9.5 Rheumatoid Arthritis Flashcards
What are the 2 types of crystal arthritis?
gout
pseudogout
What is a tendon?
cords of strong fibrous collagen tissue attaching muscle to bone
What is a ligament?
flexible fibrous connective tissue which connects two bones
What are the four components of a synovial joint?
Bone
Articular cartilage
Synovium
Synovial fluid
Why is chronic inflammation of the synovium bad?
leads to permanent damage; inflammatory markers can also attack articular cartilage leaving exposed bone
What is the synovium?
1-3 cell deep lining containing macrophage-like-phagocytic cells (type A synoviocyte) and fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)
AND
Type 1 Collagen
What is the synovial fluid?
hyaluronic acid-rich viscous fluid
What is the articular cartilage?
Type 2 Collagen
Proteoglycan (aggrecan)
What is arthritis?
disease of the joints
What are the main two types of arthritis?
Degenerative (osteoarthritis)
Inflammatory (rheumatoid)
What is inflammation?
A physiological response to deal with injury or infection
What are the 5 clinical manifestations of inflammation?
red (rubor) pain (dolor) hot (calor) swelling (tumor) loss of function
What are 4 physiological, cellular and molecular changes we see when inflammation occurs? (not 5 clinical manifestations)
- increased blood flow
- migration of white blood cells (leucocytes) into the tissues
- activation/differentiation of leucocytes
- cytokine production (TNF alpha, IL-1,6,17)
What are 3 causes of joint inflammation?
Crystal arthritis
Immune mediated-arthritis
Infection
What is crystal arthritis?
Inflammation of the joint triggered by crystals of synovial fluid
What is gout?
syndrome caused by deposition of monosodium urate (uric acid) crystals
What are the risk factors for gout?
high uric acid levels
genetic tendency
increased intake of purine rich foods
reduced excretion (kidney failure)
How does gout present?
abrupt onset (couple of hours) extremely painful 11/10 joint red, warm, swollen, tender resolves spontaneously in 3-10 days affects one large joint - usually big toe
What is pseudogout?
syndrome caused by calcium pyrophosphate dihydrate crystal deposition crystals (CPPD)
What are the risk factors for pseudogout?
background osteoarthritis
elderly patient
intercurrent infection
What will you see on an X ray showing gout
rat bite errosions
How to investigate gout?
joint aspiration- synovial fluid analysis
can blood test to show high uric acid levels
What medication is prescribed for gout?
acute - colchicine, NSAIDs, steroids
chronic - allopurinol
How are synovial fluid samples examined for pathogens and crystals?
rapid gram stain followed by culture and antibiotic sensitivity assays
polarising light microscopy to detect crystals
What will analysis of crystals in gout show?
crystal: urate
shape: needle
birefringence (polarising light microscopy): negative
What will analysis of crystals in pseudogout show?
crystal: CPPD
shape: brick
birefringence: positive
What is rheumatoid arthritis?
chronic autoimmune disease characterised by pain stiffness and symmetrical synovitis
What happens to the synovium in RA?
What controls the immune activation in RA?
Cytokine network
What causes the synovitis, bone erosion, pannus and cartilage degradation in RA?
Excess of pro-inflammatory vs anti inflammatory cytokines
What is the main pro-inflammatory cells in RA?
TNFa
What’s the pattern of joint involvement in RA?
Polyarthritis - many joints involved
Affects large and small joints, primarily MCP and PIP in hands
What is the primary site of pathology in RA?
The synovium
What are som extra-articular features of RA?
Common:
Fever
Weight loss
Subcutaneous nodules
Uncommon: Vasculitis Ocular inflammation Neuropathies Amyloidosis
What are subcutaneous nodules?
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
What % of RA patients have subcutaneous nodules?
30%
Associated with severed disease and extra-articular manifestations and high levels of RF
Where is the typical position of the rheumatoid nodule?
Ulnar body of forearm
Hands
What are the two types of antibodies found in the blood of RA patients?
- Rheumatoid Factor
2 Antibodies to citrullinated protein antigens (ACPA)
What is RF?
Antibodies which recognise the Fc portion of IgG antibody
How many RA patients are RF positive?
70%
Further 10-15% after 2 years of diagnosis
What does it mean if a patient is seronegative?
Absence of RF (in case of RA)
What is the treatment goal of RA?
Prevent joint damage
What requires successful treatment of RA?
Early recognition of symptoms, referral, diagnosis
Joint destruction = inflammation x time
Aggressive treatment
What types of drugs are given to RA patients?
DMARDs
Disease modifying anti rheumatic drugs = drugs that control the disease process
What is the 1st line treatment for RA?
Methotrexate with hydroxychlorquine
What is the 2nd line treatment for RA?
Biological therapies and targeted treatment
Why don’t we prescribe prednisolone for RA?
Avoid long term use because of side effects
What do we use in conjunction with medical treatment for RA?
Physiotherapist
Occupational therapy
Surgery
Etc
What are biological therapies?
Proteins (usually antibodies) that specifically target a protein such as an inflammatory cytokine
What are the 4 biological therapies for RA?
- Anti TNF (infliximab)
2 B cell depletion (rituximab) - Modulation of T cell co stimulation
- Inhibition of interleukin 6 signalling
What is a spondyloarthropathy?
Joint disease of vertebrae
What does seronegative mean?
No positive auto antibodies
What is ankylosing spondylitis
Seronegative spondyloarthropathy
Chronic sacroillitis - inflammation of sacroiliac joints
Results in spinal fusion
What is the common demographic for a patient with AS?
20-30 year old male
What is AS associated with?
HLA B27
Psoriatic arthritis
IBD
How does AS present?
Lower back pain Early morning stiffness - improves with exercise Reduced spinal movements Peripheral arthritis Plantar fasciitis, Achilles tendinitis Fatigue Hyperextended neck
How to we manage AS?
Physiotherapy
Exercise regime
NSAIDs
If peripheral joint disease - DMARDs
What will we see in the blood for AS?
Normocytic anaemia
Raised CRP, ESR
HLA-B27
What is HLA-B27?
human leukocyte antigen B27
HLA is protein that is found on the surface of white blood cells, tells body it is self
HLA-B27 destroys it, indicated autoimmune disease
What would an x ray of AS show?
Squaring vertebral bodies Erosion, sclerosis Narrowing sacroiliac joint Bamboo spine Bone marrow oedema
What is psoriatic arthritis?
Seronegative autoimmune disease affecting the skin (scaly red plaques on extensor surfaces elbows and knees), but patients also have joint inflammation.
Psoriatic arthritis is 10% of psoriasis
How can psoriatic arthritis manifest?
Classically asymmetrical arthritis affecting IPJs
Can be symmetrical involvement of small joints (rheumatoid pattern)
Spinal and sacroiliac joint inflammation
How is psoriatic arthritis investigated?
X ray of affected joint - pencil in a cup abnormality (arthritis mutilans)
MRI- sacroilitis (inflammation)
Bloods - nothing as seronegative
How is psoriatic arthritis managed?
DMARDs - methotrexate
Avoid oral steroids
Why are oral steroids avoided in psoriatic arthritis?
Risk of pustular psoriasis due to skin lesions
What is reactive arthritis?
Sterile inflammation of the joints following infection especially urogenital, (Chlamydia) and gastrointestinal (salmonella, campylobacter)
What are extra articulate manifestations of reactive arthritis?
Enthesitis - tendon inflammation
Skin inflammation
Eye inflammation
What can reactive arthritis be the first manifestation of?
HIV
Hep c infection
What does a typical case of reactive arthritis look like?
Young adult with:
- genetic predisposition (HLA-B27)
- environmental trigger (salmonella)
How long after the initial infection does reactive arthritis occur?
1-4 weeks
How do we treat reactive arthritis?
NSAIDs
DMARDs if required
What is lupus?
A multi system autoimmune disease
What is systemic lupus erthymatous? SLE
Multi site inflammation; can affect any organ
Often joints, skin, kidneys.
Associated with autoantibodies directed against components of the cell nucleus
What are the clinical tests for SLE?
Antinuclear-antibodies (ANA) - high sensitivity for SLE but not specific (negative test rules out)
Anti double stranded DNA antibodies (anti dsDNA Abs) - high specificity in appropriate contex
