Rheumatoid Arthiritis Flashcards
What is Rheumatoid Arthritis?
It is a systemic autoimmune disease.
It is a chronic, progressive, systemic, inflammatory disorder affecting the synovial joints.
- The inflammation occurring in RA may also affect eyes, lungs and heart
- RA can affect any joint but commonly hand, feet, knee and hip
- RA develops between the ages of 25 and 50
- More women are affected than men
Does RA have a genetic predisposition?
RA has a specific genetic predisposition and approximately 70% of RA patients express human leukocyte antigen (HLA)-DR4
What other environmental factors may be involved in the development of RA?
- Tobacco smoke
- Air pollution
- Occupational exposure to mineral oil and silica
- Infectious agents
- Female hormones
What is the pathophysiology of Rheumatoid Arthritis?
- Initiator phase:
The initiating event is unknown and the reason for joint specific localisation is unknown
- May be due to injury, infection, exposure to toxic substance
- Antigen presenting cells and citrullination of proteins which are now seen as non-self therefore triggering an immune response
- Inflammation phase:
The self antigens (citrillinated proteins present and that leads to an immune reaction.
- There’s a clonal expansion of T and B cells
- They are insufficiently controlled by the regulatory T cells
- So we now get T and B cells activated in the joint where we don’t want them activated.
- Self perpetuating phase:
Because we are now causing inflammatory damage in the synovial, we now start to release self antigens that previously haven’t been seen by the immune system. Therefore the self-antigens are now exposed.
- This means we have an immune response against the cartilage
- There’s also infiltration of the immune cells
- Destruction phase:
The synovial fibroblasts and osteoclasts are activated by cytokines (TNF, IL-6)
- This then starts to destroy the bone and cartilage causing damage in the tissue
How are B cells involved in the pathophysiology of RA?
They produce autoantibodies which can activate complement system and also bind to activated macrophages in the synovial joint. Activated macrophages continue/perpetuate the inflammation.
How are autoantibodies involved in the pathophysiology of RA?
Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated peptides are directed against antigens commonly resent outside of the joint.
Hence a whole range of autoantibodies produced against self
How are T cells involved in the pathophysiology of RA?
T cells activate monocytes. macrophages and synovial fibroblasts to produce TNFa, IL-1 and IL-6.
These cytokines induce the production of MMPs which degrade the cartilage.
This joint destruction might be caused by CD4 T cell cytokine: RANK ligand, which promotes osteoclasts (they reabsorb the bone- losing bone)
What are the signs and symptoms for Rheumatoid Arthritis?
- Insidious (subtle gradual) onset of fever, malaise, weakness.
- Symmetrical - inflammation- pain, tenderness, swelling, stiffness, redness and joint warmth
- Usually in the small synovial lined joints of the hands and wrists or feet
- Can affect any joint - Progressive articular deterioration - loss of function
- Inflammation, destruction of bone and cartilage
- Deformity, limited motion, pain on motion - General symptoms
- Weight loss
- Fatigue
- Mental health changes - Extra-articular manifestations - including lungs, heart, eyes, skin
- RA nodules
- Clinical course
- Generally exacerbations/flares and remissions with general chronic progression
- Less likely self limiting
- Can be chronic intermittent - Comorbidities increases patients:
- Cardiovascular risk
- Risk of infection
- Risk of respiratory disease
- Risk of osteoporosis
- Risk of malignancy
- Risk of depression
- Patient outcomes are compromised when treatment is delayed
- Appropriate treatments can alter the course of the disease
What tests can be done for diagnosis of RA?
- Blood tests:
INFLAMMATORY MARKERS
- Erythrocyte sedimentation rate (ESR)
- C-reactive protein (CRP)
IMMUNOLOGICAL PARAMETERS
- Rheumatoid factor (RF)
- Antinuclear antibody (ANA)
- Anti-cyclic citrullinated peptide (anti-CCP)
- Radiology
What indicates RA on examination? (physical examination)
- Limitation of motion
- Tenderness on palpation
What factors are needed for the diagnosis of RA?
Dependent on complete history taking, clinical presentation and investigations.
- History:
- Morning stiffness for greater than 30mins
- Stiffness after quiescence (inactivity)
- Family history
- Lifestyle - Clinical presentation:
- Symmetrical effects on synovial joints - Investigations:
- Inflammatory markers
- Haematological parameters
- Immunological parameters
- Radiological investigations
What does the NICE guidelines suggest for diagnosis of RA?
Referral - Primary care to specialist - refer those with suspected persistent synovitis.
URGENTLY if: Affecting small joints of hands and feet, more than 1 joint, delay of > 3 months before seeking medical advice
Diagnosis:
If found to have synovitis on clinical examination - determine rheumatoid factor, consider anti-CCP antibodies (if negative for RF), x-ray hands and feet.
What is DAS28?
It is a way of monitoring the disease. A measure of disease activity - 4 different measures.
- Number of swollen joints (out of 28)
- Number of tender joints (out of 28)
- Measure ESR or CRP
- ‘Global assessment of health’ -> Which gives overall disease activity score
Scores:
DAS 28 = > 5.1 = Active disease
DAS 28 = < 3.2 = Low disease activity
DAS 28 = < 2.6 = Remission
This score allows disease/treatment monitoring, criteria for eligibility for biologic treatment.
What are the aims when treating rheumatoid arthritis?
- Minimising joint pain and swelling
- Preventing deformity and radiological damage (i.e. erosion)
- Maintaining QoL (Quality of life)
- Controlling extra-articulate manifestations
What are the treatment options available for Rheumatoid Arthritis?
- Analgesia - NSAIDs
- Glucocorticoids
- DMARDs- Disease Modifying Anti-rheumatic Drugs
There are 3 different types of DMARDS:
1. Conventional DMARDS (cDMARD) - E.g. Methotrexate, Sulfasalazine, Leflunomide
- Biologic DMARDs (bDMARD) - E.g. Anti0TNF and other biologics
- Targeted DMARDs (tDMARD)- JAK inhibitors
According to the NICE guidelines, a strategy used to treat Rheumatoid Arthritis is ‘Treat to target’.
What is meant by ‘Treat to target’?
A strategy which should include frequent review, formal assessment of joints and escalation of therapy if inflammation is still present until good control is reached.
- Patients have an individual target (DAS score)
- Requiring tight control (strict)
The target should be remission if there is increased risk of radiological progression.
- CRP and disease activity (i.e. with DAS 28) monthly in specialist care until target reached.
What is the initial treatment (newly diagnosed active RA) for rheumatoid arthritis according to NICE guidelines?
First line- Conventional DMARD as Monotherapy. As soon as possible (ideally within 3 months of onset of symptoms).
Examples include:
- Methotrexate (oral)
- Leflunomide
- Sulfasalazine
Dose should be escalated as tolerated.
Consider short term bridging with glucocorticoid therapy when starting a new DMARD.
What is the ‘step-up strategy’ for RA according to the NICE treatment?
Step- up strategy should be considered when the treatment target has not been achieve (despite dose escalation).
Offer ADDITIONAL cDMARD
If still target not achieved then consider biologics and targeted DMARDs.
What can be used for symptoms control of RA?
Consider NSAIDs (traditional and COX 2 inhibitors) when control of pain and stiffness is inadequate.
- Consider drug toxicities and patients risk factors
- Use the lowest affective dose for the shortest time
- Offer a PPI (proton pump inhibitor - e.g. Omeprazole)
- Review risk factors regularly
What is done for flare management of RA?
For patients with recent onset or established RA:
Short term glucocorticoids can rapidly reduce inflammation
- These should be STOPPED
- The ONLY reason these may continue is when ALL other treatment options have been offered.
What is done in terms of monitoring of Rhematoid Arthritis?
- Patients should be provided with information on how and when to access specialist care:
- Have rapid access during a flare
- Ongoing drug monitoring
- Review 6 months after achieving target to ensure maintenance
- Annual review
- Assess disease activity, damage and functional ability (i.e. with HAQ (health assessment questionnaire)
- Check for development of comorbidities
- Organise cross referral in the MDT (multidisciplinary team)
- Assess the effect on personal life
What is drug choice decision making dependant on in RA?
- Patient preference
- Patient characteristics
- co-morbidites
- risk factors - Treat characteristics
- Cautions
- Contraindications
- Side effects
- Dosing
- Interactions
- Monitoring requirements etc.
