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
