- modifying anti-rheumatic drugs - ‘DMARDs’
What are DMARDs?
What is their MOA and use?
drugs that may induce remission (not cure) and prevent joint damage in Rheumatoid Arthritis via
- reducing the amount of inflammation in the synovium
- slow or prevent structural joint damage e.g. bone erosions
- slow onset of action
- e.g. methotrexate, sulphalazine etc. etc.
But all have significant side-effects
What are the side effects / cons of biological treatments in Rheumatoid Arthritis?
Expensive –> Therefore not NICE approved
- all increase risk of infection (because of immunosupression)
E.g.
- •TNFα inhibition iincreased susceptibility to mycobacterial infection e.g. tuberculosis
- •B cell depletion hepatitis B reactivation
- •B cell depletion therapy JC virus infection and progressive multifocal leukoencephalopathy (PML) - rare
