Rheumatoid Arthritis Flashcards
What is rheumatology?
The medical specialty dealing with diseases of the musculoskeletal system
What are the components of synovial joints?
Two bones forming the join
Joint cavity with synovial fluid and cartilage on either side (type II cartilage)
What is Arthritis?
Disease of the joints
What are the 2 types of arthritis?
Osteoarthritis Inflammatory arthritis (rheumatoid)
What is inflammation?
a physiological response to deal with injury or infection
However, excessive/inappropriate inflammatory reactions can damage the host tissues
How does inflammation clinically manifest?
Rubor Dolor Calor Tumor Loss of function
What are the physiological changes associated with inflammation?
- Increased blood flow
-Migration of white blood cells (leucocytes) into the tissues
-Activation/differentiation of leucocytes
-Cytokine production
E.g. TNF-alpha, IL1, IL6, IL17
What are the two types of crystal arthritis?
Gout
Pseudogout
What is gout caused by?
syndrome caused by deposition of urate (uric acid) crystals -> inflammation
What is a risk factor for gout?
High uric acid levels (hyperuricaemia)
What causes hyperuricaemia?
Genetic tendency Increased intake of purine rich foods Reduced excretion (kidney failure)
What is pseudogout caused by?
a syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystal deposition crystals -> inflammation
What are the risk factors for pseudogout?
background osteoarthritis, elderly patients, intercurrent infection
What does gout cause?
Gouty arthritis
Tophi (aggregated deposits of MSU in tissue)
Extreme pain
What does gouty arthritis commonly affect?
Metatarsophalangeal joint of the big toe (‘1st MTP joint’)
What are the affects of gouty arthritis?
Abrupt onset
Extremely painful
Joint red, warm, swollen and tender
Resolves spontaneously over 3-10 days
What investigation is done in gout?
Joint aspiration – synovial fluid analysis
What is the management of gout?
Acute attack – colcihine, NSAIDs, Steroids
Chronic – allopurinol
What are synovial fluid samples examined for?
Pathogens
Crystals
Rapid Gram stain followed by culture and antibiotic sensitivity assays
Polarising light microscopy to detect crystals which can be seen in arthritis due to gout or pseudogut
What are the features of synovial fluid in gout?
Crystal - urate
Shape - needles
Polarizing light microscopy - negative
What are the features of synovial fluid in pseudogout?
Crystal - Calcium pyrophosphate dihydrate (‘CPPD’)
Shape - brick shaped
Polarizing light microscopy - positive
What are the immune mediated inflammatory joint diseases?
SLE
Rheumatoid arthritis
Vasculitis
What is the most common Immune-mediated inflammatory joint disease?
Rheumatoid arthritis
What is RA?
chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis
(inflammation of the synovial membrane) of synovial (diarthrodial) joints
What is the pathogenesis of RA?
Synovial membrane is abnormal in rheumatoid arthritis:
The synovium becomes a proliferated mass of tissue (pannus
What is the dominant cytokine in RA?
TNF Alpha
How has the role of TNF alpha been proven?
validated by the therapeutic success of TNFα inhibition in this condition
How is TNF alpha inhibited
TNFα inhibition is achieved through parenteral administration (most commonly sub-cutaneous injection) of antibodies or fusion proteins
What are the key features of RA?
Polyarthritis - swelling of the small joints of the hand and wrists is common
Symmetrical
Early morning stiffness in and around joints
May lead to joint damage and destruction - ‘joint erosions’ on radiographs
What are the extra-articular manifestation of RA?
Rheumatoid nodules
Others rare e.g. vasculitis, episcleritis
What might be detected in the blood in RA?
Rheumatoid factor
Autoantibody against IgG - should really call this rheumatoid ‘antibody’ not ‘factor’
What is the joint pattern of involvement in RA?
Affects small and large joints, but particularly hands and feet
Symmetrical
Affects multiple joints (polyarthritis)
Which joints are most affected by RA?
Metacarpophalangeal joints (MCP) Proximal interphalangeal joints (PIP) Wrists Knees Ankles Metatarsophalangeal joints (MTP)
What are the effects of synovial inflammation?
joint synovitis
tenosynovitis
bursa
What are common extra-articular features?
Fever, weight loss
Subcutaneous nodules
What are less common extra-articular features?
vasculitis
Ocular inflammation e.g. episcleritis
Neuropathies
Amyloidosis
Lung disease – nodules, fibrosis, pleuritis
Felty’s syndrome – triad of splenomegaly, leukopenia and rheumatoid arthritis
What are subcutaneous nodules?
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Occur in ~30% of patients
What are subcutaneous nodules associated with?
Severe disease
Extra-articular manifestations
Rheumatoid factor
What is rheumatoid factors?
Antibodies that recognize the Fc portion of IgG as their target antigen
typically IgM antibodies i.e. IgM anti-IgG antibody
Positive in 70% at disease onset and further 10-15% become positive over the first 2 years of diagnosis
What are the second type of antibodies seen in RA?
Antibodies to citrullinated protein antigens
What are ACPA’s?
highly specific for rheumatoid arthritis
Anti-cyclic citrullinated peptide antibody ‘anti-CCP antibody’
Citrullination of peptides is mediated by enzymes termed:
Peptidyl arginine deiminases (PADs)
What is the treatment goal in RA?
Prevent joint damage
What are the requirements regarding management?
Early recognition of symptoms, referral and diagnosis
Prompt initiation of treatment: joint destruction = inflammation x time
Aggressive treatment to suppress inflammation
What is the drug treatment in RA?
Disease-modifying anti-rheumatic drugs (‘DMARDs’) = drugs that control the disease process
What is the first line treatment for RA?
1st line treatment:
methotrexate in combination with hydroxychloroquine or sulfasalazine
What is 2nd line treatment for RA?
2nd line:
Biological therapies offer potent and targeted treatment strategies
New therapies include Janus Kinase inhibitors : Tofacitinib & Baricitinib
What drugs can be used short term?
Important roles for glucocorticoid therapy (prednisolone) but avoid long-term use because of side-effects.
What is important in the management of RA?
Multidisciplinary approach also important e.g. physiotherapy, occupational therapy, hydrotherapy, surgery
What are biologics?
Biological therapies are proteins (usually antibodies) that specifically target a protein such as an inflammatory cytokine
What are the main features with ankylosing spondylitis?
Seronegative spondyloarthropathy – no positive autoantibodies
Chronic sacroillitis – inflammation of sacroiliac joints
Results in spinal fusion – ankylosis
Common demographic: 20-30yrs, M
Associated with HLA B27
What is the clinical presentation of AS?
Lower back pain + stiffness Early morning Improves with exercise Reduced spinal movements Peripheral arthritis Plantar Fasciitis, Achilles Tendonitis Fatigue
What might you find on inspection in AS?
Hyperextended neck
Loss of Lumbar lordosis
Flexed hips and knees
What bloods are important in AS?
Normocytic anaemia
Raised CRP, ESR
HLA-B27
What imaging is done in AS?
X-rays
MRI
What would you look for on a MRI re AS?
Squaring Vertebral bodies, Romanus lesion
Erosion, sclerosis, narrowing SIJ
Bamboo Spine
Bone Marrow Oedema
What is the management for AS?
Physiotherapy
Exercise regimes
NSAIDs
Peripheral joint disease - DMARDs
What is psoriasis?
autoimmune disease affecting the skin (scaly red plaques on extensor surfaces eg elbows and knees)
What are the main features of psoriasis?
~10% of psoriasis patients also have joint inflammation
Unlike RA, rheumatoid factors are not present (“seronegative”)
Varied clinical presentations:
What is classical presentation of PA?
Classically asymmetrical arthritis affecting IPJs
How can PA clinically manifest?
- Symmetrical involvement of small joints (rheumatoid pattern)
- Spinal and sacroiliac joint inflammation
- Oligoarthritis of large joints
- Arthritis mutilans
What investigations are done in PA?
X-rays of affected joints – pencil in cup abnormality
MRI – sacroiliitis and enthesitis
Bloods – no antibodies as seronegative
What is the management for psoriatic arhritis?
DMARDs – methotrexate
Avoid oral steroids – risk of pustular psoriasis due to skin lesions
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 manifestations of reactive arthritis?
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
What can Reactive arthritis be a first manifestation of ?
HIV
Hep C
Who is reactive arthritis often seen in?
Commonly young adults with genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. Salmonella infection)
When does reactive arthritis occur?
Symptoms follow 1-4 weeks after infection and this infection may be mild
What is the management of reactive arthritis?
Condition is usually self-limiting – can be managed with NSAIDS or DMARDs if required
What is SLE?
a multi-system autoimmune disease
Multi-site inflammation: can affect any almost any organ.
Often joints, skin, kidneys, haematology. Also: lungs, CNS involvement
What is SLE associated with?
with antibodies to self antigens (‘autoantibodies’)
Autoantibodies are directed against components of the cell nucleus (nucleic acids and proteins)
What are the clinical tests for Lupus?
- Antinuclear antibodies (ANA):
High sensitivity for SLE but not specific.
A negative test rules out SLE, but a positive test does not mean SLE. - Anti-double stranded DNA antibodies (anti-dsDNA Abs):
High specificity for SLE in the context of the appropriate clinical signs
What are the epidemiological features of SLE?
F:M ratio 9:1
Presentation 15 - 40 yrs
Increased prevalence in African and Asian ancestry populations
Prevalence varies 4-280/100,000
