Rheumatoid Arthritis Flashcards
What is rheumatology?
medical speciality of diseases of the MSK system
What is a tendon?
cords of strong fibrous collagen tissue attaching muscle to bone
What is a ligament?
flexible fibrous tissue with connects 2 bones
What is synovium?
1-3 deep cell lining containing:
- macrophage-like phagocytic cells (type A synoviocyte)
- fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)
What is synovial fluid?
hyaluronic acid-rich viscous fluid
What is articular cartilage?
- Type 2 collagen
- proteoglycan (aggrecan)
What are the main 2 different types of arthritis?
- osteoarthritis (degenerative)
- inflammatory (rheumatoid)
What is inflammation?
a physiological response to deal with injury or infection
How does inflammation manifest?
- red
- painful
- hot
- swelling
- loss of function
What are the physiological, cellular and molecular changes caused by inflammation?
- increased blood flow
- WBC migration (leukocytes) into tissues
- activation/differentiation of leucocytes
- cytokine production
What are the different causes of joint inflammation?
- crystal arthritis (gout/pseudogout)
- autoimmune
- inflection
What are some examples of different autoimmune causes of joint inflammation?
- rheumatoid arthritis
- seronegative spondyloarthropathies
- connective tissue diseases
What is gout?
a syndrome caused by the deposition of uric crystals leading to inflammation
What are the causes of hyperuricaemia?
- genetic tendency
- increased intake of purine rich food
- reduced excretion (kidney failure)
What is pseudogout?
a syndrome cause by the deposition of calcium pyrophosphate dehydrate (CPPD) crystal deposition.
What are the risk factors of developing pseudogout?
- Hx osteoarthritis
- elederly
- intercurrent infection
How does gout arthritis present?
- metatarophalangeal joint of the big toe (juxta-articular erosions)
- sudden onset
- painful
- joint: red, warm, swollen and tendon
- resolves spontaneously
What investigation is done in suspected gout arthritis?
joint aspiration: synovial fluid analysis
What management is done in suspected gout arthritis?
acute:
- colcihine
- NSAIDs
- Steroids
chronic:
- allopurinol
What is tested in a synovial fluid test?
- gram stain, culture and ABx sensitivity
- light microscopy to stop what is in here brain
What is the shape of the gout crystal?
needle
What is the shape of the pseudogout crystal?
brick-shaped
What is rheumatoid arthritis?
chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis
(inflammation of the synovial membrane)
What happens in rheumatoid arthritis?
synovium becomes a proliferate mass of tissue
What causes the synovium to become a proliferated mass of tissue?
- neovascularisation
- lymphangiogenensis
- activated B and T cells
- plasma cells
- mast cells
- activated macrophages
- excess of pro-inflammatory cytokines
What is the dominant pro-inflammatory cytokine in rheumatoid arthritis?
- TNF-alpha
- produced by activated macrophages
- inhibition prevents the release of IL1/6/8
What is the impact of the excess TNF-alpha production?
- osteoclast activation
- chemokine release
- endothelial cell activation
- leukocyte accumulation
- angiogenesis
- chondrocyte activation
- pro-inflammatory cytokine release
What are the key features of rheumatoid arthritis?
- polyarthritis (swelling of small joints)
- symmetrical
- early morning stiffness
- may cause joint damage and destruction
- rheumatoid nodules
What can be used to detect rheumatoid arthritis?
rheumatoid factor, autoantibody against IgE
What are the most commonly affected joints with rheumatoid arthritis?
- Metacarpophalangeal joints (MCP)
- Proximal interphalangeal joints (PIP)
- Wrists
- Knees
- Ankles
- Metatarsophalangeal joints (MTP)
Where is the primary site of the pathology of rheumatoid arthritis?
- synovial joints
- tenosynovium surrounding tendons
- bursa
What are the extra-articular features of rheumatoid arthritis?
- fever
- weight loss
- subcutaneous nodules
- vasculitis
- ocular inflammation
- neuropathies
- amyloidosis
- lung disease (nodules, fibrosis and pleuritis)
- Felty’s syndrome
What is Felty’s syndrome?
- slpnomegaly
- leukopenia
- rheumatoid arthritis
What are subcutaneous nodules in rheumatoid arthritis?
central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
What are subcutaneous nodules associated with?
- severe disease
- extra-articular manifestations
- rheumatoid factor
Where do subcutaneous nodules tend to be found?
- the ulnar border of the forearm
- in the hands
What antibodies are found in those with rheumatoid arthritis?
- rheumatoid factor
- antibodies to citrullinated protein antigens
What is a rheumatoid factor?
- Antibodies that recognize the Fc portion of IgG as their target antigen
(typically IgM antibodies i.e. IgM anti-IgG antibody)
What are antibodies to citrullinated protein antigens?
- Citrullination of peptides is mediated by enzymes termed:
Peptidyl arginine deiminases (PADs)
What does rheumatoid arthritis treatment require?
- Early recognition of symptoms, referral and diagnosis
- Prompt initiation of treatment
(joint destruction = inflammation x time) - Aggressive treatment to suppress inflammation
What is the first line treatment of rheumatoid arthritis?
methotrexate in combination with hydroxychloroquine or sulfasalazine
What is the second line treatment of rheumatoid arthritis?
- Biological therapies offer potent and targeted treatment strategies
- New therapies include Janus Kinase inhibitors : Tofacitinib & Baricitini
What drugs are involved in the treatment of rheumatoid arthritis?
Disease-modifying, anti rheumatic drugs
What are the targets of the biologics used in the treatment of rheumatoid arthritis?
- Inhibition of tumour necrosis factor-alpha (‘anti-TNF’)
- B cell depletion
- Modulation of T cell co-stimulation
- Inhibition of IL-6 signalling
What is the mechanism of infliximab and etanercept?
Inhibition of tumour necrosis factor-alpha (‘anti-TNF’)
What is the mechanism of rituximab?
B cell depletion
What is the mechanism of Abatacept?
Modulation of T cell co-stimulation
What is the mechanism of Tocilizumab and Sarilumab?
Inhibition of interleukin-6 signalling
How does Ankylosing spondylitis present?
- lower back pain (>3months) and stiffness (early morning, better with exercise)
- reduced spinal movements
- peripheral arthritis
- plantar faciitis
- achilles tendonitis
- fatigue
What are the visual signs of Ankylosing spondylitis?
- hyperextended neck
- loss of lumbar lordosis
- flexed hips and knees
What is reactive arthritis?
Sterile inflammation in joints following infection especially urogenital (e.g. Chlamydia trachomatis) and gastrointestinal (e.g. Salmonella, Shigella, Campylobacter infections) infections
What are the extra-articular features of reactive arthritis?
- Enthesitis (tendon inflammation)
- Skin inflammation
- Eye inflammation
What can reactive arthritis be a sign of?
- HIV
- Hep C
How do you treat reactive arthritis?
self-limiting
- NSAIDs
- DMARDs
What are the risk factors of reactive arthritis?
- genetic predisposition and environmental trigger
How long does it take for reactive arthritis to present after an infection?
1-4 weeks
What is Psoriasis?
an autoimmune disease affecting the skin (scaly red plaques on extensor surfaces eg elbows and knees)
Can you use rheumatoid factors to diagnose psoriatic arthritis?
not present (seronegative)
How does Psoriatic arthritis present?
- Classically asymmetrical arthritis affecting IPJs
- Symmetrical involvement of small joints (rheumatoid pattern)
- Spinal and sacroiliac joint inflammation
- Oligoarthritis of large joints
- Arthritis mutilans
What investigations can be done for suspected Psoriatic arthritis?
- XR of affected joints
- MRI (scaroiliitis and enhteisitis)
What is the management plan for Psoriatic arthritis?
- DMARDs (methotrexate)
- avoid oral steroids
What is lupus?
a multi-system autoimmune disease associated with antibodies to self antigens (‘autoantibodies’) which are directed against components of the cell nucleus
What is associated with lupus?
- Multi-site inflammation: can affect any almost any organ.
- Often joints, skin, kidneys, haematology.
- Also: lungs, CNS involvement
What clinical tests can be done when lupus is suspected?
- Antinuclear antibodies (ANA)
- Anti-double stranded DNA antibodies (anti-dsDNA Abs):
Why are antinuclear antibodies measured for suspected lupus?
- High sensitivity for SLE but not specific.
- A negative test rules out SLE, but a positive test does not mean SLE.
Why are Anti-double stranded DNA antibodies measured for suspected lupus?
High specificity for SLE in the context of the appropriate clinical signs.
When is lupus most common?
- 15-40 years old
- asian and african populations
What is management plan for Ankylosing spondylitis?
- physiotherapy
- exercise regimes
- NSAIDs
- peripheral joint deposition (DMARDs)
Can you definitively test for Ankylosing spondylitis?
no, seronegative spondyloarthropathy – no positive autoantibodies
What happens in Ankylosing spondylitis?
- Chronic sacroillitis (inflammation of sacroiliac joints)
- Results in spinal fusion (ankylosis) and deformity
What is Ankylosing spondylitis associated with?
HLA B27
When is Ankylosing spondylitis most common?
- 20-30 years old
- male
What tests should be done in suspected Ankylosing spondylitis?
- FBC
- CRP, ESR
- test for HLA-B27
- XR
- MRI
What would blood tests show in Ankylosing spondylitis?
FBC: normocytic anaemia
CRP, ESR: raised
HLA-B27: present
What would imaging (MRI/XR) show in Ankylosing spondylitis?
- Squaring Vertebral bodies, Romanus lesion
- Erosion, sclerosis, narrowing SIJ
- Bamboo Spine
- Bone Marrow Oedema
What are some other examples of connective tissue disorders?
- Systemic Sclerosis
- Myositis
- Sjogrens syndrome
- Mixed connective tissue disease
What is the site of inflammation in Ankylosing spondylitis?
enthesis
what are the seronegative spondyloarthropathies?
- Ankylosing spondylitis
- Reactive Arthritis (Reiters syndrome)
- Psoriatic arthritis
- Arthritis associated with GI inflammation (enteropathic synovitis)
What is SLE?
Chronic tissue inflammation in the presence of antibodies directed against self antigens
(multi-site inflammation: joints, skin and kidney)
What autoantibodies are associated with SLE?
- Antinuclear antibodies
- Anti-double stranded DNA antibodies
- Anti-phospholipid antibodies
What are the connective tissue diseases?
- SLE
- Sjogren’s syndrome
- Autoimmune Inflammatory muscle disease
- Systemic sclerosis (scleroderma)
- Overlap syndromes
What is common in connective tissue disorders?
Reynaud’s phenomenon
What is Reynaud’s phenomenon?
Intermittent vasospasm of digits on exposure to cold
(white to blue to red)
- leads to blanching of digit
- Cyanosis as static venous blood deoxygenates
- Reactive hyperaemia
What information do serum autoantibodies provide?
- correlate to disease activity
- directly pathogenic
- can aid in diagnosis
What is typically non-erosive?
- arthralgia
- arthritis
When is SLE typically diagnosed?
in females aged 15-45 years old
What are the different clinical manifestations of SLE?
- Malar rash
- Photosensitive rash
- Mouth ulcers
- Hair loss
- Raynaud’s phenomenon
- Arthralgia and sometimes arthritis
- Serositis (pericarditis, pleuritis, less commonly peritonitis)
- Renal disease – glomerulonephritis (‘lupus nephritis’)
- Cerebral disease – ‘cerebral lupus’ e.g. psychosis
What is a Malar rash?
erythema that spares the nasolabial fold
What is the pathogenesis of SLE?
- Apoptosis leads to translocation of nuclear antigens to membrane surface
- Impaired clearance of apoptotic cells results in enhanced presentation of nuclear antigens to immune cells
- B cell autoimmunity
- Tissue damage by antibody effector mechanisms e.g. complement activation and Fc receptor engagement
What are anti-phospholipid antibodies associated with?
risk of arterial and venous thrombosis
What autoantibodies are associated with systemic vasculitis?
antinuclear cytoplasmic antibodies (ANCA)
What is the significance of antinuclear antibodies in SLE?
- seen in all SLE cases
- not specific for SLE
What is the significance of anti-double stranded DNA antibodies in SLE?
- specific to SLE
- serum level correlates to disease activity
What is the significance of anti-phospholipid antibodies in SLE?
- associated with risk of arterial and venous thrombosis in SLE
- may also occur in absence of SLE in what is termed the ‘primary anti-phospholipid antibody syndrome
What is the significance of anti-Sm antibodies in SLE?
- specific to SLE
- serum level does not correlate to disease activity
What is the significance of anti-Ro and Anti-La antibodies in SLE?
- secondary sjögren’s syndrome
- neonatal lupus syndrome (transient rash, permanent heart block)
What is the significance of anti-ribosomal P antibodies in SLE?
cerebral lupus
