Rheumatoid arthritis Flashcards
Name 4 sources of musculoskeletal pain
Soft tissue
Bone
Joint
Refered/central
What are the two main types of joint disorder?
Give and example of each
What is affected in these disorders?
Inflammatory disorders
Rheumatoid arthritis
Synovial membrane
Degenerative disorders
Osteoarthritis
Cartilage
Give 3 examples of autoimmune disorders
Rheumatoid arthritis
Connective tissue disorder
Spondylo-arthritis
Name some causes of inflammatory polyarthritis
Infection - septic arthritis
Crystal arthritis
Rheumatoid arthritis
Reactive arthritis
Sarcoidosis
What is the synovium?
Specialised layer of fibrous connective tissue that lines the inner aspect of the fibrous joint capsule and tendon sheaths
It secretes synovial fluid
What is the function of synovial fluid?
Synovial fluid acts as:
Metabolite exchange medium
Lubricant for synovial joints
Why does the prevalence of autoantibodies increase with advancing age?
One theory is that repeat exposure to infection causes an increase in autoantibodies
Everyone has autoantibodies, however autoantibodies don’t always result in autoimmune disease
How can autoimmune T-cells be responsible for autoimmune diseases?
Millions of T cells made daily in the thymic cortex
Many of these are deleted as they recognise self-peptides strongly, others do not recognise anything and die
A few recognise self-peptide weakly and are allowed to mature and leave the thymus
Autoimmune disorders can occur when there are defects in the regulatory T cells
Name some theories of autoimmunity
Defects in regulatory T cells
Molectular mimicry between pathogens and self-peptides
Polycolonal activation of B calls during immune responses or infection, leads to recognition of self antigens
Sequestered antigen not seen by developing T and B cells, so therefore seen as a foreign antigen eg. sperm
If everyone has autoantibodies, why dont all people have autoimmune disorders?
Some people are more genetically susseptible = AI disorders run in families
A person who has one AI disorder, is more susseptible to get another that a person without a AI disorder. eg. AIDS
Name 2 factors that can increase the likelyhood of a geneticlaly susseptible person getting a autoimmune disorder?
Fermale hormones
A enviromental trigger such as infection
When would a test for Rheumatoid factor be high?
>70% positve in Rheumatoid arthritis
In other rheumatic disorders eg. Sarcoidosis and infections
Old age
Why is Rheumatoid factor not a accurate screen for Rheumatoid arthritis?
As age increases Rh factor also increases
>70years = 10-25%
Do not have to have RA for the test to be positive
Which gender is more susseptable to genetic diseases?
Female dominant
What are the clinical features of RA?
Often young-middle age females (20-50 years)
Pain and stiffness in joints
Gradual or sudden onset
Usually symmetrical, hands, feet, other joints
Often a family member has RA
Smoking increases risk of developing RA
What are the 3 S’s of inflamatory arthritis?
Stiffness
Early mornign joint stiffness lasting over 30 min
Swelling
Persistant swelling of one joint or more - especially hand joints
Squeezing
Squeezing of the joints is painful
Regarding RA, what are the following?
- Gender prevalance
- incidence
- Prevalance
- Genetics
- Peak onset
- Female:Male = 3:1
- 30/100,000 pop/year
- 1% of the adult population
- Association with HLA-DR4 and HLA-DR1
- Between 20-50 years
How would RA typically present in a patient?
Symmetrical arthropathy
Hands & feet > 80% cases
Early morning stiffness
Symptoms:
- Systemic: fatigue, anorexia, weight loss
- Low grade fever, anaemia
- Articular- joint aching and stiffness
Name 4 RA hand deformaties you may see on clinical examination
Early fusiform swelling
Ulnar deviation
Swan neck deformities
Boutonniere deformities
In RA, what may be present on the joints of the hands?
Rheumatoid nodules
Packed ith fibroblasts
Normally seen alongside ulnar deviation
Describe the pathogensis of RA
Inflammation of the synovium
Secondary changes then occurring in the cartilage
Circulating autoantibody – rheumatoid factor in 80% (seropositive arthritis).
This complexes to IgG to form immune complexes found in joint synovium, fluid and elsewhere.
Wayward immune response causes synovial inflammation
Recruitment of PMNs, macrophages and lymphocytes
Phagocytosis of immune complexes and release of lysosomal enzymes
Destruction of joint cartilage and recruitment of further inflammatory cells
Vasodilation causes redness and swelling
Hyperplasia of synovium and angiogenesis: vascular granulation tissue = pannus
Inflammatory cells in pannus destroy cartilage and bone and cause ankylosis (stiffening and fusion)
What are the tests you would do for RA?
FBC : anaemia (anaemia of chronic disease)
ESR /CRP : moderately raised
Immunology:
•Rheumatoid factor (RF) : raised in ~70% of cases
(and in some healthy people)
•Anti-cyclic citrillunated peptides antibodies (Anti CCP): positive in ~60% patients with RA
What would you see from a radiological investigations fo someone with RA?
Early disease:
X-rays usually normal
Detect synovitis on ultrasound or MRI
Late disease:
Soft tissue swelling
Juxta-articular osteopenia
Joint space narrowing
Erosion of bone
Loss of cartilage
Deformity
Describe the analgesic treatment route for RA
ONLY TREATS THE SYMPTOMS/PAIN
Paracetamol
=>
Paracetamol and NSAIDS
=>
Weak opiod - Codiene
=>
Moderate opiod - tramadol
=>
Strong opiod - morphine
Describe the combination treatment route for RA
Sulfasalazine + Methotrexate
Also use Analgesic therapys for pain
Corticosteriod therapy is used as a quick fix while the combination therapy takes effect
Biological therapies may also be used (best, but very expensive)
Describe how corticosteroids work to treat RA
Give and example of a corticosteroid used to treat RA
Result in blanket immunosuppression
Administered orally or intra-articular
Prednisolone
Inhibition of trascription factors
=>
Reduced transcription of many cytokine genes e.g. ↓IL1, IL2 and TNF
=>
Reduced clonal proliferation of Th Cells
Give examples of disease modifying drugs used to treat RA
Antiproliferative (cancer drugs)
Methotrexate (against folate activity)
Azathioprine (against purine synthesis)
Immunomodulator
Sulfasalazine
What are the side effects of disease modifying drugs such as methotrexate?
- Increased risk of infections
- Teratogenic e.g. methotrexate (avoid if planning pregnancy)
- GI-mouth ulcers, nausea, diarrhoea
- Hair loss
What are the pros and cons of using biological agents to treat RA?
Give examples of biological agents
Monocolonal antibody therapy (MAb)
Infliximab = Anti TNF
Rituximab = Anti CD20 on B cells
Specific to one single target
Very expensive (£6-9,000/patient/year)
NICE aproval needed
Must be administered by injection or infusion as they are protien drugs so will be digested on ingestion
What is the general prognosis for someone diagnosed with RA?
Are there any potential complications?
In general, good providing there is early diagnosis, managment, disease control and treatment
<10% will become severly disabeld
Complications:
Periodic flare ups requiring drug therapy
Reduced immunity from immunosuppression
Complications of drug treatments
